Gleevec

[Guest guest]

Emmanuel,

thanks you so much for taking to time to respond to my query.

My patient has a history of raging alcoholism, but has been sober for about 12 years.

He has no side effects except perhaps slight anemia. But he has a history of this already. I can’t recall his kidney pulse offhand, but I will pay special attention next week. Overall they are full, slippery. Huge in the liver position and above it, in the diaphragm region. Phlegm heat. His tongue is beefy red and peeled. Like a piece of steak. With cracks, indicating long term fluid and yin deficiency. I have no idea if the Gleevec has altered the color of his tongue.

His energy is great. Normal appetite, sleep, bowel function and filled with good spirit.

Up until now, we’ve only used acupuncture. He has been concerned about skewing the results of the research study that he’s a part of. Now he’s reassesed that and would like to bring herbs into the treatment picture.

 

Cara

 

 

Hi Cara,

 

Based on the paper below, you might note that Gleevec is typical of a class of chemotheraputic agents that are protein kinase inhibitors. They unhinge the connection between reading a gene and the subsequent polypeptide production. Great for stopping a malignancy ... not great for the overall function of the body. So you will have to give support for general debilitation, weakness, fatigue and so on.

 

A special side-effect of Gleevec is Severe periorbital edema secondary to STI571 (Gleevec). You can look up this paper title in Medline or other search engine if you want to read the paper, or ask me and I'll send you an abstract. Apparently some people taking Gleevec need surgical intervention for edema that forms inside the orbit of the eye and may cause visual obstruction. You can think about what that means in Chinese medicine. Since normal kidney activity represents 25% of a resting basal metabolic rate, you can probably get a clue as to what Gleevec does to kidney function if periorbital edema is a major side-effect. My guess is that the kidney pulse of your patient will have a special story to tell you.

 

Emmanuel Segmen

 

-

Cara Frank <herbbabe

Wednesday, June 25, 2003 6:19 PM

Re: Gleevac

 

thank you Emmanuel:

my question remains: what should be thinking about if I want to prescribe herbs ( I mean besides responding to signs and symptoms). For instance, we know that some chemotherapeutics are cardiotoxic- we know that there are herbs to mitigate these effects.

what, if anything, do I need to be aware of with Gleevec.

 

Cara

Emmanuel Segmen

 

Gleevec (STI571) influences metabolic enzyme activities and glucose carbon flow toward nucleic acid and fatty acid synthesis in myeloid tumor cells.

J Biol Chem 2001 Oct 12;276(41):37747-53 (ISSN: 0021-9258)

Boren J; Cascante M; Marin S; Comin-Anduix B; Centelles JJ; Lim S; Bassilian S; Ahmed S; Lee WN; Boros LG

Department of Biochemistry and Molecular Biology, Institut d'Investigacions Biomediques August Pi i Sunyer, University of Barcelona, Marti i Franques 1, Barcelona 08028, Spain.

Chronic myeloid leukemia cells contain a constitutively active Bcr-Abl tyrosine kinase, the target protein of Gleevec (STI571) phenylaminopyrimidine class protein kinase inhibitor. Here we provide evidence for metabolic phenotypic changes in cultured K562 human myeloid blast cells after treatment with increasing doses of STI571 using [1,2-13C2]glucose as the single tracer and biological mass spectrometry. In response to 0.68 and 6.8 microm STI571, proliferation of Bcr-Abl-positive K562 cells showed a 57% and 74% decrease, respectively, whereas glucose label incorporation into RNA decreased by 13.4% and 30.1%, respectively, through direct glucose oxidation, as indicated by the decrease in the m1/Sigma(m)n ratio in RNA. Based on the in vitro proliferation data, the IC50 of STI571 in K562 cultures is 0.56 microm. The decrease in 13C label incorporation into RNA ribose was accompanied by a significant fall in hexokinase and glucose-6-phosphate 1-dehydrogenase activities. The activity of transketolase, the enzyme responsible for nonoxidative ribose synthesis in the pentose cycle, was less affected, and there was a relative increase in glucose carbon incorporation into RNA through nonoxidative synthesis as indicated by the increase in the m2/Sigma(m)n ratio in RNA. The restricted use of glucose carbons for de novo nucleic acid and fatty acid synthesis by altering metabolic enzyme activities and pathway carbon flux of the pentose cycle constitutes the underlying mechanism by which STI571 inhibits leukemia cell glucose substrate utilization and growth. The administration of specific hexokinase/glucose-6-phosphate 1-dehydrogenase inhibitor anti-metabolite substrates or competitive enzyme inhibitor compounds, alone or in combination, should be explored for the treatment of STI571-resistant advanced leukemias as well as that of Bcr-Abl-negative human malignancies.