Foods alternatives/complimentary to Gleevec (GIST)

Sil The precise book reference is "Cooking with fords that fight cancer" by Richard Beliveau and Denis Gingras, published by A&U. I got it from the ABC bookshop a few years ago but assume its widely available. There is also one which doesn't have the recipes by the same authors. They say in the book that it has recently been observed that lueolin and apigenin (found in mint, thyme and parsley) powerfully inhibit the activity of a key enzyme activated by the growth factor PDGF and involved in the establishment of new blood vessels in tumours. They go on to say that luteolin and apigenin posses an activity comparable to Gleevec. I am currently on Gleevec which thankfully is working, so I have not really looked into how much of parsley mint etc you need to eat to get an equivalent effect, nor whether it actually works on GIST. However, the book is very interesting in that it explains how cancer is currently thought to work, and explains how different foods may inhibit it. Also it suggests red wine and chocolate have ingredients that inhibit cancer so it has my vote!

Genistein vs Gleevec: natural TKI?

Genistein differs from Gleevec in that genistein is a natural phytoestrogen and targets tyrosine kinase inhibitors (among other things) while Gleevec is a man made small molecule generated to bind specifically to the fusion protein called bcr-abl created by the rearrangement occurring following the break and fusion between chromosomes 9 and 22 specific to CML (GIST also seem to be sensitive to Gleevec). Gleevec works because this fusion protein is present only in tumor cells and it is essential for tumor cell growth. Thus, Gleevec tends to have few side effects and unless the tumor cells develop resistance (which happens in a very small percentage of cases) the drug is effective in killing cells carrying the fusion protein. The presence of a unique protein like bcr-abl is not common in cancers (though others have been identified). So you have the difference between using an nonspecific tki like genistein which is likely to have significant side effects at higher doses as it targets many tkis and has estrogenic activity, and a specific molecule designed to inhibit one specific tyrosine kinase that is known to be involved in tumor cell survival and growth.

   So while the may be some benefits from eating foods containing genistein (besides isoflavones it has anti-oxidant activity) there are doses and side effects to consider - I am also not sure that the amounts present in foods are therapeutically significant. However, before you decide to do any of this and especially if your are thinking of taking supplements, you need to have a discussion with your doctor.


Traganos, Ph.D.
Emeritus Professor of Pathology

Gist and ketogenic diet

Its not clear if GIST will respond to ketogenic diet. But, based on some general information, GIST are likely to because:
1. Neuro origin of cells.
2. "Tracing the roots of this disease to cellular respiration has yielded a promising lead on how GIST tumors might form,": cellular respiration typically means a defect in the mitochondrial function of oxidative phosphorylation. That would make this tumor dependent on fermentation of glucose for its energy.
3. The researchers examined tissue from 34 GIST patients for mutations in the genes for succinate dehydrogenase, an enzyme that processes oxygen to obtain energy for cells. [Again, cellular respiration of oxygen occurs in mitochondria-lacking this the cell metabolizes glucose with no alternatives]
4. Although the remaining patients did not have any of these mutations, succinate dehydrogenase in tissue from their tumors did not appear to be functioning and cellular respiration was disrupted. [disrupted CR means glucose is left for energy]
Therefore it is likely that these tumors are glucose sensitive. Deprivation of glucose with a Very Low Carbohydrate diet (ketogenic diet) may be effective in stopping progression or enhancing the effects of other cancer agents, like imatinib

Dr P.   M.D

egcg and gist tumors

Green tea (-)-epigalocatechin-3-gallate inhibits KIT activity and causes caspase-dependent cell death in gastrointestinal stromal tumor including imatinib-resistant cells.

Chi HT, Vu HA, Iwasaki R, Thao le B, Hara Y, Taguchi T, Watanabe T, Sato Y.

Source

Division of Ultrafine Structure, Department of Pathology, Research Institute of International Medical Center of Japan, Tokyo, Japan.

Abstract

Imatinib, a selective tyrosine kinase inhibitor, has been used as a standard first-line therapy for gastrointestinal stromal tumor (GIST) patients. Unfortunately, most patients responding to imatinib will eventually exhibit the resistance, the cause of which is not fully understood. The serious clinical problems of imatinib-resistance demand alternative treatment strategy. (-)-Epigallocatechin-3-gallate (EGCG), a main component of green tea catechin, has been demonstrated potential anti-tumor effects on various types of cancer cells. Here, we report for the first time that EGCG has shown anti-tumor effects on gastrointestinal stromal tumor cell line GIST-T1 by suppressing cell proliferation and eventually inducing cell death via caspase-dependent pathways. GIST-T1 and imatinib resistant GIST-T1 (GIST-T1 IR) cells were used to assess the effects of EGCG. In both cell types, KIT activity was completely inhibited after 4 h treatment with 60 muM EGCG. EGCG specifically inhibited activated KIT, which was demonstrated by using Ba/F3 cells transfected with human wild-type KIT construct. At a dose of 30 muM EGCG, the KIT activity remains but at more than 40 muM EGCG, the KIT activity was abolished in these transfected-Ba/F3 cells. Our results suggest that EGCG has a promising potential as a natural KIT inhibitor and therefore it could be used as a novel therapeutic or preventive reagent for GISTs including the imatinib-resistant cases.

Stomach cancer
Laboratory studies have found that green tea polyphenols inhibit the growth of stomach cancer cells in test tubes. The exposure of human stomach cancer KATO III cells to egcg led to both growth inhibition and the induction of programmed cell death (apoptosis) (Oncol Rep, 5(2):527-9 1998 Mar-Apr).


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DOSAGE

http://newsblog.mayoclinic.org/2010/06/04/green-tea-extract-appears-to-keep-cancer-in-check-in-majority-of-cll-patients/

The article that was published about this study is available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2727287/?tool=pubmed. The sentence defining the dosage states, “Polyphenon E with a standardized dose of epigallocatechin-3-gallate (EGCG) was administered using the standard phase I design with three to six patients per dose level (range, 400 to 2,000 mg by mouth twice a day).” The article later suggests that people tolerated the maximum dose well and that some people who received the higher doses seemed to do better in some respects, which is probably why they used the highest dosage in the next study. Still, as someone with no expertise in this area, I wouldn’t try to dose myself based on this information, and I can see why the Mayo people don’t want to specify a dosage in the context of patients asking what they should take. I went to an integrative medicine specialist at a major cancer center, who recommended 1,000 mg. twice a day. I’m not sure whether a regular oncologist would necessarily know about this; some of them tend to be dismissive of anything other than meds as such.


EM says:

February 2, 2012 at 3:11 pm

I was diagnosed with CLL about 6 months ago. I am 52 years old, female and otherwise in really good health. Since it is very early in the diagnosis with no symptoms (other than some slightly enlarged lymph nodes), I have been in the watch and wait phase. My internist (who discovered the CLL through a routine blood test) prescribed a series of supplements included EGCG. I have been taking AOR Active Green tea (700mg/455 catechins) twice a day. Along with the EGCG I have also been taking Tumeric, Reservatrol, Vitamin D and Omega-3 Fish oil twice a day. I just went back for my check several weeks ago and the news was great! My WBC went down to 6800 from 11,500 and my LYMPH went down 51% from 61% and NEUT up to 36% from 31%! Yay! Of course, we can’t be 100% sure that is all the supplements at work, but I will take the good news nonetheless and continue with my course as is. I have also read “Anti-Cancer – A New Way of Life” by David Servan-Schrieber. Though at times it can be a bit technical, the diet/mind/body portion of it is wonderfully written and I would highly recommend it to read
 

 

 

KIT or PDGFRA mutations may initiate the start of GIST. Epigenetic changes, which sometimes may be affected by environmental factors, could activate the KIT or PDGFRA mutated cells to be more aggressive GISTs.

I guess the following might be more accurate.

KIT or PDGFRA mutations may initiate the start of GIST. Epigenetic changes, which sometimes may be affected by environmental factors, could activate the KIT or PDGFRA mutated cells to be more aggressive GISTs.

Thank you.

Y.
 -

Thank you so much Y. Do I have your permission to share this? I believe it's an important study.

If I understand correctly...

Epigenetic changes from environmental factors may initiate the start of GIST. Those changes could activate the mutated cells KIT or PDGFRA to be expressed.
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Dear b.

Thank you for your interest in our study.

The majority of GISTs have activating mutations in KIT or PDGFRA tyrosine-kinase receptor genes.  These mutations are thought to be part of the initiation phase of GIST development and other genetic and epigenetic abnormalities may be involved when GISTs progress to a malignant phenotype.

We conducted, for the first time, genome-wide DNA methylation analysis in GISTs.  Our extensive analyses revealed that DNA methylation accumulates on a genome-wide basis during tumor progression.

Both genetic alterations in epigenetic regulators (i.e. epigenetic enzymes) and environmental factors induce epigenetic alterations, which may affect the phenotype of tumor cells via alteration of gene expression.

Thank you again.

Y.

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Dr Y.
I found your study on the epigenetics of GIST fascinating and very helpful.

Whats the role of epigenetics in GIST tumors? Can the mutated cells that causes GISTs be turned on or turned off? My understanding of epigenetics is many factors like out environment can cause genes to be expressed or silenced.

Sauna and GIST

Now this is a confusing topic to research. Most of what I've found has either dismissed it as pseudoscience or tried to sell me something. The one paper I found that might be of some use indicated that infrared treatment may be effective for certain tumours containing low levels of a protein called hsp70. Hsp70 is a heat-shock protein that indicates stress in the body and protects cells and proteins from heat damage. The paper stated:  "This finding suggested that FIR should be very effective medical treatment for some cancer cells which have a low level of HSP70. Still more, if the level of HSP70 in any cancer of a patient was measured, the effect of medical treatment by FIR can be foreseen for the cancer." (1)

So, essentially, the level of HSP70 determines how effective far infrared therapy might be. Heat shock proteins are apparently over-expressed in some cancers, and under-expressed in others (2). For GIST tumours, at least one study has found that hsp70 level is positively correlated with the severity of the tumour. Essentially, if you have been told that your GIST is low to moderate risk, then chances are there is a low level of hsp70, which would make the infrared sauna more likely to be effective. (3) 

I don't know if any of that is of any help, but it's the best information I've been able to find so far. 

1. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2386844/

2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1176476/

3. http://mt.china-papers.com/2/?p=13971