PCOS diagnosis in adolescents: the timeline of a controversy in a systematic review.

Study objective Polycystic ovary syndrome (PCOS) in adolescence, a disorder of exclusion, has proved to be a timeless diagnostic challenge for the clinician. Since 1990, several attempts to provide clear diagnostic criteria have been published, most of the time leading to inconsistencies. We attempted to elucidate the controversies and convergences of this subject by conducting a systematic review of the literature concerning official guidelines or proposed criteria for the diagnosis of PCOS in adolescent girls. Design Based on a term search sequence via electronic databases such as Pubmed, Cochrane, Embase, Scopus and a hands-on review of references and learned societies, all available data were classified and analyzed. Single case reports, original studies with adult population or articles with incomplete diagnostic guidelines were excluded. Results Twelve reports dated from 2006 to 2018 fulfilled the inclusion criteria. Seven of them were endorsed or published by learned societies. All suggested a stricter diagnosis than in adulthood. Polycystic ovarian morphology was used as a necessary criterion only in three guidelines, and there was a tendency for a more objective diagnosis of hyperandrogenism, defined either by clinical features or by biochemical hyperandrogenemia, although in one case both were required. Conclusion Irregular menstrual cycles, allowing for an interval of at least 2 years postmenarche, and hyperandrogenism, usually reinforced by biochemical confirmation, are the main accepted features for PCOS diagnosis in adolescence. Discrepancies among endocrine and reproductive medicine societies still remain, although recent intensified attempts at reaching a consensus should allow for more universally accepted diagnostic criteria.

Excision-repair-cross-complement-1 protein as a prognostic factor in patients with advanced non-small cell lung cancer treated with platinum-based first-line chemotherapy.

Excision-repair-cross-complement-1 (ERCC1) protein expression in tumor cells has been associated with resistance to platinum compounds, the backbone of treatment in NSCLC. In the current study the impact of the tumoral ERCC1 protein expression on the outcome of patients with advanced stage NSCLC treated with platinum-based chemotherapy, was investigated. Ninety-four patients with inoperable stage III-IV NSCLC, treated with platinum-based first-line chemotherapy, were retrospectively analyzed. Pretreatment tumor samples were analyzed for ERCC1 protein expression using immunohistochemistry. Response to treatment, time to tumor progression (TTP), and overall survival (OS) were correlated with patients' clinicopathological characteristics and ERCC1 protein expression on tumor cells. ERCC1 protein low expression was detected in 39 (41.5%) patients and did not correlate with patients' clinicopathological characteristics or response to chemotherapy. However, ERCC1 protein low expression showed a trend for better disease control rate (p = 0.059), longer TTP (5.3 vs. 3.2 months; p = 0.051) and significantly longer OS (18.7 vs. 9.7 months; p = 0.009). ERCC1 could have a role in refining prognosis and thus individualizing chemotherapy for advanced stage NSCLC.

DNA repair gene polymorphisms predict favorable clinical outcome in advanced non-small-cell lung cancer.

BACKGROUND: Genetic polymorphisms of genes involved in DNA repair and glutathione metabolic pathways may affect patients' response to platinum-based chemotherapy. We retrospectively assessed whether single nucleotide polymorphisms (SNP) of DNA-repair genes ERCC1, XPD, XRCC1 and glutathione S-transferase genes GSTP1, GSTT1 and GSTM1 predict overall survival (OS), response and toxicity in 119 non-small-cell lung cancer (NSCLC) patients treated with platinum-based regimens as first- or second-line chemotherapy. PATIENTS AND METHODS: Patients' genotypes were determined by PCR-RFLP and sequencing approaches. RESULTS: ERCC1 (Asn118Asn) genotype was significantly associated with response to treatment. Patients with either one or two C alleles (C/C, C/T) at Asn118Asn were more likely to respond to platinum-based chemotherapy compared with those without the C allele (Odds ratio, 0.10; 95% CI, 0.013-0.828; P = .033, by binary logistic regression). There was a significant association between the ERCC1 C8092A polymorphism and OS (P = .009, by log-rank test), with median survival times of 9.8 (C/C) and 14.1 (C/A or A/A) months, respectively, suggesting that any copies of the A allele were associated with an improved outcome. Cox's multivariate analysis suggested that the joint effect of ERCC1 polymorphic variants (C8092A and N118N) (0 vs. 2, hazard ratio 2.5; 95% CI, 1.26-4.96; P = .009) as well as the XRCC1 N399Q polymorphism (AA vs. GA/GG, hazard ratio 3.1; 95% CI, 1.4-6.8; P = .005) were independent prognostic factors for OS in advanced NSCLC patients treated with platinum-based chemotherapy. CONCLUSION: These findings support the notion that assessment of genetic variations of ERCC1 and XRCC1 could facilitate therapeutic decisions for individualized therapy in advanced NSCLC.

Estrogen exerts neuroprotective effects via membrane estrogen receptors and rapid Akt/NOS activation.

The neuroprotective role of estrogen (E2) is supported by a multitude of experimental and epidemiological data, although its mode of action is not fully understood. The present work was conducted to study the underlying mechanisms of its neuroprotective action, using the rat cell line PC12, an established model for neuronal cell apoptosis and survival. Our results show that E2 (but not androgens or progestins) prevent growth inhibition and apoptosis of PC12 cells, induced by serum deprivation. Several mechanisms of action were investigated: 1) intracellular estrogen receptors (ERs) have been identified but do not appear to mediate the protective effect of E2. 2) The antioxidant properties of E2 cannot explain their protective actions at the concentrations used (10(-12)-10(-6) M). 3) Finally, membrane sites for E2 have been identified, and the underlying initial signaling cascade (2-30 min after E2) has been tested, showing Ca(2+) mobilization-->PI3K activation-->Akt phosporylation-->NOS activation. Inhibition of PI3K or NOS completely reversed the anti-apoptotic effect of E2. These results suggest a new mechanism of neuroprotective action of estrogen.