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Step Eight: Inhibiting Angiogenesis
Angiogenesis, the growth of new vessels from preexisting blood
vessels, is critical during fetal development but occurs minimally in
healthy adults. Exceptions occur during wound healing, in inflammation,
following a myocardial infarction, in female reproductive organs, and
in pathologic conditions such as cancer (Shammas et al. 1993; Suh
2000).
Angiogenesis is a strictly controlled process in the healthy, adult
human body, a process regulated by endogenous angiogenic promoters and
inhibitors. Dr. Judah Folkman, the father of the angiogenesis theory of
cancer, explains: "Blood vessel growth is controlled by a balancing of
opposing factors. A tilt in favor of stimulators over inhibitors might
be what trips the lever and begins the process of tumor angiogenesis."
According to the National Cancer Institute, solid tumors cannot grow
beyond the size of a pinhead, that is, 1-2 cubic mm, without inducing
the formation of new blood vessels to supply the nutritional needs of
the tumor. Since rapid vascularization and tumor growth appear to occur
concurrently, interrupting the vascular growth cycle is paramount to
overcoming the malignancy.
Tumor angiogenesis results from a cascade of molecular and cellular
events, usually initiated by the release of angiogenic growth factors.
At a critical phase in the growth of a tumor, the tumor sends out
signals to nearby endothelial cells to activate new blood vessel
growth. The pro - angiogenic growth factors diffuse in the direction of
preexisting blood vessels, encouraging development (Folkman 1992 b;
Folkman et al. 1992 a).
Various agents are known to activate endothelial cell growth,
including angiogenin, estrogen, interleukin-8, fibroblast growth
factors (both acidic and basic), prostaglandin E2, tumor necrosis
factor, granulocyte colony-stimulating factor, and VEGF. VEGF and basic
fibroblast growth factors are expressed by many tumors and appear
particularly important to tumor development and angiogenesis (NIH/NCI
1998)
A number of substances from orthodox and natural pharmacology
(angiostatin, endostatin, interferons, interleukin-2, curcumin, green
tea, lactoferrin, N-acetyl-cysteine (NAC), resveratrol, grape seed-skin
extract, retinoic acid (vitamin A), and vitamin D) are anti -
angiogenic in nature ( to read more about natural products with an anti - angiogenesis profile, please turn to the Cancer Adjuvant Therapy protocol).
Endostatin, a fragment of collagen XVIII, and angiostatin, a fragment
of plasminogen involved in the coagulation process, have produced
remarkable results in animal models.
Anti-angiogenesis drugs approved by the FDA to consider include Avastatin® and thalidomide.
How to implement step Eight
- There are clinical trials using other anti-angiogenesis agents. Call (800) 422-6237 or log on to www.cancer.gov/clinicaltrials to find out if you are eligible to participate.
- In the Cancer Adjuvant Therapy protocol of
this book, there are nutrients that have demonstrated potential
antiangiogenesis effects such as green tea extract and curcumin. Refer
to the Cancer Adjuvant Therapy protocol for information and dosing recommendations.
SUMMARY
This protocol has described therapies that a leading-edge oncologist
can prescribe to improve the odds of long-term survival and possible
cure.
The fundamental message is to have your oncologist thoroughly assess
the individual characteristics of your tumor, your blood system, and
available treatments. Based on this evaluation, patients can interact
with their oncologists to determine what therapies may work
synergistically with standard conventional treatments.
The objective of this multimodality approach is to attack tumor
cells where they are most vulnerable. The primary determining factor in
choosing the specific drugs is finding the various tumor cell and blood
tests recommended in this protocol, along with historical statistical
data that can help ascertain how your tumor will respond to specific
therapies.
The following summary is a succinct reiteration of the eight approaches discussed in this protocol:
Step One: Evaluating the Molecular Biology of the Tumor Cell Population
How to implement: Make certain your surgeon sends a specimen of your tumor to IMPATH (Telephone: (800) 447-5816, website: www.impath.com )
for immunohistochemistry testing, using the contact information just
provided. You may have to pay out-of-pocket for this test.
Step Two: Analyzing the Patient's Living Tumor Cells to
Determine Sensitivity or Resistance to Chemotherapy
How to implement: Get in touch with Rational Therapeutics (Telephone: (562) 989-6455, website: www.rationaltherapeutics.com)
using the contact information provided so that your surgeon can follow
the precise instructions required to send a living specimen of your
tumor for chemosensitivity testing. It is important that your surgeon
carefully coordinate with Rational Therapeutics in order to ensure your
cells arrive in a viable condition. You may have to pay for this test
yourself because insurance may not reimburse you for it.
Step Three: Protecting Against Anemia
How to implement: If
your hemoglobin or hematocrit levels are not in the optimal ranges, ask
your physician to prescribe an individualized dose of Procrit.
In order for Procrit to effectively boost red blood cell production,
it is essential that your body have adequate iron stores. Even if you
have adequate iron stores prior to Procrit therapy, the rapid
production of red blood cells induced by Procrit may deplete iron
stores. Anyone using Procrit should have periodic assessment of their
iron stores by means of a serum ferritin level. If less than 200, a
soluble transferrin receptor (sTfR) level should be obtained. If
evidence of iron deficiency is found, your physician will consider iron
supplementation after ruling out excessive blood loss due to a variety
of causes.
Dietary supplements that can help protect against anemia due to
other causes include folic acid (800 mcg/day), vitamin B12 (500
mcg/day), and melatonin (3-10 mg/day, at night) (Vaziri et al. 1996;
Herrera et al 2001).
Step Four: Inhibiting the COX-2 Enzyme
How to implement: Ask your physician to prescribe one of the following COX-2 inhibiting drugs:
- Lodine XL, 1000 mg once daily, or
- Celebrex, 100-200 mg every 12 hours, or
Step Five: Suppressing Ras Oncogene Expression
How to implement: Ask your physician to prescribe one of the following statin drugs to inhibit the activity of Ras oncogenes:
- Lovastatin, 40 mg twice daily, or
- Zocor, 40 mg twice daily, or
- Pravachol, 40 mg once daily
Note: These
statin drugs can produce toxic effects in a minority of patients.
Physician oversight and monthly blood tests to evaluate liver function
are suggested.
In addition to statin drug therapy, consider supplementing with the
following nutrients to further suppress the expression of Ras
oncogenes:
- Fish Oil Capsules: 8-12 capsules of Mega EPA/DHA w/Sesame Lignans per day.
- Green Tea Extract: two-three 725 mg capsules daily.
- Garlic Extract: 3 tablets daily with meals.
Step Six: Correcting Coagulation Abnormalities
How to implement: Ascertain
if you are in a hypercoagulable (prethrombotic) state by having your
blood tested for prothrombin (PT), partial thromboplastin time (PTT),
and D-dimers. A prethrombotic state is indicated by a shortening of PT
and/or PTT and an increase in D-dimers.
If there is any evidence of a prethrombotic state, ask your
physician to prescribe the appropriate individualized dose of LMWH. If
you cannot afford LMWH, ask that lower-cost Coumadin be prescribed
instead. Anticoagulation requires significant patient education and
monitoring of laboratory tests to minimize the risks of hemorrhage due
to overanticoagulation. As in all biological systems, a balance must be
established if health is to be restored.
Step Seven: Maintaining Bone Integrity
How to implement: If
you have a type of cancer with a proclivity to metastasize to the bone
(breast or prostate), ask your physician for a bisphosphonate drug
before evidence of bony metastasis occurs. An oral bisphosphonate drug
to consider is Actonel at a dose of 30 mg twice a week or Fosamax at a
dose of 70 mg once a week. Either drug must be taken at least 1 hour
before breakfast and with water only. Some people experience
gastroesophageal side effects from oral bisphosphonate drug therapy and
prefer administration directly into the vein. An IV-administered
bisphosphonate drug such as Aredia may be administered monthly
beginning at 30 mg the first month, 60 mg the second month, and working
up to 90 mg for subsequent months.
A newer, more potent IV bisphosphonate, Zometa, can be used at a
starting dose of 1-2 mg for the first dose and then 4 mg every 3-4
weeks thereafter. Zometa is routinely given as a 15-minute infusion.
When taking a bisphosphonate drug, it is important to take a wide array
of bone-protecting supplements such as calcium, magnesium, zinc,
manganese, and vitamin D3. Six capsules a day of a product called Bone
Restore provide optimal potencies of bone protecting nutrients. Some
physicians also prescribe a synthetic vitamin D such as Calcitriol
(Rocaltrol) or Hectorol.
Since excessive bone breakdown releases growth factors into the
bloodstream that can fuel cancer cell growth, the DPD urine test (which
can be ordered through the Vitamin Depot Online.com Foundation (800)-208-3444)
should be done every 60-90 days to detect bone loss. A QCT bone density
scan should be done annually. If either of these tests reveals bone
loss, ask your physician to initiate bisphosphonate drug therapy. Every
cancer patient should take a bone-protecting supplement like Bone
Restoree to protect against excess bone deterioration.
Step Eight: Inhibiting Angiogenesis
How to implement: There are a number of clinical trials using anti - angiogenesis agents such as angiostatin. Call (800) 422-6237 or log on to www.cancer.gov/clinicaltrials to find out if you are eligible to participate. In the Cancer Adjuvant Therapy protocol of
this book, there are nutrients that have demonstrated potential
antiangiogenesis effects such as green tea extract and curcumin. Refer
to the Cancer Adjuvant Therapy protocol for
information and dosing recommendations. The drug Avastatin® is now
approved, and may be considered as an anti-angiogenesis therapy against
a variety of cancers.
Implementing the Eight Steps
As
can be seen from the eight-step list, a patient might be prescribed
several treatments in addition to standard therapy for the purposes of
inhibiting the COX-2 enzyme, suppressing the r R as oncogene,
protecting against anemia/hypercoagulation, inhibiting blood vessel
growth in the tumor (angiogenesis), maintaining bone integrity, and so
forth.
While these therapies are substantiated in the published scientific
literature and most are part of mainstream medicine, few cancer
patients are benefiting from this knowledge.
If you are determined to wage modern medicine against your tumor,
some or all of these therapies should be considered, depending on your
individual situation. The reader is advised to refer to the Cancer Adjuvant Therapy protocol for additional guidance. If standard therapies such as radiation or chemotherapy are being contemplated , please refer to the Cancer Surgery, Cancer Radiation and/or Cancer Chemotherapy protocols.
Product availability
Super EPA/DHA w/Sesame Lignans, Mega Green Tea Extract, Kyolic® Reserve Garlic Extract and melatonin, folic acid, vitamin B12, and Bone Restore are available by telephoning (800) 544-4440 or by ordering online.
Staying Informed
The information published in this protocol is only as current as the
day the manuscript was sent to the printer. This protocol raises many
issues that are subject to change as new data emerge. Furthermore,
cancer is still a disease with unacceptably high mortality rates, and
none of our suggested regimens can guarantee a cure.
The Vitamin Depot Online.com Foundation is constantly uncovering information
to provide to cancer patients. A special website has been established
for the purpose of updating patients on new findings that directly
pertain to the published cancer protocols. Whenever Vitamin Depot Online.com
discovers information that may benefit cancer patients it will be
posted on the website www.lefcancer.org.
Before utilizing the cancer protocols in this book, we suggest that you check www.lefcancer.org
to see if any substantive changes have been made to the recommendations
described in this protocol. Based on the sheer number of newly
published findings, there could be significant alterations to the
information you have just read.
Alternatively, call 1-800-226-2370 and ask a Health Advisor if your topic of interest has been updated on the website - www.lefcancer.org. | 
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