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https://www.readbyqxmd.com/read/28097235/a-patient-derived-xenograft-platform-to-study-brca-deficient-ovarian-cancers
#1
Erin George, Hyoung Kim, Clemens Krepler, Brandon Wenz, Mehran Makvandi, Janos L Tanyi, Eric Brown, Rugang Zhang, Patricia Brafford, Stephanie Jean, Robert H Mach, Yiling Lu, Gordon B Mills, Meenhard Herlyn, Mark Morgan, Xiaochen Zhang, Robert Soslow, Ronny Drapkin, Neil Johnson, Ying Zheng, George Cotsarelis, Katherine L Nathanson, Fiona Simpkins
Approximately 50% of high-grade serous ovarian cancers (HGSOCs) have defects in genes involved in homologous recombination (HR) (i.e., BRCA1/2). Preclinical models to optimize therapeutic strategies for HR-deficient (HRD) HGSOC are lacking. We developed a preclinical platform for HRD HGSOCs that includes primary tumor cultures, patient-derived xenografts (PDXs), and molecular imaging. Models were characterized by immunohistochemistry, targeted sequencing, and reverse-phase protein array analysis. We also tested PDX tumor response to PARP, CHK1, and ATR inhibitors...
January 12, 2017: JCI Insight
https://www.readbyqxmd.com/read/28096903/anxiety-and-depression-symptoms-among-women-attending-group-based-patient-education-courses-for-hereditary-breast-and-ovarian-cancer
#2
Wenche Listøl, Hildegunn Høberg-Vetti, Geir Egil Eide, Cathrine Bjorvatn
BACKGROUND: Women carrying BRCA-mutations are facing significant challenges, including decision making regarding surveillance and risk-reducing surgery. They often report that they are left alone with these important decisions. In order to enhance the genetic counselling session we organized a group-based patient education (GPE) course for women with BRCA-mutations. The study aims were to characterize women attending a group-based patient education (GPE) course for hereditary breast and ovarian cancer, consider the usefulness of the course, evaluate symptoms of anxiety and depression among the participants, and finally investigate whether their levels of anxiety and depression changed from before to after the course session...
2017: Hereditary Cancer in Clinical Practice
https://www.readbyqxmd.com/read/28096648/identification-of-genetic-and-epigenetic-variants-associated-with-breast-cancer-prognosis-by-integrative-bioinformatics-analysis
#3
Arunima Shilpi, Yingtao Bi, Segun Jung, Samir K Patra, Ramana V Davuluri
INTRODUCTION: Breast cancer being a multifaceted disease constitutes a wide spectrum of histological and molecular variability in tumors. However, the task for the identification of these variances is complicated by the interplay between inherited genetic and epigenetic aberrations. Therefore, this study provides an extrapolate outlook to the sinister partnership between DNA methylation and single-nucleotide polymorphisms (SNPs) in relevance to the identification of prognostic markers in breast cancer...
2017: Cancer Informatics
https://www.readbyqxmd.com/read/28094039/cisplatin-can-be-safely-administered-to-ovarian-cancer-patients-with-hypersensitivity-to-carboplatin
#4
A Bergamini, C Pisano, M Di Napoli, L Arenare, C Della Pepa, R Tambaro, G Facchini, P Gargiulo, S Rossetti, G Mangili, S Pignata, S C Cecere
OBJECTIVE: Hypersensitivity reactions (HSR) are frequently reported in patients rechallenged with carboplatin for recurrent ovarian cancer (ROC) and represent a critical issue, since discontinuation of the platinum-based therapy could affect prognosis. Several strategies to allow platinum rechallenge have been described, with controversial outcomes. The aim of this study is to illustrate a 10-year experience with cisplatin in patients with a previous HSR to carboplatin or at risk for allergy...
January 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28093663/large-prospective-analysis-of-the-reasons-patients-do-not-pursue-brca-genetic-testing-following-genetic-counseling
#5
Sommer Hayden, Sarah Mange, Debra Duquette, Nancie Petrucelli, Victoria M Raymond
Genetic counseling (GC) and genetic testing (GT) identifies high-risk individuals who benefit from enhanced medical management. Not all individuals undergo GT following GC and understanding the reasons why can impact clinical efficiency, reduce GT costs through appropriate identification of high-risk individuals, and demonstrate the value of pre-GT GC. A collaborative project sponsored by the Michigan Department of Health and Human Services prospectively collects anonymous data on BRCA-related GC visits performed by providers in Michigan, including demographics, patient/family cancer history, GT results, and reasons for declining GT...
January 16, 2017: Journal of Genetic Counseling
https://www.readbyqxmd.com/read/28092355/highly-favorable-outcome-in-brca-mutated-metastatic-breast-cancer-patients-receiving-high-dose-chemotherapy-and-autologous-hematopoietic-stem-cell-transplantation
#6
L Boudin, A Gonçalves, R Sabatier, J Moretta, P Sfumato, P Asseeva, D Livon, F Bertucci, J-M Extra, C Tarpin, G Houvenaeghel, E Lambaudie, A Tallet, M Resbeut, H Sobol, E Charafe-Jauffret, B Calmels, C Lemarie, J-M Boher, P Viens, F Eisinger, C Chabannon
No abstract text is available yet for this article.
January 16, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28078645/parp-inhibitors-in-reproductive-system-cancers-current-use-and-developments
#7
REVIEW
Geraldine O'Sullivan Coyne, Alice P Chen, Robert Meehan, James H Doroshow
The repair of DNA damage is a critical cellular process governed by multiple biochemical pathways that are often found to be defective in cancer cells. The poly(ADP-ribose) polymerase (PARP) family of proteins controls response to single-strand DNA breaks by detecting these damaged sites and recruiting the proper factors for repair. Blocking this pathway forces cells to utilize complementary mechanisms to repair DNA damage. While PARP inhibition may not, in itself, be sufficient to cause tumor cell death, inhibition of DNA repair with PARP inhibitors is an effective cytotoxic strategy when it is used in patients who carry other defective DNA-repair mechanisms, such as mutations in the genes BRCA 1 and 2...
January 11, 2017: Drugs
https://www.readbyqxmd.com/read/28073972/awareness-and-attitude-regarding-reproductive-options-of-persons-carrying-a-brca-mutation-and-their-partners
#8
J J G Gietel-Habets, C E M de Die-Smulders, I A P Derks-Smeets, A Tibben, V C G Tjan-Heijnen, R van Golde, E Gomez-Garcia, C M Kets, L A D M van Osch
STUDY QUESTION: To what extent are BRCA mutation carriers and their partners in the Netherlands aware about preimplantation genetic diagnosis (PGD) and prenatal diagnosis (PND) as reproductive options and what is their attitude towards these options? SUMMARY ANSWER: Awareness of PGD (66%) and PND (61%) among BRCA mutation carriers and their partners is relatively high and 80% and 26%, respectively, of BRCA carriers and their partners find offering PGD and PND for hereditary breast and ovarian cancer (HBOC) acceptable...
January 9, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28069876/targeting-plk1-to-enhance-efficacy-of-olaparib-in-castration-resistant-prostate-cancer
#9
Xiaoqi Liu, Jie Li, Ruixin Wang, Yifan Kong, Meaghan M Broman, Colin Carlock, Long Chen, Zhiguo Li, Elia Farah, Timothy L Ratliff
Olaparib is a FDA-approved PARP inhibitor (PARPi) that has shown promise as a synthetic lethal treatment approach for BRCA-mutant castration-resistant prostate cancer (CRPC) in clinical use. However, emerging data has also shown that even BRCA-mutant cells may be resistant to PARPi. The mechanistic basis for these drug resistances is poorly understood. Polo-like kinase 1 (Plk1), a critical regulator of many cell cycle events, is significantly elevated upon castration of mice carrying xenograft prostate tumors...
January 9, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28066861/the-incidence-of-cardiomyopathy-in-brca1-and-brca2-mutation-carriers-after-anthracycline-based-adjuvant-chemotherapy
#10
Edward J Pearson, Anju Nair, Yahya Daoud, Joanne L Blum
PURPOSE: Breast cancer remains the fourth-leading cause of death in the United States. Nearly 10% of breast cancers are hereditary, with deleterious mutations in BRCA1 and BRCA2 genes being the leading cause. Anthracycline chemotherapy, used commonly for breast cancer, carries cardiotoxicity risk. Recent studies demonstrated anthracycline-induced cardiac failure in homozygous BRCA2-deficient mice and increased rates of heart failure in homozygous BRCA1-deficient mice following ischemic insult...
January 9, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28057616/rucaparib-approved-for-ovarian-cancer
#11
(no author information available yet)
The FDA approved the PARP inhibitor rucaparib to treat women with advanced ovarian cancer who have already been treated with at least two chemotherapies and have a BRCA1 or BRCA2 gene mutation identified by an approved companion diagnostic test. The agency also gave a nod to the FoundationFocus CDxBRCA test to detect BRCA alterations.
January 5, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28055979/-back-to-a-false-normality-new-intriguing-mechanisms-of-resistance-to-parp-inhibitors
#12
REVIEW
Lorena Incorvaia, Francesc Passiglia, Sergio Rizzo, Antonio Galvano, Angela Listì, Nadia Barraco, Rossella Maragliano, Valentina Calò, Clara Natoli, Marcello Ciaccio, Viviana Bazan, Antonio Russo
Several evidences have shown that BRCA mutations increased tumor-cells sensitivity to PARP inhibitors by synthetic lethality leading to an accelerated development of several compounds targeting the PARP enzymes system as anticancer agents for clinical setting. Most of such compounds have been investigated in ovarian and breast cancer, showing promising efficacy in BRCA-mutated patients. Recently clinical studies of PARP-inhibitors have been extended across different tumor types harboring BRCA-mutations, including also "BRCA-like" sporadic tumors with homologous recombination deficiency (HRD)...
December 31, 2016: Oncotarget
https://www.readbyqxmd.com/read/28049253/prostate-cancer-in-a-patient-with-a-family-history-of-brca-mutation-a-case-report-and-literature-review
#13
Won Hoon Song, Sung Han Kim, Jae Young Joung, Weon Seo Park, Ho Kyung Seo, Jinsoo Chung, Kang Hyun Lee
One of the most significant risk factors for prostate cancer (PC) is a family history of the disease, with germ-line mutations in the breast cancer predisposition gene (BRCA) 2 conferring the highest risk. We here report a 56-year-old man presented with painful gait disturbance and diagnosed PC with multiple disseminated bone metastases. The patient had a strong family history of breast cancer with his 2 nieces affected. Furthermore, his aunts and uncles from both sides were diagnosed with stomach, ovarian, and colorectal cancers...
February 2017: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/28034904/rad51-mediates-resistance-of-cancer-stem-cells-to-parp-inhibition-in-triple-negative-breast-cancer
#14
Yajing Liu, Monika L Burness, Rachel Martin-Trevino, Joey Guy, Shoumin Bai, Ramdane Harouaka, Michael D Brooks, Li Shang, Alex Fox, Tahra K Luther, April Davis, Trenton L Baker, Justin Colacino, Shawn G Clouthier, Zhi-Ming Shao, Max S Wicha, Suling Liu
INTRODUCTION: PARP inhibitors have shown promising results in early studies for treatment of breast cancer susceptibility gene (BRCA)-deficient breast cancers; however, resistance ultimately develops. Furthermore, the benefit of PARP inhibitors (PARPi) in triple-negative breast cancers (TNBC) remains unknown. Recent evidence indicates that in TNBCs, cells that display "cancer stem cell" properties are resistant to conventional treatments, mediate tumor metastasis, and contribute to recurrence...
December 29, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28029807/physicians-perspectives-and-practice-patterns-toward-opportunistic-salpingectomy-in-high-and-low-risk-women
#15
Nathaniel L Jones, Jay Schulkin, Renata R Urban, Jason D Wright, William M Burke, June Y Hou, Cora A McElwain, Ana I Tergas
BACKGROUND: Opportunistic bilateral salpingectomy (OBS) has been proposed as an ovarian cancer risk-reducing strategy. METHODS: A survey was emailed to 300 members of the American College of Obstetricians and Gynecologists. RESULTS: 125 (42%) surveys were returned: 60% female, 88% generalists, 67% private practice. Only 36% correctly identified the lifetime risk of ovarian cancer, only 23% understood the risk-reducing benefit of bilateral salpingo-oophorectomy...
December 28, 2016: Cancer Investigation
https://www.readbyqxmd.com/read/28026205/preoperative-breast-mri-surgeons-patient-selection-patterns-and-potential-bias-in-outcomes-analyses
#16
Jiyon Lee, Elaine Tanaka, Peter R Eby, Shouhao Zhou, Wei Wei, Christine Eppelheimer, Vilert A Loving
OBJECTIVE: The purpose of this study is to determine which patient- and tumor-related and clinical variables influence dedicated breast surgeons' and general surgeons' referrals for preoperative breast MRI for patients with newly diagnosed breast cancer. MATERIALS AND METHODS: Surgeons who perform breast surgery responded to a survey from June 16, 2014, through August 11, 2014. Participants self-identified as breast or general surgeons and provided professional practice details...
December 27, 2016: AJR. American Journal of Roentgenology
https://www.readbyqxmd.com/read/28012689/oncofertility-for-women-with-gynecologic-malignancies
#17
REVIEW
Jessica L Chan, Erica T Wang
The emerging field of oncofertility addresses fertility and the reproductive health needs for cancer patients, a key topic in cancer survivorship. Given that the standard treatment for gynecologic malignancies involves removal of reproductive organs, pelvic radiation, or chemotherapy, the effect of such treatment on fertility and options for fertility preservation are even more relevant than for other malignancies. In young women with new diagnoses of cervical, endometrial, or ovarian cancers, viable strategies for fertility preservation without compromising oncological outcome exist and should be considered...
December 21, 2016: Gynecologic Oncology
https://www.readbyqxmd.com/read/28012317/a-mass-spectrometry-based-multiplex-snp-genotyping-by-utilizing-allele-specific-ligation-and-strand-displacement-amplification
#18
Jung Hun Park, Hyowon Jang, Yun Kyung Jung, Ye Lim Jung, Inkyung Shin, Dae-Yeon Cho, Hyun Gyu Park
We herein describe a new mass spectrometry-based method for multiplex SNP genotyping by utilizing allele-specific ligation and strand displacement amplification (SDA) reaction. In this method, allele-specific ligation is first performed to discriminate base sequence variations at the SNP site within the PCR-amplified target DNA. The primary ligation probe is extended by a universal primer annealing site while the secondary ligation probe has base sequences as an overhang with a nicking enzyme recognition site and complementary mass marker sequence...
November 24, 2016: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28008216/understanding-genetic-breast-cancer-risk-processing-loci-of-the-brca-gist-intelligent-tutoring-system
#19
Christopher R Wolfe, Valerie F Reyna, Colin L Widmer, Elizabeth M Cedillos-Whynott, Priscila G Brust-Renck, Audrey M Weil, Xiangen Hu
The BRCA Gist Intelligent Tutoring System helps women understand and make decisions about genetic testing for breast cancer risk. BRCA Gist is guided by Fuzzy-Trace Theory, (FTT) and built using AutoTutor Lite. It responds differently to participants depending on what they say. Seven tutorial dialogues requiring explanation and argumentation are guided by three FTT concepts: forming gist explanations in one's own words, emphasizing decision-relevant information, and deliberating the consequences of decision alternatives...
July 2016: Learning and Individual Differences
https://www.readbyqxmd.com/read/28006668/design-and-synthesis-of-novel-7-aminosubstituted-pyrido-2-3-b-pyrazines-exhibiting-anti-breast-cancer-activity
#20
Orestis Argyros, Nikolaos Lougiakis, Eva Kouvari, Alexandra Papafotika, Catherine P Raptopoulou, Vassilis Psycharis, Savvas Christoforidis, Nicole Pouli, Panagiotis Marakos, Constantin Tamvakopoulos
Breast cancer (BrCa) remains an unmet medical need despite the revolutionary development of antibody treatments and protein kinase inhibitors. In the current study, a series of novel substituted pyridopyrazine derivatives have been rationally designed and evaluated as multi-kinase inhibitors in the PI3K pathway. The target compounds were prepared from 6-amino-2-picoline, which upon nitration and selective reduction was converted to suitably substituted 6-methyl-7-aminopyrido[2,3-b]pyrazines. Suitable manipulation of the former amines provided the designed analogues, which were then assessed in vitro against several BrCa cell lines using the MTT cytotoxicity assay...
December 12, 2016: European Journal of Medicinal Chemistry
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