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P53 -apoptosis

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https://www.readbyqxmd.com/read/27906449/differential-mutation-frequencies-in-metastatic-cutaneous-squamous-cell-carcinomas-versus-primary-tumors
#1
Ayse Selen Yilmaz, Hatice Gulcin Ozer, Jessica L Gillespie, Dawn C Allain, Madison N Bernhardt, Karina Colossi Furlan, Leticia T F Castro, Sara B Peters, Priyadharsini Nagarajan, Stephen Y Kang, O Hans Iwenofu, Thomas Olencki, Theodoros N Teknos, Amanda Ewart Toland
BACKGROUND: Exome and targeted sequencing studies have identified potential driver mutations for a variety of tumor types. Cutaneous squamous cell carcinoma (cSCC) is one of the most highly mutated cancers but typically is associated with low rates of metastasis and high survival rates. Nevertheless, metastatic cSCC is a significant health threat; up to 8800 individuals die each year of this disease. METHODS: Because it is difficult to predict which cSCCs are more likely to metastasize, and because to the best of the authors' knowledge there are no targeted therapies specifically designated for patients with metastatic cSCC, exome and/or targeted sequencing of 18 metastatic and 10 primary cSCCs was performed to identify mutations that were more frequent in metastatic tumors and might be targeted for therapeutic benefit...
December 1, 2016: Cancer
https://www.readbyqxmd.com/read/27906185/anti-proliferative-activity-of-the-npm1-interacting-natural-product-avrainvillamide-in-acute-myeloid-leukemia
#2
Vibeke Andresen, Bjarte S Erikstein, Herschel Mukherjee, André Sulen, Mihaela Popa, Steinar Sørnes, Håkon Reikvam, Kok-Ping Chan, Randi Hovland, Emmet McCormack, Øystein Bruserud, Andrew G Myers, Bjørn T Gjertsen
Mutated nucleophosmin 1 (NPM1) acts as a proto-oncogene and is present in ~30% of patients with acute myeloid leukemia (AML). Here we examined the in vitro and in vivo anti-leukemic activity of the NPM1 and chromosome region maintenance 1 homolog (CRM1) interacting natural product avrainvillamide (AVA) and a fully syntetic AVA analog. The NPM1-mutated cell line OCI-AML3 and normal karyotype primary AML cells with NPM1 mutations were significantly more sensitive towards AVA than cells expressing wild-type (wt) NPM1...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27906043/exosomes-play-an-important-role-in-the-process-of-psoralen-reverse-multidrug-resistance-of-breast-cancer
#3
Xiaohong Wang, Chengfeng Xu, Yitong Hua, Leitao Sun, Kai Cheng, Zhongming Jia, Yong Han, Jianli Dong, Yuzhen Cui, Zhenlin Yang
BACKGROUND: Release of exosomes have been shown to play critical roles in drug resistance by delivering cargo. Targeting the transfer of exosomes from resistant cells to sensitive cells may be an approach to overcome some cases of drug resistance. METHOD: In this study, we investigated the potential role of exosomes in the process of psoralen reverse multidrug resistance of MCF-7/ADR cells. Exosomes were isolated by differential centrifugation of culture media from MCF-7/ADR cells (ADR/exo) and MCF-7 parental cells (S/exo)...
December 1, 2016: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/27905468/protein-peptide-molecular-docking-with-large-scale-conformational-changes-the-p53-mdm2-interaction
#4
Maciej Pawel Ciemny, Aleksander Debinski, Marta Paczkowska, Andrzej Kolinski, Mateusz Kurcinski, Sebastian Kmiecik
Protein-peptide interactions are often associated with large-scale conformational changes that are difficult to study either by classical molecular modeling or by experiment. Recently, we have developed the CABS-dock method for flexible protein-peptide docking that enables large-scale rearrangements of the protein chain. In this study, we use CABS-dock to investigate the binding of the p53-MDM2 complex, an element of the cell cycle regulation system crucial for anti-cancer drug design. Experimental data suggest that p53-MDM2 binding is affected by significant rearrangements of a lid region - the N-terminal highly flexible MDM2 fragment; however, the details are not clear...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27904708/overexpression-of-carboxypeptidase-a4-cpa4-is-associated-with-poor-prognosis-in-patients-with-gastric-cancer
#5
Lichao Sun, Chunguang Guo, Hebao Yuan, Joseph Burnett, Jian Pan, Zhihua Yang, Yuliang Ran, Ila Myers, Duxin Sun
CarboxypeptidaseA4 (CPA4) is a zinc-containing exopeptidases, and its aberrant expression has been implicated in cancer development and progression. However, few studies have investigated the association between CPA4 over-expression and clinical significance in gastric cancer (GC). In this study, we employed immunohistochemistry to evaluate the expression of CPA4 in gastric cancer tissues, and found that elevated CPA4 expression was detected in 64% (n=100) of primary GCs, but was weak or no staining in the normal mucosa...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27904700/detection-of-gene-copy-number-alterations-in-dcis-and-invasive-breast-cancer-by-qm-fish
#6
Aifeng Pan, Yawei Zhou, Kun Mu, Yansong Liu, Feifei Sun, Peng Li, Li Li
The exact roles of copy number alteration (CNA) in initiation, progression and immunotherapy of breast cancer and the genomic alterations behind progression from ductal carcinoma in situ (DCIS) to invasive carcinoma remain unknown. Quantitative multi-gene fluorescence in situ hybridization (QM-FISH) opens a possibility of large scale genomic analysis of specific deletions and amplifications with high-resolution at one cell level. We detected CNAs of 30 genes using QM-FISH and analyzed their association with clinicopathological parameters and patients' outcomes in 66 breast cancers with synchronous invasive carcinoma and DCIS...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27904674/bmi1-plays-an-important-role-in-dentin-and-mandible-homeostasis-by-maintaining-redox-balance
#7
Ying Yin, Xian Xue, Qian Wang, Ning Chen, Dengshun Miao
To explore whether polycomb repressor Bmi1 plays an important role in dentin and mandible development homeostasis by maintaining redox balance, 3-week-old Bmi1 gene knockout (Bmi1(-/-)) mice were treated with the antioxidant N-acetylcysteine (NAC) for 2 weeks in their drinking water and phenotypes of the tooth and mandibles were compared with vehicle-treated Bmi1(-/-) mice and wild-type mice by radiograph, histochemistry and immunohistochemistry. Alterations of oxidative stress, DNA damage, cell proliferation and cell cycle-related parameters were also examined in mandibles...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27903905/human-mlh1-suppresses-the-insertion-of-telomeric-sequences-at-intra-chromosomal-sites-in-telomerase-expressing-cells
#8
Pingping Jia, Megan Chastain, Ying Zou, Chengtao Her, Weihang Chai
Aberrant formation of interstitial telomeric sequences (ITSs) promotes genome instabilities. However, it is unclear how aberrant ITS formation is suppressed in human cells. Here, we report that MLH1, a key protein involved in mismatch repair (MMR), suppresses telomeric sequence insertion (TSI) at intra-chromosomal regions. The frequency of TSI can be elevated by double-strand break (DSB) inducer and abolished by ATM/ATR inhibition. Suppression of TSI requires MLH1 recruitment to DSBs, indicating that MLH1's role in DSB response/repair is important for suppressing TSI...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27903710/the-hippo-p53-pathway-in-megakaryopoiesis
#9
EDITORIAL
Praveen K Suraneni, John D Crispino
No abstract text is available yet for this article.
December 2016: Haematologica
https://www.readbyqxmd.com/read/27903487/disturbed-p53-mdm2-feedback-loop-contributes-to-thoracic-aortic-dissection-formation-and-may-be-a-result-of-trim-25-overexpression
#10
Bin Gong, Zhiwei Wang, Min Zhang, Zhipeng Hu, Zongli Ren, Zheng Tang, Wanli Jiang, Lianghao Cheng, Jun Huang, Wei Ren, Qingtao Wang
BACKGROUND: The development of thoracic aortic dissection (TAD) is attributed to a broad range of degenerative, genetic, structural, oxidative, apoptotic, and acquired disease states. In this study, we examined the role of the disturbed p53-MDM2 feed-back loop in the formation of TAD, and one of a potential feed-back loop regulator, TRIM-25. METHODS: Surgical specimens of the aorta from TAD patients (n=10) and controls (n=10) were tested for α-smooth muscle actin (α-SMA),p53,murine double minute2(MDM2) and tripartite motif protein-25(TRIM-25) by western blot, immunohistochemical staining and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) , respectively...
November 26, 2016: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/27902843/ridge-estimation-of-the-var-1-model-and-its-time-series-chain-graph-from-multivariate-time-course-omics-data
#11
Viktorian Miok, Saskia M Wilting, Wessel N van Wieringen
Omics experiments endowed with a time-course design may enable us to uncover the dynamic interplay among genes of cellular processes. Multivariate techniques (like VAR(1) models describing the temporal and contemporaneous relations among variates) that may facilitate this goal are hampered by the high-dimensionality of the resulting data. This is resolved by the presented ridge regularized maximum likelihood estimation procedure for the VAR(1) model. Information on the absence of temporal and contemporaneous relations may be incorporated in this procedure...
November 7, 2016: Biometrical Journal. Biometrische Zeitschrift
https://www.readbyqxmd.com/read/27902457/tfdp3-confers-chemoresistance-in-minimal-residual-disease-within-childhood-t-cell-acute-lymphoblastic-leukemia
#12
Ming Chu, Kailin Yin, Yujun Dong, Pingzhang Wang, Yun Xue, Peng Zhou, Yuqi Wang, Yuedan Wang
Acquired drug resistance in childhood T-cell acute lymphoblastic leukemia (T-ALL) remains a significant clinical problem. In this study, a novel gene therapy target for childhood T-ALL to overcome chemoresistance was discovered: TFDP3 increased in the minimal residual disease (MRD) positive childhood T-ALL patients. Then, we established a preclinical model of resistance to induction therapy to examine the functional relevance of TFDP3 to chemoresistance in MRD derived from Jurkat/E6-1. Jurkat xenografts in NOD/SCID mice were exposed to a four drug combination (VXLD) of vincristine (VCR), dexamethasone (DEX), L-asparaginase (L-asp) and daunorubicin (DNR)...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27902328/hepatitis-c-virus-core-activates-proteasomal-activator-28-gamma-expression-via-upregulation-of-p53-levels-to-control-virus-propagation
#13
Juri Kwak, Indira Tiwari, Kyung Lib Jang
The proteasomal activator PA28γ, frequently overexpressed in hepatocellular carcinoma (HCC), is believed to play several important roles in hepatitis C virus (HCV) replication and viral pathogenesis. However, the underlying mechanism for PA28γ overexpression in HCC and its role during HCV replication are still unclear. In the present study, we found that HCV Core derived from either ectopic expression or HCV infection upregulates PA28γ levels in p53-positive human hepatocytes. For this effect, HCV Core sequentially activated ataxia telangiectasia mutated and checkpoint kinase 2 via phosphorylation at Ser-1981 and Thr-68 residues, respectively, resulting in stabilization of p53 via phosphorylation at Ser-15 and Ser-20 residues and subsequent transcriptional activation of PA28γ expression...
November 11, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27902314/newcastle-disease-virus-degrades-hif-1%C3%AE-through-proteasomal-pathways-independent-of-vhl-and-p53
#14
Noraini Abd-Aziz, Eric Stanbridge, Norazizah Shafee
Newcastle disease virus (NDV) is a candidate agent for oncolytic virotherapy. Despite its potential, the exact mechanism of its oncolysis is still not known. Recently, we reported that NDV exhibited an increased oncolytic activity in hypoxic cancer cells. These types of cells negatively affect therapeutic outcome by overexpressing pro-survival genes under the control of the hypoxia-inducible factor (HIF). HIF-1 is a heterodimeric transcriptional factor consisting of a regulated alpha (HIF-1α) and a constitutive beta subunit (HIF-1β)...
October 6, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27901482/hyperglycemia-triggers-hipk2-protein-degradation
#15
Silvia Baldari, Alessia Garufi, Marisa Granato, Laura Cuomo, Giuseppa Pistritto, Mara Cirone, Gabriella D'Orazi
Homeodomain interacting protein kinase-2 (HIPK2) is an evolutionary conserved kinase that modulates several key molecular pathways to restrain tumor growth and induce p53-depending apoptotic cell-death in response to anticancer therapies. HIPK2 silencing in cancer cells leads to chemoresistance and cancer progression, in part due to p53 inhibition. Recently, hyperglycemia has been shown to reduce p53 phosphorylation at serine 46 (Ser46), the target residue of HIPK2, thus impairing p53 apoptotic function. Here we asked whether hyperglycemia could, upstream of p53, target HIPK2...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27899992/beside-p53-and-pten-identification-of-molecular-alterations-of-the-ras-mapk-and-pi3k-akt-signaling-pathways-in-high-grade-serous-ovarian-carcinomas-to-determine-potential-novel-therapeutic-targets
#16
Shuhui Chen, Elisa Cavazza, Catherine Barlier, Julia Salleron, Pierre Filhine-Tresarrieu, Céline Gavoilles, Jean-Louis Merlin, Alexandre Harlé
Despite great histological and molecular heterogeneity, the clinical management of high-grade ovarian carcinomas remains unspecialized. As a major subgroup, high-grade serous ovarian carcinomas (HGSOCs) require novel therapies. In addition to utilizing conventional histological prognostic markers and performing oncogenetic investigations, the molecular diagnostic method of next generation sequencing (NGS) was performed to identify 'druggable' targets that could provide access to innovative therapy. The present study was performed in 45 HGSOC patients (mean age, 59...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899979/aspirin-inhibits-the-proliferation-and-migration-of-gastric-cancer-cells-in-p53-knockout-mice
#17
Xue-Fu Li, Bing-Zhong Xu, Shi-Zhen Wang
The aim of the present study was to investigate the effect of aspirin on the cell proliferation and migration of gastric cancer cells in p53-knockout mice. Twenty p53(-/-) male mice aged 6 to 7 weeks, with an average weight of 20±3 g were used. The model of gastric cancer was established by the implantation of a mouse forestomach carcinoma cell line, subcutaneously, at the back of the neck, and then the mice were randomly divided into two groups after establishment of the model (control group, n=10; experimental group, n=10)...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899973/expression-patterns-of-maspin-and-mutant-p53-are-associated-with-the-development-of-gestational-trophoblastic-neoplasia
#18
Pengming Sun, Qibin Wu, Guanyu Ruan, Xiu Zheng, Yiyi Song, Jianfan Zhun, Lixiang Wu, Walter H Gotlieb
Gestational trophoblastic disease (GTD) is a group of conditions that originate from the abnormal proliferation of trophoblastic cells. GTDs encompass hydatidiform moles (HMs) and gestational trophoblastic neoplasia (GTN). GTNs are a group of malignant diseases that require chemotherapy, or more aggressive treatment. There is a requirement for more tumor markers to predict the development of GTN from HMs. The current study evaluated the expression of maspin and tumor protein p53 (p53) in GTD, and their role in predicting the development of GTN...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899971/the-targetable-role-of-herpes-virus-associated-ubiquitin-specific-protease-hausp-in-p190-bcr-abl-leukemia
#19
Giovanna Carrà, Cristina Panuzzo, Sabrina Crivellaro, Deborah Morena, Riccardo Taulli, Angelo Guerrasio, Giuseppe Saglio, Alessandro Morotti
Philadelphia chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL) is driven by the p190 breakpoint cluster region (BCR)-ABL isoform. Although effectively targeted by BCR-ABL tyrosine kinase inhibitors (TKIs), ALL is associated with a less effective response to TKIs compared with chronic myeloid leukemia. Therefore, the identification of additional genes required for ALL maintenance may provide possible therapeutic targets to aid the eradication of this cancer. The present study demonstrated that p190 BCR-ABL is able to interact with the deubiquitinase herpesvirus-associated ubiquitin-specific protease (HAUSP), which in turn affects p53 protein stability...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27898737/transcriptomic-analysis-implicates-the-p53-signaling-pathway-in-the-establishment-of-hiv-1-latency-in-central-memory-cd4-t-cells-in-an-in-vitro-model
#20
Cory H White, Bastiaan Moesker, Nadejda Beliakova-Bethell, Laura J Martins, Celsa A Spina, David M Margolis, Douglas D Richman, Vicente Planelles, Alberto Bosque, Christopher H Woelk
The search for an HIV-1 cure has been greatly hindered by the presence of a viral reservoir that persists despite antiretroviral therapy (ART). Studies of HIV-1 latency in vivo are also complicated by the low proportion of latently infected cells in HIV-1 infected individuals. A number of models of HIV-1 latency have been developed to examine the signaling pathways and viral determinants of latency and reactivation. A primary cell model of HIV-1 latency, which incorporates the generation of primary central memory CD4 T cells (TCM), full-length virus infection (HIVNL4-3) and ART to suppress virus replication, was used to investigate the establishment of HIV latency using RNA-Seq...
November 2016: PLoS Pathogens
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