STK295900, a Dual Inhibitor of Topoisomerase 1 and 2, Induces G<inf>2</inf> Arrest in the Absence of DNA Damage

STK295900, a small synthetic molecule belonging to a class of symmetric bibenzimidazoles, exhibits antiproliferative activity against various human cancer cell lines from different origins. Examining the effect of STK295900 in HeLa cells indicates that it induces G2 phase arrest without invoking DNA damage. Further analysis shows that STK295900 inhibits DNA relaxation that is mediated by topoisomerase 1 (Top 1) and topoisomerase 2 (Top 2) in vitro. In addition, STK295900 also exhibits protective effect against DNA damage induced by camptothecin. However, STK295900 does not affect etoposide-induced DNA damage. Moreover, STK295900 preferentially exerts cytotoxic effect on cancer cell lines while camptothecin, etoposide, and Hoechst 33342 affected both cancer and normal cells. Therefore, STK295900 has a potential to be developed as an anticancer chemotherapeutic agent. © 2013 Kim et al

Cdk2 Is Required for p53-Independent G2/M Checkpoint Control

The activation of phase-specific cyclin-dependent kinases (Cdks) is associated with ordered cell cycle transitions. Among the mammalian Cdks, only Cdk1 is essential for somatic cell proliferation. Cdk1 can apparently substitute for Cdk2, Cdk4, and Cdk6, which are individually dispensable in mice. It is unclear if all functions of non-essential Cdks are fully redundant with Cdk1. Using a genetic approach, we show that Cdk2, the S-phase Cdk, uniquely controls the G2/M checkpoint that prevents cells with damaged DNA from initiating mitosis. CDK2-nullizygous human cells exposed to ionizing radiation failed to exclude Cdk1 from the nucleus and exhibited a marked defect in G2/M arrest that was unmasked by the disruption of P53. The DNA replication licensing protein Cdc6, which is normally stabilized by Cdk2, was physically associated with the checkpoint regulator ATR and was required for efficient ATR-Chk1-Cdc25A signaling. These findings demonstrate that Cdk2 maintains a balance of S-phase regulatory proteins and thereby coordinates subsequent p53-independent G2/M checkpoint activation

Validating alcohol use measures among male drinkers in Goa: implications for research on alcohol, sexual risk, and HIV in India.

Assessment of heavy drinking patterns is vital for HIV/AIDs studies in India and developing countries. A population survey in northern Goa included urban and rural male drinkers (n = 743) who completed a new Fractional Graduated Frequencies (F-GF) alcohol patterns measure assessing seven beverage types and drink sizes for the largest daily amount, then drinking frequencies at fractional amounts. The new measure was compared to a simpler quantity-frequency (QF) summary and, in a validity subsample of hazardous drinkers (n = 56), 28-day diaries of drinking events. Approximately 56% of total volume came from peak drinking (averaging 60 g ethanol/day). For AUDIT-based Hazardous Drinkers, QF and F-GF volumes (drinks/day) were not significantly different from diary volume (correlations 0.65 and 0.57, respectively). F-GF well captured the profile of daily amounts in drinking event data. In addition, the F-GF showed evidence of better predicting any sexual risk behavior or partner violence perpetration than the QF measure. Summary drinking pattern measures, especially the new F-GF, are more cost efficient than intensive event records, and appear valid when carefully assessing quantities with local beverage types and drink ethanol content

Abuse and other correlates of common mental disorders in youth: a cross-sectional study in Goa, India.

PURPOSE: There is a paucity of known correlates of common mental disorders (CMDs) among the youth age group in India. This analysis aims to determine risk factors associated with a probable diagnosis of CMD in a youth sample in India. METHODS: This is a secondary analysis of data collected via a door-to-door (community) survey of 3,662 youth (aged 16-24 years) in selected urban and rural areas in Goa. The urban and rural areas were selected based on their engagement with a Goan-based mental health charity organisation, Sangath. Point prevalence of CMD was estimated using the general health questionnaire-12 (GHQ-12). Multivariate logistic regression analyses determined factors associated with CMD and associations were stratified by gender. RESULTS: In total, 3,649 (1,796 urban; 1,853 rural) youth were assessed for probable diagnosis of CMD. There was an almost equal ratio of males (49 %) to females (51 %) in the sample. During the time of the survey, 91 % of the sample was residing with parents, with 83 % being between the ages of 22 and 24 years living with parents. A small proportion of the sample never attended school (1.1 %) with the rest either educated, employed or unemployed. The point prevalence of probable CMD in the sample was 7.87 %; 95 % CI 7.01-8.80 %. Those living in urban areas had a higher prevalence of CMD (9.12 %; 95 % CI 7.90-10.52 %) compared to those living in rural areas (6.60 %; 95 % CI 5.50-7.82 %). After adjusting for a range of potential confounders, independent risk factors for CMD were being older, i.e., between 22- and 24-years old, (OR 1.60; 95 % CI 1.10-2.24; p = 0.015), residing in urban areas (OR 1.51; 95 % CI 1.12-2.04; p = 0.007), physical abuse (beaten in the last 3 months) by parents, teachers or others (OR 3.10; 95 % CI 2.11-4.51; p < 0.001), sexual harassment (OR 2.01; 95 % CI 1.30-3.20; p = 0.003) and sexual abuse (OR 2.54; 95 % CI 1.94-3.33; p < 0.001). Being able to talk about personal problems (OR 0.52; 95 % CI 0.34-0.80; p = 0.003) was a protective factor. After stratifying by gender, sexual harassment, physical and sexual abuse were associated with a likely CMD diagnosis in females and males. CONCLUSIONS: Sexual and recent physical abuses were independent risk factors for CMD in both genders. In addition, being older and being able to discuss problems were associated with CMD diagnosis in females but not in males