ABSTRACT
BACKGROUND: Obesity is a known risk factor for developing endometrial cancer. However, the association of obesity with endometrial cancer (EC) outcomes has not been clearly established. This study examined how outcomes in women with early stage EC vary with body composition measured via computed tomography (CT). METHODS: In this retrospective study, patients diagnosed with EC international Federation of Gynecology and Obstetrics stages I-III and available CT scans were included. Automatica software was used to assess the areas of visceral adipose tissue, subcutaneous adipose tissue (SAT), and intermuscular adipose tissue (IMAT) and skeletal muscle area. RESULTS: Of 293 patient charts assessed, 199 met eligibility criteria. Median body mass index (BMI) was 32.8 kg/m2 (interquartile range [IQ] = 26.8-38.9); 61.8% had histologic subtype endometrioid carcinoma. Adjusted for age, international Federation of Gynecology and Obstetrics stage, and histologic subtype, a BMI of at least 30 vs less than 30 kg/m2 was associated with lower endometrial cancer-specific survival (ECSS) (hazard ratio [HR] = 2.32, 95% confidence interval [CI] = 1.27 to 4.25) and overall survival (OS) (HR = 2.7, 95% CI = 1.35 to 5.39). Higher IMAT 75th vs 25th percentile and SAT of at least 225.6 vs less than 225.6 cm2 were associated with lower ECSS (HR = 1.53, 95% CI = 1.1 to 2.13, and HR = 2.57, 95% CI = 1.13 to 5.88) and OS (HR = 1.50, 95% CI = 1.11 to 2.02, and HR = 2.46, 95% CI = 1.2 to 5.01), respectively. The association of visceral adipose tissue (75th vs 25th percentile) with ECSS and OS was not statistically significant (HR = 1.42, 95% CI = 0.91 to 2.22, and HR = 1.24, 95% CI = 0.81 to 1.89). CONCLUSION: Higher BMI, IMAT, and SAT were associated with higher mortality from EC and lower OS. A better understanding of the mechanisms underlying these relationships could inform strategies to improve patient outcomes.
Subject(s)
Carcinoma, Endometrioid , Endometrial Neoplasms , Humans , Female , Retrospective Studies , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/epidemiology , Endometrial Neoplasms/etiology , Carcinoma, Endometrioid/pathology , Obesity/complications , Obesity/diagnosis , Obesity/epidemiology , Body CompositionABSTRACT
OBJECTIVE: The contribution of actomyosin contractile rings in the wound healing program of somatic cells as never been directly assessed. This contrast with the events characterising the wound healing response of in wounded Xenopus oocytes, in which formation and contraction of an actomyosin ring provides a platform for cytoskeletal repair and drives the restoration of proper plasma membrane composition at the site of injury. As such, we aimed to characterize, using high-resolution live-cell confocal microscopy, the cytoskeletal repair dynamics of HeLa cells. RESULTS: We confirm here that the F-actin enrichment that characterizes the late repair program of laser-wounded cells is mostly uniform and is not associated with co-enrichment of myosin-II or the formation of concentric zones of RhoA and Cdc42 activity.
Subject(s)
Actins/metabolism , Cell Membrane/metabolism , Mammals/metabolism , Polymerization , Single-Cell Analysis/methods , Actomyosin/metabolism , Animals , Cytoskeleton/metabolism , HeLa Cells , Humans , Kinetics , Microscopy, Confocal , cdc42 GTP-Binding Protein/metabolism , rhoA GTP-Binding Protein/metabolismABSTRACT
Cytokinesis and single-cell wound repair both involve contractile assemblies of filamentous actin (F-actin) and myosin II organized into characteristic ring-like arrays. The assembly of these actomyosin contractile rings (CRs) is specified spatially and temporally by small Rho GTPases, which trigger local actin polymerization and myosin II contractility via a variety of downstream effectors. We now have a much clearer view of the Rho GTPase signaling cascade that leads to the formation of CRs, but some factors involved in CR positioning, assembly, and function remain poorly understood. Recent studies show that this regulation is multifactorial and goes beyond the long-established Ca2+ -dependent processes. There is substantial evidence that the Ca2+ -independent changes in cell shape, tension, and plasma membrane composition that characterize cytokinesis and single-cell wound repair also regulate CR formation. Elucidating the regulation and mechanistic properties of CRs is important to our understanding of basic cell biology and holds potential for therapeutic applications in human disease. In this review, we present a primer on the factors influencing and regulating CR positioning, assembly, and contraction as they occur in a variety of cytokinetic and single-cell wound repair models. Anat Rec, 301:2051-2066, 2018. © 2018 Wiley Periodicals, Inc.
