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https://www.readbyqxmd.com/read/30315225/mir-126-negatively-regulates-plk-4-to-impact-the-development-of-hepatocellular-carcinoma-via-atr-chek1-pathway
#1
Jie Bao, Yan Yu, Jianan Chen, Yuting He, Xiaolong Chen, Zhigang Ren, Chen Xue, Liwen Liu, Qiuyue Hu, Juan Li, Guangying Cui, Ranran Sun
Emerging evidence has shown that microRNA-126 (miR-126) is aberrantly downregulated and plays a vital role in carcinogenesis in various cancers, including HCC. However, the underlying biological mechanisms of miR-126 in HCC are still largely unknown. In present study, we found that miR-126 was downregulated both in HCC tissues and cell lines. Low expression level of miR-126 was associated with poor overall survival (OS), late TNM stage and the presence of recurrence. Overexpression of miR-126 significantly decreased cell proliferation, metastasis and promoted apoptosis in vitro...
October 12, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/30234181/prevalence-of-homologous-recombination-related-gene-mutations-across-multiple-cancer-types
#2
Arielle L Heeke, Michael J Pishvaian, Filipa Lynce, Joanne Xiu, Jonathan R Brody, Wang-Juh Chen, Tabari M Baker, John L Marshall, Claudine Isaacs
Purpose: The prevalence of homologous recombination DNA damage repair (HR-DDR) deficiencies among all tumor lineages is not well characterized. Therapy directed toward homologous recombination DDR deficiency (HRD) is now approved in ovarian and breast cancer, and there may be additional opportunities for benefit for patients with other cancers. Comprehensive evaluations for HRD are limited in part by the lack of a uniform, cost-effective method for testing and defining HRD. Methods: Molecular profiles of 52,426 tumors were reviewed to identify pathogenic mutations in the HR-DDR genes ARID1A , ATM , ATRX , BAP1 , BARD1 , BLM , BRCA1/2 , BRIP1 , CHEK1/2 , FANCA/C/D2/E/F/G/L , MRE11A , NBN , PALB2 , RAD50 , RAD51 , RAD51B , or WRN ...
2018: JCO Precision Oncology
https://www.readbyqxmd.com/read/30228980/analysis-of-transcription-factor-related-regulatory-networks-based-on-bioinformatics-analysis-and-validation-in-hepatocellular-carcinoma
#3
Shui Liu, Xiaoxiao Yao, Dan Zhang, Jiyao Sheng, Xin Wen, Qingyu Wang, Gaoyang Chen, Zhaoyan Li, Zhenwu Du, Xuewen Zhang
Hepatocellular carcinoma (HCC) accounts for a significant proportion of liver cancer, which has become the second most common cause of cancer-related mortality worldwide. To investigate the potential mechanisms of invasion and progression of HCC, bioinformatics analysis and validation by qRT-PCR were performed. We found 237 differentially expressed genes (DEGs) including EGR1, FOS, and FOSB, which were three cancer-related transcription factors. Subsequently, we constructed TF-gene network and miRNA-TF-mRNA network based on data obtained from mRNA and miRNA expression profiles for analysis of HCC...
2018: BioMed Research International
https://www.readbyqxmd.com/read/30211163/melanoma-lamp-2c-modulates-tumor-growth-and-autophagy
#4
Liliana Pérez, Anthony L Sinn, George E Sandusky, Karen E Pollok, Janice S Blum
Autophagy plays critical but diverse roles in cellular quality control and homeostasis potentially checking tumor development by removing mutated or damaged macromolecules, while conversely fostering tumor survival by supplying essential nutrients during cancer progression. This report documents a novel inhibitory role for a lysosome-associated membrane protein, LAMP-2C in modulating autophagy and melanoma cell growth in vitro and in vivo . Solid tumors such as melanomas encounter a variety of stresses in vivo including inflammatory cytokines produced by infiltrating lymphocytes directed at limiting tumor growth and spread...
2018: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/30171229/prevalence-of-dna-repair-gene-mutations-in-localized-prostate-cancer-according-to-clinical-and-pathologic-features-association-of-gleason-score-and-tumor-stage
#5
Catherine Handy Marshall, Wei Fu, Hao Wang, Alexander S Baras, Tamara L Lotan, Emmanuel S Antonarakis
BACKGROUND: DNA repair gene mutations are present in 8-10% of localized prostate cancers. It is unknown whether this is influenced by clinicopathologic factors. METHODS: We interrogated localized prostate adenocarcinomas with tumor DNA sequencing information from the TCGA validated (n = 333) and Nature Genetics (n = 377) datasets. Homologous recombination repair genes included in our analysis were: ATM, BRCA1/2, CDK12, CHEK1/2, FANCA, FANCD2, FANCL, GEN1, NBN, PALB2, RAD51, and RAD51C...
August 31, 2018: Prostate Cancer and Prostatic Diseases
https://www.readbyqxmd.com/read/30145203/integrated-proteomic-and-phosphoproteomic-analyses-of-cisplatin-sensitive-and-resistant-bladder-cancer-cells-reveal-cdk2-network-as-a-key-therapeutic-target
#6
Jae Hun Jung, Sungyong You, Jae Won Oh, Junhee Yoon, Austin Yeon, Muhammad Shahid, Eunho Cho, Vikram Sairam, Taeeun D Park, Kwang Pyo Kim, Jayoung Kim
BACKGROUND: Cisplatin-based chemotherapy is currently part of the standard of care for bladder cancer (BC). Unfortunately, some patients respond poorly to chemotherapy and have acquired or developed resistance. The molecular mechanisms underlying this resistance remain unclear. Here, we introduce a multidimensional proteomic analysis of a cisplatin-resistant BC model that provides different levels of protein information, including that of the global proteome and phosphoproteome. METHODS: To characterize the global proteome and phosphoproteome in cisplatin-resistant BC cells, liquid chromatography-mass spectrometry/mass spectrometry experiments combined with comprehensive bioinformatics analysis were performed...
November 28, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29988075/transient-inhibition-of-p53-homologs-protects-ovarian-function-from-two-distinct-apoptotic-pathways-triggered-by-anticancer-therapies
#7
So-Youn Kim, Devi M Nair, Megan Romero, Vanida A Serna, Anthony J Koleske, Teresa K Woodruff, Takeshi Kurita
Platinum-based chemotherapies can result in ovarian insufficiency by reducing the ovarian reserve, a reduction believed to result from apoptosis of immature oocytes via activation/phosphorylation of TAp63α by multiple kinases including CHEK2, CK1, and ABL1. Here we demonstrate that cisplatin (CDDP) induces oocyte apoptosis through a novel pathway and that temporary repression of this pathway fully preserves ovarian function in vivo. Although ABL kinase inhibitors effectively block CDDP-induced apoptosis of oocytes, oocytic ABL1, and ABL2 are dispensable for damage-induced apoptosis...
July 9, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29928473/association-of-genetic-variants-in-atr-chek1-and-atm-chek2-pathway-genes-with-risk-of-colorectal-cancer-in-a-chinese-population
#8
Shijia Wang, Yue Zhang, Min Chen, Yong Wang, Yifei Feng, Ziwei Xu, Dongsheng Zhang, Yueming Sun, Zan Fu
Objective: The ATR-CHEK1 and ATM-CHEK2 pathway have been confirmed to be related with the DNA damage response (DDR). Many studies have reported that genetic variants in ATR/CHEK1 and ATM/CHEK2 are associated with cancer risk. However, the association between genetic variants in ATR-CHEK1, ATM-CHEK2 pathway genes and colorectal cancer susceptibility is still unknown. In this study, we aim to explore whether these variants are correlated with the risk of colorectal cancer in a Chinese population...
June 1, 2018: Oncotarget
https://www.readbyqxmd.com/read/29870138/comparison-of-tumor-related-signaling-pathways-with-known-compounds-to-determine-potential-agents-for-lung-adenocarcinoma
#9
Song Xu, Renwang Liu, Yurong Da
BACKGROUND: This study compared tumor-related signaling pathways with known compounds to determine potential agents for lung adenocarcinoma (LUAD) treatment. METHODS: Kyoto Encyclopedia of Genes and Genomes signaling pathway analyses were performed based on LUAD differentially expressed genes from The Cancer Genome Atlas (TCGA) project and genotype-tissue expression controls. These results were compared to various known compounds using the Connectivity Mapping dataset...
August 2018: Thoracic Cancer
https://www.readbyqxmd.com/read/29805632/exploration-of-the-molecular-mechanisms-of-cervical-cancer-based-on-mrna-expression-profiles-and-predicted-microrna-interactions
#10
Liang Zhao, Zhechao Zhang, Hongyan Lou, Jingjing Liang, Xiaojian Yan, Wenfeng Li, Yunsheng Xu, Rongying Ou
The molecular mechanisms of cervical cancer have been minimally explored with multi-omics data. In the present study, mRNA expression profiles were analyzed and combined with predicted miRNA interactions to contribute to the characterization of the underlying regulatory mechanisms of cervical cancer. A total of 92 significantly differentially expressed genes (DEGs) were identified in 33 tumor samples by comparison with 29 normal samples. mRNA-miRNA interaction network analysis revealed that 16 out of the 92 DEGs, including checkpoint kinase 1 ( CHEK1 ), SRY-box 17 ( SOX17 ), centrosomal protein 55, cyclin dependent kinase inhibitor 2A ( CDKN2A ), and inhibitor of DNA binding 4, were the targets of 4 miRNAs which were previously reported to be involved in the regulation of cervical cancer...
June 2018: Oncology Letters
https://www.readbyqxmd.com/read/29781781/gene-expression-microarray-analysis-reveals-prognostic-markers-of-survival-in-high-grade-astrocytomas
#11
Jun Yang, Ziming Hou, Changjiang Wang, Hao Wang, Hongbing Zhang
OBJECTIVE: High grade astrocytoma (HGA) as an aggressive brain tumor, is always correlated with poor prognosis. In this paper, we aimed to explore the genetic prognostic biomarkers for HGA. METHODS: The genome-wide expression profile of 26 brain tumor samples obtained from 26 patients with HGA was downloaded from Gene Expression Omnibus. The risk genes for prognosis of HGA were identified and verified by the data in TCGA database. Protein-protein interaction (PPI) network of risk factor genes was constructed and significant module was screened...
September 2018: Neurological Research
https://www.readbyqxmd.com/read/29731985/association-between-homologous-recombination-repair-gene-mutations-and-response-to-oxaliplatin-in-pancreatic-cancer
#12
Tomohiro Kondo, Masashi Kanai, Tadayuki Kou, Tomohiro Sakuma, Hiroaki Mochizuki, Mayumi Kamada, Masahiko Nakatsui, Norimitsu Uza, Yuzo Kodama, Toshihiko Masui, Kyoichi Takaori, Shigemi Matsumoto, Hidehiko Miyake, Yasushi Okuno, Manabu Muto
Objectives: We aimed to examine the association between homologous recombination repair (HRR)-related gene mutations and efficacy of oxaliplatin-based chemotherapy in patients with pancreatic ductal adenocarcinoma (PDAC). Results: Non-synonymous mutations in HRR-related genes were found in 13 patients and only one patient had a family history of pancreatic cancer. Eight patients with HRR-related gene mutations (group A) and nine without HRR-related gene mutations (group B) received oxaliplatin-based chemotherapy...
April 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29727754/genomic-instability-in-adult-men-involved-in-processing-electronic-waste-in-northern-china
#13
Yan Wang, Xiaohui Sun, Lianying Fang, Keqiu Li, Ping Yang, Liqing Du, Kaihua Ji, Jinhan Wang, Qiang Liu, Chang Xu, Guang Li, John P Giesy, Markus Hecker
BACKGROUND: Managing and recycling electronic waste (e-waste), while useful and necessary, has resulted in significant contamination of several environments in China. The area around Tianjin, China has become one of the world's largest e-waste disposal centers, where electronics are processed by manually disassembly or burning, which can result in serious exposure of workers to a multitude of toxicants. OBJECTIVE: The present study assessed potential genomic damage in workers involved in recycling e-waste...
August 2018: Environment International
https://www.readbyqxmd.com/read/29720561/androgen-receptor-signaling-reduces-radiosensitivity-in-bladder-cancer
#14
Hiroki Ide, Satoshi Inoue, Taichi Mizushima, Guiyang Jiang, Kuang-Hsiang Chuang, Mototsugu Oya, Hiroshi Miyamoto
Although radiotherapy often with chemotherapy has been shown to offer a survival benefit comparable with that of radical cystectomy in select patients with bladder cancer, the development of radiosensitization strategies may significantly enhance its application. Notably, emerging preclinical evidence has indicated the involvement of androgen receptor (AR) signaling in urothelial cancer progression. We here assessed whether AR signals could contribute to modulating radiosensitivity in bladder cancer cells. Ionizing radiation reduced the numbers of viable cells or colonies of AR-negative lines more significantly than those of AR-positive lines...
July 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29656007/mir-195-potentiates-the-efficacy-of-microtubule-targeting-agents-in-non-small-cell-lung-cancer
#15
Xiaojie Yu, Yiqiang Zhang, Xiuye Ma, Alexander Pertsemlidis
Microtubule-targeting agents (MTAs) are widely used for the treatment of non-small cell lung cancer (NSCLC). The response rate is only ∼25%, mainly attributable to drug resistance. To identify determinants of resistance in NSCLC, we performed a high-throughput screen using a library of miRNA mimics. Here we report that miR-195 synergizes with MTAs to inhibit the growth of NSCLC cells in vitro, that increased expression of miR-195 sensitizes NSCLC cells to MTAs and that repression of miR-195 confers resistance to MTAs...
July 28, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29575713/functional-transcriptomic-annotation-and-protein-protein-interaction-analysis-identify-ezh2-and-ube2c-as-key-upregulated-proteins-in-ovarian-cancer
#16
Sandra Martínez-Canales, Miguel López de Rodas, Miriam Nuncia-Cantarero, Raquel Páez, Eitan Amir, Balázs Győrffy, Atanasio Pandiella, Eva María Galán-Moya, Alberto Ocaña
Although early stage ovarian cancer is in most cases a curable disease, some patients relapse even with appropriate adjuvant treatment. Therefore, the identification of patient and tumor characteristics to better stratify risk and guide rational drug development is desirable. Using transcriptomic functional annotation followed by protein-protein interacting (PPI) network analyses, we identified functions that were upregulated and associated with detrimental outcome in patients with early stage ovarian cancer...
May 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29535131/endogenous-replication-stress-marks-melanomas-sensitive-to-chek1-inhibitors-in-vivo
#17
Zay Yar Oo, Alexander J Stevenson, Martina Proctor, Sheena M Daignault, Sebastian Walpole, Catherine Lanagan, James Chen, Dubravka Škalamera, Loredana Spoerri, Stephen A Ainger, Richard A Sturm, Nikolas K Haass, Brian Gabrielli
Purpose: Checkpoint kinase 1 inhibitors (CHEK1i) have single-agent activity in vitro and in vivo Here, we have investigated the molecular basis of this activity. Experimental Design: We have assessed a panel of melanoma cell lines for their sensitivity to the CHEK1i GNE-323 and GDC-0575 in vitro and in vivo The effects of these compounds on responses to DNA replication stress were analyzed in the hypersensitive cell lines. Results: A subset of melanoma cell lines is hypersensitive to CHEK1i-induced cell death in vitro , and the drug effectively inhibits tumor growth in vivo In the hypersensitive cell lines, GNE-323 triggers cell death without cells entering mitosis...
June 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29360988/chek1-coordinates-dna-damage-signaling-and-meiotic-progression-in-the-male-germline-of-mice
#18
Hironori Abe, Kris G Alavattam, Yasuko Kato, Diego H Castrillon, Qishen Pang, Paul R Andreassen, Satoshi H Namekawa
The continuity of life depends on mechanisms in the germline that ensure the integrity of the genome. The DNA damage response/checkpoint kinases ATM and ATR are essential signaling factors in the germline. However, it remains unknown how a downstream transducer, Checkpoint Kinase 1 (CHEK1 or CHK1), mediates signaling in the male germline. Here, we show that CHEK1 has distinct functions in both the mitotic and meiotic phases of the male germline in mice. In the mitotic phase, CHEK1 is required for the resumption of prospermatogonia proliferation after birth and the maintenance of spermatogonia...
April 1, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29353882/igf1r-signaling-drives-antiestrogen-resistance-through-pak2-pix-activation-in-luminal-breast-cancer
#19
Yinghui Zhang, Lynn Wester, Jichao He, Tamar Geiger, Marja Moerkens, Ram Siddappa, Jean A Helmijr, Mieke M Timmermans, Maxime P Look, Caroline H M van Deurzen, John W M Martens, Chantal Pont, Marjo de Graauw, Erik H J Danen, Els M J J Berns, John H N Meerman, Maurice P H M Jansen, Bob van de Water
Antiestrogen resistance in estrogen receptor positive (ER+ ) breast cancer is associated with increased expression and activity of insulin-like growth factor 1 receptor (IGF1R). Here, a kinome siRNA screen has identified 10 regulators of IGF1R-mediated antiestrogen with clinical significance. These include the tamoxifen resistance suppressors BMPR1B, CDK10, CDK5, EIF2AK1, and MAP2K5, and the tamoxifen resistance inducers CHEK1, PAK2, RPS6KC1, TTK, and TXK. The p21-activated kinase 2, PAK2, is the strongest resistance inducer...
April 2018: Oncogene
https://www.readbyqxmd.com/read/29287241/serine-threonine-kinase-chek1-dependent-transcriptional-regulation-of-rad54l-promotes-proliferation-and-radio-resistance-in-glioblastoma
#20
Xiaobin Bai, Jia Wang, Longwei Huo, Yuchen Xie, Wanfu Xie, Gaofeng Xu, Maode Wang
Accumulating evidence indicates that Checkpoint kinase 1 (CHEK1) plays an essential role in tumor cells and that it could induce cell proliferation and could be related to prognosis in multiple types of cancer. However, the biological role and molecular mechanism of CHEK1 in GBM still remain unclear. In this study, we identified that CHEK1 expression was enriched in glioblastoma (GBM) tumors and was functionally required for tumor proliferation and that its expression was associated to poor prognosis in GBM patients...
February 2018: Translational Oncology
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