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https://www.readbyqxmd.com/read/28223716/preoperative-red-cell-distribution-width-and-neutrophil-to-lymphocyte-ratio-predict-survival-in-patients-with-epithelial-ovarian-cancer
#1
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
#2
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
#3
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...
February 21, 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
#4
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
#5
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
#6
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
#7
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...
January 20, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28111004/single-cell-sequencing-reveals-heterogeneity-within-ovarian-cancer-epithelium-and-cancer-associated-stromal-cells
#8
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...
January 19, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28097235/a-patient-derived-xenograft-platform-to-study-brca-deficient-ovarian-cancers
#9
Erin George, Hyoung Kim, Clemens Krepler, Brandon Wenz, Mehran Makvandi, Janos L Tanyi, Eric Brown, Rugang Zhang, Patricia Brafford, Stephanie Jean, Robert H Mach, Yiling Lu, Gordon B Mills, Meenhard Herlyn, Mark Morgan, Xiaochen Zhang, Robert Soslow, Ronny Drapkin, Neil Johnson, Ying Zheng, George Cotsarelis, Katherine L Nathanson, Fiona Simpkins
Approximately 50% of high-grade serous ovarian cancers (HGSOCs) have defects in genes involved in homologous recombination (HR) (i.e., BRCA1/2). Preclinical models to optimize therapeutic strategies for HR-deficient (HRD) HGSOC are lacking. We developed a preclinical platform for HRD HGSOCs that includes primary tumor cultures, patient-derived xenografts (PDXs), and molecular imaging. Models were characterized by immunohistochemistry, targeted sequencing, and reverse-phase protein array analysis. We also tested PDX tumor response to PARP, CHK1, and ATR inhibitors...
January 12, 2017: JCI Insight
https://www.readbyqxmd.com/read/28073843/active-estrogen-receptor-alpha-signaling-in-ovarian-cancer-models-and-clinical-specimens
#10
Courtney L Andersen, Matthew J Sikora, Michelle M Boisen, Tianzhou Ma, Alec Christie, George Tseng, Yong Seok Park, Soumya Luthra, Uma Chandran, Paul Haluska, Gina Mantia-Smaldone, Kunle Odunsi, Karen McLean, Adrian V Lee, Esther Elishaev, Robert P Edwards, Steffi Oesterreich
PURPOSE: High-grade serous ovarian cancer (HGSOC) is an aggressive disease with few available targeted therapies. Despite high expression of estrogen receptor-alpha in ~80% of HGSOC and some small but promising clinical trials of endocrine therapy, estrogen receptor-alpha has been understudied as a target in this disease. We sought to identify hormone-responsive, estrogen receptor-alpha-dependent HGSOC. EXPERIMENTAL DESIGN: We characterized endocrine response in HGSOC cells across culture conditions (2-D, 3-D, forced suspension) and in patient-derived xenograft (PDX) explants, assessing proliferation and gene expression...
January 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28065619/tumor-associated-macrophage-expression-of-pd-l1-in-implants-of-high-grade-serous-ovarian-carcinoma-a-comparison-of-matched-primary-and-metastatic-tumors
#11
Chelsea E Gottlieb, Anne M Mills, Janet V Cross, Kari L Ring
OBJECTIVE: Data on PD-L1 expression in high grade serous ovarian carcinoma (HGSOC) is mixed. Some studies report robust tumor staining and others identify expression limited to tumor-associated macrophages (TAM). TAM PD-L1 expression is induced in HGSOC metastatic implants from patients who have undergone chemotherapy. However, it is unclear whether TAM acquisition of PD-L1 plays a role in treatment naïve tumors. We investigated PD-L1 expression in primary ovarian tumors and matched metastatic implants from predominantly treatment-naïve HGSOC...
January 5, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28017893/circulating-mirna-landscape-identifies-mir-1246-as-promising-diagnostic-biomarker-in-high-grade-serous-ovarian-carcinoma-a-validation-across-two-independent-cohorts
#12
Paola Todeschini, Elisa Salviato, Lara Paracchini, Manuela Ferracin, Marco Petrillo, Laura Zanotti, Germana Tognon, Angela Gambino, Enrica Calura, Giulia Caratti, Paolo Martini, Luca Beltrame, Lorenzo Maragoni, Daniela Gallo, Franco E Odicino, Enrico Sartori, Giovanni Scambia, Massimo Negrini, Antonella Ravaggi, Maurizio D'Incalci, Sergio Marchini, Eliana Bignotti, Chiara Romualdi
High-grade serous ovarian carcinoma (HGSOC) is the most lethal gynecologic neoplasm, with five-year survival rate below 30%. Early disease detection is of utmost importance to improve HGSOC cure rate. Sera from 168 HGSOC patients and 65 healthy controls were gathered together from two independent collections and stratified into a training set, for miRNA marker identification, and a validation set, for data validation. An innovative statistical approach for microarray data normalization was developed to identify differentially expressed miRNAs...
March 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/27997533/exploratory-analysis-of-tp53-mutations-in-circulating-tumour-dna-as-biomarkers-of-treatment-response-for-patients-with-relapsed-high-grade-serous-ovarian-carcinoma-a-retrospective-study
#13
Christine A Parkinson, Davina Gale, Anna M Piskorz, Heather Biggs, Charlotte Hodgkin, Helen Addley, Sue Freeman, Penelope Moyle, Evis Sala, Karen Sayal, Karen Hosking, Ioannis Gounaris, Mercedes Jimenez-Linan, Helena M Earl, Wendi Qian, Nitzan Rosenfeld, James D Brenton
BACKGROUND: Circulating tumour DNA (ctDNA) carrying tumour-specific sequence alterations may provide a minimally invasive means to dynamically assess tumour burden and response to treatment in cancer patients. Somatic TP53 mutations are a defining feature of high-grade serous ovarian carcinoma (HGSOC). We tested whether these mutations could be used as personalised markers to monitor tumour burden and early changes as a predictor of response and time to progression (TTP). METHODS AND FINDINGS: We performed a retrospective analysis of serial plasma samples collected during routine clinical visits from 40 patients with HGSOC undergoing heterogeneous standard of care treatment...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27993965/targeting-the-atr-chk1-axis-with-parp-inhibition-results-in-tumor-regression-in-brca-mutant-ovarian-cancer-models
#14
Hyoung Kim, Erin George, Ryan L Ragland, Stavros Rafail, Rugang Zhang, Clemens Krepler, Mark Morgan, Meenhard Herlyn, Eric J Brown, Fiona Simpkins
PURPOSE: PARP inhibition (PARPi) has modest clinical activity in recurrent BRCA mutant (BRCAMUT) high-grade serous ovarian cancers (HGSOC). We hypothesized that PARPi increases dependence on ATR/CHK1 such that combination PARPi with ATR/CHK1 blockade results in increased cell death and tumor regression. EXPERIMENTAL DESIGN: Effects of PARPi (olaparib), CHK1 inhibition (CHK1i;MK8776) or ATR inhibition (ATRi;AZD6738) alone or in combination on survival, colony formation, cell-cycle, genome instability and apoptosis were evaluated in BRCA1/2MUT HGSOC cells...
December 19, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27984374/cd56-neural-cell-adhesion-molecule-expression-in-ovarian-carcinomas-association-with-high-grade-and-advanced-stage-but-not-with-neuroendocrine-differentiation
#15
Hans-Christian Bösmüller, Philipp Wagner, Deborah Lam Pham, Anna K Fischer, Karen Greif, Christine Beschorner, Bence Sipos, Falko Fend, Annette Staebler
OBJECTIVE: Neural cell adhesion molecule (CD56) has been proposed as a potential marker for neuroendocrine differentiation in carcinomas, together with synaptophysin and chromogranin A. However, CD56 immunoreactivity by itself can be found in a broad variety of tumors, including ovarian neoplasms. CD56 has recently been suggested as a potential target for antibody-based therapy. However, for ovarian carcinoma, there is only limited data available regarding the pattern of CD56 immunoreactivity, coexpression of neuroendocrine markers, and correlation with histological types and clinical parameters...
February 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/27940126/comparative-transcriptome-analysis-links-distinct-peritoneal-tumor-spread-types-miliary-and-non-miliary-with-putative-origin-tubes-and-ovaries-in-high-grade-serous-ovarian-cancer
#16
Katharina Auer, Anna Bachmayr-Heyda, Stefanie Aust, Thomas W Grunt, Dietmar Pils
High grade serous ovarian cancer (HGSOC) is characterized by extensive local, i.e. peritoneal, tumor spread, manifested in two different clinical presentations, miliary (many millet sized peritoneal implants) and non-miliary (few large exophytically growing peritoneal nodes), and an overall unfavorable outcome. HGSOC is thought to arise from fallopian tube secretory epithelial cells, via so called serous tubal intraepithelial carcinomas (STICs) but an ovarian origin was never ruled out for at least some cases...
March 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/27899992/beside-p53-and-pten-identification-of-molecular-alterations-of-the-ras-mapk-and-pi3k-akt-signaling-pathways-in-high-grade-serous-ovarian-carcinomas-to-determine-potential-novel-therapeutic-targets
#17
Shuhui Chen, Elisa Cavazza, Catherine Barlier, Julia Salleron, Pierre Filhine-Tresarrieu, Céline Gavoilles, Jean-Louis Merlin, Alexandre Harlé
Despite great histological and molecular heterogeneity, the clinical management of high-grade ovarian carcinomas remains unspecialized. As a major subgroup, high-grade serous ovarian carcinomas (HGSOCs) require novel therapies. In addition to utilizing conventional histological prognostic markers and performing oncogenetic investigations, the molecular diagnostic method of next generation sequencing (NGS) was performed to identify 'druggable' targets that could provide access to innovative therapy. The present study was performed in 45 HGSOC patients (mean age, 59...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899818/bnc2-is-a-putative-tumor-suppressor-gene-in-high-grade-serous-ovarian-carcinoma-and-impacts-cell-survival-after-oxidative-stress
#18
Laura Cesaratto, Eleonora Grisard, Michela Coan, Luigi Zandonà, Elena De Mattia, Elena Poletto, Erika Cecchin, Fabio Puglisi, Vincenzo Canzonieri, Maria Teresa Mucignat, Antonella Zucchetto, Gabriele Stocco, Alfonso Colombatti, Milena S Nicoloso, Riccardo Spizzo
Rs3814113 is the single-nucleotide polymorphism (SNP) showing the strongest association with high-grade serous ovarian carcinoma (HGSOC) incidence and is located in an intergenic region about 44 kb downstream of basonuclin 2 (BNC2) gene. Lifetime number of ovulations is associated with increased risk to develop HGSOC, probably because of cell damage of extrauterine Müllerian epithelium by ovulation-induced oxidative stress. However, the impact of low-penetrance HGSOC risk alleles (e.g. rs3814113) on the damage induced by oxidative stress remains unclear...
September 22, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27899771/-perspectives-of-individualized-treatment-by-genome-wide-analyses-in-ovarian-cancer
#19
Noriomi Matsumura, Ken Yamaguchi, Ryusuke Murakami, Masaki Mandai, Ikuo Konishi
Genome-wide analyses have recently been reported for ovarian cancer. High-grade serous ovarian carcinoma(HGSOC) almost exclusively harbor TP53 mutations and prominent copy number aberrations. Approximately 20% of HGSOCs harbor BRCA mutations, in which case PARP inhibitors may be effective. HGSOCs are classified into 4 molecular subtypes with distinct histopathological features by transcriptional profiling. These subtypes differ in prognosis and drug sensitivity. Additionally, a whole-genome analysis for HGSOC has revealed various factors that can induce resistance to chemotherapy...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/27898521/pathogenesis-and-heterogeneity-of-ovarian-cancer
#20
Paul T Kroeger, Ronny Drapkin
PURPOSE OF REVIEW: The most common type of ovarian cancer, high-grade serous ovarian carcinoma (HGSOC), was originally thought to develop from the ovarian surface epithelium. However, recent data suggest that the cells that undergo neoplastic transformation and give rise to the majority of HGSOC are from the fallopian tube. This development has impacted both translational research and clinical practice, revealing new opportunities for early detection, prevention, and treatment of ovarian cancer...
February 2017: Current Opinion in Obstetrics & Gynecology
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