Chapter 53.The Trophoblastic Theory of Cancer

Chapter 53.The Trophoblastic Theory of Cancer

Have you ever wondered why cancer treatment has not changed much in over 70 years?  Why is chemotherapy still the mainstay of conventional cancer treatment after all these years of disappointing results for the majority of cancer cell types?  Perhaps we should be exploring alternatives.  At a medical meeting I attended, Nicholas Gonzalez MD presented his views on the etiology of cancer and cancer treatment.  Dr. Gonzalez is actively engaged in medical practice in Manhattan where he treats advanced cancer successfully with high dose oral pancreatic enzymes.  (1-7)  This treatment regimen is based on the Trophoblastic Theory of cancer.  This theory was originally proposed by a Scottish embryologist named John Beard (1858-1924), and was resurrected by William Donald Kelley, DDS (1926-2005).(8-16)

John Beard and the Trophoblast Theory

John Beard (1858-1924), was a Scottish embryologist who used the light microscope to study developmental embryology as well as cancer pathology.(10-12)  In 1905, Beard was the first to report that trophoblast cells act and behave in a manner identical to cancer cells, acting invasively, and inducing their own blood supply.(40-41)  This observation has been confirmed with more recent research.(56)   The trophoblast cell is a cell derived from the Placenta, a structure inside the uterus of a pregnant mother which serves as blood supply for the developing embryo.

What are Trophoblasts? Similarity with Cancer Cells

In the pregnant mother, trophoblasts are the infiltrative components of the developing embryo which form the placenta.  These cells invade and infiltrate into the wall of the mother’s uterus.  This behavior is very similar to the way cancer cells infiltrate and invade surrounding tissues.  These trophoblast cells are known to produce human chorionic gonadotropin (HCG).  In fact, production of HCG is the basis for the widely used pregnancy test.  If cancer cells and trophoblast cells are similar, one would expect cancer cells to also produce HCG.  That is exactly what they do.  This was reported in 1995 by Hernan Acevedo, PhD, and published in the journal, Cancer. (42-44)  He found that every cancer produces HCG, same as the trophoblast cells of pregnancy.   Since John Beard's day about one hundred years ago, modern biologists have found even more similarities between trophoblasts and malignant cancer cells.  Dr. C. Ferretti in the October 2006 issue of Human Reproduction Update, states that both cancer and trophoblast cells share the same molecular circuitry for their proliferative, invasive and migratory capacities.(53)

CT Antigens Discovered

Another twist to the story is the recent discovery of a new class of human tumor antigens called CT (cancer/testis) antigens.(49-52)  About 90 genes have been found having messenger RNA expression in both germ cells (testis) and cancer cells, and no expression in otherwise normal cells.  This is further evidence linking the trophoblast cells, which are, in fact, germ cells (also called stem cells), with cancer cells.  These recent advances in molecular biology have shown that John Beard was quite correct to point out the similarity between placental trophoblast cells and malignant cancer cells.  Beard's forgotten predictions in the early 1900's seem to have an uncanny way of resurfacing 100 years later.

Pancreatic Enzymes on Day 56

On Day Fifty Six of embryonic development, John Beard observed through his microscope trophoblast cells suddenly transform from malignant, invasive cells into mature and well behaved cells.  This day 56 transformation also coincides with the appearance of enzyme granules (also called zymogen granules) in the fetal pancreas.  Obviously, since all nutrition comes from the maternal blood supply, the developing fetus in-utero has no need for pancreatic enzymes.  These are used later after the fetus is born when the baby starts eating food.  Beard theorized the appearance of pancreatic enzymes was no accident, and that the enzymes caused transformation of the trophoblast cells behavior from "malignant" to a "benign" cell type.  This logic suggested the use of digestive enzymes to control cancer cells.  A number of studies in both animal models and humans have actually confirmed the utility of pancreatic enzyme for cancer treatment.  

About the same time as John Beard's early work, Madam Curie's (1867-1934) work treating cancer with radiation took the spotlight, and captured the imagination of the media and the public.  John Beard's work on the Trophoblast Theory was dismissed by mainstream medical science and almost forgotten. 

An excellent review of recent research confirming John Beard's work as well as the value of enzyme treatments for cancer is: “A Critique of the Kelley Nutritional-Metabolic Cancer Program” by Melina A. Roberts BSc. From the Townsend Letter for Doctors & Patients June 2003. (30)  A leading biochemist, Ernst Krebs, wrote an important 1950 paper supporting the Trophoblast Theory of Cancer entitled “The Unitarian or Trophoblastic Thesus of Cancer” by Ernst T. Krebs, Jr., Ernst T. Krebs, Sr., and Howard H. Beard. (57)

William Donald Kelley Resurrects John Beard's Work

Years later in the 1960's, William Kelly discovered Beard's forgotten papers, and resurrected the treatment of cancer with pancreatic enzymes.  Kelly had considerable success treating patients with this alternative cancer treatment approach.  However, Kelly was a dentist, and bitterly opposed by mainstream medicine, and as expected, had difficulties with the authorities.  Kelly was convicted of practicing medicine without a license in 1970, his dental license was suspended in 1976, and he passed away on Jan. 30, 2005 at the age of 79.

Nicholas Gonzalez' Research

In 1981, during the Kelly's early years, a medical student at Cornell Medical School by the name of Nicholas Gonzalez was given a summer project to interview William Donald Kelly and evaluate his results with cancer patients using the pancreatic enzyme treatment.   Gonzalez did a retrospective review of 1300 patients who had been treated over a 20-year period with the Kelley protocol with enzymes, diet and nutritional support.  Gonzalez was so impressed with the data, and the superior patient outcomes, that this summer project expanded into a book, and later adopted as his own life's work.

Continuing after Kelly, Nicholas Gonzalez MD carried on with his legacy at a Manhattan office, documenting remarkable success over the past decade or so.  Selected case reports from the Gonzalez Manhattan office show dramatic clinical results not possible with conventional mainstream cancer treatment.  This information is posted on the Dr Gonzalez web site.(1)   

In 1999, Gonzalez published a 2 year pilot study of 10 patients with inoperable advanced pancreatic cancer treated with large doses of orally ingested pancreatic enzymes.(92)   Results showed 80% survival after 1 year, 45% survival after 2 years and 36% survival after 3 years. (92)  These results are far above the 25% one year, 10% two year, and 6 % three year survival reported in the National Cancer Data Base for inoperable pancreatic cancer. (93)   Shortly after this, Gonzalez received a $1.4 million grant from the National Center for Complementary and Alternative Medicine at the National Institutes of Health for further study on enzyme therapy and pancreatic cancer. (94) The study was to be conducted at Columbia-Presbyterian Medical Center in New York under the supervision of the NCI and with approval from the FDA.  This study ran into snags and is yet to be completed or published.

Otto Warburg

Otto Warburg made important contributions to the understanding of the metabolic activity of cancer.  All cancers, as well as trophoblast cells have a high glucose utilization using the primitive glycolysis pathway.  They tend not to use oxidative phosphorylation and thrive in a low oxygen environment.  This is known as the Warburg Effect.  Recent work has built on Warburg's ideas using inhibitors of glycolysis such as 3 bromopyruvate to kill cancer cells by stopping glycolysis.(77)(82)   Others have used insulin induced hypoglycemia to starve cancer cells of their glucose substrate.  (84-90)  Avid glucose uptake is the basis of modern PET (positron emission tomography) imaging of the body which is capable of showing cancer deposits with radiolabeled 17-Flouro-deoxyglucose. This has prompted interest in compounds which inhibit glucose metabolism such as  2-De-Oxy-Glucose, which kills cancer cells.(73)

Aneuploidy - and Confined Placental Mosaicism

Recently there has been resurgence of interest in aneuploidy and cancer championed by Peter Duesberg in his 2007  article in Scientific American, “Chromosomal Chaos and Cancer”. (95)  Aneuploidy or abnormal and multiple sets of chromosomes is commonly found in cancer, and also found in the placenta. (65-70)  Using ultrasound guided chorionic villous sampling, it has been discovered that between 2-5% of placental samples show aneuploid cells; this is called confined placental mosaicism, which apparently does not affect the developing embryo.

No Coexistence of Cancer with Circulating Enzymes of Pancreatitis

One last point I am compelled to mention.  During my 30 year career as a radiologist much of my time was spent reading images of metastatic cancer on CAT scans.  One of the things I noticed was that I never witnessed the presence of metastatic cancer in patients who had pancreatic enzymes circulating freely in the bloodstream from acute or chronic diffuse pancreatitis.  Excluded of course was focal pancreatitis caused by an obstructed pancreatic duct due to a small pancreatic cancer.  Thus I had independently confirmed the major tenet of John Beard and Ernst Krebs many years before I even heard of the trophoblastic theory of cancer.

Cancer of Small Bowel Relatively Rare

Another observation most experienced radiologists and surgeons will make is the relative rarity of neoplasm involving the small bowel compared to the relative common appearance (50 times more common) of neoplasm in the colon and the stomach.  Ernst Krebs makes this same observation in his landmark 1950 paper on the Unified Trophoblast Theory of Cancer, and Krebs suggests that pancreatic enzymes released into the duodenum at the duct of Wirsung and Santorini are responsible for this 50 times reduction in small bowel cancer. (57)   The age-adjusted death rate for cancer of the colon is 47 times higher than cancer of the small bowel, at 0.4 for small bowel and 18.8 for colon cancer per 100,000 men and women per year. (96)

NIH Grant Proposal to Study Cancer

The NIH (National Institute of Health) has spent literally trillions over four decades on failed cancer research.  It is time to take a different approach with a few proposals to investigate the trophoblast theory of cancer.  A widely used technique in molecular biology is the tracer study.  The older tracer method involved the use of Carbon 14 radio-labeling.  The newer method uses insertion of the green florescent protein (GFP) into the protein one wishes to study.

Carbon 14 Radio-Labeled Trypsin

The proposed study can be done by using Carbon 14 radio-labeling of key amino acids in the pancreatic enzyme, trypsin, and feeding these radio-labeled amino acids to the pigs used to harvest the trypsin for later use.  Then administer the radio-labeled trypsin enzymes to an animal model of cancer looking for the distribution of the radio-label in the sacrificed animals. If there is an effect on the cancer cells, I would expect to find the radio-labeled enzymes at the surface of the cancer cells. 

GFP Green Florescent Protein

Another more elegant approach would be to genetically modify the pancreatic trypsin enzyme in mice by adding a green florescent marker gene (GFP), a common technique used in molecular biology.  If pancreatic enzymes control the trophoblast, then the experiments should confirm the presence of the florescent marker at the trophoblast cells after day 56 in the developing embryo.  To study cancer, the green florescent gene (GFP) can be inserted into DNA of the animals (usually pigs) used to manufacture the pancreatic enzymes.  These labeled enzymes can then be administered to mice pretreated with cancer cells.  Knowledge about the rate of survival of the treated vs. control mice as well as the fate of the labeled enzymes would be useful.  If the enzymes are having an effect on the cancer cells, then I would expect the florescent label or radio-label to be found at the tumor site.

Using the NIH to Find a Cure for Cancer

A few decades ago, Richard Nixon, declared a war against cancer and ramped up funding for NIH research which mostly went towards proving the idea that cancer was caused by a virus.  This line of research expended massive amounts of money and ended a dismal failure.  A new and more promising direction for cancer research would be to investigate the mysteries of the trophoblast which shares so many features in common with cancer cells.  We now have the molecular tools that John Beard a century ago could only imagine.  How do we get the NIH to pursue this?  Use political pressure by contacting your congressman and asking them to push the NIH to fund the research.

 Conclusion: Advances in molecular biology now make it fairly straightforward to validate and expand on the early work of Scottish embryologist John Beard, Ernst Krebs and Otto Warburg.  The research costs for such a program would be minimal and the potential gains enormous.

For references and links, see my web site: www.bioidenticalhormones101.com

References for Chapter 53.  The Trophoblastic Theory of Cancer

(1) http://www.dr-gonzalez.com/index.htm Nicholas J. Gonzalez, M.D. Web Site

(2) http://www.michaelspecter.com/ny/2001/2001_02_05_gonzalez.html
Annals of medicine the outlaw doctor Cancer researchers used to call him a fraud.  What's changed? february 5, 2001. Michael Specter. The New Yorker

(3) http://www.dr-gonzalez.com/totalhealth_7b_00.htm
Dr Nicholas Gonzalez video presentation on John Beard's theories. A recording of Dr. Gonzalez's speech at Boulderfest 2008, sponsored by Crayhon Research, is available (for purchase) at the following link:  http://www.newspringpress.com/lectures.html

(4) http://www.alternative-therapies.com/at/web_pdfs/isaacs.pdf
EVALUATING ANECDOTES AND CASE REPORTS Linda L. Isaacs, MD. Alternative Therapies.

(5) http://www.prevention.com/cda/article/alternative-medicine-saved-our-lives/4b8b9f9ad6914110VgnVCM10000013281eac____/health/healthy.living.centers/cancer/
Alternative Medicine Saved Our Lives How unconventional treatments paid off for 4 desperately ill womenTalk to these four women and their health care providers on our discussion forums September 4 through 30. Prevention Magazine.

(6) http://www.alternative-therapies.com/at/web_pdfs/gonzalez1.pdf
THE GONZALEZ THERAPY AND CANCER:A COLLECTION OF CASE REPORTS. Nicholas J. Gonzalez, MD; Linda L. Isaacs, MD. Alternative Therapies.

(7) http://www.dr-gonzalez.com/best_cases.htm  On July 7, 1993, at the NCI I presented 25 histories of my "best cases": patients with diagnosed, biopsy-proven cancer who enjoyed either documented regression of disease or long-term survival on their nutritional protocol. Here are three of those 25 cases.  Nicholas Gonzalez MD.

(8) http://www.alternative-doctor.com/cancer/kelley.htm
 Dr. Kelley’s Do-it-Yourself Book one answer to cancer Reviewed after 32 years 1967 — 1999 By Dr. William Donald Kelley, D.D.S., M.S. 1999 THIS IS THE ENTIRE BOOK ON ONE WEB PAGE!

(9) http://www.alternative-doctor.com/cancer/beard.htm John Beard's Trophoblast Cell Theory

(10)  Beard, J: "The Action of Trypsin..." Br Med J 4, 140-41, 1906.

(11). Beard, J: "The Enzyme Treatment of Cancer" London: Chatto and Windus, 1911.

(12). Cutfield, A: "Trypsin Treatment in Malignant Disease" Br Med J 5, 525, 1907.

(13) Wiggin, FH: "Case of Multiple Fibrosarcoma Of The Tongue, With Remarks on the Use of Trypsin and Amylopsin in the Treatment of Malignant Disease" JAMA 47, 2003-08. 1906.

(14). Gotze, H, Rotham SS: Enterohepatic Circulation of Digestive Enzymes As A Conservative Mechanism" Nature 257 (5527).

(15). Shively, FL: "Multiple Proteolytic Enzyme Therapy Of Cancer." Dayton, Johnson-Watson, 1969.

(16) Little, WL: "A Case Of Malignant Tumor, With Treatment." JAMA 50, 1724, 1908.

(17)  Kelley, WD: "One Answer To Cancer" latest update - 33,000 cancer cases over three decades. New Century Promotions 3711 Alta Loma Drive Bonita, CA 91902 800-768-8484 or 619-479-3829.

(18) http://www.medscape.com/medline/abstract/11561867?prt=true
Mixture of trypsin, chymotrypsin and papain reduces formation of metastases and extends survival time of C57Bl6 mice with syngeneic melanoma B16. Cancer Chemother Pharmacol.  2001; 47 Suppl:S16-22 (ISSN: 0344-5704) Wald M ; Olejár T ; Sebková V ; Zadinová M ; Boubelík M ; Poucková P

(19) http://www.mucos.cz/eng/onko/con_onco_com.htm references for proteolytic enzymes

(20) Wald M, Olejár T, Poucková P, Zadinová M. Proteinases Reduce Metastatic Dissemination and Increase Survival Time in C57BI6 Mice with the Lewis Lung Carcinoma. Life Sciences 1998a; 63(17):237-243.

(21) Wald M, Olejár T, Poucková P, Zadinová M. The influence of proteinases on in vivo blastic transformation in rat species SD/Ipcv with spontaneous lymphoblastic leukemia. British Journal of Haematology 1998b;102 (1): 294.

(22) Wald M, Olejár T, Sebkova V, Zadinová M, Boubelík M, Pouckova P. Mixture of trypsin, chymotrypsin and papain reduces formation of metastases and extends survival time of C57BI6 mice with syngeneic melanoma B16. Cancer Chemother Pharmacol 2001;47(Suppl):S16-S22.

(23) Wald M, Poucková P, Hloušková D, Altnerová M, Olejár T. The influence of trypsin, chymotrypsin and papain on the growth of human pancreatic adenocarcinoma transplanted to nu/nu mice. The European Journal of Cancer 1999;35(4),No. 543:148.

(24) http://users.navi.net/~rsc/beard066.htm
MEDICAL RECORD Page 1020, [June 23, 1906] Correspondence TRYPSIN AND AMYLOPSIN IN CANCER.

(25) http://whale.to/cancer/kelley.html Dr. William Donald Kelley, D.D.S., M.S.

(26) http://www.cancerdecisions.com/070202.html Part Two of the Beard Paper Centenary

(27) http://www.outsmartyourcancer.com/pdf/ScientificArticleForSite.PDF.pdf
The Scientific Basis Behind Alternative Cancer Treatments by Tanya Harter Pierce, MA, MFCC This is the second article in a 3-part series on alternative cancer treatments.

(28) http://www.cancure.org/science_paper1.htm
Trophoblasts: On the Cause of Birth And Its Relationship to Cancer Regression

(29) http://www.holisticjunction.com/articles/2404.html
The Cure for Cancer: Theory, History and Treatment by Owen R. Fonorow

(30) (http://www.townsendletter.com/June2003/kelleycritique0603.htm
A Critique of the Kelley Nutritional-Metabolic Cancer Program by Melina A. Roberts BSc. (Hons.) University of Waterloo, 3rd year at the Canadian College of Naturopathic Medicine. From the Townsend Letter for Doctors & Patients June 2003

(31) http://hungerforhealth.wordpress.com/2008/05/29/enzyme-therapy-for-cancer-prevention-and-treatment/   see also http://members.aol.com/pbchowka/gonzalez2002.html
One Man, Alone Dr. Nicholas Gonzalez has compelling results and a landmark grant from the National Cancer Institute. Now he just needs to convince doctors to trust him with their patients. By Peter Barry Chowka with Kathi Head, N.D. Alternative Medicine Magazine. April 2002

(32) http://scholar.google.com/scholar?hl=en&lr=&q=related:jNPD1mSZmHcJ:scholar.google.com/

(33) http://www.cancure.org/trophoblastic_nature_of_cancer.htm
The Trophoblastic Nature of Cancer and Pregnancy Cycle as the Basis for the Enzyme Treatment of Cancer by Roger Cathey

(34) http://www.alkalizeforhealth.net/Lstemcells.htm
Ralph W. Moss, Ph.D. Weekly CancerDecisions.com. Newsletter #81 04/26/03 Scientists Identify Stem Cells As Hidden Cause of Cancer

(35) Al-Hajj M, et al. From the cover: prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3983-8.

(36) http://www.med.umich.edu/opm/newspage/2003/tumorsc.htm Steinberg D. Stem cell discoveries stir debate. The Scientist 2000;14:1. Accessed at
http://www.the-scientist.com/yr2000/nov/steinberg_p1_001113.html.

(37) Thomson JL, et al.  Embryonic stem cell lines derived from human blastocysts. Science 1998;282:1145-7.

(38) Goshen R, et al. Hyaluronan, CD44 and its variant exons in human trophoblast invasion and placental angiogenesis. Mol Hum Reprod. 1996;2:685-91.

(39) U.S. Patent No. 5,843,780, "Primate embryonic stem cells"; accessible at www.uspto.gov.

(40) Beard J. Embryological aspects and etiology of carcinoma. Lancet 1902;1:1758.

(41) Beard J. The Enzyme Treatment of Cancer. London: Chatto & Windus, 1911.

(42) Acevedo HF, et al. Detection of membrane-associated human chorionic gonadotropin and its subunits on human cultured cancer cells of the nervous system. Cancer Detect Prev. 1997;21(4):295-303.

(43) Acevedo HF and Hartsock RJ. Metastatic phenotype correlates with high expression of membrane-associated complete beta-human chorionic gonadotropin in vivo. Cancer. 1996 Dec 1;78(11):2388-99.

(44) Acevedo HF, et al. Human chorionic gonadotropin-beta subunit gene expression in cultured human fetal and cancer cells of different types and origins. Cancer. 1995 Oct 15;76(8):1467-75.

(45) Regelson W. Have we found the "definitive cancer biomarker"? The diagnostic and therapeutic implications of human chorionic gonadotropin-beta expression as a key to malignancy. Cancer. 1995;76:1299-301.

(46) http://www.oasisadvancedwellness.com/health-articles/2008/06/suppression-of-alternative-cancer.html  June 24, 2008 The Suppression of Alternative Cancer Treatments CancerDecisions Newsletter Archives For June 22, 2008 A GREAT OPPORTUNITY LOST Ralph Moss, Ph.D

(47) http://tsienlab.ucsd.edu/Publications/Tsien%201998%20Annu.%20Rev.%20Biochem%20-%20GFP.pdf THE GREEN FLUORESCENT PROTEIN by Roger Y. Tsien. 

(48) http://www.cancerimmunity.org/v7p19/071019.htm Cancer Immunity, Vol. 7, p. 19 (6 November 2007) . Cancer is a somatic cell pregnancy. Lloyd J. Old. Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, New York, NY, USA

(49) http://www.medscape.com/viewarticle/510222?rss From Nature Reviews Cancer. Cancer/Testis Antigens, Gametogenesis and Cancer Posted 08/12/2005 Andrew J. G. Simpson; Otavia L. Caballero; Achim Jungbluth; Yao-Tseng Chen; Lloyd J. Old Nat Rev Cancer.  2005;5(8):615-625.

(50) http://www.ncbi.nlm.nih.gov/pubmed/11934257 Can J Physiol Pharmacol. 2002 Feb;80(2):142-9.
Human placental trophoblast as an in vitro model for tumor progression. Lala PK, Lee BP, Xu G, Chakraborty C.

(51) http://cancerres.aacrjournals.org/cgi/content/abstract/67/19/9528
Immunology A Placenta-Specific Gene Ectopically Activated in Many Human Cancers Is Essentially Involved in Malignant Cell Processes. Michael Koslowski1, Ugur Sahin1, Rita Mitnacht-Kraus2, Gerhard Seitz3, Christoph Huber1 and Özlem Türeci2

(52) http://www.cancerci.com/content/5/1/4  see also
http://www.biomedcentral.com/content/pdf/1475-2867-5-4.pdf
Cancer/testis antigens and gametogenesis: a review and "brain-storming" session Martins Kalejs* and Jekaterina Erenpreisa Cancer Cell International 2005, 5:4

(53) http://humupd.oxfordjournals.org/cgi/reprint/dml048v1
Molecular circuits shared by placental and cancer cells, and their implications in the proliferative, invasive and migratory capacities of trophoblasts. C.Ferretti et al. Human Reproduction Update Advance Access published October 26, 2006

(54) http://www.stopcancer.com/enzymes_wobenzym.htm
Wobenzym enzymes 1-(888) 484-8264  http:// www.wobenzym.com

(55) http://www.oasisadvancedwellness.com/health-articles/2008/06/suppression-of-alternative-cancer.html  Tuesday, June 24, 2008 The Suppression of Alternative Cancer Treatments

(56) http://www.ncbi.nlm.nih.gov/pubmed/9458933
Review: analogies between trophoblastic and malignant cells. Mullen CA.Am J Reprod Immunol. 1998 Jan;39(1):41-9.

(57) http://www.cancergnosis.com/History/Trophablastic%20theory.pdf
THE UNITARIAN OR TROPHOBLASTIC THESIS OF CANCER by Ernst T. Krebs, Jr., Ernst T. Krebs, Sr., and Howard H. Beard (Reprinted From the Medical Record, 163:149-174, July 1950)

(58) http://users.navi.net/~rsc/thesis.htm On the Cause of Birth and Its Relation to Cancer Regression. Roger S. Cathey Updated July 12, 2003

(59) http://lib.bioinfo.pl/pmid:15141079/pmid/cit Mol Biol Cell. 2005 Apr ;16 (4):1901-12
Hypoxia-inducible factor regulates alphavbeta3 integrin cell surface expression.  
Karen D Cowden Dahl, Sarah E Robertson, Valerie M Weaver, M Celeste Simon

(60) http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1073670
Mol Biol Cell. 2005 April; 16(4): 1901–1912.  Hypoxia-inducible Factor Regulates αvβ3 Integrin Cell Surface Expression. Karen D. Cowden Dahl,* Sarah E. Robertson,† Valerie M. Weaver,‡§ and M. Celeste Simon*

(61) http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=407853
Reprod Biol Endocrinol. 2004; 2: 15.  Trophoblast 'pseudo-tumorigenesis': Significance and contributory factors . Rama Soundararajan1 and A Jagannadha Rao1,2

(62)  http://www.redorbit.com/news/science/94009/trophoblast_differentiation_during_embryo_implantation_and_formation_of_the_maternalfetal/  see also http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=15372095

J Clin Invest. 2004 September 15; 114(6): 744–754.  American Society for Clinical Investigation. Trophoblast differentiation during embryo implantation and formation of the maternal-fetal interface Kristy Red-Horse et al.

(63) http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17288592
Reprod Biol Endocrinol. 2007; 5: 6. Control of human trophoblast function, Laura Lunghi,1 Maria E Ferretti,1 Silvia Medici,1 Carla Biondi,1 and Fortunato Vesce2

(64) http://www.ncbi.nlm.nih.gov/pubmed/16234296
Hum Reprod Update. 2006 Mar-Apr;12(2):137-44 The regulation of trophoblast differentiation by oxygen in the first trimester of pregnancy.James JL, Stone PR, Chamley LW.

(65) http://www.sciencemag.org/cgi/content/abstract/221/4611/665
Science 12 August 1983:Vol. 221. no. 4611, pp. 665 – 667. Chromosomal mosaicism confined to the placenta in human conceptions . DK Kalousek and FJ Dill

(66) http://www.ncbi.nlm.nih.gov/pubmed/16333823
Am J Med Genet A. 2006 Jan 1;140(1):24-30. Investigation of confined placental mosaicism (CPM) at multiple sites in post-delivery placentas derived through intracytoplasmic sperm injection (ICSI).Minor A, Harmer K, Peters N, Yuen BH, Ma S.

(67) http://www.ncbi.nlm.nih.gov/pubmed/16274964
Mech Dev. 2005 Dec;122(12):1266-81. Fate of tetraploid cells in 4n<-->2n chimeric mouse blastocysts.Mackay GE, West JD.   

(68) http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1735725&blobtype=pdf
Detection of cell free placental DNA in maternal plasma: direct evidence from three cases of confined placental mosaicism. H Masuzaki, K Miura, K-i Yoshiura, S Yoshimura, N Niikawa, T Ishimaru J Med Genet 2004;41:289–292. doi: 10.1136/jmg.2003.015784

(69) http://www.ncbi.nlm.nih.gov/pubmed/11973523 J Gynecol Obstet Biol Reprod (Paris). 2002 Feb;31(1 Suppl):2S70-4.[Confined placental mosaicism: definition, consequences and outcome][Article in French] Viot G.

(70) http://www.ncbi.nlm.nih.gov/pubmed/8338621 Fetal Diagn Ther. 1993 Mar-Apr;8(2):102-8.
Viable pregnancies after diagnosis of trisomy 16 by CVS: lethal aneuploidy compartmentalized to the trophoblast. Johnson MP, Childs MD, Robichaux AG 3rd, Isada NB, Pryde PG, Koppitch FC 3rd, Evans MI.

(71) http://www.whale.to/a/warburg.html
The Prime Cause and Prevention of Cancer with two prefaces on prevention

(72) http://healingtools.tripod.com/primecause2.html
Revised lecture at the meeting of the Nobel-Laureates on June 30, 1966 at Lindau, Lake Constance, Germany by Otto Warburg. Director, Max Planck-Institute for Cell Physiology, Berlin-Dahlem

(73) http://www.nature.com/bjc/journal/v87/n7/abs/6600547a.html
Experimental Therapeutics British Journal of Cancer (2002) 87, 805-812. Evaluation of 2-deoxy-D-glucose as a chemotherapeutic agent: mechanism of cell death R L Aft, F W Zhang and D Gius

(74) http://lib.bioinfo.pl/pmid:17879147
J Bioenerg Biomembr. 2007 Sep 19; : 17879147  Warburg, me and Hexokinase 2: Multiple discoveries of key molecular events underlying one of cancers' most common phenotypes, the "Warburg Effect", i.e., elevated glycolysis in the presence of oxygen. [My paper] Peter Pedersen

(75) http://www.ncbi.nlm.nih.gov/pubmed/11578813
Ko YH, Pedersen PL, Geschwind JF (2001). "Glucose catabolism in the rabbit VX2 tumor model for liver cancer: characterization and targeting hexokinase". Cancer Lett. 173 (1): 83–91. PMID 11578813. 

(76) http://www.ncbi.nlm.nih.gov/pubmed/17879147
Pedersen PL (2007). "Warburg, me and Hexokinase 2: Multiple discoveries of key molecular events underlying one of cancers' most common phenotypes, the "Warburg Effect", i.e., elevated glycolysis in the presence of oxygen". doi:10.1007/s10863-007-9094-x. PMID 17879147. 

(77) http://www.ncbi.nlm.nih.gov/pubmed/15465013 Ko YH, Smith BL, Wang Y, et al (2004). "Advanced cancers:  eradication in all cases using 3-bromopyruvate therapy to deplete ATP". Biochem. Biophys. Res. Commun. 324 (1): 269–75.

(78) http://www.ncbi.nlm.nih.gov/pubmed/17404823
J Bioenerg Biomembr. 2007 Feb;39(1):1-12. The cancer cell's "power plants" as promising therapeutic targets: an overview. Pedersen PL.

(79) http://cancerres.aacrjournals.org/cgi/content/full/62/14/3909
Geschwind JF, Ko YH, Torbenson MS, Magee C, Pedersen PL (2002).  "Novel therapy for liver cancer: direct intraarterial injection of a potent inhibitor of ATP production".  Cancer Res. 62 (14): 3909–13.

(80) http://www.kosen21.org/upload_repository2/community/01230411451209597a.pdf
full text REVIEW Glycolysis inhibition for anticancer treatment. H Pelicano1, DS Martin2,{, R-H Xu3 and P Huang1 Oncogene (2006) 25, 4633–4646

(81) http://www.hopkinskimmelcancercenter.org/news/details.cfm?documentid=673
 OCTOBER 14, 2004. Audio file of Peter Pedersen, Ph.D., discussing the success in treating advanced liver cancers in rats. "ENERGY BLOCKER" KILLS BIG TUMORS IN RATS

(82) http://www.kjronline.org/abstract/view_articletext.asp?year=2007&page=216
FDG-PET for Evaluating the Antitumor Effect of Intraarterial 3-Bromopyruvate Administration in a Rabbit VX2 Liver Tumor Model .  Hee Sun Park, MD et al.  Korean Journal of Radiology; 2007 June; 8(3):216-224

(83) http://acs.confex.com/acs/norm07/techprogram/P44814.HTM June 20, 2007. Glycolytic enzyme inhibitors as novel anti-cancer drugs. James C.K. La et al.

(84) http://www.iptq.com/  Insulin Potentiation Therapy (IPT)

(85) http://www.contemporarymedicine.net/pub06_insulin_chemotherapy.htm
Insulin, Chemotherapy and the Mechanisms of Malignancy: The Design and the Demise of Cancer
S.G. Ayre, D.P. Garcia y Bellon, D.P. Garcia Jr  Medical Hypotheses (2000) 55(4), 330-334

(86) Ayre SG, Perez Garcia y Bellon D, Perez Garcia D Jr. Insulin potentiation therapy: a new concept in the management of chronic degenerative disease. Med Hypotheses 1986;20(2):199-210

(87) Ayre SG, Garcia y Bellon DP, Garcia DP Jr. Insulin, chemotherapy, and the mechanisms of malignancy: the design and the demise of cancer. Med Hypotheses 2000;55(4):330-4

(88) http://www.ncbi.nlm.nih.gov/pubmed/14655024 Lasalvia-Prisco E, Cucchi S, Vazquez J et al. Insulin-induced enhancement of antitumoral response to methotrexate in breast cancer patients. Cancer Chemother Pharmacol 2004;53(3):220-4

(89) http://www.ncbi.nlm.nih.gov/pubmed/14458502
Koroljow, S. Two cases of malignant tumors with metastases apparently treated successfully with hypoglycemic coma. Psychiatric Quarterly 1962; 36(1):261-270.

(90) http://www.ncbi.nlm.nih.gov/pubmed/14479168 Neufeld, O. Insulin therapy in terminal cancer: a preliminary report. J Amer Geriatric Soc 1962; 10(3):274-6.

(91) Warburg O. The metabolism of carcinoma cells. J Cancer Res 1925; 9:148-163.

(92) http://www.ncbi.nlm.nih.gov/pubmed/10368805 Nutr Cancer. 1999;33(2):117-24.Evaluation of pancreatic proteolytic enzyme treatment of adenocarcinoma of the pancreas, with nutrition and detoxification support..  Gonzalez NJ, Isaacs LL.

(93) http://www.ncbi.nlm.nih.gov/pubmed/8635074  Cancer. 1995 Nov 1;76(9):1671-7. The National Cancer Data Base report on pancreatic cancer. Niederhuber JE, Brennan MF, Menck HR.

(94) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1071044/  West J Med. 2000 September; 173(3): 153–154.  US cancer institute funds trial of complementary therapy Deborah Josefson

(95) http://www.nature.com/bjc/journal/v87/n7/abs/6600547a.html  Chromosomal Chaos and Cancer By Peter Duesberg, Scientific American 296, May 52-59.

(96) http://seer.cancer.gov/statfacts/   National Cancer Institute, Cancer Stat Fact Sheets are a collection of statistical summaries for a number of common cancer types.

Author: Jeffrey Dach MD