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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
#1
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
#2
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
#3
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
#4
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...
November 26, 2016: Current Opinion in Obstetrics & Gynecology
https://www.readbyqxmd.com/read/27856443/genomics-of-ovarian-cancer-progression-reveals-diverse-metastatic-trajectories-including-intraepithelial-metastasis-to-the-fallopian-tube
#5
Mark A Eckert, Shawn Pan, Kyle M Hernandez, Rachel M Loth, Jorge Andrade, Samuel L Volchenboum, Pieter Faber, Anthony Montag, Ricardo Lastra, Marcus E Peter, S Diane Yamada, Ernst Lengyel
: Accumulating evidence has supported the fallopian tube rather than the ovary as the origin for high-grade serous ovarian cancer (HGSOC). To understand the relationship between putative precursor lesions and metastatic tumors, we performed whole-exome sequencing on specimens from eight HGSOC patient progression series consisting of serous tubal intraepithelial carcinomas (STIC), invasive fallopian tube lesions, invasive ovarian lesions, and omental metastases. Integration of copy number and somatic mutations revealed patient-specific patterns with similar mutational signatures and copy-number variation profiles across all anatomic sites, suggesting that genomic instability is an early event in HGSOC...
October 7, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27852697/chromosomal-instability-in-cell-free-dna-as-a-highly-specific-biomarker-for-detection-of-ovarian-cancer-in-women-with-adnexal-masses
#6
Adriaan Vanderstichele, Pieter Busschaert, Dominiek Smeets, Chiara Landolfo, Els Van Nieuwenhuysen, Karin Leunen, Patrick Neven, Frederic Amant, Sven Mahner, Elena Ioana Braicu, Robert Zeilinger, An Coosemans, Dirk Timmerman, Diether Lambrechts, Ignace Vergote
PURPOSE: Chromosomal instability is a hallmark of ovarian cancer. Here, we explore copy number alteration (CNA) profiling in cell-free DNA as a potential biomarker to detect malignancy in patients presenting with an adnexal mass. EXPERIMENTAL DESIGN: We prospectively enrolled 68 patients with an adnexal mass, of which 57 were diagnosed with invasive or borderline carcinoma and 11 with benign disease. Cell-free DNA was extracted from plasma and analyzed by low-coverage whole-genome sequencing...
November 14, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27833898/nuak1-ark5-is-associated-with-poor-prognosis-in-ovarian-cancer
#7
Neil T Phippen, Nicholas W Bateman, Guisong Wang, Kelly A Conrads, Wei Ao, Pang-Ning Teng, Tracy A Litzi, Julie Oliver, G Larry Maxwell, Chad A Hamilton, Kathleen M Darcy, Thomas P Conrads
BACKGROUND AND OBJECTIVE: Nua kinase 1 (NUAK1) was identified in multigene signatures of survival and suboptimal debulking in high-grade serous ovarian cancer (HGSOC). This study investigates the individual clinical and biologic contributions of NUAK1 in HGSOC patients and cell lines. METHODS: Public transcript expression, clinical, and outcome data were used to interrogate the relationship between NUAK1 and clinicopathologic factors and patient outcomes including progression-free survival (PFS) and molecular subtypes using logistic and Cox modeling...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27798111/the-ring-finger-domain-e3-ubiquitin-ligases-brca1-and-the-rnf20-rnf40-complex-in-global-loss-of-the-chromatin-mark-histone-h2b-monoubiquitination-h2bub1-in-cell-line-models-and-primary-high-grade-serous-ovarian-cancer
#8
Kristie-Ann Dickson, Alexander J Cole, Anthony J Gill, Adele Clarkson, Gregory B Gard, Angela Chou, Catherine J Kennedy, Beric R Henderson, Sian Fereday, Nadia Traficante, Kathryn Alsop, David D Bowtell, Anna deFazio, Roderick Clifton-Bligh, Deborah J Marsh
Enzymatic factors driving cancer-associated chromatin remodelling are of increasing interest as the role of the cancer epigenome in gene expression and DNA repair processes becomes elucidated. Monoubiquitination of histone H2B at lysine 120 (H2Bub1) is a central histone modification that functions in histone cross-talk, transcriptional elongation, DNA repair, maintaining centromeric chromatin and replication-dependent histone mRNA 3'-end processing, as well as being required for the differentiation of stem cells...
October 25, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27788210/nuclear-commd1-is-associated-with-cisplatin-sensitivity-in-ovarian-cancer
#9
Alina Fedoseienko, Hylke W Wieringa, G Bea A Wisman, Evelien Duiker, Anna K L Reyners, Marten H Hofker, Ate G J van der Zee, Bart van de Sluis, Marcel A T M van Vugt
Copper metabolism MURR1 domain 1 (COMMD1) protein is a multifunctional protein, and its expression has been correlated with patients' survival in different types of cancer. In vitro studies revealed that COMMD1 plays a role in sensitizing cancer cell lines to cisplatin, however, the mechanism and its role in platinum sensitivity in cancer has yet to be established. We evaluated the role of COMMD1 in cisplatin sensitivity in A2780 ovarian cancer cells and the relation between COMMD1 expression and response to platinum-based therapy in advanced stage high-grade serous ovarian cancer (HGSOC) patients...
2016: PloS One
https://www.readbyqxmd.com/read/27788148/a-systems-biology-comparison-of-ovarian-cancers-implicates-putative-somatic-driver-mutations-through-protein-protein-interaction-models
#10
Mary Qu Yang, Laura Elnitski
Ovarian carcinomas can be aggressive with a high mortality rate (e.g., high-grade serous ovarian carcinomas, or HGSOCs), or indolent with much better long-term outcomes (e.g., low-malignant-potential, or LMP, serous ovarian carcinomas). By comparing LMP and HGSOC tumors, we can gain insight into the mechanisms underlying malignant progression in ovarian cancer. However, previous studies of the two subtypes have been focused on gene expression analysis. Here, we applied a systems biology approach, integrating gene expression profiles derived from two independent data sets containing both LMP and HGSOC tumors with protein-protein interaction data...
2016: PloS One
https://www.readbyqxmd.com/read/27775699/susd2-expression-in-high-grade-serous-ovarian-cancer-correlates-with-increased-patient-survival-and-defective-mesothelial-clearance
#11
J N Sheets, M Iwanicki, J F Liu, B E Howitt, M S Hirsch, J A A Gubbels, R Drapkin, K A Egland
The cause of death among the majority of epithelial ovarian cancer (EOC) patients involves passive dissemination of cancer cells within the peritoneal cavity and subsequent implantation of cancer spheroids into adjacent organs. Thus, it is important to identify the factors that mediate EOC metastasis and implantation, including clearance of the mesothelium. Sushi domain containing 2 (SUSD2) encodes a type I transmembrane protein containing several functional domains inherent to adhesion molecules. Immunohistochemical analysis determined the presence of SUSD2 in several subtypes of EOC, with the strongest staining observed in high-grade serous ovarian carcinomas (HGSOCs)...
October 24, 2016: Oncogenesis
https://www.readbyqxmd.com/read/27765068/genome-wide-methylation-profiling-of-ovarian-cancer-patient-derived-xenografts-treated-with-the-demethylating-agent-decitabine-identifies-novel-epigenetically-regulated-genes-and-pathways
#12
Tushar Tomar, Steven de Jong, Nicolette G Alkema, Rieks L Hoekman, Gert Jan Meersma, Harry G Klip, Ate Gj van der Zee, G Bea A Wisman
BACKGROUND: In high-grade serous ovarian cancer (HGSOC), intrinsic and/or acquired resistance against platinum-containing chemotherapy is a major obstacle for successful treatment. A low frequency of somatic mutations but frequent epigenetic alterations, including DNA methylation in HGSOC tumors, presents the cancer epigenome as a relevant target for innovative therapy. Patient-derived xenografts (PDXs) supposedly are good preclinical models for identifying novel drug targets. However, the representativeness of global methylation status of HGSOC PDXs compared to their original tumors has not been evaluated so far...
October 20, 2016: Genome Medicine
https://www.readbyqxmd.com/read/27764122/blood-plasma-derived-anti-glycan-antibodies-to-sialylated-and-sulfated-glycans-identify-ovarian-cancer-patients
#13
Tatiana Pochechueva, Alexander Chinarev, Andreas Schoetzau, André Fedier, Nicolai V Bovin, Neville F Hacker, Francis Jacob, Viola Heinzelmann-Schwarz
Altered levels of naturally occurring anti-glycan antibodies (AGA) circulating in human blood plasma are found in different pathologies including cancer. Here the levels of AGA directed against 22 negatively charged (sialylated and sulfated) glycans were assessed in high-grade serous ovarian cancer (HGSOC, n = 22) patients and benign controls (n = 31) using our previously developed suspension glycan array (SGA). Specifically, the ability of AGA to differentiate between controls and HGSOC, the most common and aggressive type of ovarian cancer with a poor outcome was determined...
2016: PloS One
https://www.readbyqxmd.com/read/27634150/update-on-poly-adp-ribose-polymerase-inhibition-for-ovarian-cancer-treatment
#14
REVIEW
Anselmo Papa, Davide Caruso, Martina Strudel, Silverio Tomao, Federica Tomao
BACKGROUND: Despite standard treatment for epithelial ovarian cancer (EOC), that involves cytoreductive surgery followed by platinum-based chemotherapy, and initial high response rates to these, up to 80 % of patients experience relapses with a median progression-free survival of 12-18 months. There remains an urgent need for novel targeted therapies to improve clinical outcomes in ovarian cancer. Of the many targeted therapies currently under evaluation, the most promising strategies developed thus far are antiangiogenic agents and Poly(ADP-ribose) polymerase (PARP) inhibitors...
2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27617304/epigenetic-remodeling-regulates-transcriptional-changes-between-ovarian-cancer-and-benign-precursors
#15
Kevin M Elias, Megan M Emori, Thomas Westerling, Henry Long, Anna Budina-Kolomets, Fugen Li, Emily MacDuffie, Michelle R Davis, Alexander Holman, Brian Lawney, Matthew L Freedman, John Quackenbush, Myles Brown, Ronny Drapkin
Regulation of lineage-restricted transcription factors has been shown to influence malignant transformation in several types of cancer. Whether similar mechanisms are involved in ovarian cancer pathogenesis is unknown. PAX8 is a nuclear transcription factor that controls the embryologic development of the Müllerian system, including the fallopian tubes. Recent studies have shown that fallopian tube secretory epithelial cells (FTSECs) give rise to the most common form of ovarian cancer, high-grade serous ovarian carcinomas (HGSOCs)...
August 18, 2016: JCI Insight
https://www.readbyqxmd.com/read/27614696/in-vivo-anti-tumor-activity-of-the-parp-inhibitor-niraparib-in-homologous-recombination-deficient-and-proficient-ovarian-carcinoma
#16
Mariam M AlHilli, Marc A Becker, S John Weroha, Karen S Flatten, Rachel M Hurley, Maria I Harrell, Ann L Oberg, Matt J Maurer, Kieran M Hawthorne, Xiaonan Hou, Sean C Harrington, Sarah McKinstry, X Wei Meng, Keith M Wilcoxen, Kimberly R Kalli, Elizabeth M Swisher, Scott H Kaufmann, Paul Haluska
OBJECTIVE: Poly(ADP-ribose) polymerase (PARP) inhibitors have yielded encouraging responses in high-grade serous ovarian carcinomas (HGSOCs), but the optimal treatment setting remains unknown. We assessed the effect of niraparib on HGSOC patient-derived xenograft (PDX) models as well as the relationship between certain markers of homologous recombination (HR) status, including BRCA1/2 mutations and formation of RAD51 foci after DNA damage, and response of these PDXs to niraparib in vivo...
September 7, 2016: Gynecologic Oncology
https://www.readbyqxmd.com/read/27602775/epithelialization-of-mouse-ovarian-tumor-cells-originating-in-the-fallopian-tube-stroma
#17
Yuanyuan Hua, Pui-Wah Choi, Alexander J Trachtenberg, Allen C Ng, Winston P Kuo, Shu-Kay Ng, Daniela M Dinulescu, Martin M Matzuk, Ross S Berkowitz, Shu-Wing Ng
Epithelial ovarian carcinoma accounts for 90% of all ovarian cancer and is the most deadly gynecologic malignancy. Recent studies have suggested that fallopian tube fimbriae can be the origin of cells for high-grade serous subtype of epithelial ovarian carcinoma (HGSOC). A mouse HGSOC model with conditional Dicer-Pten double knockout (Dicer-Pten DKO) developed primary tumors, intriguingly, from the fallopian tube stroma. We examined the growth and epithelial phenotypes of the Dicer-Pten DKO mouse tumor cells contributable by each gene knockout...
September 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27563818/cadherin-6-type-2-k-cadherin-cdh6-is-regulated-by-mutant-p53-in-the-fallopian-tube-but-is-not-expressed-in-the-ovarian-surface
#18
Subbulakshmi Karthikeyan, Daniel D Lantvit, Dam Hee Chae, Joanna E Burdette
High-grade serous ovarian cancer (HGSOC) is the most lethal gynecological malignancy and may arise in either the fallopian tube epithelium (FTE) or ovarian surface epithelium (OSE). A mutation in p53 is reported in 96% of HGSOC, most frequently at R273 and R248. The goal of this study was to identify specific gene targets in the FTE that are altered by mutant p53, but not in the OSE. Gene analysis revealed that both R273 and R248 mutant p53 reduces CDH6 expression in the oviduct, but CDH6 was not detected in murine OSE cells...
August 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27561551/integrative-proteomic-profiling-of-ovarian-cancer-cell-lines-reveals-precursor-cell-associated-proteins-and-functional-status
#19
F Coscia, K M Watters, M Curtis, M A Eckert, C Y Chiang, S Tyanova, A Montag, R R Lastra, E Lengyel, M Mann
A cell line representative of human high-grade serous ovarian cancer (HGSOC) should not only resemble its tumour of origin at the molecular level, but also demonstrate functional utility in pre-clinical investigations. Here, we report the integrated proteomic analysis of 26 ovarian cancer cell lines, HGSOC tumours, immortalized ovarian surface epithelial cells and fallopian tube epithelial cells via a single-run mass spectrometric workflow. The in-depth quantification of >10,000 proteins results in three distinct cell line categories: epithelial (group I), clear cell (group II) and mesenchymal (group III)...
August 26, 2016: Nature Communications
https://www.readbyqxmd.com/read/27558279/abnormal-plasma-dna-profiles-in-early-ovarian-cancer-using-a-non-invasive-prenatal-testing-platform-implications-for-cancer-screening
#20
Paul A Cohen, Nicola Flowers, Stephen Tong, Natalie Hannan, Mark D Pertile, Lisa Hui
BACKGROUND: Non-invasive prenatal testing (NIPT) identifies fetal aneuploidy by sequencing cell-free DNA in the maternal plasma. Pre-symptomatic maternal malignancies have been incidentally detected during NIPT based on abnormal genomic profiles. This low coverage sequencing approach could have potential for ovarian cancer screening in the non-pregnant population. Our objective was to investigate whether plasma DNA sequencing with a clinical whole genome NIPT platform can detect early- and late-stage high-grade serous ovarian carcinomas (HGSOC)...
August 24, 2016: BMC Medicine
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