Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hereditary peculiarities in individual responses to environmental chemicals are a common occurrence in human populations. Genetic variation in glutathione S-transferase, CYP1A2, N-acetyltransferase, and paraoxonase exemplify the relationship of metabolic variation to individual susceptibility to cancer and other toxicants of environmental origin. Heritable receptor protein variants, a subset of proteins of enormous pharmacogenetic potential that have not thus far been extensively explored from the pharmacogenetic standpoint, are also considered. Examples of interest that are considered include receptor variants associated with retinoic acid resistance in acute promyelocytic leukemia, with paradoxical responses to antiandrogens in prostate cancer, and with retinitis pigmentosa. Additional heritable protein variants of pharmacogenetic interest that result in antibiotic-induced deafness, glucocorticoid-remediable aldosteronism and hypertension, the long-QT syndrome, and beryllium-induced lung disease are also discussed. These traits demonstrate how knowledge of the molecular basis and mechanism of the variant response may contribute to its prevention in sensitive persons as well as to improved therapy for genetically conditioned disorders that arise from environmental chemicals.
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PMID:Influence of heredity on human sensitivity to environmental chemicals. 778 56

Voltage-operated calcium channels play a crucial role in signal transduction in many excitable and non-excitable cell types. While a rapid modulation of their activity by hormone-activated kinases and/or G proteins has been recognized for a long time, a sustained control of their expression level has been only recently demonstrated. In adrenal H295R cells, for example, aldosterone treatment selectively increased low threshold T-type calcium current density without affecting L-type currents. Antagonizing the mineralocorticoid receptor (MR) with spironolactone prevented aldosterone action on T-type currents. By RT-PCR, we detected in these cells the presence of two different isoforms of L-type channels, alpha(1)C and alpha(1)D, and one isoform of T channel, alpha(1)H. A second T channel isoform (alpha(1)G) was also observed under particular culture conditions. Quantification of the specific messenger RNA by real time RT-PCR allowed us to show a 40% increase of the alpha1H messenger levels upon aldosterone treatment (alpha(1)G was insensitive), a response that was also completely prevented by spironolactone. Because T-type, but not L-type channel activity is linked to steroidogenesis, this modulation represents a positive, intracrine feed back mechanism exerted by aldosterone on its own production. Aldosterone has been also implicated in the pathogenesis and progression of ventricular hypertrophy and heart failure independently of its action on arterial blood pressure. We have observed that, in rat neonatal cardiomyocytes, aldosterone increases (by two-fold) L-type calcium current amplitude in ventricular but not in atrial cells. No significant effect of aldosterone could be detected on T-type currents, that were much smaller than L-type currents in these cells. However, aldosterone exerted opposite effects on T channel isoform expression, increasing alpha(1)H and decreasing alpha(1)G. Although the functional role of T channels is still poorly defined in ventricular cardiomyocytes, an overexpression of alpha(1)H could be partially responsible for the arrhythmias linked to hyperaldosteronism.Finally, T channels also appear to be involved in the neuroendocrine differentiation of prostate epithelial cells, a poor prognosis in prostate cancer. We have shown that the only calcium channel expressed in the prostatic LNCaP cells is the alpha(1)H isoform and that induction of cell differentiation with cAMP leads to a concomitant increase in both T-type current and alpha(1)H mRNA. In spite of the presence of MR in these cells, aldosterone only modestly increased alpha(1)H mRNA levels. A functional role for these channels was suggested by the observation that low nickel concentrations prevent neuritic process outgrowth. In conclusion, it appears that T-type calcium channel expression vary in different patho-physiological conditions and that aldosterone, in several cell types, is able to modulate this expression.
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PMID:Aldosterone regulation of T-type calcium channels. 1294 26

Again, we present a rich issue with great information to address common clinical questions. A common class of drug (proton pump inhibitors) and insufficiently common diet (high fiber content) are related to improved diabetes control. Four good health habits make a huge difference, especially for obese patients. Meaningful use is just not always that meaningful. Computed tomography scans for common chest complaints probably are overused in emergency rooms. Continuous insurance is important to receipt of prevention services, even for those with access to care when they do not have insurance. Practice-based research can be difficult to accomplish, yet can yield some good results--in this case, improved colon cancer screening rates. Consider hyperaldosteronism in patients with resistant hypertension. Reflect on the mistakes other family physicians report; we often learn from others' mistakes. Surgical mesh migration can cause many things, but would you guess it would cause symptoms of irritable bowel syndrome? A nice primer on what is known about chemoprevention of prostate cancer. And, how to influence care outcomes: high-leverage, not just measurable, activities.
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PMID:Answers to common clinical questions. 2221 15

There is no standard treatment for metastatic prostate cancer that progresses despite castration and cytotoxic chemotherapy. Abiraterone inhibits both testicular and extratesticular androgen synthesis. It has been approved in the European Union for use in this situation, in which treatment options are extremely limited. Clinical evaluation is based on a double-blind comparative trial of good methodological quality that included 1195 patients. The median overall survival time was 4 months longer in the group treated with abiraterone + prednisone (or prednisolone) than in the group treated with placebo + prednisone (or prednisolone): 15.8 versus 11.2 months. The addition of prednisone (or prednisolone) reduced but did not eliminate the effects of hyperaldosteronism induced by abiraterone; oedema occurred in 26.7% of patients, arterial hypertension in 8.5%, and hypokalaemia in 17.1%. Moderate hepatotoxicity was reported with abiraterone and needs to be better assessed. Abiraterone was also associated with cardiac arrhythmias (7.2% versus 4.6% with placebo) and heart failure (1% versus 0.3%). Abiraterone is metabolised by cytochrome P450 isoenzyme CYP3A4 and inhibits isoenzyme CYP2D6, resulting in a high potential for drug interactions. Treatment is somewhat inconvenient. Abiraterone must be taken between meals, serum potassium levels must be monitored, and care must be taken to avoid interactions. Overall, the known risks of abiraterone appear to be acceptable in view of its efficacy, but patients must be carefully monitored. Abiraterone is one option to discuss with patients with metastatic prostate cancer after other treatments fail.
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PMID:Abiraterone. After prostate cancer treatment failure: 4-month survival advantage. 2282 91