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P53 mutation

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https://www.readbyqxmd.com/read/28535155/elevated-apobec3b-expression-drives-a-kataegic-like-mutation-signature-and-replication-stress-related-therapeutic-vulnerabilities-in-p53-defective-cells
#1
Jenni Nikkilä, Rahul Kumar, James Campbell, Inger Brandsma, Helen N Pemberton, Fredrik Wallberg, Kinga Nagy, Ildikó Scheer, Beata G Vertessy, Artur A Serebrenik, Valentina Monni, Reuben S Harris, Stephen J Pettitt, Alan Ashworth, Christopher J Lord
BACKGROUND: Elevated APOBEC3B expression in tumours correlates with a kataegic pattern of localised hypermutation. We assessed the cellular phenotypes associated with high-level APOBEC3B expression and the influence of p53 status on these phenotypes using an isogenic system. METHODS: We used RNA interference of p53 in cells with inducible APOBEC3B and assessed DNA damage response (DDR) biomarkers. The mutational effects of APOBEC3B were assessed using whole-genome sequencing...
May 23, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28534505/proteomic-identification-of-erp29-as-a-key-chemoresistant-factor-activated-by-the-aggregating-p53-mutant-arg282trp
#2
Y Zhang, Y Hu, J-L Wang, H Yao, H Wang, L Liang, C Li, H Shi, Y Chen, J-Y Fang, J Xu
Mutation of the TP53 gene represents a prevalent genetic alteration in human cancers, and a subset of p53 mutants may form amyloid-like aggregates that contribute to the gain of oncogenic functions (GOFs) and chemoresistance. Here we identify the pathways that may mediate the aggregation-associated GOF by using combined proteomic analysis and genome-wide recruitment profiling. Mass spectrometry revealed activation of unfolded protein response (UPR) pathway and upregulation of endoplasmic reticulum protein 29 (ERp29) in (R282W)TP53-expressing cells that were exposed to cisplatin stress...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28533538/proteomic-analysis-of-jak2v617f-induced-changes-identifies-potential-new-combinatorial-therapeutic-approaches
#3
S Pearson, A J K Williamson, R Blance, T C P Somervaille, S Taylor, N Azadbakht, A D Whetton, A Pierce
In excess of 90% of patients with polycythemia vera express a mutated form of JAK2, JAK2V617F. Such aberrant proteins offer great potential for the treatment of these diseases however inhibitors to JAK2 have had limited success in the clinic in terms of curing the disease. To understand the effects of this oncogene in hematopoietic cells with the aim of improving treatment strategies we undertook a systematic evaluation of the effects of JAK2V617F expression using proteomics. The effects of JAK2V617F on over 5000 proteins and 2000 nuclear phosphopeptides sites were relatively quantified using either SILAC or eight channel iTRAQ mass spectrometry...
May 23, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28533220/triptolide-assisted-phosphorylation-of-p53-suppresses-inflammation-induced-nf-%C3%AE%C2%BAb-survival-pathways-in-cancer-cells
#4
Li Zheng, Jia Jia, Huifang Dai, Lei Wan, Jian Liu, Lin Hu, Mian Zhou, Michael Qiu, Xufeng Chen, Lufen Chang, Jae Y Kim, Karen Reckamp, Dan J Raz, Zongping Xia, Binghui Shen
Chronic inflammation plays important roles in cancer initiation and progression. Resolving chronic inflammation or blocking inflammatory signal transduction may prevent cancer development. Here, we report that the combined low-dose use of two anti-inflammatory drugs, aspirin and triptolide, reduces spontaneous lung cancer incidence from 70% to 10% in a mouse model. Subsequent studies reveal that such treatment has little effect in resolving chronic inflammatory conditions in the lung, but it significantly blocks NF-κB-mediated expression of proliferation and survival genes in cancer cells...
May 22, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28531304/replication-studies-of-carboxymethylated-dna-lesions-in-human-cells
#5
Jun Wu, Pengcheng Wang, Lin Li, Nicole L Williams, Debin Ji, Walter J Zahurancik, Changjun You, Jianshuang Wang, Zucai Suo, Yinsheng Wang
Metabolic activation of some N-nitroso compounds (NOCs), an important class of DNA damaging agents, can induce the carboxymethylation of nucleobases in DNA. Very little was previously known about how the carboxymethylated DNA lesions perturb DNA replication in human cells. Here, we investigated the effects of five carboxymethylated DNA lesions, i.e. O6-CMdG, N6-CMdA, N4-CMdC, N3-CMdT and O4-CMdT on the efficiency and fidelity of DNA replication in HEK293T human embryonic kidney cells. We found that, while neither N6-CMdA nor N4-CMdC blocked DNA replication or induced mutations, N3-CMdT, O4-CMdT and O6-CMdG moderately blocked DNA replication and induced substantial frequencies of T→A (81%), T→C (68%) and G→A (6...
May 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28531108/regulation-of-metabolic-activity-by-p53
#6
REVIEW
Jessica Flöter, Irem Kaymak, Almut Schulze
Metabolic reprogramming in cancer cells is controlled by the activation of multiple oncogenic signalling pathways in order to promote macromolecule biosynthesis during rapid proliferation. Cancer cells also need to adapt their metabolism to survive and multiply under the metabolically compromised conditions provided by the tumour microenvironment. The tumour suppressor p53 interacts with the metabolic network at multiple nodes, mostly to reduce anabolic metabolism and promote preservation of cellular energy under conditions of nutrient restriction...
May 20, 2017: Metabolites
https://www.readbyqxmd.com/read/28529742/intraductal-tubulopapillary-neoplasm-accompanied-by-invasive-carcinoma-of-the-pancreas-a-case-report-and-review-of-the-literature
#7
Li Niu, Zhigao Xu, Huan Liu, Hong Cao, Guifang Yang
Intraductal tubulopapillary neoplasms (ITPNs) are rare pancreatic neoplasms accounting for ~0.4% of pancreatic tumors. However, their clinicopathological characteristics have not been clearly determined and the number of available clinical studies on this type of tumor is limited at present. Due to the rare incidence of ITPN, diagnosis is often delayed. We herein present a unique case of a 38-year-old man who was diagnosed with ITPN accompanied with invasive carcinoma of the pancreas and underwent total pancreatectomy...
May 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28529621/hoxa5-and-p53-cooperate-to-suppress-lung-cancer-cell-invasion-and-serve-as-good-prognostic-factors-in-non-small-cell-lung-cancer
#8
Chi-Jen Chang, Yen-Lin Chen, Chia-Hung Hsieh, Ya-Jung Liu, Sung-Liang Yu, Jeremy J W Chen, Chi-Chung Wang
Lung cancer is the leading cause of cancer mortality worldwide and tumor metastasis is the major cause of cancer-related death. Our previous study suggested that Homeobox A5 (HOXA5) could inhibit lung cancer cell invasion via regulating cytoskeletal remodeling and involved in tumor metastasis. Recently, consensus HOX binding sites was found in the p53 gene promoter region. However, whether the HOXA5 could cooperate with p53 and contribute the inhibition of lung cancer cell invasion is still unclear. The aim of the current study is to elucidate the correlation of HOXA5 and p53 in tumor invasion and its prognostic influence in lung cancer patient specimens...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28527674/analysis-of-full-coding-sequence-of-the-tp53-gene-in-invasive-vulvar-cancers-implications-for-therapy
#9
Karl Kashofer, Sigrid Regauer
OBJECTIVE: This study evaluates the frequency and type of TP53 gene mutations and HPV status in 72 consecutively diagnosed primary invasive vulvar squamous cell carcinomas (SCC) during the past 5years. METHODS: DNA of formalin-fixed and paraffin embedded tumour tissue was analysed for 32 HPV subtypes and the full coding sequence of the TP53 gene, and correlated with results of p53 immunohistochemistry. RESULTS: 13/72 (18%) cancers were HPV-induced squamous cell carcinomas, of which 1/13 (8%) carcinoma harboured a somatic TP53 mutation...
May 17, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28527113/mutant-p53-promotes-cell-spreading-and-migration-via-arhgap44
#10
Jinjin Xu, Jian Jiao, Wei Xu, Lei Ji, Dongjie Jiang, Shaofang Xie, Syeda Kubra, Xiaotao Li, Junjiang Fu, Jianru Xiao, Bianhong Zhang
The tumor suppressor p53 protein is either lost or mutated in about half of all human cancers. Loss of p53 function is well known to influence cell spreading, migration and invasion. While expression of mutant p53 is not equivalent to p53 loss, mutant p53 can acquire new functions to drive cell spreading and migration via different mechanisms. In our study, we found that mutant p53 significantly increased cell spreading and migration when comparing with p53-null cells. RNA-Seq analysis suggested that Rho GTPase activating protein 44 (ARHGAP44) is a new target of mutant p53, which suppressed ARHGAP44 transcription...
May 16, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28524155/statin-use-candidate-mevalonate-pathway-biomarkers-and-colon-cancer-survival-in-a-population-based-cohort-study
#11
Ronan T Gray, Maurice B Loughrey, Peter Bankhead, Chris R Cardwell, Stephen McQuaid, Roisin F O'Neill, Kenneth Arthur, Victoria Bingham, Claire McGready, Anna T Gavin, Jacqueline A James, Peter W Hamilton, Manuel Salto-Tellez, Liam J Murray, Helen G Coleman
BACKGROUND: Statin use after colorectal cancer diagnosis may improve survival but evidence from observational studies is conflicting. The anti-cancer effect of statins may be restricted to certain molecular subgroups. In this population-based cohort study, the interaction between p53 and 3-hydroxy-3-methylglutaryl coenzyme-A reductase (HMGCR) expression, KRAS mutations, and the association between statin use and colon cancer survival was assessed. METHODS: The cohort consisted of 740 stage II and III colon cancer patients diagnosed between 2004 and 2008...
May 18, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28522693/histone-h3-3k27m-represses-p16-to-accelerate-gliomagenesis-in-a-murine-model-of-dipg
#12
Francisco J Cordero, Zhiqing Huang, Carole Grenier, Xingyao He, Guo Hu, Roger E McLendon, Susan K Murphy, Rintaro Hashizume, Oren J Becher
Diffuse Intrinsic Pontine Glioma (DIPG) is a highly aggressive pediatric brainstem tumor genetically distinguished from adult GBM by the high prevalence of the K27M mutation in the histone H3 variant H3.3 (H3F3A). This mutation reprograms the H3K27me3 epigenetic landscape of DIPG by inhibiting the H3K27-specific histone methyltransferase EZH2. This globally reduces H3K27me2/3, critical repressive marks responsible for cell fate decisions, and also causes focal gain of H3K27me3 throughout the epigenome. To date the tumor-driving effects of H3...
May 18, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28521467/upregulation-of-maspin-expression-in-human-cervical-carcinoma-cells-by-transforming-growth-factor-%C3%AE-1-through-the-convergence-of-smad-and-non-smad-signaling-pathways
#13
Ariyaphong Wongnoppavich, Nahathai Dukaew, Sirinthip Choonate, Kongthawat Chairatvit
Mammary serine protease inhibitor (maspin), encoded by the serpin family B member 5 gene, serves as a tumor suppressor through the inhibition of cancer cell invasion and metastasis. Paradoxically, maspin levels are upregulated in a number of types of malignant cells. Therefore, the regulation of maspin expression may depend on the genetic or epigenetic background and the specific microenvironment of carcinoma cells. In the present study, it was demonstrated that transforming growth factor β1 (TGF-β1) induced maspin expression at the transcript and protein levels in the human cervical carcinoma HeLa and human oral squamous carcinoma HSC4 cell lines...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28515047/centrosome-amplification-a-suspect-in-breast-cancer-and-racial-disparities
#14
Angela Ogden, Padmashree C G Rida, Ritu Aneja
The multifaceted involvement of centrosome amplification (CA) in tumorigenesis is coming into focus following years of meticulous experimentation, which have elucidated the powerful abilities of CA to promote cellular invasion, disrupt stem cell division, drive chromosomal instability (CIN), and perturb tissue architecture, activities that can accelerate tumor progression. Integration of the extant in vitro, in vivo, and clinical data suggests that in some tissues CA may be a tumor-initiating event, in others a consequential "hit" in multistep tumorigenesis, and in still others non-tumorigenic...
May 17, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28513830/association-between-mutations-of-critical-pathway-genes-and-survival-outcomes-according-to-the-tumor-location-in-colorectal-cancer
#15
Dae-Won Lee, Sae-Won Han, Yongjun Cha, Jeong Mo Bae, Hwang-Phill Kim, Jaemyun Lyu, Hyojun Han, Hyoki Kim, Hoon Jang, Duhee Bang, Iksoo Huh, Taesung Park, Jae-Kyung Won, Seung-Yong Jeong, Kyu Joo Park, Gyeong Hoon Kang, Tae-You Kim
BACKGROUND: Colorectal cancer (CRC) develops through the alteration of several critical pathways. This study was aimed at evaluating the influence of critical pathways on survival outcomes for patients with CRC. METHODS: Targeted next-generation sequencing of 40 genes included in the 5 critical pathways of CRC (WNT, P53, RTK-RAS, phosphatidylinositol-4,5-bisphosphate 3-kinase [PI3K], and transforming growth factor β [TGF-β]) was performed for 516 patients with stage III or high-risk stage II CRC treated with surgery followed by adjuvant fluoropyrimidine and oxaliplatin chemotherapy...
May 17, 2017: Cancer
https://www.readbyqxmd.com/read/28512352/stem-cells-stem-cell-based-therapies-threatened-by-the-accumulation-of-p53-mutations
#16
Kim Baumann
No abstract text is available yet for this article.
May 17, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28512217/loss-of-the-homologous-recombination-gene-rad51-leads-to-fanconi-anemia-like-symptoms-in-zebrafish
#17
Jan Gregor Botthof, Ewa Bielczyk-Maczyńska, Lauren Ferreira, Ana Cvejic
RAD51 is an indispensable homologous recombination protein, necessary for strand invasion and crossing over. It has recently been designated as a Fanconi anemia (FA) gene, following the discovery of two patients carrying dominant-negative mutations. FA is a hereditary DNA-repair disorder characterized by various congenital abnormalities, progressive bone marrow failure, and cancer predisposition. In this report, we describe a viable vertebrate model of RAD51 loss. Zebrafish rad51 loss-of-function mutants developed key features of FA, including hypocellular kidney marrow, sensitivity to cross-linking agents, and decreased size...
May 16, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28511869/markers-of-the-p53-pathway-further-refine-molecular-profiling-in-high-risk-endometrial-cancer-a-transportec-initiative
#18
R J Edmondson, E J Crosbie, M Nickkho-Amiry, A Kaufmann, E Stelloo, H W Nijman, A Leary, A Auguste, L Mileshkin, P Pollock, H J MacKay, M E Powell, T Bosse, C L Creutzberg, H C Kitchener
BACKGROUND: The morphological classification of high-risk endometrial cancer is of limited prognostic value. Recent attempts to stratify tumours according to molecular signatures have shown considerable promise. Here we attempted to further refine molecular classifications using markers of the p53 pathway. METHODS: We analysed the expression of p53 as well as three downstream markers of the p53 pathway, p21, mdm2 and phospho-p63 (pp63), by immunohistochemistry in a series of 114 endometrial cancers (86 endometrioid, 28 non-endometrioid subtype) with high-risk features (such as high tumour grade and deep myometrial invasion) and correlated results with clinical outcome...
May 13, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28508718/frondoside-a-induces-aif-associated-caspase-independent-apoptosis-in-burkitt-lymphoma-cells
#19
Sergey A Dyshlovoy, Stefanie Rast, Jessica Hauschild, Katharina Otte, Winfried H Alsdorf, Ramin Madanchi, Vladimir I Kalinin, Alexandra S Silchenko, Sergey A Avilov, Judith Dierlamm, Friedemann Honecker, Valentin A Stonik, Carsten Bokemeyer, Gunhild von Amsberg
For patients with refractory or relapsed Burkitt lymphoma (BL), no standard therapy is available for second-line treatment to date. Nonfunctional caspases-dependent apoptosis pathways, inactivating p53 mutations and pro-survival autophagy prevent activity of conventional chemotherapy. Thus, new drugs bypassing these mechanisms of resistance are required. Here, we investigated the efficacy of the marine natural compound frondoside A (FrA) in eight BL cell lines. FrA revealed cytotoxic effects in all cell lines tested including the multiresistant CA46 cells...
May 16, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28507791/the-mutational-status-of-p53-can-influence-its-recognition-by-human-t-cells
#20
Katerina Shamalov, Shlomo N Levy, Miryam Horovitz-Fried, Cyrille J Cohen
p53 was reported to be an attractive immunotherapy target because it is mutated in approximately half of human cancers, resulting in its inactivation and often accumulation in tumor cells. Peptides derived from p53 are presented by class I MHC molecules and may act as tumor-associated epitopes which could be targeted by p53-specific T cells. Interestingly, it was recently shown that there is a lack of significant correlation between p53 expression levels in tumors and their recognition by p53-TCR transduced T cells...
2017: Oncoimmunology
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