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https://www.readbyqxmd.com/read/27934959/hopx-functions-as-a-tumour-suppressor-in-head-and-neck-cancer
#1
Lee Fah Yap, Sook Ling Lai, Sathya Narayanan Patmanathan, Ravindran Gokulan, C Max Robinson, Joe B White, San Jiun Chai, Pathmanathan Rajadurai, Narayanan Prepageran, Yew Toong Liew, Victor Lopes, Wenbin Wei, Robert J Hollows, Paul G Murray, Daniel W Lambert, Keith D Hunter, Ian C Paterson
Head and neck squamous cell carcinoma (HNSCC) is generalized term that encompasses a diverse group of cancers that includes tumours of the oral cavity (OSCC), oropharynx (OPSCC) and nasopharynx (NPC). Genetic alterations that are common to all HNSCC types are likely to be important for squamous carcinogenesis. In this study, we have investigated the role of the homeodomain-only homeobox gene, HOPX, in the pathogenesis of HNSCC. We show that HOPX mRNA levels are reduced in OSCC and NPC cell lines and tissues and there is a general reduction of HOPX protein expression in these tumours and OPSCCs...
December 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27928380/facial-dystonia-with-facial-grimacing-and-vertical-gaze-palsy-with-round-the-houses-sign-in-a-29-year-old-woman
#2
J Crespi, G Bråthen, P Quist-Paulsen, J Pagonabarraga, C Roig-Arnall
A 29-year-old woman developed progressive dysarthria and coordination problems from the age of 15. Examination showed dysarthria, facial dystonia, bibrachial dystonia, hyperreflexia, ataxia, and emotional incontinence. Downward supranuclear gaze palsy was prominent with a "Round the Houses" sign. Magnetic resonance imaging of the brain and medulla, electroneurography, and cerebrospinal fluid were normal. A computed tomography scan showed hepatosplenomegaly. This combination of progressive neurological symptoms together with hepatosplenomegaly was suggestive of inborn error of metabolism...
February 2016: Neuro-ophthalmology
https://www.readbyqxmd.com/read/27927756/surrogate-end-points-for-overall-survival-in-loco-regionally-advanced-nasopharyngeal-carcinoma-an-individual-patient-data-meta-analysis
#3
Federico Rotolo, Jean-Pierre Pignon, Jean Bourhis, Sophie Marguet, Julie Leclercq, Wai Tong Ng, Jun Ma, Anthony T C Chan, Pei-Yu Huang, Guopei Zhu, Daniel T T Chua, Yong Chen, Hai-Qiang Mai, Dora L W Kwong, Yoke Lim Soong, James Moon, Yuk Tung, Kwan-Hwa Chi, George Fountzilas, Li Zhang, Edwin Pun Hui, Anne W M Lee, Pierre Blanchard, Stefan Michiels
BACKGROUND: Our objective was to evaluate progression-free survival (PFS) and distant metastasis-free survival (DMFS) as surrogate end points for overall survival (OS) in randomized trials of chemotherapy in loco-regionally advanced nasopharyngeal carcinomas (NPCs). METHODS: Individual patient data were obtained from 19 trials of the updated Meta-Analysis of Chemotherapy in Nasopharyngeal Carcinoma (MAC-NPC) plus one additional trial (total = 5144 patients). Surrogacy was evaluated at the individual level using a rank correlation coefficient ρ and at the trial level using a correlation coefficient R(2) between treatment effects on the surrogate end point and OS...
April 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/27927055/improving-the-therapeutic-efficacy-of-neural-progenitor-cell-transplantation-following-spinal-cord-injury
#4
Michael A Lane, Angelo C Lepore, Itzhak Fischer
There have been a wide range of preclinical studies testing cellular therapies to repair the injured spinal cord, yet they remain a challenge to translate because of inconsistencies in efficacy, difficulties in obtaining reliable and safe sources of donor cells, limited number of patients with acute/subacute SCI and the high costs of clinical trials. Area covered: This paper focusses on the therapeutic potential of neural precursor cells (NPCs) because they can provide the cellular components capable of promoting repair and enhancing functional improvement following spinal cord injury (SCI)...
December 7, 2016: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/27926491/early-pathogenic-event-of-alzheimer-s-disease-documented-in-ipscs-from-patients-with-psen1-mutations
#5
Juan Yang, Hanzhi Zhao, Yu Ma, Guilai Shi, Jian Song, Yu Tang, Song Li, Ting Li, Nan Liu, Fan Tang, Junjie Gu, Lingling Zhang, Zhuohua Zhang, Xiaohui Zhang, Ying Jin, Weidong Le
Alzheimer's disease (AD) is the most common age-related dementia characterized by progressive neuronal loss. However, the molecular mechanisms for the neuronal loss is still debated. Here, we used induced pluripotent stem cells (iPSCs) derived from somatic cells of familial AD patients carrying PSEN1 mutations to study the early pathogenic event of AD. We found that premature neuronal differentiation with decreased proliferation and increased apoptosis occured in AD-iPSC-derived neural progenitor cells (AD-NPCs) once neuronal differentiation was initiated, together with higher levels of Aβ42 and phosphorylated tau...
December 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926490/positive-regulation-of-taz-expression-by-ebv-lmp1-contributes-to-cell-proliferation-and-epithelial-mesenchymal-transition-in-nasopharyngeal-carcinoma
#6
Jiang He, Feiyu Tang, Liyu Liu, Lin Chen, Jiang Li, Danming Ou, Lu Zhang, Zhi Li, Deyun Feng, Wenzheng Li, Lun-Quan Sun
The Epstein-Barr virus latent membrane protein 1 (LMP1) is an integral membrane protein. LMP1 has been reported to activate the NF-κB and mitogen-activated protein kinase pathways. However, these effects alone are unable to account for the profound oncogenic properties of LMP1. TAZ is one of the nuclear effectors of Hippo-related pathways and highly expressed in many human tumors. Here, we reported that TAZ was frequently expressed in LMP1-positive nasopharyngeal carcinoma. In NPC cell lines, we showed that LMP1 promoted TAZ expression...
December 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27923823/bortezomib-relieves-immune-tolerance-in-nasopharyngeal-carcinoma-via-stat1-suppression-and-indoleamine-2-3-dioxygenase-downregulation
#7
Guan-Min Jiang, Jun Du, Wei-Feng Ma, Hui Wang, Yu Qiu, Qiu-Gui Zhang, Wei Xu, Hui-Fang Liu, Hong-Sheng Wang, Jian-Ping Liang
Radiotherapy is the primary treatment for nasopharyngeal carcinoma (NPC). Patients with intermediate and advanced stage NPC receiving only radiotherapy have limited survival, so newer immunotherapeutic approaches are sought. The major impediment to better clinical outcomes is tumor immune tolerance. Indoleamine 2, 3-dioxygenase (IDO), an interferon-γ (IFNγ)-inducible enzyme, is a major inducer of immune tolerance during tumor development; therefore, inhibition of the IDO pathway is an important modality for cancer treatment...
December 6, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27923664/arhgef1-is-expressed-in-cortical-neural-progenitor-cells-and-regulates-neurite-outgrowth-of-newly-differentiated-neurons
#8
Xiaoliang Xiang, Xiaoji Zhuang, Shengnan Li, Lei Shi
Neurite outgrowth is crucial for the maturation of neurons and the establishment of anatomical connections during development of the nervous system. We report here that Arhgef1, a RhoA guanine nucleotide exchange factor previously found expressed in the early stages of neuronal development to regulate neurite outgrowth, is also highly expressed in cortical neural progenitor cells (NPCs). To better dissect its role in NPCs, we knocked down Arhgef1 expression in these cells and induced differentiated of them into neurons...
December 3, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27923544/niemann-pick-disease-type-c-and-roscoe-brady
#9
REVIEW
Marc C Patterson, Steven U Walkley
The Niemann-Pick family of diseases was poorly understood until Roscoe Brady and his colleagues began their investigations in the 1960s. Following Brady's discovery of the defect in acid sphingomyelinase in Niemann-Pick disease, types A and B, Peter Pentchev, a senior scientist in the group, launched a series of investigations of an unusual lipid storage disease in a spontaneous mouse model. These led initially to identification of the cholesterol trafficking defect in the mouse, and then in human Niemann-Pick disease, type C (NPC)...
November 29, 2016: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/27919278/microrna-19b-3p-regulates-nasopharyngeal-carcinoma-radiosensitivity-by-targeting-tnfaip3-nf-%C3%AE%C2%BAb-axis
#10
Teng Huang, Li Yin, Jing Wu, Jia-Jia Gu, Jian-Zhong Wu, Dan Chen, Hong-Liang Yu, Kai Ding, Nan Zhang, Ming-Yu Du, Lu-Xi Qian, Zhi-Wei Lu, Xia He
BACKGROUND: Nasopharyngeal carcinoma (NPC) is among the most common squamous cell carcinoma in South China and Southeast Asia. Radiotherapy is the primary treatment for NPC. However, radioresistance acts as a significant factor that limits the efficacy of radiotherapy for NPC patients. Growing evidence supports that microRNAs (miRNAs) play an important role in radiation response. METHODS: Real-time quantitative PCR was used to analyze the expression of miR-19b-3p in NPC cell lines and NP69...
December 5, 2016: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/27911864/effect-of-interrupted-time-during-intensity-modulated-radiation-therapy-on-survival-outcomes-in-patients-with-nasopharyngeal-cancer
#11
Guo-Zeng Xu, Ling Li, Xiao-Dong Zhu
OBJECTIVE: To evaluate the influence of interrupted time (IT) during intensity-modulated radiotherapy (IMRT) on survival outcomes in patients with nasopharyngeal cancer (NPC). MATERIALS AND METHODS: 515 NPC patients receiving IMRT between January 2007 and December 2011 were retrospectively reviewed. The association of IT with loco-regional failure-free survival (LRFS), progression free survival (PFS) and overall survival (OS) was assessed by univariate and multivariate analysis...
November 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27904660/comparison-of-mri-ct-and-18f-fdg-pet-ct-in-the-diagnosis-of-local-and-metastatic-of-nasopharyngeal-carcinomas-an-updated-meta-analysis-of-clinical-studies
#12
Wang-Sheng Chen, Jian-Jun Li, Lan Hong, Zeng-Bao Xing, Fen Wang, Chang-Qing Li
BACKGROUND: A meta-analysis was conducted to evaluate the accuracy of MRI, CT and FDG PET/CT in TNM stage of nasopharyngeal carcinoma patients (NPC). METHODS: Through a search of studies from 1996 to April 2015, pooled estimated sensitivity, specificity, pooled diagnostic odds ratio (DOR), summary receiver operating characteristic (SROC) curves and Q*-index were calculated. RESULTS: Totally 23 studies were included for analysis. In T stage, the pooled sensitivity, specificity, DOR and SROC of MRI were 0...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27904451/the-ratio-of-weight-loss-to-planning-target-volume-significantly-impacts-setup-errors-in-nasopharyngeal-cancer-patients-undergoing-helical-tomotherapy-with-daily-megavoltage-computed-tomography
#13
Wei-Hsien Hou, Chun-Wei Wang, Chiao-Ling Tsai, Feng-Ming Hsu, Jason Chia-Hsien Cheng
BACKGROUND: Changes in head and neck anatomy during radiation therapy (RT) produce setup uncertainties of nasopharyngeal cancer (NPC) irradiation. We retrospectively analyzed image guidance data to identify clinical predictors of setup errors. PATIENTS AND METHODS: The data of 217 NPC patients undergoing definitive RT on a helical tomotherapy (HT) unit were analyzed. Factors including tumor stage, body mass index, weight loss, and planning target volume (PTV) were assessed as predictors of daily megavoltage computed tomography (MVCT) setup displacements, which were automatically registered using software...
December 1, 2016: Radiology and Oncology
https://www.readbyqxmd.com/read/27902765/loss-of-cathepsin-b-and-l-leads-to-lysosomal-dysfunction-npc-like-cholesterol-sequestration-and-accumulation-of-the-key-alzheimer-s-proteins
#14
Stjepko Cermak, Marko Kosicek, Aleksandra Mladenovic-Djordjevic, Kosara Smiljanic, Selma Kanazir, Silva Hecimovic
Proper function of lysosomes is particularly important in neurons, as they cannot dilute accumulated toxic molecules and aggregates by cell division. Thus, impairment of lysosomal function plays an important role in neuronal degeneration and in the pathogenesis of numerous neurodegenerative diseases. In this work we analyzed how inhibition and/or loss of the major lysosomal proteases, the cysteine cathepsins B and L (CtsB/L), affects lysosomal function, cholesterol metabolism and degradation of the key Alzheimer's disease (AD) proteins...
2016: PloS One
https://www.readbyqxmd.com/read/27902699/modeling-cellular-noise-underlying-heterogeneous-cell-responses-in-the-epidermal-growth-factor-signaling-pathway
#15
Kazunari Iwamoto, Yuki Shindo, Koichi Takahashi
Cellular heterogeneity, which plays an essential role in biological phenomena, such as drug resistance and migration, is considered to arise from intrinsic (i.e., reaction kinetics) and extrinsic (i.e., protein variability) noise in the cell. However, the mechanistic effects of these types of noise to determine the heterogeneity of signal responses have not been elucidated. Here, we report that the output of epidermal growth factor (EGF) signaling activity is modulated by cellular noise, particularly by extrinsic noise of particular signaling components in the pathway...
November 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27901642/a-generic-rna-pulsed-dc-based-approach-for-developing-therapeutic-intervention-against-nasopharyngeal-carcinoma
#16
Rajeev K Tyagi, Rajesh Parmar, Naisargee Patel
The recurrent nasopharyngeal carcinoma of head-and-neck cancers pathology showed unique symptoms and clinical characteristics. The complexity of pathology poses challenges for developing therapeutic interventional approaches against nasopharyngeal carcinoma (NPC). The conventional treatment regimens offer limited local control and survival, which, leads to adverse delayed complications. Our study present a generic monocyte derived dendritic cell (MoDC) vaccine strategy for NPC in which RNA is used as a source of tumor-associated antigens (TAAgs)...
November 30, 2016: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/27901109/coupling-template-nanocasting-and-self-activation-for-fabrication-of-nanoporous-carbon
#17
Lingjun Kong, Mingxiang Liu, Zenghui Diao, Diyun Chen, Xiangyang Chang, Ya Xiong
Hierarchical nanoporous carbon (NPC) with great surface area and developed pore size distribution has been intently concerned. Herein, we report a facile method coupling template nanocasting and self-activation to fabricate nanoporous carbon with continuous micro, meso and macro pores, in which CaCO3 acted as template and activation reagent while the flour was the carbon precursor. Effects of mass ratio of CaCO3 to flour and carbonized temperature on the pore structures of NPC were investigated by nitrogen adsorption-desorption isotherms and SEM analysis...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27900365/genome-sequencing-in-a-case-of-niemann-pick-type-c
#18
Max Dougherty, John Lazar, Jason C Klein, Karina Diaz, Theodore Gobillot, Eli Grunblatt, Nicholas Hasle, Daniel Lawrence, Megan Maurano, Maria Nelson, Gregory Olson, Sanjay Srivatsan, Jay Shendure, C Dirk Keene, Thomas Bird, Marshall S Horwitz, Desiree A Marshall
Adult-onset Niemann-Pick disease type C (NPC) is an infrequent presentation of a rare neurovisceral lysosomal lipid storage disorder caused by autosomal recessive mutations in NPC1 (∼95%) or NPC2 (∼5%). Our patient was diagnosed at age 33 when he presented with a 10-yr history of difficulties in judgment, concentration, speech, and coordination. A history of transient neonatal jaundice and splenomegaly with bone marrow biopsy suggesting a lipid storage disorder pointed to NPC; biochemical ("variant" level cholesterol esterification) and ultrastructural studies in adulthood confirmed the diagnosis...
November 2016: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/27900236/identification-of-two-sulfated-cholesterol-metabolites-found-in-the-urine-of-a-patient-with-niemann-pick-disease-type-c-as-novel-candidate-diagnostic-markers
#19
Masamitsu Maekawa, Kaoru Omura, Shoutaro Sekiguchi, Takashi Iida, Daisuke Saigusa, Hiroaki Yamaguchi, Nariyasu Mano
In the urine of a Niemann-Pick disease type C (NPC) patient, we have identified three characteristic intense peaks that have not been observed in the urine of a 3β-hydroxysteroid-Δ(5)-C27-steroid dehydrogenase deficiency patient or a healthy infant and adult. Based on accurate masses of the protonated molecules, we focused on two of them as candidate NPC diagnostic markers. Two synthesized authentic preparations agreed with the two compounds found in NPC patient urine in regard to both chromatographic behavior and accurate masses of the deprotonated molecules...
2016: Mass Spectrometry
https://www.readbyqxmd.com/read/27900042/antitumor-activity-of-7rh-a-discoidin-domain-receptor-1-inhibitor-alone-or-in-combination-with-dasatinib-exhibits-antitumor-effects-in-nasopharyngeal-carcinoma-cells
#20
Qiu-Ping Lu, Wen-Dan Chen, Jie-Ren Peng, Yao-Dong Xu, Qian Cai, Gong-Kan Feng, Ke Ding, Xiao-Feng Zhu, Zhong Guan
Dysregulation of the discoidin domain receptors (DDRs) has been implicated in the development of numerous types of tumors, including head and neck cancer, and nasopharyngeal, breast, ovarian and esophageal carcinomas. Furthermore, agents that inhibit DDR1 activity are hypothesized to be useful for the treatment of nasopharyngeal carcinoma (NPC). The aim of the present study was to evaluate the effect of the DDR1 inhibitory (3-(2-(pyrazolo(1,5-a)pyrimidin-6-yl)-ethynyl)benzamide compound, 7RH, in NPC cells both in vitro and in vivo, and its effect when used in combination with dasatinib, a SRC family kinase (SFK) inhibitor...
November 2016: Oncology Letters
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