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The Ocular Surface Jan 2023Rho kinase inhibitors (ROCKi) have attracted growing multidisciplinary interest, particularly in Ophthalmology where the question as to how they promote corneal... (Review)
Review
A systematic review on the effects of ROCK inhibitors on proliferation and/or differentiation in human somatic stem cells: A hypothesis that ROCK inhibitors support corneal endothelial healing via acting on the limbal stem cell niche.
Rho kinase inhibitors (ROCKi) have attracted growing multidisciplinary interest, particularly in Ophthalmology where the question as to how they promote corneal endothelial healing remains unresolved. Concurrently, stem cell biology has rapidly progressed in unravelling drivers of stem cell (SC) proliferation and differentiation, where mechanical niche factors and the actin cytoskeleton are increasingly recognized as key players. There is mounting evidence from the study of the peripheral corneal endothelium that supports the likelihood of an internal limbal stem cell niche. The possibility that ROCKi stimulate the endothelial SC niche has not been addressed. Furthermore, there is currently a paucity of data that directly evaluates whether ROCKi promotes corneal endothelial healing by acting on this limbal SC niche located near the transition zone. Therefore, we performed a systematic review examining the effects ROCKi on the proliferation and differentiation of human somatic SC, to provide insight into its effects on various human SC populations. An appraisal of electronic searches of four databases identified 1 in vivo and 58 in vitro studies (36 evaluated proliferation while 53 examined differentiation). Types of SC studied included mesenchymal (n = 32), epithelial (n = 11), epidermal (n = 8), hematopoietic and other (n = 8). The ROCK 1/2 selective inhibitor Y-27632 was used in almost all studies (n = 58), while several studies evaluated ≥2 ROCKi (n = 4) including fasudil, H-1152, and KD025. ROCKi significantly influenced human somatic SC proliferation in 81% of studies (29/36) and SC differentiation in 94% of studies (50/53). The present systemic review highlights that ROCKi are influential in regulating human SC proliferation and differentiation, and provides evidence to support the hypothesis that ROCKi promotes corneal endothelial division and maintenance via acting on the inner limbal SC niche.
Topics: Humans; Endothelium, Corneal; Limbal Stem Cells; Adult Stem Cells; Cell Differentiation; Cell Proliferation; Limbus Corneae; Epithelium, Corneal; Stem Cell Niche
PubMed: 36586668
DOI: 10.1016/j.jtos.2022.12.008 -
Actas Urologicas Espanolas Nov 2022Urothelial dysplasia and carcinoma in situ (CIS) are related to recurrence and progression of urothelial carcinoma. Differentiating CIS and dysplasia from reactive... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Urothelial dysplasia and carcinoma in situ (CIS) are related to recurrence and progression of urothelial carcinoma. Differentiating CIS and dysplasia from reactive atypia is often difficult based only on histological features. The integration of histological findings with immunohistochemistry is used in routine practice to make a diagnosis of CIS and, for this purpose, the immunohistochemical markers CK20, CD44, Ki67 and p53 are used to supplement histology. In this work, we aimed to assess CK20, CD44, Ki67 and p53 as immunohistochemical markers in patients with CIS through a systematic review and meta-analysis.
MATERIALS AND METHODS
A systematic review was performed by searching electronic databases for English-language studies published from January 2010 to April 2021. Studies were considered eligible if they evaluated the CK20, CD44, Ki67 and p53 expression in CIS.
RESULTS
In total, 15 references were suitable for quantitative review. The overall rate of CK20, CD44, Ki67 and p53 expression in CIS was 43%, 31%, 44%, 38%, respectively.
CONCLUSIONS
Our study supports the 2014 International Society of Urologic Pathology consensus that histological assessment remains the gold standard to diagnose urothelial CIS and suggests that a very close correlation between morphological, immunohistochemical and clinical data is essential to provide the best management for patients with bladder carcinoma.
Topics: Humans; Biomarkers, Tumor; Carcinoma in Situ; Carcinoma, Transitional Cell; Hyaluronan Receptors; Keratin-20; Ki-67 Antigen; Tumor Suppressor Protein p53; Urinary Bladder; Urinary Bladder Neoplasms; Urothelium
PubMed: 36216762
DOI: 10.1016/j.acuroe.2022.08.013 -
Urologie (Heidelberg, Germany) Jul 2022The treatment options for locally advanced and metastatic urothelial carcinoma (UC) are currently limited to established chemotherapy and immunotherapy protocols.... (Review)
Review
BACKGROUND
The treatment options for locally advanced and metastatic urothelial carcinoma (UC) are currently limited to established chemotherapy and immunotherapy protocols. Targeted treatment is so far restricted to a small subgroup of patients. Urothelial organoid systems could make a decisive contribution in establishing effective personalized treatment options by enabling drug response prediction through testing the sensitivity of individual patients. The aim of this article is to describe the state of the science of clinically applicable organoid systems for UC.
METHODOLOGY
A systematic literature search was conducted in several medical databases (Medline, Cochrane Library) and study registers (ClinicalTrials.gov, the EU Clinical Trials Register and the WHO International Clinical Trials Registry). The search terms and the search strategy were adapted to the databases used.
RESULTS
Overall, 7 studies met the inclusion criteria on the topic of UC organoids. These studies describe the fundamental workflow in establishing organoid systems in patients with tumors of the urinary bladder or the renal pelvis. The success rates in generating organoids from non-muscle-invasive bladder cancer were 70-77% and for muscle-invasive bladder cancer 42%. For patient organoids systematic drug testing was carried out.
CONCLUSION
The generation of UC organoids is feasible and the ex vivo testing of individual treatment forms is possible. Due to the lack of a standardized methodology, their implementation remains experimental at the moment. The methodology has a high potential to provide a personalized treatment concept to patients with urothelial cancer.
Topics: Carcinoma, Transitional Cell; Humans; Organoids; Precision Medicine; Urinary Bladder Neoplasms; Urothelium
PubMed: 35925247
DOI: 10.1007/s00120-022-01854-z -
Journal of Drugs in Dermatology : JDD Feb 2022Rice bran extracts (RB) derived from Oryza sativa are part of cultural skin and hair care practices in Asia. Given the knowledge gap regarding clinical efficacy,...
BACKGROUND
Rice bran extracts (RB) derived from Oryza sativa are part of cultural skin and hair care practices in Asia. Given the knowledge gap regarding clinical efficacy, marketplace availability, and safety, the growing popularity of nutraceuticals calls for better clinician awareness and scientific understanding of their applications and limitations.
OBJECTIVE
To review available scientific evidence regarding therapeutic efficacy, safety, and consumer availability of RB on hair health.
MATERIALS AND METHODS
A primary literature search was conducted using PubMed to identify articles on RB and hair growth in May 2021. A limited market analysis of rice-derivative-containing hair products was also conducted on Amazon.com.
RESULTS
10 studies were analyzed: six regarding the efficacy of RB for hair growth, and four analyzing the safety profile of RB. Topically applied RB increases expression of growth factors and molecular signals which promote cell proliferation in the anagen phase including β-catenin, while inhibiting enzymes responsible for propagating anagen to catagen/telogen transition including TGFβ and Type I 5α-reductase. RB is non-genotoxic, non-cytotoxic, and appropriate for human use in cosmetics. The Amazon.com search yielded 119 rice-containing hair products, reflecting their over-the-counter popularity.
CONCLUSIONS
Current literature is promising for RB promoting hair growth given its ability to increase expression of growth factors and molecular signals associated with maintaining anagen phase, decreasing inflammation, inhibiting 5α-reductase, and promoting melanogenesis. J Drugs Dermatol. 2022;21(2):177-185. doi:10.36849/JDD.6345.
Topics: Cell Proliferation; Cosmetics; Hair; Hair Follicle; Humans; Oryza
PubMed: 35133117
DOI: 10.36849/jdd.6345 -
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 -
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 -
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 -
The Journal of Urology Dec 2020The currently available evidence regarding the prognostic and clinical significance of each variant histology subtype of urothelial bladder cancer remains scarce. We... (Meta-Analysis)
Meta-Analysis
PURPOSE
The currently available evidence regarding the prognostic and clinical significance of each variant histology subtype of urothelial bladder cancer remains scarce. We assessed the prognostic value of variant histology in patients with urothelial carcinoma of the bladder treated with radical cystectomy.
MATERIALS AND METHODS
PubMed®, Web of Science™, Cochrane Library and Scopus® databases were searched for articles published before October 2019 according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. We identified 39 studies comprising 20,544 patients matching our eligibility criteria.
RESULTS
Studies were deemed eligible if they compared overall, cancer specific and recurrence-free survival in patients with urothelial carcinoma of the bladder with and without variant histology. Formal meta-analyses were performed for these outcomes. Variant histology was associated with worse cancer specific (pooled HR 1.37, 95% CI 1.24-1.50), overall (pooled HR 1.44, 95% CI 1.26-1.65) and recurrence-free survival (pooled HR 1.32, 95% CI 1.20-1.45). Subgroup analyses demonstrated that "micropapillary" (pooled HR 1.20, 95% CI 1.02-1.41), "plasmacytoid" (pooled HR 2.03, 95% CI 1.17-3.52) and "small cell" variant histology (HR 3.32, 95% CI 1.98-5.59) were also associated with worse overall survival.
CONCLUSIONS
Variant histology in patients with urothelial carcinoma of the bladder is associated with increased risks of disease recurrence as well as cancer specific and overall mortality. Variant histology was independently associated with overall survival in the "micropapillary," "plasmacytoid" and "small cell" subgroups. Variant histology should be integrated into prognostic tools to guide risk stratification, treatment planning and patient counseling. However, caution should be exercised in interpreting the conclusions drawn from this study given the limitations, which include the heterogeneity of the population of interest and the retrospective nature of the primary data evaluated.
Topics: Carcinoma, Transitional Cell; Cystectomy; Disease-Free Survival; Humans; Neoplasm Recurrence, Local; Prognosis; Risk Assessment; Urinary Bladder; Urinary Bladder Neoplasms; Urothelium
PubMed: 32716694
DOI: 10.1097/JU.0000000000001305 -
Urology Oct 2020Chemoablation is an emerging treatment for urothelial carcinomas. This review provides an overview of the evidence for intracavitary chemoablation in the treatment of...
Chemoablation is an emerging treatment for urothelial carcinomas. This review provides an overview of the evidence for intracavitary chemoablation in the treatment of urothelial carcinomas. The benefits of such agents include a reduction in morbidity and diseased organ preservation. While numerous agents have shown promise, research is limited due to small patient cohorts, varying follow-up, and no standardized methodology to assess response. Therefore, to date, chemoablation has not been widely adopted. This may change as a novel mitomycin formulation has recently been approved for treating low-grade upper tract urothelial carcinoma. Future studies are ongoing which evaluate other promising chemoablation options in urothelial carcinoma.
Topics: Administration, Intravesical; Antineoplastic Agents; Aziridines; BCG Vaccine; Carcinoma, Transitional Cell; Clinical Trials as Topic; Cystoscopy; Deoxycytidine; Epirubicin; Ethanol; Forecasting; Humans; Indolequinones; Injections, Intralesional; Interferon-alpha; Interleukin-2; Mitomycin; Urinary Bladder Neoplasms; Urothelium; Gemcitabine
PubMed: 32540302
DOI: 10.1016/j.urology.2020.05.066 -
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