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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/29050380/inflammasomes-in-neurological-diseases-emerging-pathogenic-and-therapeutic-concepts
#2
Manmeet K Mamik, Christopher Power
Inflammasome activation in the central nervous system occurs in both health and disease. Inflammasomes are cytosolic protein complexes that sense specific infectious or host stimuli and initiate inflammatory responses through caspase activation. Assembly of inflammasomes results in caspase-1-mediated proteolytic cleavage and release of the pro-inflammatory cytokines, interleukin-1β and interleukin-18, with initiation of pyroptosis, an inflammatory programmed cell death. Recent developments in the inflammasome field have uncovered novel molecular mechanisms that contribute to a broad range of neurological disorders including those associated with specific mutations in inflammasome genes as well as diseases modulated by inflammasome activation...
September 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29050364/lncrnas-key-players-and-novel-insights-into-diabetes-mellitus
#3
REVIEW
Xiaoyun He, Chunlin Ou, Yanhua Xiao, Qing Han, Hao Li, Suxian Zhou
Long non-coding RNAs (LncRNAs) are a class of endogenous RNA molecules, which have a transcribing length of over 200 nt, lack a complete functional open reading frame (ORF), and rarely encode a functional short peptide. Recent studies have revealed that disruption of LncRNAs levels correlates with several human diseases, including diabetes mellitus (DM), a complex multifactorial metabolic disorder affecting more than 400 million people worldwide. LncRNAs are emerging as pivotal regulators in various biological processes, in the progression of DM and its associated complications, involving pancreatic β-cell disorder, insulin resistance, and epigenetic regulation, etc...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050346/identification-of-candidate-genes-related-to-pancreatic-cancer-based-on-analysis-of-gene-co-expression-and-protein-protein-interaction-network
#4
Tiejun Zhang, Xiaojuan Wang, Zhenyu Yue
Pancreatic cancer (PC) is one of the most common causes of cancer mortality worldwide. As the genetic mechanism of this complex disease is not uncovered clearly, identification of related genes of PC is of great significance that could provide new insights into gene function as well as potential therapy targets. In this study, we performed an integrated network method to discover PC candidate genes based on known PC related genes. Utilizing the subnetwork extraction algorithm with gene co-expression profiles and protein-protein interaction data, we obtained the integrated network comprising of the known PC related genes (denoted as seed genes) and the putative genes (denoted as linker genes)...
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
#5
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/29050314/applicability-of-graded-prognostic-assessment-of-lung-cancer-using-molecular-markers-to-lung-adenocarcinoma-patients-with-brain-metastases
#6
Hongwei Li, Jianhong Lian, Songyan Han, Weili Wang, Haixia Jia, Jianzhong Cao, Xiaqin Zhang, Xin Song, Sufang Jia, Jiwei Ren, Weihua Yang, Yanfeng Xi, Shengmin Lan
Several scoring systems are available to estimate prognosis and assist in selecting treatment methods for non-small cell lung cancer (NSCLC) patients with brain metastasis, including recursive partitioning analysis (RPA), basic score for brain metastases (BS-BM), and diagnosis-specific graded prognostic assessment (DS-GPA). Lung-molGPA is an update of the DS-GPA that incorporates EGFR and/or ALK mutation status. The present study tested the applicability of these four indexes in 361 lung adenocarcinoma patients with brain metastasis...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050294/the-density-of-mast-cells-c-kit-and-tryptase-correlates-with-each-other-and-with-angiogenesis-in-pancreatic-cancer-patients
#7
Michele Ammendola, Cosmo Damiano Gadaleta, Adam Enver Frampton, Tullio Piardi, Riccardo Memeo, Valeria Zuccalà, Maria Luposella, Rosa Patruno, Nicola Zizzo, Pietro Gadaleta, Patrick Pessaux, Rosario Sacco, Giuseppe Sammarco, Girolamo Ranieri
Literature data suggest that inflammatory cells such as mast cells (MCs) are involved in angiogenesis. MCs can stimulate angiogenesis by releasing of well identified pro-angiogenic cytokines stored in their cytoplasm. In particular, MCs can release tryptase, a potent in vivo and in vitro pro-angiogenic factor. Nevertheless, few data are available concerning the role of MCs positive to tryptase in primary pancreatic cancer angiogenesis. This study analyzed the correlation between mast cells positive to c-Kit receptor (c-Kit(+) MCs), the density of MCs expressing tryptase (MCD-T) and microvascular density (MVD) in primary tumor tissue from patients affected by pancreatic ductal adenocarcinoma (PDAC)...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050292/foxk1-facilitates-cell-proliferation-through-regulating-the-expression-of-p21-and-promotes-metastasis-in-ovarian-cancer
#8
Li Li, Miao Gong, Yu Zhao, Xiujun Zhao, Quanhai Li
Ovarian cancer is one of the most common cancer in the world. FOX family plays essential function in multiple cancers. In our work, FOXK1 was found to up-regulate in ovarian cancer tissue samples and cell lines; moreover, the expression of FOXK1 was correlated with tumor size, metastasis and poorly prognosis. To evaluate the function of FOXK1 in ovarian cancer, we performed colony formation analysis, CCK-8 assay and cell cycle analysis to determine the effect of FOXK1 on cell proliferation and cell cycle. We found that FOXK1 obviously improved the ability of cell proliferation through promoting cell cycle...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050271/sesquiterpene-binding-gly-leu-ser-lys-co-adaptation-pocket-to-inhibit-lung-cancer-cell-epithelial-mesenchymal-transition
#9
Xiao-Yu Ai, Heng Zhang, Shao-Yan Gao, Yuan Qin, Wei-Long Zhong, Ju Gu, Meng Li, Kai-Liang Qiao, Qin Tian, Zhan-Hong Cui, Jia-Huan Yang, Zhun Bi, Ting Xiao, Shuang Chen, Hui-Juan Liu, Hong-Gang Zhou, Tao Sun, Cheng Yang
Sesquiterpene lactones (SL) have a wide range of applications in anti-tumor and anti-inflammatory therapy. However, the pharmacological mechanism of such substances is not clear. In this study, parthenolide (PTL) was used as an example to explore the anti-tumor effect of natural molecules and their common mechanism. We showed that PTL inhibited the proliferation and migration by reverse EMT via the ERK2/NF-κB/Snail pathway in vivo and in vitro. Interestingly, Multiple potential targets of PTL contain a Gly-Leu-Ser/Lys-"co-adaptation pocket"...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050270/kit-performed-as-a-driver-gene-candidate-affecting-the-survival-status-of-patients-with-stomach-adenocarcinoma
#10
Shengli Pan, Jin Tan, Yingying Deng, Ben-Hai Wan, Xiao-Yu Zhang, Bu-Gao Guan
Stomach adenocarcinoma is estimated to cause 10,000 deaths in the US in 2016 and is the third most deadly cancer in China. We aim to identify the proteins and the genes that have impact on the prognosis of patients with stomach adenocarcinoma. Data of patients with stomach adenocarcinoma were retrieved from The Cancer Genome Atlas (TCGA). Proteins whose expression levels were highly correlated with survival status of patients were figured out. The expression levels of their mRNAs and their roles in the pathway were used to determine the driver gene candidates...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050249/profiling-cancer-associated-genetic-alterations-and-molecular-classification-of-cancer-in-korean-gastric-cancer-patients
#11
Yoonjung Kim, Mee-Yon Cho, Juwon Kim, Sung Nam Kim, Seoung Chul Oh, Kyung-A Lee
Recently, the Cancer Genome Atlas (TCGA) Research Network and Asian Cancer Research Group provided a new classification of gastric cancer (GC) to aid the development of biomarkers for targeted therapy and predict prognosis. We studied associations between genetically aberrant profiles of cancer-related genes, environmental factors, and histopathological features in 107 paired gastric tumor-non-tumor tissue GC samples. 6.5% of our GC cases were classified as the EBV subtype, 17.8% as the MSI subtype, 43.0% as the CIN subtype, and 32...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050243/cancer-specific-evaluation-system-canes-a-high-accuracy-platform-for-preclinical-single-multi-biomarker-discovery
#12
Min-Seok Kwon, Seungyoon Nam, Sungyoung Lee, Young Zoo Ahn, Hae Ryung Chang, Yon Hui Kim, Taesung Park
The recent creation of enormous, cancer-related "Big Data" public depositories represents a powerful means for understanding tumorigenesis. However, a consistently accurate system for clinically evaluating single/multi-biomarkers remains lacking, and it has been asserted that oft-failed clinical advancement of biomarkers occurs within the very early stages of biomarker assessment. To address these challenges, we developed a clinically testable, web-based tool, CANcer-specific single/multi-biomarker Evaluation System (CANES), to evaluate biomarker effectiveness, across 2,134 whole transcriptome datasets, from 94,147 biological samples (from 18 tumor types)...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050241/combination-treatment-with-rucaparib-rubraca-and-mdm2-inhibitors-nutlin-3-and-rg7388-has-synergistic-and-dose-reduction-potential-in-ovarian-cancer
#13
Maryam Zanjirband, Nicola Curtin, Richard J Edmondson, John Lunec
Ovarian cancer is the seventh most common cancer worldwide for females and the most lethal of all gynecological malignancies. The treatment of ovarian cancer remains a challenge in spite of advances in debulking surgery and changes in both chemotherapy schedules and routes of administration. Cancer treatment has recently been improving with the introduction of targeted therapies to achieve greater specificity and less cytotoxicity. Both PARP inhibitors and MDM2-p53 binding antagonists are targeted therapeutic agents entered into clinical trials...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050223/mir-23a-promotes-tgf-%C3%AE-1-induced-emt-and-tumor-metastasis-in-breast-cancer-cells-by-directly-targeting-cdh1-and-activating-wnt-%C3%AE-catenin-signaling
#14
Fei Ma, Wenjie Li, Chunxiao Liu, Wei Li, Haining Yu, Bo Lei, Yanlv Ren, Zhigao Li, Da Pang, Cheng Qian
TGF-β1-induced epithelial-mesenchymal transition (EMT) has been proved to be associated with metastasis of breast cancer cells. We attempted to detect a novel mechanism that microRNAs mediated the TGF-β1-induced EMT in the process of breast cancer metastasis. Here we reported that the expression of miR-23a was higher in breast cancer cells with high metastasis ability and patients with lymph node metastasis and the treatment of TGF-β1 significantly upregulated the expression of miR-23a in breast cancer cells...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050204/irreversible-growth-plate-fusions-in-children-with-medulloblastoma-treated-with-a-targeted-hedgehog-pathway-inhibitor
#15
Giles W Robinson, Sue C Kaste, Wassim Chemaitilly, Daniel C Bowers, Stephen Laughton, Amy Smith, Nicholas G Gottardo, Sonia Partap, Anne Bendel, Karen D Wright, Brent A Orr, William C Warner, Arzu Onar-Thomas, Amar Gajjar
The permanent defects in bone growth observed in preclinical studies of hedgehog (Hh) pathway inhibitors were not substantiated in early phase clinical studies of vismodegib in children. Consequently, vismodegib advanced into pediatric trials for malignancies suspected of being driven by aberrant activation of the Hh pathway. In one multicenter phase II trial, vismodegib was added to the therapy regimen for newly diagnosed Hh pathway activated medulloblastoma. Herein, we report on 3 children (2 on trial and one off trial) treated with vismodegib who developed widespread growth plate fusions that persist long after cessation of therapy...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050198/mtorc1-autophagy-regulated-mertk-in-mutant-brafv600-melanoma-with-acquired-resistance-to-braf-inhibition
#16
Gongda Xue, Reto Kohler, Fengyuan Tang, Debby Hynx, Yuhua Wang, Francesca Orso, Vincent Prêtre, Reto Ritschard, Petra Hirschmann, Peter Cron, Tim Roloff, Reinhard Dummer, Mario Mandalà, Sandrine Bichet, Christel Genoud, Alexandra G Meyer, Manuele G Muraro, Giulio C Spagnoli, Daniela Taverna, Curzio Rüegg, Taha Merghoub, Daniela Massi, Huifang Tang, Mitchell P Levesque, Stephan Dirnhofer, Alfred Zippelius, Brian A Hemmings, Andreas Wicki
BRAF inhibitors (BRAFi) and the combination therapy of BRAF and MEK inhibitors (MEKi) were recently approved for therapy of metastatic melanomas harbouring the oncogenic BRAFV600 mutation. Although these therapies have shown pronounced therapeutic efficacy, the limited durability of the response indicates an acquired drug resistance that still remains mechanistically poorly understood at the molecular level. We conducted transcriptome gene profiling in BRAFi-treated melanoma cells and identified that Mer tyrosine kinase (MerTK) is specifically upregulated...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29049902/emotion-dysregulation-moderates-the-effect-of-cognitive-behavior-therapy-with-prolonged-exposure-for-co-occurring-ptsd-and-substance-use-disorders
#17
Denise A Hien, Teresa Lopez-Castro, Santiago Papini, Bernard Gorman, Lesia M Ruglass
A goal of clinical trials is to identify unique baseline characteristics that can inform treatment planning. One such target is emotion dysregulation (ED), which contributes to the maintenance of co-occurring posttraumatic stress disorder (PTSD) and substance use disorder (SUD) and may be a potential moderator of treatment response. We examined the moderating impact of ED severity on treatment outcomes in an urban, socioeconomically disadvantaged, and racially/ethnically diverse sample with complex trauma and severe SUDs...
October 16, 2017: Journal of Anxiety Disorders
https://www.readbyqxmd.com/read/29049847/neurofibromatosis-type-1-and-optic-pathway-glioma-molecular-interplay-and-therapeutic-insights
#18
REVIEW
Soumen Khatua, David H Gutmann, Roger J Packer
Children with neurofibromatosis type 1 (NF1) are predisposed to develop central nervous system neoplasms, the most common of which are low-grade gliomas (LGGs). The absence of human NF1 associated LGG-derived cell lines, coupled with an inability to generate patient-derived xenograft models, represents barriers to profile molecularly targeted therapies for these tumors. Thus, genetically engineered mouse models have been identified to evaluate the interplay between Nf1-deficient tumor cells and nonneoplastic stromal cells to evaluate potential therapies for these neoplasms...
October 19, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29049843/metabolic-strategies-of-melanoma-cells-mechanisms-interactions-with-the-tumor-microenvironment-and-therapeutic-implications
#19
REVIEW
Grant M Fischer, Y N Vashisht Gopal, Jennifer L McQuade, Weiyi Peng, Ralph J DeBerardinis, Michael A Davies
Melanomas are metabolically heterogeneous, and they are able to adapt in order to utilize a variety of fuels that facilitate tumor progression and metastasis. The significance of metabolism in melanoma is supported by growing evidence of impact on the efficacy of contemporary therapies for this disease. There is also data to support that the metabolic phenotypes of melanoma cells depend upon contributions from both intrinsic oncogenic pathways and extrinsic factors in the tumor microenvironment. This review summarizes current understanding of the metabolic processes that promote cutaneous melanoma tumorigenesis and progression, the regulation of cancer cell metabolism by the tumor microenvironment, and the impact of metabolic pathways on targeted and immune therapies...
October 19, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29049738/a-genome-wide-scan-for-microrna-related-genetic-variants-associated-with-primary-open-angle-glaucoma
#20
Mohsen Ghanbari, Adriana I Iglesias, Henriët Springelkamp, Cornelia M van Duijn, M Arfan Ikram, Abbas Dehghan, Stefan J Erkeland, Caroline C W Klaver, Magda A Meester-Smoor
Purpose: To identify microRNAs (miRNAs) involved in primary open-angle glaucoma (POAG), using genetic data. MiRNAs are small noncoding RNAs that posttranscriptionally regulate gene expression. Genetic variants in miRNAs or miRNA-binding sites within gene 3'-untranslated regions (3'UTRs) are expected to affect miRNA function and contribute to disease risk. Methods: Data from the recent genome-wide association studies on intraocular pressure, vertical cup-to-disc ratio (VCDR), cupa area and disc area were used to investigate the association of miRNAs with POAG endophenotypes...
October 1, 2017: Investigative Ophthalmology & Visual Science
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