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TP53 and triple negative breast cancer

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https://www.readbyqxmd.com/read/28539722/effect-of-helix-aspersa-extract-on-tnf%C3%AE-nf-%C3%AE%C2%BAb-and-some-tumor-suppressor-genes-in-breast-cancer-cell-line-hs578t
#1
Ibtissem El Ouar, Cornelia Braicu, Dalila Naimi, Alexendru Irimie, Ioana Berindan-Neagoe
BACKGROUND: The garden snail, Helix aspersa, is a big land snail widely found in the Mediterranean countries. It is one of the most consumed species and widely used in zootherapy. OBJECTIVE: The present study was carried out to investigate for the first time the first time the antitumor activity of an aqueous extract from Helix aspersa. MATERIALS AND METHODS: The effect of H. aspersa extract was studied on a triple negative breast cancer cell line Hs578T...
April 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28486781/genomic-analysis-of-inherited-breast-cancer-among-palestinian-women-genetic-heterogeneity-and-a-founder-mutation-in-tp53
#2
Suhair Lolas Hamameh, Paul Renbaum, Lara Kamal, Dima Dweik, Mohammad Salahat, Tamara Jaraysa, Amal Abu Rayyan, Silvia Casadei, Jessica B Mandell, Suleyman Gulsuner, Ming K Lee, Tom Walsh, Mary-Claire King, Ephrat Levy-Lahad, Moein Kanaan
Breast cancer among Palestinian women has lower incidence than in Europe or North America, yet is very frequently familial. We studied genetic causes of this familial clustering in a consecutive hospital-based series of 875 Palestinian patients with invasive breast cancer, including 453 women with diagnosis by age 40, or with breast or ovarian cancer in a mother, sister, grandmother or aunt ("discovery series"); and 422 women diagnosed after age 40 and with negative family history ("older-onset sporadic patient series")...
May 9, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28394329/a-stemness-related-zeb1-msrb3-axis-governs-cellular-pliancy-and-breast-cancer-genome-stability
#3
Anne-Pierre Morel, Christophe Ginestier, Roxane M Pommier, Olivier Cabaud, Emmanuelle Ruiz, Julien Wicinski, Mojgan Devouassoux-Shisheboran, Valérie Combaret, Pascal Finetti, Christelle Chassot, Christiane Pinatel, Frédérique Fauvet, Pierre Saintigny, Emilie Thomas, Caroline Moyret-Lalle, Joël Lachuer, Emmanuelle Despras, Jean-Luc Jauffret, François Bertucci, Jérôme Guitton, Anne Wierinckx, Qing Wang, Nina Radosevic-Robin, Frédérique Penault-Llorca, David G Cox, Frédéric Hollande, Stéphane Ansieau, Julie Caramel, Daniel Birnbaum, Arnaud M Vigneron, Agnès Tissier, Emmanuelle Charafe-Jauffret, Alain Puisieux
Chromosomal instability (CIN), a feature of most adult neoplasms from their early stages onward, is a driver of tumorigenesis. However, several malignancy subtypes, including some triple-negative breast cancers, display a paucity of genomic aberrations, thus suggesting that tumor development may occur in the absence of CIN. Here we show that the differentiation status of normal human mammary epithelial cells dictates cell behavior after an oncogenic event and predetermines the genetic routes toward malignancy...
May 2017: Nature Medicine
https://www.readbyqxmd.com/read/28376176/tumor-sequencing-and-patient-derived-xenografts-in-the-neoadjuvant-treatment-of-breast-cancer
#4
Matthew P Goetz, Krishna R Kalari, Vera J Suman, Ann M Moyer, Jia Yu, Daniel W Visscher, Travis J Dockter, Peter T Vedell, Jason P Sinnwell, Xiaojia Tang, Kevin J Thompson, Sarah A McLaughlin, Alvaro Moreno-Aspitia, John A Copland, Donald W Northfelt, Richard J Gray, Katie Hunt, Amy Conners, Richard Weinshilboum, Liewei Wang, Judy C Boughey
Background: Breast cancer patients with residual disease after neoadjuvant chemotherapy (NAC) have increased recurrence risk. Molecular characterization, knowledge of NAC response, and simultaneous generation of patient-derived xenografts (PDXs) may accelerate drug development. However, the feasibility of this approach is unknown. Methods: We conducted a prospective study of 140 breast cancer patients treated with NAC and performed tumor and germline sequencing and generated patient-derived xenografts (PDXs) using core needle biopsies...
July 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28356770/breast-cancer-in-patients-with-li-fraumeni-syndrome-a-case-series-study-and-review-of-literature
#5
Amara G Nandikolla, Sangeetha Venugopal, Jesus Anampa
BACKGROUND: Li-Fraumeni Syndrome (LFS) is a rare disease with autosomal dominant inheritance linked to germline mutations of tumor suppressor gene TP53. These patients are predisposed to malignancies such as sarcoma, breast cancer, leukemia, and other malignancies. Breast cancer, the most common malignancy in adult patients with LFS, has an early-onset presentation and is usually treated as per the guidelines for the general population due to the limited literature about breast cancer in LFS...
2017: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28205193/new-therapeutic-strategies-for-triple-negative-breast-cancer
#6
REVIEW
Borbála Székely, Andrea L M Silber, Lajos Pusztai
Relatively few clinically important therapeutic advances have occurred in the treatment of triple-negative breast cancer (TNBC) since the introduction of taxanes as adjuvant therapy over 20 years ago. However, this is rapidly changing due to a variety of conceptually important clinical trials and emerging new options such as immune checkpoint inhibitors and antibody-drug conjugates. Evidence also increasingly supports that platinum drugs and inhibitors of poly (ADP-ribose) polymerase, or PARP, are particularly effective in the treatment of germline BRCA-mutant cancers, including TNBC...
February 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28153863/the-landscape-of-somatic-genetic-alterations-in-metaplastic-breast-carcinomas
#7
Charlotte K Y Ng, Salvatore Piscuoglio, Felipe C Geyer, Kathleen A Burke, Fresia Pareja, Carey Eberle, Reymond Lim, Rachael Natrajan, Nadeem Riaz, Odette Mariani, Larry Norton, Anne Vincent-Salomon, Y Hannah Wen, Britta Weigelt, Jorge S Reis-Filho
PURPOSE: Metaplastic breast carcinoma (MBC) is a rare and aggressive histologic type of breast cancer predominantly of triple-negative phenotype, and characterized by the presence of malignant cells showing squamous and/or mesenchymal differentiation. We sought to define the repertoire of somatic genetic alterations and the mutational signatures of MBCs. EXPERIMENTAL DESIGN: Whole-exome sequencing was performed in 35 MBCs, with 16, ten and nine classified as harboring chondroid, spindle and squamous metaplasia as the predominant metaplastic component...
February 2, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28139749/germline-large-genomic-alterations-on-7q-in-patients-with-multiple-primary-cancers
#8
R A R Villacis, T R Basso, L M Canto, A F Nóbrega, M I Achatz, S R Rogatto
Patients with multiple primary cancers (MPCs) are suspected to have a hereditary cancer syndrome. However, only a small proportion may be explained by mutations in high-penetrance genes. We investigate two unrelated MPC patients that met Hereditary Breast and Ovaria Cancer criteria, both presenting triple negative breast tumors and no mutations in BRCA1, BRCA2 and TP53 genes. Germline rearrangements on chromosome 7q, involving over 40 Mb of the same region, were found in both patients: one with mosaic loss (80% of cells) and the other with cnLOH (copy-neutral loss of heterozygosity) secondary to maternal allele duplication...
January 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28123851/the-fate-of-brca1-related-germline-mutations-in-triple-negative-breast-tumors
#9
Vassiliki Kotoula, Florentia Fostira, Kyriaki Papadopoulou, Paraskevi Apostolou, Eleftheria Tsolaki, Georgios Lazaridis, Kyriaki Manoussou, Flora Zagouri, Dimitrios Pectasides, Ioannis Vlachos, Ioannis Tikas, Sotiris Lakis, Irene Konstantopoulou, George Pentheroudakis, Helen Gogas, Pavlos Papakostas, Christos Christodoulou, Dimitrios Bafaloukos, Evangelia Razis, Vasilios Karavasilis, Christina Bamias, Drakoulis Yannoukakos, George Fountzilas
The preservation of pathogenic BRCA1/2 germline mutations in tumor tissues is usually not questioned, while it remains unknown whether these interact with somatic genotypes for patient outcome. Herein we compared germline and tumor genotypes in operable triple-negative breast cancer (TNBC) and evaluated their combined effects on prognosis. We analyzed baseline germline and primary tumor genotype data obtained by Sanger and Next Generation Sequencing in 194 TNBC patients. We also performed multiple tests interrogating the preservation of germline mutations in matched tumors and breast tissue from carriers with available material...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28108518/a-transposon-based-analysis-reveals-rasa1-is-involved-in-triple-negative-breast-cancer
#10
Cristian Suárez-Cabrera, Rita M Quintana, Ana Bravo, M Llanos Casanova, Angustias Page, Josefa P Alameda, Jesús M Paramio, Alicia Maroto, Javier Salamanca, Adam J Dupuy, Angel Ramírez, Manuel Navarro
RAS genes are mutated in 20% of human tumors, but these mutations are very rare in breast cancer. Here, we used a mouse model to generate tumors upon activation of a mutagenic T2Onc2 transposon via expression of a transposase driven by the keratin K5 promoter in a p53(+/-) background. These animals mainly developed mammary tumors, most of which had transposon insertions in one of two RASGAP genes, neurofibromin1 (Nf1) and RAS p21 protein activator (Rasa1). Immunohistochemical analysis of a collection of human breast tumors confirmed that low expression of RASA1 is frequent in basal (triple-negative) and estrogen receptor negative tumors...
January 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28093659/clinical-and-molecular-relevance-of-mutant-allele-tumor-heterogeneity-in-breast-cancer
#11
Ding Ma, Yi-Zhou Jiang, Xi-Yu Liu, Yi-Rong Liu, Zhi-Ming Shao
PURPOSE: Intra-tumor heterogeneity (ITH) plays a pivotal role in driving breast cancer progression and therapeutic resistance. We used a mutant-allele tumor heterogeneity (MATH) algorithm to measure ITH and explored its correlation with clinical parameters and multi-omics data. METHODS: We assessed 916 female breast cancer patients from The Cancer Genome Atlas. We calculated the MATH values from whole-exome sequencing data and further investigated their correlation with clinical characteristics, somatic mutations, somatic copy number alterations (SCNAs), and gene enrichment...
January 16, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28075450/integrated-analysis-of-differentially-expressed-genes-and-pathways-in-triple%C3%A2-negative-breast-cancer
#12
Cancan Peng, Wenli Ma, Wei Xia, Wenling Zheng
Triple‑negative breast cancer (TNBC) is a heterogeneous disease characterized by an aggressive phenotype and reduced survival. The aim of the present study was to investigate the molecular mechanisms involved in the carcinogenesis of TNBC and to identify novel target molecules for therapy. The differentially expressed genes (DEGs) in TNBC and normal adjacent tissue were assessed by analyzing the GSE41970 microarray data using Qlucore Omics Explorer, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes...
March 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28073896/patient-specific-circulating-tumor-dna-detection-during-neoadjuvant-chemotherapy-in-triple-negative-breast-cancer
#13
Francesca Riva, Francois-Clement Bidard, Alexandre Houy, Adrien Saliou, Jordan Madic, Aurore Rampanou, Caroline Hego, Maud Milder, Paul Cottu, Marie-Paule Sablin, Anne Vincent-Salomon, Olivier Lantz, Marc-Henri Stern, Charlotte Proudhon, Jean-Yves Pierga
BACKGROUND: In nonmetastatic triple-negative breast cancer (TNBC) patients, we investigated whether circulating tumor DNA (ctDNA) detection can reflect the tumor response to neoadjuvant chemotherapy (NCT) and detect minimal residual disease after surgery. METHODS: Ten milliliters of plasma were collected at 4 time points: before NCT; after 1 cycle; before surgery; after surgery. Customized droplet digital PCR (ddPCR) assays were used to track tumor protein p53 (TP53) mutations previously characterized in tumor tissue by massively parallel sequencing...
January 10, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/27923045/tumor-evolution-in-two-patients-with-basal-like-breast-cancer-a-retrospective-genomics-study-of-multiple-metastases
#14
Katherine A Hoadley, Marni B Siegel, Krishna L Kanchi, Christopher A Miller, Li Ding, Wei Zhao, Xiaping He, Joel S Parker, Michael C Wendl, Robert S Fulton, Ryan T Demeter, Richard K Wilson, Lisa A Carey, Charles M Perou, Elaine R Mardis
BACKGROUND: Metastasis is the main cause of cancer patient deaths and remains a poorly characterized process. It is still unclear when in tumor progression the ability to metastasize arises and whether this ability is inherent to the primary tumor or is acquired well after primary tumor formation. Next-generation sequencing and analytical methods to define clonal heterogeneity provide a means for identifying genetic events and the temporal relationships between these events in the primary and metastatic tumors within an individual...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27915434/differences-in-the-mutational-landscape-of-triple-negative-breast-cancer-in-african-americans-and-caucasians
#15
Foluso O Ademuyiwa, Yu Tao, Jingqin Luo, Katherine Weilbaecher, Cynthia X Ma
BACKGROUND: Triple-negative breast cancer (TNBC) occurs at higher frequency in African Americans compared with Caucasians. It is unclear if the biology of TNBC is different in African American versus Caucasians. In this study, we sought to evaluate racial differences in the molecular pathology of TNBC. METHODS: Using data from The Cancer Genome Atlas, we identified TNBC patients with information on race. We analyzed differences in clinical characteristics, tumor somatic mutations, and gene expression patterns by race from whole exome and microarray data...
February 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27900363/integration-of-genomics-and-histology-revises-diagnosis-and-enables-effective-therapy-of-refractory-cancer-of-unknown-primary-with-pdl1-amplification
#16
Stefan Gröschel, Martin Bommer, Barbara Hutter, Jan Budczies, David Bonekamp, Christoph Heining, Peter Horak, Martina Fröhlich, Sebastian Uhrig, Daniel Hübschmann, Christina Geörg, Daniela Richter, Nicole Pfarr, Katrin Pfütze, Stephan Wolf, Peter Schirmacher, Dirk Jäger, Christof von Kalle, Benedikt Brors, Hanno Glimm, Wilko Weichert, Albrecht Stenzinger, Stefan Fröhling
Identification of the tissue of origin in cancer of unknown primary (CUP) poses a diagnostic challenge and is critical for directing site-specific therapy. Currently, clinical decision-making in patients with CUP primarily relies on histopathology and clinical features. Comprehensive molecular profiling has the potential to contribute to diagnostic categorization and, most importantly, guide CUP therapy through identification of actionable lesions. We here report the case of an advanced-stage malignancy initially mimicking poorly differentiated soft-tissue sarcoma that did not respond to multiagent chemotherapy...
November 2016: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/27846853/dgca-a-comprehensive-r-package-for-differential-gene-correlation-analysis
#17
Andrew T McKenzie, Igor Katsyv, Won-Min Song, Minghui Wang, Bin Zhang
BACKGROUND: Dissecting the regulatory relationships between genes is a critical step towards building accurate predictive models of biological systems. A powerful approach towards this end is to systematically study the differences in correlation between gene pairs in more than one distinct condition. RESULTS: In this study we develop an R package, DGCA (for Differential Gene Correlation Analysis), which offers a suite of tools for computing and analyzing differential correlations between gene pairs across multiple conditions...
November 15, 2016: BMC Systems Biology
https://www.readbyqxmd.com/read/27815358/phase-i-study-of-gdc-0425-a-checkpoint-kinase-1-inhibitor-in-combination-with-gemcitabine-in-patients-with-refractory-solid-tumors
#18
Jeffrey R Infante, Antoine Hollebecque, Sophie Postel-Vinay, Todd M Bauer, Elizabeth M Blackwood, Marie Evangelista, Sami Mahrus, Franklin V Peale, Xuyang Lu, Srikumar Sahasranaman, Rui Zhu, Yuan Chen, Xiao Ding, Elaine R Murray, Jennifer L Schutzman, Jennifer O Lauchle, Jean-Charles Soria, Patricia M LoRusso
Purpose: Chk1 inhibition potentiates DNA-damaging chemotherapy by overriding cell-cycle arrest and genome repair. This phase I study evaluated the Chk1 inhibitor GDC-0425 given in combination with gemcitabine to patients with advanced solid tumors.Experimental Design: Patients received GDC-0425 alone for a 1-week lead-in followed by 21-day cycles of gemcitabine plus GDC-0425. Gemcitabine was initially administered at 750 mg/m(2) (Arm A), then increased to 1,000 mg/m(2) (Arm B), on days 1 and 8 in a 3 + 3 + 3 dose escalation to establish maximum tolerated dose (MTD)...
November 4, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27806348/clinical-outcomes-based-on-multigene-profiling-in-metastatic-breast-cancer-patients
#19
Reva K Basho, Debora de Melo Gagliato, Naoto T Ueno, Chetna Wathoo, Huiqin Chen, Maryam Shariati, Caimiao Wei, Ricardo H Alvarez, Stacy L Moulder, Aysegul A Sahin, Sinchita Roy-Chowdhuri, Mariana Chavez-MacGregor, Jennifer K Litton, Vincent Valero, Raja Luthra, Jia Zeng, Kenna R Shaw, John Mendelsohn, Gordon B Mills, Debu Tripathy, Funda Meric-Bernstam
BACKGROUND: Identifying the clinical impact of recurrent mutations can help define their role in cancer. Here, we identify frequent hotspot mutations in metastatic breast cancer (MBC) patients and associate them with clinical outcomes. PATIENTS AND METHODS: Hotspot mutation testing was conducted in 500 MBC patients using an 11 gene (N = 126) and/or 46 or 50 gene (N = 391) panel. Patients were stratified by hormone receptor (HR) and human epidermal growth factor 2 (HER2) status...
November 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27785100/current-advances-in-biomarkers-for-targeted-therapy-in-triple-negative-breast-cancer
#20
REVIEW
Brett Fleisher, Charlotte Clarke, Sihem Ait-Oudhia
Triple-negative breast cancer (TNBC) is a complex heterogeneous disease characterized by the absence of three hallmark receptors: human epidermal growth factor receptor 2, estrogen receptor, and progesterone receptor. Compared to other breast cancer subtypes, TNBC is more aggressive, has a higher prevalence in African-Americans, and more frequently affects younger patients. Currently, TNBC lacks clinically accepted targets for tailored therapy, warranting the need for candidate biomarkers. BiomarkerBase, an online platform used to find biomarkers reported in clinical trials, was utilized to screen all potential biomarkers for TNBC and select only the ones registered in completed TNBC trials through clinicaltrials...
2016: Breast Cancer: Targets and Therapy
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