Feeds:
Posts
Comments

Posts Tagged ‘Avemar’


Hormonal Therapy, Complementary and Alternative Therapies – 9.4

Writer and Curator: Larry H. Bernstein, MD, FCAP

The following material has been covered from a different vantage point in previous writings. In the previous articles the focus was both antibacterial and anticancer resistance.  Much of the focus was on the metabolomic studies of substrate fluxes across cells and extracellular analyses to determine differences between cancer cell types in vitro.  This time I shall cover some of the selected ground with a different perspective.  Alternative medicines have been around for thousands of years. Much of it was based on readily available plants that had a pharmacological action.  This also gave rise to pharmaceuticals by extraction of the active compound. Such was the case with digitalis and also with Warfarin.

9.4.1 Use of complementary medicine by adult patients participating in cancer clinical trials

9.4.2 Complementary/Alternative Medicine Use in a Comprehensive Cancer Center and the Implications for Oncology

9.4.3 Trends in Alternative Medicine Use in the United States, 1990-1997 Results of a Follow-up National Survey

9.4.4 Courses Involving Complementary and Alternative Medicine at US Medical Schools

9.4.5 38% of Adults Use Alternative Medicine

9.4.6 Wheat germ extract (Avemar, Avé, AvéULTRA, AWGE, OncoMAR)

9.4.7 How Avemar Helps Fight Cancer

9.4.8  The anti-cancer action of curcumin (turmeric)

Introduction – PENDING

9.4.1 Use of complementary medicine by adult patients participating in cancer clinical trials
Sparber ABauer LCurt GEisenberg DLevin TParks SSteinberg SMWootton J
Oncology Nursing Forum [2000, 27(4):623-630]
http://europepmc.org/abstract/med/10833691

PURPOSE/OBJECTIVES: To document the prevalence, demographic correlates, patterns of use, and beliefs about complementary and alternative medicine (CAM) therapies of adult patients enrolled in National Cancer Institute (NCI) clinical trials. DESIGN: Prospective, cross-sectional, descriptive survey.
SETTING: W.G. Magnuson Clinical Center of the National Institutes of Health in Bethesda, MD. SAMPLE: Convenience sample of 100 English-speaking, adult patients with cancer admitted to intramural clinical trials.
METHODS: A standardized, 99-item questionnaire assessing use of CAM therapies pre- and postcancer diagnosis was administered by face-to-face interview. MAIN RESEARCH VARIABLES: Use of CAM therapies, beliefs, communication with physician. FINDINGS: 63% used at least one CAM therapy, with an average use of two therapies per patient. Men were significantly less likely to use a therapy than women; women were more likely to use numerous therapies. Cancer diagnosis seems to have had no influence overall on the frequency of use of CAM therapies. The major reasons stated for CAM use were for treatment-related medical conditions as well as depression, anxiety, and insomnia. The most frequently reported therapies were spiritual, relaxation, imagery, exercise, lifestyle diet (e.g., macrobiotic, vegetarian), and nutritional supplementation. Patients unanimously believed that these complementary therapies helped to improve their quality of life through more effective coping with stress, decreasing the discomforts of treatment and illness, and giving them a sense of control. CONCLUSIONS: Patients with cancer use various complementary therapies to cope with their disease and the rigors of clinical trials. Women and those with higher educational backgrounds were more frequent users.
IMPLICATIONS FOR NURSING PRACTICE: Nurses who provide care to subjects of biomedical research have an opportunity and responsibility regarding their patients’ use of CAM therapies. Nurses may use in-house resources to help evaluate subjects’ use of a CAM modality or to provide quality-of-life therapies such as relaxation, imagery, or healing touch. Discussing these health practices in a nonjudgmental manner adds to the assessment of patients’ coping skills and ability to make decisions about their health care.

9.4.2 Complementary/Alternative Medicine Use in a Comprehensive Cancer Center and the Implications for Oncology
MA Richardson, T Sanders, JL Palmer, A Greisinger, and SE Singletary
J Clin Oncol 18:2505-2514.
http://www.integratedhealthclinic.com/assets/byTopic/IntegrativeOncology/3-CAM%20Use%20in%20MD%20Anderson-J%20Clin%20Oncol%202000.pdf

Purpose: Oncologists are aware that their patients use complementary/ alternative medicine (CAM). As cancer incidence rates and survival time increase, use of CAM will likely increase. This study assessed the prevalence and predictors of CAM use in a comprehensive cancer center. Subjects and Methods: Subjects were English-speaking cancer patients at least 18 years of age, attending one of eight outpatient clinics at The University of Texas M.D. Anderson Cancer Center, Houston, TX, between December 1997 and June 1998. After giving written informed consent, participants completed a self-administered questionnaire. Differences between CAM users and nonusers were assessed by Chi square and univariate logistic regression analysis. A multivariate logistic regression model identified the simultaneous impact of demographic, clinical, and treatment variables on CAM use; P values were two-sided. Results: Of the 453 participants (response rate, 51.4%), 99.3% had heard of CAM. Of those, 83.3% had used at least one CAM approach. Use was greatest for spiritual practices (80.5%), vitamins and herbs (62.6%), and movement and physical therapies (59.2%) and predicted (P < .001) by sex (female), younger age, indigent pay status, and surgery. After excluding spiritual practices and psychotherapy, 95.8% of participants were aware of CAM and 68.7% of those had used CAM. Use was predicted (P < .0001) by sex (female), education, and chemotherapy. Conclusion: In most categories, CAM use was common among outpatients. Given the number of patients combining vitamins and herbs with conventional treatments, the oncology community must improve patient provider communication, offer reliable information to patients, and initiate research to determine possible drug-herb-vitamin interactions.

9.4.3 Trends in Alternative Medicine Use in the United States, 1990-1997 Results of a Follow-up National Survey
DM Eisenberg, RB Davis, SL Ettner, S Appel, S Wilkey, M Van Rompay; RC Kessler
JAMA. 1998; 280(18):1569-1575.
http://dx.doi.org:/10.1001/jama.280.18.1569

Context.  A prior national survey documented the high prevalence and costs of alternative medicine use in the United States in 1990. Objective. To document trends in alternative medicine use in the United States between 1990 and 1997. Design. Nationally representative random household telephone surveys using comparable key questions were conducted in 1991 and 1997 measuring utilization in 1990 and 1997, respectively. Participants. A total of 1539 adults in 1991 and 2055 in 1997. Main Outcomes Measures. Prevalence, estimated costs, and disclosure of alternative therapies to physicians.
Results. Use of at least 1 of 16 alternative therapies during the previous year increased from 33.8% in 1990 to 42.1% in 1997 (P≤.001). The therapies increasing the most included: herbal medicine, massage, megavitamins, self-help groups, folk remedies, energy healing, and homeopathy. The probability of users visiting an alternative medicine practitioner increased from 36.3% to 46.3% (P=.002). In both surveys alternative therapies were used most frequently for chronic conditions, including back problems, anxiety, depression, and headaches. There was no significant change in disclosure rates between the 2 survey years; 39.8% of alternative therapies were disclosed to physicians in 1990 vs 38.5% in 1997. The percentage of users paying entirely out-of-pocket for services provided by alternative medicine practitioners did not change significantly between 1990 (64.0%) and 1997 (58.3%) (P=.36). Extrapolations to the US population suggest a 47.3% increase in total visits to alternative medicine practitioners, from 427 million in 1990 to 629 million in 1997, thereby exceeding total visits to all US primary care physicians. An estimated 15 million adults in 1997 took prescription medications concurrently with herbal remedies and/or high-dose vitamins (18.4% of all prescription users). Estimated expenditures for alternative medicine professional services increased 45.2% between 1990 and 1997 and were conservatively estimated at $21.2 billion in 1997, with at least $12.2 billion paid out-of-pocket. This exceeds the 1997 out-of-pocket expenditures for all US hospitalizations. Total 1997 out-of-pocket expenditures relating to alternative therapies were conservatively estimated at $27.0 billion, which is comparable with the projected 1997 out-of-pocket expenditures for all US physician services. Conclusions. Alternative medicine use and expenditures increased substantially between 1990 and 1997, attributable primarily to an increase in the proportion of the population seeking alternative therapies, rather than increased visits per patient.

9.4.4 Courses Involving Complementary and Alternative Medicine at US Medical Schools
Miriam S. Wetzel, David M. Eisenberg, Ted J. Kaptchuk
JAMA. 1998; 280(9):784-787.
http://dx.doi.org:/10.1001/jama.280.9.784

Context. With the public’s increasing use of complementary and alternative medicine, medical schools must consider the challenge of educating physicians about these therapies. Objectives. To document the prevalence, scope, and diversity of medical school education in complementary and alternative therapy topics and to obtain information about the organizational and academic features of these courses. Design. Mail survey and follow-up letter and telephone survey conducted in 1997-1998. Participants. Academic or curriculum deans and faculty at each of the 125 US medical schools.
Main Outcome Measures. Courses taught at US medical schools and administrative and educational characteristics of these courses.
Results. Replies were received from 117 (94%) of the 125 US medical schools. Of schools that replied, 75 (64%) reported offering elective courses in complementary or alternative medicine or including these topics in required courses. Of the 123 courses reported, 84 (68%) were stand-alone electives, 38 (31%) were part of required courses, and one (1%) was part of an elective. Thirty-eight courses (31%) were offered by departments of family practice and 14 (11%) by departments of medicine or internal medicine. Educational formats included lectures, practitioner lecture and/or demonstration, and patient presentations. Common topics included chiropractic, acupuncture, homeopathy, herbal therapies, and mind-body techniques.
Conclusions. There is tremendous heterogeneity and diversity in content, format, and requirements among courses in complementary and alternative medicine at US medical schools.

9.4.5  38% of Adults Use Alternative Medicine
Rob Stein – Washington Post Staff Writer Dec 11, 2008
http://washingtonpost.com/wp-dyn/content/article/2008/12/10/AR2008121001601.html

More than one-third of adults and nearly 12 percent of children in the United States use alternatives to traditional medicine, according to a large federal survey released today that documents how entrenched acupuncture, herbal remedies and other once-exotic therapies have become.

The 2007 survey of more than 32,000 Americans, which for the first time included children, found that use of yoga, “probiotics,” fish oil and other “complementary and alternative” therapies held steady among adults since the last national survey five years earlier, and that such treatments have become part of health care for many youngsters.

“It’s clear that millions of Americans every year are turning to complementary and alternative medicine,” said Richard L. Nahin of the National Institutes of Health’s National Center for Complementary and Alternative Medicine, which released the survey. “The use of complementary and alternative medicine seems to have stabilized in the United States.”

The most commonly used are dietary supplements and herbal products such as echinacea, flaxseed oil and ginseng, followed by deep-breathing exercises, meditation, chiropractic therapy, massage and yoga. Although fewer Americans were using certain diets and trying herbal remedies such as echinacea to cure colds, the popularity of acupuncture, meditation, yoga and massage grew.
9.4.6 Wheat germ extract (Avemar, Avé, AvéULTRA, AWGE, OncoMAR)
http://mskcc.org/cancer-care/herb/wheat-germ-extract

Fermented wheat germ extract (WGE) was developed in the 1990s by Hungarian chemist Mate Hidvegi. It should not be confused with wheat germ oil. WGE is used as a dietary supplement by cancer patients in Hungary to improve quality of life (QoL).

Results from in vitro studies show that WGE has anticancer (1) (2) (3) (4) (5) (19), antimetastatic (6), and immunomodulatory (2) (7) effects. Although it appears to increase estrogen receptor (ER) activity, WGE enhanced efficacy of tamoxifen, an ER antagonist, in ER+ breast cancer cells (8) as well as cisplatin in ovarian cancer cell lines (5). Animal models suggest WGE can reduce cardiovascular symptoms due to chronic hypertension, diabetes, and obesity (9), mitigate symptoms associated with lupus (10), and that its antitumor effect is comparable to other endocrine treatments (11).

Data from pilot studies indicate a beneficial role for WGE in patients with colorectal cancer (12) and in reducing treatment-associated febrile neutropenia in pediatric cancer patients (13). It also prolonged survival of patients with melanoma when used with chemotherapy (14) (15). However, these effects must be confirmed by large-scale, well-designed clinical trials.

Because it potentiates estrogen receptor activity, patients with hormone-sensitive cancers should use WGE with caution.

What is Avemar?
http://avemar.info/what_is_avemar

Avemar is an all-natural, clinically proven, dietary supplement for cancer patients. Medical experts recognize Avemar as an effective supportive cancer treatment and recommend complementing the diet of concerned patients with Avemar.Scientific studies showed that Avemar also enhances the efficacy of conventional oncological treatments (surgery, radio-, chemo- and immunotherapy). With regular intake of Avemar, patients can relish a better quality of life and can enjoy a better lifestyle. Avemar is available in granulate and film-coated tablet form.

The active ingredient is Avemar pulvis, an all-natural compound made from fermented wheat germ extract using patented biotechnological processes. Since the invention of Avemar pulvis significant research has been undertaken – not only in the laboratory, but in test animals and human cancer patients as well. Numerous scientific studies have been conducted to study its safety profile and its effectiveness, including in vitroin vivo and human clinical research. Over 100 reports have been written for presentation or publication since 1998, and over 33 peer-reviewed scientific papers are currently accessible at PubMed database. All scientific publications are accessible at the official Avemar Research website.

9.4.7 How Avemar Helps Fight Cancer
Dr. David Williams
http://drdavidwilliams.com/avemar-cancer

Avemar is a naturally fermented wheat germ extract that has been subjected to a great deal of research scrutiny, particularly in the area of cancer treatment. What makes Avemar stand out among other known therapies is the fact that its effectiveness isn’t limited to any one specific type of cancer. So far it has exhibited positive effects against all forms of cancer cell lines tested.

Whether cancer cells proceed to replicate, grow, and eventually spread throughout the body is determined by enzymatic activity and their accessibility to various nutrients.

Pharmaceutical companies have focused their efforts to find cures for various forms of cancer. One of their top priorities (and one area with the greatest potential) has always been to uncover compounds that inhibit glucose metabolism in tumor cells.

Every form of cancer cell utilizes glucose at rates 10 to 50 times higher than that of normal healthy cells (a well-known phenomenon referred to as “the Warburg effect”). Unlike normal, healthy cells that utilize glucose primarily for energy, tumor cells use glucose to replicate cells. They convert glucose to nucleic acids (necessary for the formation of additional RNA) by a hexose monophosphate pathway. They also have to break down tissue in order to make proteins (needed for the cancer to continue to grow). This is termed cachexia.  In this sense the behavior of cancer proliferation is like a systemic infection.

In simple terms, cancer cells have only one function: proliferation. To achieve this function, cancer cells need large amounts of glucose that they can convert into building materials for new cells. As the tumor grows, more and more glucose is consumed.

Research indicates that Avemar works through several different mechanisms. One of its most unique benefits, however, is its ability to inhibit glucose metabolism in cancer cells.

Research at UCLA has demonstrated that Avemar reduces glucose flow into cancer cells—which inhibits their ability to produce additional nucleic acids and subsequently reduces their proliferation or growth. In the presence of Avemar compounds, cancer cells begin to utilize the available glucose to produce substances that actually inhibit cell division and stimulate programmed cell death (apoptosis) within the tumor.

As one report explains, decreased glucose consumption of the tumors results in a harmonizing of the patient’s metabolism—as well as weight gain, even in people with advanced cancers. As a result, patients treated with Avemar also have improved tolerance for surgery, radiation, and chemotherapy. Further, Avemar achieves these results without creating any toxicity or damage to normal, healthy cells. (Ann N Y Acad Sci. 07;1110:348–61)

This particular feature of Avemar explains why cancer patients using the product routinely experience an improved quality of life. They have less fatigue, pain, and depression, and experience an increase in appetite that can help them regain lost weight. (Medicus Anonymus/Pulmono 03;11 (Suppl 1):13–14) (24th Congress of the Hungarian Cancer Society, Budapest, Hungary 2001)

9.4.8  The anti-cancer action of curcumin (turmeric)
http://canceractive.com/cancer-active-page-link.aspx?n=1571

* Importantly, the spice can stop the action of the enzyme COX-2 known to produce negative, inflammation causing localised enzymes (eicosanoids). Such inflammation is a known precursor to cancer.

* It has also been shown to inhibit vascular epithelial growth factors. Every tumor needs a blood supply – the growth factors build one, but curcumin seems to stop them.

* It has been shown to ´re-awaken´ a key tumor suppressor gene.

* It has been shown to inhibit metastases.

* It has been shown to kill cancer cells (B lymphoma cells).

* It prevents regrowth of cancer stem cells which lie at the heart of many tumors

In the journal ´Genes and Nutrition´ (2011; 6(2):93-108) the whole issue of ´Epigenetics´ was exposed. It used to be thought that your genes controlled all and a problem in a gene meant you were in some way ´doomed´. This theory has been disproven and replaced by one that shows genes are just your blueprint; these blueprints are controlled, activated or suppressed by the localized environment. So hormones can affect their action, as can natural compounds in food. And curcumin seems to affect gene expression significantly. Such ´signaling pathways´ have been shown to be affected by curcumin.

An example of this ´signaling pathway´ modification came in research from the Ludwig-Maximilians University in Munich, Germany in 2012 which showed that curcumin can inhibit the formation of metastases in both prostate and breast cancer.  Both cancers spread throughout the body through the release of chemical messengers, pro-inflammatory cytokines CXCL1 and CXCL2, but curcumin alters the expression of these two damaging proteins.

Next, Cheryl Myers (head of Scientific Affairs and Education for EuroPharma Inc.) refers to curcumin as ´the anti-cancer herb´ because of its success in stopping cancer formation, replication and spread. Research also shows that curcumin increases the activity of certain anti-cancer drugs while protecting healthy cells and organs. It has been proven to reduce systemic inflammation and oxidative stress.

And researchers from the Dept. of Natural Science at Middlesex University have shown that curcumin and chokeberry can work together to induce cancer cell death (apoptosis) and stop the spread of malignant cancer cells. Their report (in Oncology Reports) was for brain tumors.

Dr Young S. Kim leading a team at the National Cancer Institute in America showed that curcumin was one of the natural compounds that could prevent cancer stem cells from re-growing and re-forming the cancer. Her conclusion even suggested patients could supplement!

The University of Missouri has shown curcumin can counter the dangerous effects of HRT and its link to breast cancer cause.  “The results of the study show that women could potentially take curcumin to protect themselves from developing progestin-accelerated tumors,” said the lead researcher. Synthetic progestin increases VEGF a protein that helps form blood supplies to developing tumors. Curcumin inhibits VEGF and thus reduces the potential of breast cancer to grow.

Professor Bharat Aggarwal Ph. D. in MD Anderson Department of Therapeutics has conducted a number of studies, for example showing that in a Phase II clinical trial, pancreatic cancer patients having no chemotherapy, it reduced tumor size. He believes it is effective against many types of cancer because it suppresses angiogenesis (the growth of blood vessels essential to a tumor). “The reason curcumin is so effective against cancer is that it hits not just a single target or cell signaling pathway but dozens of targets implicated in cancer.” It has also been shown to have a strong synergistic effect against cancer with resveratrol, and also with EGCG in green tea.

What is exciting the experts in cancer centers in America is that it can play a role against several of the steps in what is a multi-step cancer process. As such it would seem stupid to ignore it as a part of an Integrative or holistic cancer treatment program.

What are curcumin and turmeric?

Curcumin is the active ingredient of the Indian/Asian curry spice Turmeric.  To put this technically, curcumin is the principal curcuminoid in turmeric.  Curcuminoids are polyphenols.  Turmeric powder is ground from the root of a plant called Curcuma Longa, which is a member of the ginger family and is found throughout Southern Asia, even growing wild in the Himalayas.

This vivid yellow to brown spice was used, like many Asian spices and chillies, to hide the taste of stronger tasting meats and fish even those that might have gone a little off in such hot climates.  Like many such spices, it also performed a necessary and functional role it was a cleanser, a bacteria-killer in the stomach, protecting against tainted foods!

Curcumin/turmeric has been used in Ayurvedic medicine for thousands of years as a cleanser of the body.  It appears to work at a number of levels:

  1. It can inhibit unwanted bacterial action in the stomach and intestine:

For example (i) , University of Chicago researchers have shown it inhibits Helicobacter pylori, a bacterium known to be responsible for stomach ulcers and some stomach cancers.  In Ayurvedic medicine, curcumin was used in poultices for this same reason to kill unwanted bacteria.

  1. It is a significant anti-inflammatory:

Arachidonic acid is a precursor/stimulator of the production of bad eicosancids (see our reviews of omega 3 and vitamin D) and thus to inflammation, which is itself a precursor to certain cancers.  Curcumin has been found to inhibit several of the pre-inflammatory enzymes (e.g. COX2 and iNOS) in vitro and in vivo with animals.  Japanese research suggests it works in much the same way as salicylin.

  1. It boosts crucial cellular glutathione levels:

Glutathione is a crucial intracellular antioxidant, helping the cell maintain its correct oxygen levels and fight off the effects of stress hormones.  Research has shown that curcumin can prevent the action of an enzyme that limits glutathione production.

  1. It is a powerful antioxidant:

Turmeric extract tested more potent than garlic, omega 3 and cat´s claw (devil´s claw) said German research.

  1. It can help prevent liver damage

2010 research from St Louis has shown that it can turn off a protein called Leptin, which causes liver damage. It has also been shown to be capable of detoxifying the liver. Thus curcumin may be of help in keeping the liver healthy during chemotherapy cancer treatments.

  1. It can prevent and even ´treat´ cancer:

As we have covered above, curcumin can suppress tumor initiation, promotion and metastasis.  Extensive research over the last 50 years has indicated it can prevent and treat cancer. The anti-cancer potential stems from its ability to control gene signaling, and affect a wide variety of tumor cells, down-regulate transcription factors, down-regulate enzymes such as COX-2 and other inflammatories, cytokines, chemokines, cell-surface adhesion molecules, down-regulate growth factors, etc., etc.

Tufts have conducted research with breast cancer patients concluding that curcumin and isoflavanoids seem to inhibit the action of environmental estrogens.

UCLA have researched its potential with colorectal cancer (San Diego, Chauhen). And there are Clinical Trials underway (according to the Mayo Clinic to investigate curcumin as a way to prevent cancer in people with precancerous conditions, as a cancer treatment, and as a remedy for signs and symptoms caused by cancer treatments.

Much of the work original used cell cultures.  Increasingly studies use a variety of animals, and there have been human trials, even clinical trials, primarily with cervical cancer lesions and with gastrointestinal cancers.  So, although the biochemical knowledge is vast, the use of oral curcumin to prevent and treat cancer is still in its infancy.

Next, there is a problem maintaining effectiveness inside the cells; there are several studies that show oral consumption needs to be maintained in order to maintain blood and cellular levels.  But it is not as simple as curry every day!

Curcumin supplements may be heavily contaminated with everything from pesticides to other spices so you must choose a reliable supplier, ideally of curcuma longa. If you are thinking of buying Curcuma Longa you might like to look at the Natural Selection as they are based in the UK and they tend to have natural compounds that avoid pesticides. Click here. Alternatively in the USA you might like to go to the Natural News or Dr Mercola websites.

Counter indications

Some supplements contain piperine, supposedly to increase bio-availability.  This can interfere with certain drugs.

Curcumin can inhibit coagulation in vitro and so may be inadvisable if you are taking anti-coagulants.  It might increase the risk of bleeding.

It might also be advisable not to take it if you are pregnant or lactating.

In summary

Clearly there is a huge enthusiasm, even expectation, overseas for curcumin, if not in British hospitals and oncology departments.  But the real issue is can you take enough of it orally to deliver it in adequate doses to your breast or prostate cells?  Certainly curcumin (curcuma longa) was seen to be an important herb in the natural and successful treatment of prostate cancer that we covered in Cancer Watch (icon 2006, issue 3 ).  We will just have to wait and see whether this longstanding Ayurvedic medicine will curry favour with the UK medical fraternity.

Read Full Post »


Larry H Bernstein, MD, FCAP, Contributor

https://pharmaceuticalintelligence.com/5-6-2014/larryhbern/ The Discovery_and_Properties_of_Avemar – Fermented_ Wheat_Germ_Extract:_Carcinogenesis_Suppressor

The following discussion will be a review of the current interest in Avemar, a nontoxic, fermentation product of wheat germ extract, garnering interest with respect to alternative and complementary medicinal use.

Extracts from an interview by Sandra Cascio with Mate Hidvegi

Mate’s Transylvania Professor Lajos David was the organizer of the Department of Pharmacy of the University of Szeged in the 1920’s. He was elected as the Dean of the Faculty of Medicine, the first and only pharmacist who reached this high position at the University since. Dr. Hidvegy’s grandfather was a devout Roman catholic, who publicly opposed Nazi persecution of Jews during the Holocaust. One of his colleagues and, perhaps his best friend, was Albert Szent­Gyorgyi, the Nobel laureate who discovered vitaminC. Szent­Gyorgyi moved to the United States after World War II, where he turned to studies of muscle biochemistry. In his later years he turned to cancer research. He  theorized that a revolutionary anticancer drug could be based upon vitamin C combined with methoxy­substituted benzoquinones, the precursors of which can be found in wheat germ. After completion of the PhD, Dr. Hidvegi spent two years with the Wheat Grain Trust in Winnipeg, Canada, before returning to Hungary in 1990.  He decided to followthepathwaythat Szent­Gyorgyi was now engaged intocompletehisgoals.He contacted anoldfriend,GaborFodor, a brilliantchemist, also a collaborator withSzent­Gyorgyiincancerresearch.

He wasinvited by Hermann Esterbauer, the head of the Institute of Biochemistry at the University of Graz, to work in his laboratory. Thanks to the generosity of Professor Esterbauer,  he accomplished much at Graz  together with his student, Dr. Rita Farkas.  It was soon after Szent­-Gyorgyi’s death when, with the help of Dr. Fodor, they prepared the chemicals to make the drug Szent­-Gyorgyi had intended to make, with encouragement from the great quantum­ biochemist, Janos Ladik.  They made wheat germ extracts with the highest free benzoquinone content.This required a  fermentation process to liberate the benzoquinone moieties from the chemical bonds which keep them in natural forms: in glycosides. He recalls the purple colored active molecules in the fermentation liquid. Living cells with their exo­ and endo­enzymes are used to split bonds and make new molecules. This is also true for the manufacturing process of Avemar. This extract contains new molecules which cannot be found elsewhere.

“WhenAvemar was voted by the majority of the more than 50,000 professionals for NutrAward, it became obvious that this product is of biological efficacy  plus safety, and it is based on good science.” It received the financial support needed. From this, he was able to complete the experiments and get the approval for the registration. The time arrived when he really had to give a name to the product which had only had a code name. One late night it just came: Avemar, from the Latin prayer: Ave Maria.

Avemar with widely used chemotherapeutic drugs completely inhibited the development of metastases. Exploring its whole activity profile might even take a lifetime of research. So far he has supervised Avemar research done in Hungary, Israel, the United States, Austria, Italy, Spain, Slovakia, the Czech Republic, Germany,the United Kingdom, Russia, Australia, Korea, Vietnam. It has been a good experience to see the scientific interest it has generated worldwide. In 2009, Dr. Hidvegy received an invitation from the Nobel laureate, James Watson, co­discoverer of DNA’s double helix. It was a great honor. Avemar, he hopes,will be a significant cancer drug.

Mate Hidvegi was born in Budapest, Hungary, in 1955. He studied, then  taughat what is now Budapest University of Technology  and Economics.  After finishing university, he worked in the cereal industry and was co­developer of patented feed advisory system based on near infrared ingredient      data. In Hungary, Hidvegi was one of the pioneers in the development of           technologies for large ­scale production of instantized extracts for  therapeutic use.

 

Carcinogenesis vol.22 no.10 pp.1649–1652, 2001

Wheat germ extract inhibits experimental colon carcino-genesis in F-344 rats

Attila Zalatnai, Karoly Lapis, Bela Szende, Erzsebet Raso, Andros Telekes, Akos Resetar, and Mate Hidvegi

 

It has been demonstrated for the first time that a wheat germ extract prevents colonic cancer in laboratory animals. Four-week-old inbred male F-344 rats were used in the study. Colon carcinogenesis was induced by azoxy-methane (AOM). Ten rats served as untreated controls (group 1). For the treatment of the animals in group 2, AOM was dissolved in physiologic saline and the animals were given three weekly subcutaneous injections at 15 mg/kg body weight (b/w). In two additional groups Avemar (MSC), a fermented wheat germ extract standardized to 2,6-dimethoxy-p-benzoquinone was administered as a tentative chemo-preventive agent. MSC was dissolved in water and was given by gavage at a dose of 3 g/kg b/w once a day. In group 3, animals started to receive MSC 2 weeks prior to the first injection of AOM daily and continuously thereafter until they were killed 32 weeks later. In group 4 only the basal diet and MSC were administered. At the end of the experiment all the rats were exsanguinated under a light ether anesthesia and necropsied. Percentage of animals developing colon tumors and number of tumors per animals: group 1 – 0 and 0; group 2– 83.0 and 2.3; group 3 – 44.8 (P ≤ 0.001) and 1.3 (P ≤ 0.004); group 4 – 0 and 0. All the tumors were histologically neoplastic. The numbers of the aberrant crypt foci (ACF) per area (cm2) in group 2 were 4.85 while in group 3 the ACF numbers were 2.03 only (P ≤ 0.0001).
Table I. Macroscopic findings in the large intestines of F-344 rats treated with MSC or MSC +  AOM
No. of animals     w/tumorw   Average
# tumors
Average
diameter

N

1 Untreated
controls (10)
0/10 0/10
2.  AOM (47) 39/47
(83.0%)
2.3 ­+ 0.21
(range 1–8)
2.35 +
0.25
3.   MSC +
AOM (29)
13/29
(44.8%)
1.3 + 0.17
(range 1–3)
2.21 +
0.12
4.  MSC (9) 0/9 0/9
Fig. 1. Experimental schedule. Colon carcinogenesis was induced by three consecutive s.c. doses of AOM 1 week apart in F-344 rats. Oral administration of MSC was started 2 weeks before the carcinogen treatments. All the animals were killed at the end of the experiment, e.g. on the 32nd week.  (not shown)

 

Summing up, although the chemoprevention of colon cancers (and their pre-neoplastic lesions) has well and long been established and could be achieved by totally different compounds, the mechanisms have still remained to be clarified. This is also true for MSC.

The exact mechanism by which the fermented wheat germ concentration can prevent colon cancer is still partly unknown. MSC did inhibit the AOM-induced ACF and colon neoplasm formation, the multiplicity of the tumors, apparently acting in the initiation phase. Regarding this, we can hypothesize that MSC acts as an immunomodulator.

 

Wheat Germ Extract Decreases Glucose Uptake and RNARibose Formation but Increases Fatty Acid Synthesis in MIAPancreatic Adenocarcinoma Cell

LG Boros, K Lapis, B Szende, R Tömösközi-Farkas, Ádám Balogh, …., and M Hidvégi

UCLA School of Medicine, Harbor-UCLA Research and Education Institute, Torrance, Ca.; First Institute of Pathology and Experimental Cancer Research, Semmelweis  Medical University, Budapest, Hungary; Central Food Research Institute, Budapest, Hungary; Department of Surgery, Albert Szent-Gyorgyi Medical and Pharmaceutical Center, School of General Medicine, University of Szeged, Szeged, Hungary; Department of Biochemistry and Molecular Biology, Institut d’Investigacions Biomediques August Pi i Sunyer, University of Barcelona, Barcelona, Spain; andDepartment of Biochemistryand Food Technology, Technical University of Budapest and Biromedicina Company, Budapest, Hungary

Pancreas 2001; 23 (2), pp. 141–147

Summary: The fermented wheat germ extract with standardized composition has potent tumor inhibitory properties. The fermented wheat germ extract controls tumor propagation. The authors show that this extract induces profound metabolic changes in cultured MIA pancreatic adenocarcinoma cells when the [1,2- 13C2] glucose isotope is used as the single tracer with biologic gas chromatography–mass spectrometry.

MIA cells treated with 0.1, 1, and 10 mg/mL wheat  germ extract showed a dose-dependent decrease in cell glucose consumption, consumption, uptake of isotope into ribosomal RNA (2.4%, 9.4%, and 8.0%), and release of 13CO2 . Conversely, direct glucose oxidation and ribose recycling in the pentose cycle showed a dose-dependent increase of 1.2%, 20.7%, and 93.4%. The newly synthesized fraction of cell palmitate and the 13C enrichment of acetyl units were also increased with all doses of wheat germ extract.

The fermented wheat germ extract controls tumor propagation primarily by regulating glucose carbon redistribution between cell proliferation–related and cell differentiation–related macromolecules. Wheat germ extract treatment is likely associated with the phosphor-ylation and transcriptional regulation of metabolic enzymes that are involved in glucose carbon redistribution between cell the direct oxidative degradation of glucose,proliferation–related structural and functional macromolecules(RNA, DNA) and the direct oxidative degradation and survival of pancreatic adenocarcinoma cells in culture.

Key Words: Pentose cycle—Ribose synthesis—Fermented wheat germ extract—Nonoxidative glucose metabolism—Cell proliferation—Avemar.

 

Fig 1 glu consumption of MIA pancreatic carcinoma cells in response to WGE

Fig 1 glu consumption of MIA pancreatic carcinoma cells in response to WGE

 

 

 

 

 

 

 

 

 

 

 

Figure 1. Glucose consumption of MIA pancreatic adenocarcinoma cells in response to increasing doses of fermented wheat germ extract (Avemar) treatment after 72 hours of culture. Glucose consumption (measured in milligrams) was estimated by the difference in media glucose content between Avemar-treated and control cultures. MIA cell glucose consumption was significantly inhibited in the presence of either 1 mg/mL (*p < 0.05) or 10 mg/mL (**p < 0.01) Avemar (x + SD;  n = 6).

 

fig-3-rna-syn-of-mia-pancreatic-carcinoma-cells-in-response-to-wge.jpg

fig-3-rna-syn-of-mia-pancreatic-carcinoma-cells-in-response-to-wge.jpg

 

 

 

 

 

 

 

 

 

 

 

Figure 3. Ribosomal RNA synthesis of MIA pancreatic adenocarcinoma cells in response to increasing doses of fermented wheat germ extract (Avemar) treatment after 72 hours of culture. Glucose carbon incorporation into ribose isolated from ribosomal RNA is expressed as molar enrichment. The dose-dependent decrease in of rRNA after Avemar treatment indicates that ribosomal RNA synthesis is the primary site significantly affected by all doses of Avemar treatment with a maximum decrease of 29% after 10 mg/mL treatment (x + SD; n = 9; *p < 0.05, **p < 0.01).

changes in metabolic activity indicate that Avemar treatment affects cell metabolism primarily by decreasing glucose uptake and nucleic acid ribose synthesis while increasing glucose oxidation through the oxidative reactions of the pentose cycle and fatty acid  synthesis from glucose carbon. The effect of Avemar treatment on lactate production and TCA cycle anapleurotic flux compared with glucose oxidation is less prominent

 

Fermented wheat germ extract induces apoptosis and downregulation of major histocompatibility complex class I proteins in tumor T and B cell lines

R FAJKA-BOJA, M HIDVÉGI, Y SHOENFELD, G  ION, D DEMYDENKO, R TÖMÖSKÖZI-FARKAS, et al.

INTL J ONCOLOGY 2002; 20: 563-570.

Lymphocyte Signal Transduction Laboratory, Institute of Genetics, and Cytokine Group, Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, Szeged; Department of Biochemistry and Food Technology, Budapest University of Technology and Economics, Budapest, Hungary; Department of Medicine ‘B’, Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel; Central Food Research Institute; National Institute of Oncology; Biromedicina Co., Budapest, Hungary
Abstract. The fermented wheat germ extract (code name:  on cyto-fluorimeter using a monoclonal antibody to the  MSC, trade name: Avemar), with standardized benzoquinone non-polymorphic region of the human MHC class I. MSC  content has been shown to inhibit tumor propagation and stimulated tyrosine phosphorylation of intracellular proteins metastases formation in vivo. The aim of this study was to  understand the molecular and cellular mechanisms of the anti-tumor effect of MSC. Therefore, we have designed in vitro model experiments using T and B tumor lymphocytic cell lines. As a result of the MSC treatment, cell surface MHC class I proteins was downregulated by 70-85% compared to the non-stimulated control.

Prominent apoptosis of and the influx of extracellular Ca2+ resulted in elevation of the amount of the intracellular Ca2+ concentration. 20-40% was detected upon 24 h of MSC treatment of the cell lines. Apoptosis was measured with cytofluorimetry by staining the DNA with propidium iodide and detecting the ‘sub-G ’ cell population.

Tyrosine phosphorylation of intra-cellular proteins and elevation of the intracellular Ca2+ concentration were examined using immunoblotting with anti-phosphotyrosine antibody and cytofluorimetry by means of Ca2+ sensitive fluorescence dyes, Fluo-3AM and FuraRed-AM, respectively. MSC did not induce a similar degree of apoptosis in healthy peripheral blood mononuclear cells.

Inhibition of the cellular tyrosine phosphatase activity or Ca2+ influx resulted in the opposite effect – increasing or diminishing the Avemar induced apoptosis as well as the MHC class I downregulation. The level of the cell surface MHC class I molecules was analysed with indirect immunofluorescence. The benzoquinone component (2,6-dimethoxi-p-benzoquinone) in MSC induced similar apoptosis and downregulation of the MHC class I molecules in the tumor T and B cell lines to that of MSC. These results suggest that MSC acts on lymphoid tumor cells by reducing MHC class I expression and selectively promoting apoptosis of tumor cells on a tyrosine phosphorylation and Ca2+ influx dependent way.  One of the components in MSC, 2,6-dimethoxi-p-benzoquinone was shown to be an important factor in MSC mediated cell response.

 

Abbreviations:MHC, major histocompatibility complex;NK, natural killer;DMBQ, 2,6-dimethoxi-p-benzoquinone; FCS, fetal calf serum;PBMC, peripheral bloodmononuclear cells; TCR, T cell receptor;BCR, B cell receptor; mAb, monoclonal antibody;PMSF,phenylmethyl-sulfonylfluoride;pNPP, para-nitrophenyl-phosphate; PHA,phytohemagglutinineKey words: fermented wheat germ extract, Avemar, MSC, 2+ benzoquinone, tyrosine phosphorylation, intracellular Ca , CD45, tyrosine phosphatase, MHC class I downregulation, apoptosis

 

fig-4-apoptosis-of-t-cell-lines-induced-by-avamer.jpg

fig-4-apoptosis-of-t-cell-lines-induced-by-avamer.jpg

 

 

 

 

 

Figure 4. Apoptosis of tumor T cell lines and healthy lymphocytes upon MSC treatment. Jurkat cells were treated with 1 mg/ml MSC or .3 µg/ml DMBQ and PBMC were treated with 1 mg/ml
MSC for 24 h (A) or Jurkat cells were treated for 12 h (thick line in panel B). Control cells were left unstimulated (black bars in panel A or thin line on panel B). Apoptotic cells were enumerated
with the DNA analysis of the ‘sub-G ’ population (A) or with staining the cells with FITC1 labeled Annexin V
(B). Representative experiments are shown. The difference between the % of apoptosis in the case of treated and non-treated Jurkat cells was significant (MSC, p<0.001, n=14; DMBQ, p<0.05, n=3,
using  paired, two-tailed t-test). No difference was found for PBMC (n=2).

MSC treatment causes prominent apoptosis in lymphoid tumor cells but it does not induce apoptosis of healthy resting mononuclear cells. Moreover, although MSC blocks the proliferation of PBM cells stimulated with PHA, it does not induce apoptosis in PHA stimulated cells (data not shown).

Read Full Post »