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https://www.readbyqxmd.com/read/29334665/i-7ab-inhibited-the-growth-of-tnbc-cells-via-targeting-hdac3-and-promoting-the-acetylation-of-p53
#1
Mei Yang, Xuefei Dang, Yue Tan, Meixing Wang, Xiaojing Li, Gang Li
Triple negative breast cancer (TNBC) is a heterogenous disease with high aggressive and poor outcome. The lack of biomarkers and targeted therapies makes it a challenge for the treatment of TNBC. Histone deacetylase inhibitors (HDACis) are emerging as novel anti-tumor agents in many types of human cancers. In this study, we found that I-7ab, a novel HDACi, inhibited the cell viability of TNBC cells and induced the cell apoptosis. Mechanistically, I-7ab specifically decreased the expression of HDAC3 and promoted the acetylation of p53 at both Lys373 and Lys382 amino acids...
January 12, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29334356/p53-suppresses-mutagenic-rad52-and-pol%C3%AE-pathways-by-orchestrating-dna-replication-restart-homeostasis
#2
Sunetra Roy, Karl-Heinz Tomaszowski, Jessica W Luzwick, Soyoung Park, Jun Li, Maureen Murphy, Katharina Schlacher
Classically, p53 tumor suppressor acts in transcription, apoptosis, and cell cycle arrest. Yet, replication-mediated genomic instability is integral to oncogenesis, and p53 mutations promote tumor progression and drug-resistance. By delineating human and murine separation-of-function p53 alleles, we find that p53 null and gain-of-function (GOF) mutations exhibit defects in restart of stalled or damaged DNA replication forks driving genomic instability genetically separable from transcription activation. By assaying protein-DNA fork interactions in single cells, we unveil a p53-MLL3-enabled recruitment of MRE11 DNA replication restart nuclease...
January 15, 2018: ELife
https://www.readbyqxmd.com/read/29334217/characterization-of-an-hsp90-independent-interaction-between-the-co-chaperone-p23-and-the-transcription-factor-p53
#3
Huiwen Wu, Jashil Hyun, Maria A Martinez-Yamout, Sung Jean Park, Jane Dyson
The cancer-suppressing transcription factor p53 is regulated by a wide variety of cellular factors, including many chaperones. The DNA-binding domain (DBD) of p53 is known to interact with the chaperone Hsp90, but the role of other members of the chaperone network, including co-chaperones such as p23 is unknown. Using a combination of NMR titration, isothermal titration calorimetry, fluorescence anisotropy and native agarose gel electrophoresis, we have identified a direct interaction between the p53 DBD and the Hsp90 co-chaperone p23 that occurs in the absence of Hsp90...
January 15, 2018: Biochemistry
https://www.readbyqxmd.com/read/29334216/lysosome-independent-intracellular-drug-gene-co-delivery-by-lipoprotein-derived-nanovector-for-synergistic-apoptosis-inducing-cancer-targeted-therapy
#4
Wei Wang, Kerong Chen, Yujie Su, Jielei Zhang, Min Li, Jianping Zhou
In this paper, reconstituted high-density lipoprotein (rHDL), a lipoprotein-derived nanovector, were constructed for co-delivery of paclitaxel (PTX) and wild type p53 gene (p53). The particle size and the zeta potential of PTX-DODAB/p53-rHDL nanoparticles were 177.2 nm and -20.06 mV, respectively. Meanwhile, they exhibited great serum stability and satisfactory sustained release characteristics in vitro. PTX-DODAB/pDNA-rHDL nanoparticles simultaneously improved the cellular uptake of PTX and pDNA via scavenger receptor B type I (SR-BI) mediated lysosome-independent internalization and promoted the transfection of pDNA in MCF-7 cells, which were revealed by flow cytometry and confocal laser scanning microscopy analyses...
January 15, 2018: Biomacromolecules
https://www.readbyqxmd.com/read/29332339/p21-does-but-p53-does-not-predict-pathological-response-to-preoperative-chemoradiotherapy-in-locally-advanced-rectal-cancer
#5
Suzana Stojanovic-Rundic, Radmila Jankovic, Marjan Micev, Vladimir Nikolic, Ivan Popov, Dusica Gavrilovic, Vesna Plesinac-Karapandzic, Aleksandra Djuric-Stefanovic, Zoran Krivokapic, Sinisa Radulovic
PURPOSE: Preoperative chemoradiotherapy (CRT) is the standard treatment option in locally advanced rectal cancer. The tumor response is assessed through tumor and nodal downstaging and the tumor regression grade. Currently, there is no method to predict a tumor response to CRT. We aimed to evaluate whether p21 and p53 expressions could be a reliable predictors of pathological response to CRT. METHODS: Fifty patients with locally advanced rectal cancer were treated with preoperative radiotherapy combined with mitomycin C and capecitabine...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29331023/temozolomide-analog-pmx-465-downregulates-mgmt-expression-in-hct116-colorectal-carcinoma-cells
#6
Zhikuan Yang, Danping Wei, Feifei Liu, Jing Liu, Xiaoming Wu, Malcolm F G Stevens, Tracey D Bradshaw, Ying Luo, Jihong Zhang
The efficacy of temozolomide (TMZ) treatment for cancers is currently limited by inherent or the development of resistance, particularly, but not exclusively, due to the expression of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) in a significant proportion of tumors. We have found that TMZ analog C8-methyl imidazole tetrazine (PMX 465) displayed good anticancer activity against the colorectal carcinoma HCT116 cells which are MGMT-overexpressing and mismatch repair (MMR)-deficient. In this study, we found that PMX 465 could downregulate the expression of MGMT in HCT116 cells at the protein and mRNA levels...
January 13, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29330147/genetic-ablation-of-rbm38-promotes-lymphomagenesis-in-the-context-of-mutant-p53-by-downregulating-pten
#7
Jin Zhang, Enshun Xu, Cong Ren, Hee Jung Yang, Yanhong Zhang, Wenqiang Sun, Xiangmudong Kong, Weici Zhang, Mingyi Chen, Eric C Huang, Xinbin Chen
Mutant p53 exerts gain-of-function effects that drive metastatic progression and therapeutic resistance, but the basis for these effects remain obscure. The RNA binding protein RBM38 limits translation of mutant p53 and is often ablated in tumors harboring it. Here we show how loss of Rbm38 significantly alters cancer susceptibility in mutant p53 knock-in mice, by shortening lifespan, altering tumor incidence and promoting T cell lymphomagenesis. Loss of Rbm38 enhanced mutant p53 expression and decreased expression of the tumor suppressor Pten, a key regulator of T cell development...
January 12, 2018: Cancer Research
https://www.readbyqxmd.com/read/29330109/friend-or-foe-micrornas-in-the-p53-network
#8
Zhenghua Luo, Ri Cui, Esmerina Tili, Carlo Croce
The critical tumor suppressor gene TP53 is either lost or mutated in more than half of human cancers. As an important transcriptional regulator, p53 modulates the expression of many microRNAs. While wild-type p53 uses microRNAs to suppress cancer development, microRNAs that are activated by gain-of-function mutant p53 confer oncogenic properties. On the other hand, the expression of p53 is tightly controlled by a fine-tune machinery including microRNAs. MicroRNAs can target the TP53 gene directly or other factors in the p53 network so that expression and function of either the wild-type or the mutant forms of p53 is downregulated...
January 9, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29330052/esco2-knockdown-inhibits-cell-proliferation-and-induces-apoptosis-in-human-gastric-cancer-cells
#9
Hongmei Chen, Lei Zhang, Wenting He, Liu Tao, Yang Zhao, Hao Chen, Yumin Li
Establishment of cohesion 1 homolog 2 (ESCO2), an essential gene for cohesion regulation and genomic stability, has not been studied in human gastric cancer (GC). We found that ESCO2 knockdown in human GC cell lines dramatically inhibited cell proliferation and induced cell apoptosis in vitro and suppressed tumor xenograft development in vivo. Furthermore, adenosine monophosphate-activated protein kinase (AMPK) was activated following the suppression of its downstream targets, including mammalian target of rapamycin (mTOR) and p70 ribosomal S6 kinase 1 (p70S6K1), and this result was consistent with p53 activation...
January 9, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29329830/theoretical-research-in-structure-characteristics-of-different-inhibitors-and-differences-of-binding-modes-with-cbp-bromodomain
#10
Xue-Song Wang, Qing-Chuan Zheng
The CBP (CREB (cAMP responsive element binding protein) binding protein) bromodomain (BRD) could recognize and bind with acetyl K382 of human tumor suppressor protein p53 which the mutation of encoding gene might cause human cancers. CBP-BRD serves as a promising drug target for several disease pathways and a series of effective drug have been discovered. In this study, molecular dynamics (MD) simulations and molecular mechanics generalized born surface area (MM-GB/SA) approaches were performed to investigate the different binding modes between five inhibitors with CBP-BRD...
December 26, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29328462/serum-and-glucocorticoid-regulated-kinase-1-sgk1-is-a-predictor-of-poor-prognosis-in-non-small-cell-lung-cancer-and-its-dynamic-pattern-following-treatment-with-sgk1-inhibitor-and-%C3%AE-ray-irradiation-was-elucidated
#11
Zhiyuan Tang, Qin Shen, Hao Xie, Zhu Zhou, Guanglin Shi, Caixin Zhang, Anaz Mohammed, Yi Wu, Songshi Ni, Xiaoyu Zhou
The tumor suppressor gene p53 and its dynamic patterns have caused widespread attention in the field of cancer research. Serum and glucocorticoid-regulated kinase 1 (SGK1) with features of serine/threonine kinase activity, which also contributes to the structural and functional similarities with the AKT family of kinases, is a key enzyme in the regulation of immune responses in tumor cells, and SGK1 was noted to be expressed in close relation to p53 protein levels, and there exists a negative feedback pathway between intracellular SGK1 and p53...
January 3, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29328445/the-effects-of-interleukin-2-and-rad-p53-as-a-treatment-for-glioblastoma
#12
Hai-Bo Qiao, Jia Li, Lian-Jie Lv, Ben-Jin Nie, Peng Lu, Feng Xue, Zhi-Ming Zhang
Interleukin 2 (IL-2) is an anti-cancer cytokine that stimulates T cell propagation, triggering innate and adaptive immunity. IL-2 has been used for cancer therapy and has achieved curative effects. Recombinant adenovirus p53 injection (rAd‑p53) is a gene therapeutic agent that may improve the prognosis of patients with glioblastoma (GBM). In the present study, the effect of combined IL‑2 and rAd‑p53 treatment was studied. The ability of IL‑2 to stimulate immunoregulation and the ability of p53 to induce apoptosis for GBM was researched in the GBM tumor model...
January 9, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29327492/a-five-gene-signature-may-predict-sunitinib-sensitivity-and-serve-as-prognostic-biomarkers-for-renal-cell-carcinoma
#13
Yuan-Lei Chen, Guang-Ju Ge, Chao Qi, Huan Wang, Huai-Lan Wang, Li-Yang Li, Gong-Hui Li, Li-Qun Xia
Sunitinib resistance is, nowadays, the major challenge for advanced renal cell carcinoma patients. Illuminating the potential mechanisms and exploring effective strategies to overcome sunitinib resistance are highly desired. We constructed a reliable gene signature which may function as biomarkers for prediction of sunitinib sensitivity and clinical prognosis. The gene expression profiles were obtained from The Cancer Genome Atlas database. By performing GEO2R analysis, numerous differentially expressed genes (DEGs) were found to be associated with sunitinib resistance...
January 12, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29324843/beta-hpv38-oncoproteins-act-with-a-hit-and-run-mechanism-in-ultraviolet-radiation-induced-skin-carcinogenesis-in-mice
#14
Daniele Viarisio, Karin Müller-Decker, Rosita Accardi, Alexis Robitaille, Matthias Dürst, Katrin Beer, Lars Jansen, Christa Flechtenmacher, Matthias Bozza, Richard Harbottle, Catherine Voegele, Maude Ardin, Jiri Zavadil, Sandra Caldeira, Lutz Gissmann, Massimo Tommasino
Cutaneous beta human papillomavirus (HPV) types are suspected to be involved, together with ultraviolet (UV) radiation, in the development of non-melanoma skin cancer (NMSC). Studies in in vitro and in vivo experimental models have highlighted the transforming properties of beta HPV E6 and E7 oncoproteins. However, epidemiological findings indicate that beta HPV types may be required only at an initial stage of carcinogenesis, and may become dispensable after full establishment of NMSC. Here, we further investigate the potential role of beta HPVs in NMSC using a Cre-loxP-based transgenic (Tg) mouse model that expresses beta HPV38 E6 and E7 oncogenes in the basal layer of the skin epidermis and is highly susceptible to UV-induced carcinogenesis...
January 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29323264/orai3-calcium-channel-and-resistance-to-chemotherapy-in-breast-cancer-cells-the-p53-connection
#15
Jessy Hasna, Frédéric Hague, Lise Rodat-Despoix, Dirk Geerts, Catherine Leroy, David Tulasne, Halima Ouadid-Ahidouch, Philippe Kischel
Orai proteins are highly selective calcium channels playing an important role in calcium entry. Orai3 channels are overexpressed in breast cancer (BC) tissues, and involved in their proliferation, cell cycle progression and survival. Herein, we sought to address the involvement of Orai3 in resistance to chemotherapeutic drugs. Using high-throughput approaches, we investigated major changes induced by Orai3 overexpression, including downstream signaling mechanisms involved in BC chemotherapy resistance. Resistance was dependent on external calcium presence and thus Orai3 functionality...
January 11, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29323062/role-of-p53-and-ki-67-immunomarkers-in-carcinoma-of-urinary-bladder
#16
Brijesh Thakur, Sanjeev Kishore, Kanika Dutta, Sanjay Kaushik, Aparna Bhardwaj
BACKGROUND: Urothelial carcinoma is common urinary malignancy responsible for a significant proportion of cancer morbidity and mortality. We carried out the present study to demonstrate the clinicohistopathological features and to correlate the p53 and Ki-67 immunoexpression with grade and stage of bladder carcinomas. MATERIALS AND METHODS: We investigated 110 cases of bladder tumor. Grading and staging were done according to the WHO-2004 and American Joint Committee on Cancer-TNM staging recommendations...
October 2017: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/29322514/the-yin-and-yang-of-yy1-in-tumor-growth-and-suppression
#17
REVIEW
Levon M Khachigian
Yin Yang-1 (YY1) is a zinc finger protein and member of the GLI-Kruppel family that can activate or inactivate gene expression depending on interacting partners, promoter context and chromatin structure, and may be involved in the transcriptional control of ∼10% of the total mammalian gene set. A growing body of literature indicates that YY1 is overexpressed in multiple cancer types and that increased YY1 levels correlate with poor clinical outcomes in many cancers. However the role of YY1 in the promotion or suppression of tumor growth remains controversial and its regulatory effects may be tumor cell type dependent at least in experimental systems...
January 11, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29322354/mutations-of-key-driver-genes-in-colorectal-cancer-progression-and-metastasis
#18
REVIEW
Dongdong Huang, Wenjie Sun, Yuwei Zhou, Peiwei Li, Fang Chen, Hanwen Chen, Dajing Xia, Enping Xu, Maode Lai, Yihua Wu, Honghe Zhang
The association between mutations of key driver genes and colorectal cancer (CRC) metastasis has been investigated by many studies. However, the results of these studies have been contradictory. Here, we perform a comprehensive analysis to screen key driver genes from the TCGA database and validate the roles of these mutations in CRC metastasis. Using bioinformatics analysis, we identified six key driver genes, namely APC, KRAS, BRAF, PIK3CA, SMAD4 and p53. Through a systematic search, 120 articles published by November 30, 2017, were included, which all showed roles for these gene mutations in CRC metastasis...
January 10, 2018: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/29321954/a-role-for-caspase-2-in-sphingosine-kinase-1-proteolysis-in-response-to-doxorubicin-in-breast-cancer-cells-implications-for-the-chk1-suppressed-pathway
#19
Brittany L Carroll, Joseph Bonica, Achraf A Shamseddine, Yusuf A Hannun, Lina M Obeid
Sphingosine kinase 1 (SK1) is a lipid kinase whose activity produces sphingosine 1-phosphate, a prosurvival lipid associated with proliferation, angiogenesis, and invasion. SK1 overexpression has been observed in numerous cancers. Recent studies have demonstrated that SK1 proteolysis occurs downstream of the tumor suppressor p53 in response to several DNA-damaging agents. Moreover, loss of SK1 in p53-knockout mice resulted in complete protection from thymic lymphoma, providing evidence that regulation of SK1 constitutes a major tumor suppressor function of p53...
January 2018: FEBS Open Bio
https://www.readbyqxmd.com/read/29321668/aatf-suppresses-apoptosis-promotes-proliferation-and-is-critical-for-kras-driven-lung-cancer
#20
Daniela Welcker, Manaswita Jain, Safiya Khurshid, Mladen Jokić, Martin Höhne, Anna Schmitt, Peter Frommolt, Carien M Niessen, Judith Spiro, Thorsten Persigehl, Maike Wittersheim, Reinhard Büttner, Maurizio Fanciulli, Bernhard Schermer, Hans Christian Reinhardt, Thomas Benzing, Katja Höpker
A fundamental principle in malignant tranformation is the ability of cancer cells to escape the naturally occurring cell-intrinsic responses to DNA damage. Tumors progress despite the accumulation of DNA lesions. However, the underlying mechanisms of this tolerance to genotoxic stress are still poorly characterized. Here, we show that replication stress occurs in Kras-driven murine lung adenocarcinomas, as well as in proliferating murine embryonic and adult tissues. We identify the transcriptional regulator AATF/CHE-1 as a key molecule to sustain proliferative tissues and tumor progression in parts by inhibiting p53-driven apoptosis in vivo...
January 11, 2018: Oncogene
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