Med Hypotheses

Nonoxidative pentose phosphate pathways and their direct role in ribose synthesis in tumors: is cancer a disease of cellular glucose metabolism?

Boros LG. Lee PW. Brandes JL. Cascante M. Muscarella P. Schirmer WJ. Melvin WS. Ellison EC.
Department of Surgery, The Ohio State University College of Medicine, Columbus 43210, USA. lboros@magnus.acs.ohio-state.edu
Pentose phosphate pathways (PPP) are considered important in tumor proliferation processes because of their role in supplying tumor cells with reduced NADP and carbons for intracellular anabolic processes. Direct involvement of PPP in tumor DNA/RNA synthesis is not considered as significant as in lipid and protein syntheses. Currently, PPP activity in tumor cells is measured by lactate production, which shows a moderate activity: about 4% to 7% compared with glycolysis. Recent data generated in our laboratory indicate that PPP are directly involved in ribose synthesis in pancreatic adenocarcinoma cells, through oxidative steps (< 31%) and transketolase reactions (69%). These findings raise serious questions about the adequacy of lactate in measuring PPP activity in tumors. We hypothesize that ribose, not lactate, is the major product of PPP in tumor cells. Control of both oxidative and nonoxidative PPP may be critical in the treatment of cancer. PPP are substantially involved in the proliferation of human tumors, which raises the prospect of new treatment strategies targeting specific biochemical reactions of PPP by hormones related to glucose metabolism, controlling thiamine intake, the cofactor of the nonoxidative transketolase PPP reaction, or treating cancer patients with antithiamine analogues.

Aspirin-like drugs cause gastrointestinal injuries by metallic cation chelation.

Year 1998
Wang X.
Department of Pathology, Cornell University Medical College, New York, NY 10021, USA. xwang@mail.med.cornell.edu
Aspirin-like (nonsteroidal anti-inflammatory) drugs may cause injuries including ulcers to the gastrointestinal tract by chelation of the divalent and/or multivalent metallic cations in the gastrointestinal mucus and mucosa, as suggested by the chemical properties of these drugs and supported by experimental and clinical data.