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Xin Zhou, Dewu Han, Ruiling Xu, Huiwen Wu, Chongxiao Qu, Feng Wang, Xiangyu Wang, Yuanchang Zhao
We set out to explore the hypothesis that glycine attenuates non-alcoholic steatohepatitis (NASH) in rats and the possible mechanism by which is it does. Male Sprague-Dawley (SD) rats were fed a diet containing high fat and high sucrose (HSHF) for 24 weeks to induce NASH. Blood and liver tissues were sampled at selected time points throughout the study. Compared with control animals, the content of alanine transaminase (ALT), triglycerides (TGs), and free fatty acids (FFAs) in plasma and the TG and FFA content in the liver was increased from week 4 to 24...
October 23, 2016: Oncotarget
Musaffe Tuna, Christopher I Amos
Approximately 18% of all human cancers have a viral etiology, and human papillomavirus (HPV) has been identified as one of the most prevalent viruses that plays causative role in nearly all cervical cancers and, in addition, in subset of head and neck, anal, penile and vulvar cancers. The recent introduction of next generation sequencing (NGS) and other 'omics' approaches have resulted in comprehensive knowledge on the pathogenesis of HPV-driven tumors. Specifically, these approaches have provided detailed information on genomic HPV integration sites, disrupted genes and pathways, and common and distinct genetic and epigenetic alterations in different human HPV-associated cancers...
October 23, 2016: Oncotarget
Kwangwoo Park, Sungjin Park, Mi-Jin Jeon, Jinhyun Choi, Jun Won Kim, Yoon Jin Cho, Won-Seok Jang, Yo Sup Keum, Ik Jae Lee
The 3D-printed boluses were used during the radiation therapy of the chest wall in six patients with breast cancer after modified radical mastectomy (MRM). We measured the in-vivo skin doses while both conventional and 3D-printed boluses were placed on the chest wall and compared the mean doses delivered to the ipsilateral lung and the heart. The homogeneity and conformity of the dose distribution in the chest wall for both types of boluses were also evaluated. The uniformity index on the chest skin was improved when the 3D-printed boluses were used, with the overall average skin dose being closer to the prescribed one in the former case (-0...
October 23, 2016: Oncotarget
Wei Tang, Zhijun Liao, Quan Zou
MicroRNAs(miRNAs) often exert their oncogenic and tumor suppressor functions by suppressing protein-coding genes expressions in cancers and thus have a strong association with cancers' generation, development and metastasis. Through comprehensively understanding differentially expressed miRNAs (oncomiRNA) in tumor tissues, we can elucidate the underlying molecular mechanisms in tumorigenesis and develop novel strategies for cancer diagnosis and treatment. The differential expression of miRNAs can now be analyzed through numerous statistical significance tests based on different principles, which are also available in various R packages...
October 23, 2016: Oncotarget
Ying Xiong, Li Liu, Jiajun Wang, Wei Xi, Yu Xia, Qi Bai, Yang Qu, Qilai Long, Jiejie Xu, Jianming Guo
BACKGROUND: Chemokine (C-C motif) ligand 21 (CCL21), a ligand of the chemokine (C-C motif) receptor 7, has recently been identified as an immuno-based anti-cancer molecule for its dendritic cells and T lymphocytes chemoattractant function. The aim of this study was to investigate prognostic values of CCL21 expression in metastatic renal cell carcinoma patients treated with targeted therapy. METHODS: This study included 111 patients with metastatic renal cell carcinoma receiving targeted therapy...
October 23, 2016: Oncotarget
Vincent Chin-Hung Chen, Chiao-Fan Lin, Yi-Hsuan Hsieh, Hsin-Yi Liang, Kuo-You Huang, Wei-Che Chiu, Yena Lee, Roger S McIntyre, Hsiang-Lin Chan
Hepatocellular carcinoma (HCC) is highly prevalent in Asia. Antidepressants have been associated with increase in hepatocellular carcinoma. This is the first Asian population-based study to evaluate the association between antidepressant use and risk of HCC. Based on Taiwan's National Health Insurance Research Database, we conducted a nationwide population-based study. A total of 49,998 cases with HCC were identified and paired with 244,236 randomly selected controls. The data was analyzed via the conditional logistic regression model adjusting for several confounding factors...
October 23, 2016: Oncotarget
Xiangji Luo, Weidong Jia, Zhiyong Huang, Xiangcheng Li, Baocai Xing, Xiaoqing Jiang, Jun Li, Anfeng Si, Tian Yang, Chunfang Gao, Wan Yee Lau, Feng Shen
Patients with unresectable and advanced intrahepatic cholangiocarcinoma (ICC) usually have short survival due to a lack of effective treatment. This multicenter, single arm, open labeled, prospective study was conducted to evaluate the effectiveness and safety of sorafenib combined with best supportive care (BSC) in these patients. We enrolled 44 patients with unresectable and advanced ICC who were treated with sorafenib (400 mg, twice daily) and BSC. The primary endpoint was disease control rate (DCR) at week 12, and the secondary endpoints included time to progression (TTP), progression-free survival (PFS), overall survival (OS), duration of therapy (DOT), and adverse events (AEs)...
October 23, 2016: Oncotarget
Siham Bibi, Yanyan Zhang, Caroline Hugonin, Mallorie Depond Mangean, Liang He, Ghaith Wedeh, Jean-Marie Launay, Sjoerd Van Rijn, Thomas Würdinger, Fawzia Louache, Michel Arock
Systemic mastocytosis are rare neoplasms characterized by accumulation of mast cells in at least one internal organ. The majority of systemic mastocytosis patients carry KIT D816V mutation, which activates constitutively the KIT receptor. Patient with advanced forms of systemic mastocytosis, such as aggressive systemic mastocytosis or mast cell leukemia, are poorly treated to date. Unfortunately, the lack of in vivo models reflecting KIT D816V+ advanced disease hampers pathophysiological studies and preclinical development of new therapies for such patients...
October 22, 2016: Oncotarget
Yiqing Pan, Yue Liu, Li Wang, Feng Xue, Yanqin Hu, Ran Hu, Chen Xu
Sertoli cells create a local tolerogenic microenvironment to maintain testicular immune privilege especially through the formation of a blood-testis barrier (BTB). However, the molecular mechanisms underlying the immune modulation function and BTB dynamics of Sertoli cells remained elusive. MAP phosphatase (MKP)-1 acts as a crucial negative regulator of the inflammatory response. Nevertheless, the role of MKP-1 in regulating Sertoli cells has not been elucidated. In this study, we have for the first time uncovered distinct cellular localization of MKP-1 in the cells at different stages of mouse testis, and the level of MKP-1 expression was significantly up-regulated by LPS-induced acute testis inflammation...
October 22, 2016: Oncotarget
Chen-Xu Ni, Yang Qi, Jin Zhang, Ying Liu, Wei-Heng Xu, Jing Xu, Hong-Gang Hu, Qiu-Ye Wu, Yan Wang, Jun-Ping Zhang
The eradication of cancer stem cells (CSCs) is significant for cancer therapy and prevention. In this study, we evaluated WM130, a novel derivative of matrine, for its effect on CSCs using human hepatocellular carcinoma (HCC) cell lines, their sphere cells, and sorted EpCAM+ cells. We revealed that WM130 could not only inhibit proliferation and colony formation of HCC cells, but also suppress the expression of some stemness-related genes and up-regulate some mature hepatocyte marker genes, indicating a promotion of differentiation from CSCs to hepatocytes...
October 22, 2016: Oncotarget
Jian Xie, Yan Feng, Ting Lin, Xiao-Yu Huang, Rui-Huan Gan, Yong Zhao, Bo-Hua Su, Lin-Can Ding, Lin She, Jiang Chen, Li-Song Lin, Xu Lin, Da-Li Zheng, You-Guang Lu
The cadherin-4 gene (CDH4) of the cadherin family encodes non-epithelial R-cadherin (R-cad); however, the function of this gene in different types of cancer remains controversial. In this study, we found higher expression of CDH4 mRNA in a salivary adenoid cystic carcinoma (SACC) cell line with low metastatic potential (SACC-83) than in a cell line with high metastatic potential (SACC-LM). By analyzing 67 samples of SACC tissues and 40 samples of paraneoplastic normal tissues, we found R-cad highly expressed in 100% of normal paraneoplastic tissue but only expressed in 64% of SACC tumor tissues (P<0...
October 22, 2016: Oncotarget
Michelle J Wilkinson, Henry G Smith, Gráinne McEntee, Joan Kyula-Currie, Tim D Pencavel, David C Mansfield, Aadil A Khan, Victoria Roulstone, Andrew J Hayes, Kevin J Harrington
Advanced extremity melanoma and sarcoma present a significant therapeutic challenge, requiring multimodality therapy to treat or even palliate disease. These aggressive tumours are relatively chemo-resistant, therefore new treatment approaches are urgently required. We have previously reported on the efficacy of oncolytic virotherapy (OV) delivered by isolated limb perfusion. In this report, we have improved therapeutic outcomes by combining OV with radiotherapy. In vitro, the combination of oncolytic vaccinia virus (GLV-1h68) and radiotherapy demonstrated synergistic cytotoxicity...
October 22, 2016: Oncotarget
Bo Yang, Shiming Zhang, Zhihao Wang, Chunxu Yang, Wen Ouyang, Fuxiang Zhou, Yunfeng Zhou, Conghua Xie
β-catenin is a crucial signal transduction molecule in the Wnt/β-catenin signal pathway, and increased β-catenin expression has consistently been found in high grade gliomas. However, the mechanisms responsible for β-catenin overexpression have remained elusive. Here we show that the deubiquitinase USP9X stabilizes β-catenin and thereby promotes high grade glioma cell growth. USP9X binds β-catenin and removes the Lys 48-linked polyubiquitin chains that normally mark β-catenin for proteasomal degradation...
October 22, 2016: Oncotarget
Wankun Chen, Yajun Xu, Jing Zhong, Huihui Wang, Meilin Weng, Qian Cheng, Qichao Wu, Zhirong Sun, Hui Jiang, Minmin Zhu, Yu Ren, Pingbo Xu, Jiawei Chen, Changhong Miao
Malignant fibrous histiocytoma amplified sequence 1 (MFHAS1) is a predicted oncoprotein that demonstrates tumorigenic activity in vivo; however, the mechanisms involved are unknown. Macrophages are divided into the pro-inflammatory M1 and anti-inflammatory/protumoral M2 subtypes. Tumor cells can induce M2 polarization of tumor-associated macrophages (TAMs) to promote metastasis; but the underlying pathways require to be elucidated. In this study, we detected a positive association between MFHAS1 expression in TAMs and human colorectal cancer (CRC) TNM stage...
October 21, 2016: Oncotarget
Liang Xiao, Bo Yang, Xiaoyu Liu, Yan Luo, Qiongmei Ji, Zhong Wen, Zhigang Liu, Ping-Chang Yang
Food allergy (FA) is an adverse immune response to certain innocent food. It is estimated about 2% to 6% of the general population suffer from FA. Symptoms of a food allergic reaction may involve the gastrointestinal tract or/and other organs. The gut microbiota plays a critical role in diet-induced health problems. Whether the changes in the composition of the intestinal microbiota regulate allergic responses to food remains poorly understood. Thus, we created an FA animal model, sequenced the V4-V5 regions of 16S rRNA genes to characterize the genera abundance of gut microbiota...
October 21, 2016: Oncotarget
Lorena P Suarez-Kelly, Gregory M Kemper, Megan C Duggan, Andrew Stiff, Tiffany C Nole, Joseph Markowitz, Eric A Luedke, Vedat O Yildiz, Lianbo Yu, Alena Cristina Jaime-Ramirez, Volodymyr Karpa, Xiaoli Zhang, William E Carson
The ubiquitin-proteasome signaling pathway is critical for cell cycle regulation and neoplastic growth. Proteasome inhibition can activate apoptotic pathways. Bortezomib, a selective proteasome inhibitor, has anti-melanoma activity. MLN2238 (ixazomib), an oral proteasome inhibitor, has improved pharmacotherapeutic parameters compared to bortezomib. Interferon-alpha (IFN-α), an immune boosting agent, is FDA-approved for treatment of melanoma. In this study in vitro and in vivo evaluation of the antitumor potential of ixazomib and combination treatments with ixazomib and IFN-α were performed...
October 21, 2016: Oncotarget
Cinthia C Stempin, Claudia C Motrán, María P Aoki, Cristian R Falcón, Fabio M Cerbán, Laura Cervi
Macrophage plasticity is critical for controlling inflammation including those produced by helminth infections, where alternatively activated macrophages (AAM) are accumulated in tissues. AAM expressing the co-inhibitory molecule programmed death ligand 2 (PD-L2), which is capable of binding programmed death 1 (PD-1) expressed on activated T cells, have been demonstrated in different parasitic infections. However, the role of PD-L2 during F. hepatica infection has not yet been explored. We observed that F. hepatica infection or a F...
October 21, 2016: Oncotarget
Cheng Shuqun, Chen Minshan, Cai Jianqiang, The National Research Cooperative Group For Diagnosis And Treatment Of Hepatocellular Carcinoma With Tumor Thrombus
Hepatocellular carcinoma is the fourth leading cause of cancer-related morbidity and mortality in China. Portal vein tumor thrombus (PVTT) is common and it worsens prognosis of hepatocellular carcinoma (HCC). There is no internationally accepted consensus or guideline for diagnosis and treatment of HCC with PVTT. Based on existing evidences and common current practices, Chinese Experts on Multidisciplinary Diagnosis and Treatment of HCC with portal vein tumor thrombus met to develop a national consensus on diagnosis and treatment of HCC with PVTT...
October 21, 2016: Oncotarget
Kelly C G Manfrere, Marina P Torrealba, Denis R Miyashiro, Luanda M S Oliveira, Gabriel C de Carvalho, Josenilson F Lima, Anna Claudia C C Branco, Nátalli Z Pereira, Juliana Pereira, José A Sanches, Maria N Sato
Sézary syndrome (SS) carries a poor prognosis, and infections represent the most frequent cause of death in SS patients. Toll-like receptors (TLRs) are a family of innate immune receptors that induce protective immune responses against infections. We sought to evaluate the ability of TLR agonists to induce inflammatory cytokine, Th2 cytokine, and type I interferon (IFN-I) production by peripheral blood mononuclear cells (PBMC) of untreated SS patients. We detected impaired IL-6, IL-10 and IL-13 secretion by PBMC induced by the agonists for TLR5, TLR3, TLR7 and TLR9 in SS patients, while it was partially recovered by TLR2/TLR4 and TLR7/8 agonists TNF secretion was restored following stimulation with TLR2/TLR4 agonists...
October 21, 2016: Oncotarget
Yifan Cao, Hao Liu, Heng Zhang, Chao Lin, Ruochen Li, Songyang Wu, He Li, Hongyong He, Weijuan Zhang, Jiejie Xu
: Backround: Abnormal expression of CXC chemokine receptor 1 (CXCR1) has shown the ability to promote tumor angiogensis, invasion and metastasis in several cancers. The purpose of our curret study is to discover the clinical prognostic significance of CXCR1 in resectable gastric cancer. METHODS: 330 gastric cancer patients who underwent R0 gastrectomy with standard D2 lymphadenectomy at Zhongshan Hospital, Fudan University between 2007 and 2008 were enrolled. CXCR1 expression was evaluated with use of immunohistochemical staining...
October 21, 2016: Oncotarget
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