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https://www.readbyqxmd.com/read/29221157/high-ptpn13-expression-in-high-grade-serous-ovarian-carcinoma-is-associated-with-a-better-patient-outcome
#1
Véronique D'Hondt, Magalie Lacroix-Triki, Marta Jarlier, Florence Boissiere-Michot, Carole Puech, Peter Coopman, Dionyssios Katsaros, Gilles Freiss
Background: Chromosome 4q loss of heterozygosity (LOH) is frequently observed in high-grade serous ovarian carcinoma (HGSOC). However, this LOH has not been clearly associated with the inactivation of any tumor suppressor gene(s). As the tumor suppressor gene PTPN13 is located on chromosome 4q21, we investigated its expression in HGSOC. Methods: PTPN13 protein expression was investigated by immunohistochemistry (IHC) in normal ovary epithelium and in 30 HGSOC samples, whereas PTPN13 mRNA expression was quantified by RT-PCR in another independent cohort of 28 HGSOC samples...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29196464/deconstruction-of-a-metastatic-tumor-microenvironment-reveals-a-common-matrix-response-in-human-cancers
#2
Oliver M T Pearce, Robin Delaine-Smith, Eleni Maniati, Sam Nichols, Jun Wang, Steffen Böhm, Vinothini Rajeeve, Dayem Ullah, Probir Chakravarty, Roanne R Jones, Anne Montfort, Tom Dowe, John Gribben, J Louise Jones, Hemant M Kocher, Jonathan S Serody, Benjamin G Vincent, John Connelly, James D Brenton, Claude Chelala, Pedro R Cutillas, Michelle Lockley, Conrad Bessant, Martin Knight, Frances R Balkwill
We have profiled, for the first time, an evolving human metastatic microenvironment, measuring gene expression, matrisome proteomics, cytokine and chemokine levels, cellularity, ECM organization and biomechanical properties, all on the same sample. Using biopsies of high-grade serous ovarian cancer (HGSOC) metastases that ranged from minimal to extensive disease, we show how non-malignant cell densities and cytokine networks evolve with disease progression. Multivariate integration of the different components allowed us to define for the first time, gene and protein profiles that predict extent of disease and tissue stiffness, whilst also revealing the complexity and dynamic nature of matrisome remodeling during development of metastases...
December 1, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29163813/the-novel-zip4-regulation-and-its-role-in-ovarian-cancer
#3
Qipeng Fan, Qingchun Cai, Pengfei Li, Wenyan Wang, Jing Wang, Emily Gerry, Tian-Li Wang, Ie-Ming Shih, Kenneth P Nephew, Yan Xu
Our RNAseq analyses revealed that ZIP4 is a top gene up-regulated in more aggressive ovarian cancer cells. ZIP4's role in cancer stem cells has not been reported in any type of cancer. In addition, the role and regulation of ZIP4, a zinc transporter, have been studied in the context of extracellular zinc transporting. Factors other than zinc with ZIP4 regulatory effects are essentially unknown. ZIP4 expression and its regulation in epithelial ovarian cancer cells was assessed by immunoblotting, quantitative PCR, or immunohistochemistry staining in human ovarian tissues...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29157627/letrozole-may-be-a-valuable-maintenance-treatment-in-high-grade-serous-ovarian-cancer-patients
#4
V Heinzelmann-Schwarz, A Knipprath Mészaros, S Stadlmann, F Jacob, A Schoetzau, K Russell, M Friedlander, G Singer, M Vetter
OBJECTIVES: Endocrine therapy is used as maintenance in estrogen receptor (ER) positive breast cancers and has been proposed in low-grade serous ovarian cancers (LGSOC). Here we examine a rationale for its use as maintenance in high-grade serous ovarian cancers (HGSOC). METHODS: We accessed the TCGA PANCAN dataset to evaluate the expression of ESR1. ESR1 expression data on all cancers (n=8901) and HGSOC (n=527) were followed by investigation of ER expression via immunohistochemistry (IHC) (n=4071)...
November 17, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/29141850/autoantibodies-against-hsf1-and-ccdc155-as-biomarkers-of-early-stage-high-grade-serous-ovarian-cancer
#5
Amy L Wilson, Laura R Moffitt, Nadine Duffield, Adam Rainczuk, Tom W Jobling, Magdalena Plebanski, Andrew N Stephens
BACKGROUND: Tumor-directed circulating autoantibodies (AAbs) are a well-established feature of many solid tumor types, and are often observed prior to clinical disease manifestation. As such, they may provide a good indicator of early disease development. We have conducted a pilot study to identify novel AAbs as markers of early stage HGSOCs. METHODS: A rare cohort of patients with early (FIGO stage Ia-c) HGSOCs for IgG, IgA and IgM-mediated AAb reactivity using high content protein arrays (containing 9184 individual proteins)...
November 15, 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/29132874/combining-serum-microrna-and-ca-125-as-prognostic-indicators-of-preoperative-surgical-outcome-in-women-with-high-grade-serous-ovarian-cancer
#6
Jaynish S Shah, Gregory B Gard, Jean Yang, Jayne Maidens, Susan Valmadre, Patsy S Soon, Deborah J Marsh
OBJECTIVES: The most widely used approach for the clinical management of women with high-grade serous ovarian cancer (HGSOC) is surgery, followed by platinum and taxane based chemotherapy. The degree of macroscopic disease remaining at the conclusion of surgery is a key prognostic factor determining progression free and overall survival. We sought to develop a non-invasive test to assist surgeons to determine the likelihood of achieving complete surgical resection. This knowledge could be used to plan surgical approaches for optimal clinical management...
November 10, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/29130934/recurrent-ubiquitin-b-silencing-in-gynecological-cancers-establishes-dependence-on-ubiquitin-c
#7
Alexia T Kedves, Scott Gleim, Xiaoyou Liang, Dennis M Bonal, Frederic Sigoillot, Fred Harbinski, Sneha Sanghavi, Christina Benander, Elizabeth George, Prafulla C Gokhale, Quang-De Nguyen, Paul T Kirschmeier, Robert J Distel, Jeremy Jenkins, Michael S Goldberg, William C Forrester
Transcriptional repression of ubiquitin B (UBB) is a cancer-subtype-specific alteration that occurs in a substantial population of patients with cancers of the female reproductive tract. UBB is 1 of 2 genes encoding for ubiquitin as a polyprotein consisting of multiple copies of ubiquitin monomers. Silencing of UBB reduces cellular UBB levels and results in an exquisite dependence on ubiquitin C (UBC), the second polyubiquitin gene. UBB is repressed in approximately 30% of high-grade serous ovarian cancer (HGSOC) patients and is a recurrent lesion in uterine carcinosarcoma and endometrial carcinoma...
November 13, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29061967/high-grade-serous-ovarian-carcinomas-originate-in-the-fallopian-tube
#8
S Intidhar Labidi-Galy, Eniko Papp, Dorothy Hallberg, Noushin Niknafs, Vilmos Adleff, Michael Noe, Rohit Bhattacharya, Marian Novak, Siân Jones, Jillian Phallen, Carolyn A Hruban, Michelle S Hirsch, Douglas I Lin, Lauren Schwartz, Cecile L Maire, Jean-Christophe Tille, Michaela Bowden, Ayse Ayhan, Laura D Wood, Robert B Scharpf, Robert Kurman, Tian-Li Wang, Ie-Ming Shih, Rachel Karchin, Ronny Drapkin, Victor E Velculescu
High-grade serous ovarian carcinoma (HGSOC) is the most frequent type of ovarian cancer and has a poor outcome. It has been proposed that fallopian tube cancers may be precursors of HGSOC but evolutionary evidence for this hypothesis has been limited. Here, we perform whole-exome sequence and copy number analyses of laser capture microdissected fallopian tube lesions (p53 signatures, serous tubal intraepithelial carcinomas (STICs), and fallopian tube carcinomas), ovarian cancers, and metastases from nine patients...
October 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/29057791/emerging-therapeutics-to-overcome-chemoresistance-in-epithelial-ovarian-cancer-a-mini-review
#9
REVIEW
Robert Cornelison, Danielle C Llaneza, Charles N Landen
Ovarian cancer is the fifth leading cause of cancer death among women and the most lethal gynecologic malignancy. One of the leading causes of death in high-grade serous ovarian cancer (HGSOC) is chemoresistant disease, which may present as intrinsic or acquired resistance to therapies. Here we discuss some of the known molecular mechanisms of chemoresistance that have been exhaustively investigated in chemoresistant ovarian cancer, including drug efflux pump multidrug resistance protein 1 (MDR1), the epithelial-mesenchymal transition, DNA damage and repair capacity...
October 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29049607/dose-response-association-of-cd8-tumor-infiltrating-lymphocytes-and-survival-time-in-high-grade-serous-ovarian-cancer
#10
Ellen L Goode, Matthew S Block, Kimberly R Kalli, Robert A Vierkant, Wenqian Chen, Zachary C Fogarty, Aleksandra Gentry-Maharaj, Aleksandra Toloczko, Alexander Hein, Aliecia L Bouligny, Allan Jensen, Ana Osorio, Andreas D Hartkopf, Andy Ryan, Anita Chudecka-Glaz, Anthony M Magliocco, Arndt Hartmann, Audrey Y Jung, Bo Gao, Brenda Y Hernandez, Brooke L Fridley, Bryan M McCauley, Catherine J Kennedy, Chen Wang, Chloe Karpinskyj, Christiani B de Sousa, Daniel G Tiezzi, David L Wachter, Esther Herpel, Florin Andrei Taran, Francesmary Modugno, Gregg Nelson, Jan Lubinski, Janusz Menkiszak, Jennifer Alsop, Jenny Lester, Jesús García-Donas, Jill Nation, Jillian Hung, José Palacios, Joseph H Rothstein, Joseph L Kelley, Jurandyr M de Andrade, Luis Robles-Díaz, Maria P Intermaggio, Martin Widschwendter, Matthias W Beckmann, Matthias Ruebner, Mercedes Jimenez-Linan, Naveena Singh, Oleg Oszurek, Paul R Harnett, Peter F Rambau, Peter Sinn, Philipp Wagner, Prafull Ghatage, Raghwa Sharma, Robert P Edwards, Roberta B Ness, Sandra Orsulic, Sara Y Brucker, Sharon E Johnatty, Teri A Longacre, Ursula Eilber, Valerie McGuire, Weiva Sieh, Yanina Natanzon, Zheng Li, Alice S Whittemore, Anna deFazio, Annette Staebler, Beth Y Karlan, Blake Gilks, David D Bowtell, Estrid Høgdall, Francisco J Candido Dos Reis, Helen Steed, Ian G Campbell, Jacek Gronwald, Javier Benítez, Jennifer M Koziak, Jenny Chang-Claude, Kirsten B Moysich, Linda E Kelemen, Linda S Cook, Marc T Goodman, María José García, Peter A Fasching, Stefan Kommoss, Suha Deen, Susanne K Kjaer, Usha Menon, James D Brenton, Paul D P Pharoah, Georgia Chenevix-Trench, David G Huntsman, Stacey J Winham, Martin Köbel, Susan J Ramus
Importance: Cytotoxic CD8+ tumor-infiltrating lymphocytes (TILs) participate in immune control of epithelial ovarian cancer; however, little is known about prognostic patterns of CD8+ TILs by histotype and in relation to other clinical factors. Objective: To define the prognostic role of CD8+ TILs in epithelial ovarian cancer. Design, Setting, and Participants: This was a multicenter observational, prospective survival cohort study of the Ovarian Tumor Tissue Analysis Consortium...
October 12, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28976449/a-2-protein-signature-predicting-clinical-outcome-in-high-grade-serous-ovarian-cancer
#11
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
#12
Elise C Kohn, Jung-Min Lee, S Percy Ivy
Rucaparib, a polyADPribose polymerase inhibitor (PARPi), was approved recently for use in women with high-grade serous ovarian cancer (HGSOC). It is now one of three approved PARPi for use in recurrent ovarian cancer, a family of agents that has changed the HGSOC treatment landscape and outcome. Clin Cancer Res; 23(23); 7155-7. ©2017 AACRSee related article by Balasubramaniam et al., p. 7165.
December 1, 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
#13
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
#14
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%)...
December 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28881656/brd4-facilitates-dna-damage-response-and-represses-cbx5-heterochromatin-protein-1-hp1
#15
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
#16
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
#17
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
#18
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
#19
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...
December 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28794804/brca-mutation-in-ovarian-cancer-testing-implications-and-treatment-considerations
#20
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
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