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https://www.readbyqxmd.com/read/28821955/targeted-next-generation-sequencing-for-analyzing-the-genetic-alterations-in-atypical-adenomatous-hyperplasia-and-adenocarcinoma-in-situ
#1
Xuan Xu, Na Li, Ruiying Zhao, Lei Zhu, Jinchen Shao, Jie Zhang
PURPOSE: Atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS) have been defined as preinvasive pulmonary adenocarcinoma lesions according to the 2015 World Health Organization lung adenocarcinoma classification. We aimed to search for the most common gene mutations in patients with AAH and AIS and investigate the distinctions between the two groups at the molecular level. METHODS: We performed targeted next-generation sequencing on 18 cases with AAH and 28 cases with AIS to screen for mutations with the Ion Torrent Oncomine Solid Tumor DNA panel...
August 18, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28821714/gadd45a-plays-a-protective-role-against-temozolomide-treatment-in-glioblastoma-cells
#2
Hsiao-Han Wang, Tsuey-Yu Chang, Wei-Chen Lin, Kuo-Chen Wei, Jyh-Wei Shin
Glioblastoma multiforme (GBM) is one of the most aggressive cancers. Despite recent advances in multimodal therapies, high-grade glioma remains fatal. Temozolomide (TMZ) is an alkylating agent used worldwide for the clinical treatment of GBM; however, the innate and acquired resistance of GBM limits its application. Here, we found that TMZ inhibited the proliferation and induced the G2/M arrest of GBM cells. Therefore, we performed microarrays to identify the cell cycle- and apoptosis-related genes affected by TMZ...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28820917/whole-exome-sequencing-of-lacrimal-gland-adenoid-cystic-carcinoma
#3
David W Sant, Wensi Tao, Matthew G Field, Daniel Pelaez, Ke Jin, Anthony Capobianco, Sander R Dubovy, David T Tse, Gaofeng Wang
Purpose: To identify genomic mutations in lacrimal gland adenoid cystic carcinoma (LGACC) samples from patients. Methods: Genomic DNA was extracted from LGACC specimens. Whole exome sequencing (exome-seq) was conducted to screen for mutations. Capillary sequencing was performed to verify mutations in genes shared by multiple samples. Luciferase assays were used to evaluate functional consequences of NOTCH1 mutations. Results: The mutation profile of LGACC was complicated...
May 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28819417/mdm2-snp309-and-snp285-act-as-negative-prognostic-markers-for-non-small-cell-lung-cancer-adenocarcinoma-patients
#4
Christophe Deben, Ken Op de Beeck, Jolien Van den Bossche, Julie Jacobs, Filip Lardon, An Wouters, Marc Peeters, Guy Van Camp, Christian Rolfo, Vanessa Deschoolmeester, Patrick Pauwels
Objectives: Two functional polymorphisms in the MDM2 promoter region, SNP309T>G and SNP285G>C, have been shown to impact MDM2 expression and cancer risk. Currently available data on the prognostic value of MDM2 SNP309 in non-small cell lung cancer (NSCLC) is contradictory and unavailable for SNP285. The goal of this study was to clarify the role of these MDM2 SNPs in the outcome of NSCLC patients. Materials and Methods: In this study we genotyped SNP309 and SNP285 in 98 NSCLC adenocarcinoma patients and determined MDM2 mRNA and protein levels...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819414/depletion-of-ctcf-in-breast-cancer-cells-selectively-induces-cancer-cell-death-via-p53
#5
Ji-Yeon Lee, Muhammad Mustafa, Clara Yuri Kim, Myoung Hee Kim
CCCTC-binding factor (CTCF), a ubiquitous 11-zinc finger multifunctional protein, has distinct molecular functions, such as transcriptional activation, repression, and chromatin barrier activity, in a locus-specific manner. Elevated CTCF levels in breast cancer cells are known to contribute to tumorigenesis; however, the underlying mechanism remains elusive. We investigated the effect of CTCF expression on breast cancer cell survival and elucidated its mechanism. CTCF depletion in MCF-7 cells led to a decreased cell growth and proliferation, surpassing the growth of normal cells under co-culture system of MCF-7-GFP and MCF10A...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819011/tp53-mutations-identify-younger-mantle-cell-lymphoma-patients-who-do-not-benefit-from-intensive-chemoimmunotherapy
#6
Christian W Eskelund, Christina Dahl, Jakob W Hansen, Maj Westman, Arne Kolstad, Lone B Pedersen, Carmen P Montano-Almendras, Simon Husby, Catja Freiburghaus, Sara Ek, Anja Pedersen, Carsten Niemann, Riikka Räty, Peter Brown, Christian H Geisler, Mette K Andersen, Per Guldberg, Mats Jerkeman, Kirsten Grønbæk
Despite recent advances in lymphoma treatment, mantle cell lymphoma (MCL) remains incurable and we are still unable to identify patients who will not benefit from the current standard-of-care. Here, we explore the prognostic value of recurrent genetic aberrations in diagnostic bone marrow (BM) specimens from 183 younger MCL patients from the Nordic MCL2 and MCL3 trials, which represent current standard-of-care regimens. In the univariate model, mutations of TP53 (11%) and NOTCH1 (4%), and deletions of TP53 (16%) and CDKN2A (20%) were significantly associated with inferior outcomes (together with MIPI, MIPI-c, Blastoid morphology and Ki67>30%); however, in multivariate analyses only TP53 mutations (HR=6...
August 17, 2017: Blood
https://www.readbyqxmd.com/read/28818808/potent-induction-of-apoptosis-by-givinostat-in-bcr-abl1-positive-and-bcr-abl1-negative-precursor-b-cell-acute-lymphoblastic-leukemia-cell-lines
#7
Chenjiao Yao, Guojuan Zhang, Alison Walker, Kevin Y Zhao, Ying Li, Lei Lyu, Yan Tang, Peng Ru, Dan Jones, Weiqiang Zhao
We have previously shown that givinostat can induce potent apoptosis in the BCR-ABL1-positive, TP53-wild type B-cell acute lymphoblastic leukemia (B-ALL) cell line SUP-B15. We extend our studies here to two additional B-ALL cell lines, BCR-ABL1-negative CCRF-SB and p210 BCR-ABL1-positive NAML1. Givinostat induced significant cell growth inhibition in both cell lines, with an IC50 of 0.65±0.052μM and 0.25±0.028μM in CCRF-SB and NAML1, respectively. The key signal protein of the BCR-ABL1, Crk-L1, was significantly reduced by givinostat treatment in NAML1...
August 9, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28818333/li-fraumeni-syndrome-disease-model-a-platform-to-develop-precision-cancer-therapy-targeting-oncogenic-p53
#8
REVIEW
Ruoji Zhou, An Xu, Julian Gingold, Louise C Strong, Ruiying Zhao, Dung-Fang Lee
Li-Fraumeni syndrome (LFS) is a rare hereditary autosomal dominant cancer disorder. Germline mutations in TP53, the gene encoding p53, are responsible for most cases of LFS. TP53 is also the most commonly mutated gene in human cancers. Because inhibition of mutant p53 is considered to be a promising therapeutic strategy to treat these diseases, LFS provides a perfect genetic model to study p53 mutation-associated malignancies as well as to screen potential compounds targeting oncogenic p53. In this review we briefly summarize the biology of LFS and current understanding of the oncogenic functions of mutant p53 in cancer development...
August 14, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28818315/screening-for-familial-cancer-risk-focus-on-breast-cancer
#9
REVIEW
Christine Rousset-Jablonski, Anne Gompel
A breast or an ovarian cancer occurring at a young age and/or in a family where other cases preexist suggests that those patients should be candidates for screening for mutations. Despite decades of medical research, less than 30% of cases with a suggestive personal and/or family history of hereditary breast cancer have an identified causative gene mutation. The vast majority of these cases are due to a mutation in one of the highly penetrant breast cancer genes (BRCA1, BRCA2, PTEN, TP53, CDH1, and STK11) and various guidelines direct the management of these patients...
August 7, 2017: Maturitas
https://www.readbyqxmd.com/read/28817102/anticancer-activity-of-ramalin-a-secondary-metabolite-from-the-antarctic-lichen-ramalina-terebrata-against-colorectal-cancer-cells
#10
Sung-Suk Suh, Tai Kyoung Kim, Jung Eun Kim, Ju-Mi Hong, Trang Thu Thi Nguyen, Se Jong Han, Ui Joung Youn, Joung Han Yim, Il-Chan Kim
Colorectal cancer is a leading cause of death worldwide and occurs through the highly complex coordination of multiple cellular pathways, resulting in carcinogenesis. Recent studies have increasingly revealed that constituents of lichen extracts exhibit potent pharmaceutical activities, including anticancer activity against various cancer cells, making them promising candidates for new anticancer therapeutic drugs. The main objective of this study was to evaluate the anticancer capacities of ramalin, a secondary metabolite from the Antarctic lichen Ramalina terebrata, in the human colorectal cancer cell line HCT116...
August 17, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28815764/aligning-digital-cd8-scoring-and-targeted-next-generation-sequencing-with-pd-l1-expression-a-pragmatic-approach-in-early-stage-squamous-cell-lung-carcinoma
#11
Esther Conde, Alejandra Caminoa, Carolina Dominguez, Antonio Calles, Stefan Walter, Barbara Angulo, Elena Sánchez, Marta Alonso, Luis Jimenez, Luis Madrigal, Florentino Hernando, Julian Sanz-Ortega, Beatriz Jimenez, Pilar Garrido, Luis Paz-Ares, Javier de Castro, Susana Hernandez, Fernando Lopez-Rios
AIMS: To study PD-L1 expression, tumour-infiltrating T lymphocytes (TILs) and the molecular context in patients with early-stage squamous cell lung carcinomas (SCCs). METHODS AND RESULTS: The study included samples from 40 patients (discovery cohort) and 29 patients (validation cohort) diagnosed with early-stage SCC. PD-L1 immunohistochemistry (IHC) was performed with three commercially available clones (E1L3N, SP263 and SP142). CD8(+) TILs were scored with a digital algorithm...
August 16, 2017: Histopathology
https://www.readbyqxmd.com/read/28814964/milk-disrupts-p53-and-dnmt1-the-guardians-of-the-genome-implications-for-acne-vulgaris-and-prostate-cancer
#12
Bodo C Melnik
There is accumulating evidence that milk shapes the postnatal metabolic environment of the newborn infant. Based on translational research, this perspective article provides a novel mechanistic link between milk intake and milk miRNA-regulated gene expression of the transcription factor p53 and DNA methyltransferase 1 (DNMT1), two guardians of the human genome, that control transcriptional activity, cell survival, and apoptosis. Major miRNAs of milk, especially miRNA-125b, directly target TP53 and complex p53-dependent gene regulatory networks...
2017: Nutrition & Metabolism
https://www.readbyqxmd.com/read/28814946/protein-signatures-of-molecular-pathways-in-non-small-cell-lung-carcinoma-nsclc-comparison-of-glycoproteomics-and-global-proteomics
#13
Shuang Yang, Lijun Chen, Daniel W Chan, Qing Kay Li, Hui Zhang
BACKGROUND: Non-small cell lung carcinoma (NSCLC) remains the leading cause of cancer deaths in the United States. More than half of NSCLC patients have clinical presentations with locally advanced or metastatic disease at the time of diagnosis. The large-scale genomic analysis of NSCLC has demonstrated that molecular alterations are substantially different between adenocarcinoma (ADC) and squamous cell carcinoma (SqCC). However, a comprehensive analysis of proteins and glycoproteins in different subtypes of NSCLC using advanced proteomic approaches has not yet been conducted...
2017: Clinical Proteomics
https://www.readbyqxmd.com/read/28814763/spatial-genomic-heterogeneity-in-multiple-myeloma-revealed-by-multi-region-sequencing
#14
L Rasche, S S Chavan, O W Stephens, P H Patel, R Tytarenko, C Ashby, M Bauer, C Stein, S Deshpande, C Wardell, T Buzder, G Molnar, M Zangari, F van Rhee, S Thanendrarajan, C Schinke, J Epstein, F E Davies, B A Walker, T Meissner, B Barlogie, G J Morgan, N Weinhold
In multiple myeloma malignant plasma cells expand within the bone marrow. Since this site is well-perfused, a rapid dissemination of "fitter" clones may be anticipated. However, an imbalanced distribution of multiple myeloma is frequently observed in medical imaging. Here, we perform multi-region sequencing, including iliac crest and radiology-guided focal lesion specimens from 51 patients to gain insight into the spatial clonal architecture. We demonstrate spatial genomic heterogeneity in more than 75% of patients, including inactivation of CDKN2C and TP53, and mutations affecting mitogen-activated protein kinase genes...
August 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28813679/the-tumor-suppressor-p53-limits-ferroptosis-by-blocking-dpp4-activity
#15
Yangchun Xie, Shan Zhu, Xinxin Song, Xiaofang Sun, Yong Fan, Jinbao Liu, Meizuo Zhong, Hua Yuan, Lin Zhang, Timothy R Billiar, Michael T Lotze, Herbert J Zeh, Rui Kang, Guido Kroemer, Daolin Tang
Ferroptosis is a form of regulated cell death that may facilitate the selective elimination of tumor cells. The tumor suppressor p53 (TP53) has been demonstrated to promote ferroptosis via a transcription-dependent mechanism. Here, we show that TP53 limits erastin-induced ferroptosis by blocking dipeptidyl-peptidase-4 (DPP4) activity in a transcription-independent manner. Loss of TP53 prevents nuclear accumulation of DPP4 and thus facilitates plasma-membrane-associated DPP4-dependent lipid peroxidation, which finally results in ferroptosis...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813624/tp53-mutational-status-and-ros-effect-the-expression-of-the-survivin-associated-radio-adaptive-response
#16
Jeffrey S Murley, Richard C Miller, Ralph R Weichselbaum, David J Grdina
A survivin-associated radio-adaptive response, characterized by increased radiation resistance or sensitization, was induced by exposure to 5 mGy of ionizing radiation and was correlated to the TP53 mutational status of exposed cells. Ten human cancer lines were investigated: colorectal carcinomas HCT116 and RKO [TP53 wild-type (WT)] and their respective TP53 null isogenic lines; breast adenocarcinomas MCF7 (TP53 WT) and MDA-MB-231 (TP53 Mut); lung carcinomas A549 (TP53 WT) and NCI-H1975 (TP53 Mut); and pancreatic carcinomas Hs766T (TP53 WT) and Panc-1 (TP53 Mut)...
August 16, 2017: Radiation Research
https://www.readbyqxmd.com/read/28811362/nuclear-envelope-rupture-is-enhanced-by-loss-of-p53-or-rb
#17
Zhe Yang, John Maciejowski, Titia de Lange
The mammalian nuclear envelope (NE) forms a stable physical barrier between the nucleus and the cytoplasm, normally breaking down only during the cell cycle phase of mitosis. However, spontaneous transient NE rupture in interphase can occur when NE integrity is compromised such as when the nucleus experiences mechanical stress. For instance, deficiencies in the nuclear lamins and their associated proteins can cause NE rupture that is promoted by forces exerted by actin filaments. NE rupture can allow cytoplasmic nucleases to access chromatin, potentially compromising genome integrity...
August 15, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28810144/integrated-genomic-characterization-of-pancreatic-ductal-adenocarcinoma
#18
(no author information available yet)
We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFβR2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations...
August 14, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28809762/elucidation-of-novel-chromosomal-abnormalities-in-pancreatic-cancer-conventional-and-molecular-cytogenetic-characterization-of-16-pancreatic-cell-lines
#19
David Shabsovich, Carlos A Tirado
Pancreatic carcinoma is a major cause of cancer-related death in the United States, with a five-year survival rate of approximately 5%. Cytogenetic analysis has identified clinically significant chromosomal abnormalities in numerous malignancies, but it is not utilized in the clinical management of pancreatic carcinoma. We performed conventional and molecular cytogenetic analysis of 16 pancreatic carcinoma cell lines using Giemsa banding and DNA-based fluorescence in situ hybridization (FISH). Conventional cytogenetic analysis revealed a diversity of recurrent and clonal numerical and structural abnormalities in all cell lines analyzed, many of which occurred at loci of genes implicated in pancreatic or related cancers...
2017: Journal of the Association of Genetic Technologists
https://www.readbyqxmd.com/read/28807937/hnf1b-loss-exacerbates-the-development-of-chromophobe-renal-cell-carcinomas
#20
Eric Jonasch, Mianen Sun, Pan Tong, Wen Kong, Baijun Dong, Yiran Huang, In Young Park, Lijun Zhou, Xian-De Liu, Zhiyong Ding, Xuesong Zhang, Shanshan Bai, Peter German, Reid Powell, Quan Wang, Xuefei Tong, Nizar M Tannir, Surena F Matin, W Kimryn Rathmell, Gregory N Fuller, Ian E McCutcheon, Cheryl Lyn Walker, Jing Wang
Chromophobe renal cell carcinoma (ChRCC) is characterized by major changes in chromosomal copy number (CN). No model is available to precisely elucidate the molecular drivers of this tumor type. HNF1B is a master regulator of gene expression. Here we report that the transcription factor HNF1B is downregulated in the majority of ChRCC and that the magnitude of HNF1B loss is unique to ChRCC. We also observed a strong correlation between reduced HNF1B expression and aneuploidy in ChRCC patients. In murine embryonic fibroblasts or ACHN cells, HNF1B deficiency reduced expression of the spindle checkpoint proteins MAD2L1 and BUB1B, and the cell cycle checkpoint proteins RB1 and p27...
August 14, 2017: Cancer Research
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