New Perspectives on Cancer Parrish Marcenaro 1961-2011

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Ocular Melanoma – Dx and standard Tx

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The Business of Cancer – A failed paradigm (for patients)

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The Science of Cancer – Cancer cell physiology

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Surviving Cancer – The alternative to death

Ocular Melanoma

http://www.ocularmelanoma.org/  It is the most common type of primary intraocular cancer in adults.

 2000-2500 cases in US per year (vs. 70K dermal).

 Incidence increases sharply after age 50.

 50% will metastasize within 10-15 years.

 80 - 90% of metastases will first appear in the liver.



“Metastatic disease is universally fatal.”

(OM Fdn. website)

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Risk Factors

Lightly pigmented individuals  Blue eyes  No study has ever proven a link to UV exposure

Diagnosis

 DFE  Retinal photos – p200  Ultrasound  FA  Biopsy, mostly for gene typing  MRI & PET Scan – both more useful for metastatic disease.

Differential Dx

 Choroidal Nevus (1/8845 convert per Singh 2005)  Choroidal Detachment  Intraocular Foreign Body  Glaucoma, Hyphema  Neovascular Glaucoma  Cavernous Hemangioma  Vitreous Hemorrhage  Hyphema  Ciliary Body Melanoma  Conjunctival Melanoma  Iris Melanoma

Amelanotic Melanoma

Prognostic Indicators of Metastatic Potential

 Large tumor size  Gene type  General tumor location (anterior locations being more correlated with metastasis)  Ciliary body involvement  Presence of orange pigment (lipofuscin) overlying the tumor  Higher

age

at diagnosis

Lipofuscin – dead cell debris

Melanoma Histology

Spindle Cell Epithelioid Cell Higher risk of metastasis

Histone deacetylase inhibitors induce growth arrest and differentiation in uveal melanoma.

Clinical Cancer Research 10/2011; DOI: 10.1158/1078 0432.CCR-11-0946  The purpose of this study was to identify therapeutic agents that reverse the phenotypic effects of BAP1 (a tumor supressor gene) loss in uveal melanoma (UM).

 CONCLUSIONS: These findings suggest that HDAC inhibitors may have therapeutic potential for inducing differentiation and prolonged dormancy of micrometastatic disease in uveal melanoma (UM).

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(HDACs have anti-estrogenic properties!)

Genetics

Mutation status is the key for targeted gene therapy.

 Monosomy 3 – complete loss of chromosome 3. A very powerful prognostic indicator for metastatic potential.

 GNAQ – about half of uveal melanomas.



BRAF

(skin & iris), CKIT (colon) – less common in ocular melanoma.

 Wild Type- yours truly

Treatment – Size Matters

Tumors of less than 2-2.5 mm in elevation and 10 mm in diameter can be observed until growth is documented. (MEDSCAPE Choroidal Melanoma Author: Enrique Garcia-Valenzuela, MD, PhD; Chief Editor: Hampton Roy Sr, MD)  Radioactive plaques or brachytherapy – once the most common initial therapy.

 Less common treatments include transpupillary thermotherapy, external beam therapy, surgical tumor resection and gamma knife.

 Ennucleation? – Not proven to enhance survivability.

COMS The Collaborative Ocular Melanoma Study

http://www.jhu.edu/wctb/coms/  Based on the COMS study, there is no statistical difference in risk of metastasis between enucleation and plaque radiotherapy, or of undergoing brachytherapy or not before undergoing enucleation for large or medium tumors.

 National Eye Institute (NEI) Press Release – “Radiation Treatment for Eye Cancer Does Not Change Patients' Five-Year Survival.” 

Plain English – treatment doesn’t work.

Governmental Response

 "The COMS findings are a striking example of the role that clinical trials play in improving patient care," said Richard Klausner, M.D., director of the NCI.

 D. C. Dean OD says, “These findings are striking example of the failure of billions of dollars and decades of research to accomplish anything that might remotely resemble progress.”  This is also a striking example of how politically (and financially) motivated entities will spin the most dismal failures to sound like success.

Treatment of Metastases

Standard Chemotherapy – Systemic (IV) application of chemotherapeutic agents. This will be done virtually 100% of the time.

 Liver Isolation techniques – the liver is isolated and treated with high dose chemotherapy or immunotherapy agents to reduce systemic toxicity.

 Surgical Resection – best to be ready to perform other ablation techniques on small tumors found during surgery. Radio frequency ablation (RFA) is commonly used.

PET/CT scan of metastases

Treatment Success?

 Treat the primary tumor? Despite seeming advances in treating the primary tumor, there has been no improvement whatsoever in survival rates.

 Treat the metastatic disease? There is no

improvement in survival rates when metastatic

disease is treated.  “Treatment” is defined as standard medical practice based upon their definition of “best evidence.”

Cancer Overview

 One person in three in developed countries will get cancer.

 Since 1971 the U.S. has invested over $200 billion on cancer research; that total includes money invested by public and private sectors and foundations.

 Despite this substantial investment, there has been a small decrease in mortality rates since the peak in the early 1990s. (

May be attributable to adding in benign skin tumors & DCIS!)

The Good Stuff

 Gleevec (Imatinib) – FDA approved 2001. Targets receptor sites for very specific mutations on cancer cells. Most useful for some leukemias.

 BRAF inhibitors – vemurafenib, dabrafenib /trametinib combo  Focused Radiation Technologies

– “If I can see it, I can guarantee you 100% that I will kill it dead.”

Dr. Thomas Schroeder, UNM Radiation Oncology Dept.

Cancer is Big Business

 Cancer care accounted for an estimated $104.1 billion in medical care expenditures in the United States in 2006 (NCI) and the numbers are rising.

 Multi-billion dollar ethics are different.

 Big oil, automakers, big pharma, food/seed producers, retail giants have one criterion for success: PROFIT  Their goals are never an altruistic desire to help humanity.

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They are not required by law to sell cheaper, more effective products, even if they hold the patent.

Regulatory Capture

 An economic theory most often associated with Nobel Laureate George Stigler.

 Regulatory capture occurs when a regulatory agency created to act in the public interest instead advances the commercial or special interests that dominate the industry or sector it is charged with regulating.  i.e., the fox is in charge of the henhouse.

 FDA, NCI, FAA, FCC, ICC, SEC, NRC, FRBNY, EPA…state optometric boards in the good old days.

Your Tax Dollars at Work

 Li-Chuan Chen, PhD, who worked as a scientist for the National Cancer Institute from 1991-1997, said that when the NCI or assigned entities conducted trials on alternative cancer therapies they always altered the

protocol and let it fail in order to discredit the therapy!

Stop wondering why effective alternative therapies don’t show up in establishment publications.

Drug Economics

 It is incredibly expensive to bring a drug to market. 700$-800$ million is not uncommon.

 Only the richest companies (Big Pharm) can sponsor “proper” clinical trials.

 These economically motivated trials are then forced upon the medical world as “evidence based medicine.”  It is far more profitable to “manage” a disease than to cure it.

Bad Medicine, Good Economics

Few chemotherapy drugs will likely ever run the FDA gauntlet that are not:  Patentable, and thus  Profitable  Most often highly toxic (48 hour “kill” tests)  Minimally effective  Necessary for long term management

MD Priorities, one pts. opinion

1. Don’t get sued.

2. Make a large amount of money.

3. Establish that the MD is significantly smarter than the patient.

4. Keep the medical license safe.

5. Hurry up and get to the next patient.

???

Cure this patient’s disease

Alternatives to Big Pharm Products?

If a compound shows any anti-cancer activity, one of two things will then take place.

1.

If the compound can be synthesized and altered while retaining its anti-cancer properties, “research” into it will commence.

2.

If the compound can never be synthesized, altered or novelized in any manner, then the cancer industry begins a process of demonization, disinformation and sometimes illegalization.

Cancer cell physiology

 To realistically expect to kill cancer, one must take advantage of its inherent vulnerabilities.

 Virtually all differences to normal cells are vulnerabilities.

 Most chemo drugs ignore all of these differences!

Traditional Chemo Approach Destroy actively replicating cells

Bad Ideas Promoted by MDs

=

Cancer Cells typically…

 Anaerobically ferment sugar for energy  Have a high concentration of insulin receptors  Have a low, acidic pH (6.25-7.0)  Have a low electrical potential across the cell membrane  Exist in a narrow temperature range  Can be highly vulnerable to viruses

“So in war, the way is to avoid what is strong and to strike at what is weak.”

Sun Tzu, The Art of War

Ca. 500 BCE

Anaerobic Metabolism

(The Warburg Hypothesis)  Cancer cells typically ferment sugar for energy (anaerobic glycolysis) even in the presence of O2.

 Malignant rapidly-growing tumor cells typically have glycolytic rates typically 10-17 times higher than those of their normal tissues of origin; this occurs even if oxygen is plentiful.

 PET scan – works because cancer cells soak up glucose at 10-17 times the rate of a normal cell.

 Kreb’s cycle is inactivated. 2 ATP vs. 38 ATP

Aerobic Anaerobic

Glycolosis Inhibitors

 3 BRoP – MD Anderson’s patented drug.

 Pre-clinically, 3-BrOP has already been proven effective against many cancers including neuroblastoma , glioblastoma, colon cancer, lymphoma and acute leukemia.

 "As we explore alternative options to standard chemotherapy agents, we are finding drugs, like 3 BrOP, that have the potential to destroy cancer cells while leaving healthy cells unharmed."

Mol Cancer Ther. 2011 Oct 12. [Epub ahead of print]

Dual inhibition of Tumor Energy Pathway by 2-deoxy glucose and metformin Is Effective Against a Broad Spectrum of Preclinical Cancer Models.

 This study investigated the preclinical efficacy of targeting the tumor bioenergetic pathway using a glycolysis inhibitor 2-deoxyglucose (2DG) and AMPK agonists, AICAR and metformin*…2DG and

metformin led to significant cell death

…Deprivation of tumor bioenergetics by dual inhibition of energy pathways might be an effective novel therapeutic approach for a broad spectrum of human tumors.

*adding insulin would work even better! DCD

Cancer Res. 2010 Mar 15;70(6):2465-75. Epub 2010 Mar 9.

Targeting cancer cell metabolism: the combination of metformin and 2-deoxyglucose induces p53-dependent apoptosis in prostate cancer cells.

 Targeting cancer cell metabolism is a new promising strategy to fight cancer. In this study, the addition of metformin to 2-deoxyglucose (2DG) inhibited mitochondrial respiration and glycolysis in prostate cancer cells leading to a severe depletion in ATP. The combination of the two drugs was much more harmful for cancer cells than the treatment with metformin or 2DG alone, leading to 96% inhibition of cell viability in LNCaP prostate cancer cells.

Insulin Receptors

 Cancer cells are covered with insulin receptors.

 This adaptation helps feed the enormous appetite for glucose.

 Having this many open receptors makes the cancer cell vulnerable to attack.

 Metformin helps insulin bind to receptors.

Electron micrograph of insulin activated cancer cells

IPT- Insulin Potentiation Therapy

 When blood sugar levels drop, insulin receptors increase in number and metabolic activity.

 Activated insulin receptors greatly increase cell membrane permeability.

 IPT involves giving a pt. insulin til BS levels drop down to 35-45 mg/dL, then feeding the hungry cancer a lethal dose of chemotherapeutic agent.

 Doses are typically around 1/10 that of normal chemo.

 Insulin is not approved as an anti-cancer agent. It won’t kill cancer by itself. Nobody ever said it would.

pH

 Because Kreb’s cycle is inactivated lactic acid builds up in the cell.

 The active proton pump requires energy to transport H+ across the cell membrane.

 Cancer cells don’t have enough energy to get rid of the excess hydrogen ions.



Cancer cells have adapted to thrive in this low pH environment.

pH 6.25-7.00

Cesium Chloride

 Ce-132 chloride salt  Rapidly absorbed by cancer cells through the passive potassium pump mechanism.

 Cesium then can’t get out of the cell.

 Raises pH rapidly  Halts glucose transport  Cells rapidly starve and lyse.

 This is the big dog of the alternative cancer universe for late stage saves.

Cesium Chloride con’t.



Must be taken with potassium supplementation

 Liquid CeCl can be mixed with DMSO for a transdermal application.

 Overdose on this stuff and your heart stops.

 An in-depth consultation is necessary to order safely.

 The old grump at Essense-of-Life.com

wouldn’t sell me this stuff cause my metastatic load was so low.

 Alternative cancer treatment clinics in Arizona and Nevada are starting to use IV Cesium therapy.

Membrane Potential

 Typically run in the range of -10mV to 90mV for healthy cells.

 There is generally an inverse relationship between membrane potential and proliferative potential.

 Cancer cells exist in this low voltage, highly proliferative state (10-20mV).

 Thyroid hormone (T3) raises cell voltages!

Cancell/Protocel

 Developed initially by a research chemist at the Detroit Institute of Cancer Research back in the 1950s.

 Problems began when they informed the ACS about initial results and plans for more extensive clinical trials.

 One of the few alternative treatments that actually made it to NCI trials.

Webnd.com

http://alternativecancer.us/testr.htm

Protocel Use

 In the NCI test, it reduced the mass of half of the 60 tumors tested by 80% or more in just two days.

 In practice, Protocel is about 50% effective.

 Since its mechanism is to lower the intracellular energy of cancer cells, there are a host of normally healthy supplements that should not be taken with it.

 Protocel interferes with the anaerobic glycolysis which reduces the membrane potential so low that glucose cannot enter the cell.

 Since you’re starving the cancer cells, you have to take this at least every 6 hours, preferably 4 or 5.

Hyperthermia and Cancer

 There is an interesting link between documented cases of spontaneous remission of cancer and recent severe fevers.

 The mechanism was once thought to be related to immune function. It is now thought to be related primarily to temperature.

 Cancer cells typically die at a lower temperature than healthy cells (brain cells above 107.6 F)  Hyperthermia is now becoming more mainstream therapy in the US.

Hyperthermia Treatments

 The most obvious way to utilize this therapeutic effect is to stop breaking the fevers of cancer patients.

 German cancer clinics routinely use whole body hyperthermia with solid results.

 The National Cancer Institute now has a page devoted to hyperthermia research and information: http://www.cancer.gov/cancertopics/factsheet/Therapy/hyperthermia  Quackwatch.com still has it listed in an article called, “How Quackery Harms Cancer Patients.”

DCA - Dichloroacetate

 It takes more energy to produce apoptosis/senescence than to divide.

 Cancer cells are stuck in first gear, they only have enough energy to divide.

 Raising the energy level of the cell allows the reactivation of the metabolic processes leading to apoptosis/senescence.

 DCA is used for metabolism disorders in children such as lactic acidosis (just like cancer cells).

DCA Protocol

 Many patients are having excellent results with doses starting around 10mg/Kg per day taking 2 days off a week. (1 g per day @220 lbs)  Benfotiamine (synthetic vitamin B-1) is used to mitigate peripheral neuropathy.  Creatine, alpha lipoic acid, CoQ10/ubiquinol, any androgenic substance, T3, caffeine, cortisol control agents, B vitamins… Amazon.com

DCA Clinical trials

 Evangelos D Michelakis, MD at the University of Alberta is the most notable investigator.

 In the US trials, patients are given a stupid combination of DCA and chemotherapy agents (metabolism inhibition).

 This protocol is supposed to mesh with a compound that raises intracellular metabolism.

 The trials are being funded by philanthropic groups and individuals, not major cancer organizations.

DCA on FOX news

 Search for “Glenn Beck DCA” on any video site for a rare story on alternative cancer treatment.



“Once in a while, maybe capitalism needs to be reminded of the value of human life!”

 www.youtube.com/watch?v=h Lb9UyitdHs

Annonaceous Acetogenins

 Graviola (Annona Murieta)– low concentration of AA’s and some neurotoxicity.

 Paw Paw - extract taken from the twigs of the tree during a small window of time in the spring. Higher concentration of active compound, lower toxicity.

Prairie Banana

Design, synthesis of symmetrical bivalent mimetics of annonaceous acetogenins and their cytotoxicities.

Xiao Q, Liu Y, Qiu Y, Yao Z, Zhou G, Yao ZJ, Jiang S.

 A new series of linear dimeric compounds

mimicking naturally occurring annonaceous acetogenins have been

synthesized by bivalent analogue design,

and their cytotoxicities have been evaluated against the growth of cancer cells by MTT method. Most of these compounds show selective action favored to human cancer cell lines over normal cell lines.

Paw Paw Therapy

 Paw Paw is about 40% effective as a standalone for cancer treatment.

 Works great together with Protocel.

 Has been proposed as an effective agent to halt the active transport of chemotherapeutic agents out of the cancer cells of MDR (multi-drug resistant) tumors.

Amazon.com

Nitrilosides - Amygdalin

 Often associated with Laetrile/Vitamin B17 – lots of claims made, lots of different formulations. Lots of inconsistent data. Very little science.

 Seems to work better to stop cancer from spreading through the blood. Able to kill the little cells, but not as effective against solid tumors.

 Breaks down into a benzaldehyde and a cyanide molecule that normal cells can metabolize, cancer cells cannot.

 Easiest way to get it is by eating bitter apricot kernels.

Amygdalin 2 sugars Laetrile 1 sugar

The Problems with Laetrile

 It was not developed and patented by a large pharmaceutical interest. (Ernest T. Krebs)  Many people assigned to discredit Laetrile at the Sloane-Kettering Cancer Institute went public with their findings and started a massive PR battle. (Ralph Moss, Kanematsu Sugiura)  It is commonly more effective when used in tandem with other therapies. No consensus or research.

 Laetrile clinics have been known to use Laetrile, Amygalin or something entirely different and all are called Laetrile.

Amygdalin Benzaldehyde Beta-Glucosidase BA Highly Toxic In normal cells: Oxidation Rhodanese

Mechanism of Nitrilosides

Benzoic Acid Inert Metabolites SCN Thiocyanate

Cardiac Glycosides

 Anvirzel – a patented, not yet approved IV anticancer drug that is derived from the Oleander plant.

 “International clinicians have been treating patients suffering from the above referenced disorders on a compassionate use basis since 1997. Many of these patients were previously diagnosed as terminal. These clinicians have experienced a high level of success

with disease stabilization, partial remission, and complete remission, almost always accompanied by a very marked improvement in the patients'

quality of life.”

Presentation at the 2001 ASCO Annual Meeting

• •

Phase I Study of Anvirzel TM Advanced Solid Tumors.

in Patients with

Background: Anvirzel TM , an extract of the plant Nerium oleander,

is toxic to human (BRO melanoma) cell lines

by inducing a block in the G2/M phase the of cell cycle. Anecdotal reports from Europe of partial and complete remissions and symptomatic improvement in patients (pts) with advanced malignancy prompted formal evaluation of this novel agent.

How it Works…

Acta Pol Pharm. 2006 Mar-Apr;63(2):109-15.

Cardiac glycosides in cancer research and cancer therapy.

 The well known and accepted mode of action of cardiac glycosides is inhibition of the ubiquitous plasma membrane Na+, K+-ATPase that leads to increased intracellular Ca2+ ion concentrations. It has been suggested that some forms of cardiac glycosides inhibit proliferation and induce apoptosis in prostate cancer cells in clinically relevant concentrations. There is growing interest in evaluating the

oleander products

and possibly other cardiac glycosides as antineoplastic agents.

You Can’t Have it!

 Nobody came forward to fund the 800 million dollar price tag for full FDA testing protocols.

 So what? Commercially available products have all the same benefits in an oral preparation.

 Rose Laurel OPC Plus Utopiasilver.com

Virotherapy

 Melanoma cells are especially vulnerable to viral attack. These viruses have virtually no activity against normal cells.

 Rigvir – Latvian product. Works on ocular melanoma!

 Oncovex – US - Even with melanoma, you can’t get it!

 Oncovex is used in the worst possible manner. Only after your immune system is blasted by traditional chemo. Even then it’s injected into the primary tumor, which is probably dead in the center anyway.

Vegan Diets (Gerson Therapy)

Why do I think this works for some cancer patients.

1.

2.

There is a high amount of amygdalin in natural plant based foods. Almost all wild fruits and most seeds have some amygdalin content.

The pancreatic enzymes that break down dietary animal protein are freed up to concentrate their effect on the cancer cells.

Comparing Treatment Modalities

Orthodox  Must go through MD  Expensive*  Highly toxic  Poor rate of cures  Bound by standards imposed by self-serving political and economic entities Alternative  Order it yourself  Cheap  Non-toxic  Higher cure rates  Roll your own, adapt and combine multiple strategies *

Medical insurance pays costs

Treatment Strategies

 Measure and normalize if necessary levels of estrogen and cortisol.

 Supplement Test/DHT in men, progesterone in women.

 Start with a stack of Protocel, Paw Paw and bitter apricot kernels (make a trail mix).

 Switch to Oleander extract, at as high a dose as tolerated along with Paw Paw and the apricot kernels.

 Use the Cesium Chloride protocol as a last resort, or as an aggressive therapy in late stage cancer.

Resources

Websites:  Alternativecancer.us

 Cancertutor.com

Books  Outsmart Your Cancer by Tanya Harter Pierce  The Cancer Industry by Ralph Moss Ph.D

 Cancer – Step Outside the Box by Ty bollinger

Be positive at all times. If you expect to fail, you will. Before the battle begins, make sure you expect to win—then there will be no battle, for you will have won before it starts.