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https://www.readbyqxmd.com/read/28235006/genome-wide-effects-of-melk-inhibitor-in-triple-negative-breast-cancer-cells-indicate-context-dependent-response-with-p53-as-a-key-determinant
#1
Marisa Simon, Fahmi Mesmar, Luisa Helguero, Cecilia Williams
Triple-negative breast cancer (TNBC) is an aggressive, highly recurrent breast cancer subtype, affecting approximately one-fifth of all breast cancer patients. Subpopulations of treatment-resistant cancer stem cells within the tumors are considered to contribute to disease recurrence. A potential druggable target for such cells is the maternal embryonic leucine-zipper kinase (MELK). MELK expression is upregulated in mammary stem cells and in undifferentiated cancers, where it correlates with poor prognosis and potentially mediates treatment resistance...
2017: PloS One
https://www.readbyqxmd.com/read/28235003/p53-and-ki-67-as-prognostic-markers-in-triple-negative-breast-cancer-patients
#2
Yunbao Pan, Yufen Yuan, Guoshi Liu, Yongchang Wei
Triple-negative breast cancer (TNBC) is an aggressive subgroup of breast cancer lack of effective target therapy. This study was to investigate the prognostic role of p53 and Ki-67 in 156 cases of TNBC patients. Logistic regression analysis was used to examine the association between clinical parameters and recurrence. Univariate and multivariate analyses were used to examine the association between clinical characteristics and disease-free survival (DFS) or overall survival (OS). Survival analyses using the Kaplan-Meier method were performed to examine the association between p53/Ki-67 and DFS and OS...
2017: PloS One
https://www.readbyqxmd.com/read/28234922/conventional-colon-adenomas-harbor-various-disturbances-in-microsatellite-stability-and-contain-micro-serrated-foci-with-microsatellite-instability
#3
Piotr Lewitowicz, Stanislaw Gluszek, Dorota Koziel, Agata Horecka-Lewitowicz, Magdalena Chrapek, Przemyslaw Wolak, Justyna Klusek, Anna Nasierowska-Guttmejer
INTRODUCTION: Colorectal cancer belongs to the most frequent occurring malignancies. A prediction of the clinical outcome and appropriate choice of neoadjuvant chemotherapy needs personalized insight to the main driving pathways. Because most CRCs have polyps as progenitor lesions, studying the pathways driving to adenomagenesis is no less important. GOALS: Our purpose was the evaluation of microsatellite stability status within conventional colon adenomas and also β-catenin, BRAFV600E and p53 contribution...
2017: PloS One
https://www.readbyqxmd.com/read/28234008/-strebloside-induced-cytotoxicity-in-ovarian-cancer-cells-is-mediated-through-cardiac-glycoside-signaling-networks
#4
Wei-Lun Chen, Yulin Ren, Jinhong Ren, Christian Erxleben, Michael E Johnson, Saverio Gentile, A Douglas Kinghorn, Steven M Swanson, Joanna E Burdette
(+)-Strebloside, a cardiac glycoside isolated from the stem bark of Streblus asper collected in Vietnam, has shown some potential for further investigation as an antineoplastic agent. A mechanistic study using an in vitro assay and molecular docking analysis indicated that (+)-strebloside binds and inhibits Na(+)/K(+)-ATPase in a similar manner to digitoxin. Inhibition of growth of different high-grade serous ovarian cancer cells including OVCAR3, OVSAHO, Kuramochi, OVCAR4, OVCAR5, and OVCAR8 resulted from treatment with (+)-strebloside...
February 24, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28233940/enhancement-of-antiangiogenic-efficacy-of-iron-ii-complex-by-selenium-substitution
#5
Haoqiang Lai, Xiang Zhang, Pengju Feng, Lina Xie, Jinjin Chen, Tianfeng Chen
Antiangiogenic therapy is a potent and specific strategy for the treatment of cancers. Herein we demonstrate that Iron(II) complexes containing 1,10-phenanthroline (phen) derivaties are capable of suppressing angiogenesis in vitro dose-dependently. Interestingly, introduction of selenium into iron(II) complex ((Fe(phenSe)3(ClO4)2, (phenSe=2-selenicimidazole[4,5-f]1,10-phenanthroline)) could enhance its anti-angiogenic efficacy. Mechanistic studies demonstrate that the complex effectively induces endothelial cells apoptosis, as evidenced by caspases activation and PARP cleavage...
February 24, 2017: Chemistry, An Asian Journal
https://www.readbyqxmd.com/read/28233861/ubiquitin-specific-peptidase-48-regulates-mdm2-protein-levels-independent-of-its-deubiquitinase-activity
#6
Kateřina Cetkovská, Hana Šustová, Stjepan Uldrijan
The overexpression of Mdm2 has been linked to the loss of p53 tumour suppressor activity in several human cancers. Here, we present results suggesting that ubiquitin-specific peptidase 48 (USP48), a deubiquitinase that has been linked in previous reports to the NF-κB signaling pathway, is a novel Mdm2 binding partner that promotes Mdm2 stability and enhances Mdm2-mediated p53 ubiquitination and degradation. In contrast to other deubiquitinating enzymes (DUBs) that have been previously implicated in the regulation of Mdm2 protein stability, USP48 did not induce Mdm2 stabilization by significantly reducing Mdm2 ubiquitination levels...
February 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28233083/molecular-markers-in-glioma
#7
REVIEW
Kirsten Ludwig, Harley I Kornblum
Gliomas are the most malignant and aggressive form of brain tumors, and account for the majority of brain cancer related deaths. Malignant gliomas, including glioblastoma are treated with radiation and temozolomide, with only a minor benefit in survival time. A number of advances have been made in understanding glioma biology, including the discovery of cancer stem cells, termed glioma stem cells (GSC). Some of these advances include the delineation of molecular heterogeneity both between tumors from different patients as well as within tumors from the same patient...
February 23, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28232952/identification-validation-and-targeting-of-the-mutant-p53-parp-mcm-chromatin-axis-in-triple-negative-breast-cancer
#8
Wei-Gang Qiu, Alla Polotskaia, Gu Xiao, Lia Di, Yuhan Zhao, Wenwei Hu, John Philip, Ronald C Hendrickson, Jill Bargonetti
Over 80% of triple negative breast cancers express mutant p53. Mutant p53 often gains oncogenic function suggesting that triple negative breast cancers may be driven by p53 protein type. To determine the chromatin targets of this gain-of-function mutant p53 we used inducible knockdown of endogenous gain-of-function mtp53 in MDA-MB-468 cells in conjunction with stable isotope labeling with amino acids in cell culture and subcellular fractionation. We sequenced over 70,000 total peptides for each corresponding reciprocal data set and were able to identify 3010 unique cytoplasmic fraction proteins and 3403 unique chromatin fraction proteins...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/28232485/linc00672-contributes-p53-mediated-gene-suppression-and-promotes-endometrial-cancer-chemosensitivity
#9
Wei Li, Hua Li, Liyuan Zhang, Min Hu, Fang Li, Jieqiong Deng, Mingxing An, Siqi Wu, Rui Ma, Jiachun Lu, Yifeng Zhou
Thousands of long intergenic non-protein coding RNAs (lincRNAs) have been identified in mammals in genome-wide sequencing studies. Some of these RNAs have been consistently conserved during the evolution of species and, could presumably function in important biological processes. We, therefore, measured the levels of 26 highly conserved lincRNAs in a total of 176 pairs of endometrial carcinoma (EC) and surrounding non-tumor tissues of two distinct Chinese populations. Here, we report that a lincRNA, LINC00672, which possesses an ultra-conserved region, is aberrantly downregulated during the development of EC...
February 23, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28232385/the-cytidine-deaminase-apobec3-family-is-subject-to-transcriptional-regulation-by-p53
#10
Daniel Menendez, Thuy-Ai Nguyen, Joyce Snipe, Michael A Resnick
: The APOBEC3 (A3) family of proteins are DNA cytidine deaminases that act as sentinels in the innate immune response against retroviral infections and are responsive to interferon. Recently, a few A3 genes were identified as potent enzymatic sources of mutations in several human cancers. Using human cancer cells and lymphocytes we show that under stress conditions and immune challenges all A3 genes are direct transcriptional targets of the tumor suppressor p53. While the expression of most A3 genes (including A3C and A3H) was stimulated by activation of p53, treatment with the DNA damaging agent doxorubicin or the p53 stabilizer Nutlin, led to repression of the A3B gene...
February 23, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28232188/pneumolysin-induces-cellular-senescence-by-increasing-ros-production-and-activation-of-mapk-nf-%C3%AE%C2%BAb-signal-pathway-in-glial-cells
#11
Ii-Seul Kwon, Jinwook Kim, Dong-Kwon Rhee, Byung-Oh Kim, Suhkneung Pyo
Senescence is an irreversible proliferation arrest that is induced by various stress stimuli including genotoxin. Pneumolysin (PLY) is a pathogenicity factor unique to Streptococcus pneumoniae that is important in pneumococcal-induced diseases such as otitis media, meningitis and pneumonia. However, the cell fate response to the toxin is mechanistically unclear. We investigated the effect of PLY on cellular senescence in BV-2 microglial cells. Exposure to PLY resulted in changes in the expression of phospho-p53, p21, p16, pRb and CDK2 and increased the number of senescence associated β-gal positive cells...
February 19, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28231749/flavonoids-and-tannins-from-smilax-china-l-rhizome-induce-apoptosis-via-mitochondrial-pathway-and-mdm2-p53-signaling-in-human-lung-adenocarcinoma-cells
#12
San Fu, Yanfang Yang, Dan Liu, Yan Luo, Xiaochuan Ye, Yanwen Liu, Xin Chen, Song Wang, Hezhen Wu, Yuhang Wang, Qiwei Hu, Pengtao You
In vitro evidence indicates that Smilax china L. rhizome (SCR) can inhibit cell proliferation. Therefore, in the present study, we analyzed the effects in vitro of SCR extracts on human lung adenocarcinoma A549 cells. Our results showed that A549 cell growth was inhibited in a dose- and time-dependent manner after treatment with SCR extracts. Total flavonoids and total tannins from SCR induced A549 apoptosis in a dose-dependent manner, as shown by our flow cytometry analysis, which was consistent with the alterations in nuclear morphology we observed...
February 23, 2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/28231747/saikosaponin-a-induces-apoptosis-through-mitochondria-dependent-pathway-in-hepatic-stellate-cells
#13
Chang-Han Chen, Ming-Feng Chen, S Joseph Huang, Chun-Yen Huang, Hao-Kuang Wang, Wen-Chuan Hsieh, Chih-Hao Huang, Li-Feng Liu, Li-Yen Shiu
Saikosaponin a (SSa) is one of the main active components of Bupleurum falcatum. It is commonly used to treat liver injury and fibrosis in traditional Chinese medicine. Our previous study showed that SSa induces apoptosis and inhibits the proliferation of rat hepatic stellate cell (HSC) line HSC-T6. The aim of the present study was to elucidate the mechanism of SSa-mediated apoptosis. Rat HSC cell line HSC-T6 and human HSC cell line LX-2 were used in this study. SSa triggered cell death mainly by apoptosis, as indicated by the typical morphological changes, sub-G1 phase of cell cycle increase, and activation of the caspase-9/caspase-3 cascade...
February 23, 2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/28230866/oridonin-induces-autophagy-via-inhibition-of-glucose-metabolism-in-p53-mutated-colorectal-cancer-cells
#14
Zhuo Yao, Fuhua Xie, Min Li, Zirui Liang, Wenli Xu, Jianhua Yang, Chang Liu, Hongwangwang Li, Hui Zhou, Liang-Hu Qu
The Warburg effect is an important characteristic of tumor cells, making it an attractive therapeutic target. Current anticancer drug development strategies predominantly focus on inhibitors of the specific molecular effectors involved in tumor cell proliferation. These drugs or natural compounds, many of which target the Warburg effect and the underlying mechanisms, still need to be characterized. To elucidate the anticancer effects of a natural diterpenoid, oridonin, we first demonstrated the anticancer activity of oridonin both in vitro and in vivo in colorectal cancer (CRC) cells...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28230820/the-distribution-of-tp53-gene-polymorphisms-in-chronic-lymphocytic-leukemia-patients-sufferers-of-chornobyl-nuclear-power-plant-accident
#15
N I Bilous, I V Abramenko, A A Chumak, I S Dyagil, Z V Martina
: Previous analyses in a cohort of Chornobyl cleanup workers revealed significantly increased radiation-related risk for all leukemia types, including chronic lymphocytic leukemia (CLL). Numerous investigations emphasized the significance of genetic susceptibility to the radiation carcinogenesis. The aim of the work was to study the distribution of TP53 single nucleotide polymorphisms (SNPs) in CLL patients exposed to ionizing radiation (IR) due to Chornobyl nuclear power plant accident and estimate their impact on disease development...
December 2016: Experimental Oncology
https://www.readbyqxmd.com/read/28230797/zyz-772-prevents-cardiomyocyte-injury-by-suppressing-nox4-derived-ros-production-and-apoptosis
#16
Ying Wang, Liangjie Zhong, Xinhua Liu, Yi Zhun Zhu
Nox-dependent signaling plays critical roles in the development of heart failure, cardiac hypertrophy, and myocardial infarction. NADPH oxidase 4 (Nox4) as a major source of oxidative stress in the heart offers a new therapeutic target in cardiovascular disease. In the present work, a novel flavonoid was isolated from Zanthoxylum bungeanum. Its structure was elucidated as Quercetin-3-O-(6''-O-α-l-rhamnopyransoyl)-β-d-glucopyranoside-7-O-β-d-glucopyranoside (ZYZ-772) for the first time. ZYZ-772 exhibited significant cardio-protective property against CoCl₂ induced H9c2 cardiomyocyte cells injury...
February 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28230750/targeting%C3%A2-mdm4%C3%A2-splicing%C3%A2-in%C3%A2-cancers
#17
REVIEW
Boris Bardot, Franck Toledo
MDM4, an essential negative regulator of the P53 tumor suppressor, is frequently overexpressed in cancer cells that harbor a wild-type P53. By a mechanism based on alternative splicing, the MDM4 gene generates two mutually exclusive isoforms: MDM4-FL, which encodes the full-length MDM4 protein, and a shorter splice variant called MDM4-S. Previous results suggested that the MDM4-S isoform could be an important driver of tumor development. In this short review, we discuss a recent set of data indicating that MDM4-S is more likely a passenger isoform during tumorigenesis and that targeting MDM4 splicing to prevent MDM4-FL protein expression appears as a promising strategy to reactivate p53 in cancer cells...
February 20, 2017: Genes
https://www.readbyqxmd.com/read/28229982/circulating-free-dna-mutation-associated-with-response-of-targeted-therapy-in-human-epidermal-growth-factor-receptor-2-positive-metastatic-breast-cancer
#18
Qing Ye, Fan Qi, Li Bian, Shao-Hua Zhang, Tao Wang, Ze-Fei Jiang
BACKGROUND: The addition of anti-human epidermal growth factor receptor 2 (HER2)-targeted drugs, such as trastuzumab, lapatinib, and trastuzumab emtansine (T-DM1), to chemotherapy significantly improved prognosis of HER2-positive breast cancer patients. However, it was confused that metastatic patients vary in the response of targeted drug. Therefore, methods of accurately predicting drug response were really needed. To overcome the spatial and temporal limitations of biopsies, we aimed to develop a more sensitive and less invasive method of detecting mutations associated with anti-HER2 therapeutic response through circulating-free DNA (cfDNA)...
2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28229963/constitutively-activated-erk-sensitizes-cancer-cells-to-doxorubicin-involvement-of-p53-egfr-erk-pathway
#19
Ratna Kumari, Surbhi Chouhan, Snahlata Singh, Rishi Raj Chhipa, Amrendra Kumar Ajay, Manoj Kumar Bhat
The tumour suppressor gene p53 is mutated in approximately 50% of the human cancers. p53 is involved in genotoxic stress-induced cellular responses. The role of EGFR and ERK in DNA-damage-induced apoptosis is well known. We investigated the involvement of activation of ERK signalling as a consequence of non-functional p53, in sensitivity of cells to doxorubicin. We performed cell survival assays in cancer cell lines with varying p53 status: MCF-7 (wild-type p53, WTp53), MDA MB-468 (mutant p53, MUTp53), H1299 (absence of p53, NULLp53) and an isogenic cell line MCF-7As (WTp53 abrogated)...
March 2017: Journal of Biosciences
https://www.readbyqxmd.com/read/28229640/effect-of-cerebrolysin-on-oxidative-stress-induced-apoptosis-in-an-experimental-rat-model-of-myocardial-ischemia
#20
V Boshra, A Atwa
Apoptosis plays a role in the process of tissue damage after myocardial infarction (MI). This study was designed to investigate the possible effect of cerebrolysin against apoptosis triggered by oxidative cell stress in myocardial ischemia induced by isoproterenol in rat. Rats were pretreated with cerebrolysin 5 mL/kg intraperitoneally for 7 days and intoxicated with isoproterenol (ISO, 85 mg/kg, sc) on the last 2 days. Hearts were excised and stained to detect the infarction size. Serum levels of cardiotoxicity indices as creatine kinase isoenzyme (CK-MB) and troponin I (cTnI) as well as the cardiac oxidative stress parameters as thiobarbituric acid reactive substances and superoxide dismutase were estimated...
September 2016: Physiol Int
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