cyproterone 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

The authors report 3 personal cases of recurrent, strictly superficial phlebitis of the lower limbs which developed in young women and responded dramatically to corticosteroid therapy. The phlebitis was oestrogen dependent: it has started during pregnancy and was exacerbated in the second part of the menstrual cycle. Clinically, the disease presented as red, dilated veins and/or isolated inflammatory nodules mimicking acute nodular panniculitis. Histology confirmed the diagnosis by showing a major polymorphous inflammatory infiltrate in the venous wall and extending well beyond it, and an intraluminal occasionally occlusive thrombus. A search for thrombosis-inducing diseases, such as disorders of coagulation or fibrinolysis, connective tissue disease, neoplasia or infraction, was negative. Since the phlebitis was strongly inflammatory, frequently recurred and resisted numerous treatments, systemic corticosteroid therapy was instituted, resulting in a dramatic improvement. The steroids were then successfully replaced by antiplatelet agents or, because of the oestrogen dependence, cyproterone maleate. After a mean follow-up period of 2 years, the patients are doing well.

Topics: Adrenal Cortex Hormones; Adult; Antithrombin III Deficiency; Bacterial Infections; Contraceptive Agents, Female; Cyproterone; Female; Humans; Neoplasms; Pregnancy; Protein C Deficiency; Recurrence; Thrombophlebitis

DNA-dependent RNA polymerase activity has been studied in isolated nuclei from canine mammary tumours. Initial experiments showed high levels of RNase activity in this tissue; accordingly, routine assays were terminated before loss of acid-precipitable radioactivity was evident. RNA polymerase A and B activity in isolated nuclei were shown to be increased by addition of receptor-containing cytosol previously incubated with oestradiol-17 beta, dihydrotestosterone or R5020. Where no receptor was present, as measured by saturation binding assays and sucrose density gradient analysis, there was no corresponding increase in polymerase activity. The steroid antagonists tamoxifen and cyproterone did not elicit any response even when their corresponding steroids produced a 1- to 2-fold stimulation of polymerase activity. Steroid-induced effects proved to be dose-dependent, with half maximal responses for oestradiol-17 beta 8 X 10(-8)M, R5020 2 X 10(-6)M and dihydrotestosterone 9 X 10(-6)M.

Topics: Animals; Binding Sites; Cell Nucleus; Cyproterone; Cytoplasm; Diethyl Pyrocarbonate; Dihydrotestosterone; DNA-Directed RNA Polymerases; Dog Diseases; Dogs; Dose-Response Relationship, Drug; Estradiol; Mammary Glands, Animal; Neoplasms; Promegestone; Tamoxifen

Topics: Androgen Antagonists; Antibiotics, Antineoplastic; Bleomycin; Coumarins; Cyproterone; Endocarditis; Humans; Male; Neoplasms; Paraphilic Disorders; Pneumonia; Pregnadienes; Structure-Activity Relationship; Tetracycline; Urinary Tract Infections; Vitiligo