Download Ocular Melanoma - Wyoming Optometric Association

New Perspectives on Cancer
Parrish Marcenaro 1961-2011
 Ocular Melanoma – Dx and standard Tx
 The Business of Cancer – A failed
paradigm (for patients)
 The Science of Cancer – Cancer cell
physiology
 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)
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: 10.1158/10780432.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).
 (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 $104.1 billion
in medical care expenditures in the United States in
2006 (NCI) and the numbers are rising.
 Multi-billion dollar ethics are different.
 Big oil, automakers, big pharma, food/seed producers,
retail giants have one criterion for success: PROFIT
 Their goals are never an altruistic desire to help
humanity.
 They are not required by law to sell cheaper, more
effective products, even if they hold the patent.
Regulatory Capture
 An economic theory most often associated with Nobel
Laureate George Stigler.
 Regulatory capture occurs when a regulatory agency
created to act in the public interest instead advances
the commercial or special interests that dominate the
industry or sector it is charged with regulating.
 i.e., the fox is in charge of the henhouse.
 FDA, NCI, FAA, FCC, ICC, SEC, NRC, FRBNY,
EPA…state optometric boards in the good old days.
Your Tax Dollars at Work
 Li-Chuan Chen, PhD, who
worked as a scientist for the
National Cancer Institute from
1991-1997, said that when the NCI
or assigned entities conducted
trials on alternative cancer
therapies they always altered the
protocol and let it fail in order
to discredit the therapy!
Stop wondering why effective alternative therapies
don’t show up in establishment publications.
Drug Economics
 It is incredibly expensive to bring a drug to
market. 700$-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 3BrOP, 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
Mechanism of
Nitrilosides
Beta-Glucosidase
BA
In normal cells:
Benzoic Acid
Oxidation
Highly Toxic
Rhodanese
Inert Metabolites
SCNThiocyanate
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 AnvirzelTM in Patients with
Advanced Solid Tumors.
• Background: AnvirzelTM, 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.
There is a high amount of amygdalin in natural plant
based foods. Almost all wild fruits and most seeds
have some amygdalin content.
2. The pancreatic enzymes that break down dietary
animal protein are freed up to concentrate their
effect on the cancer cells.
1.
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
*Medical insurance pays costs
Alternative
 Order it yourself
 Cheap
 Non-toxic
 Higher cure rates
 Roll your own, adapt
and combine multiple
strategies
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.
Sun Tzu, The Art of
War