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Chaosen Yue, Yaoyao Ren, Hua Ge, Chaojie Liang, Yingchen Xu, Guangming Li, Jixiang Wu
Background: Hepatocellular carcinoma (HCC) is an extremely common malignant tumor with worldwide prevalence. The aim of this study was to identify potential prognostic genes and construct a competing endogenous RNA (ceRNA) regulatory network to explore the mechanisms underlying the development of HCC. Methods: Integrated analysis was used to identify potential prognostic genes in HCC with R software based on the GSE14520, GSE17548, GSE19665, GSE29721, GSE60502, and the Cancer Genome Atlas databases...
2019: OncoTargets and Therapy
Patrick H Dinkelborg, Meng Wang, Liliana Gheorghiu, Joseph M Gurski, Theodore S Hong, Cyril H Benes, Dejan Juric, Rachel B Jimenez, Kerstin Borgmann, Henning Willers
PURPOSE: Triple-negative breast cancers (TNBC) are often resistant to treatment with ionizing radiation (IR). We sought to investigate whether pharmacologic inhibition of Chk1 kinase, which is commonly overexpressed in TNBC, preferentially sensitizes TNBC cells to IR. METHODS: Ten breast cancer cell lines were screened with small molecule inhibitors against Chk1 and other kinases. Chk1 inhibition was also tested in isogenic KRAS mutant or wild-type cancer cells...
January 3, 2019: Breast Cancer Research and Treatment
Anneliese Krell, Marietta Wolter, Nina Stojcheva, Caroline Hertler, Franziska Liesenberg, Marc Zapatka, Michael Weller, Bastian Malzkorn, Guido Reifenberger
AIMS: Aberrant expression of microRNAs (miRNAs) is frequent in various cancers including gliomas. We aimed to characterize the role of miR-16-5p as a candidate tumour suppressor miRNA in gliomas. METHODS: Real-time PCR-based approaches were used for miRNA and mRNA expression profiling of glioma and non-neoplastic brain tissues as well as glioma cell lines. Protein levels were determined by Western blotting. In vitro analyses were performed following overexpression of miR-16-5p, trichostatin A treatment, and siRNA-mediated knock-down of HDAC3 in glioma cells...
December 13, 2018: Neuropathology and Applied Neurobiology
Sahika Cingir Koker, Ermira Jahja, Huma Shehwana, Ayse Gokce Keskus, Ozlen Konu
Cholinergic Receptor Nicotinic Alpha 5 (CHRNA5) is an important susceptibility locus for nicotine addiction and lung cancer. Depletion of CHRNA5 has been associated with reduced cell viability, increased apoptosis and alterations in cellular motility in different cancers yet not in breast cancer. Herein we first showed the expression of CHRNA5 was variable and positively correlated with the fraction of total genomic alterations in breast cancer cell lines and tumors indicating its potential role in DNA damage response (DDR)...
2018: PloS One
Gulsah Gundogdu, Yavuz Dodurga, Levent Elmas, Seymanur Yilmaz Tasci, Esen Sezen Karaoglan
Objective: Isoorientin (ISO) is a flavonoid compound extracted from plant species. The goal of this study was to determine the potential antiproliferative effects of ISO in HT-29 human colorectal adenocarcinoma cell line in vitro , specifically on cell viability, apoptosis, and cell cycle pathways. Materials and Methods: The cytotoxic effect of ISO isolated from E. spectabilis was measured using 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay in HT-29 cell lines...
October 2018: Eurasian Journal of Medicine
Zeynep Özlem Doğan Şiğva, Tuğçe Balci Okcanoğlu, Çığır Biray Avci, Sunde Yilmaz Süslüer, Çağla Kayabaşi, Burak Turna, Yavuz Dodurga, Oktay Nazli, Cumhur Gündüz
Paclitaxel, which isolated from Taxus brevifolia, is recently started to be used against prostate cancer treatment and it is a very effective compound against cancer. In this study, we aimed to test the synergistic effect of two plant active compounds (sulphoraphane (SFN) and silymarin (SILY)) and several endemic plant species from Turkey (such as Phlomis leucophracta, Rubia davisiana, Alkanna tinctoria), which are known to have anticarcinogenic effect on androgen-independent PC3 and DU145, and androgen-dependent VCaP prostate cancer cell lines, with paclitaxel on the expression of cell cycle signaling and apoptosis regulator genes...
November 17, 2018: Gene
Liping Zhuang, Zongguo Yang, Zhiqiang Meng
Objective: To evaluate the association between upregulated differentially expressed genes (DEGs) and the outcomes of patients with hepatocellular carcinoma (HCC). Methods: Using Gene Expression Omnibus (GEO) datasets including GSE45436, GSE55092, GSE60502, GSE84402, and GSE17548, we detected upregulated DEGs in tumors. KEGG, GO, and Reactome enrichment analysis of the DEGs was conducted to clarify their function. The impact of the upregulated DEGs on patients' survival was analyzed based on TCGA profile...
2018: BioMed Research International
Thomas Grellety, Celine Callens, Elodie Richard, Adrien Briaux, Valérie Vélasco, Marina Pulido, Anthony Gonçalvès, Pierre Gestraud, Gaetan MacGrogan, Herve Bonnefoi, Bruno Cardinaud
PURPOSE: Our aim was to identify predictive factors of abiraterone acetate (AA) efficacy and putative new druggable targets in androgen receptor (AR)-positive triple-negative breast cancer (TNBC) treated in the UCBG 2012-1 trial. EXPERIMENTAL DESIGN: We defined AA response as either complete or partial response, or stable disease at 6 months. We sequenced 91 general and breast cancer-associated genes from the tumor DNA samples. We analyzed transcriptomes from the extracted RNA samples on a Nanostring platform and performed immunohistochemistry (IHC) using tissue microarrays...
October 23, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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
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
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
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
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
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
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
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
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
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
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
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
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