Platinum sensitivity is an important prognostic factor in patients with ovarian cancer. Chromodomain-helicase-DNA-binding protein 4 (CHD4) is a core member of the nucleosome remodeling and deacetylase complex, which functions as a chromatin remodeler. Emerging evidence indicates that CHD4 could be a potential therapeutic target for cancer therapy. The purpose of this study was to clarify the role of CHD4 in ovarian cancer and investigate its therapeutic potential focusing on platinum sensitivity. In an analysis of the Cancer Genome Atlas ovarian cancer dataset, CHD4 gene amplification was associated with worse overall survival. CHD4 mRNA expression was significantly higher in platinum-resistant samples in a subsequent clinical sample analysis, suggesting that CHD4 overexpression conferred platinum resistance to ovarian cancer cells, resulting in poor patient survival. In concordance with these findings, CHD4 knockdown enhanced the induction of apoptosis mediated by cisplatin in ovarian cancer cells TOV21G and increased cisplatin sensitivity in multiple ovarian cancer cells derived from different subtypes. However, CHD4 knockdown did not affect the expression of RAD51 or p21, the known targets of CHD4 in other cancer types that can modulate platinum sensitivity. Knockdown and overexpression assays revealed that CHD4 positively regulated the expression of multi-drug transporter MDR1 and its coding protein p-glycoprotein. In addition, a first-in-class CHD4/SMARCA5 inhibitor ED2-AD101 showed synergistic interactions with cisplatin. Our findings suggest that CHD4 mediates platinum sensitivity by modulating MDR1 expression in ovarian cancer. Further, CHD4 suppression has a potential to be a novel therapeutic strategy in combination with platinum agents.
Multidrug resistant bacteria are marching and winning. The entire human race is at risk and new, effective antibiotics are needed for survival. Several notable routines to develop novel antibiotics are briefly compared here and possible new strategies are proposed. Key words include but not limited to nanotechnology, metal nanoparticles, natural product, medicinal plants, folk medicine, ethnopharmacology, computer-based screening, synergistic antibacterial activity, genomics, peptides, inhibitor, and structure-based virtual screening.
Fetal lung is one of the organs of interest for researchers since a long time. Though, detailed morphometric studies about adult lung weight are there in the literature but weight of lungs at different stages in the foetal period is far less available. Hence, the present study attempted to find out the relationship between the foetal lungs in relation with its development in different gestational weeks. The study was carried out on 40 human fetuses of known gestational age in the Department of Anatomy, Manipal College of Medical Sciences, Pokhara, Nepal. Ethical approval was granted by the Institutional Review Committee (IRC), MCOMS, Pokhara. The weight of the fetuses and fetal lung was measured in grams on digital weighing machine. The mean values of all parameters by gestational age was calculated and analyzed. The data was represented graphically by using appropriate statistical analysis. In the present study the body weight of fetuses showed gradual increase from 10 th week to 38 th weeks of gestation. The weight of right lung was seen more than the weight of left lung throughout the gestational weeks. Evaluating body and organ weights and measurements against known standards is an important part of perinatal pathology and also provides new insights for understanding and developing knowledge in both normal and pathological conditions.
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