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The Grouppe Kurosawa General Cancer/Leukemia Treatment Protocol

25th March 2007 by Arrow Durfee Posted in Uncategorized

Updated 2.15.07
This cancer/leukemia treatment protocol is out of date. It remains posted for informational purposes only. Our current cancer/leukemia treatment protocols are only posted to the subscription Natural Medicines blog. These protocols are not static…they often change on a weekly basis as new scientific information is provided to us. Due to substantial cost increases, we must charge for access to this blog. The cost is $35/3 months.

Subscribe to the Natural Medicines Blog.

Overview

This protocol uses both prescription and non-prescription drugs, and natural medicines. It is NOT our intention to promote ONLY the use of natural medicines or alternative medicines when many generic drugs might be more therapeutically effective. Our goal is to develop a synergistic treatment protocol for the treatment of breast cancer, prostate cancer, lung cancer, colon cancer, brain cancer and acute and chronic leukemias.

Some of the drugs referenced below require a prescription. Many fine, open minded physicians read this blog and the website. These blogs are written, and documented, so these physicians have a scientific rational for using these drugs in their practice. Of course, we also want to encourage individuals to read these essays if they intend to treat their own diseases. However, in order to change how medicine is practiced in America and elsewhere, we must reach out to the medical community. They are the ones who must pass the word to their colleagues about the efficacy of our treatment protocols. If you do not have an open minded physician, find one. So-called alternative physicians advertise in the telephone book in the US. If this doesn’t work, you can often get a prescription from Internet Online Pharmacies.

There are two distinct phases to our cancer/leukemia treatment protocol. In phase 1, we are attempting to directly kill the cancer cells. This is especially important if a person is burdened with a large tumor or leukemia mass. In phase 2, we will attempt to activate the immune system against the cancer. This is classic cancer immunotherapy. These phases are NOT compatible, i.e. you cannot activate the immune system and attempt to directly kill cancer cells at the same time.

Each phase is 6 weeks in length. The cycle repeats itself until the cancer or leukemia is controlled. At that point, only phase 2, the immunological phase, will be used. At least, this is what we would like to see happen.

Part One. The Cytotoxic Phase

The following drugs and natural medicines are listed in order of importance.

1. Histone deacetylase inhibitors.

As already posted, we have numerous choices. These inhibitors are the most powerful anti-cancer drugs/natural medicines at our disposal.

Valproic acid, a common epilepsy prescription drug, is a powerful inhibitor of both class 1 and 2 deacetylase enzymes.

Curcumin is also an excellent natural inhibitor of histone deacetylases. The dose is 15 grams a day, 5 grams three times a day in coconut milk or cream. It MUST be dissolved in fat. If you can’t stand coconut milk, dissolve the curcumin in warm flax oil or cream.

Sulforaphane is the anti-cancer agent from broccoli. This one looks like a winner. One of the studies I cited in another essay calculated that it would take 106 grams of broccoli sprounts or 3.7 pounds (1.7 kilos) of whole broccoli a day to inhibit histone deacetylases completely. Fortunately, supplements are available that are very concentrated.

The PapaNature company, referenced below, sells Jarrow Formuilas, BroccoMax Standardized Broccoli Seed Extract. This extract is from broccoli seeds, the most concentrated source of sulforaphane. Take at least 6 capsules a day. Actually, take as many as you can afford. These caps are not expensive and are totally non-toxic. Spread the caps out over the day.

Now for the good stuff. Isothiocyanates such as sulforaphane and PEITC will not accumulate in cells unless the molecules are conjugated with GSH, aka glutathione. When conjugated, these anti-cancer molecules will accumulate to VERY high concentrations in cells.

www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=11238182&itool=pubmed_docsum

However, the conjugation with GSH makes these molecules very sensitive to a rapid export from the cells via transport proteins.

www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=11988104&itool=pubmed_docsum

In order for sulforaphane to be effective as a histone deacetylase inhibitor, we MUST prevent it from being exported from the cell. This means we must inhibit the two major export transport proteins, p-glycoprotein (pgp-1) and the gene product of MRP-1.

Curcumin, at very low concentrations, inhibits the p-glycoprotein pump.

www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16038636&itool=pubmed_docsum

www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=15476675&itool=pubmed_docsum

Unfortunately, curcumin does not affect MRP-1. As it turns out, the MRP-1 gene is activated by the PI3K/AKT pathway. As you recall, retinol, common vitamin A, when bound to its storage protein inhibits the activation of PI3K/AKT.

www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=15548710&itool=pubmed_docsum

Therefore, curcumin and sulforaphane are tremendously synergistic. They are both histone deacetylase inhibitors, and curcumin inhibits the export of conjugated sulforaphane. Vitamin A inhibits the synthesis of the other export protein by inhibiting PI3K/AKT activity.

In addition, the conjugation processes uses up GSH in the cancer cell, thereby promoting its instability. The depletion of GSH is one of the reasons we use high concentrations of glutamine in our protocol.

Summary

Valproic acid inhibits most of the two major class 1 and 2 histone deacetylases. This makes it our inhibitor of choice. If this drug cannot be obtained, use curcumin, sulforaphane, and vitamin A.

Curcumin, sulforaphane and vitamin A are a dynamic natural medicine combination.

2. Retinoic acid, vitamin A.

The histone deacetylase inhibitors will “wake up” the previously quiet genes for vitamin A receptors. Retinoic acid is a powerful anti-cancer, anti-growth, pro-differentiation vitamin on its own. We have covered all this in previous essays.

See protocol below.

3. Glutamine

Glutamine gets converted to glutamate in the liver and in cells. Glutamate inhibits the synthesis of glutathione and the uptake of glutathione into the mitochondria. Cancer cells are very sensitive to depletions in the anti-oxidant concentrations of GSH.

www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=15609127&itool=pubmed_docsum

Dose. At least 45 grams a day, split into 3×15 gram doses. 45 grams is a minimum dose. Dissolve the glutamine in acidic fruit juice

4. Ascorbyl palmitate

The molecule was developed by the food industry as an anti-oxidant. As the following article suggests, ascorbyl palmitate is also a powerful oxidant capable of initiating cellular death pathways in cancer cells.

www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15104245&itool=pubmed_docsum

Dose. 2 to 5 grams a day dissolved in warm coconut milk. Start with 2 grams, 1 gram twice a day.

5. Vitamin A.

Many anti-cancer genes are inhibited by excessive DNA methylation. Retinoic acid, a form of vitamin A, inhibits DNA methyltransferase activity.

www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=11834837&itool=pubmed_docsum

As discussed above, the receptors for retinoic acid are activated by histone deaceylase inhibitors. In addition, DNA methyltransferases are inhibited by retinoic acid. Curcumin/sulforaphane plus the DNA methyltransferase inhibitor retinoic acid are an excellent therapeutic combination.

50,000IU a day in gel caps.

6. Nicotinamide (niacinamide)

This molecule activates the enzyme that converts palmitic acid and serine into ceramide, the death lipid.

6 grams a day, 3x 2 grams a day.

7. Palmitic acid and serine.

Both of these products can be obtain from the diet, although obtaining enough serine is difficult.

Palm oil contains a high concentration of palmitic acid with a low concentration of mono-unsaturated oils such as oleic acid.

Palmitic acid and serine can be purchased from me. See the Supplement Supplier file on the home page.

20 grams palmitic acid, 2×10 grams a day in coconut milk ONLY. PA cannot be mixed with milk or any product with calcium. Serine dose is 2-4 grams a day depending on body weight. Serine is soluble in water. Eat egg whites to enhance serine intake. 10 grams of PA is a rounded tablespoon. 2 grams of serine is a ½ teaspoon.

8. Vitamin D3

This steroid can be obtained in the vitamin capsules. 2000IU minimum a day. If you have colon cancer or GIST, 5000IU is a minimum dose along with lots of butter.

9. Melatonin

30 mgs a night before bed if you have breast cancer. Otherwise, 10 mgs a night.

10. Diet

NO omega six oils, such as soy, corn, safflower, or canola oil. No olive oil. Cook with coconut oil, it’s wonderful and very healthy. It is also totally toxic to cancer cells. You can also cook with palm oil. Use flax oil for salads. Fish oils are also great. If you have colon cancer or GIST, don’t forget the butter.

NOTE: You may NOT take NSAID drugs such as aspirin, ibuprofen, naproxen (Aleve), indomethacin, or sulindac during the cytotoxic phase. See the Natural Medicines blog essays for an explanation. You may take acetaminophen, Tylenol, for pain relief.

Part Two. The Immunotherapy Phase

This is a very simple protocol that can be followed by anyone. However, in order to be effective it must be followed to the letter.

Again, I will list the components of the protocol in order of importance.

1. Indomethacin.

This is an inexpensive anti-inflammatory prescription drug that is frequently used to treat gout. If your physician will not give you a prescription, you CAN get a prescription from many online pharmacies. People do this all the time.

This drug is absolutely essential for the success of the protocol.

First, you must understand that certain protaglandins synthesized by tumors promote the growth, and metastasis of the tumors and the initiation of angiogenesis. Second, these prostaglandins are EXTREMELY immunosuppressive. We must inhibit the synthesis of the Cox-2 enzyme and its activity by any means available. Indomethacin is a powerful Cox1/2 inhibitor.

Consider IL-12 and IL-18, which we talked about in a recent blog. Prostaglandin PGE2 inhibits the activity of both hormones by blocking gamma interferon synthesis. PGE2 can also inhibit the synthesis of the IL-12 and IL-2 immune hormones, and the development of TH1 cell mediated immunity.

www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15009430&itool=pubmed_docsum

www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=12753465&itool=pubmed_docsum

www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=14530307&itool=pubmed_docsum

There is NO question, no dispute whatsoever, that cyclic AMP elevating prostaglandins such as PGE2 can completely inhibit the immune response against cancers. As we recently blogged, stressed induced epinephrine (adrenaline) synthesis (which increases cyclic AMP synthesis) promotes ovarian cancer growth. The following article can be read online and is an excellent review of cyclic AMP induced immunosuppression.

www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=14993030&itool=pubmed_docsum

Can ibuprofen substitute for indomethacin?

NO! Ibuprofen, aspirin, sulindac and other NSAID drugs also inhibit the activation of NF-kappaB. NF-kappaB promotes the survival of cancer cells. But NF-kappaB is absolutely necessary for proper immune functioning. Indomethacin does NOT inhibit NF-kappaB activation, nor is it a histone deacetylase inhibitor like sulindac. HDAC inhibitors are immunosuppressive, massively so.

www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16285893&itool=pubmed_docsum

www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=11641233&itool=pubmed_docsum

Indomethacin is the perfect anti-inflammatory drug for this protocol. Thank God it exists.

2. Lactoferrin

This iron binding protein from milk stimulates the GI tract immune system to produce IL-18. Although IL-18 does not activate the immune system like IL-12, it works synergistically with IL-12 to prolong the immune response. I have already written extensively about lactoferrin.

3. Cimetidine

This anti-histamine is a weird molecule. In a previous essay, I recommended the use of inosine to promote histamine synthesis. Histamine is a powerful activator of IL-18 gene activity OR secretion. Unfortunately, inosine may stimulate too much histamine release if one isn’t careful. So I removed it from the protocol and substituted cimetidine.

Cimetidine is a histamine H2 blocker, but it is not specific in how it functions. Cimetidine, unlike other H2 blockers, also stimulates histamine release to some extent. In our case, cimetidine activates the caspase-1 enzyme. This enzymes cleaves inactive IL-18 into an active form that is suitable for secretion. IL-18 is one of those molecules that is synthesized in an inactive form. It must be processed by caspase-1 into a form that is biologically active. This involves proteolytic cleavage of certain inhibitory portions of the newly synthesized IL-18 molecule. By its activation of caspase-1 activity, cimetidine controls IL-18 secretion. Cimetidine and lactoferrin appear to have great synergy for the production of IL-18. This is very exciting.

www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16723495&itool=pubmed_docsum

Cimetidine also promotes IL-12 secretion and general cell mediated immune activity.

www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=10084818&itool=pubmed_docsum

In addition, cimetidine, but NOT other H2 antagonists, promotes the antigen processing ability of dendritic cells removed from advanced colon cancer patients. This is very exciting, because it suggests that cimetidine can protect dendritic cells from the immunosuppressive and toxic factors released by tumor cells.

www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=11953882&itool=pubmed_docsum

Cimetidine can also block the activity of suppressor lymphocytes removed from cancer patients. Again, this affect was specific to cimetidine and not other H2 antagonists.

www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=7770717&itool=pubmed_docsum

Cimetidine is a very useful immune adjuvant for many different reasons.

4. Theanine

A breakdown product of theanine is an activator of gammadelta T cells, a major component of our innate immune system.

Recently, gammadelta T cells were found to be professional antigen presenting cells like dendritic cells and macrophages. These cells can activate naive CD4 T cells. This is a very important arm of our immune system that only now is becoming appreciated.

www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15933162&itool=pubmed_docsum

The following is a great article that can be read online. When this paper was published, most of the major papers ran Associated Press articles touting the use of TEA to boost our immune systems. Sounds stupid, but it turned out to be true. The active ingredient in the tea was theanine, an amino acid found only in tea plants. A break down product of theanine activates gammadelta T cells to secrete gamma interferon and other immune hormones upon exposure to bacteria and other pathogens. Gamma interferon is a non-specific activator of both innate and genetic immune systems.

www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=12719524&itool=pubmed_docsum

5. Melatonin

Melatonin is a great activator of cell mediated immunity. 6 mgs a night.

6. Vitamin A

Many immune hormone genes, such as that for gamma interferon, are inhibited by DNA methylation. Retinoic acid, an active form of vitamin A, can inhibit DNA methyltransferase activity.

www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=11834837&itool=pubmed_docsum

7. Anti-oxidants

Anti-oxidants like vitamin C, E, alpha lipoic acid and N-acetylcysteine inhibit the generation of free radicals. Sounds great…but not always. Antioxidants inhibit the activation of NF-kappaB. Low doses of these compounds are fine because they increase the synthesis of glutathione which enhances immune responsiveness. High doses impair immunity.

www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16723122&itool=pubmed_docsum

There is also nothing wrong with taking multi-vitamins. Unfortunately, people tend to take heavy doses of anti-oxidants in a misguided effort to enhance immunity. It does just the opposite. The immune system needs NF-kappaB and NF-kappaB is commonly activated by free oxygen radicals. Lactoferrin also requires the presence of oxygen radicals in order stimulate IL-18 release.

Dosages

1. Indomethacin. At least the dose used for severe gout inflammations. Probably 2x 50 mgs a day, maybe double this amount if you have a large tumor/leukemia load. If stomach irritation is a problem, use Prilosec to block the stomach problem. It works great. Remember, the use of indomethacin is an absolute MUST for this protocol.

2. Lactoferrin. At least 2 grams a day, divided into smaller doses during the day. Try to dissolve lactoferrin in warm cream or coconut milk to improve bioavailability.

3. Cimetidine. 800 mgs a day, 4x 200 mgs. This dose is NOT toxic in any way.

4. Theanine. 600 mgs a day, 3 x 200 mgs. Theanine will make you sleepy.

5. Melatonin. 6 mgs at night before bed.

6. Vitamin A. 15,000IU a day in a gel cap.

7. Anti-oxidants. 400 mgs alpha lipoic acid, 1000 mgs n-acetylcysteine, 1 gram of vitamin C ester a day.

That is all.

SUMMARY

This is an overview of a complex cancer/leukemia treatment protocol. In order to understand WHY these compounds are included and how they contribute to cancer cell death, you really must subscribe to the Natural Medicines Blog, a subscription site. This site is different from the free Natural Medicines Public Blog. You can view present essay titles by clicking here.

www.grouppekurosawa.com/blogs.htm

This treatment protocol changes as new information becomes available.

END

Copyright © 2006, Stephen Martin, Ph.D
Chief Scientist, Grouppe Kurosawa
All Rights Reserved
grouppekurosawa.com

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