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https://www.readbyqxmd.com/read/29149532/exploitation-of-micrornas-by-japanese-encephalitis-virus-in-human-microglial-cells
#1
Meghana Rastogi, Neha Srivastava, Sunit K Singh
JEV infection in CNS leads to the JE neuroinflammation. Children and old age individual have been reported to be more prone to JEV infection. MicroRNAs are endogenous, small non-coding RNAs, which regulate the gene expression. These are ∼22 nucleotide long, conserved RNA sequence that binds at the 3'UTR of a target mRNA and regulate the post-transcriptional gene expression. The role of microRNAs has been reported in several diseases like cancer, viral infection, neuro-degeneration, diabetes etc. In the present study, the human microglial cells were infected with JEV (JaOAr strain)...
November 17, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/29149104/cumulative-incidence-rates-for-cns-and-non-cns-progression-in-two-phase-ii-studies-of-alectinib-in-alk-positive-nsclc
#2
Shirish Gadgeel, Alice T Shaw, Fabrice Barlesi, Lucio Crinò, James Chih-Hsin Yang, Anne-Marie C Dingemans, Dong-Wan Kim, Filippo de Marinis, Mathias Schulz, Shiyao Liu, Ravindra Gupta, Ahmed Kotb, Sai-Hong Ignatius Ou
BACKGROUND: We evaluated the cumulative incidence rate (CIR) of central nervous system (CNS) and non-CNS progression in alectinib-treated patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) to determine the extent to which alectinib may treat or control CNS disease. METHODS: Patients with crizotinib-pretreated locally advanced or metastatic disease received alectinib 600 mg orally twice daily in two phase II trials. All patients underwent baseline imaging and regular centrally reviewed scans...
November 16, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29145972/cancer-immunotherapy-getting-brainy-visualizing-the-distinctive-cns-metastatic-niche-to-illuminate-therapeutic-resistance
#3
Mark Owyong, Niloufar Hosseini-Nassab, Gizem Efe, Alexander Honkala, Renske J E van den Bijgaart, Vicki Plaks, Bryan Ronain Smith
The advent of cancer immunotherapy (CIT) and its success in treating primary and metastatic cancer may offer substantially improved outcomes for patients. Despite recent advancements, many malignancies remain resistant to CIT, among which are brain metastases, a particularly virulent disease with no apparent cure. The immunologically unique niche of the brain has prompted compelling new questions in immuno-oncology such as the effects of tissue-specific differences in immune response, heterogeneity between primary tumors and distant metastases, and the role of spatiotemporal dynamics in shaping an effective anti-tumor immune response...
November 2017: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/29134510/drug-design-for-alk-positive-nsclc-an-integrated-pharmacophore-based-3d-qsar-and-virtual-screening-strategy
#4
Nivya James, V Shanthi, K Ramanathan
The increasing death rates related to anaplastic lymphoma kinase (ALK)-positive lung cancer culminated in a significant interest in the discovery of novel inhibitors for ALK. In the present research work, pharmacophore-based 3D QSAR modeling and virtual screening strategy have been carried out to address these issues. Initially, a five-point pharmacophore model was developed using the biological data of 50 compounds which includes an FDA-approved ALK inhibitor, crizotinib. Using the generated pharmacophore, a 3D QSAR model was developed and used as a query to screen the DrugBank database...
November 13, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/29132872/an-nrg-oncology-gog-study-of-molecular-classification-for-risk-prediction-in-endometrioid-endometrial-cancer
#5
Casey M Cosgrove, David L Tritchler, David E Cohn, David G Mutch, Craig M Rush, Heather A Lankes, William T Creasman, David S Miller, Nilsa C Ramirez, Melissa A Geller, Matthew A Powell, Floor J Backes, Lisa M Landrum, Cynthia Timmers, Adrian A Suarez, Richard J Zaino, Michael L Pearl, Paul A DiSilvestro, Shashikant B Lele, Paul J Goodfellow
OBJECTIVES: The purpose of this study was to assess the prognostic significance of a simplified, clinically accessible classification system for endometrioid endometrial cancers combining Lynch syndrome screening and molecular risk stratification. METHODS: Tumors from NRG/GOG GOG210 were evaluated for mismatch repair defects (MSI, MMR IHC, and MLH1 methylation), POLE mutations, and loss of heterozygosity. TP53 was evaluated in a subset of cases. Tumors were assigned to four molecular classes...
November 10, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/29129392/targeting-obesity-and-cachexia-identification-of-the-gfral-receptor-mic-1-gdf15-pathway
#6
Samuel N Breit, Vicky Wang-Wei Tsai, David A Brown
Macrophage inhibitory cytokine-1/growth differentiation factor 15 (MIC-1/GDF15) is a divergent transforming growth factor (TGFβ) superfamily cytokine implicated in biological and disease processes including metabolism, cancer, and chronic inflammation, but whose receptor has remained elusive. Four laboratories have recently identified GFRAL, an orphan receptor of the glial-derived neurotrophic factor (GDNF) receptor α family, as the receptor for MIC-1/GDF15, signaling though the coreceptor Ret. These data identify a new systemic to central nervous system (CNS) circuit that regulates metabolism in response to stress and which could be targeted to treat both severe obesity and anorexia/cachexia syndrome...
November 9, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29116209/preoperative-n-terminal-pro-b-type-natriuretic-peptide-concertation-and-prognosis-of-brain-tumor-patients-a-5-year-follow-up-study
#7
Adomas Bunevicius, Vytenis Deltuva, Edward R Laws, Giorgio Iervasi, Arimantas Tamsauskas, Robertas Bunevicius
Increased N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration predicts poor prognosis of non-CNS cancer patients. We evaluated the association of NT-proBNP concentration with disease severity, discharge outcomes and prognosis of patients undergoing craniotomy for brain tumor. From January, 2010 until September, 2011 two-hundred and forty-five patients (age 55.05 ± 14.62 years) admitted for brain tumor surgery were evaluated for NT-proBNP serum concentration. Outcome at hospital discharge was evaluated with the Glasgow Outcome Scale (GOS)...
November 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29113950/reviewing-recist-in-the-era-of-prolonged-and-targeted-therapy
#8
REVIEW
Rustain L Morgan, D Ross Camidge
Accurate assessment of disease response is the foundation of therapeutic trails, which is why the Response Evaluation Criteria in Solid Tumors (RECIST) criteria serves as an international standard investigators can utilize when examining patient outcomes. Nine years after the initial RECIST criteria were released, an update, RECIST 1.1, was published to improve on initial criteria and address technologic advancements in imaging. Since then advancements in both standard clinical and trial practices, combined with improvements in our understanding of cancer biology have resulted in the identification of a number of limitations of the current RECIST 1...
November 4, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29110845/an-international-epidemiological-analysis-of-young-patients-with-non-small-cell-lung-cancer-adujov-clicap
#9
Luis Corrales-Rodríguez, Oscar Arrieta, Luis Mas, Renata Báez-Saldaña, Omar Castillo-Fernández, Normand Blais, Claudio Martín, Melissa Juárez, Priyanka Khanna, Allan Ramos-Esquivel, Ludwing Bacon, Leonardo Rojas, Beatriz Wills, George Oblitas, María Angelina Pérez, Mauricio Cuello, Andrés Felipe Cardona
BACKGROUND: A proportion of patients with NSCLC is diagnosed at 40 years or younger. These patients tend to be never-smokers, usually present with stage IV adenocarcinoma, and have somatic genomic alterations. Few studies have documented and analyzed epidemiological characteristics of this population. MATERIALS AND METHODS: We performed an international epidemiological analysis of 389 young patients with NSCLC. Data was collected from centers participating in the Latin American Consortium for Lung Cancer Research (AduJov-CLICaP)...
November 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29110768/cerebrospinal-fluid-biomarkers-of-malignancies-located-in-the-central-nervous-system
#10
Cassandra Verheul, Anne Kleijn, Martine L M Lamfers
CNS malignancies include primary tumors that originate within the CNS as well as secondary tumors that develop as a result of metastatic cancer. The delicate nature of the nervous systems makes tumors located in the CNS notoriously difficult to reach, which poses several problems during diagnosis and treatment. CSF can be acquired relatively easy through lumbar puncture and offers an important compartment for analysis of cells and molecules that carry information about the malignant process. Such techniques have opened up a new field of research focused on the identification of specific biomarkers for several types of CNS malignancies, which may help in diagnosis and monitoring of tumor progression or treatment response...
2017: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/29104289/inflammatory-cns-disease-caused-by-immune-checkpoint-inhibitors-status-and-perspectives
#11
REVIEW
Lidia M Yshii, Reinhard Hohlfeld, Roland S Liblau
Cancer treatment strategies based on immune stimulation have recently entered the clinical arena, with unprecedented success. Immune checkpoint inhibitors (ICIs) work by indiscriminately promoting immune responses, which target tumour-associated antigens or tumour-specific mutations. However, the augmented immune response, most notably the T cell response, can cause either direct neurotoxicity or, more commonly, indirect neurotoxic effects through systemic or local inflammatory mechanisms or autoimmune mechanisms...
November 6, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/29103666/identification-of-single-nucleotide-polymorphisms-of-the-pi3k-akt-mtor-pathway-as-a-risk-factor-of-central-nervous-system-metastasis-in-metastatic-breast-cancer
#12
Emilie Le Rhun, Nicolas Bertrand, Aurélie Dumont, Emmanuelle Tresch, Marie-Cécile Le Deley, Audrey Mailliez, Matthias Preusser, Michael Weller, Françoise Revillion, Jacques Bonneterre
INTRODUCTION: The PI3K-AKT-mTOR pathway may be involved in the development of central nervous system (CNS) metastasis from breast cancer. Accordingly, herein we explored whether single nucleotide polymorphisms (SNPs) of this pathway are associated with altered risk of CNS metastasis formation in metastatic breast cancer patients. METHODS: The GENEOM study (NCT00959556) included blood sample collection from breast cancer patients treated in the neoadjuvant, adjuvant or metastatic setting...
November 2, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29102237/patient-and-treatment-factors-associated-with-survival-among-pediatric-glioblastoma-patients-a-surveillance-epidemiology-and-end-results-study
#13
Sandi Lam, Yimo Lin, Pascal Zinn, Jack Su, I-Wen Pan
Glioblastoma (GBM) is a rare malignancy in children. The United States Surveillance, Epidemiology, and End Results (SEER) database allows large-scale analyses of clinical characteristics and prognostic features. We used it to study patients aged <20 years with histologically confirmed GBM (2000-2010) and examined the relationship between patient demographics, tumor characteristics, patterns of treatment, and outcomes. The primary outcome was disease-specific survival. 302 subjects were identified, with median age 11 years...
October 25, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/29101057/cost-effectiveness-of-osimertinib-for-egfr-mutation-positive-non-small-cell-lung-cancer-after-progression-of-first-line-egfr-tki-therapy
#14
Bin Wu, Xiaohua Gu, Qiang Zhang
INTRODUCTION: To investigate the cost-effectiveness of osimertinib for the treatment of advanced non-small-cell lung cancer (NSCLC) with an epidermal growth factor receptor (EGFR) T790M mutation after the failure of first-line EGFR-tyrosine kinase inhibitor (EGFR-TKI) therapy. METHODS: A mathematical model was established by combining a decision tree and the Markov approach to project the cost-effectiveness of osimertinib for the treatment of patients who harbor an EGFR T790M mutation compared to that of standard chemotherapy, who had disease progression after first-line EGFR-TKI therapy with or without metastases to the central nervous system...
October 31, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29095266/carbon-nanoparticles-facilitate-lymph-nodes-dissection-and-parathyroid-glands-identification-in-reoperation-of-papillary-thyroid-cancer
#15
An-Ping Su, Bin Wang, Yan-Ping Gong, Wen-Shuang Wu, Ri-Xiang Gong, Zhi-Hui Li, Jing-Qiang Zhu
The aim of the study was to investigate whether carbon nanoparticles (CNs) can improve the dissection of lymph nodes and protect parathyroid glands (PGs) during reoperation for patients with papillary thyroid carcinoma (PTC).PTC patients who previously underwent thyroidectomy and later received reoperation between January 2009 and January 2016 were retrospectively recruited. We compared the patients who had CN suspension injected into the residual thyroid gland with a control group of patients who did not have the injection...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29081735/targeting-wnt-signaling-for-multifaceted-glioblastoma-therapy
#16
REVIEW
Matthew McCord, Yoh-Suke Mukouyama, Mark R Gilbert, Sadhana Jackson
The WNT signaling pathway has been of great interest to developmental biologists for decades and has more recently become a central topic for study in cancer biology. It is vital for cell growth and regulation of embryogenesis in many organ systems, particularly the CNS and its associated vasculature. We summarize the role of WNT in CNS development and describe how WNT signaling makes key contributions to malignant glioma stemness, invasiveness, therapeutic resistance, and angiogenesis. The role of WNT in these mechanisms, along with creation and maintainance of the blood-brain barrier (BBB), points to the potential of WNT as a multi-faceted target in malignant glioma therapy...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29074604/prospective-feasibility-trial-for-genomics-informed-treatment-in-recurrent-and-progressive-glioblastoma
#17
Sara A Byron, Nhan L Tran, Rebecca F Halperin, Joanna J Phillips, John G Kuhn, John F de Groot, Howard Colman, Keith L Ligon, Patrick Y Wen, Timothy F Cloughesy, Ingo K Mellinghoff, Nicholas Butowski, Jennie Taylor, Jennifer L Clarke, Susan M Chang, Mitchel S Berger, Annette M Molinaro, Gerald M Maggiora, Sen Peng, Sara Nasser, Winnie S Liang, Jeffrey M Trent, Michael E Berens, John D Carpten, David Wesley Craig, Michael D Prados
PURPOSE: Glioblastoma is an aggressive and molecularly heterogeneous cancer with few effective treatment options. We hypothesized that next-generation sequencing can be used to guide treatment recommendations within a clinically acceptable time frame following surgery for patients with recurrent glioblastoma. METHODS: We conducted a prospective genomics-informed feasibility trial in adults with recurrent and progressive glioblastoma. Following surgical resection, genome-wide tumor/normal exome-sequencing and tumor RNA-sequencing was performed to identify molecular targets for potential matched therapy...
October 26, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29074098/lorlatinib-in-non-small-cell-lung-cancer-with-alk-or-ros1-rearrangement-an-international-multicentre-open-label-single-arm-first-in-man-phase-1-trial
#18
Alice T Shaw, Enriqueta Felip, Todd M Bauer, Benjamin Besse, Alejandro Navarro, Sophie Postel-Vinay, Justin F Gainor, Melissa Johnson, Jorg Dietrich, Leonard P James, Jill S Clancy, Joseph Chen, Jean-François Martini, Antonello Abbattista, Benjamin J Solomon
BACKGROUND: Most patients with anaplastic lymphoma kinase (ALK)-rearranged or ROS proto-oncogene 1 (ROS1)-rearranged non-small-cell lung cancer (NSCLC) are sensitive to tyrosine kinase inhibitor (TKI) therapy, but resistance invariably develops, commonly within the CNS. This study aimed to analyse the safety, efficacy, and pharmacokinetic properties of lorlatinib, a novel, highly potent, selective, and brain-penetrant ALK and ROS1 TKI with preclinical activity against most known resistance mutations, in patients with advanced ALK-positive or ROS1-positive NSCLC...
October 23, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/29069445/tcsbn-a-database-of-tissue-and-cancer-specific-biological-networks
#19
Sunjae Lee, Cheng Zhang, Muhammad Arif, Zhengtao Liu, Rui Benfeitas, Gholamreza Bidkhori, Sumit Deshmukh, Mohamed Al Shobky, Alen Lovric, Jan Boren, Jens Nielsen, Mathias Uhlen, Adil Mardinoglu
Biological networks provide new opportunities for understanding the cellular biology in both health and disease states. We generated tissue specific integrated networks (INs) for liver, muscle and adipose tissues by integrating metabolic, regulatory and protein-protein interaction networks. We also generated human co-expression networks (CNs) for 46 normal tissues and 17 cancers to explore the functional relationships between genes as well as their relationships with biological functions, and investigate the overlap between functional and physical interactions provided by CNs and INs, respectively...
October 24, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29068161/dcc-mutation-update-congenital-mirror-movements-isolated-agenesis-of-the-corpus-callosum-and-developmental-split-brain-syndrome
#20
Ashley Pl Marsh, Timothy J Edwards, Charles Galea, Helen M Cooper, Elizabeth C Engle, Saumya S Jamuar, Aurélie Méneret, Marie-Laure Moutard, Caroline Nava, Agnès Rastetter, Gail Robinson, Guy Rouleau, Emmanuel Roze, Megan Spencer-Smith, Oriane Trouillard, Thierry Billette de Villemeur, Christopher A Walsh, Timothy W Yu, Delphine Heron, Elliott H Sherr, Linda J Richards, Christel Depienne, Richard J Leventer, Paul J Lockhart
The deleted in colorectal cancer (DCC) gene encodes the netrin-1 receptor DCC, a transmembrane protein required for the guidance of commissural axons. Germline DCC mutations disrupt the development of predominantly commissural tracts in the central nervous system (CNS) and cause a spectrum of neurological disorders. Monoallelic, missense and predicted loss-of-function DCC mutations cause congenital mirror movements, isolated agenesis of the corpus callosum, or both. Biallelic, predicted loss-of-function DCC mutations cause developmental split brain syndrome...
October 25, 2017: Human Mutation
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