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Frontiers in Endocrinology 2020Abnormal endometrial receptivity is one of the major causes of embryo implantation failure and infertility. The plasma membrane transformation (PMT) describes the...
BACKGROUND
Abnormal endometrial receptivity is one of the major causes of embryo implantation failure and infertility. The plasma membrane transformation (PMT) describes the collective morphological and molecular alterations occurring to the endometrial luminal epithelium across the mid-secretory phase of the menstrual cycle to facilitate implantation. Dysregulation of this process directly affects endometrial receptivity and implantation. Multiple parallels between these alterations to confer endometrial receptivity in women have been drawn to those seen during the epithelial-mesenchymal transition (EMT) in tumorigenesis. Understanding these similarities and differences will improve our knowledge of implantation biology, and may provide novel therapeutic targets to manage implantation failure.
METHODS
A systematic review was performed using the Medline (Ovid), Embase, and Web of Science databases without additional limits. The search terms used were "(plasma membrane* or cell membrane*) and transformation*" and "endometrium or endometrial." Research studies on the PMT or its regulation in women, discussing either the endometrial epithelium, decidualized stroma, or both, were eligible for inclusion.
RESULTS
A total of 198 articles were identified. Data were extracted from 15 studies that matched the inclusion criteria. Collectively, these included studies confirmed the alterations occurring to the endometrial luminal epithelium during the PMT are similar to those seen during the EMT. Such similarities included alterations to the actin cytoskeleton remodeling of adherens junctions, integrin expression and epithelial-stromal communication. These were also some differences between these processes, such as the regulation of tight junctions and mucins, which need to be further researched.
CONCLUSIONS
This review raised the prospect of shared and distinct mechanisms existing in PMT and EMT. Further investigation into similarities between the PMT in the endometrium and the EMT in tumorigenesis may provide new mechanistic insights into PMT and new targets for the management of implantation failure and infertility.
Topics: Animals; Cell Polarity; Embryo Implantation; Endometrium; Epithelial Cells; Epithelial-Mesenchymal Transition; Female; Humans
PubMed: 33193109
DOI: 10.3389/fendo.2020.596324 -
European Journal of Cancer (Oxford,... Jul 2021Platinum-based combination chemotherapy is the standard treatment for patients with chemotherapy-eligible metastatic urothelial carcinoma (mUC). Immune-checkpoint... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Platinum-based combination chemotherapy is the standard treatment for patients with chemotherapy-eligible metastatic urothelial carcinoma (mUC). Immune-checkpoint inhibitors (ICIs) are currently assessed in this setting. This review aimed to assess the role of ICIs alone or in combination as first-line treatment in chemotherapy-eligible patients with mUC.
METHODS
Multiple databases were searched for articles published until November 2020. Studies were deemed eligible if they compared overall survival (OS), progression-free survival (PFS), objective response rates (ORRs), complete response rates (CRRs), durations of response (DORs) and adverse events (AEs) in chemotherapy-eligible patients with mUC.
RESULTS
Three studies met our eligibility criteria. ICI combination therapy was associated with significantly better OS and PFS, higher CRR and longer DOR than chemotherapy alone (hazard ratio [HR]: 0.85, 95% confidence interval [CI]: 0.76-0.94, P = 0.002; HR: 0.80, 95% CI: 0.71-0.90, P = 0.0002; odds ratio [OR]: 1.48, 95% CI: 1.12-1.96, P = 0.006; and mean difference: 1.39, 95% CI: 0.31-2.46, P = 0.01, respectively). ICI-chemotherapy combination therapy was also associated with significantly better OS and PFS, higher ORR and CRR and longer DOR than chemotherapy alone. Although OS and PFS benefits of ICI combination therapy were larger in patients with high expression of programmed death-ligand 1 (PD-L1), PD-L1 low expression patients also had a benefit; HR for OS (high PD-L1: HR 0.79 versus low PD-L1: HR 0.89) and PFS (high PD-L1: HR 0.74 versus low PD-L1: HR 0.82). ICI monotherapy was not associated with better oncological outcomes but was associated with better safety outcomes than chemotherapy alone.
CONCLUSIONS
Our analysis indicates a superior oncologic benefit to first-line ICI combination therapies in patients with chemotherapy-eligible mUC over standard chemotherapy. In contrast, ICI monotherapy was associated with favorable safety outcomes compared with chemotherapy but failed to show its superiority over chemotherapy in oncological benefits. PD-L1 status alone cannot help guide treatment decision-making. However, caution should be exercised in interpreting the conclusions drawn from this study, given that there is the heterogeneity of the population of interest, risk of bias and the nature of the studies evaluated whose data remain immature or unpublished.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; B7-H1 Antigen; Carcinoma; Clinical Decision-Making; Female; Humans; Immune Checkpoint Inhibitors; Male; Middle Aged; Patient Selection; Progression-Free Survival; Time Factors; Urinary Bladder Neoplasms; Urothelium
PubMed: 33962359
DOI: 10.1016/j.ejca.2021.03.049 -
Cancer Biology & Therapy Sep 2020Colorectal cancer (CRC) is a leading cause of cancer-related death. Epithelial-mesenchymal transition (EMT) is a major process in tumor metastasis development. This...
BACKGROUND
Colorectal cancer (CRC) is a leading cause of cancer-related death. Epithelial-mesenchymal transition (EMT) is a major process in tumor metastasis development. This systematic review aims to describe the role of long non-coding RNA (lncRNA) in EMT in CRC.
METHODS
The electronic databases, PubMed, Cochrane, and EMBASE, were searched from January1990 to June 2019 to identify studies examining lncRNA and their role in mediating EMT in CRC. Studies examining clinical specimens and/or in vitro experiments were included.
RESULTS
In 61 identified studies, 54 lncRNAs were increased in CRC compared to normal colorectal epithelium. Increased lncRNA expression was frequently associated with worse survival. Many lncRNAs mediate their effect through competitive endogenous RNA or transcription factor regulation. The ZEB1, 2/E-cadherin, Wnt/β-catenin signaling, and chromatin remodeling pathways are discussed in particular.
CONCLUSIONS
lncRNAs are major regulators of EMT and predictor adverse outcome in CRC patients. Future research must focus on delineating lncRNA function prior to potential clinical use.
Topics: Colorectal Neoplasms; Epithelial-Mesenchymal Transition; Humans; Neoplasm Metastasis; RNA, Long Noncoding
PubMed: 32730165
DOI: 10.1080/15384047.2020.1794239 -
Medicina Oral, Patologia Oral Y Cirugia... Mar 2020Oral potentially malignant disorders (OPMDs) comprise a range of clinical-pathological alterations that are frequently characterized as architectural and cytological...
BACKGROUND
Oral potentially malignant disorders (OPMDs) comprise a range of clinical-pathological alterations that are frequently characterized as architectural and cytological derangements upon histological analysis. Epithelial-mesenchymal transition (EMT) has been proposed as a critical mechanism for the acquisition of the malignant phenotype in neoplastic epithelial processes. This study aims to systematically review the current findings on the immunohistochemical expression of epithelial-mesenchymal transition markers in oral potentially malignant disorders and to evaluate their possible application as biomarkers associated with the progression of oral epithelial dysplasias.
MATERIAL AND METHODS
A systematic search was performed in the following databases: PubMed, EMBASE, Chinese BioMedical Literature Database, and Cochrane Library. Articles that evaluated the relationship between the expression of EMT markers and the degree of oral epithelial dysplasia were selected for the systematic review. The quality of each eligible study was evaluated by independent reviewers that used operationalized prognostic biomarker reporting guidelines (REMARK).
RESULTS
Seventeen articles met all inclusion criteria and were selected. The EMT markers analyzed exhibited an important association with the prognosis of the cases evaluated. The results showed a progressive increase in the expression of nuclear transcription factors and markers of mesenchymal differentiation, as well as negative regulation of epithelial and cell adhesion markers, according to the stage of oral epithelial dysplasia.
CONCLUSIONS
The dysregulation of expression of important EMT components in oral dysplastic epithelium is a potential prognostic marker in OPMDs.
Topics: Biomarkers; Biomarkers, Tumor; Epithelial-Mesenchymal Transition; Prognosis
PubMed: 31967982
DOI: 10.4317/medoral.23305