keyword
MENU ▼
Read by QxMD icon Read
search

BRCA1 BRCA2

keyword
https://www.readbyqxmd.com/read/29146772/cre-dependent-cas9-expressing-pigs-enable-efficient-in-vivo-genome-editing
#1
Kepin Wang, Qin Jin, Degong Ruan, Yi Yang, Qishuai Liu, Han Wu, Zhiwei Zhou, Zhen Ouyang, Zhaoming Liu, Yu Zhao, Bentian Zhao, Quanjun Zhang, Jiangyun Peng, Chengdan Lai, Nana Fan, Yanhui Liang, Ting Lan, Nan Li, Xiaoshan Wang, Xinlu Wang, Yong Fan, Pieter A Doevendans, Joost P G Sluijter, Pentao Liu, Xiaoping Li, Liangxue Lai
Despite being time-consuming and costly, generating genome-edited pigs holds great promise for agricultural, biomedical, and pharmaceutical applications. To further facilitate genome editing in pigs, we report here establishment of a pig line with Cre-inducible Cas9 expression that allows a variety of ex vivo genome editing in fibroblast cells including single- and multigene modifications, chromosome rearrangements, and efficient in vivo genetic modifications. As a proof of principle, we were able to simultaneously inactivate five tumor suppressor genes (TP53, PTEN, APC, BRCA1, and BRCA2) and activate one oncogene (KRAS), achieved by delivering Cre recombinase and sgRNAs, which caused rapid lung tumor development...
November 16, 2017: Genome Research
https://www.readbyqxmd.com/read/29145865/the-endonuclease-eepd1-mediates-synthetic-lethality-in-rad52-depleted-brca1-mutant-breast-cancer-cells
#2
Robert Hromas, Hyun-Suk Kim, Gurjit Sidhu, Elizabeth Williamson, Aruna Jaiswal, Taylor A Totterdale, Jocelyn Nole, Suk-Hee Lee, Jac A Nickoloff, Kimi Y Kong
BACKGROUND: Proper repair and restart of stressed replication forks requires intact homologous recombination (HR). HR at stressed replication forks can be initiated by the 5' endonuclease EEPD1, which cleaves the stalled replication fork. Inherited or acquired defects in HR, such as mutations in breast cancer susceptibility protein-1 (BRCA1) or BRCA2, predispose to cancer, including breast and ovarian cancers. In order for these HR-deficient tumor cells to proliferate, they become addicted to a bypass replication fork repair pathway mediated by radiation repair protein 52 (RAD52)...
November 16, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29143969/the-molecular-basis-of-cytotoxicity-of-%C3%AE-spinasterol-from-ganoderma-resinaceum-induction-of-apoptosis-and-overexpression-of-p53-in-breast-and-ovarian-cancer-cell-lines
#3
Nada K Sedky, Zaynab El Gammal, Amir E Wahba, Eman Mosad, Zahraa Y Waly, Amira Ali El-Fallal, Reem K Arafa, Nagwa El-Badri
OBJECTIVES: Despite advances in therapy of breast and ovarian cancers, they still remain among the most imperative causes of cancer death in women. The first can be considered one of the most widespread diseases among females, while the latter is more lethal and needs prompt treatment. Thus, the research field can still benefit from discovery of new compounds that can be of potential use in management of these grave illnesses. We hereby aimed to assess the antitumor activity of the phytosterol α-spinasterol isolated from Ganoderma resinaceum mushroom on human breast cancer cell lines (MCF-7, MDA-MB-231), as well as, on human ovarian cancer cell line (SKOV-3)...
November 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29138572/current-status-of-poly-adp-ribose-polymerase-inhibitors-and-future-directions
#4
REVIEW
Akihiro Ohmoto, Shinichi Yachida
Inhibitors of poly(ADP-ribose) polymerases (PARPs), which play a key role in DNA damage/repair pathways, have been developed as antitumor agents based on the concept of synthetic lethality. Synthetic lethality is the idea that cell death would be efficiently induced by simultaneous loss of function of plural key molecules, for example, by exposing tumor cells with inactivating gene mutation of BRCA-mediated DNA repair to chemically induced inhibition of PARPs. Indeed, three PARP inhibitors, olaparib, rucaparib and niraparib have already been approved in the US or Europe, mainly for the treatment of BRCA-mutant ovarian cancer...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29138343/a-phase-i-clinical-trial-of-the-poly-adp-ribose-polymerase-inhibitor-veliparib-and-weekly-topotecan-in-patients-with-solid-tumors
#5
Andrea E Wahner Hendrickson, Michael E Menefee, Lynn C Hartmann, Harry J Long, Donald W Northfelt, Joel M Reid, Felix Boakye-Agyeman, Olumide Kayode, Karen S Flatten, Maria I Harrell, Elizabeth M Swisher, Guy G Poirer, Daniel Satele, Jacob B Allred, Janet L Lensing, Alice Chen, Jiuping Jay Ji, Yiping Zhang, Charles Erlichman, Paul Haluska, Scott H Kaufmann
PURPOSE: To determine the dose limiting toxicities (DLTs), maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of veliparib in combination with weekly topotecan in patients with solid tumors. Correlative studies were included to assess the impact of topotecan and veliparib on poly(ADP-ribose) levels in peripheral blood mononuclear cells, serum pharmacokinetics of both agents, and potential association of germline repair gene mutations with outcome. EXPERIMENTAL DESIGN: Eligible patients had metastatic nonhematological malignancies with measurable disease...
November 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29137223/hormone-induced-dna-damage-response-and-repair-mediated-by-cyclin-d1-in-breast-and-prostate-cancer
#6
REVIEW
Gabriele Di Sante, Agnese Di Rocco, Claudia Pupo, Mathew C Casimiro, Richard G Pestell
Cell cycle control proteins govern events that leads to the production of two identical daughter cells. Distinct sequential temporal phases, Gap 1 (G1), Gap 0 (G0), Synthesis (S), Gap 2 (G2) and Mitosis (M) are negotiated through a series of check points during which the favorability of the local cellular environment is assessed, prior to replicating DNA [1]. Cyclin D1 has been characterized as a key regulatory subunit of the holoenzyme that promotes the G1/S-phase transition through phosphorylating the pRB protein...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29133135/characterization-detection-and-treatment-approaches-for-homologous-recombination-deficiency-in-cancer
#7
REVIEW
Grainne M O'Kane, Ashton A Connor, Steven Gallinger
Investigations of carcinogenesis have evolved from the identification of clonal driver mutations in candidate genes to the integration of large volumes of genomic and transcriptomic data revealing recurrently altered pathways and signatures of mutational processes. Inactivation of BRCA1, BRCA2, or PALB2 impairs efficient double-strand break repair (DSBR), giving rise to a spectrum of homologous recombination deficiency (HRD) cancer phenotypes. Harnessing HRD therapeutically has been promising in a number of tumors; these approaches include leveraging synthetic lethality by targeting alternative repair pathways via PARP inhibition, inducing HRD to modulate potential tumor vulnerabilities, and preventing mechanisms of drug resistance...
November 10, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29126833/brca1-and-brca2-expression-patterns-and-prognostic-significance-in-digestive-system-cancers
#8
Gui-Hua Wang, Chun-Mei Zhao, Ying Huang, Wei Wang, Shu Zhang, Xudong Wang
The role of BRCA1 and BRCA2 genes is mainly to maintain genome integrity in response to DNA damage through different mechanisms. Deregulation of BRCA1 and BRCA2 is associated with the development of tumor and altered sensitivity to chemotherapeutic agents. In this study, we determined protein expression of BRCA1 and BRCA2 in four digestive system cancers (gastric cancer, colorectal cancer, hepatocellular carcinoma, and pancreatic cancer) by immunohistochemistry (IHC) on tissue microarrays. A total of 1546 samples of four types of cancer tissues, their matched adjacent non-tumor tissues, and corresponding benign tissues were studied respectively...
November 7, 2017: Human Pathology
https://www.readbyqxmd.com/read/29126396/feasibility-of-structured-endurance-training-and-mediterranean-diet-in-brca1-and-brca2-mutation-carriers-an-interventional-randomized-controlled-multicenter-trial-libre-1
#9
Marion Kiechle, Ricarda Dukatz, Maryam Yahiaoui-Doktor, Anika Berling, Maryam Basrai, Vera Staiger, Uwe Niederberger, Nicole Marter, Jacqueline Lammert, Sabine Grill, Katharina Pfeifer, Kerstin Rhiem, Rita K Schmutzler, Matthias Laudes, Michael Siniatchkin, Martin Halle, Stephan C Bischoff, Christoph Engel
BACKGROUND: Women with pathogenic BRCA germline mutations have an increased risk for breast and ovarian cancer that seems to be modified by life-style factors. Though, randomized trials investigating the impact of lifestyle interventions on cancer prevention and prognosis in BRCA carriers are still missing. METHODS: We implemented a multicenter, prospective randomized controlled trial in BRCA1/2 patients, comparing a lifestyle intervention group (IG) with a control group (CG) with the primary aim to prove feasibility...
November 10, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29116468/young-age-at-first-pregnancy-does-protect-against-early-onset-breast-cancer-in-brca1-and-brca2-mutation-carriers
#10
D G Evans, E F Harkness, S Howel, E R Woodward, A Howell, F Lalloo
PURPOSE: Previous research assessing the impact of pregnancy and age at first pregnancy on breast cancer risk in BRCA1 and BRCA2 mutation carriers has produced conflicting results, with some studies showing an increased risk following early first pregnancy in contrast to the reduced risk in the general population of women. The present study addresses these inconsistencies. METHODS: Female BRCA1 and BRCA2 carriers from North West England were assessed for breast cancer incidence prior to 50 years of age comparing those with an early first full-term pregnancy (< 21 years) to those without a full-term pregnancy...
November 7, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29108258/transcriptional-signature-of-lymphoblastoid-cell-lines-of-brca1-brca2-and-non-brca1-2-high-risk-breast-cancer-families
#11
Marie-Christine Pouliot, Charu Kothari, Charles Joly-Beauparlant, Yvan Labrie, Geneviève Ouellette, Jacques Simard, Arnaud Droit, Francine Durocher
Approximately 25% of hereditary breast cancer cases are associated with a strong familial history which can be explained by mutations in BRCA1 or BRCA2 and other lower penetrance genes. The remaining high-risk families could be classified as BRCAX (non-BRCA1/2) families. Gene expression involving alternative splicing represents a well-known mechanism regulating the expression of multiple transcripts, which could be involved in cancer development. Thus using RNA-seq methodology, the analysis of transcriptome was undertaken to potentially reveal transcripts implicated in breast cancer susceptibility and development...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29101607/development-of-a-high-risk-pancreatic-screening-clinic-using-3-0%C3%A2-t-mri
#12
Chad A Barnes, Elizabeth Krzywda, Shannon Lahiff, Dena McDowell, Kathleen K Christians, Paul Knechtges, Parag Tolat, Mark Hohenwalter, Kulwinder Dua, Abdul H Khan, Douglas B Evans, Jennifer Geurts, Susan Tsai
Selective screening for pancreatic cancer (PC) has been proposed. We describe the establishment of a comprehensive multidisciplinary screening program using 3.0 T MRI. Criteria for screening included the presence of PC in: ≥ 2 first degree relatives (FDR), 1 FDR and 1 s degree relative (SDR), ≥ 3 any degree relatives (ADR), or any known hereditary cancer syndrome with increased PC risk. Imaging with 3.0 T MRI was performed routinely and endoscopic ultrasound was used selectively. Screening was completed in 75 patients (pts)...
November 3, 2017: Familial Cancer
https://www.readbyqxmd.com/read/29101112/prostate-cancer-germline-variations-and-implications-for-screening-and-treatment
#13
Alexander Dias, Zsofia Kote-Jarai, Christos Mikropoulos, Ros Eeles
Prostate cancer (PCa) is a highly heritable disease, and rapid evolution of sequencing technologies has enabled marked progression of our understanding of its genetic inheritance. A complex polygenic model that involves common low-penetrance susceptibility alleles causing individually small but cumulatively significant risk and rarer genetic variants causing greater risk represent the current most accepted model. Through genome-wide association studies, more than 100 single-nucleotide polymorphisms (SNPs) associated with PCa risk have been identified...
November 3, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/29094253/peritoneal-cancer-arising-after-total-abdominal-hysterectomy-and-bilateral-salpingo-oophorectomy-for-cervical-cancer-in-a-patient-with-right-breast-cancer-and-germline-mutation-of-brca1-gene-a-case-report-and-literature-review
#14
Michiko Harao, Jiro Ando, Hiroyuki Kamata, Nobuo Hoshi, Seiji Igarashi, Ryuzo Sekiguchi, Kokichi Sugano
Primary peritoneal carcinoma is usually advanced at diagnosis and curability is low unless the patient has a small tumor burden. Peritoneal carcinoma can occur in association with hereditary breast and ovarian cancer syndrome, which is thought to account for 5-6% of all breast cancer. Mutations of two breast cancer susceptibility genes, BRCA1 and BRCA2, are responsible for hereditary breast and ovarian cancer. Women with BRCA1/2 mutations often undergo risk-reducing salpingo-oophorectomy (RRSO) to prevent both ovarian and breast cancer...
November 1, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/29093993/ancient-divergence-time-estimates-in-eutropis-rugifera-support-the-existence-of-pleistocene-barriers-on-the-exposed-sunda-shelf
#15
Benjamin R Karin, Indraneil Das, Todd R Jackman, Aaron M Bauer
Episodic sea level changes that repeatedly exposed and inundated the Sunda Shelf characterize the Pleistocene. Available evidence points to a more xeric central Sunda Shelf during periods of low sea levels, and despite the broad land connections that persisted during this time, some organisms are assumed to have faced barriers to dispersal between land-masses on the Sunda Shelf. Eutropis rugifera is a secretive, forest adapted scincid lizard that ranges across the Sunda Shelf. In this study, we sequenced one mitochondrial (ND2) and four nuclear (BRCA1, BRCA2, RAG1, and MC1R) markers and generated a time-calibrated phylogeny in BEAST to test whether divergence times between Sundaic populations of E...
2017: PeerJ
https://www.readbyqxmd.com/read/29093764/clinical-and-genetic-characterization-of-hereditary-breast-cancer-in-a-chinese-population
#16
Wenjing Jian, Kang Shao, Qi Qin, Xiaohong Wang, Shufen Song, Xianming Wang
Background: Breast cancer develops as a result of multiple gene mutations in combination with environmental risk factors. Causative variants in genes such as BRCA1 and/or BRCA2 have been shown to account for hereditary nature of certain breast cancers. However,other genes, such as ATM, PALB2, BRIP1, CHEK, BARD1, while lower in frequency, may also increase breast cancer risk. There are few studies examining the role of these causative variants. Our study aimed to examine the clinical and genetic characterization of hereditary breast cancer in a Chinese population...
2017: Hereditary Cancer in Clinical Practice
https://www.readbyqxmd.com/read/29093017/a-population-of-heterogeneous-breast-cancer-patient-derived-xenografts-demonstrate-broad-activity-of-parp-inhibitor-in-brca1-2-wild-type-tumors
#17
Kurt W Evans, Erkan Yuca, Argun Akcakanat, Stephen M Scott, Natalia Paez Arango, Xiaofeng Zheng, Ken Chen, Coya Tapia, Emily Tarco, Agda K Eterovic, Dalliah M Black, Jennifer K Litton, Timothy A Yap, Debu Tripathy, Gordon B Mills, Funda Meric-Bernstam
Background: Breast cancer patients who do not respond to neoadjuvant therapy have a poor prognosis. There is a pressing need for novel targets and models for preclinical testing. Here we report characterization of breast cancer patient-derived xenografts (PDX) largely generated from residual tumors following neoadjuvant chemotherapy.Experimental Design: PDXs were derived from surgical samples of primary or locally recurrent tumors. Normal and tumor DNA sequencing, RNASeq, and reverse phase protein arrays (RPPA) were performed...
November 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29082482/germline-mutations-in-brca1-and-brca2-incidentally-revealed-in-a-biobank-research-study-experiences-from-re-contacting-mutation-carriers-and-relatives
#18
Martin P Nilsson, Monica Emmertz, Ulf Kristoffersson, Åke Borg, Christer Larsson, Martin Rehn, Christof Winter, Lao H Saal, Yvonne Brandberg, Niklas Loman
Once an incidental finding (IF) is discovered in the course of genomic research, the researchers are faced with the question of whether or not that finding should be reported back to the study participant. A large number of hypothetical studies and policy documents on this issue have been published, but there are very few empirical studies to inform the bioethics debate. Within a biobank research study of somatic mutations in breast carcinomas, ten germline BRCA1/2 mutations were incidentally detected. After thorough discussions within a group of experts, the mutation carriers (n = 7) or relatives of deceased carriers (n = 3) were re-contacted and informed about the findings...
October 30, 2017: Journal of Community Genetics
https://www.readbyqxmd.com/read/29080873/-a-bioinformatic-pipeline-for-ngs-data-analysis-and-mutation-calling-in-human-solid-tumors
#19
K Yu Tsukanov, A Yu Krasnenko, D A Plakhina, D O Korostin, A V Churov, O S Druzhilovskaya, D V Rebrikov, V V Ilinsky
We aimed to develop a pipeline for the bioinformatic analysis and interpretation of NGS data and detection of a wide range of single-nucleotide somatic mutations within tumor DNA. Initially, the NGS reads were submitted to a quality control check by the Cutadapt program. Low-quality 3¢-nucleotides were removed. After that the reads were mapped to the reference genome hg19 (GRCh37.p13) by BWA. The SAMtools program was used for exclusion of duplicates. MuTect was used for SNV calling. The functional effect of SNVs was evaluated using the algorithm, including annotation and evaluation of SNV pathogenicity by SnpEff and analysis of such databases as COSMIC, dbNSFP, Clinvar, and OMIM...
October 2017: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/29069866/germline-mutations-in-pancreatic-cancer-and-potential-new-therapeutic-options
#20
REVIEW
Rille Pihlak, Juan W Valle, Mairéad G McNamara
Due to short-lived treatment responses in unresectable disease, pancreatic ductal adenocarcinoma (PDAC) continues to be one of the deadliest cancers. There is availability of new information about germline and sporadic mutations in the deoxyribonucleic acid (DNA) damage repair pathway in PDAC in recent decades and the expectation is that novel targeted therapies will thus be developed. A variety of germline mutations (BRCA2, BRCA1, PALB2, CDKN2A, ATM, TP53 and mismatch repair genes MLH1, MSH2, MSH6) have been reported in these patients with the highest prevalence being BRCA1/2...
September 22, 2017: Oncotarget
keyword
keyword
70001
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"