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https://www.readbyqxmd.com/read/28820254/blockade-of-asparagine-endopeptidase-inhibits-cancer-metastasis
#1
Qi Qi, Obiamaka Obianyo, Yuhong Du, Haian Fu, Shiyong Li, Keqiang Ye
Asparagine endopeptidase (AEP), also called legumain, is highly expressed in various solid tumors, promoting cancer cell invasion, migration, and metastasis. It has been proposed to be a prognostic marker and therapeutic target for cancer treatment. However, an effective nonpeptide, small-molecule inhibitor against this protease has not yet been identified. Here we show that a family of xanthine derivatives selectively inhibit AEP and suppress matrix metalloproteinase (MMP) cleavage, leading to the inhibition of cancer metastasis...
August 18, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28819565/genomic-and-immune-heterogeneity-are-associated-with-differential-responses-to-therapy-in-melanoma
#2
Alexandre Reuben, Christine N Spencer, Peter A Prieto, Vancheswaran Gopalakrishnan, Sangeetha M Reddy, John P Miller, Xizeng Mao, Mariana Petaccia De Macedo, Jiong Chen, Xingzhi Song, Hong Jiang, Pei-Ling Chen, Hannah C Beird, Haven R Garber, Whijae Roh, Khalida Wani, Eveline Chen, Cara Haymaker, Marie-Andrée Forget, Latasha D Little, Curtis Gumbs, Rebecca L Thornton, Courtney W Hudgens, Wei-Shen Chen, Jacob Austin-Breneman, Robert Szczepaniak Sloane, Luigi Nezi, Alexandria P Cogdill, Chantale Bernatchez, Jason Roszik, Patrick Hwu, Scott E Woodman, Lynda Chin, Hussein Tawbi, Michael A Davies, Jeffrey E Gershenwald, Rodabe N Amaria, Isabella C Glitza, Adi Diab, Sapna P Patel, Jianhua Hu, Jeffrey E Lee, Elizabeth A Grimm, Michael T Tetzlaff, Alexander J Lazar, Ignacio I Wistuba, Karen Clise-Dwyer, Brett W Carter, Jianhua Zhang, P Andrew Futreal, Padmanee Sharma, James P Allison, Zachary A Cooper, Jennifer A Wargo
Appreciation for genomic and immune heterogeneity in cancer has grown though the relationship of these factors to treatment response has not been thoroughly elucidated. To better understand this, we studied a large cohort of melanoma patients treated with targeted therapy or immune checkpoint blockade (n = 60). Heterogeneity in therapeutic responses via radiologic assessment was observed in the majority of patients. Synchronous melanoma metastases were analyzed via deep genomic and immune profiling, and revealed substantial genomic and immune heterogeneity in all patients studied, with considerable diversity in T cell frequency, and few shared T cell clones (<8% on average) across the cohort...
2017: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/28819419/osteopontin-a-promising-biomarker-for-cancer-therapy
#3
REVIEW
Ran Wei, Janet Pik Ching Wong, Hang Fai Kwok
Osteopontin (OPN), a multifunctional protein, has emerged as a potentially valuable biomarker for diagnosing and treating cancers. Recent research focuses on its involvement in tumor biology including the cell proliferation, survival, angiogenesis, invasion, and metastasis. Understanding the molecular mechanisms and pharmacological effects of OPN in cancer development could lead to new targets for improving cancer diagnosis and treatment. This review explains how the structurally conserved domains of OPN are associated with OPN signaling mediators and CD44, and how the conserved OPN domains determine biological functions...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819407/ccr7-promote-lymph-node-metastasis-via-regulating-vegf-c-d-r3-pathway-in-lung-adenocarcinoma
#4
Jie Yu, Shaolin Tao, Pingping Hu, Ruwen Wang, Chunshu Fang, Yi Xu, Di Qi, Zhuanqin Wei, Jingge Zhang, Qunyou Tan
Lymph node metastasis is still an important issue in metastatic process of lung adenocarcinoma. C-C chemokine receptor 7 (CCR7) has been proved to be closely associated with the metastasis of lung adenocarcinoma, and the mechanism is poorly understood. In order to investigate the relationship between CCR7 and lymph node metastasis in lung adenocarcinoma, and to explore the role of CCR7 in treating lung adenocarcinoma, 40 clinical specimens were collected to define the relationship between CCR7 and lymph node metastasis in lung adenocarcinoma by immunohistochemistry...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28818106/morphoproteomics-e6-e7-in-situ-hybridization-and-biomedical-analytics-define-the-etiopathogenesis-of-hpv-associated-oropharyngeal-carcinoma-and-provide-targeted-therapeutic-options
#5
Robert E Brown, Syed Naqvi, Mary F McGuire, Jamie Buryanek, Ron J Karni
BACKGROUND: Human papillomavirus (HPV) has been identified as an etiopathogenetic factor in oropharyngeal squamous cell carcinoma. The HPV E6 and E7 oncogenes are instrumental in promoting proliferation and blocking differentiation leading to tumorigenesis. Although surgical intervention can remove such tumors, the potential for an etiologic field effect with recurrent disease is real. A downstream effector of E7 oncoprotein, enhancer of zeste homolog 2 (EZH2), is known to promote proliferation and to pose a block in differentiation and in turn, could lead to HPV-induced malignant transformation...
August 17, 2017: Journal of Otolaryngology—Head & Neck Surgery
https://www.readbyqxmd.com/read/28817967/pimavanserin-a-novel-antipsychotic-for-management-of-parkinson-s-disease-psychosis
#6
Yasaman Kianirad, Tanya Simuni
Parkinson's disease psychosis (PDP) may develop in up to 60% of Parkinson's patients and is associated with increased morbidity and mortality. It also correlates with depression and dementia, and can contribute to caregiver stress and burnout. Pimavanserin is the first FDA approved drug for the treatment of hallucinations and delusions associated with PDP. Areas covered: For this review, a MEDLINE literature search (via PubMed) and information provided by ACADIA Pharmaceuticals were used. References of our search results were screened for additional studies...
August 18, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28817119/mir-1301-inhibits-hepatocellular-carcinoma-cell-migration-invasion-and-angiogenesis-by-decreasing-wnt-%C3%AE-catenin-signaling-through-targeting-bcl9
#7
Chao Yang, Yonghua Xu, Feng Cheng, Yuanchang Hu, Shikun Yang, Jianhua Rao, Xuehao Wang
Metastasis is the major cause of the poor prognosis of hepatocellular carcinoma (HCC), and increasing evidence supports the contribution of miRNAs to cancer progression. However, the exact relationship between the level of miR-1301 expression and HCC cell migration, invasion, and angiogenesis remains largely unknown. Quantitative PCR was used to evaluate the level of miR-1301 expression in HCC tissues and cell lines. Transwell and tube-formation assays were used to measure the effects of miR-1301 on HCC cell migration and invasion, and angiogenesis, respectively...
August 17, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28816757/therapeutic-drug-monitoring-during-induction-of-anti-tumor-necrosis-factor-therapy-in-inflammatory-bowel-disease-defining-a-therapeutic-drug-window
#8
Konstantinos Papamichael, Niels Vande Casteele, Marc Ferrante, Ann Gils, Adam S Cheifetz
Anti-tumor necrosis factor (TNF) therapy has revolutionized the treatment of inflammatory bowel disease (IBD). However, up to 30% of patients with IBD show no clinical benefit and are defined as having a primary nonresponse. Primary nonresponse to a biologic can be attributed to either pharmacokinetic or pharmacodynamic issues, such as those involved in secondary loss of response. Pharmacokinetic issues are linked to undetectable or subtherapeutic drug concentrations because of either an accelerated non-immune-mediated clearance or immunogenicity and the development of antidrug antibodies, whereas pharmacodynamic issues are likely related to "non-TNF driven" disease...
September 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28816748/therapeutic-drug-monitoring-during-induction-of-anti-tumor-necrosis-factor-therapy-in-inflammatory-bowel-disease-defining-a-therapeutic-drug-window
#9
Konstantinos Papamichael, Niels Vande Casteele, Marc Ferrante, Ann Gils, Adam S Cheifetz
Anti-tumor necrosis factor (TNF) therapy has revolutionized the treatment of inflammatory bowel disease (IBD). However, up to 30% of patients with IBD show no clinical benefit and are defined as having a primary nonresponse. Primary nonresponse to a biologic can be attributed to either pharmacokinetic or pharmacodynamic issues, such as those involved in secondary loss of response. Pharmacokinetic issues are linked to undetectable or subtherapeutic drug concentrations because of either an accelerated non-immune-mediated clearance or immunogenicity and the development of antidrug antibodies, whereas pharmacodynamic issues are likely related to "non-TNF driven" disease...
August 14, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28816646/chronic-cigarette-smoke-mediated-global-changes-in-lung-mucoepidermoid-cells-a-phosphoproteomic-analysis
#10
Hitendra S Solanki, Jayshree Advani, Aafaque Ahmad Khan, Aneesha Radhakrishnan, Nandini A Sahasrabuddhe, Sneha M Pinto, Xiaofei Chang, Thottethodi Subrahmanya Keshava Prasad, Premendu Prakash Mathur, David Sidransky, Harsha Gowda, Aditi Chatterjee
Proteomics analysis of chronic cigarette smoke exposure is a rapidly emerging postgenomics research field. While smoking is a major cause of lung cancer, functional studies using proteomics approaches could enrich our mechanistic understanding of the elusive lung cancer global molecular signaling and cigarette smoke relationship. We report in this study on a stable isotope labeling by amino acids in cell culture-based quantitative phosphoproteomic analysis of a human lung mucoepidermoid carcinoma cell line, H292 cells, chronically exposed to cigarette smoke...
August 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28816592/two-faced-fcab-prevents-polymerization-with-vegf-and-reveals-thermodynamics-and-the-2-15%C3%A2-%C3%A3-crystal-structure-of-the-complex
#11
Elisabeth Lobner, Anne-Sophie Humm, Georg Mlynek, Konstantin Kubinger, Michael Kitzmüller, Michael W Traxlmayr, Kristina Djinović-Carugo, Christian Obinger
Fcabs (Fc domain with antigen-binding sites) are promising novel therapeutics. By engineering of the C-terminal loops of the CH3 domains, two antigen binding sites can be inserted in close proximity. In order to elucidate the binding mode(s) between homodimeric Fcabs and small homodimeric antigens, the interaction between the Fcabs 448 and CT6 (having the AB, CD and EF loops and the C-termini engineered) with homodimeric VEGF was investigated. The crystal structures of these Fcabs, which form polymers with the antigen VEGF in solution, were determined...
August 17, 2017: MAbs
https://www.readbyqxmd.com/read/28816107/fishing-anti-inflammatories-from-known-drugs-in-silico-repurposing-design-synthesis-and-biological-evaluation-of-bisacodyl-analogues
#12
Maité Sylla-Iyarreta Veitía, Dany Siverio Mota, Vanessa Lerari, Marta Marín, Rosa M Giner, Liliana Vicet Muro, Yankier Rivero Guerra, Françoise Dumas, Clotilde Ferroud, Peter A M de Witte, Alexander D Crawford, Vicente J Arán, Yovani Marrero Ponce
Herein is described in silico repositioning, design, synthesis, biological evaluation and structure-activity relationship (SAR) of an original class of anti-inflammatory agents based on a polyaromatic pharmacophore structurally related to bisacodyl (BSL) drug used in therapeutic as laxative. We describe the potential of TOMOCOMD-CARDD methods to find out new anti-inflammatory drug-like agents from a diverse series of compounds using the total and local atom based bilinear indices as molecular descriptors. The models obtained were validated by biological studies, identifying BSL as the first anti-inflammatory lead-like using in silico repurposing from commercially available drugs...
August 17, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28815452/-18-f-fdg-pet-radiomics-approaches-comparing-and-clustering-features-in-cervical-cancer
#13
Tetsuya Tsujikawa, Tasmiah Rahman, Makoto Yamamoto, Shizuka Yamada, Hideaki Tsuyoshi, Yasushi Kiyono, Hirohiko Kimura, Yoshio Yoshida, Hidehiko Okazawa
OBJECTIVES: The aims of our study were to find the textural features on (18)F-FDG PET/CT which reflect the different histological architectures between cervical cancer subtypes and to make a visual assessment of the association between (18)F-FDG PET textural features in cervical cancer. METHODS: Eighty-three cervical cancer patients [62 squamous cell carcinomas (SCCs) and 21 non-SCCs (NSCCs)] who had undergone pretreatment (18)F-FDG PET/CT were enrolled. A texture analysis was performed on PET/CT images, from which 18 PET radiomics features were extracted including first-order features such as standardized uptake value (SUV), metabolic tumor volume (MTV) and total lesion glycolysis (TLG), second- and high-order textural features using SUV histogram, normalized gray-level co-occurrence matrix (NGLCM), and neighborhood gray-tone difference matrix, respectively...
August 16, 2017: Annals of Nuclear Medicine
https://www.readbyqxmd.com/read/28815394/shared-dysregulation-of-homeostatic-brain-body-pathways-in-depression-and-type-2-diabetes
#14
REVIEW
Claire J Hoogendoorn, Juan F Roy, Jeffrey S Gonzalez
PURPOSE OF REVIEW: The purpose of this review is to provide an overview of shared dysregulation of the hypothalamic-pituitary-adrenal (HPA) and brain-gut-microbiome (BGM) axes associated with depression and type 2 diabetes (T2D). Clinical implications and future research are also discussed. RECENT FINDINGS: Both depression and T2D are associated with dysregulation of the HPA and BGM axes. These pathways regulate immune function, glucose metabolism, and sleep, which are altered in both illnesses...
August 16, 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28815268/temporal-stability-of-the-healthy-human-skin-microbiome-following-dead-sea-climatotherapy
#15
Michael Brandwein, Garold Fuks, Avigail Israel, Ashraf Al-Ashhab, Deborah Rosenberg-Nejman, Ravid Straussman, Emmilia Hodak, Marco Harari, Doron Steinberg, Zvi Bentwich, Noam Shental, Shiri Meshner
Dead Sea climatotherapy (DSC) is a therapeutic modality for a variety of chronic skin conditions, yet there has been scarce research on the relationship between the cutaneous microbiota and disease states in response to DSC. We characterized the skin bacterial and fungal microbiome of healthy volunteers who underwent DSC. Bacterial community diversity remained similar before and after treatment, while fungal diversity was significantly reduced as a result of the treatment. Individuals showed greater inter-individual than temporal bacterial community variance, yet the opposite was true for fungal community composition...
August 17, 2017: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/28815014/the-relationship-between-intolerance-of-uncertainty-in-chiropractic-students-and-their-treatment-intervention-choices
#16
Stanley I Innes, Charlotte Leboeuf-Yde, Bruce F Walker
BACKGROUND: Psychological factors, such as intolerance of uncertainty (IU), have been shown to impact on the quality of medical care. However, this psychological measure has not been studied in the chiropractic profession. Our objective was to investigate if higher levels of IU in chiropractic students were related to poor choices of management in specific clinical scenarios. Also, we sought to investigate if levels of IU were related to students' intentions to adopt a prescriptive chiropractic technique system and evaluate their levels of self-belief...
2017: Chiropractic & Manual Therapies
https://www.readbyqxmd.com/read/28814953/in-vitro-characterization-of-jellyfish-venom-fibrin-ogen-olytic-enzymes-from-nemopilema-nomurai
#17
Seong Kyeong Bae, Hyunkyoung Lee, Yunwi Heo, Min Jung Pyo, Indu Choudhary, Chang Hoon Han, Won Duk Yoon, Changkeun Kang, Euikyung Kim
BACKGROUND: Because jellyfish are capable of provoking envenomation in humans, they are considered hazardous organisms. Although the effects of their toxins are a matter of concern, information on the venom components, biological activity and pathological mechanisms are still scarce. Therefore, the aim of the present study was to investigate a serine protease component of Nemopilema nomurai jellyfish venom (NnV) and unveil its characteristics. METHODS: To determine the relationship between fibrinolytic activity of NnV and the serine protease, fibrin zymography was performed using metalloprotease and serine protease inhibitors...
2017: Journal of Venomous Animals and Toxins Including Tropical Diseases
https://www.readbyqxmd.com/read/28814907/new-prognostic-biomarkers-and-therapeutic-effect-of-bevacizumab-for-patients-with-non-small-cell-lung-cancer
#18
Maiko Niki, Takashi Yokoi, Takayasu Kurata, Shosaku Nomura
BACKGROUND: Several biomarkers have emerged as potential prognostic and predictive markers for non-small-cell lung cancer (NSCLC). Successful inhibition of angiogenesis with the antivascular endothelial growth factor antibody, bevacizumab, has improved the efficacy seen with standard cytotoxic therapy of NSCLC. However, despite such enhanced treatment strategies, the prognosis for patients with advanced NSCLC remains poor. PATIENTS AND METHODS: We assessed potential biomarkers in 161 NSCLC patients and 42 control patients...
2017: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28814877/mechanism-and-therapeutic-effectiveness-of-nerve-growth-factor-in-osteoarthritis-pain
#19
REVIEW
Xiushuai Shang, Zhaofei Wang, Hairong Tao
Osteoarthritis (OA) is the most common form of articular joint arthritis and a cause of significant morbidity. In this review, we present the role of nerve growth factor (NGF) in pain generation, relationship between NGF and OA pain, and pathogenic factors (interleukin-1β, transforming growth factor-β1, mechanical loading, and adipokines) involved in OA development. Since NGF blocking is an efficient way to inhibit OA-associated pain, we summarize four categories of drugs that target NGF/tropomyosin receptor kinase A (TrkA) signaling...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28814823/relationship-between-the-antifungal-susceptibility-profile-and-the-production-of-virulence-related-hydrolytic-enzymes-in-brazilian-clinical-strains-of-candida-glabrata
#20
Maria Helena Galdino Figueiredo-Carvalho, Lívia de Souza Ramos, Leonardo Silva Barbedo, Jean Carlos Almeida de Oliveira, André Luis Souza Dos Santos, Rodrigo Almeida-Paes, Rosely Maria Zancopé-Oliveira
Candida glabrata is a facultative intracellular opportunistic fungal pathogen in human infections. Several virulence-associated attributes are involved in its pathogenesis, host-pathogen interactions, modulation of host immune defenses, and regulation of antifungal drug resistance. This study evaluated the in vitro antifungal susceptibility profile to five antifungal agents, the production of seven hydrolytic enzymes related to virulence, and the relationship between these phenotypes in 91 clinical strains of C...
2017: Mediators of Inflammation
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