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Lizhi Yi, Zhenbing Lv, Jianmei Wang, Xianfei Zhong
Currently, with the increase of morbidity and mortality rate, gastric cancer (GC) is attracting increasing attention in China. Bcl‑2‑associated athanogene 4 (BAG4) has been identified as a tumor promoter in several tumors, but its role in GC remains unknown. The present study aimed to detect the expression of BAG4 and determine its function in the progression of GC. The results from reverse transcription‑quantitative polymerase chain reaction and western blotting revealed that BAG4 was markedly upregulated in highly metastatic cell lines (SGC7901 and MGC803), compared with the lower‑metastatic cell lines (AGS and BGC823)...
October 2017: Molecular Medicine Reports
Lan Deng, Ling Jiang, Xiang-Hua Lin, Kuo-Fu Tseng, Yuan Liu, Xing Zhang, Rui-Hong Dong, Zhi-Gang Lu, Xiu-Ju Wang
Aberrant activation of the PI3K/Akt/mTOR pathway contributes to the proliferation of malignant cells, and may confer resistance to chemotherapy in various malignancies, including acute myeloid leukemia (AML). Chemoresistance is the major reason for relapse in AML. RAD001 (everolimus) has been used at d1 and d7 of an induction chemotherapy regimen for AML, which has acceptable toxicity and may improve conventional chemotherapeutic treatment. Dual inhibitors of PI3K and mTOR overcome some of the intrinsic disadvantages of rapamycin and its derivatives...
March 2017: Acta Pharmacologica Sinica
Jingqin Luo, Shuzhen Liu, Samuel Leung, Alejandro A Gru, Yu Tao, Jeremy Hoog, Julie Ho, Sherri R Davies, D Craig Allred, Andrea L Salavaggione, Jacqueline Snider, Elaine R Mardis, Torsten O Nielsen, Matthew J Ellis
Fibroblast growth factor receptor 1 (FGFR1) amplification drives poor prognosis and is an emerging therapeutic target. We sought to construct a multigene mRNA expression signature to efficiently identify FGFR1-amplified estrogen receptor-positive (ER+ ) breast tumors. Five independent breast tumor series were analyzed. Genes discriminative for FGFR1 amplification were screened transcriptome-wide by receiver operating characteristic analyses. The METABRIC series was leveraged to construct/evaluate four approaches to signature composition...
January 2017: Journal of Molecular Diagnostics: JMD
Jung-Hyun Rho, Jon J Ladd, Christopher I Li, John D Potter, Yuzheng Zhang, David Shelley, David Shibata, Domenico Coppola, Hiroyuki Yamada, Hidenori Toyoda, Toshifumi Tada, Takashi Kumada, Dean E Brenner, Samir M Hanash, Paul D Lampe
OBJECTIVE: To discover and confirm blood-based colon cancer early-detection markers. DESIGN: We created a high-density antibody microarray to detect differences in protein levels in plasma from individuals diagnosed with colon cancer <3 years after blood was drawn (ie, prediagnostic) and cancer-free, matched controls. Potential markers were tested on plasma samples from people diagnosed with adenoma or cancer, compared with controls. Components of an optimal 5-marker panel were tested via immunoblotting using a third sample set, Luminex assay in a large fourth sample set and immunohistochemistry (IHC) on tissue microarrays...
March 2018: Gut
Huijun Xie, Xiaoli Ren, Sainan Xin, Xiaoliang Lan, Guifeng Lu, Yuan Lin, Shaoshan Yang, Zhicheng Zeng, Wenting Liao, Yan-Qing Ding, Li Liang
Circular RNAs (circRNAs), a large class of RNAs, have recently shown huge capabilities as gene regulators in mammals. Some of them bind with microRNAs (miRNAs) and act as natural miRNA sponges to inhibit related miRNAs' activities. Here we showed that hsa_circ_001569 acted as a positive regulator in cell proliferation and invasion of colorectal cancer (CRC). Moreover, hsa_circ_001569 was identified as a sponge of miR-145 and up-regulated miR-145 functional targets E2F5, BAG4 and FMNL2. In CRC tissues, circ_001569 negatively correlated with miR-145, and miR-145 correlated negatively with E2F5, BAG4 and FMNL2 expressions...
May 3, 2016: Oncotarget
Claire Rooney, Catherine Geh, Victoria Williams, Johannes M Heuckmann, Roopika Menon, Petra Schneider, Katherine Al-Kadhimi, Michael Dymond, Neil R Smith, Dawn Baker, Tim French, Paul D Smith, Elizabeth A Harrington, J Carl Barrett, Elaine Kilgour
FGFR1 amplification occurs in ~20% of sqNSCLC and trials with FGFR inhibitors have selected FGFR1 amplified patients by FISH. Lung cancer cell lines were profiled for sensitivity to AZD4547, a potent, selective inhibitor of FGFRs 1-3. Sensitivity to FGFR inhibition was associated with but not wholly predicted by increased FGFR1 gene copy number. Additional biomarker assays evaluating expression of FGFRs and correlation between amplification and expression in clinical tissues are therefore warranted. We validated nanoString for mRNA expression analysis of 194 genes, including FGFRs, from clinical tumour tissue...
2016: PloS One
Yue Du, Yuhong Huang, Yue Gao, Bo Song, Jun Mao, Lina Chen, Lulu Bai, Jianwu Tang
Annexin A7 caused an anti-apoptosis phenotype in mouse hepatocarcinoma cells. Yet, the underlying mechanism remains unclear. In this study, we found that Annexin A7 had an inhibitory effect on the mitochondrial Cytochrome C release and Caspase-3 cleavage. Furthermore, Annexin A7 was identified to form a complex with BAG4 which is a negative regulator of apoptosis. Moreover, Annexin A7 was positively correlated with the protein levels of BAG4, Hsp70 and Bcl-2. Both Hsp70 and Bcl-2 bind BAG4 and inhibit Cytochrom C dependent activation of Caspase-3...
August 2015: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Rebeca González-Fernández, Julio Ávila, María F Arteaga, Cecilia M Canessa, Pablo Martín-Vasallo
The Serum- and Glucocorticoid-induced Kinase 1, SGK1, exhibits a broad range of cellular functions that include regulation of the number of ion channels in plasma membrane and modulation of signaling pathways of cell survival. This diversity of functions is made possible by various regulatory processes acting upon the SGK1 gene, giving rise to various isoforms: SGK1_v1-5, each with distinct properties and distinct aminotermini that serve to target proteins to different subcellular compartments. Among cellular effects of SGK1 expression is to indirectly modulate gene transcription by phosphorylating transcriptional factors of the FOXO family...
2015: International Journal of Molecular Sciences
Rui Wang, Lei Wang, Yuan Li, Haichuan Hu, Lei Shen, Xuxia Shen, Yunjian Pan, Ting Ye, Yang Zhang, Xiaoyang Luo, Yiliang Zhang, Bin Pan, Bin Li, Hang Li, Jie Zhang, William Pao, Hongbin Ji, Yihua Sun, Haiquan Chen
PURPOSE: The fibroblast growth factor receptor (FGFR)-3 fusion genes have been recently demonstrated in a subset of non-small cell lung cancer (NSCLC). To aid in identification and treatment of these patients, we examined the frequency, clinicopathologic characteristics, and treatment outcomes of patients who had NSCLC with or without FGFR fusions. EXPERIMENTAL DESIGN: Fourteen known FGFR fusion variants, including FGFR1, FGFR2, and FGFR3, were detected by RT-PCR and verified by direct sequencing in 1,328 patients with NSCLC...
August 1, 2014: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Yongshun Chen, Ying Wang, Haixia Song, Jin Wang, Haijun Yang, Yubing Xia, Jianxin Xue, Shidong Li, Ming Chen, You Lu
Definitive chemoradiation is a curative treatment option for patients with locoregional esophageal squamous cell carcinoma (ESCC) who are not suitable for surgical resection, but many tend to develop local recurrence. The purpose of the study was to investigate factors affecting local recurrence of the tumor. Seventy-two patients with stage II-III thoracic ESCC who received definitive concurrent chemoradiation (CRT) and completely responded to the treatment were enrolled into this study. The case patients were 49 patients who recurred locally within 24 months after definitive CRT and 23 patients who did not have a local recurrence within 24 months were considered as controls...
May 2014: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Samuel A Hasson, Lesley A Kane, Koji Yamano, Chiu-Hui Huang, Danielle A Sliter, Eugen Buehler, Chunxin Wang, Sabrina M Heman-Ackah, Tara Hessa, Rajarshi Guha, Scott E Martin, Richard J Youle
An increasing body of evidence points to mitochondrial dysfunction as a contributor to the molecular pathogenesis of neurodegenerative diseases such as Parkinson's disease. Recent studies of the Parkinson's disease associated genes PINK1 (ref. 2) and parkin (PARK2, ref. 3) indicate that they may act in a quality control pathway preventing the accumulation of dysfunctional mitochondria. Here we elucidate regulators that have an impact on parkin translocation to damaged mitochondria with genome-wide small interfering RNA (siRNA) screens coupled to high-content microscopy...
December 12, 2013: Nature
Monika Sharma
Apoptosis-antagonizing transcription factor (AATF) is involved in transcriptional regulation, cell cycle control, DNA damage responses and in the execution of cell death programs. It also interacts directly with nuclear hormone receptors to enhance their transactivation. This study highlights the RNomics of AATF gene in the pathogenesis of breast cancer: RNA interference gave 64% reduction in AATF mRNA and 47% decline in AATF protein expression in MCF-7 breast cancer cells. Cell proliferation decreased by 41% after transfection and was accompanied by apoptosis induction in 30% MCF-7 cells...
October 2013: Biotechnology Letters
Jessica L Fleming, Dustin L Gable, Somayeh Samadzadeh-Tarighat, Luke Cheng, Lianbo Yu, Jessica L Gillespie, Amanda Ewart Toland
Mus spretus mice are highly resistant to several types of cancer compared to Mus musculus mice. To determine whether differences in microRNA (miRNA) expression account for some of the differences in observed skin cancer susceptibility between the strains, we performed miRNA expression profiling of skin RNA for over 300 miRNAs. Five miRNAs, miR-1, miR-124a-3, miR-133a, miR-134, miR-206, were differentially expressed by array and/or qPCR. miR-1 was previously shown to have tumor suppressing abilities in multiple tumor types...
2013: PeerJ
Nicole A Perry, Marey Shriver, Marie G Mameza, Bryan Grabias, Eric Balzer, Aikaterini Kontrogianni-Konstantopoulos
Obscurins (∼70 - 870 kDa), encoded by the single OBSCN gene, are cytoskeletal proteins originally identified in striated muscles with structural and regulatory roles. Recently, analysis of 13,023 genes in breast and colorectal cancers identified OBSCN as one of the most frequently mutated genes, implicating it in cancer formation. Herein we studied the expression profile of obscurins in breast, colon, and skin cancer cell lines and their involvement in cell survival. Immunoblot analysis demonstrated significant reduction of obscurin proteins [corrected] in cancer cells, resulting from decreased mRNA levels and/or the presence of mutant transcripts...
July 2012: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Parvin Rahman, Richard D Huysmans, Fenny Wiradjaja, Rajendra Gurung, Lisa M Ooms, David A Sheffield, Jennifer M Dyson, Meredith J Layton, Absorn Sriratana, Hidetoshi Takada, Tony Tiganis, Christina A Mitchell
Phosphoinositide 3-kinase (PI3K) regulates cell polarity and migration by generating phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P(3)) at the leading edge of migrating cells. The serine-threonine protein kinase Akt binds to PI(3,4,5)P(3), resulting in its activation. Active Akt promotes spatially regulated actin cytoskeletal remodeling and thereby directed cell migration. The inositol polyphosphate 5-phosphatases (5-ptases) degrade PI(3,4,5)P(3) to form PI(3,4)P(2), which leads to diminished Akt activation...
August 26, 2011: Journal of Biological Chemistry
Zeng-Quan Yang, Gang Liu, Aliccia Bollig-Fischer, Craig N Giroux, Stephen P Ethier
Amplification of the 8p11-12 region has been found in about 15% of human breast cancers and is associated with poor prognosis. Earlier, we used genomic analysis of copy number and gene expression to perform a detailed analysis of the 8p11-12 amplicon to identify candidate oncogenes in breast cancer. We identified 21 candidate genes and provided evidence that three genes, namely, LSM-1, TC-1, and BAG4, have transforming properties when overexpressed. In the present study, we systematically investigated the transforming properties of 13 newly identified 8p11-12 candidate oncogenes in vitro...
November 1, 2010: Cancer Research
Santhi Potireddy, Uros Midic, Cheng-Guang Liang, Zoran Obradovic, Keith E Latham
Mechanisms providing for temporally complex patterns of maternal mRNA translation after fertilization are poorly understood. We employed bioinformatics analysis to compare populations of mRNAs enriched specifically on polysomes at the metaphase II (MII) stage oocyte and late one-cell stages and a detailed deletion/truncation series to identify elements that regulate translation. We used the Bag4 3' untranslated region (UTR) as a model. Bioinformatics analysis revealed one conserved motif, subsequently confirmed by functional studies to be a key translation repressor element...
October 2010: American Journal of Physiology. Cell Physiology
Elisabetta Caprini, Cristina Cristofoletti, Diego Arcelli, Paolo Fadda, Mauro Helmer Citterich, Francesca Sampogna, Armando Magrelli, Federica Censi, Paola Torreri, Marina Frontani, Enrico Scala, Maria Cristina Picchio, Paola Temperani, Alessandro Monopoli, Giuseppe Alfonso Lombardo, Domenica Taruscio, Maria Grazia Narducci, Giandomenico Russo
In this study, we used single nucleotide polymorphism and comparative genomic hybridization array to study DNA copy number changes and loss of heterozygosity for 28 patients affected by Sézary syndrome (SS), a rare form of cutaneous T-cell lymphoma (CTCL). Our data identified, further confirming previous studies, recurrent losses of 17p13.2-p11.2 and 10p12.1-q26.3 occurring in 71% and 68% of cases, respectively; common gains were detected for 17p11.2-q25.3 (64%) and chromosome 8/8q (50%). Moreover, we identified novel genomic lesions recurring in >30% of tumors: loss of 9q13-q21...
November 1, 2009: Cancer Research
Isabelle Bernard-Pierrot, Nadège Gruel, Nicolas Stransky, Anne Vincent-Salomon, Fabien Reyal, Virginie Raynal, Céline Vallot, Gaëlle Pierron, François Radvanyi, Olivier Delattre
The 8p11-12 chromosome region is one of the regions most frequently amplified in breast carcinoma (10-15% of cases). Several genes within this region have been identified as candidate oncogenes, as they are both amplified and overexpressed. However, very few studies have explored the role of these genes in cell transformation, with the aim of identifying valuable therapeutic targets. An analysis of comparative genomic hybridization array and expression profiling data for a series of 152 ductal breast carcinomas and 21 cell lines identified five genes (LSM1, BAG4, DDHD2, PPAPDC1B, and WHSC1L1) within the amplified region as consistently overexpressed due to an increased gene copy number...
September 1, 2008: Cancer Research
B M Riley, R E Schultz, M E Cooper, T Goldstein-McHenry, S Daack-Hirsch, K T Lee, E Dragan, A R Vieira, A C Lidral, M L Marazita, J C Murray
Isolated or nonsyndromic cleft lip and palate (NS CLP) is a complex disorder resulting from multiple genetic and environmental factors. NS CLP has a birth prevalence of 1 per 500 in the Philippines where large families provide an opportunity for gene localization. Genotyping of 392 microsatellite repeat markers at 10 cM intervals over the genome was performed by the Center for Inherited Disease Research (CIDR) on 220 Filipino families with 567 affected and 1,109 unaffected family members genotyped. Among the most statistically significant results from analysis of the genome-wide scan data was a 20 cM region at 8p11-23 in which markers had LODs > or =1...
April 15, 2007: American Journal of Medical Genetics. Part A
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