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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
#1
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
#2
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...
May 10, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28495238/uncovering-the-role-of-nuclear-lysyl-oxidase-lox-in-advanced-high-grade-serous-ovarian-cancer
#3
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...
May 8, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28490612/pathology-update-to-the-manchester-scoring-system-based-on-testing-in-over-4000-families
#4
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
#5
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)...
April 28, 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
#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, 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
#7
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
#8
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
https://www.readbyqxmd.com/read/28297660/progesterone-prevents-high-grade-serous-ovarian-cancer-by-inducing-necroptosis-of-p53-defective-fallopian-tube-epithelial-cells
#9
Na-Yiyuan Wu, Hsuan-Shun Huang, Tung Hui Chao, Hsien Ming Chou, Chao Fang, Chong-Zhen Qin, Chueh-Yu Lin, Tang-Yuan Chu, Hong Hao Zhou
High-grade serous ovarian carcinoma (HGSOC) originates mainly from the fallopian tube (FT) epithelium and always carries early TP53 mutations. We previously reported that tumors initiate in the FT fimbria epithelium because of apoptotic failure and the expansion of cells with DNA double-strand breaks (DSB) caused by bathing of the FT epithelial cells in reactive oxygen species (ROSs) and hemoglobin-rich follicular fluid (FF) after ovulation. Because ovulation is frequent and HGSOC is rare, we hypothesized that luteal-phase progesterone (P4) could eliminate p53-defective FT cells...
March 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28289945/a-novel-representation-of-inter-site-tumour-heterogeneity-from-pre-treatment-computed-tomography-textures-classifies-ovarian-cancers-by-clinical-outcome
#10
Hebert Alberto Vargas, Harini Veeraraghavan, Maura Micco, Stephanie Nougaret, Yulia Lakhman, Andreas A Meier, Ramon Sosa, Robert A Soslow, Douglas A Levine, Britta Weigelt, Carol Aghajanian, Hedvig Hricak, Joseph Deasy, Alexandra Snyder, Evis Sala
PURPOSE: To evaluate the associations between clinical outcomes and radiomics-derived inter-site spatial heterogeneity metrics across multiple metastatic lesions on CT in patients with high-grade serous ovarian cancer (HGSOC). METHODS: IRB-approved retrospective study of 38 HGSOC patients. All sites of suspected HGSOC involvement on preoperative CT were manually segmented. Gray-level correlation matrix-based textures were computed from each tumour site, and grouped into five clusters using a Gaussian Mixture Model...
March 13, 2017: European Radiology
https://www.readbyqxmd.com/read/28280090/pooled-clustering-of-high-grade-serous-ovarian-cancer-gene-expression-leads-to-novel-consensus-subtypes-associated-with-survival-and-surgical-outcomes
#11
Chen Wang, Sebastian M Armasu, Kimberly R Kalli, Matthew J Maurer, Ethan P Heinzen, Gary Keeney, William A Cliby, Ann L Oberg, Scott H Kaufmann, Ellen L Goode
PURPOSE: Here we assess whether molecular subtyping identifies biological features of tumors that correlate with survival and surgical outcomes of high-grade serous ovarian cancer (HGSOC). EXPERIMENTAL DESIGN: Consensus clustering of pooled mRNA expression data from over 2,000 HGSOC cases was used to define molecular subtypes of HGSOCs. This de novo classification scheme was then applied to 381 Mayo Clinic HGSOC patients with detailed survival and surgical outcome information...
March 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28251557/establishment-and-characterization-of-a-platinum-and-paclitaxel-resistant-high-grade-serous-ovarian-carcinoma-cell-line
#12
Pang-Ning Teng, Nicholas W Bateman, Guisong Wang, Tracy Litzi, Brian E Blanton, Brian L Hood, Kelly A Conrads, Wei Ao, Kate E Oliver, Kathleen M Darcy, William P McGuire, Keren Paz, David Sidransky, Chad A Hamilton, G Larry Maxwell, Thomas P Conrads
High grade serous ovarian cancer (HGSOC) patients have a high recurrence rate after surgery and adjuvant chemotherapy due to inherent or acquired drug resistance. Cell lines derived from HGSOC tumors that are resistant to chemotherapeutic agents represent useful pre-clinical models for drug discovery. Here, we describe establishment of a human ovarian carcinoma cell line, which we term WHIRC01, from a patient-derived mouse xenograft established from a chemorefractory HGSOC patient who did not respond to carboplatin and paclitaxel therapy...
March 1, 2017: Human Cell
https://www.readbyqxmd.com/read/28223716/preoperative-red-cell-distribution-width-and-neutrophil-to-lymphocyte-ratio-predict-survival-in-patients-with-epithelial-ovarian-cancer
#13
Zheng Li, Na Hong, Melissa Robertson, Chen Wang, Guoqian Jiang
Several parameters of preoperative complete blood count (CBC) and inflammation-associated blood cell markers derived from them have been reported to correlate with prognosis in patients with epithelial ovarian cancer (EOC), but their prognostic importance and optimal cutoffs are still needed be elucidated. Clinic/pathological parameters, 5-year follow-up data and preoperative CBC parameters were obtained retrospectively in 654 EOC patients underwent primary surgery at Mayo Clinic. Cutoffs for neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) were optimized by receiver operating characteristic (ROC) curve...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28223274/long-term-responders-on-olaparib-maintenance-in-high-grade-serous-ovarian-cancer-clinical-and-molecular-characterization
#14
Stephanie Lheureux, Zhongwu Lai, Brian A Dougherty, Sarah Runswick, Darren Hodgson, Kirsten M Timms, Jerry S Lanchbury, Stanley B Kaye, Charlie Gourley, David D L Bowtell, Elise C Kohn, Clare L Scott, Ursula A Matulonis, Tony Panzarella, Katherine Karakasis, Julia V Burnier, Blake Gilks, Mark J O'Connor, Jane D Robertson, Jonathan Ledermann, J Carl Barrett, Tony W Ho, Amit M Oza
PURPOSE: Maintenance therapy with olaparib has improved progression-free survival in women with high-grade serous ovarian cancer (HGSOC), particularly those harboring BRCA1/2 mutations. The objective of this study was to characterize long-term (LT) versus short-term (ST) responders to olaparib. EXPERIMENTAL DESIGN: A comparative molecular analysis of Study 19 (NCT00753545), a randomized Phase II trial assessing olaparib maintenance after response to platinum-based chemotherapy in HGSOC, was conducted...
February 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28221868/somatic-brca1-2-recovery-as-a-resistance-mechanism-after-exceptional-response-to-poly-adp-ribose-polymerase-inhibition
#15
Stephanie Lheureux, Jeff P Bruce, Julia V Burnier, Katherine Karakasis, Patricia A Shaw, Blaise A Clarke, S Y Cindy Yang, Rene Quevedo, Tiantian Li, Mark Dowar, Valerie Bowering, Trevor J Pugh, Amit M Oza
Purpose Durable and long-term responses to the poly (ADP-ribose) polymerase inhibitor olaparib are observed in patients without BRCA1/2 mutations. However, beyond BRCA1/2 mutations, there are no approved biomarkers for olaparib in high-grade serous ovarian cancer (HGSOC). To determine mechanisms of durable response and resistance to olaparib therapy, we performed an analysis of HGSOC tumors from three patients without germline BRCA1/2 mutations who experienced exceptional responses to olaparib. Patients and Methods We performed integrated exome, low-pass genome, and RNA sequence analysis of tumors at diagnosis and upon relapse from patients with platinum-sensitive HGSOC recurrence who were treated > 5 years with olaparib therapy as a single agent...
April 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28218502/serous-tubal-intraepithelial-carcinomas-associated-with-high-grade-serous-ovarian-carcinomas-a-systematic-review
#16
REVIEW
F Chen, K Gaitskell, M J Garcia, A Albukhari, J Tsaltas, A A Ahmed
BACKGROUND: Serous tubal intraepithelial carcinomas (STICs) have been documented in high-grade serous ovarian carcinomas (HGSOCs). However, the rate of association between STICs and HGSOCs and, therefore, the fraction of HGSOCs that are likely to have originated from the fallopian tube (FT), has remained unclear. OBJECTIVE: To appraise the literature describing the association between STICs and established HGSOCs. SEARCH STRATEGY: Ovid MEDLINE and EMBASE were searched...
February 20, 2017: BJOG: An International Journal of Obstetrics and Gynaecology
https://www.readbyqxmd.com/read/28134933/inhibition-of-the-integrin-fak-signaling-axis-and-c-myc-synergistically-disrupts-ovarian-cancer-malignancy
#17
B Xu, J Lefringhouse, Z Liu, D West, L A Baldwin, C Ou, L Chen, D Napier, L Chaiswing, L D Brewer, D St Clair, O Thibault, J R van Nagell, B P Zhou, R Drapkin, J-A Huang, M L Lu, F R Ueland, X H Yang
Integrins, a family of heterodimeric receptors for extracellular matrix, are promising therapeutic targets for ovarian cancer, particularly high-grade serous-type (HGSOC), as they drive tumor cell attachment, migration, proliferation and survival by activating focal adhesion kinase (FAK)-dependent signaling. Owing to the potential off-target effects of FAK inhibitors, disruption of the integrin signaling axis remains to be a challenge. Here, we tackled this barrier by screening for inhibitors being functionally cooperative with small-molecule VS-6063, a phase II FAK inhibitor...
January 30, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28117679/the-potential-of-targeting-ribosome-biogenesis-in-high-grade-serous-ovarian-cancer
#18
REVIEW
Shunfei Yan, Daniel Frank, Jinbae Son, Katherine M Hannan, Ross D Hannan, Keefe T Chan, Richard B Pearson, Elaine Sanij
Overall survival for patients with ovarian cancer (OC) has shown little improvement for decades meaning new therapeutic options are critical. OC comprises multiple histological subtypes, of which the most common and aggressive subtype is high-grade serous ovarian cancer (HGSOC). HGSOC is characterized by genomic structural variations with relatively few recurrent somatic mutations or dominantly acting oncogenes that can be targeted for the development of novel therapies. However, deregulation of pathways controlling homologous recombination (HR) and ribosome biogenesis has been observed in a high proportion of HGSOC, raising the possibility that targeting these basic cellular processes may provide improved patient outcomes...
January 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28115208/activin-a-stimulates-migration-of-the-fallopian-tube-epithelium-an-origin-of-high-grade-serous-ovarian-cancer-through-non-canonical-signaling
#19
Matthew Dean, David A Davis, Joanna E Burdette
Factors that stimulate the migration of fallopian tube epithelial (FTE)-derived high-grade serous ovarian cancer (HGSOC) to the ovary are poorly elucidated. This study characterized the effect of the ovarian hormone, activin A, on normal FTE and HGSOC. Activin A and TGFβ1 induced an epithelial-to-mesenchymal transition in murine oviductal epithelial (MOE) cells, but only activin A increased migration. The migratory effect of activin A was independent of Smad2/3 and required phospho-AKT, phospho-ERK, and Rac1...
April 10, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28111004/single-cell-sequencing-reveals-heterogeneity-within-ovarian-cancer-epithelium-and-cancer-associated-stromal-cells
#20
Boris J Winterhoff, Makayla Maile, Amit Kumar Mitra, Attila Sebe, Martina Bazzaro, Melissa A Geller, Juan E Abrahante, Molly Klein, Raffaele Hellweg, Sally A Mullany, Kenneth Beckman, Jerry Daniel, Timothy K Starr
OBJECTIVES: The purpose of this study was to determine the level of heterogeneity in high grade serous ovarian cancer (HGSOC) by analyzing RNA expression in single epithelial and cancer associated stromal cells. In addition, we explored the possibility of identifying subgroups based on pathway activation and pre-defined signatures from cancer stem cells and chemo-resistant cells. METHODS: A fresh, HGSOC tumor specimen derived from ovary was enzymatically digested and depleted of immune infiltrating cells...
March 2017: Gynecologic Oncology
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