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https://www.readbyqxmd.com/read/28698296/prkci-promotes-immune-suppression-in-ovarian-cancer
#1
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...
July 11, 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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/28548929/brd4-facilitates-dna-damage-response-and-represses-cbx5-heterochromatin-protein-1-hp1
#11
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...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28545541/mal-gene-overexpression-as-a-marker-of-high-grade-serous-ovarian-carcinoma-stem-like-cells-that-predicts-chemoresistance-and-poor-prognosis
#12
Laura Zanotti, Chiara Romani, Laura Tassone, Paola Todeschini, Renata Alessandra Tassi, Elisabetta Bandiera, Giovanna Damia, Francesca Ricci, Laura Ardighieri, Stefano Calza, Sergio Marchini, Luca Beltrame, Germana Tognon, Maurizio D'Incalci, Sergio Pecorelli, Enrico Sartori, Franco Odicino, Antonella Ravaggi, Eliana Bignotti
BACKGROUND: The existence of cancer stem cells (CSCs) within a tumor bulk has been demonstrated for many solid tumors including epithelial ovarian carcinoma (EOC). CSCs have been associated to tumor invasion, metastasis and development of chemoresistant recurrences. In this context, we aim to characterize EOC CSCs from the molecular point of view in order to identify potential biomarkers associated with chemoresistance. METHODS: We isolated a population of cells with stem-like characteristics (OVA-BS4 spheroids) from a primary human EOC cell line under selective conditions...
May 25, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28525846/exploring-the-clonal-evolution-of-cd133-aldehyde-dehydrogenase-1-aldh1-positive-cancer-stem-like-cells-from-primary-to-recurrent-high-grade-serous-ovarian-cancer-hgsoc-a-study-of-the-ovarian-cancer-therapy-innovative-models-prolong-survival-octips-consortium
#13
Ilary Ruscito, Dan Cacsire Castillo-Tong, Ignace Vergote, Iulia Ignat, Mandy Stanske, Adriaan Vanderstichele, Ram N Ganapathi, Jacek Glajzer, Hagen Kulbe, Fabian Trillsch, Alexander Mustea, Caroline Kreuzinger, Pierluigi Benedetti Panici, Charlie Gourley, Hani Gabra, Mirjana Kessler, Jalid Sehouli, Silvia Darb-Esfahani, Elena Ioana Braicu
BACKGROUND: High-grade serous ovarian cancer (HGSOC) causes 80% of all ovarian cancer (OC) deaths. In this setting, the role of cancer stem-like cells (CSCs) is still unclear. In particular, the evolution of CSC biomarkers from primary (pOC) to recurrent (rOC) HGSOCs is unknown. Aim of this study was to investigate changes in CD133 and aldehyde dehydrogenase-1 (ALDH1) CSC biomarker expression in pOC and rOC HGSOCs. METHODS: Two-hundred and twenty-four pOC and rOC intrapatient paired tissue samples derived from 112 HGSOC patients were evaluated for CD133 and ALDH1 expression using immunohistochemistry (IHC); pOCs and rOCs were compared for CD133 and/or ALDH1 levels...
May 16, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28501328/evaluation-of-venous-thrombosis-and-tissue-factor-in-epithelial-ovarian-cancer
#14
Joshua G Cohen, Emily Prendergast, Julia E Geddings, Ann E Walts, Hasmik Agadjanian, Yohei Hisada, Beth Y Karlan, Nigel Mackman, Christine S Walsh
OBJECTIVE: Ovarian clear cell carcinoma (OCCC) and high grade serous ovarian cancer (HGSOC) are associated with the highest risk of VTE among patients with epithelial ovarian cancer (EOC). Tissue factor (TF) is a transmembrane glycoprotein which can trigger thrombosis. We sought to evaluate if there is an association between VTE and tumor expression of tissue factor (TF), plasma TF, and microvesicle TF (MV TF) activity in this high-risk population. METHODS: We performed a case-control study of OCCC and HGSOC patients with and without VTE...
July 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28495238/uncovering-the-role-of-nuclear-lysyl-oxidase-lox-in-advanced-high-grade-serous-ovarian-cancer
#15
Marta De Donato, Marco Petrillo, Enrica Martinelli, Flavia Filippetti, Gian Franco Zannoni, Giovanni Scambia, Daniela Gallo
OBJECTIVE: Lysyl oxidase (LOX) is an enzyme that catalyzes the cross-linking of collagen and elastin in the extracellular matrix, thus controlling the tensile strength of tissues. Along with this primary function, there are evidences supporting a role for LOX in many critical biological functions, including gene expression regulation, cell growth, adhesion and migration. Accordingly, recent studies have supported a pivotal role for LOX in cancer progression and metastasis. The current study aimed at investigating the prognostic significance and the functional role of intracellular LOX in ovarian cancer...
July 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28490612/pathology-update-to-the-manchester-scoring-system-based-on-testing-in-over-4000-families
#16
D Gareth Evans, Elaine F Harkness, Inga Plaskocinska, Andrew J Wallace, Tara Clancy, Emma R Woodward, Tony A Howell, Marc Tischkowitz, Fiona Lalloo
BACKGROUND: While the requirement for thresholds for testing for mutations in BRCA1/2 is being questioned, they are likely to remain for individuals unaffected by a relevant cancer. It is still useful to provide pretesting likelihoods, but models need to take into account tumour pathology. METHODS: The Manchester Scoring System (MSS) is a well-used, simple, paper-based model for assessing carrier probability that already incorporates pathology data. We have used mutation testing data from 4115 unrelated samples from affected non-Jewish individuals alongside tumour pathology to further refine the scoring system...
May 10, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28455291/hyper-phosphorylation-of-sequestosome-1-distinguishes-resistance-to-cisplatin-in-patient-derived-high-grade-serous-ovarian-cancer-cells
#17
Elizabeth V Nguyen, Kaisa Huhtinen, Young Ah Goo, Katja Kaipio, Noora Andersson, Ville Rantanen, Johanna Hynninen, Riitta Lahesmaa, Olli Carpen, David R Goodlett
Platinum-resistance is a major limitation to effective chemotherapy regimens in high-grade serous ovarian cancer (HGSOC). To better understand the mechanisms involved we characterized the proteome and phosphoproteome in cisplatin sensitive and resistant HGSOC primary cells using a mass spectrometry-based proteomic strategy. PCA analysis identified a distinctive phosphoproteomic signature between cisplatin sensitive and resistant cell lines. The most phosphorylated protein in cisplatin resistant cells was sequestosome-1 (p62/SQSTM1)...
July 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28404948/germline-whole-exome-sequencing-and-large-scale-replication-identifies-fancm-as-a-likely-high-grade-serous-ovarian-cancer-susceptibility-gene
#18
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, Paul D P 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 = 1.8x10-3). 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...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28350129/apoptosis-is-augmented-in-high-grade-serous-ovarian-cancer-by-the-combined-inhibition-of-bcl-2-bcl-xl-and-parp
#19
Takuhei Yokoyama, Elise C Kohn, Ethan Brill, Jung-Min Lee
The aim of our study was to evaluate possible synergistic cytotoxic effects of the combination treatment with the BH3-mimetic ABT-263 and the PARP inhibitor BMN 673 in high-grade serous ovarian cancer (HGSOC) cells using clinically achievable concentrations of each drug. In vitro cytotoxic effects of ABT-263 and BMN 673 were assessed by XTT assay in three HGSOC cell lines: OVCAR3, OVCAR8, and OV90 cells. Combination index values and synergy/antagonism volumes were used to determine synergy. The drug effects on DNA damage accumulation, cell cycle progression, apoptosis induction, and expression levels of Bcl-2 family proteins were examined to dissect molecular mechanisms...
March 15, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28299955/niraparib-for-the-treatment-of-ovarian-cancer
#20
REVIEW
Yada Kanjanapan, Stephanie Lheureux, Amit M Oza
Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors are being developed in maintenance and recurrence treatment settings in ovarian cancer. They inhibit single-stranded DNA repair, inducing synthetic lethality in cells with underlying homologous recombination deficiency (HRD). Marked responses are seen in ovarian cancers with breast cancer gene 1 (BRCA1) or 2 (BRCA2) mutation, although up to 50% of high-grade serous ovarian cancers (HGSOC) have HRD may also benefit. Areas covered: This review focuses on niraparib (oral PARP I and II inhibitor), its clinical testing in ovarian cancer, including the Myriad MyChoice HRD test as a potential companion diagnostic...
April 2017: Expert Opinion on Pharmacotherapy
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