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Cell Cycle Arrest Biomarkers

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https://www.readbyqxmd.com/read/27922189/optimal-arac-cytotoxicity-to-aml-cells-requires-erk5-activity
#1
Ruifang Zheng, George P Studzinski
Cytarabine (AraC) has been the primary treatment agent for Acute Myeloid Leukemia (AML) in the past 30 years, but the precise mechanism of its action is not completely known. Here we assessed the role of ERK5 in AraC-induced cell death in AML cell lines HL60 and U937 using ERK5 inhibitors BIX02189 and XMD8-92. We report that inhibition of MEK5/ERK5 activity reduces AraC-induced cell death, DNA damage, the upregulated DNA damage biomarkers, and produced G2 phase cell cycle arrest. In addition, the pro-survival protein P-Bcl2 Ser70 was found to be associated with decreased AraC-induced cell death following XMD8-92 treatment, suggesting a regulatory role of ERK5 on Bcl2 phosphorylation...
December 6, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27916938/comprehensive-analysis-of-mirnome-alterations-in-response-to-sorafenib-treatment-in-colorectal-cancer-cells
#2
Anna-Maria Pehserl, Anna Lena Ress, Stefanie Stanzer, Margit Resel, Michael Karbiener, Elke Stadelmeyer, Verena Stiegelbauer, Armin Gerger, Christian Mayr, Marcel Scheideler, Georg C Hutterer, Thomas Bauernhofer, Tobias Kiesslich, Martin Pichler
MicroRNAs (miRNAs) are master regulators of drug resistance and have been previously proposed as potential biomarkers for the prediction of therapeutic response in colorectal cancer (CRC). Sorafenib, a multi-kinase inhibitor which has been approved for the treatment of liver, renal and thyroid cancer, is currently being studied as a monotherapy in selected molecular subtypes or in combination with other drugs in metastatic CRC. In this study, we explored sorafenib-induced cellular effects in Kirsten rat sarcoma viral oncogene homolog olog (KRAS) wild-type and KRAS-mutated CRC cell lines (Caco-2 and HRT-18), and finally profiled expression changes of specific miRNAs within the miRNome (>1000 human miRNAs) after exposure to sorafenib...
December 1, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27911910/molecular-markers-of-radiation-induced-attenuation-in-intrahepatic-plasmodium-falciparum-parasites
#3
Miranda S Oakley, Nitin Verma, Hong Zheng, Vivek Anantharaman, Kazuyo Takeda, Yamei Gao, Timothy G Myers, Phuong Thao Pham, Babita Mahajan, Nirbhay Kumar, Davison Sangweme, Abhai K Tripathi, Godfree Mlambo, L Aravind, Sanjai Kumar
Experimental immunization with radiation attenuated sporozoites (RAS) and genetically attenuated sporozoites has proved to be a promising approach for malaria vaccine development. However, parasite biomarkers of growth attenuation and enhanced immune protection in response to radiation remain poorly understood. Here, we report on the effect of an attenuating dose of γ-irradiation (15 krad) on the Plasmodium falciparum sporozoite (PfSPZ) ultrastructure by electron microscopy, growth rate of liver stage P. falciparum in liver cell cultures, and genome-wide transcriptional profile of liver stage parasites by microarray...
2016: PloS One
https://www.readbyqxmd.com/read/27904773/upregulation-of-fam83d-promotes-malignant-phenotypes-of-lung-adenocarcinoma-by-regulating-cell-cycle
#4
Run Shi, Jing Sun, Qi Sun, Quanli Zhang, Wenjie Xia, Gaochao Dong, Anpeng Wang, Feng Jiang, Lin Xu
The family with sequence similarity 83, member D (FAM83D) gene is upregulated in hepatocellular carcinoma and ovarian cancer, and its overexpression has been reported to positively correlate with tumor progression. However, the clinical significance and biological function of FAM83D in lung adenocarcinoma has not been investigated. We determined the expression profile and clinical significance of FAM83D using The Cancer Genome Atlas (TCGA) and immunohistochemistry (IHC) analysis. Considerable upregulation of FAM83D was observed in LUAD tissues compared with adjacent normal tissues, and its overexpression was significantly associated with more advanced clinicopathological characteristics...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27904689/mir-4295-promotes-cell-growth-in-bladder-cancer-by-targeting-btg1
#5
Yong-Hao Nan, Jun Wang, Yao Wang, Peng-Hao Sun, Yu-Ping Han, Li Fan, Kai-Chen Wang, Fu-Jun Shen, Wei-Hua Wang
microRNAs (miRNAs) have been demonstrated to contribute to tumor progression and metastasis, and have been proposed to be key regulators of diverse biological processes. In this study, we report that miR-4295 is deregulated in bladder cancer tissues and cell lines. To characterize the role of miR-4295 in bladder cancer cells, we performed functional assays. The overexpression of miR-4295 significantly promoted bladder cancer cell proliferation, colony formation, and migration. Moreover, its downregulation induced cell cycle arrest and apoptosis of bladder cancer cells...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27895742/comparative-analysis-of-gene-expression-profiles-of-gastric-cardia-adenocarcinoma-and-gastric-non-cardia-adenocarcinoma
#6
Bin Song, Juan Du, Neng Deng, Ji-Chen Ren, Zhen-Bo Shu
In the present study, gene expression profiles were analyzed to identify the molecular mechanisms underlying gastric cardia adenocarcinoma (GCA) and gastric non-cardia adenocarcinoma (GNCA). A gene expression dataset (accession number GSE29272) was downloaded from Gene Expression Omnibus, and consisted of 62 GCA samples and 62 normal controls, as well as 72 GNCA samples and 72 normal controls. The two groups of differentially-expressed genes (DEGs) were compared to obtain common and unique DEGs. A differential analysis was performed using the Linear Models for Microarray Data package in R...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27882937/ezh2-mediates-lidamycin-induced-cellular-senescence-through-regulating-p21-expression-in-human-colon-cancer-cells
#7
Ming-Quan Sha, Xiao-Li Zhao, Liang Li, Li-Hui Li, Yi Li, Tian-Geng Dong, Wei-Xin Niu, Li-Jun Jia, Rong-Guang Shao, Yong-Su Zhen, Zhen Wang
Lidamycin (LDM) is a novel member of the enediyne antibiotics identified in China with potent antitumor activity. However, it remains unclear whether LDM has potential molecular targets that may affect its antitumor activity. Enhancer of zeste homolog 2 (EZH2) functions as a histone lysine methyltransferase and mediates trimethylation on histone 3 lysine 27 (H3K27me3). High EZH2 level is found to be positively correlated with the aggressiveness, metastasis and poor prognosis of cancer. Here, we aim to study the role of EZH2 in LDM-induced senescence, as well as in the cytotoxicity of LDM in human colon cancer cells...
November 24, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27867568/the-overexpression-of-kifc1-was-associated-with-the-proliferation-and-prognosis-of-non-small-cell-lung-cancer
#8
Yafang Liu, Ping Zhan, Zejun Zhou, Ze Xing, Suhua Zhu, Chenhui Ma, Qian Li, Qingqing Zhu, Yingying Miao, Jianya Zhang, Tangfeng Lv, Yong Song
BACKGROUND: The kinesin family member C1 (KIFC1, also known as HSET) is a kinesin superfamily protein (KIFs). Although KIFC1 acts as a crucial role in the development of several human cancers, the KIFC1 expression profile and functional remain unclear in non-small cell lung cancer (NSCLC). METHODS: We collected the fresh NSCLC samples and paired normal lung tissue in patients with lung cancer operation, and detected KIFC1 expression using quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and Western blotting...
October 2016: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/27862991/down-regulation-of-microrna-320d-predicts-poor-overall-survival-and-promotes-the-growth-and-invasive-abilities-in-glioma
#9
Chong-Zhen Qin, Qiao-Li Lv, Yan-Tao Yang, Jing-Min Zhang, Xiao-Jian Zhang, Hong-Hao Zhou
Previous studies have demonstrated that miRNAs play an important role in tumor development and progression. The role of miR-320d has been studied in several cancers except for glioma. The aim of the study was to investigate the expression levels, biological function, and mechanism of miR-320d in glioma. The expression levels of miR-320d were detected in glioma tissues and cell lines (U87 and U251) by RT-qPCR. Cell proliferation, colony formation, apoptosis, cell cycle and transwell assays were performed in glioma cell lines transfected with miR-320d mimics or controls to evaluate the effects of miR-320d in vitro...
November 12, 2016: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/27862966/ncapg2-promotes-tumour-proliferation-by-regulating-g2-m-phase-and-associates-with-poor-prognosis-in-lung-adenocarcinoma
#10
Ping Zhan, Guang-Min Xi, Bin Zhang, Ying Wu, Hong-Bing Liu, Ya-Fang Liu, Wu-Jian Xu, Qingqing Zhu, Feng Cai, Ze-Jun Zhou, Ying-Ying Miu, Xiao-Xia Wang, Jia-Jia Jin, Qian Li, Tang-Feng Lv, Yong Song
NCAPG2 is a component of the condensin II complex and contributes to chromosome segregation via microtubule-kinetochore attachment during mitosis. It is well known that NCAPG2 plays a critical role in cell mitosis; however, the role of altered NCAPG2 expression and its transcriptional regulatory function in cancer development remains mostly unknown. Here, for the first time we reported that NCAPG2 was evidently increased in non-small cell lung cancer tissues compared to adjacent normal lung tissues. Clinicopathological data analysis showed that NCAPG2 overexpression was significantly correlated with lymph node metastasis and pathologic-Tumour Nodes Metastasen stages, and was an independent prognostic factor in lung adenocarcinoma patients...
November 15, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27851604/1970-acute-kidney-injury-cell-cycle-arrest-biomarkers-in-acute-on-chronic-heart-failure-a-case-report
#11
Savneek Chugh, Sohaib Tariq
No abstract text is available yet for this article.
December 2016: Critical Care Medicine
https://www.readbyqxmd.com/read/27845896/ribosomal-protein-l34-promotes-the-proliferation-invasion-and-metastasis-of-pancreatic-cancer-cells
#12
Feng Wei, Lijuan Ding, Zhentong Wei, Yandong Zhang, Yang Li, Luo Qinghua, Yuteng Ma, Liang Guo, Guoyue Lv, Yan Liu
Ribosomal proteins (RPs) are the main components of ribosomes and participate in the self-assembly of ribosomes and protein synthesis. Recent advance has shown that RPs play important roles in the tumorigenesis and drug resistance of various cancers. However, the expression status and function of RPL34 in pancreatic cancer (PC) remains unclear. In this study, we find that RPL34 is overexpressed in PC tissues and cell lines, which is correlated with decreased methylation of its promoter. Knockdown of RPL34 effectively suppresses the proliferation, colony formation, migration and drug-resistance of PC cells, which are accompanied by cell cycle arrest at the G2 phase and induction of apoptosis...
November 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27835911/prognostic-and-predictive-values-of-cdk1-and-mad2l1-in-lung-adenocarcinoma
#13
Yuan-Xiang Shi, Tao Zhu, Ting Zou, Wei Zhuo, Yi-Xin Chen, Ma-Sha Huang, Wei Zheng, Chen-Jing Wang, Xi Li, Xiao-Yuan Mao, Wei Zhang, Hong-Hao Zhou, Ji-Ye Yin, Zhao-Qian Liu
Lung cancer remains as the leading cause of cancer-related death worldwide, and lung adenocarcinoma (LUAD) is the most common histological subtype. This study aims to investigate biomarkers associated with cancer progression and prognosis of LUAD. We integrated expression profiles of 668 lung cancer patients in five datasets from the Gene Expression Omnibus (GEO) and identified a panel of differentially expressed genes (DEGs). Function enrichment analysis highlighted that these genes were closely associated with the carcinogenesis of LUAD, such as cell cycle, ECM-receptor interaction and p53 signaling pathway...
November 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/27835881/il-37-suppresses-hepatocellular-carcinoma-growth-by-converting-psmad3-signaling-from-jnk-psmad3l-c-myc-oncogenic-signaling-to-psmad3c-p21-tumor-suppressive-signaling
#14
Rui Liu, Chengyong Tang, Ai Shen, Huating Luo, Xufu Wei, Daofeng Zheng, Chao Sun, Zhongtang Li, Di Zhu, Tingting Li, Zhongjun Wu
IL-37 has been characterized as a fundamental inhibitor of innate immunity and a tumor suppressor in several cancers. However, the molecular mechanism of IL-37 in hepatocellular carcinoma (HCC) is largely unclear. In this study we found IL-37 expression was down-regulated in human HCC tissues and cell lines, and was negatively correlated with tumor size, vascular invasion, as well as overall-survial and disease-free survival (OS and DFS) of HCC. Multivariate Cox analysis revealed that IL-37 was an independent prognostic indicator for OS and DFS in HCC...
November 8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27835869/otx015-mk-8628-a-novel-bet-inhibitor-exhibits-antitumor-activity-in-non-small-cell-and-small-cell-lung-cancer-models-harboring-different-oncogenic-mutations
#15
Maria E Riveiro, Lucile Astorgues-Xerri, Ramiro Vazquez, Roberta Frapolli, Ivo Kwee, Andrea Rinaldi, Elodie Odore, Keyvan Rezai, Mohamed Bekradda, Giorgio Inghirami, Maurizio D'Incalci, Kay Noel, Esteban Cvitkovic, Eric Raymond, Francesco Bertoni
Inhibitors targeting epigenetic control points of oncogenes offer a potential mean of blocking tumor progression in small cell and non-small cell lung carcinomas (SCLC, NSCLC). OTX015 (MK-8628) is a BET inhibitor selectively blocking BRD2/3/4. OTX015 was evaluated in a panel of NSCLC or SCLC models harboring different oncogenic mutations. Cell proliferation inhibition and cell cycle arrest were seen in sensitive NSCLC cells. MYC and MYCN were downregulated at both the mRNA and protein levels. In addition, OTX015-treatment significantly downregulated various stemness cell markers, including NANOG, Musashi-1, CD113 and EpCAM in H3122-tumors in vivo...
November 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27815358/phase-i-study-of-gdc-0425-a-checkpoint-kinase-1-inhibitor-in-combination-with-gemcitabine-in-patients-with-refractory-solid-tumors
#16
Jeffrey R Infante, Antoine Hollebecque, Sophie Postel-Vinay, Todd M Bauer, Elizabeth Blackwood, Marie Evangelista, Sami Mahrus, Franklin Peale, Xuyang Lu, Srikumar Sahasranaman, Rui Zhu, Yuan Chen, Xiao Ding, Elaine Murray, Jennifer Schutzman, Jennifer O Lauchle, Jean-Charles Soria, Patricia M LoRusso
PURPOSE: Chk1 inhibition potentiates DNA-damaging chemotherapy by overriding cell cycle arrest and genome repair. This Phase I study evaluated the Chk1 inhibitor GDC-0425 given in combination with gemcitabine to patients with advanced solid tumors. EXPERIMENTAL DESIGN: Patients received GDC-0425 alone for a 1-week lead-in followed by 21-day cycles of gemcitabine plus GDC-0425. Gemcitabine was initially administered at 750 mg/m2 (Arm A), then increased to 1000 mg/m2 (Arm B), on Days 1 and 8 in a 3+3+3 dose escalation to establish maximum tolerated dose (MTD)...
November 4, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27801668/upregulation-of-mir-99a-is-associated-with-poor-prognosis-of-acute-myeloid-leukemia-and-promotes-myeloid-leukemia-cell-expansion
#17
Xiaohui Si, Xiaoyun Zhang, Xing Hao, Yunan Li, Zizhen Chen, Yahui Ding, Hui Shi, Jie Bai, Yingdai Gao, Tao Cheng, Feng-Chun Yang, Yuan Zhou
Leukemia stem cells (LSCs) can resist available treatments that results in disease progression and/or relapse. To dissect the microRNA (miRNA) expression signature of relapse in acute myeloid leukemia (AML), miRNA array analysis was performed using enriched LSCs from paired bone marrow samples of an AML patient at different disease stages. We identified that miR-99a was significantly upregulated in the LSCs obtained at relapse compared to the LSCs collected at the time of initial diagnosis. We also found that miR-99a was upregulated in LSCs compared to non-LSCs in a larger cohort of AML patients, and higher expression levels of miR-99a were significantly correlated with worse overall survival and event-free survival in these AML patients...
October 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27783255/targeting-the-protein-ubiquitination-machinery-in-melanoma-by-the-nedd8-activating-enzyme-inhibitor-pevonedistat-mln4924
#18
Kit Man Wong, Lindsey N Micel, Heather M Selby, Aik Choon Tan, Todd M Pitts, Stacey M Bagby, Anna Spreafico, Peter J Klauck, Stephen J Blakemore, Peter F Smith, Alice McDonald, Allison Berger, John J Tentler, S Gail Eckhardt
Background The neddylation pathway conjugates NEDD8 to cullin-RING ligases and controls the proteasomal degradation of specific proteins involved in essential cell processes. Pevonedistat (MLN4924) is a selective small molecule targeting the NEDD8-activating enzyme (NAE) and inhibits an early step in neddylation, resulting in DNA re-replication, cell cycle arrest and death. We investigated the anti-tumor potential of pevonedistat in preclinical models of melanoma. Methods Melanoma cell lines and patient-derived tumor xenografts (PDTX) treated with pevonedistat were assessed for viability/apoptosis and tumor growth, respectively, to identify sensitive/resistant models...
October 25, 2016: Investigational New Drugs
https://www.readbyqxmd.com/read/27779808/functional-and-therapeutic-relevance-of-hepatocyte-growth-factor-c-met-signaling-in-synovial-sarcoma
#19
Yoshinori Imura, Takaaki Nakai, Shutaro Yamada, Hidetatsu Outani, Satoshi Takenaka, Kenichiro Hamada, Nobuhito Araki, Kazuyuki Itoh, Hideki Yoshikawa, Norifumi Naka
Synovial sarcoma (SS) is an aggressive soft-tissue sarcoma with a poor prognosis and thus novel therapeutic strategies for SS are urgently required. In the present study, we investigated functional and therapeutic relevance of hepatocyte growth factor (HGF)/c-MET signaling in SS. Both HGF and c-MET were highly expressed in Yamato-SS cells, resulting in activation of c-MET and its downstream AKT and extracellular signal-regulated kinase signaling pathways, whereas c-MET was expressed but not activated in SYO-1 or HS-SY-II cells...
October 24, 2016: Cancer Science
https://www.readbyqxmd.com/read/27777512/long-non-coding-rna-dbccr1-003-regulate-the-expression-of-dbccr1-via-dnmt1-in-bladder-cancer
#20
Defeng Qi, Jinhui Li, Biao Que, Jialin Su, Mengxi Li, Chaofeng Zhang, Mei Yang, Guoren Zhou, Weidong Ji
BACKGROUND: Many long non coding RNAs have been identified as key modulators in cancer development. A lncRNA, DBCCR1-003, derived from the locus of tumor suppressor gene DBCCR1 (deleted in bladder cancer chromosome region 1), has unknown function. In the present study, we explored function and molecular mechanism of DBCCR1-003 in bladder cancer (BC) development. METHODS: We evaluated the expression levels of DBCCR1-003 in tissues and cells with western blot and quantitative real-time polymerase chain reaction...
2016: Cancer Cell International
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