Cure Alveolar Soft Part Sarcoma International (iCureASPS)

Phosphoenolpyruvate carboxykinase (PEPCK) is an enzyme in the lyase family used in the metabolic pathway of gluconeogenesis. It converts oxaloacetate into phosphoenolpyruvate and carbon dioxide

Damian has a concept of a possible study to be performed to benefit research on behalf of ASPS

http://www.cureasps.org/forum/viewtopic ... t=75#p8891

I think ASPS likes glocose and lactate (which to my understanding comes from carbohydrate breakdown) and is happy to use glutamine as a building block and for fuel. They have some early work on PEPCK being a way for tumours to use glutamine as fuel. I'd love to know if ASPS uses GTP as well as ATP. I also think some people respond to vegan diets as they are low in methionine, which many cancers need, rhabdomyosarcoma is one of these. I'd also like to know if ASPS can function in a ketogenic environment.

So basically I have more questions than answers! I think a very low sugar, low GI, moderate protein diet full of vegetables is probably best. I'd love to know more info about what aSPS cells can handle, has anybody tried a vegan low methionine approach in the lab? They can also use methionase to break methionine down to push levels even lower, normal cells can use homocystesine to systhesise methionine, cancer cells may lack this pathway.

I spent ten months last year in ketosis to test it out, I was really good on it and ran 3000km and a tough mudder, so you definitely don't need carbs to run!

We need a researcher to test these things in the lab!

Levels in the lung

Abstract
Send to:
Oncogene. 2015 Feb 19;34(8):1044-50. doi: 10.1038/onc.2014.47. Epub 2014 Mar 17.

PCK2 activation mediates an adaptive response to glucose depletion in lung cancer.

Leithner K1, Hrzenjak A2, Trötzmüller M3, Moustafa T4, Köfeler HC3, Wohlkoenig C1, Stacher E5, Lindenmann J6, Harris AL7, Olschewski A8, Olschewski H1.

Author information


Abstract

Cancer cells are reprogrammed to utilize glycolysis at high rates, which provides metabolic precursors for cell growth. Consequently, glucose levels may decrease substantially in underperfused tumor areas. Gluconeogenesis results in the generation of glucose from smaller carbon substrates such as lactate and amino acids. The key gluconeogenic enzyme, phosphoenolpyruvate carboxykinase (PEPCK), has been shown to provide metabolites for cell growth. Still, the role of gluconeogenesis in cancer is unknown. Here we show that the mitochondrial isoform of PEPCK (PCK2) is expressed and active in three lung cancer cell lines and in non-small cell lung cancer samples. PCK2 expression and activity were enhanced under low-glucose conditions. PEPCK activity was elevated threefold in lung cancer samples over normal lungs. To track the conversion of metabolites along the gluconeogenesis pathway, lung cancer cell lines were incubated with (13)C₃-lactate and label enrichment in the phosphoenolpyruvate (PEP) pool was measured. Under low glucose, all three carbons from (13)C₃-lactate appeared in the PEP pool, further supporting a conversion of lactate to pyruvate, via pyruvate carboxylase to oxaloacetate, and via PCK2 to phosphoenolpyruvate. PCK2 small interfering RNA and the pharmacological PEPCK inhibitor 3-mercaptopicolinate significantly enhanced glucose depletion-induced apoptosis in A549 and H23 cells, but not in H1299 cells. The growth of H23 multicellular spheroids was significantly reduced by 3-mercaptopicolinate. The results of this study suggest that lung cancer cells may utilize at least some steps of gluconeogenesis to overcome the detrimental metabolic situation during glucose deprivation and that in human lung cancers this pathway is activated in vivo.



https://www.ncbi.nlm.nih.gov/pubmed/24632615

This is very interesting and possibly drugable.

https://www.mcgill.ca/channels/news/new ... cer-256202

Also:
http://healthnews.uc.edu/news/?/26962/

Metformin is safe and well understood, it also keeps cropping up in energy research as being potentially useful in cancer treatment.
https://www.researchgate.net/publicatio ... _migration