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https://www.readbyqxmd.com/read/28976449/a-2-protein-signature-predicting-clinical-outcome-in-high-grade-serous-ovarian-cancer
#1
Chengjuan Jin, Yingfeng Xue, Yingwei Li, Hualei Bu, Hongfeng Yu, Tao Zhang, Zhiwei Zhang, Shi Yan, Nan Lu, Beihua Kong
OBJECTIVE: High-grade serous ovarian cancer (HGSOC) accounts for approximately 70% deaths in ovarian cancer. The overall survival (OS) of HGSOC is poor and still remains a clinical challenge. High-grade serous ovarian cancer can be divided into 4 molecular subtypes. The prognosis of different molecular subtypes is still unclear. We aimed to investigate the prognostic values of immunohistochemistry-based different molecular subtypes in patients with HGSOC. METHODS: We analyzed the protein expression of representative biomarkers (CXCL11, HMGA2, and MUC16) of 3 different molecular subtypes in 110 formalin-fixed, paraffin-embedded HGSOC by tissue microarrays...
October 3, 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28974545/the-hrd-decision-which-parp-inhibitor-to-use-for-whom-and-when
#2
Elise C Kohn, Jung-Min Lee, S Percy Ivy
Rucaparib, a polyADPribose polymerase (PARP) inhibitor, was approved recently for use in women with high grade serous ovarian cancer (HGSOC). It is now one of 3 approved PARPi for use in recurrent ovarian cancer, a family of agents that has changed the HGSOC treatment landscape and outcome.
October 3, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28972047/a-complex-network-of-tumor-microenvironment-in-human-high-grade-serous-ovarian-cancer
#3
Caroline Kreuzinger, Angelika Geroldinger, Dominiek Smeets, Elena I Braicu, Jalid Sehouli, Julia Koller, Andrea Wolf, Silvia Darb-Esfahani, Korinna Jöhrens, Ignace Vergote, Adriaan Vanderstichele, Bram Boeckx, Diether Lambrechts, Hani Gabra, G B A Wisman, Fabian Trillsch, Georg Heinze, Reinhard Horvat, Stephan Polterauer, Els M J J Berns, Charles G Theillet, Dan Cacsire Castillo-Tong
PURPOSE: Most high grade serous ovarian cancer (HGSOC) patients develop recurrent disease after first line treatment, frequently with fatal outcome. This work aims at studying the molecular biology of both primary and recurrent HGSOC. EXPERIMENTAL DESIGN: Gene expression profiles of matched primary and recurrent fresh frozen tumor tissues from 66 HGSOC patients were obtained by RNA sequencing. Clustering analyses and pairwise comparison of the profiles between matched samples and subsequent functional alignment were used for the identification of molecular characteristics of HGSOC...
October 2, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28964622/intraperitoneal-disease-dissemination-patterns-are-associated-with-residual-disease-extent-of-surgery-and-molecular-subtypes-in-advanced-ovarian-cancer
#4
Diogo Torres, Amanika Kumar, Sumer K Wallace, Jamie N Bakkum-Gamez, Gottfried E Konecny, Amy L Weaver, Michaela E McGree, Ellen L Goode, William A Cliby, Chen Wang
OBJECTIVE: To investigate the association between intraperitoneal (IP) disease dissemination patterns, residual disease (RD), surgical complexity, and molecular subtypes in advanced high-grade serous ovarian cancer (HGSOC). METHODS: 741 patients with operable stage III-IV HGSOC undergoing primary debulking surgery at Mayo Clinic from 1994 to 2011 were categorized into four mutually exclusive IP disease dissemination patterns: upper abdominal (60%), miliary (16%), lower abdominal (15%), and pelvic (9%)...
September 27, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28881656/brd4-facilitates-dna-damage-response-and-represses-cbx5-heterochromatin-protein-1-hp1
#5
Georgios Pongas, Marianne K Kim, Dong J Min, Carrie D House, Elizabeth Jordan, Natasha Caplen, Sirisha Chakka, Joyce Ohiri, Michael J Kruhlak, Christina M Annunziata
Ovarian cancer (OC) is a heterogeneous disease characterized by defective DNA repair. Very few targets are universally expressed in the high grade serous (HGS) subtype. We previously identified that CHK1 was overexpressed in most of HGSOC. Here, we sought to understand the DNA damage response (DDR) to CHK1 inhibition and increase the anti-tumor activity of this pathway. We found BRD4 suppression either by siRNA or BRD4 inhibitor JQ1 enhanced the cytotoxicity of CHK1 inhibition. Interestingly, BRD4 was amplified and/or upregulated in a subset of HGSOC with statistical correlation to overall survival...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881617/germline-whole-exome-sequencing-and-large-scale-replication-identifies-fancm-as-a-likely-high-grade-serous-ovarian-cancer-susceptibility-gene
#6
Ed Dicks, Honglin Song, Susan J Ramus, Elke Van Oudenhove, Jonathan P Tyrer, Maria P Intermaggio, Siddhartha Kar, Patricia Harrington, David D Bowtell, Aocs Study Group, Mine S Cicek, Julie M Cunningham, Brooke L Fridley, Jennifer Alsop, Mercedes Jimenez-Linan, Anna Piskorz, Teodora Goranova, Emma Kent, Nadeem Siddiqui, James Paul, Robin Crawford, Samantha Poblete, Shashi Lele, Lara Sucheston-Campbell, Kirsten B Moysich, Weiva Sieh, Valerie McGuire, Jenny Lester, Kunle Odunsi, Alice S Whittemore, Natalia Bogdanova, Matthias Dürst, Peter Hillemanns, Beth Y Karlan, Aleksandra Gentry-Maharaj, Usha Menon, Marc Tischkowitz, Douglas Levine, James D Brenton, Thilo Dörk, Ellen L Goode, Simon A Gayther, D P Paul Pharoah
We analyzed whole exome sequencing data in germline DNA from 412 high grade serous ovarian cancer (HGSOC) cases from The Cancer Genome Atlas Project and identified 5,517 genes harboring a predicted deleterious germline coding mutation in at least one HGSOC case. Gene-set enrichment analysis showed enrichment for genes involved in DNA repair (p = 1.8×10(-3)). Twelve DNA repair genes - APEX1, APLF, ATX, EME1, FANCL, FANCM, MAD2L2, PARP2, PARP3, POLN, RAD54L and SMUG1 - were prioritized for targeted sequencing in up to 3,107 HGSOC cases, 1,491 cases of other epithelial ovarian cancer (EOC) subtypes and 3,368 unaffected controls of European origin...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881577/a-comprehensively-characterized-cell-line-panel-highly-representative-of-clinical-ovarian-high-grade-serous-carcinomas
#7
Kelsie L Thu, Mahboubeh Papari-Zareei, Victor Stastny, Kai Song, Michael Peyton, Victor D Martinez, Yu-An Zhang, Isabel B Castro, Marileila Varella-Garcia, Hanquan Liang, Chao Xing, Ralf Kittler, Sara Milchgrub, Diego H Castrillon, Heather L Davidson, C Patrick Reynolds, Wan L Lam, Jayanthi Lea, Adi F Gazdar
Recent literature suggests that most widely used ovarian cancer (OVCA) cell models do not recapitulate the molecular features of clinical tumors. To address this limitation, we generated 18 cell lines and 3 corresponding patient-derived xenografts predominantly from high-grade serous carcinoma (HGSOC) peritoneal effusions. Comprehensive genomic characterization and comparison of each model to its parental tumor demonstrated a high degree of molecular similarity. Our characterization included whole exome-sequencing and copy number profiling for cell lines, xenografts, and matched non-malignant tissues, and DNA methylation, gene expression, and spectral karyotyping for a subset of specimens...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28846888/prognostic-value-of-tumor-pd-l1-expression-combined-with-cd8-tumor-infiltrating-lymphocytes-in-high-grade-serous-ovarian-cancer
#8
Qiaohong Wang, Weihua Lou, Wen Di, Xia Wu
Expression of programmed cell death-ligand 1 (PD-L1) is known to be a mechanism whereby cancer can escape immune surveillance, but the relationship between tumor PD-L1 expression and tumor-infiltrating lymphocytes (TILs), and their association with clinical outcomes in patients with high grade serous ovarian cancer (HGSOC) remain ambiguous. We detected the expression of PD-L1 and CD3(+), CD4(+), CD8(+) TILs in 107 patients with HGSOC by immunohistochemical analysis. Using a 5% threshold, 24.30% and 15.89% cases were found with positive expression of PD-L1 in the membrane of tumor cells and TILs respectively...
November 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28800130/mir-130a-upregulates-mtor-pathway-by-targeting-tsc1-and-is-transactivated-by-nf-%C3%AE%C2%BAb-in-high-grade-serous-ovarian-carcinoma
#9
Yuqiong Wang, Xiyu Zhang, Wei Tang, Zhenghong Lin, Limei Xu, Ruifen Dong, Yinuo Li, Jieyin Li, Zaixin Zhang, Xiangzhi Li, Ling Zhao, Jian-Jun Wei, Changshun Shao, Beihua Kong, Zhaojian Liu
Activation of mammalian target of rapamycin (mTOR) signaling pathway is associated with poor prognosis of epithelial ovarian cancer. The TSC1-TSC2 complex is a critical negative regulator of mTOR signaling. Here, we demonstrated that TSC1 was frequently downregulated in high-grade serous ovarian carcinoma (HGSOC) and low TSC1 expression level is associated with advanced tumor stage. We next identified miR-130a to be a negative regulator of TSC1 by targeting its 3'UTR. miR-130a was overexpressed in HGSOC and could drive proliferation and invasion/metastasis of ovarian cancer cells...
August 11, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28794804/brca-mutation-in-ovarian-cancer-testing-implications-and-treatment-considerations
#10
REVIEW
Robert T Neff, Leigha Senter, Ritu Salani
Ovarian cancer is a heterogeneous disease that encompasses a number of different cellular subtypes, the most common of which is high-grade serous ovarian cancer (HGSOC). Still today, ovarian cancer is primarily treated with chemotherapy and surgery. Recent advances in the hereditary understanding of this disease have shown a significant role for the BRCA gene. While only a minority of patients with HGSOC will have a germline BRCA mutation, many others may have tumor genetic aberrations within BRCA or other homologous recombination proteins...
August 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28698296/prkci-promotes-immune-suppression-in-ovarian-cancer
#11
Sharmistha Sarkar, Christopher A Bristow, Prasenjit Dey, Kunal Rai, Ruth Perets, Alejandra Ramirez-Cardenas, Shruti Malasi, Emmet Huang-Hobbs, Monika Haemmerle, Sherry Y Wu, Michael McGuire, Alexei Protopopov, Shan Jiang, Joyce F Liu, Michelle S Hirsch, Qing Chang, Alexander J Lazar, Anil K Sood, Ronny Drapkin, Ronald DePinho, Giulio Draetta, Lynda Chin
A key feature of high-grade serous ovarian carcinoma (HGSOC) is frequent amplification of the 3q26 locus harboring PRKC-ι (PRKCI). Here, we show that PRKCI is also expressed in early fallopian tube lesions, called serous tubal intraepithelial carcinoma. Transgenic mouse studies establish PRKCI as an ovarian cancer-specific oncogene. Mechanistically, we show that the oncogenic activity of PRKCI relates in part to the up-regulation of TNFα to promote an immune-suppressive tumor microenvironment characterized by an abundance of myeloid-derived suppressor cells and inhibition of cytotoxic T-cell infiltration...
June 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28679689/two-different-mutually-exclusively-distributed-tp53-mutations-in-ovarian-and-peritoneal-tumor-tissues-of-a-serous-ovarian-cancer-patient-indicative-for-tumor-origin
#12
Nyamdelger Sukhbaatar, Anna Bachmayr-Heyda, Katharina Auer, Stefanie Aust, Simon Deycmar, Reinhard Horvat, Dietmar Pils
High-grade serous ovarian cancer (HGSOC) is characterized by a TP53 mutation rate of up to 96.7% and associated with a more aggressive tumor biology. The origin of HGSOC is thought to arise either from fallopian tube secretory cells or the ovarian surface epithelium/inclusion cysts, the former with more evidence. Peritoneal tumor spread is heterogeneous, either excessive in the peritoneum (with miliary appearance) or more confined to the ovaries with only few (bigger and exophytically growing) peritoneal implants...
July 2017: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/28670378/overexpression-of-cd47-predicts-poor-prognosis-and-promotes-cancer-cell-invasion-in-high-grade-serous-ovarian-carcinoma
#13
Yinuo Li, Shuhua Lu, Ying Xu, Chunping Qiu, Chengjuan Jin, Yuqiong Wang, Zhaojian Liu, Beihua Kong
CD47 is an antiphagocytic signal that cancer cells employ to inhibit macrophage-mediated destruction. CD47 is overexpressed in various human malignancies. However, the expression and functional significance of CD47 in high-grade serous ovarian carcinoma (HGSOC) has not been completely understood. In this study, we reported that CD47 was commonly overexpressed in HGSOC. Higher CD47 expression was significantly correlated with poor prognosis of HGSOC patients. Functional investigations revealed that CD47 overexpression in ovarian cancer cells significantly promoted migration and invasion...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28641578/methylome-analysis-of-extreme-chemoresponsive-patients-identifies-novel-markers-of-platinum-sensitivity-in-high-grade-serous-ovarian-cancer
#14
Tushar Tomar, Nicolette G Alkema, Leroy Schreuder, Gert Jan Meersma, Tim de Meyer, Wim van Criekinge, Harry G Klip, Heidi Fiegl, Els van Nieuwenhuysen, Ignace Vergote, Martin Widschwendter, Ed Schuuring, Ate G J van der Zee, Steven de Jong, G Bea A Wisman
BACKGROUND: Despite an early response to platinum-based chemotherapy in advanced stage high-grade serous ovarian cancer (HGSOC), the majority of patients will relapse with drug-resistant disease. Aberrant epigenetic alterations like DNA methylation are common in HGSOC. Differences in DNA methylation are associated with chemoresponse in these patients. The objective of this study was to identify and validate novel epigenetic markers of chemoresponse using genome-wide analysis of DNA methylation in extreme chemoresponsive HGSOC patients...
June 23, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28641043/radiogenomics-of-high-grade-serous-ovarian-cancer-multireader-multi-institutional-study-from-the-cancer-genome-atlas-ovarian-cancer-imaging-research-group
#15
Hebert Alberto Vargas, Erich P Huang, Yulia Lakhman, Joseph E Ippolito, Priya Bhosale, Vincent Mellnick, Atul B Shinagare, Maria Anello, Justin Kirby, Brenda Fevrier-Sullivan, John Freymann, C Carl Jaffe, Evis Sala
Purpose To evaluate interradiologist agreement on assessments of computed tomography (CT) imaging features of high-grade serous ovarian cancer (HGSOC), to assess their associations with time-to-disease progression (TTP) and HGSOC transcriptomic profiles (Classification of Ovarian Cancer [CLOVAR]), and to develop an imaging-based risk score system to predict TTP and CLOVAR profiles. Materials and Methods This study was a multireader, multi-institutional, institutional review board-approved, HIPAA-compliant retrospective analysis of 92 patients with HGSOC (median age, 61 years) with abdominopelvic CT before primary cytoreductive surgery available through the Cancer Imaging Archive...
June 22, 2017: Radiology
https://www.readbyqxmd.com/read/28628421/high-grade-serous-ovarian-cancer-associations-between-brca-mutation-status-ct-imaging-phenotypes-and-clinical-outcomes
#16
Stephanie Nougaret, Yulia Lakhman, Mithat Gönen, Debra A Goldman, Maura Miccò, Melvin D'Anastasi, Sarah A Johnson, Krishna Juluru, Angela G Arnold, Ramon E Sosa, Robert A Soslow, Hebert Alberto Vargas, Hedvig Hricak, Noah D Kauff, Evis Sala
Purpose To investigate the associations between BRCA mutation status and computed tomography (CT) phenotypes of high-grade serous ovarian cancer (HGSOC) and to evaluate CT indicators of cytoreductive outcome and survival in patients with BRCA-mutant HGSOC and those with BRCA wild-type HGSOC. Materials and Methods This HIPAA-compliant, institutional review board-approved retrospective study included 108 patients (33 with BRCA mutant and 75 with BRCA wild-type HGSOC) who underwent CT before primary debulking...
June 16, 2017: Radiology
https://www.readbyqxmd.com/read/28623900/characterization-of-microrna-200-pathway-in-ovarian-cancer-and-serous-intraepithelial-carcinoma-of-fallopian-tube
#17
Junzheng Yang, Yilan Zhou, Shu-Kay Ng, Kuan-Chun Huang, Xiaoyan Ni, Pui-Wah Choi, Kathleen Hasselblatt, Michael G Muto, William R Welch, Ross S Berkowitz, Shu-Wing Ng
BACKGROUND: Ovarian cancer is the leading cause of death among gynecologic diseases in Western countries. We have previously identified a miR-200-E-cadherin axis that plays an important role in ovarian inclusion cyst formation and tumor invasion. The purpose of this study was to determine if the miR-200 pathway is involved in the early stages of ovarian cancer pathogenesis by studying the expression levels of the pathway components in a panel of clinical ovarian tissues, and fallopian tube tissues harboring serous tubal intraepithelial carcinomas (STICs), a suggested precursor lesion for high-grade serous tumors...
June 17, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28607529/ev-associated-mmp9-in-high-grade-serous-ovarian-cancer-is-preferentially-localized-to-annexin-v-binding-evs
#18
Agnes T Reiner, Sisareuth Tan, Christiane Agreiter, Katharina Auer, Anna Bachmayr-Heyda, Stefanie Aust, Nina Pecha, Mattias Mandorfer, Dietmar Pils, Alain R Brisson, Robert Zeillinger, Sai Kiang Lim
High-grade serous ovarian cancer (HGSOC) is the most aggressive type of ovarian cancer and is responsible for most deaths caused by gynecological cancers. Numerous candidate biomarkers were identified for this disease in the last decades, but most were not sensitive or specific enough for clinical applications. Hence, new biomarkers for HGSOC are urgently required. This study aimed to identify new markers by isolating different extracellular vesicle (EV) types from the ascites of ovarian cancer patients according to their affinities for lipid-binding proteins and analyzing their protein cargo...
2017: Disease Markers
https://www.readbyqxmd.com/read/28588698/clinical-significance-of-the-estrogen-modifying-enzymes-steroid-sulfatase-and-estrogen-sulfotransferase-in-epithelial-ovarian-cancer
#19
Felicitas Mungenast, Stefanie Aust, Ignace Vergote, Adriaan Vanderstichele, Jalid Sehouli, Elena Braicu, Sven Mahner, Dan Cacsire Castillo-Tong, Robert Zeillinger, Theresia Thalhammer
17β-estradiol (E2) can contribute to the progression of epithelial ovarian cancer (EOC). Although the majority of patients with EOC are postmenopausal woman, when de novo estrogen production in the ovary has ceased, ovarian cancer cells remain exposed to estrogens synthesized locally in the cancer cells from inactive sulfonated steroid hormone precursors-such as estrone sulfate taken up from the circulation via the sulfatase pathway. An abundance of the estrogen-modifying enzymes, including estrogen-activating steroid sulfatase (STS) and estrogen-inactivating estrogen-sulfotransferase (SULT1E1), is important for providing active estrogen to EOC cells...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28561656/whence-high-grade-serous-ovarian-cancer
#20
Elise C Kohn, S Percy Ivy
Our understanding of epithelial ovarian cancer has blossomed, and we now recognize that it is a collection of varied histologic and molecularly different malignancies, many of which may not derive from a true ovarian anatomic precursor. High-grade serous ovarian cancer (HGSOC) is a unique type of epithelial cancer. It is characterized by nearly universal mutation in and dysfunction of p53, genomic instability rather than driver mutations, advanced stage at onset, and probable fallopian tube epithelium origin, with a serous tubal in situ carcinoma precursor...
2017: American Society of Clinical Oncology Educational Book
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