Targeting P16INK4A in uterine serous carcinoma through inhibition of histone demethylation.

Targeting P16INK4A in uterine serous carcinoma through inhibition of histone demethylation. Oncol Rep. 2019 Mar 14;: Authors: Xiao Z, He Y, Liu C, Xiang L, Yi J, Wang M, Shen T, Shen L, Xue Y, Shi H, Liu P Abstract Uterine serous carcinoma (USC) is a subtype of endometrial cancer. Compared with endometrial endometroid carcinoma, the majority of USC cases are more aggressive. Cyclin-dependent kinase inhibitor 2A (P16INK4A) is a canonical tumor suppressor that blocks cell cycle progression; however, P16INK4A is overexpressed in USC. The aim of the present study was to determine the role of P16INK4A in P16INK4A‑positive endometrial cancer, with the hope of elucidating a novel therapeutic approach for this type of malignancy. A total of 2 endometrial cancer cell lines, ETN‑1 and EFE‑184, were selected for further investigation, due to them being known to express high levels of P16INK4A. Using short hairpin RNA targeting P16INK4A, P16INK4A was downregulated in these cancer cell lines. Cell viability and migration were examined via 2D/3D clonogenic and wound healing assays. Subsequently, GSK‑J4, a histone demethylase inhibitor, was employed to deplete P16INK4A in these cancer cell lines and an ex vivo culture system of a patient‑derived xenograft (PDX) endometrial tumor sample. Following P16INK4A knockdown, the proliferation and migration of ETN‑1 and EFE‑184 cells markedly declined. When exposed to GSK‑J4, the levels of KDM6B and P16INK4A were ...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research

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We report a case of misdiagnosed endometrial cancer by D&C, but with a positive cytopathological finding. Following that, a meta-analysis including 4,179 patients of endometrial diseases with cyto-histopathological results was performed to assess the value of the endometrial cytological method in endometrial cancer diagnosis. The pooled sensitivity and specificity of the cytological method in detecting endometrial atypical hyperplasia or cancer was 0.91[95% confidence interval (CI) 0.74–0.97] and 0.96 (95% CI 0.90–0.99), respectively. The pooled positive likelihood ratio and negative likelihood ratio was 25.4 (...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Abstract OBJECTIVE: Endocrine therapy is often considered as a treatment for hormone-responsive gynecologic malignancies. In breast cancer, activating mutations in the estrogen receptor (mutESR1) contribute to therapeutic resistance to endocrine therapy, especially aromatase inhibitors (AIs). The purpose of this study was to evaluate the frequency and clinical relevance of ESR1 genomic alterations in gynecologic malignancies. METHODS: DNA from FFPE tumor tissue obtained during routine clinical care for 9645 gynecologic malignancies (ovary, fallopian tube, uterus, cervix, vagina, vulvar, and placenta) was anal...
Source: Gynecologic Oncology - Category: Cancer & Oncology Authors: Tags: Gynecol Oncol Source Type: research
Vit Weinberger1, Marketa Bednarikova2, Jitka Hausnerova3, Petra Ovesna4, Petra Vinklerova1, Lubos Minar1, Michal Felsinger1, Eva Jandakova3, Marta Cihalova3 and Michal Zikan5* 1Department of Gynecology and Obstetrics, University Hospital in Brno and Masaryk University, Brno, Czechia2Department of Internal Medicine – Hematology and Oncology, University Hospital in Brno and Masaryk University, Brno, Czechia3Department of Pathology, University Hospital in Brno and Masaryk University, Brno, Czechia4Faculty of Medicine, Institute of Biostatistics and Analyses, Masaryk University, Brno, Czechia5Institute of Biostati...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
CONCLUSION: Our findings showed similar survival outcomes for adjuvant radiotherapy and chemotherapy in stage I UPSC and CCC of the endometrium. Further large study with analysis stratified by MI or LVSI is required. PMID: 30887761 [PubMed - in process]
Source: Journal of Gynecologic Oncology - Category: OBGYN Tags: J Gynecol Oncol Source Type: research
The aim was to investigate MAGE-A4 and MAGE-A1 protein expression in high-grade endometrial cancer and determine its correlation with histologic subtype, FIGO stage, presence of vascular invasion, disease free, and overall survival. Immunohistochemical staining was performed by using 77B (MAGE-A1) and 57B (MAGE-A4) monoclonal antibodies on paraffin-embedded sections from high-grade endometrial cancers diagnosed in University Hospital Split between 1998 and 2011 (n=77). Median follow-up time for survivors was 48 mo. MAGE-A4 was found to be expressed in 33% of endometrioid type endometrial cancers grade 3 and in 27% o...
Source: International Journal of Gynecological Pathology - Category: Pathology Tags: PATHOLOGY OF THE CORPUS: ORIGINAL ARTICLES Source Type: research
This study is aimed to assess the prevalence of unanticipated gynecologic neoplasms in anterior pelvic exenteration specimens. A retrospective review of pathology reports to identify women undergoing anterior pelvic exenteration for UC was performed (N=221), and incidentally discovered gynecologic tract neoplasms were recorded. Concomitant malignant or premalignant lesions of the gynecologic tract were identified in 8 patients (3.6%). These included endometrial adenocarcinoma [endometrioid type, International Federation of Gynecology and Obstetrics grade 1 (n=2, 0.9%)], cervical high-grade squamous intraepithelial lesion (...
Source: International Journal of Gynecological Pathology - Category: Pathology Tags: PATHOLOGY OF THE UPPER GENITAL TRACT: ORIGINAL ARTICLES Source Type: research
ConclusionTP53 mutations are potential prognostic markers that can be used to further improve the accuracy of predicting survival and disease-free survival times of cancer patients.
Source: Journal of Cancer Research and Clinical Oncology - Category: Cancer & Oncology Source Type: research
CONCLUSIONS: Our results suggest brachytherapy benefits stages I-II serous/clear cell cancers, chemotherapy benefits stage III serous/clear cell cancers, and both chemotherapy and brachytherapy benefit stages I-II serous cancers. PMID: 30551884 [PubMed - as supplied by publisher]
Source: Gynecologic Oncology - Category: Cancer & Oncology Authors: Tags: Gynecol Oncol Source Type: research
Conclusions: PIK3CA amplification is a strong prognostic marker and a potential marker for the aggressive SCNA-high subgroup of UCEC. Although PIK3CA amplification associates with some surrogate measures of increased PI3K activity, markers for AKT1-3 and MTOR signaling are decreased, suggesting that this signaling is not a predominant pathway to promote cancer growth of aggressive serous-like UCEC. Moreover, these associations may reflect features of the SCNA-high subgroup of UCEC rather than effects of PIK3CA amplification itself. Clin Cancer Res; 1-12. ©2018 AACR. PMID: 30442683 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
Abstract OBJECTIVE: Mutational signatures provide insights into the biological processes shaping tumor genomes and may inform patient therapy. We sought to define the mutational signatures of i) endometrioid and serous endometrial carcinomas (ECs), stratified into the four molecular subtypes, ii) uterine carcinosarcomas, and iii) matched primary and metastatic ECs. METHODS: Whole-exome sequencing MC3 data from primary endometrioid and serous carcinomas (n = 232) and uterine carcinosarcomas (n = 57) from The Cancer Genome Atlas (TCGA), and matched primary and metastatic ECs (n = 61, 26 patients) we...
Source: Gynecologic Oncology - Category: Cancer & Oncology Authors: Tags: Gynecol Oncol Source Type: research
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