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Ovarian poly

Heng Yang, Shan Lin, Xiaoping Lei, Cong Yuan, Zhanwei Tian, Yaosheng Yu, Zongsheng Zhao, Jingbo Chen
Estrous regulation in sheep has an important role in the sheep industry in improving production of meat and wool. It has been reported that an enhanced nutritional status can induce estrus resulting in an end of the anestrous season earlier than occurs in ewes with a lesser nutritional status. However, the endocrine and physiological mechanisms that induce the increased incidence of estrus remains unclear. In the present study, the differences in amounts and characteristics of miRNAs in ewes at estrus or during the anestrous season were screened by using the Illumina HiSeq sequencing technology...
October 19, 2016: Animal Reproduction Science
Robbert D A Weren, Arjen R Mensenkamp, Michiel Simons, Astrid Eijkelenboom, Aisha S Sie, Hicham Ouchene, Monique van Asseldonk, Encarna B Gomez-Garcia, Marinus J Blok, Joanne A de Hullu, Marcel R Nelen, Alexander Hoischen, Johan Bulten, Bastiaan B J Tops, Nicoline Hoogerbrugge, En Marjolijn J L Ligtenberg
With the recent introduction of Poly(ADP-ribose) polymerase (PARP) inhibitors, a promising novel therapy has become available for ovarian carcinoma patients with inactivating BRCA1 or BRCA2 mutations in their tumour. To select patients who may benefit from these treatments, assessment of the mutation status of BRCA1 and BRCA2 in the tumour is required. For reliable evaluation of germline and somatic mutations in these genes in DNA derived from formalin-fixed, paraffin-embedded (FFPE) tissue, we have developed a single molecule molecular inversion probe (smMIP)-based targeted next generation sequencing (NGS) approach...
October 21, 2016: Human Mutation
Luc Dirix, Helen Swaisland, Henk M W Verheul, Sylvie Rottey, Karin Leunen, Guy Jerusalem, Christian Rolfo, Dorte Nielsen, L Rhoda Molife, Rebecca Kristeleit, Judith de Vos-Geelen, Morten Mau-Sørensen, Patricia Soetekouw, Carla van Herpen, Anitra Fielding, Karen So, Wendy Bannister, Ruth Plummer
PURPOSE: The metabolism of olaparib, a potent inhibitor of poly(ADP-ribose) polymerase (PARP) with demonstrated efficacy in patients with BRCA-mutated ovarian cancer, is mediated by cytochrome P450 (CYP) enzymes (predominantly CYP3A4/5). We assessed the potential of a CYP3A4 inhibitor (itraconazole) and inducer (rifampin) to alter the pharmacokinetic (PK) profile of olaparib following single oral tablet doses. METHODS: Two Phase I, open-label, non-randomized trials were conducted in patients with advanced solid tumors...
October 10, 2016: Clinical Therapeutics
Youn Jin Choi, Je-Keun Rhee, Soo Young Hur, Min Sung Kim, Sung Hak Lee, Yeun-Jun Chung, Tae-Min Kim, Sug Hyung Lee
Intra-individual tumoural heterogeneity (ITH) is a hallmark of solid tumours and impedes accurate genomic diagnosis and selection of proper therapy. The purpose of this study was to identify ITH of ovarian high-grade serous carcinomas (OSCs) and to determine the utility of ascitic cancer cells as a resource for mutation profiling in spite of ITH. We performed whole-exome sequencing, copy number profiling, and DNA methylation profiling of four OSC genomes using multiregional biopsy from 13 intra-ovarian lesions, 12 extra-ovarian tumour lesions (omentum/peritoneum), and ascitic cells...
October 14, 2016: Journal of Pathology
Steven J Isakoff, Shannon Puhalla, Susan M Domchek, Michael Friedlander, Bella Kaufman, Mark Robson, Melinda L Telli, Véronique Diéras, Hyo Sook Han, Judy E Garber, Eric F Johnson, David Maag, Qin Qin, Vincent L Giranda, Stacie P Shepherd
Veliparib is an orally administered poly(ADP-ribose) polymerase inhibitor that is being studied in Phase I-III clinical trials, including Phase III studies in non-small-cell lung cancer, ovarian cancer and breast cancer. Tumor cells with deleterious BRCA1 or BRCA2 mutations are deficient in homologous recombination DNA repair and are intrinsically sensitive to platinum therapy and poly(ADP-ribose) polymerase inhibitors. We describe herein the design and rationale of a Phase II trial investigating whether the addition of veliparib to temozolomide or carboplatin/paclitaxel provides clinical benefit over carboplatin/paclitaxel with placebo in patients with locally recurrent or metastatic breast cancer harboring a deleterious BRCA1 or BRCA2 germline mutation (Trial registration: EudraCT 2011-002913-12, NCT01506609)...
October 14, 2016: Future Oncology
G E Konecny, R S Kristeleit
Poly(ADP-ribose) polymerase (PARP) inhibitors cause targeted tumour cell death in homologous recombination (HR)-deficient cancers, including BRCA-mutated tumours, by exploiting synthetic lethality. PARP inhibitors are being evaluated in late-stage clinical trials of ovarian cancer (OC). Recently, olaparib was the first PARP inhibitor approved in the European Union and United States for the treatment of advanced BRCA-mutated OC. This paper reviews the role of BRCA mutations for tumorigenesis and PARP inhibitor sensitivity, and summarises the clinical development of PARP inhibitors for the treatment of patients diagnosed with OC...
October 13, 2016: British Journal of Cancer
Aymeric Chartier, Willy Joly, Martine Simonelig
mRNA regulation by poly(A) tail length variations plays an important role in many developmental processes. Recent advances have shown that, in particular, deadenylation (the shortening of mRNA poly(A) tails) is essential for germ-line stem cell biology in the Drosophila ovary. Therefore, a rapid and accurate method to analyze poly(A) tail lengths of specific mRNAs in this tissue is valuable. Several methods of poly(A) test (PAT) assays have been reported to measure mRNA poly(A) tail lengths in vivo. Here, we describe two of these methods (PAT and ePAT) that we have adapted for Drosophila ovarian germ cells and germ-line stem cells...
2017: Methods in Molecular Biology
Mansoor R Mirza, Bradley J Monk, Jørn Herrstedt, Amit M Oza, Sven Mahner, Andrés Redondo, Michel Fabbro, Jonathan A Ledermann, Domenica Lorusso, Ignace Vergote, Noa E Ben-Baruch, Christian Marth, Radosław Mądry, René D Christensen, Jonathan S Berek, Anne Dørum, Anna V Tinker, Andreas du Bois, Antonio González-Martín, Philippe Follana, Benedict Benigno, Per Rosenberg, Lucy Gilbert, Bobbie J Rimel, Joseph Buscema, John P Balser, Shefali Agarwal, Ursula A Matulonis
Background Niraparib is an oral poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) 1/2 inhibitor that has shown clinical activity in patients with ovarian cancer. We sought to evaluate the efficacy of niraparib versus placebo as maintenance treatment for patients with platinum-sensitive, recurrent ovarian cancer. Methods In this randomized, double-blind, phase 3 trial, patients were categorized according to the presence or absence of a germline BRCA mutation (gBRCA cohort and non-gBRCA cohort) and the type of non-gBRCA mutation and were randomly assigned in a 2:1 ratio to receive niraparib (300 mg) or placebo once daily...
October 7, 2016: New England Journal of Medicine
Jennifer McLachlan, Angela George, Susana Banerjee
ABSTRACTRecent advances in our understanding of the molecular biology of epithelial ovarian cancer have led to the development of a number of targeted therapies, including poly-ADP-ribose polymerase (PARP) inhibitors. PARP inhibitors are a novel class of therapeutic agents that target tumors with deficiencies in the homologous recombination DNA repair pathway. Early studies have shown significant efficacy for PARP inhibitors in patients with germline BRCA1/2 mutations. It has become evident that BRCA wild-type patients with other defects in the homologous recombination repair pathway benefit from this therapeutic approach...
September 24, 2016: Tumori
Aiste McCormick, Peter Donoghue, Michelle Dixon, Richard O'Sullivan, Rachel Louise O'Donnell, James Murray, Angelika Kaufmann, Nicola J Curtin, Richard J Edmondson
PURPOSE: DNA damage defects are common in ovarian cancer and can be used to stratify treatment. Although most work has focussed on Homologous Recombination (HR), DNA double strand breaks are repaired primarily by non-homologous end joining (NHEJ). Defects in NHEJ have been shown to contribute to genomic instability and have been associated with the development of chemoresistance. EXPERIMENTAL DESIGN: NHEJ was assessed in a panel of ovarian cancer cell lines and 47 primary ascitic derived ovarian cancer cultures, by measuring the ability of cell extracts to end-join linearized plasmid monomers into multimers...
October 4, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Elizabeth H Stover, Panagiotis A Konstantinopoulos, Ursula A Matulonis, Elizabeth M Swisher
Drugs targeting DNA damage repair (DDR) pathways are exciting new agents in cancer therapy. Many of these drugs exhibit synthetic lethality with defects in DNA repair in cancer cells. For example, ovarian cancers with impaired homologous recombination DNA repair show increased sensitivity to poly- (ADP-ribose) polymerase (PARP) inhibitors. Understanding the activity of different DNA repair pathways in individual tumors, and the correlations between DNA repair function and drug response, will be critical to patient selection for DNA repair targeted agents...
September 27, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Rowan E Miller, Jonathan A Ledermann
Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors have shown clinical activity in epithelial ovarian cancer, leading both the US Food and Drug Administration (FDA) and the European Medicines Agency to approve olaparib for tumors characterized by BRCA1 and BRCA2 mutations. However, it is becoming increasingly evident that tumors that share molecular features with BRCA-mutant tumors-a concept known as BRCAness-also may exhibit defective homologous recombination DNA repair, and therefore will respond to PARP inhibition...
September 2016: Clinical Advances in Hematology & Oncology: H&O
Shan Su, Xueyan Lin, Ning Ding, Hong Zhang, Qinghua Zhang, Yumei Ding, Xiaoman Hou, Yongjie Tian
BACKGROUND: To assess the effects of the poly (ADP-ribose) polymerase-1 (PARP-1) inhibitor PJ34 and ERK1/2 inhibitor U0126 on the proliferation and epithelial mesenchymal transitions (EMT) of cisplatin resistant ovarian cancer SKOV-3 cells. METHODS: Proliferation of SKOV-3 cells was evaluated using a 3-(4,5-dimethylthazol-2-yl)-2,5-diphenyl tetrazolium bromide assay with PJ34 and U0126 treatment. Expression changes of E-cadherin and vimentin with PJ34 and U0126 treatment was examined using Western blot and quantitative PCR...
August 2, 2016: Pharmacological Reports: PR
Stephen Murata, Catherine Zhang, Nathan Finch, Kevin Zhang, Loredana Campo, Eun-Kyoung Breuer
Poly(ADP-ribose) polymerase (PARP) inhibitors have proven to be successful agents in inducing synthetic lethality in several malignancies. Several PARP inhibitors have reached clinical trial testing for treatment in different cancers, and, recently, Olaparib (AZD2281) has gained both United States Food and Drug Administration (USFDA) and the European Commission (EC) approval for use in BRCA-mutated advanced ovarian cancer treatment. The need to identify biomarkers, their interactions in DNA damage repair pathways, and their potential utility in identifying patients who are candidates for PARP inhibitor treatment is well recognized...
2016: BioMed Research International
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
Patrick R Benusiglio, Marina Di Maria, Leila Dorling, Anne Jouinot, Antoine Poli, Sophie Villebasse, Marine Le Mentec, Béatrice Claret, Diane Boinon, Olivier Caron
The increase in referrals to cancer genetics clinics, partially associated with the "Angelina Jolie effect", presents a challenge to existing services, many are already running at full capacity. More efficient ways to deliver genetic counselling are therefore urgently needed. We now systematically offer group instead of standard individual counselling to patients with suspected Hereditary Breast and Ovarian Cancer. Group sessions last 30 min. The first twenty consist of a presentation by the genetic counsellor, the next ten of a discussion involving a cancer geneticist and a psychologist...
September 13, 2016: Familial Cancer
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
Ruoxi Hong, Fei Ma, Weimin Zhang, Xiying Yu, Qing Li, Yang Luo, Changjun Zhu, Wei Jiang, Binghe Xu
BACKGROUND: Mutations in DNA damage response factors BRCA1 and BRCA2 confer sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors in breast and ovarian cancers. BRCA1/BRCA2-defective tumors can exhibit resistance to PARP inhibitors via multiple mechanisms, one of which involves loss of 53BP1. Deficiency in the DNA damage response factor ataxia-telangiectasia mutated (ATM) can also sensitize tumors to PARP inhibitors, raising the question of whether the presence or absence of 53BP1 can predict sensitivity of ATM-deficient breast cancer to these inhibitors...
September 9, 2016: BMC Cancer
Ursula A Matulonis, Anil K Sood, Lesley Fallowfield, Brooke E Howitt, Jalid Sehouli, Beth Y Karlan
Ovarian cancer is not a single disease and can be subdivided into at least five different histological subtypes that have different identifiable risk factors, cells of origin, molecular compositions, clinical features and treatments. Ovarian cancer is a global problem, is typically diagnosed at a late stage and has no effective screening strategy. Standard treatments for newly diagnosed cancer consist of cytoreductive surgery and platinum-based chemotherapy. In recurrent cancer, chemotherapy, anti-angiogenic agents and poly(ADP-ribose) polymerase inhibitors are used, and immunological therapies are currently being tested...
August 25, 2016: Nature Reviews. Disease Primers
Sijing Yan, Min Lu, Xiaoya Ding, Fei Chen, Xuemei He, Chunyan Xu, Hang Zhou, Qi Wang, Lan Hao, Jianzhong Zou
This study is to prepare a hematoporphyrin monomethyl ether (HMME)-loaded poly(lactic-co-glycolic acid) (PLGA) microcapsules (HMME/PLGA), which could not only function as efficient contrast agent for ultrasound (US)/photoacoustic (PA) imaging, but also as a synergistic agent for high intensity focused ultrasound (HIFU) ablation. Sonosensitizer HMME nanoparticles were integrated into PLGA microcapsules with the double emulsion evaporation method. After characterization, the cell-killing and cell proliferation-inhibiting effects of HMME/PLGA microcapsules on ovarian cancer SKOV3 cells were assessed...
2016: Scientific Reports
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