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!

natural alternative to HBOT to saturate cancer cells?

What would be a natural alternative to HBOT to saturate cancer cells with oxygen? Would exercise in a forest help or are there ways to increase our lung capacity? I understand the air we breathe is 21% oxygen.


There is nothing I know of that would be more effective than HBOT to saturate cancerous tissues with oxygen.
Professor Seyfried

Exercise in general or perhaps breathing from an oxygen tank and normobaric pressure.  100% O2
Dominic D'Agostino, PhD

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

Ketogenic diet diary

Day 1. (6th July)
Transition phase, only replaced snack with low carb.
Headache fatigue at night

Day 2
110.0lbs
Ate 3 keto meals but added carbs squash

Headache fatigue
Constipation
Rectal pain

Felt less bloated, lighter

Day 3
110.4

Morning Headache
Legs tired
Stool hard and slow
Brain dead/mental unfocused
Throat clogged

Drank more bone broth, salt

Day 4 (9th July)
110.0
No headache
No fatigue
Ph 7.4
Stool long and easy pass
Stomach lump feels hard/bigger
Lung pain/shortness of breath (mild acidosis or reactive hypogleciemia, eat more carbs/protein)
More acne (not unusual symptom.)

shortness of breath while in ketosis?

Does anybody ele experience shortness of breath while in ketosis?

I have the last two times i tried the diet. As soon as i get back on a mod carb approach it goes away. its really stressing me out feeling like i cant breathe all day. I am not anemic and have 98-99% blood oxygen level.

is this common?

#2   08-05-2009, 11:23 AM

lylemcd Administrator   Join Date: Feb 2008 Posts: 19,795

First time I've heard of it. There is some loss of ketones and there was some weird data point (I'm going to forget the details) where resting RQ (a measure of fuel utilization) ould drop below 0.7 due to something related to extra CO2 being lost or some such. But I refer you to the parable of "Doc it hurts when I do this."

#3   08-05-2009, 11:34 AM

bretter Junior Member   Join Date: Aug 2009 Posts: 24

I finished carbing up sunday and I'm within a pound of baseline this morning.it is a symptom of ketoacidosis should I be concerned? Really enjoyed ur book btw.

#4   08-05-2009, 11:40 AM

lylemcd Administrator   Join Date: Feb 2008 Posts: 19,795

No, ketoacidosis doesn't develop in non-diabetics. Again, the details are hazy, it had something to do with how ketones are handled in the body and maybe a loss of base or something, it's been too many years and I never paid much attention to it. If it's causing problems, I'd say to continue dieting with a moderate carb non-keto diet (e.g. carbs around 1 g/lb bodyweight or 120-150 grams minimum) to avoid the issue entirely. Still low enough for various benefits, high enough to avoid ketosis, etc, etc.

#5   08-05-2009, 12:09 PM

ragiarn Member   Join Date: Jul 2009 Location: Connecticut Posts: 49

Ketoacidosis occurs in diabetics because there is not enough glucose within the cell mitochondria to allow the entry of the ketone bodies into the krebs cycle. Ketones are the result of partial metabolism of fat and requires the Krebs cycle to complete the total metobolism. The Krebs cycle needs glucose to keep it going. As the saying goes"Fat burns in the flame of glucose" (or something to that effect). As a result, in these diabetics, massive amount ketones enter the blood stream and overwhelm the buffering system of the blood. Despite the elevated blood glucose in diabetics ( most of these patients present with blood glucose levels in the range of 600-1400 mg/dl and blood pH as low as 7.1) the glucose is unable to enter the cell because of a lack of insulin. In non diabetics even on a low carb diet there is still enough glucose to run the krebs cycle. In low carb diets amino acids can, and often are, converted into glucose through gluconeogenesis to maintain a normal blood sugar level. Because insulin is still present the glucose can enter the cell and keep the krebs cycle going and thus prevent massive elevation of ketones and severe ketoacidosis. The buffering of the ketoacids is rather complicated since there are mulitple systems involved in this process. Many of these systems are compromised in diabetics and are not generally not a problem for an otherwise healthy person. This is a somewhat simplistic explanation of the process. For further clarification consutl with a bichemistry textbook. Ralph

#6   08-05-2009, 12:29 PM

lylemcd Administrator   Join Date: Feb 2008 Posts: 19,795

Or my first book. As well, in non-diabetics there are at least two failsafe systems to prevent runaway ketoacidosis First and foremost, when ketone concentrations get high enough, insulin is released, this shuts down FFA release from fat cells and ketone production in the liver. There'ss another one but the bottom line is that ketoacidosis in the sense of runaway ketone production as occurs in Type I diabetics, does NOT occur in non-diabetic humans. As long as there is some potential for insulin release, it won't ever get out of hand.

#7   08-05-2009, 02:33 PM

bretter Junior Member   Join Date: Aug 2009 Posts: 24

i think im going to throw in some carbs instead of fats for a few of my meals thanks

#8   10-02-2009, 11:17 PM

shwi Junior Member   Join Date: Oct 2009 Posts: 2

Quote: Originally Posted by bretter Does anybody ele experience shortness of breath while in ketosis? Yup, I've been doing a CKD for a few weeks now and I've definitely noticed a shortness of breath at times. I put it down to a loss in my cardiovascular fitness due to a decrease in the amount of cardio I've been doing. I realise I'm probably wrong.

#9   09-01-2010, 04:43 PM

Aminal Member   Join Date: Aug 2010 Posts: 80

Bump from the grave, but I searched and this was the only place on here I could find this, sorry if it's been discussed again. I am doing RFL (5 days now) and now seem to be experiencing the joys of ketosis (amongst other things). I am noticably short of breath but surprisingly energetic. A quick google seems to reveal that shortness of breath is a recognised symptom of ketosis in some (and ketoacidosis of course). I'm hoping it will pass as I enter the second week. People keep asking me why I'm sighing Last edited by Aminal : 09-01-2010 at 04:45 PM.

#10   09-07-2010, 07:06 AM

bretter Junior Member   Join Date: Aug 2009 Posts: 24

I bulked and got on HRT for low testosterone and it went away. I think I dieted too long and hard. dont do what i did.

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

Gleevec natural alternatives? Natural tyrosine kinase inhibitor

The natural tyrosine kinase inhibitor genistein produces cell cycle arrest and apoptosis in Jurkat T-leukemia cells.

Spinozzi F, Pagliacci MC, Migliorati G, Moraca R, Grignani F, Riccardi C, Nicoletti I.

Source

Istituti di Medicina Interna e Scienze Oncologiche, Università di Perugia, Italy.

Abstract

Genistein, a natural isoflavonoid phytoestrogen, is a strong inhibitor of protein tyrosine kinases. We analyzed the effects of genistein on in vitro growth, cell-cycle progression and chromatin structure of Jurkat cells, a T-cell leukemia line with a constitutively increased tyrosine phosphorylation pattern. Exposure of in vitro cultured Jurkat cells to genistein resulted in a dose-dependent, growth inhibition. Cell-cycle analysis of genistein-treated cells revealed a G2/M arrest at low genistein concentrations (5-10 micrograms/ml), while at higher doses (20-30 micrograms/ml) there was also a perturbation in S-phase progression. The derangements in cell-cycle control were followed by apoptotic death of genistein-treated cells. Immunocytochemical analysis of cells stained with a FITC-conjugated anti-phosphotyrosine monoclonal antibody showed that 30 micrograms/ml genistein effectively inhibit tyrosine kinase activity in cultured Jurkat cells. Our results indicate that the natural isoflavone genistein antagonizes tumor cell growth through both cell-cycle arrest and induction of apoptosis and suggest that it could be a promising new agent in cancer therapy.

Genistein-induced mitotic arrest of gastric cancer cells by downregulating KIF20A, a proteomics study.

Yan GR, Zou FY, Dang BL, Zhang Y, Yu G, Liu X, He QY.

Source

Institute of Life and Health Engineering, and National Engineering and Research Center for Genetic Medicine, Jinan University, Guangzhou, China.

Abstract

Genistein exerts its anticarcinogenic effects by inducing G2/M arrest and apoptosis of cancer cells. However, the precise molecular mechanism of action of genistein has not been completely elucidated. In this study, we used quantitative proteomics to identify the genistein-induced protein alterations in gastric cancer cells and investigate the molecular mechanism responsible for the anti-cancer actions of genistein. Total 86 proteins were identified to be regulated by genistein, most of which were clustered into the regulation of cell division and G2/M transition, consistent with the anti-cancer effect of genistein. Many proteins including kinesin family proteins, TPX2, CDCA8, and CIT were identified for the first time to be regulated by genistein. Interestingly, five kinesin family proteins including KIF11, KIF20A, KIF22, KIF23, and CENPF were found to be simultaneously downregulated by genistein. Significantly decreased KIF20A was selected for further functional studies. The silencing of KIF20A inhibited cell viability and induced G2/M arrest, similar to the effects of genistein treatment in gastric cancer. And the silencing of KIF20A also increased cancer cell sensitivity to genistein inhibition, whereas overexpression of KIF20A markedly attenuated genistein-induced cell viability inhibition and G2/M arrest. These observations suggested that KIF20A played an important role in anti-cancer actions of genistein, and thus may be a potential molecular target for drug intervention of gastric cancer.
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sources of Genistein

Genistein is found in plant foods such as soybeans, chickpeas, broccoli, cauliflower, alfalfa sprouts, clover sprouts, barley meal, sunflower seeds, and clover seeds. It is also found in many soy-based products such as soy milk, tempeh, miso, soy flour, infant formula, sports drinks, protein bars, and textured soy protein. Textured soy protein (TSP) is used as a meat substitute in vegetarian hamburgers, hot dogs, sausages, and meatballs. Though soy is by far the most common dietary source of genistein, it is not found in soy sauce or soybean oil. Genistein is also available as a dietary supplement in powder, pill, or capsule form.

Curcumin Inhibits Tyrosine Kinase Activity of p185^neu and Also Depletes p185^neu1

1. Ruey-Long Hong,
2. William H. Spohn and
3. Mien-Chie Hung2

+ Author Affiliations

1. Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan 10016 [R-L. H.], and Department of Tumor Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030 [R-L. H., W. H. S., M-C. H.]

Next Section

Abstract

Curcumin, a natural compound present in turmeric, possessing both anti-inflammatory and antioxidant effects, has been studied vigorously as a chemopreventative in several cancer models. The erbB2/neu gene-encoded p185^neu tyrosine kinase is a potent oncoprotein. Overexpression of p185^neu in breast cancer is known to be a poor prognostic factor. We investigated the effect of curcumin on p185^neu tyrosine kinase and on the growth of breast cancer cell lines. Curcumin dose-dependently inhibited p185^neu autophosphorylation and transphosphorylation in vitro and depleted p185^neu protein in vivo. It dissociated the binding of p185^neu with GRP94 (glucose-regulated protein), a molecular chaperone, and enhanced the depletion of p185^neu. The amount of p185^neu protein on the cell membrane was drastically decreased after curcumin treatment. These data demonstrated a new mechanism of the anti-tyrosine kinase activity of curcumin. The growth of several breast cancer cell lines was inhibited; the IC₅₀ ranged from 7 to 18 μm, which, however, did not correlate with the expression level of p185^neu. Colony formation in the soft agar assay, a hallmark of the transformation phenotype, was preferentially suppressed in p185^neu-overexpressing cell lines by 5 μm curcumin (% of control, basal level versus overexpression: 59.3 versus 16.7%; P < 0.001 by Student’s t test). Because curcumin effectively inhibited p185^neu tyrosine kinase activity by depleting p185^neu and potently suppressed the growth of multiple breast cancer cell lines, its therapeutic potential in advanced breast cancer is worthy of further investigation.

Emodin, a Protein Tyrosine Kinase Inhibitor from Polygonum cuspidatum

 

Emodin is being studied as a potential agent that could reduce the impact of type 2 diabetes. It is a potent selective inhibitor of the enzyme 11β-HSD1.^[2] In studies in obese mice, emodin limits the effect of glucocorticoids and may therefore ameliorate diabetes and insulin resistance.^[3]
Pharmacological studies have demonstrated that emodin when isolated from rhubarb exhibits anti-cancer effects on several human cancers, including human pancreatic cancer.^[4][5][6] Emodin in rhubarb extracts may also have neuroprotective properties against glutamate toxicity,^[7]
Aloe-emodin (1,3,8-trihydroxyanthraquinone) is a variety of emodin found in Socotrine, Barbados, and Zanzibar aloes, but not in Natal aloes.^{[citation needed]}
Emodin is also shown to block cytomegalovirus infections as well as herpes simplex. Research is currently being performed in this area.

List of plants that contain the chemical

• Senna obtusifolia^[8] (syn. Cassia obtusifolia^[9])
• Fallopia japonica^[10] (syn. Polygonum cuspidatum^[11])
• Ventilago madraspatana^[12]
• Kalimeris indica^[13]
• Rumex nepalensis^[14]
• Polygonum hypoleucum^[15]
• Cassia occidentalis^[16]
• Cassia siamea^[17]
• Acalypha australis^[18]
• Rheum palmatum^[19]