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https://www.readbyqxmd.com/read/29050400/metformin-reverses-trap1-mutation-associated-alterations-in-mitochondrial-function-in-parkinson-s-disease
#1
Julia C Fitzgerald, Alexander Zimprich, Daniel A Carvajal Berrio, Kevin M Schindler, Brigitte Maurer, Claudia Schulte, Christine Bus, Anne-Kathrin Hauser, Manuela Kübler, Rahel Lewin, Dheeraj Reddy Bobbili, Lisa M Schwarz, Evangelia Vartholomaiou, Kathrin Brockmann, Richard Wüst, Johannes Madlung, Alfred Nordheim, Olaf Riess, L Miguel Martins, Enrico Glaab, Patrick May, Katja Schenke-Layland, Didier Picard, Manu Sharma, Thomas Gasser, Rejko Krüger
The mitochondrial proteins TRAP1 and HTRA2 have previously been shown to be phosphorylated in the presence of the Parkinson's disease kinase PINK1 but the downstream signalling is unknown. HTRA2 and PINK1 loss of function causes parkinsonism in humans and animals. Here, we identified TRAP1 as an interactor of HTRA2 using an unbiased mass spectrometry approach. In our human cell models, TRAP1 overexpression is protective, rescuing HTRA2 and PINK1-associated mitochondrial dysfunction and suggesting that TRAP1 acts downstream of HTRA2 and PINK1...
September 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29050399/diagnostic-criteria-for-chronic-lymphocytic-inflammation-with-pontine-perivascular-enhancement-responsive-to-steroids-clippers
#2
W Oliver Tobin, Yong Guo, Karl N Krecke, Joseph E Parisi, Claudia F Lucchinetti, Sean J Pittock, Jay Mandrekar, Divyanshu Dubey, Jan Debruyne, B Mark Keegan
Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a central nervous system inflammatory syndrome predominantly affecting the brainstem, cerebellum, and spinal cord. Following its initial description, the salient features of CLIPPERS have been confirmed and expanded upon, but the lack of formalized diagnostic criteria has led to reports of patients with dissimilar features purported to have CLIPPERS. We evaluated clinical, radiological and pathological features of patients referred for suspected CLIPPERS and propose diagnostic criteria to discriminate CLIPPERS from non-CLIPPERS aetiologies...
September 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29050387/temporal-lobe-networks-supporting-the-comprehension-of-spoken-words
#3
Leonardo Bonilha, Argye E Hillis, Gregory Hickok, Dirk B den Ouden, Chris Rorden, Julius Fridriksson
Auditory word comprehension is a cognitive process that involves the transformation of auditory signals into abstract concepts. Traditional lesion-based studies of stroke survivors with aphasia have suggested that neocortical regions adjacent to auditory cortex are primarily responsible for word comprehension. However, recent primary progressive aphasia and normal neurophysiological studies have challenged this concept, suggesting that the left temporal pole is crucial for word comprehension. Due to its vasculature, the temporal pole is not commonly completely lesioned in stroke survivors and this heterogeneity may have prevented its identification in lesion-based studies of auditory comprehension...
September 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29050366/the-resistance-mechanisms-and-treatment-strategies-for-egfr-mutant-advanced-non-small-cell-lung-cancer
#4
REVIEW
Wen-Zhao Zhong, Qing Zhou, Yi-Long Wu
Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) have been established as the standard therapy for EGFR-sensitizing mutant advanced non-small-cell lung cancer (NSCLC). However, patients ultimately develop resistance to these drugs. There are several mechanisms of both primary and secondary resistance to EGFR-TKIs. The primary resistance mechanisms include point mutations in exon 18, deletions or insertions in exon 19, insertions, duplications and point mutations in exon 20 and point mutation in exon 21 of EGFR gene...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050361/bet-inhibitors-as-novel-therapeutic-agents-in-breast-cancer
#5
REVIEW
Alberto Ocaña, Cristina Nieto-Jiménez, Atanasio Pandiella
Tumoral cells not only depend on oncogenic abnormalities to maintain its malignant phenotype but on non-oncogenic vulnerabilities. Targeting epigenomics can modify specific cellular functions required for malignant transformation. The Bromodomain (BRD) family mediates their effect by recruiting proteins of the transcription machinery, recognizing acetylated-lysine residues in nucleosomal histones. Bromodomain and extra-terminal (BET) inhibitors have shown to produce growth inhibition in several tumors through the inhibition of the expression of several transcription factors...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050360/immunomodulatory-and-antitumor-effects-of-type-i-interferons-and-their-application-in-cancer-therapy
#6
REVIEW
Ruan F V Medrano, Aline Hunger, Samir Andrade Mendonça, José Alexandre M Barbuto, Bryan E Strauss
During the last decades, the pleiotropic antitumor functions exerted by type I interferons (IFNs) have become universally acknowledged, especially their role in mediating interactions between the tumor and the immune system. Indeed, type I IFNs are now appreciated as a critical component of dendritic cell (DC) driven T cell responses to cancer. Here we focus on IFN-α and IFN-β, and their antitumor effects, impact on immune responses and their use as therapeutic agents. IFN-α/β share many properties, including activation of the JAK-STAT signaling pathway and induction of a variety of cellular phenotypes...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050357/oncomir-17-5p-alarm-signal-in-cancer
#7
REVIEW
Madhusudhan Reddy Bobbili, Robert M Mader, Johannes Grillari, Hanna Dellago
Soon after microRNAs entered the stage as novel regulators of gene expression, they were found to regulate -and to be regulated by- the development, progression and aggressiveness of virtually all human types of cancer. Therefore, miRNAs in general harbor a huge potential as diagnostic and prognostic markers as well as potential therapeutic targets in cancer. The miR-17-92 cluster was found to be overexpressed in many human cancers and to promote unrestrained cell growth, and has therefore been termed onco-miR-1...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050345/differential-diagnosis-of-hemangiomas-from-spinal-osteolytic-metastases-using-3-0-t-mri-comparison-of-t1-weighted-imaging-chemical-shift-imaging-diffusion-weighted-and-contrast-enhanced-imaging
#8
Yan-Jie Shi, Xiao-Ting Li, Xiao-Yan Zhang, Yu-Liang Liu, Lei Tang, Ying-Shi Sun
The retrospective study investigated accuracy of quantitative evaluation of T1-weighted imaging (T1WI) with and without fat suppression (FS), chemical-shift, diffusion-weighted imaging (DWI) and enhanced imaging at 3.0 T MRI for distinguishing spinal hemangiomas from metastases. 27 patients with 33 spinal hemangiomas (15 atypical hemangiomas) and 26 patients with 71 metastases were recruited. T1WI, FS T1WI, in- and out-phase, DWI and enhanced T1WI were acquired. Signal intensities (SIs) of lesions were obtained...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050344/microrna-141-3p-promotes-glioma-cell-growth-and-temozolomide-resistance-by-directly-targeting-p53
#9
Xu Zhou, Weining Wu, Ailiang Zeng, Er Nie, Xin Jin, Tianfu Yu, Tongle Zhi, Kuan Jiang, Yingyi Wang, Junxia Zhang, Yongping You
Glioblastoma multiforme is the most common primary malignancy in the brain and confers a uniformly poor prognosis. MicroRNAs have been shown to activate or inhibit tumorigenesis. Abnormalities in the p53 signaling pathway are found in various cancers and correlate with tumor formation. We examined the expression of microRNA-141-3p (miR-141-3p) in glioma of different grades by analysis of expression profiling databases and clinical specimens. Cell proliferation and flow cytometry assays were performed to evaluate the promotion of miR-141-3p in proliferation, cell cycle, apoptosis, and temozolomide resistance of glioblastoma cells in vitro...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050341/geraniol-alleviates-lps-induced-acute-lung-injury-in-mice-via-inhibiting-inflammation-and-apoptosis
#10
Kangfeng Jiang, Tao Zhang, Nannan Yin, Xiaofei Ma, Gan Zhao, Haichong Wu, Changwei Qiu, Ganzhen Deng
Geraniol (GOH), a special type of acyclic monoterpene alcohol, has been widely used to treat many diseases associated with inflammation and apoptosis. Acute lung injury (ALI) is a common clinical disease in humans characterized by pulmonary inflammation and apoptosis. In the present study, we investigated the protective effects of GOH in a mouse model of ALI induced by the intranasal administration of lipopolysaccharide (LPS) and elucidated the underlying molecular mechanisms in RAW 264.7 cells. In vivo, GOH treatment markedly ameliorated pathological injury and pulmonary cell apoptosis and reduced the wet/dry (W/D) weight ratio of lungs, myeloperoxidase (MPO) activity and the production of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α)...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050339/aberrant-expression-of-oatp1b3-in-colorectal-cancer-liver-metastases-and-its-clinical-implication-on-gadoxetic-acid-enhanced-mri
#11
Seung Hyun Park, Honsoul Kim, Eun Kyung Kim, Hogeun Kim, Dong Kyu Choi, Yong Eun Chung, Myeong-Jin Kim, Jin-Young Choi
PURPOSE: To investigate the factors associated with hepatobiliary phase (HBP) enhancement at gadoxetic acid-enhanced magnetic resonance imaging (MRI) and to determine whether HBP images could be used to predict prognosis in patients with colorectal cancer liver metastasis (CRLM). RESULTS: Of the 96 total nodules, 65 and 31 nodules were in the mixed and clearly hypointense groups, respectively. In the 55 nodules without preoperative chemotherapy, organic anionic transporting polypeptide 1B3 (OATP1B3) expression was a significant factor regarding the HBP enhancement (P=0...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050337/comprehensive-immune-transcriptomic-analysis-in-bladder-cancer-reveals-subtype-specific-immune-gene-expression-patterns-of-prognostic-relevance
#12
Runhan Ren, Kathrin Tyryshkin, Charles H Graham, Madhuri Koti, D Robert Siemens
Recent efforts on genome wide profiling of muscle invasive bladder cancer (MIBC) have led to its classification into distinct genomic and transcriptomic molecular subtypes that exhibit variability in prognosis. Evolving evidence from recent immunotherapy trials has demonstrated the significance of pre-existing tumour immune profiles that could guide treatment decisions. To identify immune gene expression patterns associated with the molecular subtypes, we performed a comprehensive in silico immune transcriptomic profiling, utilizing transcriptomic data from 347 MIBC cases from The Cancer Genome Atlas (TCGA)...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050326/different-effection-of-p-1125val-ala-and-rs11954856-in-apc-on-wnt-signaling-pathway
#13
Fei-Feng Li, Zhi-Xun Zhao, Peng Yan, Song Wang, Zheng Liu, Qiong Zhang, Xiao-Ning Zhang, Chang-Hao Sun, Xi-Shan Wang, Gui-Yu Wang, Shu-Lin Liu
Colorectal cancer (CRC) is among the most common and fatal forms of solid tumors worldwide and more than two thirds of CRC and adenomas patients have APC gene mutations. APC is a key regulator in the Wnt/β-catenin signaling pathway but its roles in CRC remains to be elucidated. In this study, we compared APC genes between CRC patients and controls to determine possible associations of nucleotide changes in the APC gene with the pathways involved in CRC pathogenesis. All participants received physical and enteroscopic examinations...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050323/histone-deacetylase-inhibitor-thailandepsin-a-activates-notch-signaling-and-suppresses-neuroendocrine-cancer-cell-growth-in-vivo
#14
Samuel Jang, Andrew Janssen, Zviadi Aburjania, Matthew B Robers, April Harrison, Ajitha Dammalapati, Yi-Qiang Cheng, Herbert Chen, Renata Jaskula-Sztul
Novel therapies for neuroendocrine (NE) cancers are desperately needed as they frequently present as metastatic disease and cause debilitating symptoms by secreting excessive hormones. Induction of Notch isoforms has a tumor suppressive effect in NE cancer cell lines, and we have observed that histone deacetylase inhibitors (HDACi) potently activate Notch. In this study, we describe the potential for Burkholderia thailandensis-derived class I HDACi thailandepsin A (TDP-A) as a Notch activator and therapeutic agent against NE cancer...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050317/microrna-542-3p-inhibits-oral-squamous-cell-carcinoma-progression-by-inhibiting-ilk-tgf-%C3%AE-1-smad2-3-signaling
#15
Bin Qiao, Jing-Hua Cai, Alfred King-Yin Lam, Bao-Xia He
In this study, we investigated the effects of microRNA-542-3p (miR-542-3p) on ILK/TGF-β1/Smad2/3 signaling and oral squamous cell carcinoma (OSCC) progression. Levels of miR-542-3p were lower in OSCC tissues (n=108) than adjacent normal tissues, whereas levels of ILK, TGF-β1 and Smad2/3 were higher. Patients with undifferentiated tumors, advanced TNM stage and lymph node metastasis showed low miR-542-3p levels. This was accompanied by high ILK expression and poor survival. Dual luciferase reporter assays of SCC-9 cells showed that miR-542-3p inhibited ILK gene expression by binding to its 3'UTR at 233-240 bp...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050312/non-alcoholic-steatohepatitis-related-liver-tumorigenesis-is-suppressed-in-mice-lacking-hepatic-retinoid-storage
#16
Takayasu Ideta, Yohei Shirakami, Masaya Ohnishi, Akinori Maruta, Koki Obara, Tsuneyuki Miyazaki, Takahiro Kochi, Hiroyasu Sakai, Hiroyuki Tomita, Takuji Tanaka, William S Blaner, Masahito Shimizu
Non-alcoholic fatty liver disease has become one of the most common causes of chronic liver disease that can develop into a more serious form, non-alcoholic steatohepatitis, leading to liver cirrhosis and hepatocellular carcinoma. Although hepatic retinoid stores are progressively lost during the development of liver disease, how this affects steatohepatitis and its related hepatocarcinogenesis is unknown. In order to investigate these, we used subcutaneous injection of streptozotocin (0.2 mg/body) and high-fat diet to induce steatohepatitis and hepatic tumorigenesis in lecithin:retinol acyltransferase -deficient mice (n = 10), which lack stored retinoid in the liver, and control mice (n = 12)...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050311/tmem17-depresses-invasion-and-metastasis-in-lung-cancer-cells-via-erk-signaling-pathway
#17
Xiupeng Zhang, Yong Zhang, Yuan Miao, Haijing Zhou, Guiyang Jiang, Enhua Wang
Transmembrane protein 17(TMEM17) is a newly identified protein, its expression pattern and clinicopathological relevance is still unclear. In this study, western blot assay was performed in 20 paired lung cancer samples and found that TMEM17 protein levels were lower in lung cancer tissues than that in the corresponding normal lung tissues (p=0.010). Immunohistochemistry staining in 143 cases lung cancer specimens also showed that TMEM17 expression in lung cancer tissues were significantly lower than adjacent normal lung tissues (35...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050309/fibronectin-in-cell-adhesion-and-migration-via-n-glycosylation
#18
Cheng-Te Hsiao, Hung-Wei Cheng, Chi-Ming Huang, Hao-Ru Li, Meng-Hsin Ou, Jie-Rong Huang, Kay-Hooi Khoo, Helen Wenshin Yu, Yin-Quan Chen, Yang-Kao Wang, Arthur Chiou, Jean-Cheng Kuo
Directed cell migration is an important step in effective wound healing and requires the dynamic control of the formation of cell-extracellular matrix interactions. Plasma fibronectin is an extracellular matrix glycoprotein present in blood plasma that plays crucial roles in modulating cellular adhesion and migration and thereby helping to mediate all steps of wound healing. In order to seek safe sources of plasma fibronectin for its practical use in wound dressing, we isolated fibronectin from human (homo) and porcine plasma and demonstrated that both have a similar ability as a suitable substrate for the stimulation of cell adhesion and for directing cell migration...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050300/tfcp2-activates-beta-catenin-tcf-signaling-in-the-progression-of-pancreatic-cancer
#19
Dai Yuedi, Cai Yuankun, Zhao Jiaying, Liu Han, Wang Yueqi, Liu Houbao, Zhang Dexiang
Aberrant activation of beta-catenin/TCF (T-cell factor) signaling is frequently observed in the pancreatic cancer. However, the regulation of nuclear beta-catenin/TCF transcription machinery remains largely unknown. In this study, TFCP2 (transcriptional factor CP2) expression in pancreatic cancer was detected by qPCR, immunohistochemistry and western blot. Western blot, colony formation assay, migration and invasion experiment were performed to investigate the effects of TFCP2 on the growth and migration of pancreatic cancer cells...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050298/overexpression-of-col3a1-confers-a-poor-prognosis-in-human-bladder-cancer-identified-by-co-expression-analysis
#20
Lushun Yuan, Bo Shu, Liang Chen, Kaiyu Qian, Yongzhi Wang, Guofeng Qian, Yuan Zhu, Xinyue Cao, Conghua Xie, Yu Xiao, Xinghuan Wang
Human bladder cancer (BCa) is one of the worldwide cancers in men and women populations, with the etiology and mechanism unknown. In our study, we constructed a weighted gene co-expression network to identify gene modules associated with the progression of BCa (n = 93). In the significant module (R(2) = 0.48), a total of 103 network hub genes were identified, and 4 of them were hub nodes in the protein-protein interaction network as well. In validation, COL3A1 showed a higher correlation with the disease progression than any other hub genes in hub module in the test set (p < 0...
September 19, 2017: Oncotarget
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