mobiflex and Neoplasms

The oxidative pentose phosphate pathway (PPP) contributes to tumour growth, but the precise contribution of 6-phosphogluconate dehydrogenase (6PGD), the third enzyme in this pathway, to tumorigenesis remains unclear. We found that suppression of 6PGD decreased lipogenesis and RNA biosynthesis and elevated ROS levels in cancer cells, attenuating cell proliferation and tumour growth. 6PGD-mediated production of ribulose-5-phosphate (Ru-5-P) inhibits AMPK activation by disrupting the active LKB1 complex, thereby activating acetyl-CoA carboxylase 1 and lipogenesis. Ru-5-P and NADPH are thought to be precursors in RNA biosynthesis and lipogenesis, respectively; thus, our findings provide an additional link between the oxidative PPP and lipogenesis through Ru-5-P-dependent inhibition of LKB1-AMPK signalling. Moreover, we identified and developed 6PGD inhibitors, physcion and its derivative S3, that effectively inhibited 6PGD, cancer cell proliferation and tumour growth in nude mice xenografts without obvious toxicity, suggesting that 6PGD could be an anticancer target.

Topics: AMP-Activated Protein Kinase Kinases; AMP-Activated Protein Kinases; Humans; Lipogenesis; Neoplasms; Oxidative Stress; Pentose Phosphate Pathway; Phosphogluconate Dehydrogenase; Protein Serine-Threonine Kinases; Ribulosephosphates; Signal Transduction

Palliate care is concerned with oncologic patients and its aim is to reduce their suffering, i.e. in the first place to eliminate or reduce pain. As a rule, the WHO prescriptions are followed, administering progressively nonsteroid analgesic agents (NSAIDs), weak opioids, strong opioids. The most convenient channels of administration are oral and subcutaneous. So far, NSAIDs could not be given subcutaneously due to the local side effects (pain and irritation at the point of injection) they cause. On the basis of experience with tenoxicam in our Department, subcutaneous administration is suggested. Our study involved 27 subjects with treatment-refractory tumors, in order to assess topical tolerability. In all cases, the drug was administered via a subcutaneous permanent teflon needle-catheter. Tenoxicam was found to have better gastric tolerability compared to other NSAIDs. It can be concluded that for the palliative treatment of cancer patients tenoxicam ampoules are an additional drug that can be administered subcutaneously.

Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Drug Tolerance; Female; Humans; Injections, Subcutaneous; Male; Middle Aged; Neoplasms; Pain; Palliative Care; Piroxicam; Time Factors