Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0277787 (stigma)
 13,352 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ovarian cells within the area of impending follicular rupture in the sheep exhibit evidence of DNA fragmentation. Most cells undergo a degenerative process indicative of apoptosis and are deleted before ovulation. However, some ovarian surface epithelial cells located along the margins of ruptured follicles persist (with damaged DNA) into the ensuing luteal phase. It is conceivable that a genetically-altered progenitor cell that has survived a sub-lethal insult at ovulation (i.e. with unrepaired DNA but not committed to death) could give rise to a malignant phenotype that is propagated during the postovulatory ovarian surface wound-repair process. It was hypothesized that progesterone derived from the formative corpus luteum reestablishes genomic integrity among ovarian surface epithelial cells contiguous with the ovulatory site and that this response is mediated by the DNA repair/apoptosis-activating enzyme poly(ADP-ribose) polymerase (PARP). Ovarian surface epithelial cells immediately surrounding the ovulatory stigma of sheep follicles were recovered on luteal days 1, 2 or 4; control cells were obtained from an ipsilateral ovarian region removed from the point of ovulation. Immunofluorescent staining of end-linked digoxigenin or poly(ADP-ribose) was used to detect fragmented DNA or PARP-modified proteins within individual cells. Approximately 25% of surface epithelial cells that bordered the ovarian rupture site contained damaged DNA on days 1 and 2; there was a dramatic decrease by day 4 (< 5%). The decline in DNA-compromised cells was negated by in vivo inhibition of lutein progesterone production invoked by ovarian perivascular injection (day 1) of the 3 beta-hydroxysteroid dehydrogenase inhibitor isoxazol; this effect was reversed by exogenous progesterone. There was a positive relationship on day 2 between the level of ovarian progesterone and immunostaining of ADP-ribose polymers in surface epithelial cells associated with the ovulatory site. Evidence of DNA fragmentation or PARP activity in control cells was low and not affected by time of sample collection or treatments. The progesterone receptor antagonist RU486 and the transcriptional inhibitor actinomycin D blocked increases in PARP in ovarian surface epithelial cells incubated with progesterone. It is suggested that DNA damage to ovarian surface epithelium that is inflicted at ovulation is (normally) reconciled on a localized basis by progesterone/PARP-mediated repair or dedicated apoptotic cell death thereby conferring protection against clonal transformation.
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PMID:Perturbation of sheep ovarian surface epithelial cells by ovulation: evidence for roles of progesterone and poly(ADP-ribose) polymerase in the restoration of DNA integrity. 958 7

Hereditary breast cancers, mainly due to BRCA1 and BRCA2 mutations, account for only 5-10% of this disease. The threshold for genetic testing is a 10% likelihood of detecting a mutation, as determined by validated models such as BOADICEA and Manchester Scoring System. A 90-95% reduction in breast cancer risk can be achieved with bilateral risk-reducing mastectomy in unaffected BRCA mutation carriers. In patients with BRCA-associated breast cancer, there is a 40% risk of contralateral breast cancer and hence risk-reducing contralateral mastectomy is recommended, which can be performed simultaneously with surgery for unilateral breast cancer. Other options for risk management include surveillance by mammogram and breast magnetic resonance imaging, and chemoprevention with hormonal agents. With the advent of next-generation sequencing and development of multigene panel testing, the cost and time taken for genetic testing have reduced, making it possible for treatment-focused genetic testing. There are also drugs such as the PARP inhibitors that specifically target the BRCA mutation. Risk management multidisciplinary clinics are designed to quantify risk, and offer advice on preventative strategies. However, such services are only possible in high-income settings. In low-resource settings, the prohibitive cost of testing and the lack of genetic counsellors are major barriers to setting up a breast cancer genetics service. Family history is often not well documented because of the stigma associated with cancer. Breast cancer genetics services remain an unmet need in low- and middle-income countries, where the priority is to optimise access to quality treatment.
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PMID:Global Disparities in Breast Cancer Genetics Testing, Counselling and Management. 3061 Feb 70

Heat stress impairs both pollen germination and pollen tube elongation, resulting in pollination failure caused by energy imbalance. Invertase plays a critical role in the maintenance of energy homoeostasis; however, few studies investigated this during heat stress. Two rice cultivars with different heat tolerance, namely, TLY83 (heat tolerant) and LLY722 (heat susceptible), were subjected to heat stress. At anthesis, heat stress significantly decreased spikelet fertility, accompanied by notable reductions in pollen germination on stigma and pollen tube elongation in ovule, especially in LLY722. Acid invertase (INV), rather than sucrose synthase, contributed to sucrose metabolism, which explains the different tolerances of both cultivars. Under heat stress, larger enhancements in NAD(H), ATP, and antioxidant capacity were found in TLY83 compared with LLY722, whereas a sharp reduction in poly(ADP-ribose) polymerase (PARP) activity was found in the former compared with the latter. Importantly, exogenous INV, 3-aminobenzamide (a PARP inhibitor), sucrose, glucose, and fructose significantly increased spikelet fertility under heat stress, where INV activity was enhanced and PARP activity was inhibited. Therefore, INV can balance the energy production and consumption to provide sufficient energy for pollen germination and pollen tube growth under heat stress.
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PMID:Acid invertase confers heat tolerance in rice plants by maintaining energy homoeostasis of spikelets. 3199 45