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https://www.readbyqxmd.com/read/28631775/-innovations-in-the-treatment-of-ovarian-cancer-analysis-of-the-therapeutic-development-from-platinum-to-immunotherapy
#1
Gesuino Angius, Pierangela Sepe, Anselmo Papa, Silverio Tomao, Federica Tomao
Ovarian cancer is the seventh most common cancer in women. The therapeutic approach provides for an appropriate integration between surgery and chemotherapy. Surgery is an important step for diagnosis, staging and therapy, aiming at the complete cytoreduction of all macroscopic visible disease. At the moment, adjuvant and first-line chemotherapy has as a standard the carboplatin-paclitaxel combination. Further, the addition of bevacizumab in the advanced stage (IIIB-IV) is strongly recommended. Despite the initial effectiveness, however, 70-80% of patients develop relapsed disease within the first two years and require subsequent treatment lines that have palliative, rather than curative purposes and that seek to reach a chronic state for the disease...
June 2017: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/28628421/high-grade-serous-ovarian-cancer-associations-between-brca-mutation-status-ct-imaging-phenotypes-and-clinical-outcomes
#2
Stephanie Nougaret, Yulia Lakhman, Mithat Gönen, Debra A Goldman, Maura Miccò, Melvin D'Anastasi, Sarah A Johnson, Krishna Juluru, Angela G Arnold, Ramon E Sosa, Robert A Soslow, Hebert Alberto Vargas, Hedvig Hricak, Noah D Kauff, Evis Sala
Purpose To investigate the associations between BRCA mutation status and computed tomography (CT) phenotypes of high-grade serous ovarian cancer (HGSOC) and to evaluate CT indicators of cytoreductive outcome and survival in patients with BRCA-mutant HGSOC and those with BRCA wild-type HGSOC. Materials and Methods This HIPAA-compliant, institutional review board-approved retrospective study included 108 patients (33 with BRCA mutant and 75 with BRCA wild-type HGSOC) who underwent CT before primary debulking...
June 16, 2017: Radiology
https://www.readbyqxmd.com/read/28625312/traitement-des-rechutes-tardives-du-cancer-de-l%C3%A2-ovaire
#3
Anne Floquet, Dominique Berton-Rigaud, Gwenael Ferron, Gilles Freyer, Anne Claire Hardy-Bessard, Benoit You
Despite large improvements in treatment efficacy, the cure rate of ovarian cancer has not radically changed. Relapses both remain frequent and are still synonymous with chronic disease. Most of them are platinum-sensitive, and can be successfully treated with successive lines of chemotherapy. Surgery may have a role to play but its real impact, population selection criteria, and adequate timing still have to be established. Regarding medical treatments, the availability of new targeted therapeutics, such as bevacizumab and olaparib, complicates decision making...
May 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/28617445/acquired-cross-linker-resistance-associated-with-a-novel-spliced-brca2-protein-variant-for-molecular-phenotyping-of-brca2-disruption
#4
Stefan Meyer, Adam Stevens, Roberto Paredes, Marion Schneider, Michael J Walker, Andrew J K Williamson, Maria-Belen Gonzalez-Sanchez, Stephanie Smetsers, Vineet Dalal, Hsiang Ying Teng, Daniel J White, Sam Taylor, Joanne Muter, Andrew Pierce, Chiara de Leonibus, Davy A P Rockx, Martin A Rooimans, Elaine Spooncer, Stacey Stauffer, Kajal Biswas, Barbara Godthelp, Josephine Dorsman, Peter E Clayton, Shyam K Sharan, Anthony D Whetton
BRCA2 encodes a protein with a fundamental role in homologous recombination that is essential for normal development. Carrier status of mutations in BRCA2 is associated with familial breast and ovarian cancer, while bi-allelic BRCA2 mutations can cause Fanconi anemia (FA), a cancer predisposition syndrome with cellular cross-linker hypersensitivity. Cancers associated with BRCA2 mutations can acquire chemo-resistance on relapse. We modeled acquired cross-linker resistance with an FA-derived BRCA2-mutated acute myeloid leukemia (AML) platform...
June 15, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28614062/brca-mutations-in-the-manifestation-and-treatment-of-ovarian-cancer
#5
REVIEW
Zimin Pan, Xing Xie
BRCA genes are important for the integrity and stability of genetic material and play key roles in repairing DNA breaks via high fidelity homologous recombination. BRCA mutations are known to predispose carriers to gynecological malignancies, accounting for a majority of hereditary OC cases. Known to be lethal, OC is difficult to detect and control. Testing for BRCA mutations is a key step in the risk assessment, prognosis, treatment and prevention of OC and current clinical guidelines recommend BRCA mutation testing for all OCs of epithelial origin...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28610746/a-universal-genetic-testing-initiative-for-patients-with-high-grade-non-mucinous-epithelial-ovarian-cancer-and-the-implications-for-cancer-treatment
#6
Erica M Bednar, Holly D Oakley, Charlotte C Sun, Catherine C Burke, Mark F Munsell, Shannon N Westin, Karen H Lu
OBJECTIVE: Genetic counseling (GC) and germline genetic testing (GT) for BRCA1 and BRCA2 are considered standard of care for patients with high-grade, non-mucinous epithelial ovarian, fallopian tube, and primary peritoneal cancers (HGOC). We describe a universal genetic testing initiative to increase the rates of recommendation and acceptance of GC and GT to >80% for patients with HGOC at our institution. METHODS: Data from a consecutive cohort of patients seen in our gynecologic oncology clinics between 9/1/2012 and 8/31/2015 for evaluation of HGOC were retrospectively analyzed...
June 10, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28601509/olaparib-hydroxamic-acid-derivatives-as-dual-parp-and-hdac-inhibitors-for-cancer-therapy
#7
Zigao Yuan, Shaopeng Chen, Qinsheng Sun, Ning Wang, Dan Li, Shuangshuang Miao, Chunmei Gao, Yuzong Chen, Chunyan Tan, Yuyang Jiang
Olaparib was the first PARP inhibitor approved by the FDA for patients with BRCA-mutated ovarian cancer. Recent studies have demonstrated enhanced anticancer effects of combination therapy consisting of olaparib and HDAC inhibitors. Herein, based on rational drug design strategy, hydroxamic acid derivatives of olaparib were constructed as dual PARP and HDAC inhibitors. These hybrid compounds showed potent inhibitory activities against PARP1/2 and HDAC1/6 with IC50 values in the nanomolar range. Furthermore, compound P1 exhibited broad-spectrum antiproliferative activities in selected human cancer cell lines...
May 31, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28577564/high-frequency-of-the-recurrent-c-1310_1313delaaga-brca2-mutation-in-the-north-east-of-morocco-and-implication-for-hereditary-breast-ovarian-cancer-prevention-and-control
#8
Fatima-Zahra Laarabi, Ilham Ratbi, Siham Chafai Elalaoui, Loubna Mezzouar, Yassamine Doubaj, Laila Bouguenouch, Karim Ouldim, Noureddine Benjaafar, Abdelaziz Sefiani
BACKGROUND: To date, a limited number of BRCA1/2 germline mutations have been reported in hereditary breast and/or ovarian cancer in the Moroccan population. Less than 20 different mutations of these two genes have been identified in Moroccan patients, and recently we reported a further BRCA2 mutation (c.1310_1313delAAGA; p.Lys437IlefsX22) in three unrelated patients, all from the North-East of the country. We aimed in this study to evaluate the frequency and geographic distribution of this BRCA2 frameshift mutation, in order to access its use as the first-line BRCA genetic testing strategy for Moroccan patients...
June 2, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28559958/hereditary-and-non-hereditary-branches-of-family-eligible-for-brca-test-cancers-in-other-sites
#9
M Digennaro, D Sambiasi, S Tommasi, B Pilato, S Diotaiuti, A Kardhashi, G Trojano, A Tufaro, A V Paradiso
BACKGROUND: The analysis of relationships of BRCA alterations with cancer at sites other than breast/ovary may provide innovative information concerning BRCA pathogenic role and support additional clinical decisions. Aim of this study is to compare presence of cancers in other sites in members of hereditary (H) and not-hereditary (nH) branches of families of patients eligible to BRCA test. METHODS: We retrospectively analyzed the incidence of cancer in other sites in members of 136 families eligible for hereditary breast/ovarian cancer genetic counseling at Centro Studi Tumori Eredo-familiari of our Institute; we compared the frequency of other cancer types in 1156 members of the H-branch with respect to 1062 members of nH-Branch...
2017: Hereditary Cancer in Clinical Practice
https://www.readbyqxmd.com/read/28559769/next-generation-sequencing-reveals-a-nonsense-mutation-p-arg364ter-in-mre11a-gene-in-an-indian-patient-with-familial-breast-cancer
#10
Pratibha Sharma Bhai, Deepak Sharma, Renu Saxena, Ishwar C Verma
BACKGROUND: The MRN complex consisting of MRE11A-RAD50-NBS1 proteins is involved in the repair of double-strand breaks, and mutations in genes coding for the MRN complex have been identified in families with breast and ovarian cancer. CASE REPORT: In a BRCA-negative family with positive history of breast and endometrial cancer, next-generation sequencing-based panel testing identified a mutation in the MRE11A gene (NM_005590 c.1090C>T: p.Arg364Ter). This mutation results in a shorter mutated protein lacking 2 DNA binding domains (the GAR domain and the RAD50 binding site), abolishing the function of protein...
May 2017: Breast Care
https://www.readbyqxmd.com/read/28549976/brca-mutational-status-initial-disease-presentation-and-clinical-outcome-in-high-grade-serous-advanced-ovarian-cancer-a-multicenter-study
#11
Marco Petrillo, Claudia Marchetti, Rossella De Leo, Angela Musella, Ettore Capoluongo, Ida Paris, Pierluigi Benedetti Panici, Giovanni Scambia, Anna Fagotti
BACKGROUND: In the last decades, there have been several efforts to clarify the role of BRCA mutational status in women with advanced ovarian cancer, demonstrating its role in cancer development, as well as the prognostic significance of BRCA genotype. OBJECTIVE: Our aim is to evaluate the correlation between BRCA mutational status and disease presentation in a large series of advanced high-grade serous ovarian cancer patients. STUDY DESIGN: This is a retrospective multicenter study including a consecutive series of newly diagnosed high-grade serous ovarian cancer patients with International Federation of Gynecology and Obstetrics stage IIIC-IV disease, at least 18 months of follow-up time, and tested for BRCA 1/2 germline mutation status...
May 23, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28548905/brca-associated-cancers-role-of-imaging-in-screening-diagnosis-and-management
#12
Michelle V Lee, Venkata S Katabathina, Michyla L Bowerson, Marina I Mityul, Anup S Shetty, Khaled M Elsayes, Aparna Balachandran, Priya R Bhosale, Ann E McCullough, Christine O Menias
Harmful mutations of the BRCA tumor suppressor genes result in a greater lifetime risk for malignancy-breast and ovarian cancers in particular. An increased risk for male breast, fallopian tube, primary peritoneal, pancreatic, prostate, and colon cancers also has been reported. The BRCA gene is inherited in an autosomal dominant pattern and tends to be highly penetrant; thus, there is an increased incidence of these cancers in affected families. Compared with sporadic tumors, BRCA-associated malignancies have unique manifestations, clinical features, and pathologic profiles...
May 26, 2017: Radiographics: a Review Publication of the Radiological Society of North America, Inc
https://www.readbyqxmd.com/read/28546758/distinct-implications-of-different-brca-mutations-efficacy-of-cytotoxic-chemotherapy-parp-inhibition-and-clinical-outcome-in-ovarian-cancer
#13
REVIEW
Robert L Hollis, Michael Churchman, Charlie Gourley
Approximately a fifth of ovarian carcinoma (OC) is associated with inherited germline mutations, most commonly in the DNA repair genes BRCA1 or BRCA2 (BRCA). BRCA1- and BRCA2-associated OCs have historically been described as a single subgroup of OC that displays a distinct set of characteristics termed the "BRCAness" phenotype. The hallmarks of this phenotype are superior clinical outcome and hypersensitivity to platinum-based chemotherapy and poly-(ADP-ribose) polymerase (PARP) inhibitors. However, growing evidence suggests that BRCA1- and BRCA2-associated OCs display distinct characteristics, most notably in long-term patient survival...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28527614/n-o-344-salpingectomie-opportuniste-et-autres-m%C3%A3-thodes-pour-r%C3%A3-duire-le-risque-de-cancer-de-l-ovaire-de-la-trompe-de-fallope-et-du-p%C3%A3-ritoine-dans-la-population-g%C3%A3-n%C3%A3-rale
#14
Shannon Salvador, Stephanie Scott, Julie Ann Francis, Anita Agrawal, Christopher Giede
OBJECTIF: La présente directive clinique examine les avantages potentiels de la salpingectomie opportuniste pour prévenir le développement du cancer séreux de grade élevé de l'ovaire, de la trompe de Fallope et du péritoine à la lumière de données probantes actuelles selon lesquelles ce type de cancer prendrait naissance dans la trompe de Fallope. UTILISATEURS CIBLES: Gynécologues, obstétriciens, médecins de famille, infirmières autorisées, infirmières praticiennes, résidents et fournisseurs de soins de santé...
June 2017: Journal of Obstetrics and Gynaecology Canada: JOGC, Journal D'obstétrique et Gynécologie du Canada: JOGC
https://www.readbyqxmd.com/read/28527613/no-344-opportunistic-salpingectomy-and-other-methods-of-risk-reduction-for-ovarian-fallopian-tube-peritoneal-cancer-in-the-general-population
#15
Shannon Salvador, Stephanie Scott, Julie Ann Francis, Anita Agrawal, Christopher Giede
OBJECTIVE: This guideline reviews the potential benefits of opportunistic salpingectomy to prevent the development of high grade serous cancers (HGSC) of the ovary/fallopian tube/peritoneum based on current evidence supporting the fallopian tube origin of disease. INTENDED USERS: Gynaecologists, obstetricians, family doctors, registered nurses, nurse practitioners, residents, and health care providers. TARGET POPULATION: Adult women (18 and older): OPTIONS: Women considering hysterectomy who wish to retain their ovaries in situ have traditionally also retained their fallopian tubes...
June 2017: Journal of Obstetrics and Gynaecology Canada: JOGC, Journal D'obstétrique et Gynécologie du Canada: JOGC
https://www.readbyqxmd.com/read/28525846/exploring-the-clonal-evolution-of-cd133-aldehyde-dehydrogenase-1-aldh1-positive-cancer-stem-like-cells-from-primary-to-recurrent-high-grade-serous-ovarian-cancer-hgsoc-a-study-of-the-ovarian-cancer-therapy-innovative-models-prolong-survival-octips-consortium
#16
Ilary Ruscito, Dan Cacsire Castillo-Tong, Ignace Vergote, Iulia Ignat, Mandy Stanske, Adriaan Vanderstichele, Ram N Ganapathi, Jacek Glajzer, Hagen Kulbe, Fabian Trillsch, Alexander Mustea, Caroline Kreuzinger, Pierluigi Benedetti Panici, Charlie Gourley, Hani Gabra, Mirjana Kessler, Jalid Sehouli, Silvia Darb-Esfahani, Elena Ioana Braicu
BACKGROUND: High-grade serous ovarian cancer (HGSOC) causes 80% of all ovarian cancer (OC) deaths. In this setting, the role of cancer stem-like cells (CSCs) is still unclear. In particular, the evolution of CSC biomarkers from primary (pOC) to recurrent (rOC) HGSOCs is unknown. Aim of this study was to investigate changes in CD133 and aldehyde dehydrogenase-1 (ALDH1) CSC biomarker expression in pOC and rOC HGSOCs. METHODS: Two-hundred and twenty-four pOC and rOC intrapatient paired tissue samples derived from 112 HGSOC patients were evaluated for CD133 and ALDH1 expression using immunohistochemistry (IHC); pOCs and rOCs were compared for CD133 and/or ALDH1 levels...
May 16, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28508305/recent-advances-in-targeting-dna-repair-pathways-for-the-treatment-of-ovarian-cancer-and-their-clinical-relevance
#17
REVIEW
Katsutoshi Oda, Michihiro Tanikawa, Kenbun Sone, Mayuyo Mori-Uchino, Yutaka Osuga, Tomoyuki Fujii
Poly (ADP-ribose) polymerase (PARP) inhibitors have attracted much attention as one of the major molecular-targeted therapeutics for inhibiting DNA damage response. The PARP inhibitor, olaparib, has been clinically applied for treating certain recurrent ovarian cancer patients with BRCA1/2 mutations in Europe and the United States. It was also designated on 24 March 2017 as an orphan drug in Japan for similar clinical indications. In this review, we discuss (i) the prevalence of BRCA1/2 mutations in ovarian cancer, (ii) clinical trials of PARP inhibitors in ovarian cancer, (iii) genetic counseling for hereditary breast and ovarian cancer patients, and (iv) non-BRCA genes that may be associated with homologous recombination deficiency...
May 15, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28500412/-hereditary-breast-and-ovarian-cancer
#18
REVIEW
S F Lax
Hereditary breast and ovarian carcinomas are frequently caused by germline mutations of the BRCA1 and BRCA2 genes (BRCA1/2 syndromes) and are often less associated with other hereditary syndromes such as Li-Fraumeni and Peutz-Jeghers. The BRCA1/2 proteins have a special role in DNA repair. Therefore, loss of function due to mutation causes an accumulation of mutations in other genes and subsequent tumorigenesis at an early age. BRCA1/2 mutations are irregularly distributed over the length of the genes without hot spots, although special mutations are known...
May 12, 2017: Der Pathologe
https://www.readbyqxmd.com/read/28498247/practice-patterns-of-hereditary-ovarian-cancer-management-in-korea
#19
Min Chul Choi, Myong Cheol Lim, Maria Lee, Min Kyu Kim, Dong Hoon Suh, Yong Jung Song, Tae-Joong Kim, Suk-Joon Chang, Jae-Weon Kim
OBJECTIVE: This study aims to evaluate practice patterns for managing hereditary ovarian cancer among Korean gynecologic oncologic physicians. METHODS: Members of the Korean Society of Gynecologic Oncology participated in the inaugural Hereditary Gynecologic Cancer Symposium or were invited to this survey by e-mail from January to February 2016. The survey was conducted using a self-administered questionnaire. RESULTS: Most physicians (66...
June 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28497333/next-generation-sequencing-based-genomic-profiling-of-brain-metastases-of-primary-ovarian-cancer-identifies-high-number-of-brca-mutations
#20
S Balendran, S Liebmann-Reindl, A S Berghoff, T Reischer, N Popitsch, C B Geier, L Kenner, P Birner, B Streubel, M Preusser
Ovarian cancer represents the most common gynaecological malignancy and has the highest mortality of all female reproductive cancers. It has a rare predilection to develop brain metastases (BM). In this study, we evaluated the mutational profile of ovarian cancer metastases through Next-Generation Sequencing (NGS) with the aim of identifying potential clinically actionable genetic alterations with options for small molecule targeted therapy. Library preparation was conducted using Illumina TruSight Rapid Capture Kit in combination with a cancer specific enrichment kit covering 94 genes...
May 11, 2017: Journal of Neuro-oncology
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