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https://www.readbyqxmd.com/read/29665859/morphology-and-genomic-hallmarks-of-breast-tumours-developed-by-atm-deleterious-variant-carriers
#1
Anne-Laure Renault, Noura Mebirouk, Laetitia Fuhrmann, Guillaume Bataillon, Eve Cavaciuti, Dorothée Le Gal, Elodie Girard, Tatiana Popova, Philippe La Rosa, Juana Beauvallet, Séverine Eon-Marchais, Marie-Gabrielle Dondon, Catherine Dubois d'Enghien, Anthony Laugé, Walid Chemlali, Virginie Raynal, Martine Labbé, Ivan Bièche, Sylvain Baulande, Jacques-Olivier Bay, Pascaline Berthet, Olivier Caron, Bruno Buecher, Laurence Faivre, Marc Fresnay, Marion Gauthier-Villars, Paul Gesta, Nicolas Janin, Sophie Lejeune, Christine Maugard, Sébastien Moutton, Laurence Venat-Bouvet, Hélène Zattara, Jean-Pierre Fricker, Laurence Gladieff, Isabelle Coupier, Georgia Chenevix-Trench, Janet Hall, Anne Vincent-Salomon, Dominique Stoppa-Lyonnet, Nadine Andrieu, Fabienne Lesueur
BACKGROUND: The ataxia telangiectasia mutated (ATM) gene is a moderate-risk breast cancer susceptibility gene; germline loss-of-function variants are found in up to 3% of hereditary breast and ovarian cancer (HBOC) families who undergo genetic testing. So far, no clear histopathological and molecular features of breast tumours occurring in ATM deleterious variant carriers have been described, but identification of an ATM-associated tumour signature may help in patient management. METHODS: To characterise hallmarks of ATM-associated tumours, we performed systematic pathology review of tumours from 21 participants from ataxia-telangiectasia families and 18 participants from HBOC families, as well as copy number profiling on a subset of 23 tumours...
April 17, 2018: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29664016/the-evolving-landscape-of-predictive-biomarkers-of-response-to-parp-inhibitors
#2
Anish Thomas, Junko Murai, Yves Pommier
Poly(ADP-ribose) polymerase inhibitors (PARPis) are DNA-damaging agents that trap PARP-DNA complexes and interfere with DNA replication. Three PARPis - olaparib, niraparib, and rucaparib - were recently approved by the FDA for the treatment of breast and ovarian cancers. These PARPis, along with 2 others (talazoparib and veliparib), are being evaluated for their potential to treat additional malignancies, including prostate cancers. While lack of PARP-1 confers high resistance to PARPis, it has not been established whether or not the levels of PARP-1 directly correlate with tumor response...
April 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29662617/premature-ovarian-aging-in-brca-carriers-a-prototype-of-systemic-precocious-aging
#3
Irit Ben-Aharon, Mattan Levi, David Margel, Rinat Yerushalmi, Shulamith Rizel, Shlomit Perry, Eran Sharon, Noa Hasky, Ronit Abir, Benny Fisch, Ana Tobar, Ruth Shalgi, Salomon Marcello Stemmer
Purpose: Though former evidence implies a correlation of breast cancer susceptibility gene ( BRCA ) mutation with reduced ovarian reserve, the data is yet inconsistent. Our aim was to investigate biomarkers of ovarian aging in a cohort of young healthy carriers of the BRCA mutation. We hypothesized that the role played by BRCA genes in aging pathways is not exclusive to the ovary. Experimental Design: Healthy female BRCA carriers, 40 years or younger and healthy male BRCA carriers, 50 years or younger, were enrolled in the study...
March 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29661166/high-ox40-expression-in-recurrent-ovarian-carcinoma-is-indicative-for-response-to-repeated-chemotherapy
#4
Michaela Ramser, Simone Eichelberger, Silvio Däster, Benjamin Weixler, Marko Kraljević, Robert Mechera, Athanasios Tampakis, Tarik Delko, Uwe Güth, Sylvia Stadlmann, Luigi Terracciano, Raoul A Droeser, Gad Singer
BACKGROUND: Ovarian carcinoma (OC) is the fifth most common female cancer and mostly diagnosed at an advanced stage. Surgical debulking is usually followed by adjuvant platinum-based chemotherapy. Only few biomarkers are known to be related to chemosensitivity. OX40 is a TNF receptor member and expressed on activated CD4+ and CD8+ T cells. It is known that OX40 signaling promotes survival and responds to various immune cells of the innate and adaptive immune system. Therefore we investigated the indicative value of OX40 expression for recurrence and survival in OC...
April 16, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29659871/rare-variants-in-the-gene-alpl-that-cause-hypophosphatasia-are-strongly-associated-with-ovarian-and-uterine-disorders
#5
Kathryn M Dahir, Daniel R Tilden, Jeremy L Warner, Lisa Bastarache, Derek K Smith, Aliya Gifford, Andrea H Ramirez, Jill Simmons, Margo M Black, John H Newman, Josh C Denny
Background: Mutations in ALPL, which encodes tissue-nonspecific isozyme alkaline phosphatase (TNSALP), cause hypophosphatasia (HPP). HPP is suspected by a low serum alkaline phosphatase (AlkP). We hypothesized that some patients with bone or dental disease have undiagnosed HPP caused by ALPL variants. Our objective was to discover the prevalence of these gene variants in the Vanderbilt DNA biobank (BioVU) and to assess phenotypic associations. Methods: We identified subjects in BioVU, a repository of DNA, that had at least one of three known rare HPP disease-causing variants in ALPL: rs199669988, rs121918007, rs121918002...
April 6, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29659191/optimised-arid1a-immunohistochemistry-is-an-accurate-predictor-of-arid1a-mutational-status-in-gynaecological-cancers
#6
Saira Khalique, Kalnisha Naidoo, Ayoma D Attygalle, Divya Kriplani, Frances Daley, Anne Lowe, James Campbell, Thomas Jones, Michael Hubank, Kerry Fenwick, Nicholas Matthews, Alistair G Rust, Christopher J Lord, Susana Banerjee, Rachael Natrajan
ARID1A is a tumour suppressor gene that is frequently mutated in clear cell and endometrioid carcinomas of the ovary and endometrium and is an important clinical biomarker for novel treatment approaches for patients with ARID1A defects. However, the accuracy of ARID1A immunohistochemistry (IHC) as a surrogate for mutation status has not fully been established for patient stratification in clinical trials. Here we tested whether ARID1A immunohistochemistry could reliably predict ARID1A mutations identified by next-generation sequencing...
April 16, 2018: Journal of Pathology. Clinical Research
https://www.readbyqxmd.com/read/29658437/decreased-expression-of-hoxa10-may-activate-the-autophagic-process-in-ovarian-endometriosis
#7
Jingjie Zheng, Xishao Luo, Jiaping Bao, Xiaowang Huang, Yi Jin, Lin Chen, Feiyun Zheng
Autophagy is a survival process that maintains homeostasis in all eukaryotic cells. Recent studies show an abnormal autophagic activity in endometriosis, but the role of autophagy is controversial. Homeobox A10 (HOXA10) is a transcription factor necessary for embryonic and adult uterine development, and studies indicate that its expression decreases in endometriosis. Homeobox A10 may negatively regulate autophagy in endometriosis. To test this hypothesis, we measured the expression levels of autophagic biomarkers (beclin-1 and LC3-II) and HOXA10 proteins by Western blotting and messenger RNA (mRNA) by quantitative real-time polymerase chain reaction...
January 1, 2018: Reproductive Sciences
https://www.readbyqxmd.com/read/29650809/-molecular-targeted-therapies-for-hereditary-cancer-syndrome
#8
Hideki Shimodaira
Development of molecular targeted drugs has achieved remarkable improvement of systemic cancer therapy. Recently, the several molecular targeted drugs have become available which associated with the status of responsible genes for hereditary cancer syndrome. These drugs would allow to establish specific strategy for hereditary cancer syndrome or sporadic cancers with similar biological phenotype with hereditary cancer. Genetic tests for the diagnosis of hereditary cancer syndrome will have the meaning of biomarker for predicting the efficacy of these molecular targeted drugs...
April 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29644491/update-on-parp-inhibitors-in-breast-cancer
#9
REVIEW
Alexandra S Zimmer, Mitchell Gillard, Stanley Lipkowitz, Jung-Min Lee
The single agent activity of PARP inhibitors (PARPi) in germline BRCA mutated (gBRCAm) breast and ovarian cancer suggests untapped potential for this new class of drug in breast cancer. The US Food and Drug Administration has approved three PARPi (olaparib, rucaparib, and niraparib) so far to treat certain ovarian cancers, including those with gBRCAm and olaparib for treatment of gBRCAm breast cancers. Several PARPi are now under clinical development for breast cancer in the various treatment settings. Recently, two phase III trials of olaparib (OlympiaD) and talazoparib (EMBRACA) demonstrated 3-month progression-free survival improvement with PARPi compared to physician's choice single agent chemotherapy in metastatic gBRCAm breast cancer...
April 11, 2018: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/29630008/ovarian-cancer-prevention-and-screening
#10
Usha Menon, Chloe Karpinskyj, Aleksandra Gentry-Maharaj
There has been much progress in ovarian cancer screening and prevention in recent years. Improved tools that combine genetic and epidemiologic factors to predict an individual's ovarian cancer risk are set to become available for tailoring preventive and screening approaches. The increasing evidence on tubal origins of a proportion of ovarian cancer has paved the way to use of opportunistic bilateral salpingectomy at tubal ligation and hysterectomy in the general population. Clinical trials are in progress to estimate the long-term effects on endocrine function...
April 6, 2018: Obstetrics and Gynecology
https://www.readbyqxmd.com/read/29624102/exogenous-testosterone-does-not-induce-or-exacerbate-the-metabolic-features-associated-with-pcos-among-transgender-men
#11
Kelly J Chan, Jennifer J Liang, Divya Jolly, Jamie D Weinand, Joshua D Safer
OBJECTIVES: Polycystic ovarian syndrome (PCOS) is a complex condition which can include menstrual irregularity, metabolic derangement, and increased androgen levels. The mechanism of PCOS is unknown. Some suggest that excess production of androgens by the ovaries may cause or exacerbate the metabolic findings. The purpose of this study was to assess the role of increased testosterone on metabolic parameters on individuals presumed to be chromosomally female by examination of these parameters in hormone-treated transgender men...
April 6, 2018: Endocrine Practice
https://www.readbyqxmd.com/read/29620165/foxd1-is-targeted-by-mir-30a-5p-and-mir-200a-5p-and-suppresses-the-proliferation-of-human-ovarian-carcinoma-cells-by-promoting-p21-expression-in-a-p53-independent-manner
#12
Yu Wang, Chunping Qiu, Nan Lu, Zhaojian Liu, Chengjuan Jin, Chenggong Sun, Hualei Bu, Hongfeng Yu, Samina Dongol, Beihua Kong
High-grade serous ovarian carcinoma (HGSOC) accounts for the highest number of deaths among patients with epithelial ovarian cancer. However, the molecular mechanisms underlying HGSOC tumorigenesis are currently unclear. In the present study, a lentiviral expression system was employed to manipulate forkhead box D1 (FOXD1) expression in ovarian cancer cells. Immunohistochemical staining was used to examine the expression of FOXD1 in tissue samples. Clonogenic and MTT assays were employed to evaluate cell proliferation, and flow cytometry was applied for cell cycle analysis...
April 4, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29607232/falsely-elevated-ca-15-3-levels-in-ovarian-sarcoidosis-with-peritoneal-involvement-and-ascites
#13
Sotirios Tsiodras, Alina-Roxani Gouloumi, Zoi Tsakiraki, George Chrelias, Charalambos Chrelias, Stylianos Loukides, Ioannis Panayiotides
A rare case of ovarian sarcoidosis with peritoneal and omental involvement presenting as an ovarian malignancy is presented. Clinical, laboratory, and radiological evaluation of the patient revealed ascites and high levels of serum CA 125 and CA 15.3. The diagnosis of sarcoidosis was confirmed with pathology findings on tissues obtained during surgical laparotomy. Establishing the diagnosis of sarcoidosis can be treacherous and was complicated in this case by the falsely elevated biomarkers and ascites.
2018: Case Reports in Obstetrics and Gynecology
https://www.readbyqxmd.com/read/29606854/rucaparib-a-novel-parp-inhibitor-for-brca-advanced-ovarian-cancer
#14
REVIEW
Ilaria Colombo, Stephanie Lheureux, Amit Manulal Oza
Rucaparib is a potent small-molecule inhibitor of poly (ADP-ribose) polymerase (PARP) proteins (PARP-1, PARP-2 and PARP-3) that play an important role in repairing DNA damage and maintaining genomic stability. Tumors with mutations in BRCA1/2 or other homologous recombination deficiency (HRD) genes are particularly sensitive to PARP inhibitors because of "synthetic lethality", whereby a therapeutic agent can take advantage of an intrinsic weakness in DNA repair. Rucaparib has been investigated in several preclinical and clinical studies showing promising activity in BRCA -mutant and BRCA -wild-type epithelial ovarian cancers (EOCs)...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29604203/the-mirna-kallikrein-interaction-a-mosaic-of-epigenetic-regulation-in-cancer
#15
Ashley Di Meo, Cong Wang, Yufeng Cheng, Eleftherios P Diamandis, George M Yousef
The kallikrein-related peptidases (KLKs) constitute a family of 15 highly conserved serine proteases with trypsin- and chymotrypsin-like activities. Dysregulated expression and/or aberrant activation of KLKs have been linked to various pathophysiological processes, including cancer. Many KLKs have been identified as potential cancer biomarkers. microRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression by pairing to the 3' untranslated region (UTR) of complimentary mRNA targets. miRNAs are dysregulated in many cancers, including prostate, kidney, and ovarian cancers...
March 1, 2018: Biological Chemistry
https://www.readbyqxmd.com/read/29602379/-recommendations-for-biomarker-testing-in-epithelial-ovarian-cancer-a-national-consensus-statement-by-the-spanish-society-of-pathology-and-the-spanish-society-of-medical-oncology
#16
Ana Oaknin, Rosa Guarch, Pilar Barretina, David Hardisson, Antonio González-Martín, Xavier Matías-Guiu, Alejandro Pérez-Fidalgo, Begoña Vieites, Ignacio Romero, José Palacios
Advances in the understanding of the histological and molecular characteristics of ovarian cancer now allow 5subtypes to be identified, leading to a more refined therapeutic approach and improved clinical trials. Each of the subtypes has specific histological features and a particular biomarker expression, as well as mutations in different genes, some of which have prognostic and predictive value. CA125 and HE4 are examples of ovarian cancer biomarkers used in diagnosis and follow-up. Currently, somatic or germinal mutations on BRCA1 and BRCA2 genes are the most important biomarkers in epithelial ovarian cancer, having prognostic and predictive value...
April 2018: Revista Española de Patología
https://www.readbyqxmd.com/read/29599904/targeting-multidrug-resistant-ovarian-cancer-through-estrogen-receptor-%C3%AE-dependent-atp-depletion-caused-by-hyperactivation-of-the-unfolded-protein-response
#17
Xiaobin Zheng, Neal Andruska, Michael J Lambrecht, Sisi He, Amadeo Parissenti, Paul J Hergenrother, Erik R Nelson, David J Shapiro
Ovarian cancers often recur and tumors acquire resistance to chemotherapy due to overexpression of the ATP-dependent efflux pump, multidrug resistance protein 1 (MDR1/P-glycoprotein/ABCB1). Nontoxic small molecule inhibitors targeting MDR1 have remained largely elusive. Instead, in a novel application of our recently described estrogen receptor α (ERα) biomodulator, BHPI, we targeted MDR1's substrate, ATP. BHPI depletes intracellular ATP and nearly blocks MDR1-mediated drug efflux in ovarian cancer cells by inducing toxic hyperactivation of the endoplasmic reticulum stress sensor, the unfolded protein response (UPR)...
March 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29598846/the-role-of-mitochondrial-activity-in-female-fertility-and-assisted-reproductive-technologies-overview-and-current-insights
#18
REVIEW
Gustavo Nardini Cecchino, Emre Seli, Eduardo Leme Alves da Motta, Juan Antonio García-Velasco
Mitochondria have been implicated as key factors regulating female reproductive processes. Notable progress has been made in determining the role of mitochondria with respect to oocyte maturation, fertilization and early embryo development. In addition, mitochondrial function and dysfunction has been the subject of various studies in ovarian ageing and metabolic stress models. However, the overall mitochondrial impact on female fertility is yet to be uncovered. The mitochondrial DNA content of granulosa, cumulus and trophectoderm cells is being explored as a biomarker of oocyte quality and embryo viability...
March 8, 2018: Reproductive Biomedicine Online
https://www.readbyqxmd.com/read/29594361/mircrorna-139-sensitizes-ovarian-cancer-cell-to-cisplatin-based-chemotherapy-through-regulation-of-atp7a-b
#19
Fang Xiao, Yueran Li, Yajun Wan, Min Xue
PURPOSE: Ovarian cancer remains a most malignant female cancer nowadays. The acquisition of chemoresistance to common-used cisplatin-based chemotherapy results in a decreased overall patient survival. The present study is aimed to investigate the role and mechanism by which miR-139/ ATPases7A/B axis modulates the chemoresistance of ovarian cancer to cisplatin-based chemotherapy. METHODS: The expression of miR-139 in cisplatin-sensitive (n = 23) and cisplatin-resistant (n = 14) ovarian cancer tissues and cell lines (CAOV-3 and SNU119) was determined using real-time PCR assays; its effect on ovarian cancer cell chemoresistance to different concentrations of cisplatin was then assessed by measuring the cell viability using MTT assays...
March 28, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29589844/predicting-cancer-cell-invasion-by-single-cell-physical-phenotyping
#20
Kendra D Nyberg, Samuel L Bruce, Angelyn V Nguyen, Clara K Chan, Navjot K Gill, Tae-Hyung Kim, Erica K Sloan, Amy C Rowat
The physical properties of cells are promising biomarkers for cancer diagnosis and prognosis. Here we determine the physical phenotypes that best distinguish human cancer cell lines, and their relationship to cell invasion. We use the high throughput, single-cell microfluidic method, quantitative deformability cytometry (q-DC), to measure six physical phenotypes including elastic modulus, cell fluidity, transit time, entry time, cell size, and maximum strain at rates of 102 cells per second. By training a k-nearest neighbor machine learning algorithm, we demonstrate that multiparameter analysis of physical phenotypes enhances the accuracy of classifying cancer cell lines compared to single parameters alone...
March 28, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
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