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https://www.readbyqxmd.com/read/29662608/wt1-p53-and-p16-expression-in-the-diagnosis-of-low-and-high-grade-serous-ovarian-carcinomas-and-their-relation-to-prognosis
#1
Luis Felipe Sallum, Liliana Andrade, Susana Ramalho, Amanda Canato Ferracini, Rodrigo de Andrade Natal, Angelo Borsarelli Carvalho Brito, Luis Otávio Sarian, Sophie Derchain
Objective: To evaluate the diagnostic and prognostic value of the immunohistochemical expression of WT1, p53 and p16 in low- (LGSOCs) and high-grade serous ovarian carcinomas (HGSOCs). Results: HGSOC had a significantly higher proportion of advanced stage disease, higher CA125 levels, higher proportion of post-surgery residual disease and higher recurrence or disease progression. WT1 was expressed in 71.4% of LGSOCs and in 57.1% of HGSOCs ( p = 0.32). Focal and/or complete absence of p53 expression with negative p16 expression was found in 90...
March 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29644000/cdk4-6-inhibition-as-maintenance-and-combination-therapy-for-high-grade-serous-ovarian-cancer
#2
Mangala Iyengar, Patrick O'Hayer, Alex Cole, Tara Sebastian, Kun Yang, Lan Coffman, Ronald J Buckanovich
High grade serous ovarian cancer (HGSOC) is a disease with a high relapse rate and poor overall survival despite good initial responses to platinum-based therapy. Cell cycle inhibition with targeted CDK4/6 inhibitors is a new therapeutic approach showing promise as a maintenance therapy in cancer. As multiple genes in the CDK4/6 pathway are commonly mutated or dysregulated in ovarian cancer, we evaluated the efficacy of the CDK4/6 inhibitor Ribociclib alone, in combination with chemotherapy, and as maintenance therapy in several models of HGSOC...
March 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29620165/foxd1-is-targeted-by-mir-30a-5p-and-mir-200a-5p-and-suppresses-the-proliferation-of-human-ovarian-carcinoma-cells-by-promoting-p21-expression-in-a-p53-independent-manner
#3
Yu Wang, Chunping Qiu, Nan Lu, Zhaojian Liu, Chengjuan Jin, Chenggong Sun, Hualei Bu, Hongfeng Yu, Samina Dongol, Beihua Kong
High-grade serous ovarian carcinoma (HGSOC) accounts for the highest number of deaths among patients with epithelial ovarian cancer. However, the molecular mechanisms underlying HGSOC tumorigenesis are currently unclear. In the present study, a lentiviral expression system was employed to manipulate forkhead box D1 (FOXD1) expression in ovarian cancer cells. Immunohistochemical staining was used to examine the expression of FOXD1 in tissue samples. Clonogenic and MTT assays were employed to evaluate cell proliferation, and flow cytometry was applied for cell cycle analysis...
April 4, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29584920/genomic-rearrangement-signatures-and-clinical-outcomes-in-high-grade-serous-ovarian-cancer
#4
R Tyler Hillman, Gary B Chisholm, Karen H Lu, P Andrew Futreal
Background: To identify clinically relevant genomic rearrangement signatures in high-grade serous ovarian cancer (HGSOC), we conducted a retrospective analysis of sequenced HGSOC whole-tumor genomes. Methods: Clinical data and whole-genome sequencing (WGS) reads were obtained for primary HGSOC tumors sequenced by the Australian Ovarian Cancer Study (AOCS; n = 80). Genomic rearrangements were identified, and non-negative matrix factorization (NMF) was used to extract rearrangement signatures...
March 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29560094/reconstitution-of-high-grade-serous-ovarian-carcinoma-from-primary-fallopian-tube-secretory-epithelial-cells
#5
Kohei Nakamura, Kentaro Nakayama, Noriyoshi Ishikawa, Masako Ishikawa, Razia Sultana, Tohru Kiyono, Satoru Kyo
Fallopian tube secretory epithelial cells (FTSECs) have been suggested to be the source of high-grade serous ovarian carcinoma (HGSOC). Although several genetic alterations are known to be involved in HGSOC development, the minimal requirements remain unclear. We aimed to identify oncogenic mutations indispensable for HGSOC development in a stepwise model, using immortalized FTSECs. FTSECs were isolated from clinical samples and immortalized by overexpression of cyclin D1, CDK4R24C , and hTERT . Oncogenic mutations in the p53, c-Myc, and RAS/PI3K pathways were mimicked by lentiviral transduction...
February 27, 2018: Oncotarget
https://www.readbyqxmd.com/read/29548784/high-expression-of-integrin-%C3%AE-v%C3%AE-3-enables-uptake-of-targeted-fluorescent-probes-into-ovarian-cancer-cells-and-tumors
#6
Scott K Shaw, Cynthia L Schreiber, Felicia M Roland, Paul M Battles, Seamus P Brennan, Simon J Padanilam, Bradley D Smith
The cell line OVCAR-4 was recently ranked as one of the most representative cell lines for high grade serous ovarian cancer (HGSOC). However, little work has been done to assess the susceptibility of OVCAR-4 cells and tumors to the more common types of molecular targeting. Proteome profiles suggest OVCAR-4 express high levels of integrin αvβ3 receptors. Using flow cytometry with fluorescent antibodies we determined that OVCAR-4 cells have high number of integrin αvβ3 receptors ([9.8 ± 2.5] × 104 /cell) compared to the well-characterized cell line U87-MG ([5...
March 6, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29545475/olaparib-induced-adaptive-response-is-disrupted-by-foxm1-targeting-which-enhances-sensitivity-to-parp-inhibition
#7
Pingping Fang, Jill A Madden, Lisa Neums, K Ryan Moulder, M Laird Forrest, Jeremy Chien
FOXM1 transcription factor network is activated in over 84% of cases in high-grade serous ovarian cancer (HGSOC), and FOXM1 upregulates the expression of genes involved in the homologous recombination (HR) DNA damage and repair (DDR) pathway. However, the role of FOXM1 in poly (ADP-ribose) polymerase (PARP) inhibitor response has not yet been studied. The present study demonstrates that PARP inhibitor (PARPi), olaparib, induces the expression and nuclear localization of FOXM1. Based on ChIP-qPCR, olaparib enhances the binding of FOXM1 to genes involved in HR repair...
March 15, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29535360/mir200-regulated-cxcl12%C3%AE-promotes-fibroblast-heterogeneity-and-immunosuppression-in-ovarian-cancers
#8
Anne-Marie Givel, Yann Kieffer, Alix Scholer-Dahirel, Philemon Sirven, Melissa Cardon, Floriane Pelon, Ilaria Magagna, Géraldine Gentric, Ana Costa, Claire Bonneau, Virginie Mieulet, Anne Vincent-Salomon, Fatima Mechta-Grigoriou
High-grade serous ovarian cancers (HGSOC) have been subdivided into molecular subtypes. The mesenchymal HGSOC subgroup, defined by stromal-related gene signatures, is invariably associated with poor patient survival. We demonstrate that stroma exerts a key function in mesenchymal HGSOC. We highlight stromal heterogeneity in HGSOC by identifying four subsets of carcinoma-associated fibroblasts (CAF-S1-4). Mesenchymal HGSOC show high content in CAF-S1 fibroblasts, which exhibit immunosuppressive functions by increasing attraction, survival, and differentiation of CD25+ FOXP3+ T lymphocytes...
March 13, 2018: Nature Communications
https://www.readbyqxmd.com/read/29523763/molecular-response-to-neoadjuvant-chemotherapy-in-high-grade-serous-ovarian-carcinoma
#9
Rebecca C Arend, Angelina I Londono, Allison M Montgomery, Haller J Smith, Zachary C Dobbin, Ashwini A Katre, Alba Martinez, Eddy S Yang, Ronald D Alvarez, Warner K Huh, Kerri S Bevis, J Michael Straughn, Jacob M Estes, Lea Novak, David K Crossman, Sara J Cooper, Charles N Landen, Charles A Leath
While high-grade serous ovarian carcinoma (HGSOC) is the most common histological subtype of ovarian cancer, significant tumor heterogeneity exists. In addition, chemotherapy induces changes in gene expression and alters the mutational profile. To evaluate the notion that patients with HGSOC could be better classified for optimal treatment based on gene expression, we compared genetic variants (by DNA next-generation sequencing [NGS] using a 50 gene Ion Torrent panel) and gene expression (using the NanoString® PanCancer 770 gene Panel) in the tumor from 20 patients with HGSOC before and after neoadjuvant chemotherapy (NACT)...
March 9, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29504606/ctd-2020k17-1-a-novel-long-non-coding-rna-promotes-migration-invasion-and-proliferation-of-serous-ovarian-cancer-cells-in-vitro
#10
Linfei Zhu, Qixuan Guo, Xinxin Lu, Junhua Zhao, Jinxin Shi, Zhenning Wang, Xin Zhou
BACKGROUND Ovarian cancer is the most lethal malignant tumor of the female reproductive system, and the metastasis is one of the major factors that contribute to the poor outcome of patients with OC. Accumulating evidence indicates that lncRNAs are expressed and play important regulatory roles in ovarian cancer. MATERIAL AND METHODS Aberrant lncRNAs in primary ovarian cancer tissues (POCTs) and paired omental metastasis tissues (OMTs) of patients with HGSOC were studied via lncRNA microarray. Real-time PCR was performed to examine CTD-2020K17...
March 5, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29502561/myd88-and-tlr4-expression-in-epithelial-ovarian-cancer
#11
Matthew S Block, Robert A Vierkant, Peter F Rambau, Stacey J Winham, Philipp Wagner, Nadia Traficante, Aleksandra Tołoczko, Daniel G Tiezzi, Florin Andrei Taran, Peter Sinn, Weiva Sieh, Raghwa Sharma, Joseph H Rothstein, Teresa Ramón Y Cajal, Luis Paz-Ares, Oleg Oszurek, Sandra Orsulic, Roberta B Ness, Gregg Nelson, Francesmary Modugno, Janusz Menkiszak, Valerie McGuire, Bryan M McCauley, Marie Mack, Jan Lubiński, Teri A Longacre, Zheng Li, Jenny Lester, Catherine J Kennedy, Kimberly R Kalli, Audrey Y Jung, Sharon E Johnatty, Mercedes Jimenez-Linan, Allan Jensen, Maria P Intermaggio, Jillian Hung, Esther Herpel, Brenda Y Hernandez, Andreas D Hartkopf, Paul R Harnett, Prafull Ghatage, José M García-Bueno, Bo Gao, Sian Fereday, Ursula Eilber, Robert P Edwards, Christiani B de Sousa, Jurandyr M de Andrade, Anita Chudecka-Głaz, Georgia Chenevix-Trench, Alicia Cazorla, Sara Y Brucker, Jennifer Alsop, Alice S Whittemore, Helen Steed, Annette Staebler, Kirsten B Moysich, Usha Menon, Jennifer M Koziak, Stefan Kommoss, Susanne K Kjaer, Linda E Kelemen, Beth Y Karlan, David G Huntsman, Estrid Høgdall, Jacek Gronwald, Marc T Goodman, Blake Gilks, María José García, Peter A Fasching, Anna de Fazio, Suha Deen, Jenny Chang-Claude, Francisco J Candido Dos Reis, Ian G Campbell, James D Brenton, David D Bowtell, Javier Benítez, Paul D P Pharoah, Martin Köbel, Susan J Ramus, Ellen L Goode
OBJECTIVE: To evaluate myeloid differentiation primary response gene 88 (MyD88) and Toll-like receptor 4 (TLR4) expression in relation to clinical features of epithelial ovarian cancer, histologic subtypes, and overall survival. PATIENTS AND METHODS: We conducted centralized immunohistochemical staining, semi-quantitative scoring, and survival analysis in 5263 patients participating in the Ovarian Tumor Tissue Analysis consortium. Patients were diagnosed between January 1, 1978, and December 31, 2014, including 2865 high-grade serous ovarian carcinomas (HGSOCs), with more than 12,000 person-years of follow-up time...
March 2018: Mayo Clinic Proceedings
https://www.readbyqxmd.com/read/29487129/biomarkers-of-platinum-resistance-in-ovarian-cancer-what-can-we-use-to-improve-treatment
#12
Belinda van Zyl, Denise Tang, Nikola A Bowden
Ovarian cancer has poor survival rate due to a combination of diagnosis at advanced disease stages and disease recurrence as a result of platinum chemotherapy resistance. High grade serous ovarian cancer (HGSOC), the most common ovarian cancer subtype, is conventionally treated with surgery and paclitaxel/carboplatin combination chemotherapy. Initial response rates are 60-80%, but eventually the majority of patients become platinum resistant with subsequent relapses. Extensive research on individual biomarkers of platinum-resistance has revealed many potential targets for the development new treatments...
February 27, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29466768/dynamics-of-the-intratumoral-immune-response-during-progression-of-high-grade-serous-ovarian-cancer
#13
Mandy Stanske, Stephan Wienert, Dan Cacsire Castillo-Tong, Caroline Kreuzinger, Ignace Vergote, Sandrijne Lambrechts, Hani Gabra, Charlie Gourley, Ram N Ganapathi, Ivonne Kolaschinski, Jan Budczies, Jalid Sehouli, Ilary Ruscito, Carsten Denkert, Hagen Kulbe, Wolfgang Schmitt, Korinna Jöhrens, Ioana Braicu, Silvia Darb-Esfahani
PURPOSE: Tumor-infiltrating lymphocytes (TILs) have an established impact on the prognosis of high-grade serous ovarian carcinoma (HGSOC), however, their role in recurrent ovarian cancer is largely unknown. We therefore systematically investigated TIL densities and MHC class I and II (MHC1, 2) expression in the progression of HGSOC. EXPERIMENTAL DESIGN: CD3+, CD4+, CD8+ TILs and MHC1, 2 expression were evaluated by immunohistochemistry on tissue microarrays in 113 paired primary and recurrent HGSOC...
February 18, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29465506/brca1-ki67-and-%C3%AE-catenin-immunoexpression-is-not-related-to-differentiation-platinum-response-or-prognosis-in-women-with-low-and-high-grade-serous-ovarian-carcinoma
#14
Luis Felipe Sallum, Liliana Andrade, Larissa Bastos Eloy da Costa, Susana Ramalho, Amanda Canato Ferracini, Rodrigo de Andrade Natal, Angelo Borsarelli Carvalho Brito, Luis Otávio Sarian, Sophie Derchain
OBJECTIVE: The purpose of this study was to compare the immunohistochemical expression of BRCA1, Ki67, and β-catenin in women with low-grade (LGSOC) and high-grade serous ovarian carcinomas (HGSOC) and their relationship with clinicopathological features, response to platinum-based chemotherapy, and survival. METHODS: For this study, 21 LGSOC and 85 HGSOC stage I to IV cases, diagnosed and treated from 1996 to 2013 and followed-up until December 2016, were included...
March 2018: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/29464354/parp-inhibitors-in-platinum-sensitive-high-grade-serous-ovarian-cancer
#15
REVIEW
Robert D Morgan, Andrew R Clamp, D Gareth R Evans, Richard J Edmondson, Gordon C Jayson
PURPOSE: Poly(ADP-ribose) polymerase inhibitors (PARPi) have changed the management of high-grade serous ovarian cancer (HGSOC). The rationale for the development of PARPi was based on the concept of synthetic lethality, in which a cell can survive a deficiency of one gene/gene product, but may die if there is a deficiency in a combination of genes/gene products. In women with BRCA1/2 deficiency within their ovarian cancer tissue, inhibition of PARP imposes an intolerable burden of DNA damage repair deficiency and may induce cell death...
February 20, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29460329/population-based-testing-of-non-mucinous-epithelial-ovarian-cancer-in-scotland
#16
D G Evans, R Edmondson, E J Crosbie
Rust and colleagues provide strong support for the extension of BRCA1/2 germline testing to all high grade serous ovarian cancer (HGSOC) cases regardless of family history (Rust et al, BJOG 2018). The reflex testing of all consenting cases uncovered the deficiencies of the previous system whereby many women with a family history in the prevalent population of previous ovarian cancer were not tested despite having a Manchester score of ≥15, equivalent to a 10% detection rate or greater of a BRCA1/2 pathogenic variant (Evans et al, J Med Genet 2017;54:674-681)...
February 20, 2018: BJOG: An International Journal of Obstetrics and Gynaecology
https://www.readbyqxmd.com/read/29444438/commonly-occurring-cell-subsets-in-high-grade-serous-ovarian-tumors-identified-by-single-cell-mass-cytometry
#17
Veronica D Gonzalez, Nikolay Samusik, Tiffany J Chen, Erica S Savig, Nima Aghaeepour, David A Quigley, Ying-Wen Huang, Valeria Giangarrà, Alexander D Borowsky, Neil E Hubbard, Shih-Yu Chen, Guojun Han, Alan Ashworth, Thomas J Kipps, Jonathan S Berek, Garry P Nolan, Wendy J Fantl
We have performed an in-depth single-cell phenotypic characterization of high-grade serous ovarian cancer (HGSOC) by multiparametric mass cytometry (CyTOF). Using a CyTOF antibody panel to interrogate features of HGSOC biology, combined with unsupervised computational analysis, we identified noteworthy cell types co-occurring across the tumors. In addition to a dominant cell subset, each tumor harbored rarer cell phenotypes. One such group co-expressed E-cadherin and vimentin (EV), suggesting their potential role in epithelial mesenchymal transition, which was substantiated by pairwise correlation analyses...
February 13, 2018: Cell Reports
https://www.readbyqxmd.com/read/29434467/genomic-analysis-using-regularized-regression-in-high-grade-serous-ovarian-cancer
#18
Yanina Natanzon, Madalene Earp, Julie M Cunningham, Kimberly R Kalli, Chen Wang, Sebastian M Armasu, Melissa C Larson, David Dl Bowtell, Dale W Garsed, Brooke L Fridley, Stacey J Winham, Ellen L Goode
High-grade serous ovarian cancer (HGSOC) is a complex disease in which initiation and progression have been associated with copy number alterations, epigenetic processes, and, to a lesser extent, germline variation. We hypothesized that, when summarized at the gene level, tumor methylation and germline genetic variation, alone or in combination, influence tumor gene expression in HGSOC. We used Elastic Net (ENET) penalized regression method to evaluate these associations and adjust for somatic copy number in 3 independent data sets comprising tumors from more than 470 patients...
2018: Cancer Informatics
https://www.readbyqxmd.com/read/29416699/lgr5-and-lgr6-in-stem-cell-biology-and-ovarian-cancer
#19
REVIEW
Adam J Schindler, Arisa Watanabe, Stephen B Howell
Wnt signaling plays a fundamental role in patterning of the embryo and maintenance of stem cells in numerous epithelia. Epithelial stem cells are closeted in niches created by surrounding differentiated cells that express secreted Wnt and R-spondin proteins that influence proliferation rate and fate determination of stem cell daughters. R-spondins act through the LGR receptors to enhance Wnt signaling. This close association of stem cells with more differentiated regulatory cells expressing Wnt-pathway ligands is a feature replicated in all of the epithelial stem cell systems thus far examined...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29402501/hoxa4-hoxb3-gene-expression-signature-as-a-biomarker-of-recurrence-in-patients-with-high-grade-serous-ovarian-cancer-following-primary-cytoreductive-surgery-and-first-line-adjuvant-chemotherapy
#20
Katherine R Miller, Jai N Patel, Qing Zhang, Eric J Norris, James Symanowski, Chad Michener, Jalid Sehouli, Ioana Braicu, Darla D Destephanis, Ashley P Sutker, Wendell Jones, Chad A Livasy, Charles Biscotti, Ram N Ganapathi, David L Tait, Mahrukh K Ganapathi
OBJECTIVES: Aberrant homeobox (HOX) gene expression is reported in high-grade serous ovarian carcinoma (HGSOC), however, its prognostic significance remains unclear. METHODS: HOX genes associated with progression-free survival (PFS) in a discovery cohort of primary HGSOC samples with RNA sequencing data, and those previously reported to be associated with clinical outcomes, were selected for qPCR testing in an independent training cohort of primary HGSOC samples (n=71)...
February 2, 2018: Gynecologic Oncology
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