Cancer Adjunct and Adjuvant Therapies, Improving the Quality of Life

Paul L. Reller L.Ac. / Last Updated: August 03, 2017

Choosing viable therapies in the treatment of cancer does not involve an "either/or" but rather an "also"

A more comprehensive article on cancer and Complementary and Integrative Medicine is available on this website, entitled Cancer, but this article covers some of the more commonly understood adjunct and adjuvant therapies with CIM/TCM to prevent and treat cancer.

Even in 2015, as Complementary Medicine is part of the National Institutes of Health (NIH), endorsed by the World Health Organization (WHO), and an important part of the most advanced cancer treatment protocols, supported by a plethora of scientific study and even human clinical trials around the world, journalists continue to deride the use of Complementary therapies in cancer treatment with a very negative slant. The public is beginning to wonder whether these journalists are ill-informed, or merely paid by the big pharmaceutical and health care industries to continue to promote the notion that adjunct therapies in cancer treatment are presenting dangers, rather than benefits, to the patient. A case in point is the articles following the death of Steve Jobs, the founder and CEO of Apple, and arguably one of the most brilliant, analytic, wise and informed minds on the planet. Articles, even in the New York Times, portrayed his choice of inclusion of adjunct therapies into a complex and individualized treatment protocol for his pancreatic cancer, one of the most deadly types of cancer, as misguided. This not only denigrated the memory of this brilliant man, but also the choice of integration of therapies to achieve the best possible outcome.

Pancreatic cancer, especially the type that Steve Jobs apparently had, is one of the most deadly types of cancer on the planet, and although the incidence is relatively low in the population, it is the fourth leading cause of cancer-related deaths in the United States. Pancreatic cancer usually causes no symptoms early in the cancerous growth, and is not detected in almost all cases until it reaches an advanced stage and has spread to other organs. The only viable treatments present not a cure, but a prolonging of life expectancy with surgical removal of the parts of the pancreas affected by the tumor, extending the patient life by at most a few years. Chemotherapy and radiation are sometimes used when the surgical approach is not viable, or has failed. The American Cancer Society states that the 5-year survival rate for pancreatic cancer is only about 5 percent, and that a great percentage of patients die within 6 months of diagnosis. Steve Jobs was diagnosed in 2003, and survived until 2011, making his survival at the top of what could be expected, about 8 years. In addition, he resumed his role as the head of Apple, guiding the company to the most lucrative and creative phase it had yet seen, capturing a large percentage of the total market, changing the face of technology across the planet, and controlling the direction of his competitors. This increased quality of life, and ability to function until his death at home, not in a hospital, receiving unnecessary and fruitless therapy that often makes the last days of a cancer patient miserable, may have been attributed to his use of a variety of integrated adjunct cancer therapies.

In 2004, after his surgery, which he announced as a liver transplant, but which we now know was a Whipple Procedure to excise the affectd part of the pancreas, Steve Jobs finally revealed that he had a type of pancreatic cancer called islet cell neuroendocrine tumor. This type of pancreatic cancer typically includes symptoms of nausea, fever, weight loss, jaundice, abdominal pain, and swelling, presenting debilitating symptoms, and if not diagnosed at the early stages, as blood sugar and metabolic dysfunctions are noticed, spreads to the liver. Jobs waited for 10 months before undergoing surgery to remove the islet cells of the pancreas, consulting as many medical experts as possible, and researching the array of adjunct therapies that might not only prolong his life and alleviate symptoms, but also better prepare him for surgery. These treatments were not an "alternative" for him, but a sensible integration of holistic medicine. After this amazing 7-8 years of highly functional survival, Steve Jobs died of respiratory arrest at home, probably the result of a depressed immune system and chronic pneumonia as a result of immune suppressing drugs. His second surgery in 2009, an actual liver transplant, indicated that the cancer was not detected at an early stage, but had already spread to the liver. Dr. Khaled el-Shami, a cancer specialist at George Washington University Medical Center, explained that pancreatic cancer, even this type, is an incurable disease with virtually no chance of survival when it has spread to other organs outside of the pancreas. Dr. el-Shami explained that a liver transplant is an aggressive way to deal with this cancer: "It's a balance between removing a big chunk of cancer in the liver and the risk of having a weakened immune system, which can encourage not only the original cancer to come back but also the emergence of other cancers." Typically, the patient may rebound strongly after the liver transplant, if the organ is not rejected, but the cancer will almost certainly reemerge, or the stress on the immune system will allow common infections to threaten the patient. This last scenario was the cause of death for Steve Jobs. Subsequently, many experts on this type of cancer have suggested that the use of a liver transplant with immune suppressing drugs is counterproductive, and recent guidelines suggest that removal of just the part of the liver where the cancer cells are detected is a better strategy, with many patients now surviving for longer periods with surgical excision of the affected parts of organs, and avoidance of pharmaceutical therapy that could lead to devastating complications. Of course, integration of CIM/TCM could help keep the patient healthy in this protocol, being a valuable adjunct care, and denial of such care, which does not have serious health risks and adverse health effects, is just not logical, although it is still highly discouraged. As we see from the analysis of Steve Jobs' cancer and care, nothing is certain, and opinions on the right choices of therapy change over time. Ultimately, each individual has hard choices to make to insure greatest survival, and no one can guarantee that a particular choice is the best one. It should be up to the patient to become fully informed and make these choices in a free society. Being kept in the dark and told what to do is frightening and cruel in cancer care, and being dscouraged from integrating any type of Complementary Medicine is cruel and unnecessary as well.

While the standard media negatively portrayed Jobs' choice of including herbs, acupuncture and nutrient medicines, and perhaps even energetic therapeutics, into his treatment protocol, the public should see this rather as an endorsement. This brilliant analytic mind chose these adjunct therapies to help him in his fight to maintain a quality of life and prolong his life as much as possible. This was not a man that chose rashly without exploring and understanding his options. Jobs also chose to spend a fortune to fully analyze his genetic code and compare it to the genetic code of his tumor cells. His hope in this endeavor was to leave a legacy of information that would lead to better cancer screening markers and better guidance of targeted therapies, including biologics. He was not looking for the "magic bullet" to cure cancer, but rather supporting his belief in the science of integrating individualized therapies into protocols that would someday finally produce a cure for cancer. Today, even our most advanced oncological sciences have no cure for cancer. One could say that all cancer treatment today is palliative. The adjunct therapies in Complementary Medicine provide the patient with an array of tools to achieve the many goals in complex cancer therapy, including the palliative goals of maintaining quality of life, reducing side effects of radiation and chemotherapy, improving the immune function after surgery, and alleviating symptoms. The one thing that Complementary and Integrative Medicine (CIM/TCM) does that most standard therapy has not accomplished to date, is to enhance the body's own ability to push the cancer to remission, as well. To date, the percentage of cancers going into remission due to the body's innate mechanisms eclipses those cases where standard therapy may have induced remission. By improving the functional capacity of the immune responses to cancerous growth, Complementary and Integrative Medicine provides hope that your cancer will be one of the approximately 40 percent of all serious cancers to go into remission and preserve life. This holistic strategy does not deny the efficacy of standard treatment, but suggests working with it to achieve better outcomes.

While the example of Steve Jobs does not apply to the vast majority of those diagnosed with cancer, since his was a rare pancreatic cancer, his choice of integrative and thorough treatment protocol applies to everyone. Some of his choices were kept private, but others have been publicized, such as his adoption of the Dr. Dean Ornish Cancer Diet, and a predominantly vegetarian diet, which was well-known. He did not choose to rely on so-called alternative medicine, but integrated this Complementary Medicine with the most advanced standard medicine, receiving the Whipple pancreaticoduodectomy and subsequent liver transplant, as well as chemotherapy and radiation. In fact, he had completed another round of chemotherapy at Stanford months before his death, and the deterioration in his health after this treatment was attributed to the adverse effects of chemotherapy, as was his poor immune health due to the need of immune suppressing drugs after his liver transplant, which was the ultimate cause of his death. Steve Jobs also traveled to Basel, Switzerland to receive a form of hormone-delivered radiotherapy, where radiation is linked to peptide hormones to target endocrine cancer cells in pancreatic cancer. Such advance in the specificity of radiation and chemotherapy presents dramatic improvement in outcomes. 

While the example of Steve Jobs was touted in the press as a warning against so-called alternative medicine, it is obvious to anyone who takes a little time to analyze this case that Mr. Jobs' course of therapy was thorough and integrative, not avoiding of standard treatment, and that the choice of Integrative Medicine resulted in a best-case scenario of nearly 8 years of productive life following his diagnosis of advanced pancreatic cancer, which has a survival rate of 6 months for most patients. The many articles concerning his cancer appear to be mostly "spin" distorting the known facts of his case, not a true description of his successful and productive life while dealing with a devastating form of cancer. His story is not a 'lesson' for everyone with pancreatic neuroendocrine cancer, either, as 95 percent of such patients have a slow-growing and relatively benign form of this cancer, that needs to be monitored for growth, exactly as Steve Jobs did. Unfortunately, he was one of the 5-10 percent that experienced a metastasis. As most honest oncologists will also admit, the cause of death in these cases is not the actual pancreatic tumor itself, but the metabolic consequences, and the metastases. We cannot predict metastases, or even identify accurately where these cells will end up growing, but we can try to improve the health of the organ tissues to prevent the seeding and spread, as Steven Paget stated almost a century ago. This is one of the goals of CIM/TCM adjunct cancer care. Most patients with a diagnosis of cancer in the United States experience either a prostate or breast cancer, though, and this article will focus on well-known integrative treatment research concerning these cancers, as well as some research concerning colon cancer, cervical cancer, brain cancer, and lung cancer, with additional information and links to scientific studies at the end of the article.

Examples of the success of adjunct Complementary Medicine therapies in the most common cancers in the United States today

Breast and prostate cancers represent a large percentage of treatable cancers with long-term therapy to prevent recurrence or spread. Since most of these cancers are driven by hormonal stimulation, standard therapy involves long-term use of such drugs as Tamoxifen, Raloxifene (Evista), and Lupron. Unfortunately, these drugs present serious challenges to the overall health and welfare of the patients, which requires sound support therapies from Complementary and Integrative Medicine and Traditional Chinese Medicine (CIM/TCM) to counter side effects, support metabolic systems that will probably be damaged, and enhance the specific effects that we want to see from these drugs. To continue to ignore the problems with these therapies and fail to manage subsequent noncompliance is, in effect, failing our patients. Risk of uterine cancers, deep vein thrombosis, pulmonary embolism and stroke, and other serious consequences of these drugs, especially with long-term use, could be greatly reduced by a sensible integration of evidence-based Complementary Medicine as well. Second and third generation aromatase inhibitors have shown only slightly improved adverse health effects with long-term use, and only slightly better outcomes in terms of 5-year survival rates. The pathophysiology and the drug mechanisms of these hormonal therapies are complicated, and we must, as physicians, take a very active role in understanding the biology and keep current with research to present the best evidence-based approaches with Complementary and Integrative Medicine (CIM/TCM). Study in recent years has confirmed that the longstanding protocol of systemic estrogen ablation was misguided, and that the balance of estrogens in local tissues and the balance of expression of estrogen receptor types are responsible for the progression of estrogen receptor positive (ER2+) breast cancer, and the overall hormonal and metabolic balance is responsible for the aggressive tumors related to human endothelial growth factor, or HER2. Many misconceptions and mistakes have guided past therapies in the long-term treatment of breast cancer, and are still inhibiting sensible new guidelines.

While we are presented with the impression that standard treatment for such common cancers as breast and prostate cancer are remarkably effective, the truth is that while 95 percent of these cancers do not proceed to a metastatic, or threatening spreading type, of cancer, the ones that do proceed to metastasis are often detected in the early stages, treated with surgery, radiation, chemotherapy and hormonal ablation, and yet still proceed to stage 4 metastasis. The statistics of long-term survival for estrogen receptor positive breast cancer that spreads to the lymph, bone or other organs has not significantly improved since 1980. Studies of 10-15 year survival during the 1980-1995 era show that an average survival was 9-12 years, and today the average 5-year survival is still only 15 years. To see a review of such studies, click here: . It is obvious that we need a more comprehensive and holistic approach, yet standard medicine still stubbornly persists in denying real integration of Complementary and Integrative Medicine, instead continuing to frighten patients from this safe and effective adjunct care, despite widespread proof of success worldwide and no actual cases of clinical proof that CIM/TCM has hurt cancer patients or interfered with their standard care in any way. The prognosis for these more serious cancers is still poor, and could perhaps be improved with CIM/TCM. 

In 2015, a comprehensive health technology assessment of the use of herbal medicine as adjunct therapy in cancer care was conducted by experts at the National Health Resource Centre and Dayanand Medical College, in India. This review and assessment searched all standard medical research databases and found 76 quality studies involving thousands of patients with various types of cancer. The overall assessment was that integration of herbal medicine (phytomedicine) resulted in significant decrease in mortality and significant reduction in adverse drug reactions, as well as lower cost of care. Such studies clearly point out that the unsubstantiated standard advice against integrating herbal medicine that has been very prevalent has clearly been wrong, and that actual measurable benefits and safety are opposite to standard reporting. To see this study, just click here: . Reassuring patients that have been frightened by standard advice for some time to discourage the success of CIM/TCM as adjunct integrative cancer care will be difficult, but will result in better outcomes and quality of life.

In 2014, a comprehensive and long-term study of current treatment protocols for breast cancer and the increase in double mastectomies to prevent recurrence, even for cancer in-situ, or DCIS, which is not actually a cancer, but a potential cancerous lesion, was published in the esteemed Journal of the American Medical Association (JAMA), conducted by the Stanford University School of Medicine and the Cancer Prevention Institute of California. This high-quality and comprehensive study reviewed all cancer cases in California with an average follow-up of 7 years, and like studies before it in Europe, found that mastectomy and double mastectomy did not improve long-term survival with breast cancer at all over a simple lumpectomy and targeted radiation. Despite this knowledge, which was proven in sound studies many years ago as well, the rate of choice of double radical mastectomy and breast reconstruction to prevent breast cancer recurrence rose from just 2 percent of patients in 1998 to about 33 percent of patients diagnosed with breast cancer under the age of 40 in 2011, and has continued to rise. This approach to cancer care has occurred not because it will prevent recurrence or survivability, but because the patients have increasingly felt that the fear of recurrence was so great that they should surgically remove their breasts, despite the fact that this was not actually going to improve their outcomes. This urging of patients to adopt this costly and risky treatment also encouraged a belief that if the breast tissues were removed that there was not a substantial need to adopt a more comprehensive approach to cancer prevention with integration of Complementary Medicine. Finally, there is a greater voice of reason that is trying to curb the enormous fear of cancer and educate patients to a sensible and dependable holistic course to bring cancer recurrence to a minimum. By choosing the least invasive and least harmful, but proven effective, course of therapy, integrated with a proven and thoroughly safe, individualized course of care in Complementary Medicine, patients will be able to alleviate the fear and stress of cancer and feel certain that an intelligent pro-active treatment protocol will treat and prevent cancer to the utmost. Hopefully, the field of oncology will finally start adopting this protocol, driven by hope and assurance, not by fear and stress, and of course profits.

Not only decreased risks and enhanced effectiveness, but also Quality of Life considerations are increasingly important in discussions of options in the overall treatment protocol in cancer therapy, especially when utilizing hormonal therapies that have a large number of side effects that could seriously damage quality of life. This is especially important in the older patient. As we progress with research in Complementary and Integrative Medicine, and patients become more educated to this research, more and more oncologists are exploring an integrative treatment model to find more options in a patient centered approach. Flexibility in treatment protocol over the course of treatment is also becoming a consideration, as each patient presents a unique reaction to drug therapy, and the considerations of risks, benefit, and quality of life must fit the individual patient's reactions to drug therapy.

As the success of integrating adjunct therapy with Complementary Medicine and Traditional Chinese Medicine (CIM/TCM) progresses, this success is dependent upon a degree of belief and acceptance. To gauge this progression, research in 2013 at the University of Pennsylvania Perelman School of Medicine, in Philadelphia, Pennsylvania, U.S.A. surveyed a cross-section of cancer patients in an outpatient setting and found that over 61 percent reported using Complementary Medicine following their cancer diagnosis. Factors influencing this patient choice included gender, education, type of cancer, and time from diagnosis. Women with breast cancer diagnosis that had a higher level of education and were surviving cancer after one year accounted for the most prevalent use of Complementary Medicine. While a variety of treatment protocols were utilized, including acupuncture, herbal and nutrient medicine, dietary protocols, massage, homeopathy, energetic healing such as Qi Gong, homeopathy, chiropractic medicine, yoga and Tai chi, the survey found most satisfaction with energetic healing, dietary protocols, herbal and nutrient medicine, and massage (PMID: 23777242). Clearly, an emerging belief is occurring in the efficacy of Complementary and Integrative Medicine, even in areas of the country less likely to have traditional exposure to this specialty, in adjunct cancer treatment, yet just as clearly we see that patients are showing a clear tendency to seek indirect therapies and not selecting to utilize professional Complementary and Integrative Medicine (CIM/TCM) treatment. A long history of discouragement of the utilization of Complementary Medicine in cancer therapy, even to the extent of laws passed to prosecute claims of benefit, has led to a wide skepticism of such professional therapy, yet as more and more evidence of the array of proven benefits in scientific studies emerges, the tide is turning.

While standard oncology in the United States has slowly evolved from a complete prohibition of Complementary and Integrative Medicine and Traditional Chinese Medicine (CIM/TCM), characterizing proven, licensed and safe adjunct therapies as dangerous 'alternative' approaches with false claims of cancer cure, designed purely to discourage cancer patients from receiving proven standard oncological care, all of which has no basis at all in truth, and purely designed to frighten cancer patients, we still have a long way to go in realistically educating and reassuring patients that CIM/TCM can increase the quality of life and long-term success in all types of cancer care, and finally provide a sensible prevention of cancer. Today we see renowned cancer clinics and institutions at least differentiate realistic Complementary and Inegrative care from the almost nonexistent 'alternative' medicine that purportedly sought to discourage patients from receiving standard treatment. This is a small step forward to help cancer patients. While acupuncture stimulation will have only indirect effects on cancers, this therapy can provide significant support for the immune system, relief of cancer symptoms, and stress relief, providing significant support. Herbal and nutrient medicine, on the other hand, can have both direct and indirect effects on the wide variety of cancers, and various stages of cancer.

To see the emerging support in the West for CM/TCM and herbal and nutrient medicine, we can look at the statements from various renowned University Medical Schools and Cancer Treatment Institutions in recent years. For instance, in 2015, the Cardiff University School of Medicine, in the United Kingdom, linked to the renowned Peking University in Beijing, China with the establishment of the Cardiff University - Peking University Cancer Institute, published a meta-review of research concerning Chinese Herbal Medicine and adjunct cancer care, supporting this care for a variety of benefits, reducing side effects of chemotherapy, including bone marrow suppression (immune deficiency and anemia), nausea and vomiting, directly helping to regulate cancer proliferation, adhesion, and migration, as well as cell apoptosis (programmed cell death subverted by cancer mechanisms), suppression of angiogenesis and reduction of tumor growth. This West-East collaboration of cancer experts also highly recommended that we finally increase both study of precise mechanisms and randomized controlled human clinical trials of herbal medicines, since even in 2015, meta-reviews have found as few as 16 total RCTs yet published in standard medical journals. To see this statement by Cardiff University oncologists, click here: . You will note the complete lack of the usual warnings against herb-drug contraindications that are still largely unsupported in actual clinical care, and are still largely theoretical. 

The mentioned herbal patent formula in this review, which was proven safe and effective with in vitro study in 2015 as an adjunct cancer medicine, Yangzheng Xiaoji Jiaonang (capsules) consists of Milkvetch root (Astragalus or Huang qi), Glossy Privet fruit (Lingustri lucidi or Nu zhen zi), Ginseng (Xi yang shen), Zedoary rhizome (Curcuma zedoaria or E zhu), Ganoderma (Ling zhi or Reishi mushroom extract), Gymnostemma (Jiao gu lan), Atractylodes (Bai zhu or Cang zhu), Skullcap (Huang qin or Scutellaria), Hedyotis (Bai hua shi shi cao), Virgate Wormwood (Artemisia or Yin chen hao), Indian bread (Fu ling or Poria), Indian wild strawberry (Potentilla or Wei ling cai), Swallowroot (Bai wei), and other various gentle support herbs. These same herbs are seen in most professional Chinese Herbal Formulas in adjunct cancer care. The quality of these herbal medicines is the primary question in care, and using only such medicines obtained from professional herbalists, or Licensed Acupuncturists, is very important. To see this same cancer institute's early study in 2012 with this formula, click here: . To see the follow-up study in 2013, demonstrating an array of anti-cancer and support effects, and application to the difficult to treat bone cancers (osteosarcoma) with this herbal formula, click here: . While we may still be years away from the expensive 3-stage human clinical trials demanded, these RCTs were designed to determine safety of pharmaceuticals, and the safety of traditional standard herbal medicines is not an issue. Actual cases of harm are almost nonexistent in the clinical realm, and the wide use of such herbal formulas in Chinese, Japanese, South Korean and other countries' hospitals reveals littel cause for concern with professional herbal medicine. On the other hand, the present state of affairs in the United States and Europe has led to a majority of cancer patients buying non-professional herbal medicines outside of the clinic, which may present problems with assurance of quality and ingredients, largely unregulated. Professional herbal care is very important.

Even types of cancer that have very poor outcomes with standard therapy are shown to have improved outcomes with integration of TCM therapies, and while this has now been highly discouraged for decades, citing "potential" adverse effects, these adverse effects have not been demonstrated in actual care. The tactic of inciting fear of TCM therapy by referring to "potential" adverse effects and contraindications with just a few herbal medicines continues, yet more and more studies of the actual integration of acupuncture, herbal and nutrient medicine in the treatment and prevention of cancer show no actual adverse effects, and many beneficial and synergistic effects. Many such studies are provided on this website in the sections of 4 cancer articles entitled Additional Information and Links to Scientific Studies at the ends of the articles. One such study in 2015, involving collaboration between the famous MD Anderson Cancer Center, in Houston, Texas, U.S.A. and the Institute of Cytology and Preventive Oncology, at the University of Allahabad, in Allahabad, India, showed that 3 of the most famous anticancer herbal chemicals, Berberine, Curcumin and Resveratrol, largely derived from Coptis (Huang Lian), Curcumin (E zhu) and Polygonum (Hu zhang), are now proven to also provide synergistic effects to enhance the effects or standard chemotherapy with 5-fluouroucil in the treatment of stomach cancer (PMID: 26492225). These herbal chemicals showed no adverse effects in combination with chemotherapy, and specific benefits, such as downregulation the genetic expression of STAT3 and survivin, improved the effects of chemotherapy in the treatment of this very dangerous type of cancer. More and more evidence is finally being printed and researched by cancer centers in the United States and Europe. The history of Integrative Oncology in standard cancer care was summarized by oncologists at the University of Duisburg Essen in Germany in 2013, noting the many University Medical Schools and renowned Cancer Centers that now offer CIM/TCM. To see this summary, click here:

Breast cancer that is estrogen receptor positive - Treatment Considerations

Early stage breast cancer that is estrogen receptor positive (ER2+) is a frequent diagnosis within the totality of breast cancers in the United States. Some studies suggest that 80 percent of breast cancer is hormone receptor positive, with a great majority ER2+. Tamoxifen, an antagonist of the estrogen receptor (not an anti-estrogen), is a drug that has been used for decades and is thought to work by blocking this type of estrogen receptor stimulation of cancer growth. Tamoxifen is only proven effective in treating estrogen receptor positive breast cancer, not other types. Although this drug has been used for decades we still do not know the ideal length of time that the drug should be administered, and use of Tamoxifen for more than a year is considered a significant risk for acquiring uterine and endometrial cancer. Since demographic studies show that recurrence of cancer is much less likely if the patient survives for 5 years without recurrence, Tamoxifen, or other aromatase inhibiting (AI) drugs, are currently prescribed for this length of time. Prescription of Tamoxifen and other SERM (selective estrogen receptor modulators) drugs have been recommended for more than 5 years, and even as a preventive treatment before cancer occurs, but long-term studies show that there is no significant benefit in these uses, but that considerable side effects and long-term risks occur for almost all patients. For the postmenopausal patient, raloxifene (Evista), another selective estrogen receptor modulator (SERM) that is usually prescribed for osteoporosis, is also proven effective in long-term prevention of breast cancer recurrence. While both of these drugs are currently routinely prescribed for 5 years, harsh side effects and fear of serious health risks produce only a 37 percent compliance over this time.

In 2014, initial large trials of extended Tamoxifen use past 5 years were released, called the ATLAS and aTTom studies, (Adjuvant Tomoxifen: Longer Against Shorter and adjuvant Tamoxifen to offer more), and while the initial study results prompted a renewed call for 10-year guideline use with metastatic breast cancer, the results showed that a small decrease in risk past 10 years was seen with taking the relatively harsh therapy for 10 years, but paradoxically, only after the Tamoxifen was stopped. This means that while the patients were taking the Tamoxifen, statistically their chance of disease-free survival was not increased over not taking the drug, but that after stopping it these women experienced signifcantly better outcomes. Of course, the experts working on this conundrum came up with an explanation, but a rather elaborate one. The explanation was that it appeared that long-term inhibition of aromatase conversion of estrogens appeared to create a long-term response where resistance to the Tamoxifen induced by long-term use now apparently created a situation on the breast cells where the natural estrogens (there are 3 known types in the human body) now induce better cell apoptosis (programmed cell death) that decreases the chance of cancer mutation. In other words, we are told that first, estrogens induce the breast cancer by extending the normal cell life and inhibiting normal apoptosis, but that when we take Tamoxifen that we develop a resistance to the drug (where it no longer works) that actually creates the opposite effect of estrogens now protecting us against cancer mutations by inducing cell apoptosis. This explanation is so elaborate and makes so little sense that patients are going to have a very difficult time even thinking about it. The reasoning behind this theory is that while one would logically expect the stopping of Tamoxifen after 10 years to result in estrogens again stimulating breast cancer by inhibiting cell apoptosis, we have observed the opposite to be occurring, and while there is no actual logical explanation for this fact, we can assume that this positive result is just due to taking the harsh medication for so long. That such explanations have become common in the whole realm of standard cancer care is alarming, yet few voices speak up. What is scientifically verifiable is that when serious studies show that we perhaps should not over-prescribe some drug that is very profitable that the industry will spend an enormous amount of money to prove that this is just not right. We are just in denial of this fact. The complexity of the question also serves to divert the attention of the patients from looking at real and practical protocols that they could initiate to seriously decrease their risk of future cancer, as well as to consider that the risk is small after 5 years of disease-free survival, or that the actual risks of metastatic, or threatening breast cancer, is extremely variable, and not actually the one-size-fits-all risk that we are currently led to believe. Complexity of explanation successfully perpetuates the fear that most experts now acknowledge is a serious problem in cancer care.

A recent study in Great Britain found that 7 percent of patients prescribed Tamoxifen stopped taking the medication entirely at an early stage of therapy, and of those remaining, only 49 percent continued therapy with no gaps longer than 3 months. The median length of therapy was 2.42 years, instead of the 5 years routinely prescribed. In 2003, a study of patients in the United States found only 87 percent of patients consistent in taking Tamoxifen in the first year, and a similar rate of overall noncompliance to the Great Britain study was seen over time. This data suggests that side effects and risks create a scenario where few patients are actually 100 percent compliant with prescribed use. Obviously, modern medicine needs to quit pretending, and come up with treatment options that match the patient needs and desires. Complementary and Integrative Medicine and Traditional Chinese Medicine (CIM/TCM) provides viable options and adjunct therapy, whether the patient with estrogen-receptor type 2 positive status decides to continue with long-term Tamoxifen therapy or SERM, or not. The ability to minimize the harsh adverse effects of this therapy with Complementary Medicine is proven, but underutilized. More importantly, there is evidence that a holistic protocol will achieve the same goals as these harsh hormonal therapies. The persistent advice that there may be some adverse contraindications with herbal and nutrient medicine in adjuvant cancer care has now been well studied and found to be without merit, yet this advice is still repeated, with oncologists sticking to a 'party-line' rather than being honest with their patients. The few potential contraindications are easy to avoid in professional care, and should not prevent patients from benefiting from integrative medicine.

The National Cancer Institute, a branch of the U.S. National Institutes of Health (NIH), states that there are only two studies that confirm the benefits of taking adjuvant tamoxifen daily for 5 years, and that the ideal length of treatment with tamoxifen is not known. Some studies have shown that there is little increased risk of ovarian and endometrial cancers with short-term use, but that a majority of patients reported side effects such as menopausal-like vasomotor hot flush and sweating. In the past, oncologists had prescribed tamoxifen for a 6 month course. Ideally, the course of treatment should be determined by consultation between the oncologist and patient, and discussion of risk versus benefit in each individual case. Of course, the ultimate decisions are made by the patient, and these decisions are usually difficult when cancer risk is involved, especially when the information is presented in such a dense and confusing manner. In making these decisions, new scientific study presents a variety of data that confirms the efficacy of various herbal and nutrient therapies that achieve a similar inhibition or modulation of estrogen receptor mediated estrogen driven cancer to tamoxifen. While these effects may not be supported by as vigorous of study with human trials, or may not have as specific or strong effect as the pharmaceutical, the research support is sound, and a combination of these therapies may provide effective adjunct or replacement to long-term tamoxifen use, which would meet the desire of the patient for a decreased overall risk of side effects, endometrial cancer, osteoporosis and stroke. Some supporting data for this research, such as a 2009 study at UCSF confirming the efficacy of a Chinese herbal formula from Peking University, which was found to be significantly effective in estrogen receptor modulation and anticancer effects, will be mentioned later in this article. Nutrient medicines, such as DIM and NuLignan, have also been proven to modulate estrogen receptor activity, and will be discussed as well. Other considerations, such as use of other benign herbal and nutrient therapies that have proven anti-cancer activities specific to breast cancer, may also be considered in designing a comprehensive integrated course of therapy to reduce long-term risk of recurrence. Evidence supporting these adjuvant therapies can be found in Additional Information at the end of this article.

Since there is an acknowledged risk with tamoxifen in pregnancy, with teratogenicity (Cunha GR et al, 1987), genotoxicity (Poirier adn Schild, 2003), and reproductive toxicity (Taguchi, 1987) established, and association with ovarian follicular atrophy and degeneration (Branham et al 1996), consideration of the data supporting herbal and nutrient therapies may also be applicable to the patient that is pregnant, or wishes to become pregnant in the future.

Another consideration is the 2009 finding that women who took tamoxifen for at least 5 years had a 4.4-fold higher risk of estrogen receptor negative contralateral breast cancer than women not treated with synthetic hormone therapy (Cancer Research, Sept. 1, 2009). While long-term tamoxifen use lowered the risk of contralateral estrogen receptor positive cancer by 60 percent, it produced higher risk of other types of breast cancer, as well as a higher risk of endometrial cancer. In discussion with the patient, this risk, as well as the other cancer risks, is important. A serious consideration of reduction of risk with the use of Complementary and Integrative Medicine may be very much appreciated by a subset of patients. Integrating with a Licensed Acupuncturist knowledgeable in this area may expand the knowledge base and provide the patient with a reliable source of professional products to integrate into the overall treatment protocol, which of course should be overseen by the oncologist.

One scientific finding that complicates the 5 year prescription of tamoxifen is the significant percentage of patients on tamoxifen who become estrogen receptor negative. When this happens, prescription of tamoxifen is no longer appropriate, and may have negative consequences. Unfortunately, periodic testing requires biopsies and are not routinely performed. The prescribing physician and the patient are often unaware of changes in the metabolism where other chemicals, such as growth factors, become the stimulation of cancer growth, or anti-apoptosis, and the patient would need a different type of treatment to prevent recurrence of breast cancer. In many women, prolonged tamoxifen use may increase recurrence rates, according to some studies, because hormonal growth factors are increased with prolonged tamoxifen use, especially with a relative lack of progesterone receptors and overexpression of growth factor receptors due to localized hormonal imbalance. Newer variations on the aromatase inhibitor may provide some improvement in quality of life measures. After a number of long-term large studies comparing various options and combinations, combinations of hormonal therapies did not prove to be more beneficial, with the large ATAC trial showing that Anastrazole (Arimidex) alone produced slightly better disease-free survival times than Tamoxifen alone or combinations, and in the BIG 1-98 trial, Letrozole (Femara) alone produced slightly (3.4 percent) better disease-free survival times than Tamoxifen alone or combinations, with half as many cases developing contralateral breast cancer. No overall increased survival rates were observed with any of these different courses of long-range hormone ablation therapies.

In June of 2013, a follow-up long-term study of the outcomes with Tamoxifen treatment for more than 5 years, by women with estrogen receptor positive breast cancer that had decided to continue the therapy, showed that for this subset of women, only modest benefits of prevention of the return of breast cancer was shown. Prior studies had shown that after the 5-year mark, the risk of recurrence of breast cancer was low. Other studies have shown no benefit to continuation of aromatase inhibitors after 5 years, which is largely dismissed in standard practice. This subset of women with slightly reduced risk of recurrence from continued AI use in this study were those that experienced the mildest side effects of the therapy, though, and thus chose to continue the prophylaxis. In 2009, a study of 7145 women by the Wolfson Institute of Preventive Medicine in London, England, showed that women who were considered at high risk for breast cancer and chose to take Tamoxifen as a prophylactic for 5 years had about 50 less diagnoses of breast cancer per 3600 women over 8 years than those taking a placebo (195 versus 142), but this included the most common diagnosis of ductal carcinoma in situ (DCIS), which is not really cancer, but the presence of precancerous lesions that were not spreading. During this period, threatening deep vein thrombosis or pulmonary embolism occurred in 27 more women, per 3600, taking Tamoxifen, and the overall mortality in the Tamoxifen group was more than doubled. The rate of endometrial cancer was significantly higher in the Tamoxifen group (17 versus 11), and most patients taking Tamoxifen reported vasomotor effects mimicking menopausal symptoms, such as frequent hot flush and sweating. 

In other words, 50 fewer cases of breast cancer or pre-cancerous lesions occurred, but 44 more cases of thrombosis and endometrial cancer occurred in the large group taking Tamoxifen for more than 5 years, while a majority of patients experienced a prolonged menopausal-like syndrome, and overall mortality was higher in the group taking Tamoxifen long-term. The risk versus benefit considerations for this therapy continue to be a matter of concern for many women, but for those taking this hormone ablation therapy for the long term should consider integrating medical treatment with Complementary Medicine to reduce the side effects and adverse risks. If serious symptoms and health risks are expected they should not be ignored. With all the aromatase inhibitors there is considerable risk of osteoporosis and cardiovascular disease with prolonged use, and here too, the use of CIM/TCM therapies could reduce the risk greatly. The continued discouragement of herbal medicine in general, based on just 2 small indirect studies with laboratory animals that concern just 2 herbs, is not sensible. Obviously, herbal and nutrient medicine and acupuncture could greatly improve outcomes and reduce risks, even of cancer recurrence, and many medical schools and institutions around the world are proving this in recent years, as a majority of patients in many countries now utilize these therapies. Encouraging a better professional and evidence-based integrated therapy would be the best course, but is still largely discouraged.

Tamoxifen citrate and other Aromatase Inhibitors

Selective estrogen receptor modulators are a relatively new category of therapeutic agents that bind with high affinity to estrogen receptors and mimic the effect of estrogens in some tissues but act as estrogen antagonists in others. Tamoxifen, a triphenylethylene derivative, was the first clinically available selective estrogen receptor modulator. Research in 2000 revealed that tamoxifen metabolites induced caspase-dependant apoptosis, or programmed cell death, in breast cancer cells. By 2005, it was discovered that almost all tamoxifen-responsive breast cancer cell lines developed resistance to therapy, and that over time, tamoxifen produced estrogen-like effects in the endometrium that increased the incidence of endometrial cancer. Research into adjunct therapies to counter these problems has produced surprising results.

Tamoxifen citrate is a nonsteroidal antiestrogenic antineoplastic whose exact biological and hormonal mechanisms are still unclear. Tamoxifen may exert cytotoxic action by blocking estrogen receptors within tumor cells, or on the surface membrane of the cells, and inhibit DNA synthesis that drives tumor growth, or it may stimulate hormone receptors in a modulatory manner that induces cancer cell death. No matter what the exact anticancer mechanism is, effects are not localized to breast cancer cells, and systemic distribution is still poorly understood, resulting in numerous unwanted effects. The drug is metabolized extensively in the liver into several metabolites, which may themselves be toxic, and primarily excrete in feces. Approximately 65 percent of the tamoxifen and 4 known metabolites are excreted in feces over 2 weeks, with more than 70 percent conjugated with other molecules. Standard dosage is 20mg daily, and it may take up to 2 months to attain a relative steady state serum concentration, which varies in patients from 67-183 ng/mL of tamoxifen, and 148-654 ng/mL of its most active metabolite, N-desmethyltamoxifen. This variation of circulating levels, the individual health of liver function, and the variation of elimination half-life from patient to patient, which ranges from 3-21 days in studies, could account for significant differences of effectiveness and adverse effects in the individual patient. (Information derived from AHFS Drug Information, American Society of Health-System Pharmacists, Bethesda, Maryland).

Common side effects of tamoxifen with long-term use include decreased platelet and white blood cell counts (thrombocytopenia and leukopenia), estrogen and progesterone imbalances with menopausal-like symptoms, reduced liver function with high triglycerides, transaminase enzymes, cholesterols, and other metabolic imbalances, such as high BUN (blood urea nitrogen, the endproduct of protein catabolism), endocrine effects of increased circulating thyroid hormone T4, increased serum calcium and deposition into tissues, and musculoskeletal pain, especially bone pain. These effects increase the risk of blood clots, strokes, cataracts, and chronic infections. In addition, headache, nausea, indigestion, diarrhea, constipation, weight loss, weight gain, fluid retention, skin changes, vaginal bleeding, irregular menstruation, amenorrhea, and irregular menstrual bleeding, are all commonly seen. The most significant side effect, though, is a double to quadrupling of the risk for uterine and ovarian cancers. There is more than a doubling of the risk of uterine sarcoma and endometrial cancers, with a higher chance of acquiring a life-threatening cancer. In addition, past studies (Williams et al, 1993; Styles et al, 1994) have shown significantly increased incidence of liver and lymphatic cancers from oral intake with study animals. More recent studies cite a high risk of developing hormone receptor negative cancer in the opposite breast with long term use (Cancer Research 2009; 69; 6865-70, Li Cl et al). Estrogen receptor negative cancer that is also HER2 negative is considered the most aggressive, and most difficult to treat effectively. The risk of blood clots attributed to long term tamoxifen use is similar to that from taking hormone replacement therapy. An extensive Danish study of over 16,000 patients found that the incidence of deep vein thrombosis and pulmonary emobolism with tamoxifen use for five years was 1.2 in every 100 women, with most of the incidence within the first 2 years of taking the drug. Of course, these thrombi and emboli are responsible for a large percentage of strokes and heart attacks.

Extensive long-term study of Tamoxifen side effects and risk include the STAR (Study of Tamoxiphen and Raloxiphene) trial, which follows over 19,000 women. This study found that there was a 45 percent incidence of hot flashes with Tamoxifen use, and over 85 significant side effects that affected quality of life. Women that took tamoxifen reported a high incidence of leg cramps, bladder problems, gynecological problems, hot flashes, night sweats, and symptoms related to blood pressure. The STAR trial points to a need for effective adjunct Complementary and Integrative Medicine to provide safe and effective therapies to counter these side effects and increase quality of life for a majority of the patients taking these medications long term. A number of small studies have consistently shown significant relief of these side effects with acupuncture and herbal/nutrient medicine. While reports that Dang gui and the most common Dang gui formula, Si Wu Tang, prescribed for common blood deficiency, not cancer therapy, may inhibit the estrogen receptor antagonism of Tamoxifen has been widely reported, intended to discourage all use of Traditional Chinese Herbal Medicine in adjunct cancer therapy, there are more and more women utilizing acupuncture stimulation to alleviate these adverse effects. For instance, in 2013, at the Catholic University of Daegu, South Korea, a small randomized controlled clinical human study of a 12 treatment 4 week course of acupuncture to alleviate vasomotor symptoms of hot flush and sweat for breast cancer patients receiving Tamoxifen was conducted, and these symptoms were reduced 70-95 percent in all patients, with sustained relief lasting for the 4-week follow-up after treatment termination (PMID: 23383974). While there is a significant lack of funding for such studies, and consequently the published studies are small, they consistently show that standard acupuncture stimulation relieves these symptoms very effectively, often better than hormonal therapy. The problem with comparison to placebo acupuncture, a significant hurdle for all placebo-controlled trials of manual therapies, as creating a placebo for sticking a patient with a needle, that is blinded to the physician performing this act, is obviously very difficult. Consequently, other viable true acupuncture stimulations are usually chosen as this so-called placebo, and the effects of the studied needle stimulation compared to the other so-called placebo needle stick, is of course not great. The effects of both this so-called true and so-called placebo or sham needling is always significant, though. The headline concerning these manipulated trials state simply that while acupuncture appears to work, that it does not outperform placebo, and thus no evidence exists of efficacy. We must leave it to the reader to judge this type of analysis.

Many treating oncologists still discourage the use of adjunct herbal medicine in the treatment of hormonal or gynecological cancers, such as breast, endometrial, ovarian and cervical cancers. Often, this advice to avoid herbal medicine centers around oversimplified and unsupported anecdotal evidence of contraindication with anticancer pharmaceuticals. While most of this anecdotal evidence has been proven false, it is still an effective means to stimulate fear and avoidance of professional Complementary and Integrative Medicine (CIM).

The single most cited anecdotal warnings concerns the popular Chinese herbal medicine Dang Gui, which has long been used as a gentle tonic for blood quality and used in formulas to help correct gynecological dysfunction. Dang Gui has also been extensively studied and used in Asia as an anticancer herb. Because of its use in gynecological medicine, the herb has been cited as a potential antagonist to Tamoxifen, an aromatase inhibitor widely prescribed to prevent estrogen receptor positive breast cancers. Few studies have been conducted to actually provide proof that Dang Gui could counteract the effects of Tamoxifen, though, or present any adverse effects in cancer care. In 2014, a large retrospective study of such contraindication for Dang Gui was conducted by the National Yang-Ming University School of Medicine and Institute of Traditional Medicine, in Taipei, Taiwan. All patients in Taiwan treated with an herbal formula containing Dang Gui and receiving Tamoxifen for a diagnosis of breast cancer were studied and compared to those patients receiving only Tamoxifen and no Dang Gui containing herbal formula, and 31,970 cancer survivors were studied over a period of time from 1998 to 2008. The results showed that almost half of these patients had used an herbal formula that included Dang Gui, and the study showed that these patients taking Chinese herbal medicine with Dang Gui had a significantly decreased risk of subsequent endometrial cancer in the long term, which is a significant proven risk in taking Tamoxifen to treat breast cancer (PMID: 15485843). There was no evidence in this very large cohort study that use of Dang Gui had resulted in increased recurrence of breast cancer or shortened survival time. Hopefully, this large retrospective study puts to rest the ubiquitous advice that the breast cancer patient avoid all professional Chinese herbal medicine, and that the benign herb Dang Gui is contraindicated with Tamoxifen. Such advice is clearly intended to discourage CIM and has no basis in fact, and in fact has potentially hurt the chances of breast cancer survivors to avoid subsequent gynecological cancers after receiving standard treatment for breast cancer.

Pathophysiology of estrogen receptor mediation of estrogen stimulation of cancer growth

Invasive breast cancers appear to evolve over long periods of time from pre-malignant breast lesions, which appear to evolve from normal epithelial cells in the ends of duct lobular tissue linings. Histological studies show that nearly all of the terminal duct lobular tissues in normal adult women contain ER-positive cells. On average, only about 30 percent of these cells are ER-positive at one point in time. Cells undergoing mitosis, or cell division, are almost always ER-negative, though. One key to prevention of estrogen positive tumors is improved regeneration of breast cells, with apoptosis of old cells encouraged, and anti-apoptotic mechanisms discouraged. Many researchers, conducting studies to justify more widespread use of so-called estrogen receptor inhibitors, emphasize theories that these estrogen receptors, found in more abundance on older cells, must be responsible for mediation of estrogen stimulation of cancerous cell division. Other researchers have focused on the normal modulation of the two well known types of estrogen receptors, commonly called alpha and beta. Estrogen receptor beta seems to exert regulatory and pro-apoptotic effects on estrogen receptor alpha. Both of these lines of research are useful in producing more comprehensive treatment protocols to prevent breast cancer. The balance of estrogen receptor types is the key to prevention, but is rarely mentioned in standard oncology.

Early research on estrogen receptors in breast cancer cell lines largely ignored the role of estrogen receptor beta as a modulatory factor controlling normal regulation of cell apoptosis. Many more alpha estrogen receptors were found in cancer cell lines than beta. Like the alpha and beta testosterone, or DHT (testosterone) sensitive, receptors in prostate cancer cells, these two types of receptors are largely responsible for pro-apoptotic and anti-apoptotic cellular mechanisms that destroy aging cells before they acquire enough mutations to generate an active cancer growth. In breast cancer, stimulation of estrogen receptor beta, and stimulation of increase in estrogen receptor beta numbers, combined with inhibition of estrogen receptor alpha expression, will result in recreation of a healthy cellular environment and regulation of apoptotic mechanisms that protect the patient from recurrence of cancer growth stimulated by excess estrogen receptor alpha. The goal of overall holistic therapy is to recreate a normal physiological environment that insures a greater success in preventing cancer cell growth. Cancer is largely a metabolic disease that depends on the whole tissue environment and hormone balance, and continued attempts to define it otherwise are misguided. Both prevention of cancers, and prevention of recurrence, needs to deal with this fact and integrate a more holistic approach. Adjunct cancer care and preventive medicine, integrating CIM/TCM, or the care of the knowledgeable Licensed Acupuncturist and herbalist, into the whole choice of treatment and prevention protocol, can achieve this metabolic homeostasis and present no adverse health effects or risks.

Adjunct therapies that modulate estrogen receptors

Many women are interested in SERM protocol that is not synthetic, but derived from plant sources, such as estriol, as well as the I3C extracts from cruciferous vegetables and herbs, or the active metabolite DIM, and plant lignans that convert well to enterolactone, etc. An individualized and comprehensive treatment protocol insures greater success, and professional guidance is very important to avoid unwanted effects, as well as utilize therapeutic products of quality, and ones that are specific to your cancer. The key therapeutic products are explained below. You do need to consult with a knowledgeable Complementary care physician, such as a Licensed Acupuncturist and herbalist with this specialty, to insure that you follow a safe protocol.

Besides the use of bioidentical hormones, DIM, and NuLignan, there is a growing body of research uncovering selective estrogen receptor modulation activity in various Chinese herbs. Recent research at the University of California San Francisco (UCSF), in collaboration with Peking University in Beijing, China, has confirmed that herbal formulas may be very effective in modulating estrogen receptors that are linked to breast cancer mutations. Initial findings showed that modulation of the estrogen receptors one and two (ER-alpha and beta) by specific herbal formulas was more effective than the inhibition of estrogen receptor one, or ER-alpha, with tamoxifen. Since the problem with estrogen stimulated tumors lies in the conversion of hormones in local tissues to estradiol, which is regulated by aromatase enzymes and other metabolic and hormonal controls, the dysfunction in the body is a little complicated. Allopathic medicine seeks to block just one step in the cancer causing process, but Complementary and Integrative Medicine (CIM/TCM) takes a holistic approach and utilizes scientific findings to restore healthy function throughout the entire sequence of steps. A knowledgeable Licensed Acupuncturist can explain this metabolic process and what needs to be accomplished.

Standard medicine has developed novel drugs to treat estrogen receptors as the data on aromatase inhibitors accumulates and long-term Tamoxifen use is unpopular due to adverse effects. The CDKs4 antagonist (cyclin-dependent kinase) palbociclib (Ibrance) was fast-tracked in 2015 due to this need, but only for postmenopausal women with estrogen receptor positive breast cancer metastasis. Concurrent research by pharmaceuticals has explored novel chemicals in herbs that are shown to also inhibit the CDKs. For instance, in 2012, research at the Indian Institute of Integrative Medicine, in Jammu, India, reported that flavoalkaloids in Dysoxylum binectariferum, related closely to Dysoxylum malabaricum, contained 2 chemicals that the drug company Sanofi-Aventis used to synthesize analogs called flavopirido and and Piramal, that have passed stage 2 human clinical trials to treat metastatic cancers (PMID: 22512551). Research in the past has isolated herbal chemicals from such herbs as Vitex negundo that are inhibitors of CDKs, and a number of common Chinese herbs and formulas studied and used to treat cancer in adjunct care have demonstrated efficacy as CDK inhibitors, including Indirubin from the formula Dang gui Long hui Wan (Nature Cell Biology 1999 1, 60-67). The potential for indigoids, active chemicals in the anti-cancer herbs of the Indigo species, Qing dai et al, to treat cancers dependent on the cyclin kinases shows much potential.

An herbal formula proven to modulate estrogen receptors

In 2008, an historic agreement between California and China to share medical research in Complementary Medicine was accomplished with the help of Senator Diane Feinstein and Governor Arnold Swarzenegger. UCSF was a recipient of this collaborative scientific study and published a paper summarizing one of its first studies, a formula of Chinese herbs used to treat osteoporosis and breast cancer. Below is some of the findings of this research.

"Recent evidence suggests that selective activation of the estrogen receptor (ER)-beta subtype inhibits breast cancer cell proliferation. To establish whether ERbeta-selective ligands represent a viable approach to improve hormone therapy, we investigated whether the estrogenic activities present in an herbal extract, MF101, used to treat hot flashes, are ERbeta selective. MF101 promoted ERbeta, but not ERalpha activation of an estrogen response element upstream of the luciferase reporter gene. MF101 also selectively regulates transcription of endogenous genes through ERbeta. The ERbeta selectivity was not due to differential binding because MF101 binds equally to ERalpha and ERbeta. Fluorescence resonance energy transfer and protease digestion studies showed that MF101 produces a different conformation in ERalpha from ERbeta when compared with the conformations produced by estradiol. The specific conformational change induced by MF101 allows ERbeta to bind to an estrogen response element and recruit coregulatory proteins that are required for gene activation. MF101 did not activate the ER-regulated xenograft model. Our results demonstrate that herbal ERß-selective estrogens may be a safer alternative for hormone therapy than estrogens that nonselectively activate both ER subtypes."

The findings of this research demonstrate that the Chinese herbal formula studied exerts estrogen receptor modulation in a manner that improves normal homeostatic mechanisms of estrogen receptor regulation. The effects were quite significant, as we shall see from study findings, but the way that the herbal formula exerted estrogen receptor modulation promoted the body's natural regulatory manner of controlling excess of estrogen receptor alpha, which drives breast cancer stimulation via anti-apoptotic mechanisms, by appropriate stimulation of estrogen receptor beta, and a cascade of coregulatory proteins that insured a balanced alpha/beta anti/pro-apoptotic regulation. The end result is that normal cell death was properly regulated and cancer was prevented. Also, unlike tamoxiphen or Evista, there was no unwanted estrogen effects from the herbs.

"Estrogens possess antiinflammatory properties by repressing the expression of inflammatory genes. The repression of the TNF or IL-6 genes might be an important mechanism by which estrogens prevent inflammatory conditions, such as osteoporosis. MF101 repressed the TNF activation of the TNF and IL-6 genes in the U2OS-ERbeta cells (a particular cell line), but not in the U2OS-ERalpha cells. These studies demonstrate that MF101 selectively triggers ERbeta-mediated transcriptional pathways. MF101 is an ERbeta-selective agonist in human cervical (HeLa), breast (MDA-MB-453), and endometrial (Ishikawa) cell lines. We investigated whether MF101 has growth- promoting properties in MCF-7 breast cancer cells, which express only ERalpha. Unlike estradiol, MF101 did not stimulate cell proliferation of MCF-7 cells. These data demonstrate that MF101 does not promote proliferation of MCF-7 cells or uterine growth and are consistent with the hypothesis that ER mediates the proliferative effects of estradiol."

"Phase 1 studies indicated that MF101 was well tolerated and provided a preliminary indication that hot flashes were reduced (data not shown). However, these uncontrolled studies await confirmation in a larger clinical trial. We demonstrated that despite containing many different herbs, the MF101 extract is ERß selective. Examining the effects of the crude MF101 on estrogenic activity advantages. First, it is important to study MF101 because it is currently being studied in clinical trials as a drug under an FDA investigational new drug. Second, MF101 might be more effective at preventing hot flashes and be a better drug than the individual compounds because of synergy among many compounds. Third, MF101 provides a starting point to isolate pure ERß-selective estrogens. Our studies have found that MF101 contains at least six different ERß-selectivecompounds by thin-layer chromatography, HPLC, and liquid chromatography/mass spectrometry (data not shown). Our results suggest thatMF101 or pure ERß-selective agonists from MF101 might be a safer approach to manage menopausal symptoms because, unlike estrogens used currently in HT, they do not cause the ER-mediated breast cancer cell proliferation or uterine growth. Our study also provides a scientific foundation to explore whether MF101 and other ERß-selective agonists from herbs prevent menopausal symptoms, breast cancer, and inflammatory diseases associated with menopause, such as osteoporosis and cardiovascular disease."

The herbal formula studied is a fairly standard formula in TCM. Scutellaria barbata (Ban zhi lian) 30g, was the principle herb, and has a number of proven anti-cancer chemicals of significance in it. Sophora root (shan dou gen) 15g, Anamarrhena (zhi mu) 12g (6g infused in alcohol for 72h), Glycine (black soy bean) 12g, Glycyrrhiza (gan cao) 8g, Rhei rhizome (da huang) 8g, Tritici (fu xiao mai) 15 g, Astragalus 12g, Rehmania (sheng di) 12g, Ligustri lucidi (nu zhen zi) 15g, Zyziphi (suan zao ren) 10g, Nelumbinis (lian zi xin) 10g, Poria (fu ling) 10g, Moutan (mu dan pi) 8g, Corni (shan zhu yu) 10g, Achyranthis (huai niu xi) 10g, Concho ostrea (mu li) 12g, Asparagi (tian men dong) 12g, Pueraria (ge gen) 10g, Atractylodis macrocephalia (bai zhu) 10g, Epimedi (yin yang huo) 8g. Since there were many herbs in the formula, there were many chemical activities that were anticancer and antitumor, as well as a number of significant chemical activities modulating hormonal production, blood production, and immune function, all of which relate to breast cancer prevention. This study demonstrates that herbal formulas in TCM are being studied as effective therapies, undergoing FDA human trials, and will be proven safe and effective in integrative standard therapy.

Endocrinology, doi:10.1210/en.2006-0803 Endocrinology Vol. 148, No. 2 538-547 Copyright © 2007 by The Endocrine Society Selective Activation of Estrogen Receptor-ß Transcriptional Pathways by an Herbal Extract. Aleksandra Cvoro, Sreenivasan Paruthiyil, Jeremy O. Jones, Christina Tzagarakis-Foster, Nicola J. Clegg, Deirdre Tatomer, Roanna T. Medina, Mary Tagliaferri, Fred Schaufele, Thomas S. Scanlan, Marc I. Diamond, Isaac Cohen and Dale C. Leitman. Departments of Obstetrics, Gynecology, and Reproductive Sciences and Center for Reproductive Sciences (A.C., S.P., C.T.-F., D.T., R.T.M., D.C.L.), and Departments of Cellular and Molecular Pharmacology (A.C., S.P., J.O.J., C.T.-F., N.J.C., D.T., R.T.M., T.S.S., M.I.D., D.C.L.), Neurology (J.O.J., M.I.D.), Pharmaceutical Chemistry (N.J.C., T.S.S.), and Medicine (F.S.), University of California, San Francisco, San Francisco, California 94143; and Bionovo Inc. (I.C., M.T.), Emeryville, California 94608

Adjunct therapies that potentiate tamoxifen anticancer effects

A study at Tulane University School of Medicine (Yatrik M. Shah, Brian G. Rowan et al) found that the organic selenium compound methyseleninic acid (MSA) can potentiate growth inhibition of 4-hydroxytamoxifen in tamoxifen-sensitive MCF-7 and T47D breast cancer cell lines. Also, in tamoxifen-resistant breast cancer cell lines MCF-7-LCC2 and MCF7-H2delta16, as well as endometrial and lymphatic cancer cell lines stimulated by tamoxifen, this selenium was found to produce inhibition of cancer cell growth as well when combined with tamoxifen. The effects of selenium included decreases in estrogen receptor alpha mRNA and protein without an effect on estrogen receptor beta, showing a positive modulatory effect. This nutritional medicine can be obtained in the form of methylselenocysteine (VRP Products).

Tamoxifen is a caspase-dependent drug. Caspases are a group of enzymes derived from the amino acid cysteine. Cysteine and methionine appear to be tightly controlled amino acids via circulating homocysteine bioavailability. High circulating homocysteine levels have been revealed as a marker for a variety of diseases, and probably represent a dysfunction in the ability of the body to convert homocysteine to cysteine and methionine as needed, but also may be linked to dysfunctions in digestive enzyme metabolism, with poor betaine conversion, and to dysfunction in the glutathione metabolism. Even though this metabolic cycle and the regulation of the metabolism is complex and poorly understood, it is evident that problems with the homocysteine transamination are linked to many alarming disease processes. Caspase deficiency may be a significant aspect to this quantum metabolic imbalance, and various nutritional medicines may enhance the effectiveness of Tamoxifen significantly.

Caspases are important to the apoptotic mechanisms that trigger cell death when our cells become vulnerable to excess mutation and cancer. Activated caspases control rates of destruction of essential cellular proteins, and triggers to this caspase activation are both intrinsic and extrinsic to the cell. This apoptotic mechanism acts in a similar way to the immune complement cascade, with a variety of enzymes activated in an expanding cascade to carry out apoptosis. Unless a balanced environment is maintained apoptotic mechanisms that protect us from cancer are difficult to effect. Even an allopathic drug like tamoxifen depends upon this controlled environment. For this reason, holistic approaches to improve this environment, and increase the function of the caspase cascade may be very important to the ultimate effects of tamoxifen in prevention of the return of cancer. Certainly, supplementation with N-acetylcysteine, SamE or zinc methionine, methylselenocysteine, Vitamins B12, B9 (folic acid, or the active metabolite 5MTHF), B6 (or active P5P), and betaine, could have significant benefit for the cysteine bioavailability and function of the caspase cascade.

While many oncologists continue to repeat the mantra-like warnings against utilization of Complementary and Integrative Medicine (CIM/TCM) in the form of any herbal medicine while taking Tamoxifen or Herceptin to inhibit the return of breast cancer after lumpectomy and radiation, there is very little evidence presented to support this denial of adjunct therapy, and a lack of specificity that is astounding. A number of facts must be considered in this consideration. First, there are a large number of herbal medicines, and a blanket warning against all herbal medicines in adjunct cancer care is obviously not scientific. Secondly, no human clinical trials have shown a significant effect of any Chinese herbs to inhibit the effects of Tamoxifen or Herceptin, or chemotherapeutic agents, only small studies on laboratory animals with a few tonic herbs or tonic herbal formulas used in large dosage, and often applied directly to the cancer cells. Thirdly, in Chinese Herbal Medicine, there is a long-standing protocol to not use these tonic herbal formulas in cancer care except in short courses when obviously needed, with a protocol utilizing herbs that exert a clearing effect on inflammation and abnormal cell growth emphasized. Fourthly, Chinese Herbal Medicine is used professionally in short courses to achieve goals, and individualized for each patient, not taken continuously for the 5 years of Tamoxifen or Herceptin use. Fifthly, there are a number of treatment protocols besides these tonic herbs and formulas that are utilized in the holistic treatment, none of which have any proof of contraindication with the standard pharmaceutical strategies. 

The denial of valuable adjunct Complementary Medicine by a blanket mantra of warnings of adverse effects from herbal medicine that is non-specific and often repeated to scare patients is not acceptable. It has been somewhat effective, though. Patients need to keep in mind that the history of discouragement of Complementary Medicine in standard practice is motivated by supposed competition and economic concerns, and is not likely to change soon. Integration of adjunct therapies is a decision that the patient needs to make, and hopefully, detailed and supported information such as found in articles such as this will help patients take the needed proactive approach to their care. A growing body of scientific study, including large human clinical trials, or RCTs, are demonstrating that when CIM/TCM is integrated into standard care that there are almost no adverse effects seen, but numerous positive effects, with specific CIM/TCM therapies actually increasing the effectiveness of standard therapies, able to provide a decrease in adverse effects by decreased dose or duration, or simply relieving these adverse effects, providing a larger array of anti-cancer mechanisms, and improving quality of life considerably.

A growing body of cancer experts around the world have been countering the widespread, but unsubstantiated, warnings about combining herbal therapy with pharmaceutical drugs by conducting scientific study of herbal medicines to find specific therapies that cannot be questioned in this regard. For instance, a number of Chinese herbs are shown to exert their anti-cancer effects in other metabolic pathways than the chemical aromatase inhibitors or herceptin growth factor inhibition used in pharmaceutical therapy. As an example, an alcohol extract of the Chinese herb motherwort (Yi mu cao) was found to exert its anti-cancer effects via cytotoxic and cell cycle arrest pathways that are independent of estrogen receptors (PMID: 19330917). A number of Chinese herbs with anti-inflammatory and anti-cancer effects, such as Coptidis (Huang lian), have been found to exert their anti-cancer effects by encouraging interferon and TNF-alpha (tumor necrosis factor) in human breast cancer cells, independent of the pathways of estrogen-receptor modulation. Much scientific study and traditional observation of effects guide professional herbal therapy, and intelligent use of these medicines is safe and dependable. To both potentiate the effects of standard drug regimens such as Tamoxifen and Herceptin, and alleviate the risks and side effects, scientific proof has offered us dependable protocols that can be intelligently integrated into the therapy. This integration of safe and proven therapeutic tools that expand the array of mechanisms that inhibit cancer growth is sensible, inexpensive and safe. These are just a couple of the proven herbal effects that could expand the protocol with use of CIM/TCM, and some of these scientific studies are presented in the section entitled Additional Information at the end of this article, with links to the studies.

Aromatase, I3C, DIM, lignans, and regulation of hormone receptors

In the study of estrogen receptor activation and modulation much research has uncovered a metabolic cascade of chemicals that are responsible for hormonal stimulation of cancerous growth. Circulating estrogens may not be the most important drivers of estrogen receptor positive cancer cells. In fact, reduced circulating estrogens, in post-menopausal women, may be the driving factor for excess creation of estrogen receptors, and locally produced estradiol (E2) may be responsible for most estrogen receptor driven cancers. Aromatase is a protein enzyme that, when overexpressed, converts C19 steroids to estradiol. Aromatase activity is stimulated by a number of chemicals, including prostaglandin E2 (PGE2), and exces cyclooxygenase, or COX2, may promote excess PGE2. Certainly, for this reason, a diet with much less red meat and acid creating foods, and more fresh vegetables and whole grains, which results in less unhealthy prostaglandins and fatty acids, has been consistently shown to decrease incidence and recurrence of breast cancers. This same aromatase stimulation of conversion of other steroid hormones to estradiol locally has been found to drive endometrial cancers, which occur more readily when tamoxifen is taken long term.

Endocrine disorders are associated with inappropriately high aromatase expression. Aromatase production has been found to be highest in tissues surrounding cancer cells. There appears to be a feed-back loop that stimulates excess aromatase activity, or perhaps fails to modulate it in a healthy manner. All of these findings point to the need to restore a normal physiological environment in order to successfully prevent, or modulate, excess aromatase production. Hormonal balance, decrease in PGE2, immune health, and other factors, must be examined to effectively inhibit the imbalances that drive local aromatase production around cancer cells.

Local estradiol production, via excess local aromatase production, appears to be the important driving force in breast cancer. Systemic and circulating estradiol may have much less significance, especially when we see estrogen driven breast cancers in patients with various levels, and increased breast cancer incidence in patients with perimenopausal to postmenopausal hormone deficiencies. Most estradiol in the body is either produced from the ovaries in reproductive age women or by conversion of androstenedione to estrone and then to estradiol in peripheral tissues. Even breast cancer cell growth attributed to HER2 (human epidermal growth factor) is linked to the estrogen receptor imbalance acquired by poor regulation of local estrogen production and conversion. Cell growth is regulated by hormonal receptors on the surface and within the cells that control the rate of apoptosis, or normal programmed cell death and replacement. Hormonal and metabolic imbalances create excess surface estrogen receptors, which drives anti-apoptosis. A number of chemicals besides the local estradiol have been found that stimulate these receptors, and when the receptor imbalance occurs, inflammatory mediators such as COX2 (cyclooxygenase enzyme), epithelial growth factors, insulin-like growth factors, and other chemicals, may stimulate the cancer mechanisms. Herbal chemicals, such as resveratrol, from the Chinese herb Hu zhang, have been found to inhibit these growth factors.

Synthetic aromatase inhibitors decrease aromatase throughout the body drastically, and effectively eliminate systemic estradiol production. This has been shown to successfully treat estrogen receptor breast cancers, but not endometrial and ovarian cancers, and in fact, may have negative consequences. These findings have introduced many doubts and questions concerning our understanding of aromatase inhibition. Research has found that aromatase plays an important role in the brain, especially in hypothalamic function, and strong chemical inhibition may have a variety of negative effects in neuroendocrine function over time. In response to the side effects and negative consequences of long term prescription of aromatase inhibitors, much research has revealed effective aromatase inhibitors derived from foods and herbs that may be used, and in fact, have a modulatory effect that maintains physiologically normal aromatase levels. DIM and NuLignan are two such products. Promotion of aromatase homeostasis would seem to be the safe and effective course compared to synthetic aromatase inhibition. Of course, if a particular patient needs this more intensive drug therapy to survive, this is the course to take, but always with the aid of adjunct therapies to enhance effectiveness and counter the ill effects.

Indole-3-carbinol (I3C), and the active metabolite DIM (diindolemethane), are a derived from a nutrient found in many vegetables, especially cruciferous vegetables containing glucobrassicin. Digestion and assimilation of these nutrients produces DIM, which is used by the body to modulate aromatase activity. Since I3C needs to be transformed in the gut to DIM, DIM is the preferred supplement to insure effect. Many studies have confirmed that I3C significantly inhibits aromatase and acts as an anticancer agent. Given to study animals along with a carcinogen, oral I3C was found to inhibit estrogen driven cancer cells in the breast, uterus, stomach, colon, lung, and liver. Further studies, designed to discount I3C use, gave unnaturally high dosage to animals and found that extreme dosage could promote cancers in some animals (fish were used, which is suspect, since fish are not as close to human metabolism as rats). Further studies (Carcinogenesis 2006, Yu X et al, Oregon University) found that inclusion of I3C in the dietary supplementation with pregnant subjects provided chemoprotection against a common carcinogenic pollutant that also causes birth defects, dibenzopyrene aromatic hydrocarbon, and was safe for the mother and fetus. A study by Wake Forest University in 2009 also found that glutathione is protective against this strong carcinogen. Glutathione metabolism may be enhanced by supplementation with various Chinese herbs and even nutrient medicines, including L-cysteine, N-acetyl cysteine, P5P, zinc monomethionine, betaine, active folates, and Vitamin B12. The combination of these glutathione modulating medicines and DIM from I3C provides a potent protection against cancers, especially estrogen driven breast, ovarian and uterine cancers.

I3C has thus passed numerous hurdles in the complete sequence of studies confirming efficacy in aromatase inhibition. DIM, the active metabolite, and not dependent on the particular gut acidic environment of the individual patient, is further back in this sequence, but already has demonstated efficacy. A recent 2009 study by Carmel Medical Center in Haifa, Israel, (PMID:20010430, European Journal of Cancer Prevention), found that DIM was not toxic and has an in-vivo preventive effect against development of prostate cancer in a mouse model. A 2009 study at Wayne State University School of Medicine in Detroit, Michigan (PMID: 19693769) found that DIM down-regulates an intermediate step in aromatase conversion and stimulatio of estrogen receptors, as well as an estrogen independent cancer stimulator, the urokinase plasminogen activator receptor, which is seen overexpressed in aggressive breast cancers. The study also found that DIM, in the abscence of these receptors, directly inhibited growth factors VEGF and MMP-9, that are implicated in estrogen receptor negative tumors. Not only has DIM now been demonstrated to inhibit aromatase conversion of local hormones to estradiol and estradiol metabolites, but also to protect in a variety of ways by inhibition of various growth factors that overexpress and drive breast cancers, and it is proven in vivo to do this in a modulatory manner. Once again, Mother Nature and eons of evolution have created an apparently superior chemical that is already integrated into our biology. The numerous positive studies emerging on DIM show that it has a significant role to play as an integrative therapy to enhance cancer prevention and recurrence, whether the patient decides to take tamoxifen or a synthetic aromatase inhibitor or not.

As far back as 1997, researchers at the Strang Cancer Research laboratory at Rockefeller University discovered that DIM changes so-called strong estradiol to weak estradiol, altering metabolites of estradiol that drive cancer. This inhibits cancer cell growth and stimulates apoptosis. Subsequent study at the University of California at Berkeley found that DIM inhibits some human breast cancer cells from growing by as much as 90 percent in cultures. Other studies have shown that DIM promotes higher levels of estriol, an estrogen that does not drive cancer, and also promotes increases in a biologically inactive metabolite of estrone, 2-hydroxyestyrone. These findings show that chemicals like DIM, that evolved in the body over great periods of time, exert beneficial modulatory effects in a number of ways. The benefits of DIM are great, and the only question is bioavailability. Quality products are now concerned with absorption enhancement, and thus, in the unregulated supplement industry, it is sensible to obtain the DIM from a professional that purchases the highest quality researched product.

While prescription of DIM nutrient supplement is still not touted in standard medicine, the research supporting its use in adjunct cancer care is great, and the proven benefits, seen in a number of links to research articles and studies below in Additional Information, are many. For instance, besides that proof that DIM acts as a potent aromatase inhibitor and hormonal modulator, promoting healthy estriol and inhibiting growth factors that drive cancer, research in recent years has shown that DIM provides valuable effects in immune modulation, and protects against toxicity to the heart tissues with use of chemotherapy agents (PMID: 23376355). DIM has also been found to inhibit superantigen responses promoting chronic inflammation, promote cancer protective effects such as prostate apoptosis factor (Par-4), applicable to both prostate cancers and metastatic liver cancer, and promote healthy BRCA expressions that exert protective antioxidant and other effects in cells to prevent cancers. Once again, it would be advisable to obtain the DIM supplement from a professional supplier to insure effectiveness, such as Vitamin Research Products.

Lignans are beneficial chemicals that are also commonly found in food and herbs. Lignans in flax seed helped propel this ancient grain seed to popularity, along with healthy essential fatty acids. The common thread between these two classes of super nutrients are that they are fat based, and the common diet in the United States was slowly depleted of healthy fats by commercial food production and marketing. Hormones are generally fat based, and plants contain many beneficial hormones that are bioidentical to animal hormones, because hormones are simple molecules with much potential to stimulate lipoprotein receptors, which are found in both animals and plants. Lignans are one of the major classes of phytoestrogens, which not only help our bodies with hormone bioavailability and regulation, but also serve as potent antioxidants. This information leads us to the conclusion that specific lignans must be effective in estrogen receptor modulation and cancer prevention.

NuLignan is a product based on current European research into the use of specific plant lignans in hormonal therapy. It is a patented extract of 7-hydroxymataireinol extracted from Norway Spruce Trees (Picea abies). This lignan extract has been found to promote the body's own production of enterolactone, which protects the body against tumor formation. Enterolactone reduces excess circulating estrogen, blocks excess aromatase, binds to estrogen receptors, and selectively blocks estrogen activity in specific peripheral tissues, inhibiting cell growth and the signaling cascade that drives estrogen receptor positive cancer cells. Like tamoxifen, enterolactone may also mimic the effects of estrogens, or block estrogen receptors. Unlike tamoxifen, this chemical that evolved in our bodies also evolved modulatory effects that work with other chemicals in our bodies in a quantum, or holistic, manner. If such chemicals evolved in our bodies with effects that promoted cancers or had deliterious effects, natural selection would eliminate those animals with harmful versions of such chemicals.

How are lignan effects beneficial in our bodies? Plant lignans are composed of aromatic carbon benzene rings called phenols. Aromatic molecules have free electrons and are able to stimulate physiological activity more freely. The lignan aromatic rings are composed of monolignols, and the most potent of these lignols is coniferyl alcohol, of which the lignan and lignins in Norway Spruce are almost completely composed. Because these monolignols are produced in plant cells as glucosides, they are somewhat water soluble, alkaline, and transport to the inner part of our cells easily. The chemical reactions that create lignans is catalyzed by oxidative enzymes and proteins that dictate steriochemistry, as occurs with steroid hormones. This makes lignans inherently potent as modulators of oxidative reactions and steroid isomers in our bodies. They are also of a class of medicinal herbal chemicals called terpenes, which are highly reactive. Essential oils are composed of terpenes, and even the aromatic benzene rings of essential oils that escape into the air and are taken in by our breath have potent medicinal activities. Brassica vegetables, from which research derived I3C and DIM, also contain potent lignans. Of all the lignans studied, pinoresinol and matairesinol are the most beneficial, and these are found in abundance in sesame seeds, rye bran, and wheat bran, as well as spruce resin. Of course these most beneficial lignans are provided in concentrated dosage in NuLignan. These lignans create beneficial enterolactones. Entero- refers to chemicals created in the intestines, and lactones are chemicals that work inside molecules (intramolecular), and are carbon based oxides, meaning that they are useful as oxidizing chemicals that clear cells of harmful debris and prevent degeneration and cancerous mutation. To make the most use of NuLignan, it would be wise to promote health in the intestines as well as to provide antioxidants concurrent with use. A prescription of herbal formulas to clear unhealthy microbes and restore gastrointestinal function, if needed for the individual patient, then a quality probiotic and perhaps bovine colostrum, followed by NuLignan, and then effective antioxidants, would insure the most success with therapy.

Research into these matairesinol lignans has uncovered much evidence of medicinal effects in recent years. Some of these studies are accessible below in additional information. 7-hydroxymatairesinol has been found to have potent chemopreventive effects, immunomodulatory activity, antioxidant properties, and mild pro-estrogenic effects (stimulating increased estriol), as well as selective estrogen receptor modulation, and inibition of aromatase. Our bodies obviously have evolved to utilize these chemicals in many ways to prevent cancer. The extract NuLignan did not show estrogenic or antiestrogenic activity at either estrogen receptor alpha or beta in vitro, or antiandrogenic responses that would drive prostate cancers, but did decrease the number of growing breast cancer tumors, and regressed and stabilized tumors in animal studies in 2000 at the University of Turku, Finland. Conversion of NuLignan to enterolactone was almost 100 percent in animal studies. The course of therapy was 51 days. The anticancer effects were specific to well-differentiated adenocarcinoma, which was reduced significantly in animal studies. Combining NuLignan with other anticancer herbs which would affect estrogen receptor negative and undifferentiated tumors would be advisable in a comprehensive package of care.

As time progresses, we see no research with negative findings on NuLignan, and a series of progressive studies that confirm that NuLignan blocks estrogen receptors by substituting as a stereoisomer, acts in a modulatory manner, and has a reduced effect in the presence of tamoxifen. Studies have also revealed that NuLignan exerts an anti-tumor effect on liver cancer, which may be stimulated by the use of tamoxifen. NuLignan and enterolactone also were found to exert pro-apoptotic effects and tumor suppression of human colon cancer cells both in vitor and in vivo (Anticancer Research.2005 May-June;25(3B):2269-76). All of these findings support the inclusion of NuLignan in a preventative course of integrative therapy for estrogen receptor positive breast cancer patients.

Some of the research on aromatase overexpression has been misleading. One study, examining whether red wine consumption would increase aromatase and local estradiol production, fed wistar laboratory rats only red wine as a fluid for a prolonged time, which significantly raised aromatase and local estradiol in tissues. It was postulated that moderate or minimal red wine consumption was a risk factor. This seems to be a stretch of logic, and does not examine the effects of small amounts of red wine on aromatase production. With the widespread and complex patterns of fraud and misleading study design found by the Senate committee investigations headed by Senator Charles Grassley, all medical professionals need to take a closer look at the details of health studies to arrive at workable clinical treatment protocols, and not rely on study summaries and journal articles, which are often manipulated. It has been too easy to design studies and write papers that are misleading in this regard, and yet this practice is widely accepted in standard medicine for some time. While many intelligent patients realize the degree that industry greed and avarice has distorted the business of medicine, few speak out.

HER2 growth factor receptor and the relationship to hormonally mediated breast cancer

HER-2, or human epidermal growth factor receptor type 2, is a type of hormonal receptor that is overexpressed in a percentage of more aggressive types of hormonally mediated breast cancers. This growth factor receptor is found on the surface of cells that are stimulated to abnormal growth, and is a receptor tyrosine kinase, or protein enzyme receptor that has a high affinity for not only growth factors, but inflammatory cytokines, and hormones. The protein kinase is an enzyme that regulates the rate of transfer of phosphate groups from high-energy molecules that fuel our cells, such as ATP, to other molecules as the ATP is used for cellular energy. The main source of bioelectrical energy for our cells is ATP (adenosine triphosphate), and as the cell uses this energy, the ATP is converted to ADP, losing a phosphate group, and the ADP is then recycled to create more ATP for cell fuel. If there is an imbalance in the cellular environment, this normal process can stimulate excess receptor tyrosine kinase effects, especially if the receptor protein enzyme is mutated by poor expression, inflammatory mechanisms, or excess stimulation by the local hormones, inflammatory cytokines, or growth factors. The key amino acid in the HER-2 is tyrosine, an essential amino acid that is important for many functions in the body. As the HER-2 tyrosine kinase receptor mutates, it can be basically stuck into an "on" position and cause unregulated cell growth.

Standard medicine has responded to the problem of mutated receptor tyrosine kinase, and the continuous growth triggering, by using various chemicals that inhibit the genetic expression of this HER-2. So far, the results have been promising for these drugs, but the benefits may not outway the risks, with the benefits being a few months of survival on average for aggressive breast cancers, but many serious side effects. The most prescribed of these drugs is Herceptin (trastuzumab), manufactured by Genentech. Cancer experts are alarmed at the increase in cardiac dysfunction with Herceptin with long-term use, as well as with the greater than 40 percent of patients who experience significant pain and low energy, or asthenia, as a side effect. FDA Black Box Warnings have been issued for the risks of clinical or subclinical cardiac failure and dysfunction, most of which manifest as chronic congestive heart failure, or dysfunction, with lower extremity swelling and fatigue, which is seen most frequently with concurrent use of an anthracycline-containing chemotherapy agent. In 2011, in response to the concerns of limited effectiveness with the combination of Herceptin plus chemotherapy, two new HER-2 inhibitors were added to the protocol, pertuzumab by Genentech, and everolimus by Novartis. Clinical trials of these drugs found that average survival time was increased by 6 months with the use of an added HER-2 inhibitor. Clinical trials of the combination of everolimus plus Aromasin, a Tamoxifen-like estrogen effect inhibitor, provided women with HER-2 metastatic breast cancer with a survival time of 7.4 months. Everolimus was the first drug that showed efficacy for the drug-resistant tumor cells that frequently occur with hormonal inhibiting anti-cancer therapies. The cost of everolimus is about $7000 per month, though, and the alarming side effects, which include more than a third of patients in clinical trials experiencing significant infections, asthenia, fatigue, constipation and stomatitis with mouth sores, and more than a fourth experiencing peripheral edema, nausea, loss of appetite, diarrhea and skin rash, with black box warnings of immunosuppression and kidney toxicity with concurrent use of cyclosporine antibiotic, have discouraged many patients and doctors from using this drug regimen.

Consequently, many patients and integrative doctors are now wondering how Complementary Medicine may help with HER-2 overexpression and mutation without side effects. A number of scientific studies have produced promising effects from various Chinese herbs (with links to the studies cited below in additional information). For example, researchers at Hanyang University in Seoul, South Korea, in 2011, found that the herb Pharbitis nil, or Qian niu zi, suppressed the proliferation rate of HER-2 overexpression in MCF-7 breast cancer cells, inducing cancer cell death, or apoptosis. Flavonoids in the Chinese herb Ku shen, or Sophora flavescens, were found to inhibit multiple receptor tyrosine kinase activities, as well as key inflammatory cytokines that stimulate HER-2. The Chinese herb Magnolia officianalis (Hou pou) contains an active chemical called honokiol that researchers at Humboldt University of Berlin, Department of Oncology, found could be a valuable adjunct therapy to combine with pharmaceutical drugs in breast cancer with HER-2 overexpression (PMID: 18588872). Nutritional supplements have also been found to be a useful adjunct. Gamma linolenic acid, or GLA, was found to be a useful synergist to HER-2 inhibition with trastuzumab, or Herceptin, by the Evanston Northwestern Healthcare Research Institute, associated with Northwestern University in Chicago, Illinois. Research has also revealed that over 70 percent of breast cancers show genes that are mutated in the phosphatidylinositol 3-kinase pathway related to HER-2. Supplementation with a phosphatidylcholine plus phosphatidylserine combination may reduce these mutations considerably. Certainly, the use of L-tyrosine and various antioxidants could have a positive effect on reduction of these mutations as well. In 2013, experts at the Indiana University School of Medicine, in Indianapolis, Indiana, U.S.A. found that the combination of the omega-3 essential fatty acid docosahexaenoic acid (DHA), found in abundance in krill oil supplement, and Curcumin, an active chemical in the Chinese anticancer herb Curcuma zedoaria, or E zhu, worked synergistically to alter the growth of HR2 and estrogen receptor positive breast cancer cells by modulating the genetic expression and regulating the programmed cell death, or apoptosis, in these cancer cells. To see this study, just click here: . We see that research is confirming more and more specific protocols in CIM/TCM, and that this study is supported by institutions in a number of countries. 

As research continues, we are finding that a larger number of Chinese herbs show potential to suppress the HER-2 (human endothelial growth factor type 2). For instance, in 2015, researchers at the People's Hospital of Henan Province, in China, found that polysaccharides in Scutellaria barbata (Ban zhi lian), perhaps the most studied anticancer herb in TCM, potently inhibited HER-2 phosphorylation in vitro, and downregulated signaling molecule kinase in human lung cancer cells harboring the HER-2 mutation. Ban zhi lian has been widely studied and shown to have antitumor effects in a number of cancer cell lines, and in this study was found to reduce tumor angiogenesis, or the growth of blood vessels that create cancer growth (PMID: 26137135). So far, small laboratory studies have shown the potential for a single Chinese herbal formula, Si Wu Tang, which contains 4 simple herbs as a blood tonic, to stimulate MCF-7 breast cell growth by activating estrogen receptors and HER-2 receptors, and have warned against this particular formula when using Tamoxifen or HER-2 inhibitors (e.g. herceptin). Further studies have discounted these effects, and it does seem farfetched that low dosage of Dang gui, Shu di huang, Bai shao and Chuan xiong could actually directly stimulate HER-2 and estradiol receptors on cancer cells in a negative manner. A 2014 study at the University of Hong Kong School of Chinese Medicine and the Western University of Health Sciences, in Pomona, California, showed that this herbal formula Si Wu Tang is actually an effective preventive medicine for breast cancer by activating the antioxidant and detoxifying the Nrf-2 pathway. To see this study in depth, click here: . A 2013 study at these University medical schools also elucidated the findings that Si Wu Tang could stimulate estrogen receptors and interfere with Tamoxifen and HER-2 inhibiting drugs, finding that the effects of low-dose stimulation of estrogen and growth receptors, which many herbal and nutrient chemicals could accomplish, is not easy to analyze in a direct manner, and very difficult to conclude that this could interfere with these drugs in prevention of breast cancer recurrence. To see this study, click here: . To provide further guidance, experts at the National Yang-Ming University School of Medicin, in Taipei, Taiwan, screened various Chinese herbs and formulas for the potential to stimulate expression of Estrogen receptors and HER-2 receptors and found that the herb Chuan xiong in Si Wu Tang, and Taraxacum mongolicum were the only potential Chinese herbs that could stimulate ER2 and HER-2. Such studies provide useful guidelines for cancer care in TCM. To see this study, click here: . It seems certain that these herbs, such as Chuan xiong, could be easily avoided in integrative cancer care in this situation. It also seems sensible to first utilize a drug to inhibit HER2 for a reasonable length of time, and then start the use of questioned herbal formulas. It is very clear that not all herbs, perhaps just one or three, actually have some evidence in small in vivo and in vitro studies with high dose, not in human clinical studies with small dose, to potentially interfere with the HER2 inhibitors, and that advice to avoid all herbs is unreasonable.

Herbal medicine in the care of cervical cancer

In 2014, Dr. Richard Schlegel of the Georgetown University Medical Center, the inventor of Gardasil vaccine for prevention of cervical cancer, announced that his pioneering research in oncology found that a chemical in a Chinese herb, Artemesia Qinghao, now standardized as a very effective anti-malarial medicine, artemesinin, showed a surprising anticancer effect on cervical cancer cells. Dr. Schlegel is now collaborating with oncologists at Johns Hopkins University School of Medicine, and Dr. Connie Trimble, to complete a randomized controlled human clinical trial of artemesinin for women diagnosed with early stage cervical cancer, to prove the efficacy of this herbal chemical in prevention of a potentially deadly form of cancer. Prior studies (cited below with links in Additional Information) have showed that artemesinin and hydroartemisinin is a potent inhibitor of ovarian, cervical, colon and lung cancer cell growth, with evidence of induction of apoptosis and inhibition of G2 growth cycle effects in specific cancer cell lines.

In an interview with National Public Radio (NPR) in 2014, Dr. Schlegel described how he was able to overcome the problem of direct study of cancer cells in the laboratory, which are difficult to keep alive outside the body, and hence research on direct cancer cell effects of drugs and herbs has been sparse. Dr. Schlegel was able to take cancer cells from hundreds of patients and keep these cells in a living and growing environment in the laboratory almost indefinitely. He then systematically tested many medicines to discover unknown anticancer effects specific to cancer cell lines. To his great surprise, the most dramatic early discovery was not the effects of a pharmaceutical drug, but one derived from Chinese Herbal Medicine. As this method expands, with over 30 labs in the world using this pioneering research method in 2014, more and more research proving the efficacy of specific herbal chemicals is sure to occur. Also, the key to this research is the discovery that a medium of cells derived from the mouse is able to provide the growth factors and nutrient producing effects needed to sustain the cancer cells in the laboratory, and future research is sure to determine specific nutrient molecules, and the chemical environment, which sustain this cancer cell growth in this mouse cell medium. Such research is sure to reveal just how we may utilize nutrient and herbal medicine, integrated with synthetic biological chemistry, to alter the growth cycle of many types of cancer. Obviously, the focus on inhibiting cancerous growth, and the environment of cancerous spread and subversion of normal cell programmed death, or apoptosis, provides us finally with a way to safely inhibit and prevent cancerous growth. Hopefully, the example of the success of artemisinin, a naturally derived herbal chemical, will be a precursor to expanded integration of Complementary Medicine in cancer care.

In China, the essential oil found in Curcuma zedoaria, or E zhu, a common anticancer herb, has been used in topical application to treat cervical cancer with great success. A cotton ball or other soft device is used to apply small amounts of the herbal essential oil directly to the cervical hyperplasia. Other studies of Chinese herbal chemicals to treat cervical cancer include Feverfew, or Tanacetum parthenium, and Pei lan, or Eupatorium formosanum, and the active chemical Parthenolide, which was shown to inhibit growth and induce apoptosis in SiHa and MCF-7 cervical cancer and breast cancer cell lines, by experts at the NIMS University School of Medicine, in Jaipur, Rajasthan, India (PMID: 25289524). Feverfew was shown to potentially enhance the effects of Parthenolide when combined with the extract from Pei lan. A 2003 randomized controlled human study, at the Lampang Regional Cancer Center, in Lampang, Thailand, showed that bitter melon extract (Momordia charantia) decreased a driver of cervical cancer progression, P-glycoprotein (P-gp) on NK cells of the immune system, when used with targeted radiation therapy. NK cells are lymphocytes that are consistently decreased in patients with cervical cancer, and dysfunction of these NK cells is believed to be responsible for the progression of cervical cancer growth (PMID: 12678140). These and other studies are available in Additional Information at the end of this article.

In Japan and South Korea, much research has revealed a host of safe and effective herbal medicines that prevent and treat cervical cancer through a variety of pathways. Such novel and common therapies as ECGC catechins from grape seed, green tea, and other sources, herbal extracts of Pogostemon cablin (Huo xiang), and metabolites from phosphotidylcholine such as perifosine, have been proven effective in preventing or treating cervical cancer and safe to use as an adjunct with standard chemotherapy or excision. Study at the University of Mexico in 2014 showed that aqueous extracts of medicinal mushrooms, such as Ling zhi / Reishi (Ganoderma lucidum) was able to inhibit cervical cancer dysplasia induced by the papillomavirus (HPV) and induce cell apoptosis in HeLa, SiHa and C-33A cervical cancer cell lines. These studies may be accessed in the section of this article entitled Additional Information, with links to studies. In addition, studies have finally shown the potential of bioidentical progesterone stimulating creams to inhibit or prevent endometrial cancer growth, and further studies should confirm that professional guidance in this realm may produce significant results.

While much propaganda concerning negative herb-drug interactions in cancer care has been published, these concerns are finally being questioned in standard medicine. For example, a 2014 study at the Society for Cancer Research, of the Hiscia Institute, in Arlesheim, Switzerland, studied the effects of combining one of the most promising herbal anticancer medicines, Viscum album, or European Mistletoe, with a prominent chemotherapy drug cysplatin, and found that this herbal extract, contrary to prior opinions, did not inhibit the effects of cysplatin in treating human breast cancer, pancreatic cancer, prostate cancer, or lung cancer, and that the cytotoxicity of cysplatin on all cancer cell lines was uninhiibited with addition of Viscum album extract. These cancer experts concluded: "Our in vitro results suggest that no risk of safety by herb drug interactions has to be expected from the exposition of cancer cells to chemotherapeutic drug and VAE (Viscum album extract) simultaneously." (PMID: 24397864) - It is sad that so many cancer patients have to be denied better treatment outcomes because of the competitive commercial bias against using herbal therapy in cancer care, and that we will need to spend another many years proving each and every case of anecdotal evidence of negative herb-drug interactions before oncologists will finally fully adopt Complementary and Integrative Medicine and Traditional Chinese Medicine (CIM/TCM) into standard integrative care.

Supporting blood deficiencies, thrombocytopenia and leukopenia

One of the primary concerns with tamoxifen therapy is the subsequent thrombocytopenia and leukopenia that results from toxic therapy. The ability of your marrow to produce new blood cells may be severely hampered by the damage caused by either chemotherapy or radiation therapy, as well as the tamoxifen, if these therapies are also part of the anticancer protocol. Damage from these therapies is not limited to the site of the cancer. Standard treatment has included the use of EPO, or synthetic erythropoetin, a hormonal analog that stimulates marrow production of blood cells. A report in the Journal of the American Medical Association (JAMA), published in February of 2008, concluded that "Erythropoiesis-stimulating agent administration to patients with cancer is associated with increased risks of venous thromboembolism and mortality. Our findings, in conjuction with basic science studies on erythropoietin and erythropoietin receptors in solid cancers, raise concern about the safety of ESA administration to patients with cancer." Complementary Medicine does offer safe and effective therapy to stimulate healthy bone marrow production of blood cell lines without the risks and side effects of synthetic hormonal therapy.

A 2007 meta-review of all available published scientific study of acupuncture stimulation alone to help treat chemotherapy-induced leukopenia, or immune deficiency, by the Dana-Farber Cancer Institute, in Boston, Massachusetts, U.S.A. found that 11 human clinical trials met their standards, involving 682 patients, all in Chinese hospitals and clinics. The results of these human clinical trials of acupuncture to treat therapy-induced leukopenia found that all 7 accepted trials showed a white blood cell increase during chemotherapy or chemoradiotherapy rather than the expected decrease. All of these human clinical trials were published in Chinese medical journals, and the researchers stated that this meta-analysis should promote the serious study of acupuncture to treat drug-induced leukopenia in the United States (PMID: 17309808). The treatment involved daily acupuncture for 12 to 24 days, with a median of 16 days of therapy, which is common in Chinese hospitals that utilize TCM, but is much different than the standard protocol in the United States. In the United States, the patient more typically may utilize a combination of acupuncture with herbal and nutrient medicine, with the acupuncture performed twice per week for a longer period of time. Studies have proven that various Chinese herbs stimulate increased expression of erythropietin (EPO) and functional improvements in the EPO metabolism, including Astragalus (Huang qi), Angelica (Dang gui), Rhodiola (Hong jin tian), Ginseng (Ren shen), and various formulas with these herbs. A holistic therapeutic protocol provides an array of biological benefits, including stimulation of bone marrow progenitors, increase in amount and function of EPO, clearing of chronic inflammation and oxidative stress, restoring iron homeostasis, and replenishing common nutritional deficiencies. The benefits of this holistic and synergistic course of therapy may surprise most patients, but the choice of TCM physician is important, as well as the quality of herbal and nutrient products.

Lupron and other Androgen Deprivation Therapy in Prostate and Ovarian Cancers

The use of Lupron in prostate and ovarian cancer therapy also presents severe side effects and risks, limited benefit, and the need for a more comprehensive therapeutic approach to achieve maximum results. Lupron, and other drugs in this class, work by inhibiting hormone production throughout the body, and effect the entire endocrine system. The theory behind this treatment is that chemical androgen ablation (similar to physical castration), will decrease the stimulation of androgen receptors that are responsible for the uncontrolled growth of cancerous tumors. Recent research on hormonal receptors reveal that a gradual imbalance of hormonal cell receptors in local tissues tilts the balance of maintaining older cells with replacing these cells. This process is called apoptosis, or programmed cell death, and is utilized by your body to remove older cells and replace them with new healthier cells to avoid the cell mutations that result in cancerous growth. When the body faces hormonal imbalance, such as in menopause, andropause, or even with premenstrual syndromes, this hormonal imbalance may stimulate an increase of the receptors that prevent normal cell death, or apoptosis. This is because the deficiency in certain local hormones prompts increased creation of the receptors for these hormones. In testosterone driven cancers, such as prostate, it is now known that the deficiency of testosterone drives this process. While active testosterone metabolites, such as DHT and estradiol, do stimulate cancer growth, restoration and maintenance of physiological normal levels of hormones has been proven to reverse this process. The scientific understanding of last year is being overturned by the increased scientific understanding of the present year. Balance of homoestatic mechanisms and a quantum biochemical perspective are proving effective in the treatment of prostate cancer. Complementary Medicine is not tied to the need to promote expensive drugs based on old evidence, but is able to utilize current research to deliver a host of natural products that are not tied to the patent system. Integrating complementary medicine would allow the M.D. to address a number of variables that create environments that drive the stages of prostate cancer, as well as decrease side effects of standard therapy and provide for improve quality of life. Thinking outside of the allopathic box provides increased potential in therapeutic outcome.

In 2014, a large study of the outcomes with androgen ablating drugs for the treatment of prostate cancer, by the Rutgers Cancer Institute of New Jersey, headed by Dr. Grace L. Lu-Yao, and published in the July 14, 2014 JAMA International Medicine, following tens of thousands of men with early prostate cancer for as long as 15 years, found that for the majority of men with prostate cancer, that this standard, and in fact sometimes only, therapeutic approach was "not a good option". An article in the July 15, 2014 New York Times, entitled Study Questions Testosterone-Suppressing Therapy for Early Prostate Cancer, quotes another expert, Dr. James M. McKiernan, chairman of urology at Presbyterian Hospital Columbia University Medical Center, as stating that this study is "eye-opening and even alarming". A number of studies now confirm the obvious, that the use of testosterone ablation with biologic drugs such as Lupron does not deliver the promised inhibition of the growth of prostate cancer, and that the side effects are very harsh, often worse than the slowly advancing effects of the prostate cancer itself. Today, more than one-fourth of all patients diagnosed with prostate cancer receive this "chemical castration" of suppressed testosterone, often for the rest of their life, and this large study definitively shows that these drugs were not associated with greater long-term survival. Experts at the Dana-Farber Cancer Institute in Boston, Massachusetts, U.S.A. stated that with this study, and another large study last year in Europe, that there is now "no compelling evidence" to justify androgen ablation for men with early stages of prostate cancer. Such study calls into question the entire strategy and science of the treatment of hormone receptor positive cancers in the last two decades.

An alternative to lupron, Casodex (Bicalutamide), acts as an anti-androgen in early stages of prostate cancer and acts by specifically binding to membrane androgen receptors, accelerating the mAR degradation. This is an option in therapy adopted by a number of oncologists.

If the androgen blockade or ablation, utilizing lupron, and perhaps other androgen blockers, such as the chemotherapies carboplatinum, Taxotere, Emcyt, is given for 13 months, upon completion of this blockade, the patient can expect rather rapid increases in PSA and testosterone after stopping therapy. On average, the PSA increases to 9, and the testosterone to 80, within the next 11 months. Use of adjunct therapies is important in this scenario as well. A 2014 study at the University of Southern California Institute of Urology, in Los Angeles, California, U.S.A. noted that Medical Doctors that prescribe Androgen Deprivation Therapy (ADT) for advanced cancers should be more concerned with adverse health effects from this treatment, and be aware that acupuncture has "moderate effect in controlling hot flashes in patients on ADT". These experts also noted that intermittent ADT is associated with higher quality of life in patients and improved bone health, less metabolic and hematologic complications, fewer hot flashes, and less sexual dysfunction. They also note that acupuncture is a non-hormonal treatment that is "similar to hormonal medications" in treatment. While still not actually endorsing acupuncture and TCM, standard medicine is reluctantly admitting that it is evidence-based in cancer treatment. They still omit the fact that acupuncture has many proven beneficial effects, and may be combined in the same therapy with physiotherapy and adjunct care with herbal and nutrient medicine. To see this evaluation click here: .

New Paradigms of treatment strategy for Prostate Cancers

Research at a number of prestigious medical Universities, including Harvard, University of Chicago, UCLA, Boston University School of Medicine, Memorial Sloan-Kettering Cancer Center, Weill Medical College of Cornell University, Martiniclinic Prostate Cancer Center of Hamburg-Eppendorf, University of Brussels, McMaster University in Ontario, and others have supported a series of research studies that have entered into phase 1 and 2 of human clinical trials, that demonstrate that standard medicine has been dead wrong on prostate cancer stimulation. Prostate cancer is driven by an imbalance of hormonal stimulation that promotes anti-apoptotic mechanisms over physiologically normal pro-apoptotic mechanisms. Research has revealed that this is driven by DHT (dehydroepiandosterone), a metabolite of testosterone that is converted from hormones locally. The belief that pathologic prostate growth, benign or malignant, is stimulated by circulating androgens has been a commonly held belief without scientific basis, and has driven a false zeal to inhibit testosterone production in prostate cancer patients, most of whom are aging and have been afflicted with andropausal decreases in testosterone prior to the development of cancer. Years of castration therapy proved statistically fruitless, yet the continued push of lupron prescription to effectively achieve chemical castration, or ablation of testosterone, continues with almost religious zeal. Medical doctors who dared to challenge this pharmaceutical imperative, and patients who questioned the therapy, were ridiculed as promoters of a dangerous philosophy.

Edward Friedman of the University of Chicago provided a mathematician's analysis of conflicting data in 2005 to explain how prostate cancer is initiated and driven. Professor Friedman was dismayed at the long-standing argument over prostate cancer mechanisms that created diametrically opposed groups, one advocating that high levels of androgens are responsible, and the other proposing that high levels of androgens should be effective in the prevention and treatment of prostate cancer. While almost all prostate cancers initiated with deficient levels of androgens, which would seem to contradict the first group, small studies that correlated increased incidence of prostate cancer with higher levels of free testosterone3, seemed to contradict the second group. What was discovered with analysis is that increased free testosterone in an androgen deficient patient stimulates increased cancer growth to a point, but as testosterone levels continue to increase there is no further increase in prostate cancer growth, and in fact testosterone at physiological normal or above both exerts mechanisms of cellular maintenance and inhibits estradiol dominant initiation of new cancer cells.

The Friedman data also revealed that prostate cancer is stimulated at different stages with different mechanisms. In the initiation stage, prostate cancer seems to be stimulated by a process similar to estrogen receptor breast cancers, namely that estrogen receptor alpha stimulation is not modulated by estrogen receptor beta, and that estradiol dominance is necessary for initiation, perhaps accelerated in the androgen deficient environment. One model proposed by Friedman to explain estradiol dominance as a cancer initiator would be the excess creation of telomeres, the repetitive DNA at the ends of chromosomes that protect them from programmed cell death, which would increase the lifespan of aging cells undergoing excess mutation. In the next phase of cancer growth, activity of 5-alphadihyrotestosterone (5alphaDHT) is essential for further growth by excess stimulation of membrane androgen receptor over intracellular androgen receptor, creating an anti-apoptotic effect that protects the early cancer cells from normal destruction. Once again, both the local hormonal imbalances as well as the abnormal hormone receptor balance created in the disease environment is key to cancer progress. In the third phase of the cancer growth, testosterone appears to bind to membrane androgen receptors to upregulate proteins that promote apoptosis and kill the cancer cells. Once again, aromatase activity was found in prostate cancer cells, but not in normal cells, linking conversion of hormones locally into estradiol, as well as an excess creation of estrogen receptor alpha, as part of the cancer process, just as in breast cancer. Since DHT drives the cancer and the imbalance between pro-apoptotic mechanisms and anti-apoptotic mechanisms, and since testosterone may be converted to either estradiol or DHT in the local tissues under various conditions, it appears logical that we must seek to restore a homeostatic environment to stimulate remission and proper apoptotic balance, and treat each patient individually according to stage of disease and hormonal assessment.

Abraham Morgentaler at Harvard Medical School co-authored a 2009 study entitled Testoserone and Prostate Cancer: Revisiting Old Paradigms, which concluded: "the available literature strongly suggests that testosterone therapy neither increases the risk of prostate cancer diagnosis in normal men nor causes recurrence of cancer in men who were successfully treated for prostate cancer. " Although ablation of testosterone has demonstrated a short window of remission of metastatic prostate cancer, long term outcomes are still very poor with this treatment, and the evidence does not support the long term testosterone ablation as a cure. The Morgantaler and Traish saturation model presents hard facts that while cessation of testosterone will temporarily affect DHT driven cancer cells, increases in testosterone above deficient levels does not increase DHT and cancer growth. In fact, testosterone is well known as vital for health maintenance of the prostate cells, and restoration of a physiologically normal health maintenance environment is proving to be clinically successful in the treatment of prostate cancer. Friedman states that "The evidence is overwhelming that testosterone is capable of inducing apoptosis in prostate cancer." This model has driven extensive research that confirms that high dose, or restoration of physiological normal testosterone, with testosterone patches or inserted time-released pellets in the gluteal muscle, may help restore the cellular environment that the patient needs to reverse metastatic prostate cancer growth. The challenge to medical doctors is how to help the capability of testosterone to induce apoptosis in prostate cancer, and here Complementary Medicine may play a large role in used research evidence to create the correct physiological environment for high dose testosterone to induce apoptosis.

In 2009, Robert Gardiner et al, from the Universities of Queenland and Adelaide, and the Royal Adelaide Hospital Cancer Center, wrote in the Journal of the European Association of Urology: "Following submission of Morris et al's manuscript to the journal, an electronic publication of another study by Szmulewitz et al from the University of Chicago has become available. Their participants, who were at an earlier phase of castration resistance than those enrolled into Morris et al's study, also used topically administered testosterone. Both studies were designed to assess the safety of the exogenous testosterone administration strategy. Only 1 of 15 patients from Szmulewitz et al's cohorts was withdrawn due to grade 4 cardiac toxicity; the Morris et al trial withdrew one man who had a prior history of epidural disease and developed spinal compression but without neurological symptoms. Because there was a tumor effect in both studies (with a fall in prostate-specific antigen in 7 of 12 patients in the Morris et al trial and 3 of 15 patients in the Szmulewitz et alt trial), these findings pave the way fo further studies to examine potential therapeutic benefits from exogenous testosterone therapy in select castrate-resistant prostate cancer patients. A notable finding from Morris et al's manuscript is that despite administering three times the usual replacement dose of testosterone, serum levels did not, on average, exceed normal levels. Szmuliwitz et al experience similar findings. This may partially explain the fact that none of the 12 patients in Morris et al's study exhibited an objective response. As pointed out by these authors, prostate cancer growth is stimulated by lower doses of androgens than those that result in growth repression. Thus, while failure to reach supraphysiological testosterone serum levels may have adversely affected tumor responses in both of these trials, it may have inadvertently served to test the prime objective of safety." The outcomes presented in these initial trials shows that topical or intramuscular pellet testosterone at high dose is safe, and will probably not raise free testosterone levels above physiologic normal. This also indicates that other therapies need to be added to this testosterone therapy to achieve higher rates of success to reverse tumor growth. Complementary and Integrative Medicine strategies presented above, and below in this article offer safe protocols that are proven to be effective.

Absence of calreticulum on membrane androgen receptors is suspected as the main cause of apoptosis (programmed cell death) during hormonal blockade (with Lupron et al). Apoptotic proteins promote apoptosis, and some medical doctors have used novel approaches, including RU486, and Arimidex to increase apoptotic proteins at the membrane androgen receptors. Unfortunately, these strategies also increase bcl-2, which prevents apoptosis. Arimidex blocks estrogen receptor alpha, and use of various Chinese herbs, DIM, and NuLignan may present an effective alternative to this drug, or an adjunct to perhaps increase effects and reduce the adverse effects of prolonged dosage. RU486 blocks the effects of progesterone on progesterone receptor alpha. In patients with progesterone receptor alpha dominance, RU486 is used to block PGa selectively. Studies have shown, by monitoring elevation of alkaline phosphatase in response to treatment, that combining RU486 with topical progesterone stimulating cream may have positive effects, since increased progesterone eliminates estradiol dominance and aids healthy cell maintenance. Studies have shown that combining progesterone stimulating cream with RU486 more effectively downregulates estrogen receptor alpha as well. Various herbs also potentiate RU486 in this regard, but not nearly as effectively as progesterone stimulating cream. These herbs in order of effectiveness are Viscum alba (European mistletoe), nutmeg, and Yucca. Monitoring of hormonal levels with inexpensive laboratory analysis of saliva metabolites is recommended. Use of low dose topical progesterone stimulating cream at 5-10mg per 12 hours is used. Use of concurrent RU486 with this low dose progesterone stimulating cream topically is shown to be effective in increasing calreticulum and apoptotic proteins as well (Dr. Paul Savage). While this research concerning hormone imbalance in local tissues driving improper hormonal receptors to alter the normal programmed cell death, or apoptosis, is complicated, it has been clear that normal hormonal balance, or homeostasis, is the key to the body's ability to prevent cancer or destroy cancer cells. 

Of course, these studies are designed for the patients that have shown progression of the cancer despite the use of lupron, but that still have no evidence of metastases. When the patient fails lupron therapy and metastatic cancer is detected, especially when the cytology of distal tumors shows undifferentiated and primitive cell line, neither lupron or testosterone therapy is applicable. In these cases, there is little to offer in standard therapy, and even more reason to aggressively pursue remission with Complementary and Integrative protocols. To offer no therapy despite the growing body of evidence that the patient may benefit from a variety of complementary protocols seems cruel.

This treatment strategy has yet to be confirmed with long term stage 3 clinical human trials, but is being quickly accepted by a number of cancer experts, especially those not interested in practicing pure defensive medicine, but doing what seems most efficacious for their patients. Use of this therapeutic approach is especially applicable for those patients that have failed testosterone ablation or chemical castration with lupron, or patients that experience castrate resistant prostate cancer. While acute high-risk prostate cancer will still be treated with radiation therapy and lupron, management of the long-term therapy with hormone modulation and selective therapeutic protocols, utilizing Complementary and Integrative Medicine, will be demanded by a public that increasingly does its own research.

For these medical doctors, a comprehensive package of therapy, utilizing Integrative and Complementary Medicine, maty be essential for success. A number of strategies suggested to identify patients who are resistant to lupron have been identified. 40% of castrate-resistant prostate cancer patients have androgen receptor amplification noted in circulating tumor cells. Fluorinated dihydrotestosterone positron emission tomography tracers are suggested to identify patient with upregulation of androgen receptors. Biopsy with evaluation of androgen receptor gene amplification, or evaluation of circulating castrate-resistant prostate cancer cells, are other suggestions.

The published scientific studies of herbal medicine in adjunct cancer care so far have focused on the most simple and benign medicines, not the most effective. Nevertheless, this does present some information for patients that is useful. In 2016, a meta-review of such studies for management of recurrent prostate cancer, or biochemically recurrent prostate cancer, defined as prostate cancer that recurs after the hormonal blockade, which happens in an alarming percentage of cases, was conducted by experts at the University of Melbourne School of Medicine, in Melbourne, Australia. Here, only 5 studies met inclusion criteria, and the research found that simple adjunct herbal therapies with Pomegranate extract, soy isoflavones, sulforaphrane (like I3C and DIM, from cruciferous vegetables), and the pro-Vitamin A carotenoid lycopene pigment, showed efficacy in slowing PSA rise and reducing PSA marker, with no adverse effects. These simple and benign herbal and nutrient chemicals will be initiated into standard cancer care as an adjunct, but in no way represent the most effective herbal medicines studied over the last few decades.

Specific biological mechanisms in prostate cancer and the role of Complementary Medicine to control them

DHT, or 5alpha-dihydrotestosterone, is a biologically active androgen metabolite that drives prostate cancer within an altered cellular environment. DHT interacts with intracellular androgen receptors (iAR) to suppress the pro-apoptotic proteins that are produced by the proliferation of membrane androgen receptors (mAR). Lowering the DHT alone, rather than the beneficial testosterone, removes this iAR suppression, and allows mAR to express the pro-apoptotic proteins that remove cancer cells. DHT is primarily formed in a normal environment via rate control of conversion of inactive testosterone to DHT by the enzyme 5alpha-reductase. While free testosterone may be converted to estradiol in local tissues via the enzyme aromatase, diminishing the level of DHT, DHT cannot be converted by aromatase to estradiol. To holistically control abnormalities in hormone conversions that drive prostate cancer, we must utilize chemicals that modulate aromatase and 5alpha-reductase, as well as 17-alpha-hydroylase/C17,20 lyase. These chemicals can be found in nature, in forms that the animal organism has long adapted to through evolution, and that are without side effects.

To prevent new cancer growth, hormonal balance, correction of estrogen dominance and androgen deficiency, as well as regulation of, or inhibition of aromatase, would prevent excess estradiol from initiating cancer growth, under the Friedman model. In aging adults, testosterone falls with andropause, inducing increased DHT, estradiol dominance in relation to progesterone drops, and deficient D3 prohormone cholecalciferol, all contribute to abnormal prostate cells, and as these abnormal prostate cells avoid apoptosis and continue to mutate further. Increases in membrane androgen receptors, estrogen receptor alpha, and progesterone receptor alpha, over their counterparts, pushes anti-apoptosis over pro-apoptotic mechansisms. Including progesterone stimulating topical bioidentical hormone cream, cholecalciferol, DIM, NuLignan, saw palmetto, pumpkin seed oil, and various herbs in formula, to counter this common aging process may dramatically help to prevent early stages of development of prostate cancer.

In the later stages of prostate cancer, regulation of, or inhibition of 5alpha-reductase would decrease the excess conversion of testosterone to DHT. Since studies demonstrate that there are rate-limiting mechanisms preventing excess testosterone conversion to DHT once physiological normal levels of free testosterone are reached, even in a cancer state, use of herbal and nutrient therapy that provides the body with the tools to modulate these enzyme activities is both effective and safe.

The main reason for use of various natural 5-alpha-reductase inhibitors in long-term therapy in prostate cancer is the large percentage of cases that are shown to be resistant to chemical castration, or ablation of testosterone. Robert Gardiner et al, from the University of Queenland, Royal Adelaide Hospital Cancer Center, and University of Adelaide Hanson Institute wrote in journal of the European Association of Urology in 2009: "It has been documented recently that intratumoural androgen levels in castrate-resistant prostate cancer are sufficient to stimulate tumor growth, indicating that local synthesis of androgens is another mechanism for maintaining androgen receptor signalling in the castrate environment." Clearly, whether utilizing lupron or not, additional therapies to inhibit enzyme rate control of hormone conversion in local tissues needs to be added to provide thorough treatment protocol.

A number of herbal and nutrient chemicals have been proven effective to inhibit 5-alpha-reductase, including saw palmetto fruit, black cohosh and red clover in alcohol extracts. Krill oil is also useful as a source. As usual, conflicting studies have been presented, but benefits in reducing prostate cancer risk as well as lowering PSA by 50 percent over 12 months have been demonstrated. Negative studies using synthetic 5-alpha-reductase inhibitors, finesteride et al, show that treatment with thise chemicals increased incidence of high-grade prostate cancers, but this could be attributed to chemical adverse effects. Natural 5-alpha-reductase inhibitors in foods and herbs have shown no adverse effects. These include the foods, brussel sprouts, soybean, cashew, pineapple, peanut, asparagus, black mustard greens, collards, kale, kohlrabi stem, papaya, mandarin orange, chili, paprika and chicory root, many nuts and seeds, especially pumpkin and flax, wlanuts, and legumes, as well as many herbal medicines. The herbal chemicals Berberine and Monocaffeyltartaric acid, from Huang lian (Coptis chinensis) and Pu gong ying (wild dandelion root), as well as the nutrient chemicals daidzen, genistein, biochanin A, formononetin, and equol have been proven to be potent 5-alpha reductase inhibitors, and extracts of Pygeum and Urtica doica (stinging nettle) show benefits. Obviously, these herbal chemicals and foods should be incorporated into a broader treatment protocol that is individualized, and depending on a single product alone, especially one bought at a store or online, where quality is suspect, is not the ticket for success.

The chemicals Curcumin, linoleic acid, alpha-linolenic acid, oleic acid, palmitic acid, alizarin, and biochanin-a have been confirmed as herbal 5-alpha-reductase inhibitors. Chinese herbal formulas to treat cancer commonly include herbs with these chemicals, incorporating, E zhu (curcuma), Da huang (rheum), Ge gen, Hong hua, Nu zhen zi, Xuan shen, and others. Quality professional Chinese herbal formulas are based in part on scientific studies current with research. Specific herbs containing these chemicals include: curcumin: curcuma longa (yu jin), curcuma zedoaria (e zhu), turmeric (jiang huang); alizarin: mulberry wood (sang bai pi, sang zhi, noni), wild rhubarb root rheum (da huang), rubia cordifolia madder (qian cao gen), quinine red cinchona bark; biochanin-a: Noni wood morinda citrifolia, peuria kudzu (ge gen), Sophora japonica (huai hua), red clover; inoleic acid: honghua, xuanshen, digupi, cheqianzi, yinchenhao, gouqizi, sangshen, nuzhenzi; linolenic acid: xuanshen, digupi, cheqianzi, chaihu, congbai, duhuo; oleic acid: xuanshen, chiqianzi, yinchenhao. The essential fatty acids may also be found in passionflower, vitex, ashwaganda, walnut oil, pumpkin seed oil, and safflower seed oil. Krill oil (EPAq from Health Concerns) is high in these essential oils, as is Evening Primrose oil. Negative press concerning herbal and nutrient 5-alpha-reductase inhibitors is limited to a warning that these herbs and nutrients may mask diagnosis by lowering PSA! Medical doctors that take such warnings seriously need to think harder.

PSA velocity more accurately detects prostate cancer than total PSA. National Comprehensive Cancer Network clinical practice guidelines in oncology published in 2005, and Carter et al, JAMA, 1992;267;2215-20, show that rates of increase in PSA over a year are better determinants in detection of prostate cancer than PSA, which has been shown to produce many false positives. Prostate cancer needs to be evaluated with more than total PSA. Prostate cancers proceed through 4 stages, and it is important to adopt a diverse integrative strategy before the cancer reaches stage 4, where there are nearby metastases, spread to regional lymph nodes. In prostate cancers, tumor tissues closely resemble normal tissue in a great number of cases, making evaluation of the spread to lymph nodes and evaluation of metastases important in evaluation. Prostate cancers are heterogenous masses of various abnormal prostate cells with variable degrees of receptor expressions, gravitating toward high membrane androgen receptors relative to internal cell androgen receptors, high estrogen receptor alpha in relation to beta, and high progesterone receptor alpha in relation to beta.

When 5-alpha-reductase herbs and nutrients are used, the conversion of testosterone tilts to estradiol, which exerts anti-apoptotic mechanisms at estrogen receptor alpha (ERa) and pro-apoptotic forces at estrogen receptor beta (ERb). As with breast cancer, the use of the above mentioned therapies of formula 101, DIM, NuLignan, and other therapies, should be used to prevent the ERa over ERb mechanisms.

Viscum alba, or European mistletoe, is another herb proven effective with prostate cancer. The flavonoid silibinin (Milk thistle / Sylamarin) has proven anit-cancer activity in vivo and in vitro, specific to prostate cancer. Alcohol extract is recommended at low dose. High dosage is purported to have some reversible toxicity, which is dose dependant, and thus the patient may increase dosage as tolerated. Liver enzymes should be monitored with higher dosages.

Colon Cancer and Complementary and Integrative Medicine

Colorectal cancer is the second-leading cause of cancer death in the United States of America. Most colorectal cancers begin as benign adenomas or polyps that grown on the inner lining of the lower large intestine and rectum and take between 10-20 years to develop into a metastatic cancer. Of course, improving and maintaining the homeostatic health of the gastrointestinal system is the most important thing that an individual can do to prevent colon cancer, and standard medicine has no effective strategy to achieve this goal. Integrating Complementary Medicine into the overall treatment protocol in your life will do much to prevent colorectal cancer, as well as periodic colonoscopies with polyp removal after the age of 50. Integrating CIM/TCM into postoperative care is now proven to aid restoration of bowel function enormously with no adverse effects, and is being integrated into standard care in Asia.

Few serious studies of treatments in Complementary Medicine to prevent or treat colorectal cancer have been published, yet the few that have been published have produced surprising benefits. For instance, the Johns Hopkins Colon Cancer Center reports that for over 2 decades we have had proof that the hormone called Vitamin D, or cholecalciferol, was proven important in the prevention of colon cancer. These initial studies resulted from the demographic studies showing that people in areas of increased sun exposure had lower incidence of colon cancer. New studies have revealed that maintaining a circulating blood level of Vitamin D hormone of 34 ng/ml may reduce the incidence of colorectal cancer by half. Dr. Edward Gorham, a research epidemiologist at the Naval Health Research Center and Adjunct Professor at the University of California San Diego, was the head of a project that conducted a thorough meta-review of these studies (cited below in Additional Information) and found that not only maintaining healthy normal minimum levels of this hormone we call Vitamin D in circulation, but even maintaining higher levels than the normal minimum, is associated with dramatic benefits in preventing the advance of colorectal cancer, prostate cancer, and breast cancer. For instance, a study of 19,000 men showed that those with levels of cholecalciferol (25(OH)D, or Vitamin D3) below 16 ng/ml in circulation had a 70 percent higher incidence of prostate cancer, and in younger men the incidence was 3-5 times greater than those with at least a 16 ng/ml level, and incidence of invasive prostate cancer was 6.3 times higher in the persons with a low circulating Vitamin D level. If there were a pharmaceutical medicine with this efficacy, billions of dollars of profit would be generated in a short time, yet few results have been generated in the arena of cancer prevention and hormone Vitamin D metabolism, which is a complicated subject explained in more detail on this website in an article entitled "Vitamin D, the true story". Although sound scientific information revealed the benefits of correcting hormone Vitamin D metabolism nearly 30 years ago, today we have only a little effort to test circulating cholecalciferol levels and correct this problem, while until recently, we had standard medicine warning that higher dosage supplementation was perhaps dangerous, with no supporting data.

In 2012, the University of Chicago Comprehensive Cancer Center announced that a large multicenter trial was underway to study the effects of hormone Vitamin D supplementation on new polyp growth in patients who had polyps removed with routine colonoscopy, with results from this large randomized controlled human clinical trial expected in 2014. Dr. Yan Chun Li stated that this study focuses on the physiological explanation for why Vitamin D suppresses colon cancer, where Vitamin D receptor (VDR) activity occurs and is modulated, and where a molecule called beta-catenin, which mediates Vitamin D activity at the receptor affect VDR by intercellular overexpression. Beta-catenin is a protein regulator of cell adhesion and gene transcription, associated with a number of cancers, including endometrial cancer. Excess expression of beta-catenin is linked to colorectal cancer, prostate cancer, ovarian cancer, basal cell carcinoma, and squamous cell carcinoma in the head and neck. The Wnt signaling pathway, which regulates both intercellular calcium and beta-catenin protein levels in the cells, has long been implicated in cancer pathogenesis, in breast, prostate, colon, lung and skin cancer, is being explored to explain the mechanism behind these cancers. Ongoing research at the German Cancer Research Center in Heidelburg, Germany, found that the Chinese herbal chemical artemisinin, in Artemisia annua (Qing hao), now famous as an antimalarial, also exerts profound anticancer activity due to its effects on Wnt/beta-catenin signaling. Such research will soon produce viable combinations of herbal and nutrient molecules to prevent or treat colon and other cancers. In the meantime, it is important to monitor the circulating calcidiol, or Vitamin D3, levels and maintain a sufficient hormone Vitamin D metabolism.

Grape seeds contain a chemical called proanthocyanidins which have shown anticancer potential and are linked to beta-catenin signaling. A number of studies have now shown that proanthoycanidins and lignans were associated with prevention of colorectal cancers after polyps growths were noted. To test the safety of these nutrient medicines, the National Institutes of Health and Center for Cancer Research in Frederick, Maryland, U.S.A. examined the data from the Polyp Prevention Trial and deduced that high dosage intake of these nutrient chemicals did not increase recurrence of colorectal adenoma. While we are still a ways away from large multicenter human clinical trials to prove the anticancer efficacy for these medicines, there is sufficient proof of potential benefits and no risk of adverse outcomes to recommend these as part of the protocol in colon cancer prevention.

In recent years a number of herbal medicines have been studied and showed positive effects in prevention of colorectal cancer. These include Vitex, Cascara sagrada, Echinacea, Milk thistle, Saw palmetto, Feverfew, aged garlic, and St. John's wort, according to a 2008 meta-review of Medline research publications, according to Dr. Genoveva Murillo and Dr. Rajendra Mehta of the IIT Research Institute in Chicago, Illinois, U.S.A. The progressive University of Maryland Medical Center lists studies that show preventive and anticancer effects from extracts of Green tea, Reishi mushroom (Ling zhi, or Ganoderma lucidum), Maitake mushroom (Grifola forndosa), and Turmeric (Curcuma longa, or E zhu). Optimized curcumin has now been produced (LongVida) to increase the bioavailability of this herbal chemical in the blood and tissues. In 2008, study at Humboldt University of Berlin, Department of Oncology, found that a chemical in the Chinese herb Magnolia officianalis, honokiol, inhibited growth and helped induce cell death, or apoptosis, in various cancer cell lines, including colon cancer, and could serve as an effective adjunct therapy used in combination with standard drugs (PMID: 1858872). Of course, these and other herbal medicines should be taken only under the supervision of a professional herbalist, such as a Licensed Acupuncturist.

In 2008, multicenter research at University Medical Schools in Japan showed that a simple traditional formula used to treat adhesive bowel obstruction, Daikenchuto, consisting of Ginger (Zingberis siccatum), Zanthoxylum fruit (Hua jiao), a medicinal peppercorn, and Saccharum granorumb (prepared barley sugar), significantly improved bowel function quickly following radiation and surgery for gastric and colon cancers. A three phase randomized controlled human clinical trial was initiated at 7 University Medical Schools in Japan, and the phase 2 human trials proved in 2015 that this simple traditional herbal formula was safe and effective as adjunct therapy following gastrectomy or bowel resection (see study links in Additional Information at the end of this article). The research revealed also that the herbal chemicals exert significant anti-inflammatory effects by action on the GI nervous system, affecting nicotinic receptors and acetylcholine metabolism. Such study is finally proving that utilizing Traditional Chinese Medicine and Complementary and Intregrative Medicine (CIM/TCM) is very safe and effective, and that the decades of discouragement have led to much patient harm. There is an expected rise in such studies in the next decade, finally achieving integrative care in cancer. The warnings of adverse effects for decades have produced no tangible evidence of such harm, and are revealed a cynical discouragement of very helpful treatment protocols.

Brain Cancers and the Promise of Complementary and Integrative Medicine

Brain cancers affect many thousands of patients each year in the United States, and have a very poor prognosis, with an average 5-year survival of about 10 percent. While we continue to advance treatment protocols, with surgery, laser surgery, targeted radiation, chemotherapies, and biologics, we have not made significant progress on treating brain cancers. In 2014, researchers at St. George's University of London published the results of a randomized controlled laboratory trial that showed that integrating cannibinoids with radiation therapy dramatically improved outcomes. There are 85 known phytocannibinoids in Cannabis, commonly known as marijuana, and many of these active chemicals are now known to have dramatic benefits in medicine, such as the cessation of severe intractable seizures in children, the relief of chronic pain, the prevention of neurodegenerative disease, etc. These researchers, led by Dr. Wai Lu, found that laboratory animals given a small dose of cannibidiol (CBD) and tetrahydrocannibinol (THC) while receiving targeted radiation therapy for brain tumors showed a dramatically decreased rate of tumor growth, often with a drastic reduction in tumor size, and in some cases tumors effectively disappearing in the animals. These researchers are hoping to conduct human clinical trials as soon as possible to prove that these results are accurate. Such study shows the promise of herbal and nutrient medicines integrated with standard cancer therapies, though, as well as proof that Cannabis use in cancer care is not quackery. Studies such as these may well show the public that the prohibition of research into the beneficial effects of Cannabis after the positive findings of the La Guardia Committee report of the New York Academy of Science in 1939 may indeed have caused dramatic harm to cancer patients. The politicizing of medical treatment and denial of medical treatment and study, mostly due to economic concerns at the heart of the matter, needs to stop.

A new approach in the treatment of brain cancers is emerging, namely the use of genetic mapping in cytology to define the individualized treatment. In the past, most cancers were rated with study of the cancer cells and tissues themselves as just a stage 1-4, or a general type of tumor related to the basic type of tissue, such as organ tissue (adenocarcinoma). Now we may find the genetic subtypes of the particular cancer cells to find biologic therapies to stop its growth that are individualized, and the success rate of therapy should improve dramatically. What is overlooked so far in standard medicine is the fact that this same type of analysis could also be used to define the specific therapies in Complementary and Integrative Medicine that could be effective as adjunct therapy. These genetic analyses will reveal a host of specific factors that could be addressed to stop the cancerous metabolism of the cell, and a single biologic may not do enough to reverse the dysfunctional metabolism. By integrating Complementary Medicine, the outcomes could be improved dramatically.

While numerous studies now show the positive benefits of acupuncture to treat pain related to cancer, the recovery of brain function after severe stroke, and the numerous benefits of acupuncture to stimulate functional improvement and coordination in key areas of the brain, it may be hard to design clinical studies that prove direct effects on brain cancer with acupuncture. Likewise, there are now many studies that show the positive benefits of herbal and nutrient medicines for brain health and function, clearing of oxidative stress, and anticancer effects, but few studies exploring the direct effects of specific herbal and nutrient medicines for brain cancer. In 2013, at Guru Nanak Dev University, in Amritsar, India, researchers found evidence that an alcohol extract of the herb Tinospora cordifolia, used in Ayurvedic medicine, with an analogous herb Tinospora sinensis, or Kuan jin teng, used in Chinese Herbal Medicine to treat tendinosis and joint pain, suppressed the cell cycle growth in glioblastomas, a type of brain cancer, and prevent metastasis.

Lung Cancers and the Failure to Integrate Support and Adjunct Therapies of Complementary and Integrative Medicine with Standard Care

Lung cancers comprise a number of types of carcinoma and continue to be the biggest group of cancers contributing to cancer mortalities, despite a dramatic decrease in cigarette smoking, still touted as responsible for more than 80 percent of lung carcinomas. In recent years, medical experts have finally become concerned that, despite a dismal record in extending survival time and quality of life for patients with lung cancers, and despite a dismal record of actual prevention, there has been almost no research focused on the integration of a more thorough and holistic treatment protocol, utilizing Complementary and Integrative Medicine (CIM). A multicenter study in Europe concerning the use of CIM by patients with lung cancer, conducted by oncologists at the Franziskus Hospital, in Bielefeld, Germany, found that 54 percent reported using Complementary and Integrative Medicine as an adjunct treatment, though, with 50 percent of this care prescribed by their medical doctors (PMID: 19955808). Unfortunately, the CIM measures were very limited in scope and efficacy, with the most frequently used medicines including European Mistletoe extract (Viscum alba), selenium and other vitamin supplements. These experts in oncology stated that with such widespread use of Complementary Medicine and report of benefits that it was vitally important to obtain more scientific information and conduct human clinical trials to document and refine CIM therapies in adjunct cancer care.

Complementary and Integrative Medicine (CIM) may provide a variety of benefits in adjunct care for lung cancer patients. While the idea of stress reduction, calming, and decrease in adverse side effects of therapy are well known, the scope of therapy in this care is proving to be broad, and finally, valuable research is documenting just how such therapies as acupuncture stimulation, herbal and nutrient medicine, physiotherapies, and cognitive and energetic medicine, may contribute holistically to both better quality of life and to greater efficacy of standard therapy in prolonging survival time, as well as the important role in prevention of lung cancers. Since most lung cancers are detected at a late stage, already metastasized throughout the body, and standard care is still focused just on surgical resection when tolerated, targeted irradiation of tissues, and limited platinum-based chemotherapies, the need for a broader treatment protocol and a holistic approach is indeed needed. Currently, an anti-metabolic chemotherapy and a biologic monoclonal antibody are approved for treatment, but even with all of these medications, the average benefit is a delay of just months for the expected mortality in metastatic non-small cell lung cancer. This outcome could be extended greatly with a sensible holistic course of care, integrating Complementary Medicine, and the Quality of Life could be much improved for these patients.

Nivolumab, or Opdivo, is a biologic medicine that utilizes the immune system, inhibiting a protein receptor called PD-1 on T cells, which prevents the homeostatic mechanism that limits the T cell activity, allowing the immune system to strongly attack cancer cells. Nivolumab has been approved by the U.S. FDA for treating lung and melanoma skin cancers, and is a monoclonal antibody (mAb). It is shown to be more effective for patients screened for PD-L1, another regulatory protein that the PD-1 binds to, with much better outcomes for PD-L1 positive cancer cells. Another drug in this class, Ipilimumab, or Yervoy, is also now approved to treat melanoma skin cancer, and is a CTLA-4 receptor antagonist. In human clinical trials, Nivolumab use resulted in 6.9 months of progression-free survival, with 43.7 percent of patients that completed the study seeing objective responses within the 12 month followup period. Serious adverse health effects, called 'side effects', were seen in 16.3 percent of patients, with 1 death attributed to the drug out of about 300 patients. In a clinical trial for melanoma patients, these two monoclonal antibodies were used together, but 36.4 percent of the patients stopped treatment due to the severity of the side effects. In these clinical trials, corticosteroids (Prednisone) were used in about 35 percent of patients to decrease the severity of immune adverse effects. The results were better than chemotherapy for these dangerous cancers, but the adverse health effects were still a serious problem. Integration of Complementary Medicine could both relieve these adverse effects, improving quality of life, and potentially extend the survival time. Common adverse effects with skin rash, diarrhea, fatigue and liver dysfunction could be relieved with CIM/TCM. Hormonal problems associated with the treatment, adrenal fatigue and thyroid pathology, could also be relieved. In industry drug trials for Opdivo (Nivolumab) about 20 percent of patients experienced skin rash and itch, liver dysfunction, colon inflammation and diarrhea, cough and upper respiratory tract infection, and about 10 percent of patients chosen for these studies experienced peripheral edema, kidney dysfunction, and thyroid dysfunction. The large array of serious adverse effects could be alleviated, or prevented from continuing to a long-term problem that would greatly reduce quality of life for these patients with specific genetic markers and serious lung cancer. CIM/TCM could be used prior to this monoclonal antibody treatment, or after it is administered if there is concern about negative interactions with herbal medicine. The guidelines for use are intravenous administration every 2 weeks "until the disease progression is or unacceptable toxicity occurs". Obviously, this leaves many options for the integration of adjunct CIM/TCM care.

A large 2013 meta-review of published studies of Chinese herbal medicine as an integrated concurrent strategy to treat the deadliest type of lung cancer, Non-Small Cell, by experts in the U.S. and China, particularly the University of Hong Kong and the University of Southwestern Texas Medical Schools, found that a large number of Chinese herbs are highly supported in this protocol, extending life expectancy, survival rates, immediate tumor responses and functional performance and quality of life of cancer patients, as well as countering immediate side effects of chemotherapy, such as nausea and vomiting and leukopenia. This meta-review should have finally ended the advice against integrating TCM and Complementary and Integrative Medicine into cancer care, but it has not. In this study, Astragalus (Huang qi), Adenophorae (Sha seng), Ophiopogonos (Mai men dong), Glycyrrhiza (Gan cao), Poria (Fu ling), and Oldenlandia (Bai hua she she cao) were all heavily supported in meta-analysis (PMC: 3585199). These researchers concluded that "the evidence from the meta-analysis of the included studies shows that Chinese Herbal Medicine as adjuvant therapy has advantages in Non-Small Cell Lung Cancer patient". They also noted that more study should be funded to supply better guidelines for this therapy within a holistic medicine framework, meaning that it probably would work best by incorporating holistic physicians and combining treatment modalities into a holistic treatment system.

This same University of Hong Kong found in a 2013 meta-analysis of clinical trials of acupuncture as adjunct therapy for lung cancer that this treatment improved immune function in a modulatory manner, prevented bone marrow suppression of new blood cells, and reduced incidence of nausea. In 2015, another meta-analysis by Memorial Sloan Kettering Cancer Center in New York, U.S.A. noted that acupuncture was well liked in the treatment of lung cancer, and exerted a number of beneficial effects in studies, reducing fatigue, pain and lymphedema. In 2015, studies found that more Chinese herbal chemicals were proven to exert significant anti-cancer effects against lung cancer cell lines, including Berberine from Huang Lian, which also potentiated chemotherapy, and simple herbs such as Coriolus versicolor, Vitex and Chen pi (aged tangerine peel), and links to these studies are provided below in Additional Information. The proven potential for short courses of acupuncture with more prolonged courses of herbal and nutrient medicine from the TCM physician, or Licensed Acupuncturist and herbalist, in the adjunct care of lung cancer, should instigate greater utilization. A large 2016 multicenter randomized controlled human clinical trial with use of Chinese herbal formulas integrated with standard treatment for non-small cell lung cancer, at Capital Medical University, in Beijing, China, and four hospitals, found that this integrated treatment was well tolerated, improved the quality of life considerably, and improved the 3-month progression free survival rate signficantly. Despite decades of fierce opposition of use of Complementary Medicine in cancer care, we shall soon see such treatment with CIM/TCM widely adopted. To see this study, click here: . A 2016 randomized controlled human clinical trial at the Shanghai University of Traditional Chinese Medicine, in China, compared the use of TCM therapy with herbal formulas and acupuncture to chemotherapy in advanced non-small cell lung cancer, and the TCM therapy showed similar outcomes with time to progression and overall survival to that of the use of more chemotherapy, but much better quality of life measures, and a higher 1-year survival rate. The study is seen by clicking here: . The choices of integrated treatemnt in these cancers should be that of the patents, and the evidence should be discussed.

Acupuncture itself, considered primarily a tool to achieve stress reduction and improved vitality, is proving to provide an array of specific benefits to therapy that are significant, exerting immunomodulatory effects, alleviating pain, reducing the side effect of nausea, and alleviating the adverse side effects of bone marrow suppression and anemia seen with therapy. This therapy is now widely supported even in the United States by renowned cancer treatment centers. A combination of therapeutic tools is recommended in an effective holistic system, though, not just the addition of a few herbs by nurses or medical doctors at cancer centers. Utilization of a knowledgeable Licensed Acupuncturist and herbalist, long discouraged in cancer care, is finally being proven to be safe and very effective as an adjunct treatment protocol. By incorporating short courses of acupuncture from a knowledgeable Licensed Acupuncturist and herbalist, with more prolonged individualized herbal and nutrient therapy, into the total package of cancer care, the outcomes will be improved and quality of life maintained.

Do Medical Doctors actually support Complementary and Integrative Medicine in the overall treatment plan?

Dr. Ka-Kit Hui, Dr. Edward K. Hui, MDs, and Michael Francis Johnston, PhD, from UCLA Center for East-west Medicine wrote in Integrative Cancer Therapies, Vol. 5, No. 1, 56-62 (2006): The Potential of a Person-Centered Approach in Caring for Patients with Cancer: A Perspective from UCLA Center for East-West Medicine: "Evolving patient preferences as well as an expanding evidence base for commonly used complementary and alternative medicine therapies for patient with cancer have led to inroads by integrative medicine into clinical oncology. Traditional Chinese Medicine (TCM) has been used in conjunction with conventional biomedicine in the prevention and treatment of cancer in China for several decades. Methods: the authors, through select review of the existing literature and by drawing on clinical experience, describe a person-centered approach to care of patients with cancer that incorporates TCM concepts and techniques. Two cases are used to illustrate how this approach might address unmet needs and enhance quality of life for patients with cancer. Results: TCM's emphasis on a comprehensive understanding of imbalance in various systems and resultant compromise of homeostatic reserve as well as its ability to treat them with distinctive therapeutic modalities can add unique value to the overall management of the patient with cancer. Conclusions: TCM can be used adjunctively to improve quality of life and functional status during a patient's struggle with cancer. An approach integrating both medicines that is guided by scientific evidence, safety, and patient preferences has the potential to improve modern oncologic care."

Since this landmark 2006 report identifying acupuncture and TCM protocol as an effective adjunct treatment protocol in cancer care, many studies at prominent University Medical Schools in the United States and Europe have confirmed the great efficacy of acupuncture and herbal medicine in cancer care, with none of the alleged adverse effects or contraindications frequently mentioned in the past seen in these studies. Some of these RCTs and other types of studies are cited at the end of this article with links to the studies. One example, from 2015, exemplifies the quality of these studies, with a large randomized controlled human clinical trial at the Perelman School of Medicine at the University of Pennsylvania, and the Wright State School of Medicine, in Dayton, Ohio, with the Emory University Neil Hodgson Woodruff School of Nursing, in Atlanta, Georgia participating. Here, 120 patients with breast cancer experiencing alarming hot flush episodes were treated with electroacupuncture, standard acupuncture, Gabapentin, sham acupuncture, or placebo pills randomly assigned. The acupuncture treatments were performed daily for 8 weeks. The sustained benefits from the acupuncture and electroacupuncture were much greater at 24 weeks than these other modalities or sham/placebo, while there were none of the alarming adverse side effects of medication (PMID: 26304905). The study was sponsored by the American Society of Clinical Oncology. Such studies show that the long history of discouragement of CIM/TCM by standard medicine was depriving many cancer patients of a better quality of life. 

In 2016, the U.S. National Cancer Institute published support for Complementary and Integrative Medicine (CIM/TCM) on their website, albeit still strongly inhibited by industry pressure and lobbying. Nevertheless, we see that even this constrained source supports acupuncture, herbal and nutrient medicine, mind-body therapies such as Qi Gong and Tai Chi, and physiotherapies such as manual soft tissue mobilization and lymphatic massage (Tui Na). Most of the therapies on this website are extremely benign and perfectly safe, and it is obvious that professional care also offers evidence-based therapies that are stronger and more effective, yet very safe. Of course, the choices in cancer care should be left to the patient, and CIM/TCM offers a very wide array of choices to suit each individual and their goals and desires. To see this NIH National Cancer Institute site, just click here:  .

History in the West: A long history of medical doctors in Europe has established a firm naturopathic foundation of research and theory in the use of Complementary Medicine in cancer therapy:

The foundation of complementary medical therapies in European cancer protocol rests with the German doctor Max Gershon. Dr. Gershon examined the mechanisms of cell mutation and came up with a comprehensive list of therapies. Alone, these therapies may not be enough to significantly reverse the cancerous mutations, but together, the package of therapies has been shown to be very helpful. Many patients with this approach have gone into cancer remission and survived long term. Cancer Therapy: The Results of Fifty Cases is Dr. Gershon's classic book. Other books available include: The Topic of Cancer, Cancer: A New Breakthrough by Virginia Livingston, author of a number of books. Dr. Gershon utilized a diet high in potassium with raw food juices, oxygen therapies, and a variety of techniques combined in naturopathic clinics and hospitals devoted to treatment of the cancer patient. In the early twentieth century, two schools of thought were developing concerning the actual mechanisms of cause and spread of cancerous cell mutations. The renowned Dr. Gershon, along with Dr. Otto Warburg, a Nobel Prize winning biochemist, built their research on the evidence of Dr. Steven Paget, who saw cancerous cell mutation as primarily a metabolic disease, and recommended focus on the prevention of spread of cancerous cell growth by improving the body's homeostatic mechanisms in a variety of ways to inhibit this seeding of cancer cells in vital tissues, or metastasis. The predominant school of thought in cancer at the time focused on the possibility that cancer was caused by a small set of predetermined genes, termed oncogenes, and that destruction of these mutated genes would stop the cancer. We have now learned that cancer is rarely stopped by destroying the genes and cells where the cancer originated, and that while there are very many genes, epigenetic factors, viral genetic factors, and even mitochondrial genes, that are related to cancerous cell mutation, there are no simple oncogenes, or too many oncogenes, depending on how you now define oncogene. While the work of Drs. Gershon and Warburg were treated as a threat to cancer therapy, and unfairly ridiculed, we finally see that they were indeed right. Hopefully, sensible integration of these approaches will someday provide cancer patients with much better outcomes.

While these adjunct cancer treatment protocols in Complementary Medicine, established in the 1940s in Germany, and showing considerable efficacy and success across the world since then, have survived, they have been fought with whatever means available by standard medicine. The propaganda that such physicians that supported these adjunct therapies were promoting them over standard care has been rampant for decades, with little evidence that any physician of merit was suggesting to patients that they do not utilize whatever treatments are available. Consequently, the underutilization of Complementary Medicine in cancer care has been the norm, despite the evidence of an array of benefits. Today, the utilization of acupuncture, herbal and nutrient medicine, dietary protocols, physiotherapies, energetic medicine, yoga, Tai chi, and various stress reduction techniques are finally utilized by a majority of patients in the United States, Europe, Australia and many other countries. Following this wide acceptance by the public has been the reluctant acceptance of Complementary Medicine in many major University Medical Centers in the United States, as well as medical groups marketing integrated cancer therapy. In China, many hospitals utilize TCM (Traditional Chinese Medicine) while the patient undergoes standard treatment, and many patients continue to utilize TCM after discharge to support their health. This same protocol is now seen in hospitals in Australia, Japan, Korea, and Brazil. While there is no cure for cancer, there is the chance that remission can be achieved in a majority of cases of serious cancers if a comprehensive treatment protocol is utilized. The worst part of modern cancer therapy is the effects of harsh therapies on the quality of life and functional capacity of the patient, and Complementary and Integrative Medicine (CIM/TCM) may provide many ways to improve this aspect of care, as well as contribute to the overall goal of cancer remission. That such safe and proven therapy, and the theories that guide this care, has been unfairly criticized and condemned with no actual proof of clinical harm for nearly 80 years has only harmed patients with cancer and denied them their right to choose an integrated care that could ease their suffering. When we take a serious look at how wrong the approach in standard medicine and theory has been, and how after so long we see no inkling of the promise to find an allopathic cure, we should see some shame, but instead we see only a stubborn adherence to a failed set of theories.

Additional Information / Information Resources and Links to Scientific Studies

While much research is illuminating the exact biomechanisms of many chemicals in herbs and nutrient medicines, the number of these anticancer effects are now very large, and the effects varied. Some of these chemicals may exert mild effects and some stronger effects, and all, of course, are dose-dependent. In other words, there is no single herbal chemical that may present a miraculous cure of cancer, and these varied herbal and nutrient medicines should be used in formulas or prescriptions that are specific to each case. This requires much professional thought and assessment, and guarantee of quality of these medicines. It is important to consult with a knowledgeable physician herbalist to receive proper care. The practice of trying a single herbal or nutrient extract that is advertised and bought online or off the shelf to treat cancer is a ticket for failure. Depending on standard medical practice, which has long opposed and thwarted this adjunct care, for proper treatment with herbal and nutrient medicine, may also be a ticket for failure. A knowledgeable Licensed Acupuncturist and herbalist or Naturopathic Doctor may provide the assured care that is needed. The practice of acupuncture may enhance the effects of this herbal and nutrient medicine as well, and the ultimate goal is always to get the body itself to achieve cancer remission, which is best accomplished with a holistic approach to overall health. Other articles on this website present much information on cancer and cancer adjunct therapies, with many more links to scientific studies at the end of these articles as well. We see from these, which represent just a small portion of the total, that there is now abundant proof of high quality to confirm efficacy and safety, and even provide useful guidelines in treatment.

  1. A 2013 thorough descrption of the type of cancer that Steve Jobs had, pancreatic neuroendocrine tumor, by experts at the renowned Cedars-Sinai Medical Center in Los Angeles, California, U.S.A. makes clear the facts concerning this type of cancer and the sensible approach taken by Mr. Jobs, integrating holistic Complementary Medicine effectively as an adjunct care to insure better quality of life and improve his outcome. This thorough article reveals that standard medicine still does not understand much of the pathogenesis of this cancer, that the behavior of these cancer cells is highly variable and unpredictable, that almost all of these cases remain benign and do not spread, and that the greatest sign of potential metastasis is metabolic and hormonal imbalance or dysfunction. Due to these uncertainties a more aggressive approach has been adopted, with surgical excision rather than a "wait-and-see" monitoring, but as these experts point out, there are no facts and studies that show that this approach produces better outcomes, or whether it creates more adverse risks and complications. It is assumed that the early surgical excision will be safer, but unknown. Obviously, Steve Jobs made his own choices in this uncertain situation, which should be the rule. The experts at Cedars-Sinai recommend that treatment and monitoring of this type of cancer be handled at clinics with a multidisciplinary approach:
  2. A 2013 meta-review of all published randomized controlled human clinical trials of TCM (Traditional Chinese Medicine specialty) adjunct cancer treatment, by experts at the Beijing University of Chinese Medicine and Vanderbilt University Medical Center in the United States, found 2395 randomized controlled human clinical trials and 579 non-randomized controlled human trials, involving 253,434 patients, starting in China in 1984. 72 percent of these studies combined TCM therapies of acupuncture, herbal and nutrient medicine and other modalities with standard treatments, and almost all the studies noted significant benefits in symptom improvement, biomarker indices, quality of life in survival, reduction of side effects of chemotherapy and radiation, reduced tumor size and overall safety in treatment. These experts noted that with new guidelines for trials based on the CONSORT and TREND agreements of fairness in clinical study design and reporting, the facts reported should be improved in the future. Such study demonstrates that TCM adjunct cancer care is safe and effective, low-cost, and improves outcomes, and should have been more widely integrated long ago as a Complementary and Integrative Medicine (CIM/TCM):
  3. A 2015 study of the use of TCM therapies in adjunct cancer care and prevention, by experts at the Cardiff University - Peking University Cancer Institute, a collaboration between the United Kingdom and China, found that many studies now demonstrate the effectiveness of this integrated approach, proving that herbal medicine may be useful to reduce side effects of chemotherapy, including bone marrow suppression involving anemia and immune dysfunction, symptoms of nausea and vomiting during standard therapy, inhibition of precancerous lesions and incidence of cancer, regulation of cancer cell proliferation, apoptosis, cell adhesion and metastatic migration of cancer cells, inhibition of tumor growth and angiogenesis, and modulation of the immune system effects. These effects are broad, and these experts do not note any adverse effects of combining TCM therapies with standard care:
  4. A meta-review of all studies of TCM therapies as adjunct and adjuvant cancer care, at the Shandong University Medical School, in Shandong, China, found that ample evidence supports and array of treatment protocols for an array of benefits in all stages of cancer care, both improving outcomes with standard care and relieving the harsh adverse side effects of standard cancer therapy. Of course, with TCM practice, these proven therapies are combined in actual clinical practice, making the benefits much greater than the single studied protocols:
  5. A 2016 meta-review of all published scientific studies of a branch of TCM adjunct cancer care, by the Dalian Medical University and Peking University School of Nursing, with a protocol of acupuncture, Tuina physiotherapy, Tai chi, Qigong and TCM 5 Element Music Therapy studied, showed that these provide beneficial adjunct care for cancer patients, improving the quality of life with absolutely no negative effects:
  6. An article published in the December 15, 2009, New York Times Health cites a study that showed that only 6 percent of women with high risk for breast cancer would consider using tamoxifen when the actual risks versus benefits were fully explained. For every 1000 women taking tamoxifen, 9 cases of breast cancer might be avoided, but 21 cases of endometrial cancer would be caused by the drug, 120 would experience serious hormonal symptoms caused entirely by tamoxifen, 31 could develop cataracts, and 21 would be threatened with blood clots that could cause serious strokes:
  7. A 2009 Danish population-based cohort study, supported by the Boston University School of Public Health, and the American Cancer Society, provides data on the incidence of deep vein thrombosis (DVT) with tamoxifen use, a very threatening event:
  8. A 2007 study at Fox Chase Cancer Center in Philadelphia noted that the main active metabolite of tamoxifen is formed via the liver enzyme product of CYP2D6 gene expression, and that selective serotonin reuptake inhibitors (SSRI anti-depressants) that are prescribed to prevent hot flashes occurring as a side effect of tamoxifen, may work by inhibiting the metabolism of tamoxifen by competing with the enzyme catabolism. This would, of course, seriously weaken the effectiveness of tamoxifen, and account for the decrease in side effects (published in Steroids, Volume 72, Issue 13, November, 2007, Pages 829-842). Such drug-drug negative effects are rarely mentioned in standard care, while the repetition of vague warnings against herbal medicine are ubiquitous, nonspecific, and not supported by sound studies:
  9. A 2006 published initial results of the long-term STAR (Study of Tamoxifen and Raloxifene) study found that long-term use of raloxifene in prevention of recurrence of estrogen receptor positive breast cancer in postmenopausal women was as effective as tamoxifen with fewer risks and side effects, although the number and type of side effects is still alarming:
  10. A 2007 article in Oncology Times gives the facts on rates of noncompliance with tamoxifen use due to side effects:
  11. A 2009 article by reports that a study published in the September issue of Cancer Research found a 4.4-fold higher risk of getting estrogen receptor negative breast cancer in the opposite breast when taking tamoxifen long-term:
  12. A comprehensive 2007 report on hormonal therapies in breast cancer prevention after initial therapies, by experts at the University of Kansas Medical Center, outline the many adverse effects from these therapies with long-term use, but of course do not mention the studies of benefits with Complementary and Integrative Medicine (CIM/TCM) to alleviate these "side effects" which occur in almost all patients. Instead, more and more drugs are added to the protocol, increasing the adverse drug effects, without considering the potential of benign adjuvant therapies:
  13. A 2013 meta-review of all published studies of herbal medicine and acupuncture adjuvant, or integrated care in breast cancer, by experts at the National Defense Medical Center and Taipei Medical University, in Taiwan, concluded that many studies support the use of herbal medicine and acupuncture in cancer care, with a variety of benefits, including boosting the immune system, relieving side effects of radiation and chemotherapy, relieving cancer pain, fatigue and gastrointestinal complaints, liver toxicity and generating healthy blood cells. The study cites the growing support in general for herbal medicine and acupuncture but states that it will take many more studies and clinical trials to reverse bias against the profession in standard oncology:
  14. A 2013 randomized controlled study at Harbin Medical University, in China, showed that integration with individualized Chinese herbal medicine for patients with breast cancer where chemotherapy failed to prevent progression, or metastasis, was both safe and effective when combined with standard biologic medicines - improving both survival time and quality of life:
  15. A 2011 human clinical study of the safety and efficacy of integrating Chinese Herbal Medicine with standard Pharmaceuticals in the treatment of cancer, at the Fudan University School of Medicine with the University of Texas M.D. Anderson Cancer Center, in Houston, Texas, showed in a study of 164 patients with pancreatic cancer and liver metastases that the addition of a common Chinese formula was well tolerated, could prolong survival, and improved quality of life. The formula used consisted of Heydotis (Bai hua she she cao), Skullcap (Huang qin), Job's tears (pearl barley), Ganoderma (Ling zhi or Reishi mushroom extract), and Hawthorn (Shan zha), and the patients were chosen for the study between 2002 and 2007:
  16. A 2005 study at Tulane University School of Medicine found that selenium was effective as an adjunct therapy to tamoxifen, helping to disrupt estrogen type A receptor signaling to potentiate tamoxifen influence. Unfortunately, this was never adopted by standard oncology, even though it was inexpensive, effective and perfectly safe:
  17. A 2015 study at Fudan University and the Shanghai University School of Medicine, in Shanghai, China, showed that the Chinese Herbal Formula called Bu Shen Ning Xin Tang, widely used to treat postmenopausal osteoporosis, works by inhibiting bone breakdown, or resorption, by effecting RANKL proteins downstream of estrogen receptors, suppressing NF-kbeta and activated T-cell activity. Such study demonstrates the benefits that may be seen by integrating with current biologics, perhaps increasing the effectiveness of biologics with similar effects, or affording a lower dose is adverse side effects are great:
  18. A 2012 study at the State Key Laboratory of Quality Research, in Macau, China, found that a chemical in the Chinese herb Curcuma zedoaria (E zhu), Furanodiene, enhanced the growth inhibition of estrogen receptor type a positive (ERa+) breast cancer cells when combined with tamoxifen, apparently exerting its effects independent of PPARy, but dependent on mitochondrial caspase modulation and CDK cyclins. Such study shows how herbal anticancer chemicals could broaden the scope of treatment inducing cancer apoptosis and preventing recurrence. E zhu, the source of Curcumin, an herbal chemical also much studied and proven to help treat cancer in adjunct care, has been perhaps the most prescribed herb in TCM cancer care:
  19. A 2015 study at the Zhejiang University College of Medicine, in Zhejiang, China, found that essential oil of Curcuma zedoaria, or E zhu, when combined with the standard chemotherapy agent Pacitaxel, was synergistically effective to suppress or inhibit ovarian cancer cell growth, and the potential for a lowered dose of the chemotherapy and reduced toxicity is possible with a combination of the two medicines:
  20. A 2010 study at Nanyang Technological University, in Singapore, discovered that chemicals in Curcuma longa, or Wen Yu jin, suppresses proliferation of HeLa cells in cervical cancer through cell cycle arrest and induction of apoptosis. The herbal chemicals were studied on human cervical cancer cells and in laboratory animals with induced cervical tumor:
  21. An article published in JAMA in February of 2008 summarizes scientific findings that synthesized erythropoietin (EPO) and darbepoetin are unsafe for cancer patients in the treatment of post-chemotherapy and radiation:
  22. A 2015 study at the Guangxi Medical University, in Guangxi, China, found that 4 common Chinese herbs used in formulas to treat anemia and bone marrow depletion, Astragalus (Huang qi), Salvia (Dan shen), Epimedii (Yin yang huo) and Saussurea (Xue lian), in the category of Kidney/Erythropoetin tonics, significantly enhanced the growth of new Bone Marrow derived stem cells, the precursors to fresh blood cells depleted by chemotherapy and radiation:
  23. A 2015 study by the Hong Kong Baptist University and Chengdu University, in China, outlines the extent of research on the Chinese tonic herb Saussurea involucrata, or Xue lian, showing that this herb contains 60 beneficial chemicals, and has been shown to exert anti-cancer, anti-inflammatory, antioxidant, and immunomodulating effects. Such study shows that both an historical documentation and modern laboratory research is extensive on such herbs. The safety of the herbal extract is documented from thousands of years of clinical use, and much study has involved its role in Traditional Chinese Herbal Formulary:
  24. A 2011 large cross-sectional survey in the United Kingdom, published in BMC Cancer, found that about 33 percent of cancer patients used Complementary and Integrative Medicine (CIM), with high satisfaction, and that a similar percentage of volunteer care workers and professionals utilized CIM as well, but that about 60 percent of health care professionals stated that they had inadequate knowledge of this medical specialty, and those that had some knowledge of CIM were more likely to recommend it to their patients:
  25. A 2007 review of published studies of Complementary and Integrative Medicine in cancer care found evidence that a number of therapies could be helpful to treat cancer-related fatigue, and recommended acupuncture, massage, levocarntine and the use of European Mistletoe extracts. This 2007 review recommended that more large studies be conducted of these interventions, showing that they presented promising results in adjuvant cancer care. All of these recommended protocols can be obtained in a single course of therapy from a Licensed Acupuncturist and herbalist skilled in physiotherapy:
  26. A 2010 meta-review of all published studies and articles concerning negative herb-drug interactions in cancer care, by the Hong Kong Baptist University School of Chinese Medicine, found 168 such published articles and almost no direct evidence of the negative interaction, but did find indirect evidence in these studies of positive benefits of the combination of herbal medicine and cancer drugs. The conclusion was that this widely touted negative herb-drug interaction in cancer care was theoretical at best, and that a better study design and more rigorous science was needed to actually present real evidence to guide care. For decades, the denial of positive benefits from professional herbal medicine has relied on anecdotal beliefs, not direct scientific facts, and it is high time that this was resolved:
  27. A 2013 meta-review of all published studies of negative herb-drug interactions in cancer care, by experts at the Utrecht University School of Medicine and the Utrecht Institute for Pharmaceutical Sciences, showed that real evidence of negative herb-drug interactions in cancer care is sparse, with few herbs studied, and evidence accumulated with in vitro studies not duplicated in clinical studies. Such widely denounced herbs as St. Johns Wort (Hypericum perforatum), not even used for cancer care, showed in studies that a dose-dependent inhibition of the CY3A4 pathway occurred in the first week of use, but changed to induction of the pathway with long-term use, and that aged garlic showed no CYP3A4 inhibition or affect drug levels, while milk thistle and ginseng (still referring to Siberian ginseng, which is not actually ginseng, but another species), showed in vitro inhibition but no negative effects in clinical interactions. There should be no doubt after this review that the subject of negative herb-drug interactions have been poorly studied and greatly exaggerated in standard medicine. There also should be no doubt as to the motivations for these gross exaggerations of risk:
  28. A 2005 study at the Kyoto Pharmaceutical University, in Japan, explored the potential for use of Traditional Chinese Herbal Medicine (THM) with anticancer drugs to decrease multidrug resistance in chemotherapy. A number of common herbs, such as Coptidis (Huang lian), Scutellaria (Huang qin), Rhei (Da huang), Poria (Fu ling) and Asari (Xi xin), as well as licorice root (Gan cao) and aged ginger, were shown to enhance sensitivity to Pacitaxel without affecting other chemotherapeutic agents, such as 5-Flourouracil. No adverse effects were noted. These experts concluded that use of Chinese Herbal Medicine with standard chemotherapy could greatly enhance outcomes and decrease multidrug resistance (MDR):
  29. A 2015 study at the Taipei University School of Medicine, in Taipei, Taiwan, found that the Chinese herb Solanum nigrum, or Long kui, safely potentiated the chemotherapeutic agents Cisplatin and Doxorubicin to increase effectiveness against human liver cancer cells, and potentially allows treating doctors to use a lower dose or shorter course of the chemotherapy to reduce adverse effects:
  30. A 2014 study at the Society for Cancer Research at the Hiscia Institute, in Arlesheim, Switzerland, found that the anticancer herb Viscum Album (European mistietoe), when used with the chemotherrapy drug cysplatin, did not inhibit the cytotoxic effects of the chemotherapy in cancer cell lines in vitro with breast, pancreas, prostate or lung cancer. These experts note that no safety risk of negative herb-drug interaction appears to exist, contrary to much published warnings in the past:
  31. A 2016 study at the Tabriz University of Medical Sciences Immunology Research Center, in Tabriz, Iran, found that the alcohol extract of Urtica doica, or Stinging Nettle, helps induce apoptosis (programmed cell death) in prostate cancer cells, with a modulatory effect, decreasing bcl-2 and increasing caspase 3 and 9 expression. Such research points to the potential for a multi-herb therapy enhancing standard treatment as an adjunct:
  32. Another 2015 study at theTaipei University School of Medicine showed that the Chinese herb Solanum nigrum, or Long kui, potentiated the effects of Cisplatin, Doxorubicin or Docetaxel in the treatment of ovarian cancer:
  33. A 2015 study at the H. Lee Moffitt Cancer Center and Research Institute, in Tampa, Florida, found that that a chemical in the Chinese herb Paris polyphylla (Qi ye yi zhi hua, or Chong lou), polyphillin D (PD), showed that it had strong anticancer effects on all ovarian cancer cell lines, and significantly decreased the adverse effects of cisplatin:
  34. A 2012 study at the Sichuan University School of Medicine, in Chengdu, China, found that the Chinese herbal chemical Wogonin, in the herb Scutellaria baicalensis, or Huang qin, safely potentiated the effects of the chemotherapy drug Cisplatin, and provided effective antioxidant effects, for both lung cancer and cervical cancer cell lines:
  35. A 2014 study at the Shandong University School of Medicine, in Shandong, China, found that the integration of the anticancer herbal medicine derived from Trypterygium wllfordii, or Lei gong teng, tripotolide, increased sensitivity of liver cancer cells to chemotherapy such as Cisplatin and 5-FU (5-Fluorouracil) in vitro and in vivo, and also inhibited Bcl-2 expression (breast, prostate, leukemia, lung and skin cancers) and Bax expression (colorectal and gastric cancers). No negative herb-drug interactions were found:
  36. A 2011 study at the National Medical Center of the Beckman Research Institute, in Duarte, California, found that a chemical flavonoid in the herb Ocimum Sanctum Linn or Tulsi (Holy Basil), called vicenin-2, was and effective anticancer agent in prostate cancer, and increased the effects of the chemotherapy drug docetaxel. No negative herb-drug interactions were noted:
  37. A 2013 study at the Zhejian University College of Pharmaceutical Science, in China, found that the active chemical in the Chinese herb Artemesia annua, or Qing hao, now standardized as dihyroartemisinin (DHA), significantly affects cancer cell angiogenesis in lung cancer when combined with cisplatin:
  38. A 2015 study of phytochemicals in medical treatment, or the use of plant-based herbal and nutrient medicine, by the University of the Urbino Carlo Bo School of Medicine, in Urbino, Italy, showed that a number of herbal and nutrient chemicals have been shown to target cancer stem cells by various pathways, including the Wnt/beta-catechin T-cell pathway. Such scientific study shows that dramatic benefits from adjunct care with herbal medicine, which is just one part of a holistic treatment received from a competent Licensed Acupuncturist and herbalist in helping to treat cancer in an integrative and complementary manner. The phytochemicals mentioned in this study summary include EGCG, curcumin, piperine, beta-carotene, genistein, and the whole extracts of various herbs, as well as sulforaphane (broccoli sprouts and cruciferous vegetable extracts with DIM):
  39. A 2003 randomized controlled human clinical study at the Lampang Regional Cancer Center, in Lampang, Thailand, showed that use of bitter melon extract (Momordia charantia) with targeted radiation therapy in the treatment of advanced cervical cancer reduced the dysfunction in NK lymphocytes to enhance the ability of the immune system to prevent growth and proliferation of cervical cancer cells. The herbal extract decreased P-glycoprotein on the NK cell membranes, and in prior studies bitter melon was shown to stimulate lymphocyte activity:
  40. A 2016 study at Assam University, in India, showed that an alcohol extract or tincture of Curcuma caesia successfully protects against adverse health effects of the chemotherapy drug cyclophosphamide on bone marrow cells, liver and kidney tissues and function. Such study demonstrates that such therapeutic tools are safe and effective, and should just be one part of a holistic strategy to improve outcomes in integrated cancer care:
  41. A 2015 study at the Chang Jung Christian University School of Medicine, and the National Cheng Kung University School of Medicine, in Taiwan, showed that the Chinese herb Pogostemon cablin (Huo xiang) effectively inhibited the growth of cervical cancer and induced cell apoptosis. This benign and gentle herb is used in many traditional formulas, for a variety of health problems, and can be used as an adjunct part of care in herbal formula to be used with standard treatments to prevent cervical cancer:
  42. A 2012 study at the Dong-A University School of Medicine, in South Korea, showed that EGCG (epigallocathechin-3-gallate) from grape seeds and other natural sources, inhibits cervical cancer and downregulates the estrogen and progesterone receptor expression that cause cervical and other cancers in sexual tissues of the cervix, uterus, ovaries and breasts. This standardized extract could be an effective part of a more comprehensive strategy in CIM/TCM to prevent or treat these cancers:
  43. Research in 2014 at the University of Mexico, in Mexico City, found that aqueous extract of the medicinal mushroom Ganaderma lucidum, called Ling Zhi in China and Reishi in Japan, effectively inhibited cervical cancer cells and dysplasia induced by human papilloma virus, or HPV, and induced cell apoptosis in 3 common cancer cell lines, HeLa, SiHa, and C-33A:
  44. A 2007 meta-review of all published scientific study of acupuncture to treat chemotherapy-induced leukopenia (immune white blood cell deficiency) by the esteemed Dana-Farber Cancer Institute in Boston, Massachusetts, U.S.A. found that 11 human clinical trials met their criteria, and 7 presented measurable white blood cell counts, with all 7 showing an increase in leukocytes during the treatment with chemotherapy or chemotherapy with radiation combined, instead of the expected drop in leukocyte counts:
  45. A 2013 study of the use of acupuncture to treat lymphedema after breast cancer treatment, by the esteemed Memorial Sloan-Kettering Cancer Center, in New York, New Yrok, U.S.A. found that average reduction in arm circumference was about 1 cm, and 11 of 33 patients exhibited a reduction of greater than 30 percent of lymphedema after just 8 acupuncture treatments in 4 weeks. The women had a diagnosis of post-treatment lymphedema for 6 months to 5 years, and the acupuncture treatment showed no adverse effects:
  46. A 2015 randomized controlled human clinical trial of acupuncture to treat lymphedema after cancer therapy, by experts at the Catholic University in Daegu, South Korea, showed that this is an effective treatment. These physicians used the Saam theory and method of Korean acupuncture, which selects points on each patient by traditional methods, using the 5-shu points in a 5-element relationship:
  47. The Saam theory and method of acupuncture point selection is explained by experts at the Wangwong University Korean Medical Hospital, in Gwangju, South Korea:
  48. A 2015 meta-review of all scientific studies of treatments for lower extremity lymphedema after cancer surgery, usually the removal of lymph nodes, by experts at the Queen Mary University of London, UK, found few quality studies that showed effective treatment, and only 5 randomized controlled human clinical trials, which showed positive effects for an herbal chemical Coumarin, standardized from medicinal cinnamon bark (Gui zhi or Rou gui), and graded compression stockings. Obviously, more research would reveal other effective herbal treatments, both oral and topical, and combined with acupuncture stimulation, lymphatic massage and fitted compression stockings, could finally provide reasonable care for lymphedema:
  49. A 2013 study of the effects of acupuncture to relieve hot flashes induced by biologic anti-estrogen drug therapy for breast cancer, at the Catholic University of Daegu, South Korea, found that a course of 12 treatments (3 times per week for a month) reduced hot flash severity 70-95 percent in all patients, and this was sustained 4 weeks after therapy:
  50. A 2015 randomized controlled human clinical trial of acupuncture with electrical stimulation for the treatment of hot flush after treatment for breast cancer with drugs such as Tamoxifen, at the Perelman School of Medicine at the University of Pennsylvania, in Philadelphia, Pennsylvania, U.S.A. and Emory University in Atlanta Georgia, showed that frequent treatment for 8 weeks was more effective than standard treatment with Gabapentin, with none of the adverse effects of the drug. These outcomes were greatest during the follow-up at 24 weeks, showing that the acupuncture produced sustained benefits:
  51. A 2013 study of the effects of acupuncture to relieve joint pain and stiffness, a common complaint with use of aromatase inhibitors in breast cancer therapy, was conducted at the University of Sydney School of Medicine, and found to be safe and effective:
  52. A 2014 randomized study by the University of Texas MD Anderson Cancer Center, in Houston, Texas, concluded that acupuncture was safe, effective and feasible as an adjunct therapy to treat pain in cancer therapy, and announced plans to design larger randomized controlled human clinical trials to positively prove and refine the use of acupuncture in standard cancer care:
  53. A 2007 announcement by the University of Leeds, Leeds, United Kingdom, showed that the world of standard medicine is finally seriously considering widespread adoption of acupuncture as standard integrated therapy for cancer. This proposal outlines the process of treatment and patient selection, and set up of randomized controlled human clinical trials with breast cancer patients undergoing chemotherapy, hoping to find proof of success in achieving improved quality of life and alleviation of harsh side-effects of therapy, such as immune deficiency, anemia, fatigue, depression, nausea, lymphedema etc.:
  54. A 2015 randomized controlled human clinical trial of acupuncture to relieve radiation and chemotherapy-induced anorexia in patients treated for thyroid cancer, by experts at Daejion University, Wongwang University and the Chungnam University Schools of Medicine, in Daejeon, South Korea, found that this short course of 6 acupuncture treatments significantly relieved the anorexia:
  55. A 2013 meta-review of all published scientific studies of acupuncture in adjunct care for lung cancer patients, conducted by The University of Hong Kong, China, found that ample evidence existed to demonstrate strong immunostimulatory effects directly related to lung cancer pathology (significant increases in beneficial IL-2, complement cells CD3,4 and 8, and NK cells), as well as alleviation of cancer therapy induced bone marrow suppression (immunodeficiency and anemia) and alleviation of nausea, vomiting and pain. These studies also showed that acupuncture improved quality of life and functional status, and immediate tumor responses to therapy:
  56. A 2013 multi-center meta-review of published studies of Chinese Herbal Medicine as an adjunct therapy for advanced Non-small Cell Lung Cancer, which has a very high mortality rate, by experts at the University of Texas Southwestern Medical Center, the Queen Elizabeth Hospital in Hong Kong, the University of Hong Kong, the Guangzhou University of Chinese Medicine, and various Chinese hospitals, found that combined therapy with standard chemotherapy and Chinese herbal medicine significantly improved survival rates, immediate tumor responses to chemotherapy, and functional performance of the cancer patients, as well as reducing immediate side effects of chemotherapy, such as nausea and vomiting and leukpenia. A large number of Chinese herbs were supported by this review:
  57. A review of all published studies concerning negative herb-drug interactions in chemotherapy practice, by Hong Kong Baptist University, found that nearly all of this evidence was theoretical, or anecdotal, although strong citation of these warnings of negative herb-drug interactions prevent use of herbs in the standard setting. These experts noted that in China, and much of the world, the use of Chinese herbal medicine concurrent with chemotherapy and other cancer drugs is high, yet no actual publication of clinical harm is available, only theoretical and anecdotal evidence. Some studies have demonstrated that high doses of St. John's Wort and Aged Garlic may exert some effects on the clearance and excretion of certain chemotherapeutic drugs, but high doses are almost never used in standard herbal practice in TCM:
  58. A 2014 study at the Society for Cancer Research a the Hiscia Institute, in Arlesheim, Switzerland, found that the rising evidence of the importance of Complementary Medicine in cancer care, and anecdotal reports of potential negative herbal and drug interactions needs to be researched. These experts found that one of the most promising herbs used as an adjunct to chemotherapy, Viscum alba (European Mistletoe) showed no risk of adverse drug-herb interactions or safety risk when used at the appropriate dosage with chemotherapeutic drugs:
  59. A 2015 meta-review of integration of Chinese Herbal Medicine into treatment for breast cancer, at the Kyung Hee University School of Medicine, in Seoul, South Korea, showed that 8 high-quality randomized controlled human clinical trials of 798 patients showed that combining Chinese Herbal Medicine with standard cancer care was effective in improving Quality of Life and reducing symptoms of therapy such as hot flush, with no evidence of adverse effects or contraindications with professional herbal prescription:
  60. A 2015 meta-review of all published scientific studies of Chinese Herbal Medicine to treat cancer pain as an adjunct therapy, by experts at the Kyung Hee University School of Medicine, in Seoul, South Korea, showed that 24 high-quality randomized controlled human clinical trials showed positive benefits from professional herbal therapy in adjunct cancer care, with a significant reduction of pain, and no evidence of adverse effects:
  61. A 2008 study, at Chia Nan University of Pharmacy and Science, in Tainan, Taiwan, found that the Chinese herbal Solanum plants (Bai ying, Long kui, and Jia Ying ye) exerted modulating effects in different cell lines on growth and inflammatory factors, but were found to be safe and effective in combination with chemotherapeutic drugs to treat lung cancer. The study showed that active chemicals in these herbs used in specialized anticancer therapy in Chinese hospitals down-regulated HER-2 and upregulated TNF-alpha and Fas anti-inflammatory cytokines in breast cancer cells lines, but upregulated HER-2 expression in lung cancer cell lines. This specific upregulation of HER-2 expression in large cell H661 and small cell H69 lung cancer lines increased the effectiveness of the chemotherapeutic agents trastuzumab and epirubicin in treating these lung cancers, and that the herbal extracts did not negatively influence other cancer cell lines. Such scientific study demonstrates that great potential of applying specific herbal therapies in adjunct cancer care:
  62. Another 2008 study, at Kaohsiung Medical University, Kaohsiung, Taiwan, found that the Chinese herbal Solanum plants (Bai ying, Long kui, and Jia Ying ye), contained an active chemical called solamargine that modulates HER-2/neu expression in breast cancer cell lines, and downregulation of the HER-2 by the herbal extract enhanced the effects of common chemotherapeutic drugs, such as MTX (methotrexate), 5-fu (5-florouracil), and CDDP (cisplatin) in treating these aggressive breast cancers. We find that overexpression of HER-2 in estrogen-receptor positive breast cancers decreases the effects of the chemotherapy, and that the simultaneous use of these herbal extracts (glycoalkaloids) negated some of the resistance to the chemotherapy:
  63. A 2013 study at The Chinese University of Hong Kong School of Medicine showed that a specific lectin in the Dioscoria species, commonly called wild mountain yam, and used both as an herbal medicine (Shan yao) and as an edible food, with specific species in Mexico used to create bioidentical hormonal creams that simulate progesterone, has the highly potent ability to prevent or treat a number of breast cancer cell lines, inducing apoptosis, or programmed cell death, in these cancer cells:
  64. A 2014 study at the University of Guangzhou, Laboratory of Tumor Molecular Biology and Targeted Therapies, found that the herbal chemical solamargine (from Solanum plants Bai ying, Long kui and Jia Ying ye) effectively inhibits proliferation of lung cancer cell lines and induces apoptosis, through the p38 MAPK-mediated suppression of phophorylation and protein expression of Stat3:
  65. A 2014 meta-analysis of use of Chinese herbal formulas combined with biologic pharmaceuticals, such as tyrosine kinase inhibitors, for treatment of advanced small-cell lung cancer, which is very deadly, performed at the Shanghai Jiaotong University School of Medicine, in China, revealed that 13 such studies met high quality standards that showed that anti-cancer and support therapies with Chinese Herbal Medicine can increase the efficacy and reduce the toxicity of chemotherapy with no significant adverse effects or contraindications. Since this standard biologic therapy for advanced lung cancer is not well tolerated for a high percentage of patients due to adverse side effects, such adjunct care with TCM integration presents great possibility for better outcomes and quality of life for these patients:
  66. An article published in JAMA in September of 2009 and outlined in the New York Times in October summarizes scientific findings that we now know that many cancers slow, stop or reverse into remission without standard therapy, the key being how to enhance this natural process with Complementary Medicine:
  67. A study of herbal chemicals in cancer treatment at the Yeditepe University Medical School, in Istanbul, Turkey, showed that this is a promising field in cancer care, and that a widely studied anticancer herb Viscum alba, or European Mistletoe, has shown in a number of randomized controlled human clinical trials that this herbal extract is effective in treating various cancer cell lines through various bioactive pathways, and recommended more study of these exact mechanisms. No adverse effects were noted:
  68. A 2013 study of combining Viscum alba alcohol extract with the chemotherapy drug doxorubicin, at the Iuliu Hajlganu University School of Medicine and Pharmacy, in Romania, noted that addition of this proven anticancer herbal extract increased the protective and antioxidant effects of the chemotherapy in laboratory animals with Ehrlich cancer cells and ascites:
  69. A 2012 study of the herbal extract from Viscum alba, or European Mistletoe, in treatment of human myeloid leukemia, showed that chemicals from this herb induced apoptosis, or programmed cell death, in a number of leukemia cancer cell lines, and exerted beneficial antioxidant effects and reduced cell toxicity via various biochemical pathways:
  70. Evidence-based herbal medicine: Anticancer and antitumor effects of a common Chinese herb, Huang qin, or Scutellaria baicalensis, conducted in 2003 at the Mount Sinai School of Medicine in New York:
  71. Anticancer and antitumor effects of a common Chinese herb, Ulmus macrocarpa or davidiana, widely used in Korean herbal medicine:
  72. Anticancer and antitumor effects of a common Chinese herb, Ban zhi lian, or Scutellaria barbata:
  73. Anticancer and antitumor effects of a common Chinese herb, Yun Zhi, or Coriolus versicolor, commonly called turkeytail mushroom:$=relatedarticles&logdbfrom=pubmed
  74. Further research into the activities that make the Chinese herb, Yun Zhi, or Coriolus versicolor, commonly called turkeytail mushroom, effective against breast cancer cells:$=relatedarticles&logdbfrom=pubmed
  75. Research in Argentina in 2006 found that parthenolide in Magnolia grandiflora and Feverfew was effective in vitro in achieving dose dependant nontoxic cell death of cancerous B-cells in chronic lymphocytic leukemia: http://www.
  76. Research in France in 2006 found that St. Johns' Wort, or Hyperforin, was effective ex vivo in achieving dose dependant nontoxic cell death of cancerous B-cells in chronic lymphocytic leukemia, and also inhibiting the cancer cell capacity to secrete a chemical that stimulates the cancerous creation of new blood vessels:
  77. Research in 2008 at the University of Alabama Birmingham's Department of Comprehensive Cancer Center found that proanthocyanidins in whole grape extract prevented the malignant spread of metastatic cancer in a number of novel metabolic ways:
  78. Research in 2014 at Nanjing Medical University and Anhui Medical University, both in China, found a mechanism of action of the Chinese herb Astragalus mongholicus (Huang qi), long touted in anticancer therapy as an adjunct therapy, in its anticancer effects with stomach cancer. It appears that this common Chinese herb regulates the toll-like receptor-4 (TLR4) and precipitates the maturation of dendritic cells to inhibit growth of human stomach cancer cells:
  79. Research in 2015, at the Institute of Cytology and Preventive Oncology, at the University of Allahabad, in India, and the MD Anderson Cancer Center, in Houston, Texas, U.S.A. found that the now famous Chinese herbal chemicals Berberine and Curcumin, largely derived from Coptis (Huang lian) and Curcuma (E zhu), along with resveratrol (Hu zhang), act synergistically with standard chemotherapy (5-fluorouracil) in the treatment of stomach cancer, improving STAT3 regulation and survivin expression to increase the effects of the chemotherapy. These same herbal chemicals already have been proven to possess significant anticancer and antioxidant effects:
  80. Research published in Clinical Cancer Research reveals that resveratrol, an herbal chemical found in Hu zhang, or polygonum cuspidatum, significantly inhibited excess growth factors in at least 5 cancer cell lines:
  81. A 2015 study of resveratrol, an active chemical found in the Chinese herb Hu zhang (Polygonum cuspidatum) and now standardized as an herbal medicine, at Hebei Medical University, in Shijiazhuang, China, found that this chemical significantly enhanced the effects of a standard chemotherapy drug, 5-Fu (Fluorouracil), an anti-metabolite, in the treatment of skin cancer melanoma. 5-Fu (Fluoruoracil) is also used to treat colorectal, head and neck cancers, and resveratrol may be thus applicable to a safe and effective adjunct treatment in these cases:
  82. Research in 2009, at Massachusetts General Hospital and Harvard Medical School, U.S.A. found that a common Chinese herb Coptis chinensis, or Huang Lian, which contains the active chemical berberine, along with other valuable chemicals, significantly inhibited growth of various breast cancer cell lines, and could be a valuable adjunct therapy to use with Tamoxifen and other aromatase inhibitors in the treatment or prevention of estrogen-receptor positive breast cancer. These scientists recommended that either Huang Lian or a standardized extract of Berberine could provide multiple effects that would aid standard breast cancer treatment, especially as concerns about drug resistance and efficacy continues to grow in this arena:
  83. Research in 2009 at the Chinese University of Hong Kong, in China, found that an herbal flavonoid found in licorice root, isoliquiritigenin, deters the growth of cells that overexpress aromatase, a key enzyme related to estrogen-receptor positive breast cancer. While licorice root, or Gan cao, a common Chinese herb, is not a guaranteed medicinal by itself to prevent such breast cancer, this study does show how various herbal and nutrient chemicals may be combined to form an effective protocol:
  84. Information on DIM, an active metabolite of the nutrient chemical I3C found in cruciferous vegetables, and its uses and activities:
  85. DIM has been found to be a potent aromatase inhibitor, hormone modulator, and inhibitor of growth factors to achieve great effects in adjunct cancer care, but a 2013 study at Nanjing University School of Life Sciences, Nanjing, China, found that DIM also exerts a potent protection against chemotherapy-induced heart damage, exerting anti-fibrotic effects and upregulating a type of beneficial BRCA gene that exerts antioxidant and other protective effects in tissues. While some BRCA genes, or their mutations, are linked to cancers, other BRCA expressions are proven to be protective against cancers:
  86. Research in 2010, at the University of Rome Sapienza, Rome, Italy, found that DIM (diindolymethane) induced Par-4 (prostate apoptosis response factor), which helped induce normal cell death, or apoptosis, which protects against cancerous mutation. This was found to be applicable to cholangiocarcinoma as well, a malignant form of liver and gallbladder cancer. While the use of pharmacological drugs is emphasized in this study, it was acknowledged that DIM was also effective in this regard:
  87. Research in 2009, at the Hong Kong Polytechnic University, Hong Kong, China, found that DIM (diindolymethane) and its derivatives, act as dimers that exert potent antitumor effects in the body, and these researchers suggest that combining dimers, such as DIM and common chemotherapy agents (cisplatin et al) could have a beneficial combined effect. The dimer in the Chinese herb Artemesia qinghao, artemesinin homo-dimer, was also mentioned in this regard:
  88. Research in 2014, at the University of South Carolina School of Medicine, U.S.A., found that the nutrient supplement DIM (diindolymethane), a metabolic product of I3C (indole-3-carbinol), was effective to inhibit superantigen T-cell responses in a modulatory manner, affecting the epigenetic expression of enterotoxins from pathogenic staphylococcus bacteria to inhibit unhealthy excess cytokine expression, acting as an HDAC (histone deactylase class) inhibitor. While this nutrient medicine, well known to act as an aromatase inhibitor to prevent of treat estrogen-receptor positive breast cancer, and as a hormonal modulator helpful in menopause and other hormone imbalances, may not be as effective as pharmacological HDAC inhibitors, it was found to inhibit HDAC-1 but not HDAC-2 in activated T-cells, providing a safer modulatory effect:
  89. Research in 2002, at the University of Kansas Medical Center, U.S.A., found that I3C, the nutrient chemical found in cruciferous vegetables, acts in a similar manner to inhibit ovarian growth and function as tamoxifen, a chemotherapy agent commonly used to prevent or treat breast and ovarian cancers. I3C was found to have effects on both the ovaries and the hypothalamus, though, in contrast to the effects of tamoxifen. The I3C metabolite, DIM, was not found to inhibit ovulation, and thus would be less problematic at a high dose in breast cancer therapy and treatment:
  90. A variety of potent anticancer activities of medicinal Lignans, such as those found in the Norwegian Spruce (NuLignan), as well as treatment and prevention of chronic systemic inflammation that drives cancer, is found in research conducted in 2009 at the University of Insubria, Varese, Italy:
  91. Significant anticancer actiivity of NuLignan specific to breast cancer was first discovered in animal studies in Finland in 2000:
  92. Further studies at the University of Turku in Finland, in 2001, showed a specificity of NuLignan for well-differentiated adenocarcinoma:
  93. Studies of NuLignan at the University of Insubria, Italy, in 2007 found that 7-hydroxymatairesinol potassium acetate (NuLignan) converted well to enterolactone, and was active at substituting for estradiol in estrogen receptors that drove breast cancer, effectively blocking this activity. They also found that when given at the same time as tamoxifen, that these effects were reduced:
  94. Research in 2009 at Wake Forest University Comprehensive Cancer Center found that glutathione was protective against the strong carcinogen benzopyrene aromatic hydrocarbon (linked to breast cancer):
  95. Research in 2005 by Edward Friedman of the University of Chicago assessed the contradictory data of prostate cancer research to find the correct model for what actually creates and drives prostate cancer:
  96. Research in 2009 at National Chung Hsing University in Taiwan, China, found that a key chemical in the Chinese herbs Mu dan pi and Chi shao (Paeonia suffructicosa and lactiflora) has a dose-dependent effect of suppressing prostate cancer metastasis and growth that is androgen receptor driven, affecting several mechanisms:
  97. Research in 2011 at Kyung Hee University in Seoul, South Korea, found that a key chemical in the Chinese herbs Mu dan pi and Chi shao (Paeonia suffructicosa and lactiflora) suppresses triple-negative breast cancer and metastasis:
  98. Research in 2012, at Columbia University College of Physicians and Surgeons, in New York, New York, U.S.A. found that an active chemical in the herb rosemary, carnosic acid, in combination with a now well-known active chemical in a number of Chinese herbs, curcumin, now available in more bio-active forms (Long Vida) and conjugated with phosphotidylcholine to increase absorption and circulating dosage, significantly inhibited growth and spread of estrogen-receptor negative breast cancers. Carnosic acid is a diterpene found in rosemary and sage (Salvia), presently used as a natural preservative and antioxidant in foods and toothpastes, mouthwash, chewing gum, and is best obtained with extraction into an alcohol or glycerite tincture from dried leaves:
  99. Research in 2010, at Ege University, in Bornova, Turkey, found that an active chemical found in the herb Rosemary, carnosic acid, had significant effect inhibiting growth and spread of 6 cancer cell lines, with an alcohol or supercritical carbon dioxide extraction, with K-562 chronic myeloid leukemia cancer cells most sensitive:
  100. Research in 2010, at the Institute for Oncology and Radiology of Serbia, noted that active chemicals in the herb rosemary, including rosmarinic and ursolic acid, had significant effects of inhibition of growth and spread of the cervical cancer HeLa cell line, as well as two breast cancer cell lines (MDA-MB-361 and 453). This herbal extract was obtained by both alcohol and water extraction methods:
  101. Research in 2011 at Hanyang University in Seoul, South Korea, showed that the Chinese herb Qian niu zi, or Pharbitis nil, exerted significant effects in inhibition of HER-2 overexpression in breast cancer:
  102. Research in 2007 at Hutchinson Medipharma in Shanghai, China, found that flavonoids in the Chinese herb Ku shen (sophora flavescens) inhibited HER-2 and other receptor tyrosine kinase activities:
  103. Research in 2008, at Humboldt University of Berlin, Department of Oncology, found that an active chemical in the Chinese herb Magnolia officianalis, honokiol, exerted significant effects inhibiting HER-2 overexpression, and could be a valuable adjunct medicine to combine with mTOR inhibitors, such as the drug Rapamycin, in breast cancer treatment:
  104. Research in 2005, at Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China, found that an active chemical in the Chinese herb Shiraia bambusicola (Tian Zhu huang, or Zhu huang Jiao nang, a fungus that grows on specific bamboos in the sap), called 11,11'-dideoxy-verticillin (related to penicillin), exhibits potent inhibition of HER-2, VEGF, and other growth factors that drive aggressive breast cancers, and shows potent anti-tumor activity:
  105. Research in 2015 at the People's Hospital of Henan Province, in Zhengzhou, China, showed that the highly studied anticancer herb Scutellaria barbata (Ban zhi lian) significantly inhibited HER-2 and downregulated signaling kinases that drive breast cancer, as well as inhibiting angiogenesis. These studies were conducted on human lung cancer cells with HER-2 mutations:
  106. Research in 2005 at Evanston Northwestern Healthcare Research Institute in Chicago, Illinois, found that the supplement GLA (gamma linolenic acid) produced a significant synergistic effect with Herceptin to increase inhibition of HER-2 overexpression:
  107. A 2009 study at Shanghai Jiao Tong University School of Medicine, in Shanghai, China, found that the Chinese herb motherwort (Yi mu cao), long studied as a significant adjunct herbal treatment in prevention of breast cancer, significantly inhibits growth and spread of both estrogen-receptor positive and negative breast cancer cell lines in a manner independent of apoptotic pathways induced by Tamoxifen, making this extract (both alcohol and water extracts studied, and alcohol extract found to be much more effective) a safe and effective herbal treatment to use with Tamoxifen therapy. The Yi mu cao extracts exerted cytoxic and cell cycle arrest effects at a low dosage:
  108. A 2012 study in Freiburg, Germany, found that addition of the anti-inflammatory immune modulator Viscum album extract (European mistletoe) increased the quality of life for patients with early stage breast cancer receiving chemotherapy:
  109. Research in 2012 at the University of Hong Kong performed a meta-review of randomized controlled human clinical trials of Chinese Herbal Medicine as an adjunct therapy combined with chemotherapy and found that this significantly increased survival time with colorectal cancer, slowed cancer progression better than chemotherapy alone, improved quality of life and reduced the adverse effects of chemotherapy treatment: http:/
  110. Research in 2006 at the University of California San Diego showed that maintaining minimum circulating levels of the hormone called Vitamin D dramatically reduced the risk of colon, prostate and breast cancers:
  111. Meta-review of research concerning the hormone Vitamin D and cancer prevention, in 2013, at the University of California San Diego, here reviewed at Johns Hopkins Colon Cancer Center showed that maintaining at least a 34 ng/ml of the hormone Vitamin D in circulation reduced the incidence of colorectal cancer in half, with even higher levels showing significant benefit, and this also produced a 72 percent reduction in colon cancer mortality. Further study, involving 190,000 individuals, showed that maintaining both a hormone Vitamin D level and health calcium metabolism offered significant protection against colon cancer, especially in men. Studies of colorectal cancer patients taking Vitamin D supplement to maintain healthy circulating levels noted that these benefits aided colon cancer much more than rectal cancer, and subsequent studies show that the hormone Vitamin D receptors were diminished in rectal cancer:
  112. Research in 2012 at the University of Chicago Comprehensive Cancer Center explores the reasons why the hormone Vitamin D and its receptor function and receptor are integral to the development of colorectal cancer, exploring the beta-catenin pathway. A 10-year multicenter randomized controlled clinical trial wil be completed in 2014, demonstrating the ability of hormone Vitamin D to prevent and potentially treat colon cancer:
  113. Research in 2013 at the University of Alabama, Birmingham, Alabama, U.S.A. found that proanthocyanidins, found in grape seeds, were among the most promising of herbal and nutrient chemicals showing significant anti-cancer activities. Proanthocyanidins in grape seed extract are shown to be effective in colon cancer, potentially associated with beta-catenin signaling:
  114. Research in 2008 at the German Cancer Research Center in Heidelburg, Germany, showed that the now famous Chinese herbal chemical artemisinin, in Artemesia annua (Qinghao) exerts significant anticancer activity via the Wnt/beta-catenin signaling pathway:
  115. Research in 2012 at the Center for Cancer Research, NIH, Frederick, Maryland, U.S.A. found that lignans and proanthocyanidins in herbal and nutrient medicine have shown significant benefits in prevention of colorectal cancers, and a human clinical trial of safety showed no association of high proanthocyanidin and lignan intake and recurrence of colorectal adenoma, demonstrating safety of this protocol:
  116. Research in 2014, at Guangzhou Medical College and Macau University of Science and Technology, in China, found that an active chemical in the Chinese herb Trypterygium wilfordii (Lei gong teng), celastrol, dramatically downregulated the expression of protein endothelial growth factor receptors (EGFR), increased the ratio of Bax/Bcl-2, and promoted cancer cell apoptosis (programmed cell death) in 2 lung cancer cell lines that were resistant to standard therapy in the form of gefitinib (Iressa), and epidermal growth factor receptor interruptor. An alcohol tincture would be most effective to capture this chemical, celastrol:
  117. Research in 2014, at the University of Macau, in China, found that an active chemical in the Chinese herb Curcuma rhizome (E Zhu), furanodiene, significantly inhibited cell proliferation and migration in lung cancer cell lines 95-D, at a relatively low dose, and affected signaling molecules that regulate apoptosis, such as Bcl-2:
  118. Research in 2013, at Kagoshima University, the University of the Ryukyus, in Japan, and Diponegro University, in Java, Indonesia, found that the active herbal chemical lignan in Arctium lappa (Niu Bang zi), arctigenin, induced apoptosis (programmed cell death) and other cytotoxic effects against lung cancer and other cancer cell lines, via epigenetic modulation of histone expression, and the intracellular glutathione level (GSH):
  119. A 2014 study at Chongqing Medical University, in China, found that the active chemical in the Chinese herb Artemesia annua, or Qing hao, now famous as artemisinin in treatment of malaria, and found to be a potent anticancer chemical by experts at Georgetown and Johns Hopkins University Medical Schools, is a very effective anticancer herbal medicine for lung cancer. These experts found that dihyroartemisinin inhibits inflammatory cancer pathways and induces cell apoptosis in A549 lung cancer cells:
  120. Research in 2014, at the University of Calcutta Guha Center, in Calcutta, India, found that pretreatment with chloroquine significantly potentiates the anticancer effects of artemisinin in treatment of non-small cell lung cancer, as well as other lung cancer cell types. Chloroquine is a generic medication on the WHO list of essential medicines used in treatment of malaria, Plasmodium falciparum, vivax, and other species, and in some autoimmune disorders, and is widely available and inexpensive:
  121. Research in 2015, at Rutgers University in the United States, the National Chung-Hsing University in Taiwan, and Huanggang Normal University in China, found that a specific active chemical in the Chinese herb Chen Pi, prepared tangerine peel, tangeritin, exerted significant anti-cancer effects in non-small cell lung cancer, as well as breast cancer and leukemia, helping induce cell cycle arrest and apoptosis (programmed cell death) in these cancer cells:
  122. Research at the Cancer Institute of Southern Medical University, in Guangzhou, China, in 2015, found that the now well known and standardized active chemical in the Chinese herb Huang Lian, berberine, showed significant anti-cancer effects for lung cancer, but also increased the effectiveness of the chemotherapy drug Doxorubicin, showing much potential as an adjunct therapy:
  123. A 2015 study at the Ottawa Hospital Research Institute, and the Canadian College of Naturopathic Medicine, in Ontario, Canada, found that the Chinese herb Coriolus versicolor (Yun zhi), and specifically the chemical polysaccharide K in the medicinal mushroom, may extend survival time and improve quality of life and symptoms in lung cancer care:
  124. A 2015 study at the Korea Institute of Oriental Medicine, in Daejeong, South Korea, found that the medicinal herb Vitex exerted significant anti-cancer and support effects for lung cancer, showing that even this common tonic herb could help in the overall protocol in adjunct care for lung cancer:
  125. A 2015 meta-analysis of published scientific studies of adjunct care with acupuncture in the treatment of cancer, by the esteemed Memorial Sloan-Kettering Cancer Center, in New York, New York, U.S.A. found that while human clinical trials of quality are still sparse, due to the study design problems, that acupuncture has been shown to improve various symptoms and problems in cancer care, including fatigue, pain and lymphedema, and has been found acceptable to lung cancer patients in the care protocol. Short courses of acupuncture with more prolonged individualized herbal and nutrient medicine could improve outcomes and quality of life considerably:
  126. A 2013 meta-analysis of all published randomized controlled human clinical trials of acupuncture as an adjunct therapy in treating lung cancer, at the University of Hong Kong, in China, found that acupuncture stimulation improved immune function, alleviated bone marrow suppression of new blood cells, and decreased incidence of nausea:
  127. Research in 2005 at Lunds University, in Sweden, noted in a questionnaire of 233 consecutive breast cancer patients undergoing surgical operations that prior to and after surgery, 14 to 18 percent of the patients reported using Complementary Medicine, with 35 different types of herbal and nutrient medicines used. The researchers noted that there was anecdotal evidence of potential adverse interactions with their aromatase inhibitors in just 7 of these products, soy, garlic, gingko biloba, echinacea, ginseng, valerian and phytoestrogens (excluding soy). It should be noted that none of these rather benign herbal and nutrient medicines has any clinical evidence of harm in public record. Such citations of vague potential drug-herb interactions has led to the wholesale discouragement of any herbal medicine with this aromatase therapy. Obviously, the use of vague and unsubstantiated warnings, when the evidence of benefit of integration of herbal and nutrient medicine is substantial, is a travesty to the health and welfare of the patients. If this is the extent of evidence available to deny patients the benefits of herbal and nutrient medicines, this is a sad affair, yet it is the reality:
  128. A 2015 phase 2 human clinical trial of a traditional herbal formula in Japan taken after gastrectomy for stomach cancer showed that this herbal formula was safe and significantly improved early recovery of postoperative bowel function. The multicenter randomized controlled human clinical trial of Daikenchuto formula, consisting of Ginger, Zanthoxylum fruit (Hua jiao), and Saccharum gramorumb (barley malt sugar), was conducted at the Tokushima University School of Medicine, Iwate Medical University, the Keio University School of Medicine, Kyoto University School of Medicine, and others, and assisted by the Japanese Foundation for Cancer Research:
  129. Research in 2008, at the Osaka University School of Medicine, in Japan, found that the traditional herbal formula Daikenchuto, long prescribed in Traditional Medicine to treat adhesive bowel obstruction was very successful in restoring healthy bowel function following radiation for colon cancer:
  130. A 2014 detailed study of the traditional herbal formula Daikenchuto, by experts at Kitasato University and The University of Tokyo, showed that the effects of this simple herbal remedy for adhesive bowel obstruction works by anti-inflammatory action through affects on nicotinic acetylcholine receptors:
  131. Research in 2014, at St. George's University of London, UK, found that 2 cannibinoids in Cannabis, commonly known as marijuana, THC and Cannabidiol (CBD), dramatically enhance the effects of radiation therapy to treat brain cancers. In a randomized controlled laboratory trial on animals, just a small dosage of these herbal chemicals resulted in a drastic reduction in tumor size and growth. The average 5-year survival time with brain cancers is about 10 percent, and these researchers will try to conduct human clinical trials as soon as possible:
  132. Research in 2013, at Guru Nanak Dev University, in Amritsar, India, showed that an alcohol extract of Tinospora cordifolia effectively arrested cell cycle growth and metastasis in glioblastomas: