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Su Jin Lee, Jeong Han Kang, Da Eun Lee, Min Jeong Nam, Hyun-Shik Lee, Oh-Shin Kwon
Chronic alcohol consumption causes hepatic steatosis, which is characterized by a considerable increase in free fatty acid (FFA) and triglyceride levels. To identify the possible proteins involved in the progression to alcoholic hepatosteatosis, we performed proteomic analysis on livers of mice exposed to alcohol. 2D-based proteomic analysis revealed that EtOH exposure in mice changed the expression of 43 proteins compared with that in mice fed a normal diet (ND). The most notable protein changes were proteins involved in Met metabolism and oxidative stress, most of which were significantly downregulated in alcohol-exposed animals...
October 20, 2016: Journal of Cellular Biochemistry
Daniel Esler, Brenda E Ballachey, Lizabeth Bowen, A Keith Miles, Rian D Dickson, John D Henderson
The authors quantified hepatic hydrocarbon-inducible cytochrome P4501A (CYP1A) expression, as ethoxyresorufin-O-deethylase (EROD) activity, in wintering harlequin ducks (Histrionicus histrionicus) captured in Prince William Sound, Alaska, during 2011, 2013, and 2014 (22 to 25 years following the 1989 Exxon Valdez oil spill). EROD activity was compared between birds from areas oiled by the spill and those from nearby unoiled areas. This work replicated studies conducted from 1998 to 2009 that demonstrated harlequin ducks using areas that were oiled in 1989 had elevated EROD activity, indicative of oil exposure, up to 2 decades post-spill...
October 20, 2016: Environmental Toxicology and Chemistry
Yuyin Li, Yuejun Sun, Lifang Jing, Jianjun Wang, Yali Yan, Yajuan Feng, Yueying Zhang, Zhenxing Liu, Long Ma, Aipo Diao
The lysosome inhibitors bafilomycin A1 and chloroquine have both lysosomotropic properties and autophagy inhibition ability, and are promising clinical agents to be used in combination with anticancer drugs. In order to investigate this combination effect, HepG2 cells were treated with bafilomycin A1, chloroquine, or/and doxorubicin, and their proliferative ability, induction of apoptosis, and the changes of lysosomal membrane permeabilization and mitochondrial membrane potential were studied. The results demonstrate that treatment with bafilomycin A1 or chloroquine alone at a relatively low concentration promotes the inhibitory effect of doxorubicin on cell growth and apoptosis...
October 21, 2016: Chemotherapy
Xiuqing Tian, Rui Guo, Yujiao Zhang, Lingling Xu, Xianbing Liu, Yinglong Hou
OBJECTIVE: To observe the effects of sympathetic overactivity on the immune system involved in the imbalance of T helper (Th) lymphocytes, we investigated the correlation between autonomic dysregulation and the generation of regulatory T (Treg) and Th1 chemokines in patients with acute coronary syndrome (ACS). METHODS: Blood samples obtained from patients with coronary artery disease and controls were analyzed for levels of Th1 and Treg cells and their associated cytokines by flow cytometry...
October 21, 2016: Neuroimmunomodulation
Naoshi Nishida, Masatoshi Kudo
Despite recent advances in the treatment of hepatocellular carcinoma (HCC), the prognosis of patients with advanced stage of disease remains unfavorable. Several immune therapies have been applied to HCC, and their responses have not been satisfactory. The immune response to cancer is determined by the balance between the antigenicity of the tumor and the microenvironment of cancer tissues. Generally, accumulated genetic mutations are observed in HCC, which may lead to increased neoantigens on cancer cells with high antigenicity...
October 21, 2016: Oncology
Anil Prasad, Nagina Khudaynazar, Ramana V Tantravahi, Amanda M Gillum, Benjamin S Hoffman
Squamous cell carcinoma of the head and neck (HNSCC) is characterized by high morbidity and mortality. Treatment failure, drug resistance and chemoradiation toxicity have necessitated the development of alternative treatment strategies. Styryl benzyl sulfones, a family of novel small molecule inhibitors, are being evaluated as anti-neoplastic agents in multiple clinical trials. The activity of these compounds has been well characterized in several preclinical tumor studies, but their activity has yet to be fully examined in HNSCC...
October 15, 2016: Oncotarget
Yanfen Fang, Yannan Kong, Jianbei Xi, Mengli Zhu, Tong Zhu, Tongtong Jiang, Wenhao Hu, Mingliang Ma, Xiongwen Zhang
NEK2 is a conserved mitotic regulator critical for cell cycle progression. Aberrant expression of NEK2 has been found in a variety of human cancers, making it an attractive molecular target for the design of novel anticancer therapeutics. In the present study, we have identified a novel compound MBM-5, which was found to bind to NEK2 with high affinity by docking simulations study. MBM-5 potently inhibited NEK2 kinase activity in vitro in a concentration-dependent manner. MBM-5 also suppressed cellular NEK2 kinase activity, as evidenced by the decreased phosphorylation of its substrate Hec1 on S165 in a concentration- and time-dependent manner...
October 15, 2016: Oncotarget
Yaoyao Shi, Yue Kuai, Lizhen Lei, Yuanyuan Weng, Friederike Berberich- Siebelt, Xinxia Zhang, Jinjie Wang, Yuan Zhou, Xin Jiang, Guoping Ren, Hongyang Pan, Zhengrong Mao, Ren Zhou
Dysregulation of the apoptotic pathway is widely recognized as a key step in lymphomagenesis. Notably, LITAF was initially identified as a p53-inducible gene, subsequently implicated as a tumor suppressor. Our previous study also showed LITAF to be methylated in 89.5% B-NHL samples. Conversely, deregulated expression of BCL6 is a pathogenic event in many lymphomas. Interestingly, our study found an oppositional expression of LITAF and BCL6 in B-NHL. In addition, LITAF was recently identified as a novel target gene of BCL6...
October 15, 2016: Oncotarget
Rui Su, Jia-Nan Gong, Ming-Tai Chen, Li Song, Chao Shen, Xin-Hua Zhang, Xiao-Lin Yin, Hong-Mei Ning, Bing Liu, Fang Wang, Yan-Ni Ma, Hua-Lu Zhao, Jia Yu, Jun-Wu Zhang
Aberrant activation of c-Myc plays an important oncogenic role via regulating a series of coding and non-coding genes in acute myeloid leukemia (AML). Histone deacetylases (HDACs) can remove acetyl group from histone and regulate gene expression via changing chromatin structure. Here, we found miR-451 is abnormally down-regulated in AML patient samples; c-Myc recruits HDAC3 to form a transcriptional suppressor complex, co-localizes on the miR-451 promoter, epigenetically inhibits its transcription and finally induces its downregulation in AML...
October 15, 2016: Oncotarget
Antonella Conforti, Nadia Starc, Simone Biagini, Luigi Tomao, Angela Pitisci, Mattia Algeri, Pietro Sirleto, Antonio Novelli, Giulia Grisendi, Olivia Candini, Cintia Carella, Massimo Dominici, Franco Locatelli, Maria Ester Bernardo
The risk of malignant transformation of ex-vivo expanded human mesenchymal stromal cells (huMSCs) has been debated in the last years; however, the biosafety of these cells after exposure to supramaximal physical and chemical stress has never been systematically investigated.We established an experimental in vitro model to induce supramaximal physical (ionizing radiation, IR) and chemical (starvation) stress on ex-vivo expanded bone marrow (BM)-derived huMSCs and investigated their propensity to undergo malignant transformation...
October 15, 2016: Oncotarget
Zhenze Zhao, Xiuye Ma, Spencer D Shelton, Derek C Sung, Monica Li, Daniel Hernandez, Maggie Zhang, Michael D Losiewiz, Yidong Chen, Alexander Pertsemlidis, Xiaojie Yu, Yuanhang Liu, Liqin Du
MYCN amplification is the most common genetic alteration in neuroblastoma and plays a critical role in neuroblastoma tumorigenesis. MYCN regulates neuroblastoma cell differentiation, which is one of the mechanisms underlying its oncogenic function. We recently identified a group of differentiation-inducing microRNAs. Given the demonstrated inter-regulation between MYCN and microRNAs, we speculated that MYCN and the differentiation-inducing microRNAs might form an interaction network to control the differentiation of neuroblastoma cells...
October 15, 2016: Oncotarget
Uday B Maachani, Uma Shankavaram, Tamalee Kramp, Philip J Tofilon, Kevin Camphausen, Anita T Tandle
Glioblastoma multiforme (GBM) continues to be the most frequently diagnosed and lethal primary brain tumor. Adjuvant chemo-radiotherapy remains the standard of care following surgical resection. In this study, using reverse phase protein arrays (RPPAs), we assessed the biological effects of radiation on signaling pathways to identify potential radiosensitizing molecular targets. We identified subsets of proteins with clearly concordant/discordant behavior between irradiated and non-irradiated GBM cells in vitro and in vivo...
October 14, 2016: Oncotarget
Yuan Ren, Nan Ji, Xixiong Kang, Renzhi Wang, Wenbin Ma, Zhenjun Hu, Xingfeng Liu, Yajie Wang
Glioblastoma is a highly vascularized brain tumor that causes high mortality. Kininogen-1 (KNG1) has demonstrated both tumor suppressor and antiangiogenesis properties in gliobastoma cells. We analyzed the microarray and proteomic profiles of tumor tissues from glioblastoma patients (N = 180), and identified potential RNA regulators of the KNG1. Validation experiments in U87 glioblastoma cells showed that the regulation of KNG1 by CTU1, KIAA1274, and RAX was mediated by miR-138. The siRNA-mediated knockdown of CTU1, KIAA1274, or RAX in U87 cells and immortalized human endothelial cells (iHECs) significantly reduced KNG1 expression (P < 0...
October 14, 2016: Oncotarget
Pei Y Liu, Nicholas Sokolowski, Su T Guo, Faraz Siddiqi, Bernard Atmadibrata, Thomas J Telfer, Yuting Sun, Lihong Zhang, Denise Yu, Joshua Mccarroll, Bing Liu, Rui H Yang, Xiang Y Guo, Andrew E Tee, Ken Itoh, Jenny Wang, Maria Kavallaris, Michelle Haber, Murray D Norris, Belamy B Cheung, Jennifer A Byrne, David S Ziegler, Glenn M Marshall, Marcel E Dinger, Rachel Codd, Xu D Zhang, Tao Liu
BET bromodomain inhibitors are very promising novel anticancer agents, however, single therapy does not cause tumor regression in mice, suggesting the need for combination therapy. After screening a library of 2697 small molecule compounds, we found that two classes of compounds, the quinone-containing compounds such as nanaomycin and anti-microtubule drugs such as vincristine, exerted the best synergistic anticancer effects with the BET bromodomain inhibitor JQ1 in neuroblastoma cells. Mechanistically, the quinone-containing compound nanaomycin induced neuroblastoma cell death but also activated the Nrf2-antioxidant signaling pathway, and the BET bromodomain proteins BRD3 and BRD4 formed a protein complex with Nrf2...
October 13, 2016: Oncotarget
Yan-Ping Liu, Hui-Fang Zhu, Ding-Li Liu, Zhi-Yan Hu, Sheng-Nan Li, He-Ping Kan, Xiao-Yan Wang, Zu-Guo Li
Decoy receptor 3 (DcR3), a novel member of the tumor necrosis factor receptor (TNFR) family, was recently reported to be associated with tumorigenesis and metastasis. However, the role of DcR3 in human colorectal cancer (CRC) has not been fully elucidated. In this study, we found that DcR3 expression was significantly higher in human colorectal cancer tissues than in paired normal tissues, and that DcR3 expression was strongly correlated with tumor invasion, lymph node metastases and poor prognoses. Moreover, DcR3 overexpression significantly enhanced CRC cell proliferation and migration in vitro and tumorigenesis in vivo...
October 13, 2016: Oncotarget
Jiaxiong Lu, Shan Guan, Yanling Zhao, Yang Yu, Yongfeng Wang, Yonghua Shi, Xinfang Mao, Kristine L Yang, Wenjing Sun, Xin Xu, Joanna S Yi, Tianshu Yang, Jianhua Yang, Jed G Nuchtern
Neuroblastoma (NB), which accounts for about 15% of cancer-related mortality in children, is the most common childhood extracranial malignant tumor. In NB, somatic mutations of the tumor suppressor, p53, are exceedingly rare. Unlike in adult tumors, the majority of p53 downstream functions are still intact in NB cells with wild-type p53. Thus, restoring p53 function by blocking its interaction with p53 suppressors such as MDM2 is a viable therapeutic strategy for NB treatment. Herein, we show that MDM2 inhibitor SAR405838 is a potent therapeutic drug for NB...
October 13, 2016: Oncotarget
Domenico Ribatti
The immune system plays a major role in the surveillance against tumors. To avoid attack from the immune system, tumor cells develop different strategies to escape immune surveillance. Evidence of immune surveillance comes from both animal models and clinical observations. Mice with a wide variety of immunodeficiencies have a high rate of tumor incidence and are more susceptible to transplanted or chemical carcinogen-induced tumors. Immunosuppressed patients have a high incidence of tumors. However, many patients develop cancer even in the presence of an apparently normal immune system...
October 18, 2016: Oncotarget
Yang Yu, Qingyun Zhang, Qinggui Meng, Chen Zong, Lei Liang, Xue Yang, Rui Lin, Yan Liu, Yang Zhou, Hongxiang Zhang, Xiaojuan Hou, Zhipeng Han, Jiwen Cheng
Prostate cancer (PCa) has become the second leading cause of male cancer-related mortality in the United States. Mesenchymal stem cells (MSCs) are able to migrate to tumor tissues, and are thus considered to be novel antitumor carriers. However, due to their immunosuppressive nature, the application of MSCs in PCa therapy remains limited. In this study, we investigated the effect of MSCs overexpressing an NAD-dependent deacetylase sirtuin 1 (MSCs-Sirt1) on prostate tumor growth, and we analyzed the underlying mechanisms...
October 18, 2016: Oncotarget
Yu-Chuan Huang, Chung-Ta Lee, Jenq-Chang Lee, Yao-Wen Liu, Ying-Jen Chen, Joseph T Tseng, Jui-Wen Kang, Bor-Shyang Sheu, Bo-Wen Lin, Liang-Yi Hung
MicorRNA-137 is silenced in human colorectal cancer tissues and colon polyps. Our study showed that the decreased expression of miR-137 is significantly different in various types of polyp which maintain different potentials to lead to CRC development. The expression of miR-137 gradually decreases during the process of colorectal carcinogenesis. Receiver operating characteristic curve (ROC) analysis indicates that the loss of miR-137 expression in colon polyps can serve as a biomarker to predict the predisposition of colorectal carcinogenesis...
October 18, 2016: Oncotarget
Hu Luo, Liang Gong, Bingjing Zhu, Ying Huang, Chunlan Tang, Shicang Yu, Zhi Yang, Xiangdong Zhou
OBJECTIVE: Few clinical studies have confirmed the role of cytokine-induced killer cells (CIKs) in the maintenance therapy of advanced lung cancer patients. We investigate effectiveness and tolerability of CIKs as a maintenance therapy in the treatment of advanced lung cancer patients. METHODS: 70 patients with advanced lung cancer (stage IIIB to IV) admitted to the First Affiliated Hospital of Third Military Medical University in Chongqing from Nov. 2011 to Jan...
October 17, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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