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Octavia Ramayanti, Mitch Brinkkemper, Sandra A W M Verkuijlen, Leni Ritmaleni, Mei Lin Go, Jaap M Middeldorp
Epstein-Barr virus (EBV) persists in nasopharyngeal (NPC) and gastric carcinomas (EBVaGC) in a tightly latent form. Cytolytic virus activation (CLVA) therapy employs gemcitabine and valproic acid (GCb+VPA) to reactivate latent EBV into the lytic phase and antiviral valganciclovir to enhance cell death and prevent virus production. CLVA treatment has proven safe in phase-I/II trials with promising clinical responses in patients with recurrent NPC. However, a major challenge is to maximize EBV lytic reactivation by CLVA...
March 22, 2018: Cancers
Yan Zhou, Jialei Zhu, Yang Lv, Chenghuan Song, Jianhua Ding, Ming Xiao, Ming Lu, Gang Hu
The loss of dopaminergic (DA) neurons in the substantia nigra (SN) is a major feature in the pathology of Parkinson's disease (PD). Using neural stem or progenitor cells (NSC/NPCs), the prospect of replacing the missing or damaged DA neurons is very attractive for PD therapy. However, little is known about the endogenous mechanisms and molecular pathways regulating the NSC/NPC proliferation and differentiation in the development of PD. Herein, using Kir6.2 knockout (Kir6.2-/- ) mice, we observed that genetic deficiency of Kir6...
March 21, 2018: Molecular Neurobiology
D Himmelhan, O Rawashdeh, H H A Oelschläger
This study characterizes the early postnatal development of the visual neocortex in C3H/HeNRj mice. These mice are homozygous for the Pde6brd1 mutation, which causes retinal degeneration starting from postnatal day 7 (P7). To monitor the development of the visual cortex between P3 and P28 we used eight antigens known to be expressed at different developmental stages (Nestin, tau3, β3- Tubulin, Calbindin, Doublecortin, MAP2, Parvalbumin and NeuN). Using semiquantitative analysis we traced the expression and localization of different developmental markers throughout the layers of the visual cortex...
March 18, 2018: Mechanisms of Development
Eveline Hoebe, Coral Wille, Stacy Hagemeier, Shannon Kenney, Astrid Greijer, Jaap Middeldorp
Epstein-Barr Virus (EBV) BamHI-A rightward frame 1 (BARF1) protein is considered a viral oncogene in epithelial cells and has immune-modulating properties. During viral lytic replication BARF1 is expressed as an early gene, regulated by the immediate early EBV protein R. However, in viral latency BARF1 is exclusively expressed in epithelial tumors such as nasopharyngeal (NPC) and gastric carcinoma (GC) but not in lymphomas, indicating that activation of the BARF1 promoter is cell type specific. Undifferentiated NPC is characterized by high expression of ΔNp63 isoforms of the epithelial differentiation marker p63, a member of the p53 family of transcription factors...
March 17, 2018: Cancers
Kathy H Y Shair, Akhil Reddy, Vaughn S Cooper
Latent membrane protein 1 (LMP1) is an Epstein-Barr virus (EBV) oncogenic protein that has no intrinsic enzymatic activity or sequence homology to cellular or viral proteins. The oncogenic potential of LMP1 has been ascribed to pleiotropic signaling properties initiated through protein-protein interactions in cytosolic membrane compartments, but the effects of LMP1 extend to nuclear and extracellular processes. Although LMP1 is one of the latent genes required for EBV-immortalization of B cells, the biology of LMP1 in the pathogenesis of the epithelial cancer nasopharyngeal carcinoma (NPC) is more complex...
March 21, 2018: Cancers
Yukun Liu, Ran Zhao, Yanmei Wei, Mengna Li, Heran Wang, Weihong Niu, Yao Zhou, Yuanzheng Qiu, Songqing Fan, Yihao Zhan, Wei Xiong, Yanhong Zhou, Xiaoling Li, Zheng Li, Guiyuan Li, Ming Zhou
BACKGROUND: miR-141 is up-regulated and plays crucial roles in nasopharyngeal carcinoma (NPC). However, the molecular mechanism underlying the dysregulation of miR-141 is still obscure. METHODS: Thus, the ChIP-PCR was performed to identify the c-Myc-binding sites in miR-141 and BRD7. qRT-PCR, western blot and immunohistochemistry assays were used to detect the expression of miR-141 and its up/down stream molecules. The rescue experiments on the c-Myc/miR-141 axis were performed in vitro and in vivo...
March 20, 2018: Journal of Experimental & Clinical Cancer Research: CR
Jiao Ji, Yan Yu, Zhi-Ling Li, Ming-Yuan Chen, Rong Deng, Xiang Huang, Guang-Feng Wang, Meng-Xia Zhang, Qi Yang, Senthilkumar Ravichandran, Gong-Kan Feng, Xue-Lian Xu, Chen-Lu Yang, Miao-Zhen Qiu, Lin Jiao, Dajun Yang, Xiao-Feng Zhu
Rationale: Nasopharyngeal carcinoma (NPC) is the most frequent head and neck tumor in South China. The presence of cancer stem cells (CSCs) in NPC contributes to tumor maintenance and therapeutic resistance, while the ability of CSCs to escape from the apoptosis pathway may render them the resistant property to the therapies. Inhibitor of apoptosis proteins family proteins (IAPs), which are overexpressed in nasopharyngeal carcinoma stem cells, may play an important role in maintaining nasopharyngeal cancer stem cell properties...
2018: Theranostics
Jingjing Li, Haiwen Li, Dechao Zhan, Mei Xiang, Jun Yang, Yufang Zuo, Yin Yu, Hechao Zhou, Danxian Jiang, Haiqing Luo, Zihong Chen, Zhonghua Yu, Zumin Xu
The aim of the present study was to investigate whether niclosamide could sensitize the nasopharyngeal carcinoma cells to radiation and further explore the underlying mechanisms. CCK-8 assay was used to determine the effect of niclosamide on the proliferation of NPC cells. Colony formation assay was used to evaluate the radiosensitizing effect of niclosamide on NPC cells. Flow cytometry analysis was used to determine the apoptosis of NPC cells induced by niclosamide. Immunofluorescent staining was used to detect the formation of γ-H2AX foci and the localization of Ku70/80 proteins in NPC cells...
2018: Journal of Cancer
Hui Chang, Jia-Wang Wei, Kai Chen, Shu Zhang, Fei Han, Li-Xia Lu, Wei-Wei Xiao, Yuan-Hong Gao
Background: In the era of intensity-modulated radiotherapy (IMRT), distant metastasis remains the major cause of death from nasopharyngeal carcinoma (NPC). This study aimed to evaluate the clinical value of pretreatment serum lipid profiles in predicting clinical outcome of NPC. Methodology / Principal Findings: A total of 1927 consecutive patients who had untreated NPC and completed radical IMRT between Jan. 2010 and Dec. 2011 were retrospectively reviewed. Pretreatment serum lipid indexes including total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A-I (apoAI) and apolipoprotein B were analyzed for their association with survivals, together with the clinical features (age, sex, pathological type, anemia, chemotherapy sequence and Epstein-Barr virus deoxyribonucleic acid)...
2018: Journal of Cancer
Lei Wu, Churong Li, Li Pan
Nasopharyngeal carcinoma (NPC) is a rare malignancy worldwide, but it is endemic in a few areas including Southern China, Southeast Asia, North Africa and the Arctic. The underlying mechanisms behind this remarkable geographic distribution remain unclear. Although Epstein-Barr virus (EBV) infection has been suggested as a necessary cause of undifferentiated NPC, EBV itself is not sufficient to cause this malignancy. Other co-factors, such as environmental risk factors, and/or genetic susceptibility, may interact with EBV to play a role in the carcinogenesis of NPC...
April 2018: Experimental and Therapeutic Medicine
Brigette Ma, Edwin P Hui, Ann King, Sing F Leung, Michael Km Kam, Frankie Mo, Leung Li, Ki Wang, Herbert Loong, Ashley Wong, Charles Ml Chan, K C Allen Chan, S C Cesar Wong, Y M Dennis Lo, Anthony Tc Chan
BACKGROUND: Plasma Epstein-Barr virus (pEBV) DNA and fluorodeoxyglucose positron emission (PET) reflect tumour burden in advanced NPC. This study hypothesised that a dual endpoint based on assessing pEBV DNA clearance and PET response could predict early drug response. METHODS: Eligible patients underwent a computed tomography (CT) scan and dual PET-CT at baseline, a PET-CT at 4 weeks, and then a CT scan at 10 weeks after starting palliative or induction chemotherapy...
March 20, 2018: British Journal of Cancer
Teng Hwee Tan, Yu Yang Soon, Timothy Cheo, Francis Ho, Lea Choung Wong, Jeremy Tey, Ivan W K Tham
PURPOSE: To determine if the addition of induction chemotherapy (IC) to concurrent chemoradiation (CCRT) in locally advanced nasopharyngeal carcinoma (LA-NPC) can improve survival. METHODS: We performed a meta-analysis of both randomized controlled trials (RCTs) and observational studies (OBS) to compare the effects of addition of IC to CCRT versus (vs) CCRT alone on overall survival (OS), progression free survival (PFS), distant metastasis-free survival (DMFS) and adverse events (AE) in LA-NPC...
March 16, 2018: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
Yun-Hsuan Lin, Tai-Lin Huang, Chih-Yen Chien, Hui-Chun Chen, Hsuan-Chih Hsu, Eng-Yen Huang, Chong-Jong Wang, Yu-Jie Huang, Yu-Ming Wang, Chun-Chieh Huang, Shang-Yu Chou, Kuan-Cho Liao, Fu-Min Fang
BACKGROUND: To scrutinize the pretreatment prognosticators on survival and late toxicities in a homogenous cohort of nasopharyngeal carcinoma (NPC) patients treated by simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT). METHODS: A total of 219 non-distant metastatic NPC patients consecutively treated by SIB-IMRT at a single institute were collected. The pretreatment factors including the socio-demographic variables, TNM stages, gross tumor volume (GTV), Epstein-Barr virus (EBV)-DNA, and hematologic inflammatory markers were analyzed...
March 20, 2018: Radiation Oncology
Cheng-Fu Cai, Li-Man Liu, Han-Jing Shangguan, Cun-Shan Liu, Xian-Yang Luo, Yi-Meng Li
The Wnt/β-catenin pathway serves important roles in cancer development. The expression and function of Chibby (Cby), as a direct antagonist of β-catenin, in nasopharyngeal carcinoma (NPC) has not been fully investigated. The present study revealed that the mRNA and protein expression of Cby was significantly lower in NPC tissue than in the adjacent normal tissue. Low expression of Cby was significantly associated with the tumor and the clinical staging. Furthermore, Cby overexpression inhibited the proliferation of human NPC SUNE1 cells and induced cell cycle arrest...
April 2018: Oncology Letters
Liangping Ni, Ying Liu
The present study aimed to assess early-stage nasopharyngeal carcinoma (NPC) with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) at 3.0 T. A total of 44 patients newly diagnosed with NPC were included in the present study. All patients underwent MR examination at 3.0 T using DCE-MRI and DWI. The volume transfer constant ( Ktrans ), flux rate constant between extravascular extracellular space and plasma ( Kep ), the volume of extravascular extracellular space per unit volume of tissue ( Ve ) and the apparent diffusion coefficient (ADC) of tumours were investigated...
April 2018: Oncology Letters
Yajie Zhao, Lin Shen, Xinqiong Huang, Yuxiang He, Jun Fu, Yujie Qian, Shan Li, Na Zhao, Liangfang Shen
The present study retrospectively analyzed the prognostic factors of 135 patients with locally advanced nasopharyngeal carcinoma (NPC) who received intensity modulated radiation therapy between August 2008 and January 2012 at Xiangya Hospital of Central South University. Patients were staged from III-IVA according to the 7th American Joint Committee on Cancer staging system. Using Statistical Analysis System 9.3 software, the present study demonstrated that, among these 135 patients, the 5-year overall survival, the 5-year local relapse-free survival, and the 5-year disease metastasis-free survival were 84, 82, and 78%, respectively...
April 2018: Oncology Letters
Sophie Outh-Gauer, Marie Alt, Christophe Le Tourneau, Jérémy Augustin, Chloé Broudin, Cassandre Gasne, Thomas Denize, Haitham Mirghani, Elizabeth Fabre, Madeleine Ménard, Florian Scotte, Eric Tartour, Cécile Badoual
Cancer occurrence can be understood as the result of dysfunctions in immune tumoral microenvironment. Here we review the recent understandings of those microenvironment changes, regarding their causes and prognostic significance in head and neck (HN) carcinoma. We will focus on HN squamous cell cancer (SCC) and nasopharyngeal carcinomas (NPC). Their overall poor prognosis may be improved with immunotherapy in a subset of patients, as supported by current clinical trials. However, finding reliable markers of therapeutic response is crucial for patient selection, due to potential severe adverse reactions and high costs...
March 1, 2018: Cancer Treatment Reviews
Hongxia Yang, Gang Zhang, Xiaolin Che, Shudong Yu
Slug is associated with the radioresistance of nasopharyngeal carcinoma (NPC) and the main current approach of treatment for NPC is radiotherapy. Hence, the aim of the current study was to determine the effect of Slug silencing on the radiosensitivity of NPC cells. Lentiviral-mediated transfection of Slug RNA interference (RNAi) in NPC cell line C666-1 was performed in vitro . Following Slug inhibition, its expression was detected using western blotting. A clonogenic survival assay and flow cytometry were then performed to evaluate the clonogenic cell survival, cell cycle distribution and apoptosis of C666-1 cells following irradiation...
April 2018: Experimental and Therapeutic Medicine
Jiawang Wei, Huixia Feng, Weiwei Xiao, Qiaoxuan Wang, Bo Qiu, Shiliang Liu, Meiling Deng, Lixia Lu, Hui Chang, Yuanhong Gao
Objective: Stage N2-3 nasopharyngeal carcinoma (NPC) shows a high risk of distant metastasis, which will finally cause death. This study aimed to evaluate the impact of neoadjuvant chemotherapy (NACT) of various cycles before radical radiotherapy on distant metastasis and survival of patients with stage N2-3 diseases. Methods: In this study, a total of 1,164 consecutive patients with non-metastatic N2-3 NPC were recruited and prospectively observed. Then 231 patients who received NACT of 4 cycles (NACT=4 group) were matched 1:2:1 to 462 patients treated with NACT of 2 cycles (NACT=2 group) and 231 patients treated without NACT (NACT=0 group), according to age, histological subtype, N stage and NACT regimen...
February 2018: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
Meixiang Zhang, Justine Ngo, Filomena Pirozzi, Ying-Pu Sun, Anthony Wynshaw-Boris
BACKGROUND: Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have been widely used to generate cellular models harboring specific disease-related genotypes. Of particular importance are ESC and iPSC applications capable of producing dorsal telencephalic neural progenitor cells (NPCs) that are representative of the cerebral cortex and overcome the challenges of maintaining a homogeneous population of cortical progenitors over several passages in vitro. While previous studies were able to derive NPCs from pluripotent cell types, the fraction of dorsal NPCs in this population is small and decreases over several passages...
March 15, 2018: Stem Cell Research & Therapy
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