May 1, 2015

Dr. Virender Sodhi, ND, MD (Ayurved) and Dr. Anup Mulakaluri, ND, AWC

This newsletter is dedicated in loving memory of Michael John Traill Duffy.

Roughly two years ago, Michael came to our office with the diagnosis of Glioblastoma multiforme—an aggressive and fatal brain cancer. He inspired us with his unwavering and courageous spirit throughout his battle with cancer. With standard treatments combined with natural treatments, he lived a longer, fuller life. He even embarked on a several-week vacation cruise for three months before his death. Glioblastoma is a fatal disease. Michael and his wife Tracy, who stood by his side, have inspired us to continue research to help other glioblastoma patients. Further case details will be discussed at the end of this article.

Introduction:

Glioblastoma multiforme is the most common cancer of the brain and central nervous system. It affects the glial cells of the brain, called astrocytes and oligodendrocytes. Normal glial cells support the neurons by providing nutrition, supportive structures and protection. Dysfunction of glial cells weakens the function of neurons significantly. As the tumors grow, nervous system function is further affected by the tumor size and invasion of other brain structures.

Prevalence and Risk Factors:[1]

In the United States, more than 17,000 new cases of brain tumor are treated each year; of these patients, 45.2% have Glioblastoma multiforme (GBM).

The risk of GBM increases with age; it is most common among people over 60 years old. Glioblastomas are also 1.5 times more common among men than in women. Among racial groups, Caucasians have more than double the risk compared to Blacks, Hispanics, Asians or Native Americans. Additional risk has been associated with eating nitrate-rich foods and other oxidative foods.[2]

Risk Factors:
Most common after age 60
1.5x more common among men
2x more common among Caucasians compared to other races
Eating nitrate-rich and pro-oxidant foods can also increase risk

Survival Rate and Western Therapies:

The mean survival rate for those with GBM is about 3 months without any treatments.[2] Patients often pass due to organ failure caused by growing and invasive tumors. With the use of conventional therapies, average survival may improve up to 15 months. Only 35% of patients survive the first year after diagnosis; 13.7% survive their second year; and less than 5% make it to 5-year survival.

Temolozamide (TMZ) or Temodar, Avastin and Novocure are all potential treatment options.

The first line of defense is chemotherapy agent Temolozamide, typically offered in 6-week cycles combined with radiation therapy. With this treatment, median survival time is extended from 12.1 to 14.6 months—a total improvement of 2.5 months.[3]

Effectiveness of TMZ is improved in patients who have a deficiency of a detoxification enzyme called O-6-methylguanine-DNA methyltransferase (MGMT).[1] Normally, this enzyme protects DNA telomeres from toxin damage. In GBM treatment, inactivation of this enzyme makes cancer cells more vulnerable to TMZ and radiation. Studies have shown some improvement in the effectiveness of Temodar, when combined in interferon therapy, which also blocks the activity of MGMT.[4]

Avastin is another chemotherapy drug that has been added to the repertoire in recent years. This drug, given in combination with standard therapy, improved survival time from 15.7 months to 16.1 months—a total improvement of 0.4 months.[5] For this modest improvement, the cost of this drug is about $100,000 per year.

Novocure is the latest treatment approved by the FDA. It does not involve any drugs or radiation. This device uses an individually-molded helmet that creates an electrical field in the brain meant to disrupt tumor cell activity. In a pilot study, 4 of 20 using Novocure survived more than 7 years.[6 ]However, in a phase III clinical trial with 230 patients, the results were less spectacular. In this study, median survival rate for patients using Novocure was 6.6 months compared to 6 months for those receiving conventional chemotherapy—a total improvement of 0.6 months.[7]

Time After Diagnosis Survival Rate
1 year 35%
2 years 13.7%
5 years < 5%
Conventional Therapy Improvement of Survival
Conventional Therapy Improvement of Survival
TMZ alone 2.5 months
Avastin with TMZ 0.4 months
Novocure 0.6 months

The Side Effects:

In addition to the high costs of these medications and mediocre survival rates, these therapies are accompanied by a wide range of side effects. Symptoms may include nausea, loss of appetite, weight loss, immune system suppression or convulsions that can be fatal independent of the cancer.

Side effects of TMZ
Seizures
Numbness and tingling on body
Diarrhea or constipation
Nausea, loss of appetite
Fatigue, hair loss
Side effects of Avastin
Bleeding gums
Burning, numbness, tingling of hands and feet
Convulsions
Chest pain or discomfort
Extreme fatigue
Side effects of Novocure
Skin rash
Fatigue
Physical weakness
Seizures

Natural Medicines to Promote Survival:

Natural therapies can go a long way in minimizing side effects, while improving quality of life for patients. Additionally, some natural therapies have shown powerful anti-cancer effects against GBM and other cancers.

Intravenous Vitamin C:

Vitamin C is one of the major antioxidants in the body that serves as buffer to support all other antioxidant systems.

Vitamin C IVs have been used in cancer care for several decades. As an antioxidant agent, Vitamin C helps control inflammatory damage to cells and DNA.[8 ]The antioxidant function protects healthy cells and DNA from becoming cancerous in nature. Intravenous administration serves this function.

Additionally, Vitamin C promotes immune cell function, which is the body’s primary defense against cancer.[8 ]High dose Vitamin C given in an IV can block the formation of new blood vessels essential for tumor growth. On the other hand, Vitamin C (ascorbic acid) which looks very similar to sugar, is readily picked up by the sugar-hungry cancer cells; however, Vitamin C proves toxic for the cancer cells.[9] At high doses, Vitamin C causes oxidative stress to cancer cells, which cannot cope with such stress because they lack proper enzymes.[10]

Intravenous Mistletoe:

The herb Mistletoe (Viscum album) is a very effective immune stimulating agent. It is one of the most extensively studied natural treatments in the European Union. Mistletoe has been shown to improve quality of life among cancer patients when used in addition to chemotherapy and radiation.[11 ]

Additionally, Mistletoe has also been proven to be an effective therapeutic agent against a wide variety of cancers.[12] Aggressive breast cancers, colorectal cancers and glioblastomas have been shown to go into remission with Mistletoe treatment.[12] This effect is attributed to its anti-inflammatory, antioxidant and immune stimulant action.

In a recent review of clinical studies, Mistletoe improved survival rates in eight studies, reduced progression in two studies, and reduced the side effects of chemo and radiation in four studies—indicating the holistic effectiveness of this herbal intervention.[12]

Ashwagandha:

This popular Ayurvedic herb provides multi-faceted benefits for cancer patients. It is a proven anti-stress herb that helps to relieve anxiety and fatigue.

In animal studies, co-administration of Ashwagandha with a carcinogenic agent reduced the development of cancer by 75%, indicating that Ashwagandha may act as an effective cancer preventive herb.[13]

In another study, Ashwagandha inhibited the growth of human breast cancer by inducing cell death, as well as blocking invasion of breast cancer cells.[14]

The liver and kidneys are the main organs for eliminating toxic chemo drugs; Ashwagandha helped reduce chemotherapy damage against liver and kidney cells, while improving levels of antioxidant enzyme in these tissues—further protecting the body beyond conventional cancer treatment.[15]

Turmeric:

Turmeric, a commonly used cooking spice, is also a source of a medicinal compound called Curcumin, which is a powerful anti-inflammatory.[16] Compared to conventional drugs in effect, it is one of the most non-toxic treatments.[16] Curcumin’s intricate action helps control cancer-causing inflammatory products like NF-KappaB and Tumor Necrosis Factor-alpha.[17,18] Inhibition of these molecules indicates change in gene-expression that protects against cancer development and progression.[18 ]This miraculous herb has proven its efficacy in a wide variety of cancers including prostate, breast, colon and more.[19,20]

In studies done against Human Glioma, Curcumin has been found to increase concentrations of certain protein (ING4) to promote death of cancer cells.[21] In addition to stopping cancer cell growth, another benefit of Curcumin is that it keeps glioblastoma cells from developing chemoresistance.[22] Curcumin may be a very helpful adjunct to conventional therapies.

Frankinscence (Boswellia Serrata):

Another powerful anti-inflammatory herb from the Ayurvedic tradition, Boswellia has proven itself as effective as conventional drugs for inflammation treatment.

The active ingredients of Boswellic acids inhibit the production of inflammatory signaling molecules, interleukins and Tumor necrosis factor-alpha.[23 ]Boswellic acids also exert an antioxidant effect to help prevent free-radical damage to cells and DNA, thus protecting from abnormal genetic activity.[24 ]

Considering these activities, Boswellia has been tested and proven to be an effective anti-cancer herb. Boswellia has been shown to be effective in blocking growth of cancers of colon,[25] prostate,[26] breast,[27] brain cells,[28] blood cells[29] and more.

In a case report of brain cancer that developed from metastatic breast cancer, Boswellia was used with great effect. The patient was given 800 mg of Boswellia three times a day for 10 weeks. At the end of the study, brain cancer had nearly reversed.[30] Figure 1 and figure 2 below show the change in 10 weeks.

Panchakarma:

The toxic burden of our cellular environment is a reflection of the toxicity of our living environment, food, lifestyle and thoughts. These toxicities add up to generate abnormal cellular activity that may be expressed in the form of physiological imbalance, inflammation and ultimately cancer. Cleansing the cellular micro-environment allows the natural healing mechanisms of the body to restore functional balance to the physiology of each cell.

Panchakarma is the main Ayurvedic method for physical, mental and emotional cleansing.[31]

Based on Ayurvedic philosophy, each individual is composed of a unique combination of three physiological humors or doshas: Vata, Pitta, and Kapha. Aggravation or depletion of one of the doshas in this unique combination leads to disease; the most general indication of Panchakarma is aggravation of all the doshas.[32]

Panchakarma has been used for many centuries to treat a wide range of disorders encountered by Ayurvedic physicians. The words ‘Pancha Karma’ mean ‘five actions’ or ‘five processes.’ Panchakarma is a complete detoxification program that utilizes food, herbs, oils and stimulative therapies to eliminate morbid or toxic matter from the elimination channels of the body, followed by rejuvenating therapies that restore balance and health. Panchakarma is divided into three phases: pre-PK therapies to help body to eliminate toxic load; main Panchakarma treatments (major detox); and post-PK therapies to help restore body and immune system.

All these and more therapies are regularly used at the Ayurvedic and Naturopathic Medical Clinic in complementary and alternative care for cancer patients. All treatment plans are designed in an individualized manner to provide optimal benefit to each individual in the most efficient and natural way. Learn more about pancha karma treatments.

Oxygenation and Glioblastoma:

The breath, food and thoughts are three major pathways of providing nourishment to our body. Breathing is the main source of oxygen for our body. Oxygen serves as an essential fuel source for all of our cells and mitochondria; oxygen is also an important tool for the immune system to create oxidation and fight off infections.

Cancer studies have demonstrated the presence of tumor cells that survive on low oxygen are more likely to be resistant to chemotherapy and radiation.[33] These cells produce compounds called hypoxia inducible factors (HIFs)—produced in response to low oxygenation. This compound causes cellular and local changes to reduce the susceptibility of cancer. Presence of HIFs has been associated with poor patient survival in early-stage cervical cancer, breast cancer, oligodendroglioma, ovarian cancer, endometrial cancer and oropharyngeal squamous cell carcinoma.[33]

On the other hand, enhanced oxygenation has been associated with increased chemo- and radio-sensitivity of cancer cells.[34,35] Knowing this, the use of hyperbaric oxygen chambers has been popularized among patients with cancer and other chronic diseases. This chamber exposes the patient to high-concentration oxygen with 1.5 to 2 times the atmospheric pressure. When the hyperbaric chamber is used directly, hyper-oxygenation causes cancer growth to slow down or even stop.[36]

Proactively, the benefit of increased oxygenation can be achieved in daily life. Deep breathing is very efficient way of increasing oxygen availability. Ayurveda offers many breathing exercises that can be adapted to various functions. In our clinic, we have seen many times that deep breathing for just a few minutes can increase oxygen saturation in blood by 10 to 15% points. Daily practice can help create a sustainable change.

Ketogenic Diet:

The Ketogenic Diet has demonstrated great cancer-fighting benefits.

Tumor cells grow fast and thrive on fast-burning fuel sources, like sugar. On the other hand, normal cells can survive very easily without sugar in our diet. Normal cells can use fats and proteins to make the sugar structures needed for fuel.

A Ketogenic Diet consists of high fat, moderate protein and very little carbohydrates. This provides fats and protein as the main nutrition that is converted by healthy cells into sugar compounds that are used as fuel. This type of diet causes very small blood sugar elevations, thus preventing cancer cells from accessing too much sugar.

Recent studies have shown that glioblastoma cells have lower amounts of enzymes that can digest ketones.[37] This makes the glioblastomas especially vulnerable to the Ketogenic Diet. A systematic review of studies on the effects of a Ketogenic Diet on glioblastoma has confirmed benefits. This diet helps reduce tumor cells’ metabolic activity, while increasing their sensitivity to chemotherapy and radiotherapy.[38]

Stress Management:

Stress is a natural part of life. However, excessive stress and inadequate stress management can become detrimental to health.

Just like a stretched rubber band loses its elasticity over time, a stressed system loses its immunity as well. Chronic stress can make a weak immune system even weaker, increasing susceptibility to disease.[39]

Chronic stress results in the expression of IL-6 from B-cells and T-cells in the immune system—a pro-inflammatory marker that induces C-reactive protein (CRP).[40] IL-6 and CRP have a combined effect of promoting low-grade systemic inflammation, which may contribute to cancer development.

A formidable disease like cancer comes with the additional stress of facing one’s mortality, fear, anger and frustrations. It comes with the stress of all the doctor’s office visits, medications and side effects. All this may burden the immune system and increase susceptibility.

The hormone melatonin, which induces sleep at night, appears to have an opposite effect on the immune system. As part of immune regulation, melatonin has been demonstrated as an effective treatment in some cancers.[41] Regular sleep cycles help with stress management and support the immune system. For optimal production of melatonin, we need to go to bed early and wake up early. To achieve optimal health and immune system function, my recommendation is to go to sleep by 10 p.m. and wake by 5 or 6 a.m.

Additionally, a similar effect on the immune system can be derived from other stress-relief activities like meditation, breathing exercise, Tai chi and Qi gong.[42] These activities demonstrate effective change in our sense of wellbeing, as well as immune system activity.

Oncolytic Viral Vaccines:

Vaccinations have been touted as one of the most important inventions of modern times. Vaccines have been attributed to the near eradication of diseases like polio and measles from human populations. Scientists have sought to use vaccines as a way of targeting cancer cells directly.

Modern capability of manipulating viral DNA has been helpful in making viruses weaker in their toxicity, while promoting oncolytic (cancer killing) activity. Here are some interesting studies that support the case for using oncolytic vaccines in treatment of cancer:

Genetic manipulation of measles virus causes it to express protein that binds to a common receptor on the tumor cells. These receptors are expressed minimally in normal cells, thus helping the virus to specifically target cancer cells. The vaccine of attenuated measles has shown significant improvement with in animal models.[43] Clinical trials on cervical cancer, glioblastoma and multiple myeloma are currently underway. A cervical cancer trial has already demonstrated some positive results. Patients with high doses had stable disease for an average of 3 months.[44]

Tetnus toxoid vaccination has also been tried as treatment for glioblastoma patients. Patients who were given the toxoid vaccine had average survival of 57 to 106 months (4.5 to 9 years) compared to average of 18.5 months (1.5 years) in control patients, who did not receive the vaccine.[45]

Polio virus, which specifically targets nerve cells, has also been modified and studied for oncolytic properties. While a clinical trial is underway, safety of the vaccine has been tested among animal models. In one study on mice, application of the vaccine improved long-term survival by 80% when it was injected directly into the tumor compared to intravenous route.[46]

As the research evidence continues to grow, we may be at the edge of very exciting and targeted therapies to fight cancer. Follow this link to learn more about such trials being done right here in the U.S.: www.cancer.duke.edu/btc/modules/Research3/index.php?id=41.

Cannabis Oil and Brain Tumor:

Cannabidiol represents the non-psychoactive oil that is extracted from the Marijuana plant (Cannabis spp.). The use of Cannabis in the medical field has been steadily growing in the past decade. In recent years, it has become a useful agent for pain relief, inflammation control and stimulating appetite among cancer patients.[47]A growing body of research is making a case for the use of this oil in glioma patients.

Review of research suggests that the use of Cannabis oil may reduce cancer growth by reducing blood supply, while promoting cell cycle arrest and cell death.[48] Administration of Cannabis oil has been shown to reduce the activity of energy-producing mitochondria in glioma cells.[49] This resulted in inhibition cancer growth in mouse models of human glioma. This indicates the capacity of the herb to deplete the cancer cells of energy. In another study, application of CBD blocked the migration of cancer cells; thus, indicating potential capacity to block cancer metastasis.[50]

Further research has shown that use of THC (Tetrahydrocannbinol), the psychoactive component of Marijuana, can promote an anti-tumor effect on glioma cells that were previously chemo-resistant. When THC was given in combination with Temozolomide (TMZ), a primary drug in glioma treatment, it reduced chemoresistance.[51] This resulted in increased cancer cell deaths.

The Case of Michael John Traill Duffy:

Michael, then 54 year old, first came to our clinic in August 2013. He appeared weak and his records showed that he had experienced double vision, dizziness, imbalance, headaches, memory loss and hand-eye coordination problems in the past months.

Michael was diagnosed with Glioblastoma multiforme in March of 2013. The tumor was about 4 cm wide. He had undergone chemotherapy and radiation treatments. While finishing up final rounds of Temozolomide (TMZ) treatment, he was on other medication to control side effects like seizures and inflammation.

Our initial complementary therapies began Aug. 8, 2013:

  • Boswellia s. (frankinsense) formulation, 750 mg per day
  • Curcumin-bound to coconut oil, 4.8 grams per day
  • Melatonin, 6 mg at night
  • Neem formulation, 900 mg per day
  • Amla jam, 1 teaspoon three times a day
  • All sugar and high carbohydrates were eliminated from his diet
    • Michael transformed his diet to eat mostly vegetables, nuts, seeds, fish, other meats, etc.
    • He minimized exposure to unhealthy diet choices
  • Vitamin C IV therapy, once every week:
    • 25 grams of Vitamin C was infused once per week
    • Michael sat in an infrared sauna during the IV

In March of 2014, a follow-up MRI showed that the tumor had shrunk from 4 cm to 2.7 cm in size. This was wonderful, very encouraging news.

Michael also reported that, since starting the complementary regimen, he had no side effects of chemotherapy, numbness and tingling was gone, nausea had retreated, and his energy and mood had significantly improved. Blisters related to Avastin treatments, pruritis related to other medication, as well as constipation had improved.

Next, additional herbal support for his adrenal glands and nervous system was added:

  • Bacopa m. formulation contains herbs like Brahmi and Gotu Kola that support nerve tissue health and may promote regeneration
  • Ashwagandha for adrenal support, as well as anti-cancer support
  • Melotonin, 20 mg at night
  • Continue Vitamin C IV therapy

We got to know Michael well while he received the Vitamin C IVs for 2 to 3 hours every week. We witnessed the courageous and stoic nature of this man who was facing certain death in his mid-50s. For the year and a half that Michael came to the clinic, he was always pleasant and endearing. Michael connected with everyone and won them over with his humor and gentle manner.

In September of 2014, while the cancer had stabilized, Michael took a cruise around the Mediterranean with his lovely wife Tracy. Michael and Tracy described it as, “the trip of a lifetime.” They had minimal to no difficulty continuing the supplements.

The following month, the MRI report had ominous news: the tumor had grown in size significantly.

Despite this, Michael was still doing fairly well. Symptoms of balance, numbness, tingling and forgetfulness were a bit worse, but not significantly debilitating. Michael still had energy to do many things, including cooking breakfast “his favorite meal of the day.”

After several weeks in deliberation, Michael decided to try Novocure electric field therapy and one more round of chemotherapy Avastin. Unfortunately, Michael was never physically the same after this. His energy, balance and coordination diminished rapidly over the course of a couple of months.

In early 2015, Michael was provided hospice services for care in his final days. He was also supported by his wife Tracy, sister, father and two daughters.

Despite failing physical health, Michael maintained his humor, love of reading and joy for the outdoors. Michael was still the loving, inspiring and courageous person he had always been.

Almost 20 years ago, I had another patient with stage 4 glioblastoma. He had a tumor the size of a grapefruit in the middle of two hemispheres. In 9 months of Ayurvedic treatment, the tumor shrank to the size of walnut and was removed surgically. The patient lost some motor functions, but he lived for more than 8 years.

As we mourn Michael’s loss, we continue our research quest to achieve more effective treatments and better health outcomes for all patients facing cancer.

References

  • [1] Thakkar JP, et al. Epidemiologic and Molecular Prognostic Review of Glioblastoma. Epidemiol Biomarkers Prev; 23(10) October 2014.
  • [2] Schwartzbaum JA, et al. Epidemiology and Molecular Pathology of Glioma. Natural Clinical Practice, Neurology, Sept. 2009; Vol. 2(9), Pg. 494-501.
  • [3] Stupp R, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005;352:987–96.
  • [4] Williams BA. Treatment Options for Glioblastoma and other Gliomas. Glioblastoma Diagnosis; March 10, 2014.
  • [5] Plenary Session of ASCO 2013. RTOG0825: Phase III double-blind placebocontrolled trial evaluating bevacizumab (BEV) in patients with newly diagnosed glioblastoma (GBM). J. Clin. Oncol, 2013; Vol. 13.
  • [6] Rulseh AM, et al. Long-term survival of patients suffering from glioblastoma multiforme treated with tumor-treating fields. World J Surg Oncol. 2012 Oct 24; Vol. 10, Pg. 220.
  • [7] Stupp R, et al. NovoTTF-100A versus physician's choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality. Eur J Cancer. 2012 Sep; Vol. 48(14): Pg. 2192-202.
  • [8] Mikirova N, et al. “Clinical experience with intravenous administration of ascorbic acid: achievable levels in blood for different states of inflammation and disease in cancer patients.” Journal of Translational Medicine, 2013: Vol. 11(191).
  • [9] Riordan NH, Riordan HRD, Meng X, Li Y, Jackson JA: Intravenous ascorbate as a tumor cytotoxic chemotherapeutic agent. Medical hypothesis 1995, 44:207–213.
  • [10] Ohno S, et al. High-dose Vitamin C (Ascorbic Acid) Therapy in the Treatment of Patients with Advanced Cancer. Anti-cancer Research, 2009; Vol. 29: 809-816.
  • [11] Bock PR, et al. “Targeting Inflammation in Cancer-Related-Fatigue: A Rationale for Mistletoe Therapy as Supportive Care in Colorectal Cancer Patients.” Inflammation & Allergy – Drug Targets, 2014, 13, 105-111.
  • [12] Kienle GS, Kiene H. “Complementary cancer therapy: a systematic review of prospective clinical trials on anthroposophic mistletoe extracts.” European Journal of Medical Research, 2007 Mar 26; Vol. 12(3), Pg. 103-19.
  • [13] S. Koduru, et al. “Notch-1 inhibition by Withaferin-A: A therapeutic target against colon carcinogenesis,” Mol Cancer Ther., Jan. 2010, Vol. 9(1), Pg. 202–210.
  • [14] S.D, Stan, et al., “Ayurvedic medicine constituent withaferin A causes G2 and M phase cell cycle arrest in human breast cancer cells,” Nutr Cancer., 2008; Vol 60 (Suppl 1), Pg. 51–60.
  • [15] T. Jeyanthi and P. Subramanian, “Protective effect of Withania somnifera root powder on lipid peroxidation and anti-oxidant status in gentamicin-induced nephrotoxic rats,” J Basic Clin Physiol Pharmacol, 2010, Vol. 21(1), Pg. 61–78.
  • [16] Nina-Chainani, N. “Safety and Anti-Inflammatory Activity of Curcumin: A Component of Tumeric (Curcuma longa).” The Journal of Complementary and Alternative Medicine, 2003; Vol 9(1), pp. 161–168.
  • [17] Plummer SM, et al. “Inhibition of cyclo-oxygenase 2 expression in colon cells by the chemopreventive agent curcumin involves inhibition of NF-kB activation via the NIK/IKK signalling complex.” Oncogene (1999); Vol. 18, Pg. 6013 – 6020.
  • [18] Kawamori T, et al. “Chemopreventive Effect of Curcumin, a Naturally Occurring Anti-Inflammatory Agent, during the Promotion/Progression Stages of Colon Cancer.” Cancer Res, February 1, 1999; Vol. 59, Pg. 597.
  • [19] Chauhan DP. “Chemotherapeutic Potential of Curcumin for Colorectal Cancer” Current Pharmaceutical Design, Sept. 2002; Vol 8(19), pp. 1695-1706.
  • [20] Bar-Sela, G, et al. “Curcumin as an Anti-Cancer Agent: Review of the Gap Between Basic and Clinical Applications.” Current Medicinal Chemistry, 2010; Vol. 17.
  • [21] Liu E, et al. Curcumin induces G2/M cell cycle arrest in a p53-dependent manner and upregulates ING4 expression in human glioma. J Neurooncol (2007) 85:263–270.
  • [22] Dhandapani K, et al. Curcumin suppresses growth and chemoresistance of human glioblastoma cells via AP-1 and NFκB transcription factors. Journal of Neurochemistry, July 2007, Volume 102, Issue 2, pages 522–538.
  • [23] G.B. Singh, et al. “Boswellic Acids— A New Class of Anti-inflammatory Drugs with a Novel Mode of Action.” International Seminar on Traditional Medicine, Calcutta, India, November 7–9, 1992.
  • [24] G.B. Singh and C.K. Atal, “Pharmacology of an extract of Boswellia guggalex–Boswellia serrata, a new non-steroidal anti-inflammatory agent,” Agents and Actions, 1986, Vol. 18, Pg. 407.
  • [25] Yadav VR, et al. Boswellic acid inhibits growth and metastasis of human colorectal cancer in orthotopic mouse model by downregulating inflammatory, proliferative, invasive and angiogenic biomarkers. Int J Cancer. 2012 May 1; Vol. 130(9), Pg. 2176-84.
  • [26] M. Lu, L. Xia, H. Hua, and Y. Jing, “Acetyl-keto-betaboswellic acid induces apoptosis through a death receptor 5-mediated pathway in prostate cancer cells,” Cancer Res., Feb 15, 2008, 68(4):1180–1186.
  • [27] Suhail MM, et al. “Boswellia sacra essential oil induces tumor cell-specific apoptosis and suppresses tumor aggressiveness in cultured human breast cancer cells” BMC Complementary and Alternative Medicine 2011; Vol. 11, Pg. 129.
  • [28] S. Kirste, et al. “Boswellia serrata acts on cerebral edema in patients irradiated for brain tumors: a prospective, randomized, placebo-controlled, double-blind pilot trial,” Cancer, Aug. 15, 2011, 117(16):3788–3795.
  • [29] A.B. Kunnumakkara, et al. “Boswellic acid blocks signal transducers and activators of transcription 3 signaling, proliferation, and survival of multiple myeloma via the protein tyrosine phosphatase SHP-1,” Mol Cancer Res., Jan. 2009, 7(1):118–128.
  • [30] Flavin DF. “A lipoxygenase inhibitor in breast cancer brain metastasis.” J Neurooncol. 2007; Vol. 82, Pg. 91-93
  • [31] Frawley D. Ayurveda and The Mind: The Healing of Consciousness. 1st edition, Lotus Press, Twin Lakes, WI, 1997.
  • [32] Lad V. Ayurveda: The Science of Self-Healing. 2nd edition, Lotus press, Twin Lakes, WI, 1985.
  • [33] Bertout JA, et al. The impact of O2 availability on human cancer. Nat Rev Cancer. 2008 December; Vol. 8(12): 967–975.
  • [34] Fayles AW, et al. Oxygenation predicts radiation response and survival in patients with cervix cancer.
  • [35] Dong XL, et al. Hypoxia decreased chemosensitivity of breast cancer cell line MCF-7 to paclitaxel through cyclin B1. Biomed Pharmacother. 2012 Feb; Vol. 66(1): Pg. 70-5.
  • [36] Moen I and Stuhr LE. Hyperbaric oxygen therapy and cancer–a review. Target Oncol. 2012 Dec; Vol. 7(4): Pg. 233-42.
  • [37] Chang HT, et al. Ketolytic and glycolytic enzymatic expression profiles in malignant gliomas: implication for ketogenic diet therapy. Nutr Metab (Lond). 2013 Jul 5; Vol. 10(1): Pg. 47.
  • [38] Woolf EC and Scheck AC. The ketogenic diet for the treatment of malignant glioma. J Lipid Res. 2015 Jan;56(1):5-10.
  • [39] Segerstrom S and Miller GE. Psychological Stress and the Human Immune System: A Meta-Analytic Study of 30 Years of Inquiry. Psychol Bull. 2004 July; Vol. 130(4), Pg. 601–630
  • [40] Glaser R and Kiecolt-Glaser JK. “Stress-induced immune dysfunction: implications for health.” Nature Review, March 2005; Vol. 5, Pg. 243-251.
  • [41] Zamfir-Chiru AA, et al. “Melatonin and cancer” J Med Life. Sep 15, 2014; Vol. 7(3): Pg. 373–374.
  • [42] Kang DH, et al. “Dose effects of relaxation practice on immune responses in women newly diagnosed with breast cancer: an exploratory study.” Oncol Nurs Forum. 2011 May; Vol. 38(3), Pg. E240-52.
  • [43] Phuong LK, et al. Use of a vaccine strain of measles virus genetically engineered to produce carcinoembryonic antigen as a novel therapeutic agent against glioblastoma multiforme. Cancer Res. 2003;63(10):2462–2469.
  • [44] Galanis E, et al. Phase I trial of intraperitoneal (IP) administration of a measles virus (MV) derivative expressing the human carcinoembryonic antigen (CEA) in recurrent ovarian cancer (OvCa) J Clin Oncol. 2008;26(15S) Abs 5538.
  • [45] Mitchell DA, et al. Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients. Nature; Vol. 519, 366–369.
  • [46] Gromeier M, Lachmann S, Rosenfeld MR, et al: Intergeneric poliovirus recombinants for the treatment of malignant glioma. Proc Natl Acad Sci, 2000; Vol 97, Pg. 6803-6808.
  • [47] Cannabis and Cannbinoids.
  • [48] Massi and Parolaro. Cannabinoids as a Potential New Therapy for Gliomas. Expert Review Neurotherapeutics, 2008; Vol. 8(1)
  • [49] Massi P, et al. Antitumor Effects of Cannabidiol, a Nonpsychoactive Cannabinoid, on Human Glioma Cell Lines. JPET March 2004; vol. 308(3), Pg. 838-845.
  • [50] Vaccani A, et al. Cannabidiol inhibits human glioma cell migration through a cannabinoid receptor-independent mechanism. BJP, 2005; Vol. 144(8).
  • [51] Torres S, et al. A Combined Preclinical Therapy of Cannabinoids and Temozolomide against Glioma. Mol Cancer Ther January 2011; Vol. 10, Pg. 90.