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https://www.readbyqxmd.com/read/28654140/epidermal-growth-factor-receptor-egfr-inhibitors-for-metastatic-colorectal-cancer
#1
REVIEW
David Lok Hang Chan, Eva Segelov, Rachel Sh Wong, Annabel Smith, Rebecca A Herbertson, Bob T Li, Niall Tebbutt, Timothy Price, Nick Pavlakis
BACKGROUND: Epidermal growth factor receptor (EGFR) inhibitors prevent cell growth and have shown benefit in the treatment of metastatic colorectal cancer, whether used as single agents or in combination with chemotherapy. Clear benefit has been shown in trials of EGFR monoclonal antibodies (EGFR MAb) but not EGFR tyrosine kinase inhibitors (EGFR TKI). However, there is ongoing debate as to which patient populations gain maximum benefit from EGFR inhibition and where they should be used in the metastatic colorectal cancer treatment paradigm to maximise efficacy and minimise toxicity...
June 27, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28652425/evaluation-of-biological-activity-of-mastic-extracts-based-on-chemotherapeutic-indices
#2
Ryuichiro Suzuki, Hiroshi Sakagami, Shigeru Amano, Kunihiko Fukuchi, Katsuyoshi Sunaga, Taisei Kanamoto, Shigemi Terakubo, Hideki Nakashima, Yoshiaki Shirataki, Mineko Tomomura, Yoshiko Masuda, Satoshi Yokose, Akito Tomomura, Hirofumi Watanabe, Masaki Okawara, Yoshiharu Matahira
BACKGROUND: Most previous mastic investigators have not considered its potent cytotoxicity that may significantly affect the interpretation of obtained data. In the present study, we re-evaluated several biological activities of mastic extracts, based on chemotherapeutic indexes. MATERIALS AND METHODS: Pulverized mastic gum was extracted with n-hexane and then with ethyl acetate or independently with methanol or n-butanol. Tumor specificity (TS) of the extracts was determined by their cytotoxicity against human malignant and non-malignant cells...
July 2017: In Vivo
https://www.readbyqxmd.com/read/28652242/preclinical-characterization-of-the-inhaled-small-molecule-respiratory-syncytial-virus-l-protein-polymerase-inhibitor-pc786
#3
Matthew Coates, Daniel Brookes, Young-In Kim, Heather Allen, Euan A F Fordyce, Elizabeth A Meals, Thomas Colley, Claire-Lise Ciana, Guillaume F Parra, Vladimir Sherbukhin, Jennifer A Stockwell, Jennifer C Thomas, S Fraser Hunt, Lauren Anderson-Dring, Stuart T Onions, Lindsey Cass, Peter J Murray, Kazuhiro Ito, Pete Strong, John P Devincenzo, Garth Rapeport
Although respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in infants and young children, attempts to develop an effective therapy have so far proved unsuccessful. Herein we report the preclinical profiles of PC786, a potent non-nucleoside RSV L-protein polymerase inhibitor, designed for inhalation treatment of RSV infection. PC786 demonstrated a potent and selective anti-viral activity against laboratory adapted or clinical isolates of RSVA (IC50: <0.09 - 0...
June 26, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28651549/6-methylmercaptopurine-riboside-a-thiopurine-nucleoside-with-antiviral-activity-against-canine-distemper-virus-in-vitro
#4
Otávio Valério de Carvalho, Daniele Mendes Félix, Claudia de Camargo Tozato, Juliana Lopes Rangel Fietto, Márcia Rogéria de Almeida, Gustavo Costa Bressan, Lindomar José Pena, Abelardo Silva-Júnior
BACKGROUND: Canine distemper (CD) is a widespread infectious disease that can severely impact a variety of species in the order Carnivora, as well as non-carnivore species such as non-human primates. Despite large-scale vaccination campaigns, several fatal outbreaks have been reported in wild and domestic carnivore populations. This, in association with expansion of the disease host range and the development of vaccine-escape strains, has contributed to an increased demand for therapeutic strategies synergizing with vaccine programs for effectively controlling canine distemper...
June 26, 2017: Virology Journal
https://www.readbyqxmd.com/read/28649618/synergistic-effects-of-influenza-and-1-methyl-4-phenyl-1-2-3-6-tetrahydropyridine-mptp-can-be-eliminated-by-the-use-of-influenza-therapeutics-experimental-evidence-for-the-multi-hit-hypothesis
#5
Shankar Sadasivan, Bridgett Sharp, Stacey Schultz-Cherry, Richard Jay Smeyne
Central Nervous System inflammation has been implicated in neurodegenerative disorders including Parkinson's disease (Ransohoff, Science 353: 777-783, 2016; Kannarkat et al. J. Parkinsons Dis. 3: 493-514, 2013). Here, we examined if the H1N1 influenza virus (Studahl et al. Drugs 73: 131-158, 2013) could synergize with the parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (Jackson-Lewis et al. in Mark LeDoux (ed) Movement Disorders: Genetics and Models: 287-306, Elsevier, 2015) to induce a greater microglial activation and loss of substantia nigra pars compacta dopaminergic neurons than either insult alone...
2017: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/28648883/molecular-cloning-and-functional-analysis-of-tumor-necrosis-factor-receptor-associated-factor-6-traf6-in-crossastrea-gigas
#6
Fan Mao, Jun Li, Yuehuan Zhang, Zhiming Xiang, Yang Zhang, Ziniu Yu
Tumor necrosis factor receptor-associated factor 6 (TRAF6) has been demonstrated to be a key signaling molecule involved in adaptive and innate immunity. In this study, we obtained the full length CgTRAF6 cDNA and analyzed the characteristics of the ORF and the peptide sequence in Crassostrea gigas. The deduced protein sequence of CgTRAF6 includes a conserved C-terminal TRAF domain following the RING and the zinc finger domain. The TRAF domain is composed of coiled-coil TRAF-N and MATH (meprin and TRAF-C homology) subdomains...
June 22, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28648760/corneal-endothelial-cells-activate-innate-and-acquired-arm-of-anti-viral-responses-after-cytomegalovirus-infection
#7
Dai Miyazaki, Ryu Uotani, Michiko Inoue, Tomoko Haruki, Yumiko Shimizu, Keiko Yakura, Satoru Yamagami, Tatsuo Suzutani, Mayumi Hosogai, Hiroki Isomura, Yoshitsugu Inoue
Infection of the corneal endothelial cells by human cytomegalovirus (CMV) is an important cause of corneal endotheliitis. CMV endotheliitis is difficult to completely cure and relapses are frequent. This can cause blinding corneal bullous keratopathy. However, the pathogenesis of CMV endotheliitis remains undetermined. To understand the immunopathology of endotheliitis, we examined how corneal endothelial cells prime the anti-viral immunity after CMV infection based on global transcriptional responses. To accomplish this, human corneal endothelial (HCEn) cells were infected with CMV, and the global transcriptional responses were determined by microarray analyses for primary anti-viral responses using network analysis...
June 22, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28647974/-cd-4-t-lymphocyte-responses-to-anti-retroviral-therapy-among-hiv-aids-patients-aged-18-and-over
#8
X X Guo, Y Ma, Z H Dou, Y S Wu, D C Zhao, W P Cai, Y Li, X X Dong
Objective: To compare the differences of CD(4) (+) T lymphocyte (CD(4)) counts between patients aged 18 and over, to explore the effect of age on treatment, 36 months after having received the China National Free AIDS Antiretroviral Treatment on HIV/AIDS. Methods: Through the National ART Information Ssystem, we selected those HIV/AIDS patients who initiated the ART 36 months after the ART, between January 1, 2010 and December 31, 2012 in Guangzhou, Liuzhou and Kunming. Patients were divided into age groups as 18-49, 50-59 and 60 or over year olds, at the baseline of treatment...
June 10, 2017: Zhonghua Liu Xing Bing Xue za Zhi, Zhonghua Liuxingbingxue Zazhi
https://www.readbyqxmd.com/read/28646236/rapamycin-adjuvant-and-exacerbation-of-severe-influenza-in-an-experimental-mouse-model
#9
Ching-Tai Huang, Chen-Yiu Hung, Tse-Ching Chen, Chun-Yen Lin, Yung-Chang Lin, Chia-Shiang Chang, Yueh-Chia He, Yu-Lin Huang, Avijit Dutta
Influenza virus infection often causes severe disease and acute respiratory distress syndrome. It is a common belief that overwhelming immune response contributes to the severe illness. Physicians and researchers have put forth immune modulation as salvage therapy for better recovery. However, empiric corticosteroid failed in both humans and animal models. Reported success with Rapamycin in humans prompted a comprehensive animal study and mechanistic dissection. Here we report the effect of Rapamycin alone or in combination with Oseltamivir for severe influenza in BALB/c mice...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28645089/drug-resistance-mechanism-of-l10f-l10f-n88s-and-l90m-mutations-in-crf01_ae-hiv-1-protease-molecular-dynamics-simulations-and-binding-free-energy-calculations
#10
C S Vasavi, Ramasamy Tamizhselvi, Punnagai Munusami
HIV-1 protease plays a crucial role in viral replication and maturation, which makes it one of the most attractive targets for anti-retroviral therapy. The majority of HIV infections in developing countries are due to non-B subtype. Subtype AE is spreading rapidly and infecting huge population worldwide. The mutations in the active site of subtype AE directly impair the interactions with the inhibitor. The non-active site mutations influence the binding of the inhibitor indirectly and their resistance mechanism is not well understood...
June 8, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28644966/an-immunosuppressive-function-of-interleukin-35-in-chronic-hepatitis-c-virus-infection
#11
Siqi Liu, Qian Zhang, Xue Shao, Wenrui Wang, Chuanhui Zhang, Zhenjing Jin
Interleukin (IL)-35, a newly identified member of the IL-12 cytokine family, has been reported to suppress inflammation and induce immunotolerance. However, little is known regarding the role of IL-35 during chronic hepatitis C virus (HCV) infection. Herein, we measured the serum IL-35 concentration of 73 patients with hepatitis C and 22 healthy individuals, as well as further investigated the modulatory function of IL-35 on CD4(+)CD25(+)CD127(dim/-) regulatory T cells (Tregs) and on hepatocytes infected with HCV in cell culture (HCVcc)...
June 20, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28644565/long-term-risk-of-infection-in-patients-with-crohn-s-disease-on-anti-tnf-treatment-a-prospective-single-center-cohort-study-in-china
#12
Yue Li, Hui Jun Shu, Hong Lu, Hong Yang, Ji Li, Bei Tan, Jiaming Qian
BACKGROUND: Anti-TNF agents have demonstrated to greatly improve management strategies for inflammatory bowel disease (IBD). Clinical trials and registry studies in Western countries have shown that infections and malignancy are the most concerned complications of anti-TNF treatment. However, data derived from clinical practice in China are limited. The aim of this study is to explore the long-term infection risk of infliximab (IFX) in treating patients with Crohn's disease (CD) from a tertiary IBD center in China...
June 23, 2017: Journal of Digestive Diseases
https://www.readbyqxmd.com/read/28643392/retroviruses-and-microtubule-associated-motor-proteins
#13
REVIEW
Gloria Arriagada
Retroviruses are obligate intracellular parasites of eukaryotic cells. After reverse transcription, the viral DNA contained in the preintegration complex (PIC) is delivered to the nucleus of the host cell, where it integrates. Before reaching the nucleus, the incoming particle and the PIC must travel throughout the cytoplasm. Likewise the newly synthesized viral proteins and viral particles must transit the cytoplasm during exit. The cytoplasm is a crowded environment and simple diffusion is difficult. Therefore, viruses have evolved to utilize the cellular mechanisms of movement through the cytoplasm, where microtubules are the roads, and the ATP dependent motors dynein and kinesin are the vehicles for retrograde and anterograde trafficking...
June 22, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28642820/intratumorally-injected-pro-inflammatory-allogeneic-dendritic-cells-as-immune-enhancers-a-first-in-human-study-in-unfavourable-risk-patients-with-metastatic-renal-cell-carcinoma
#14
Anna Laurell, Maria Lönnemark, Einar Brekkan, Anders Magnusson, Anna Tolf, Anna Carin Wallgren, Bengt Andersson, Lars Adamson, Rolf Kiessling, Alex Karlsson-Parra
BACKGROUND: Accumulating pre-clinical data indicate that the efficient induction of antigen-specific cytotoxic CD8+ T cells characterizing viral infections is caused by cross-priming where initially infected DCs produce an unique set of inflammatory factors that recruit and activate non-infected bystander DCs. Our DC-based immunotherapy concept is guided by such bystander view and accordingly, we have developed a cellular adjuvant consisting of pre-activated allogeneic DCs producing high levels of DC-recruiting and DC-activating factors...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28642806/the-efficacy-of-epigallocatechin-3-gallate-green-tea-in-the-treatment-of-alzheimer-s-disease-an-overview-of-pre-clinical-studies-and-translational-perspectives-in-clinical-practice
#15
REVIEW
Marco Cascella, Sabrina Bimonte, Maria Rosaria Muzio, Vincenzo Schiavone, Arturo Cuomo
Alzheimer's disease (AD) is a neurodegenerative disorder and the most common form of dementia characterized by cognitive and memory impairment. One of the mechanism involved in the pathogenesis of AD, is the oxidative stress being involved in AD's development and progression. In addition, several studies proved that chronic viral infections, mainly induced by Human herpesvirus 1 (HHV-1), Cytomegalovirus (CMV), Human herpesvirus 2 (HHV-2), and Hepatitis C virus (HCV) could be responsible for AD's neuropathology...
2017: Infectious Agents and Cancer
https://www.readbyqxmd.com/read/28642467/targeting-coronaviral-replication-and-cellular-jak2-mediated-dominant-nf-%C3%AE%C2%BAb-activation-for-comprehensive-and-ultimate-inhibition-of-coronaviral-activity
#16
Cheng-Wei Yang, Yue-Zhi Lee, Hsing-Yu Hsu, Chuan Shih, Yu-Sheng Chao, Hwan-You Chang, Shiow-Ju Lee
Tylophorine-based compounds exert broad spectral, potent inhibition of coronaviruses. NF-κB activation is a common pro-inflammatory response of host cells to viral infection. The aims of this study were to (i) find an effective combination treatment for coronaviral infections through targeting of the virus per se and cellular NF-κB activity; and (ii) to study the underling mechanisms. We found that tylophorine-based compounds target the TGEV viral RNA and effectively inhibit TGEV replication. NF-κB inhibition also leads to anti-TGEV replication...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28641998/construction-of-a-hepatitis-b-virus-neutralizing-chimeric-monoclonal-antibody-recognizing-escape-mutants-of-the-viral-surface-antigen-hbsag
#17
Forough Golsaz-Shirazi, Mohammad Mehdi Amiri, Samira Farid, Motahareh Bahadori, Felix Bohne, Sebastian Altstetter, Lisa Wolff, Tohid Kazemi, Jalal Khoshnoodi, Mohammad Hojjat-Farsangi, Michael Chudy, Mahmood Jeddi-Tehrani, Ulrike Protzer, Fazel Shokri
Hepatitis B virus (HBV) infection is a global burden on the health-care system and is considered as the tenth leading cause of death in the world. Over 248 million patients are currently suffering from chronic HBV infection worldwide and annual mortality rate of this infection is 686000. The "a" determinant is a hydrophilic region present in all antigenic subtypes of hepatitis B surface antigen (HBsAg), and antibodies against this region can neutralize the virus and are protective against all subtypes. We have recently generated a murine anti-HBs monoclonal antibody (4G4), which can neutralize HBV infection in HepaRG cells and recognize most of the escape mutant forms of HBsAg...
June 19, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28641512/molecular-docking-and-molecular-dynamics-simulation-based-approach-to-explore-the-dual-inhibitor-against-hiv-1-reverse-transcriptase-and-integrase
#18
Subhash Chander, Rajan Kumar Pandey, Ashok Penta, Bhanwar Singh Choudhary, Manish Sharma, Ruchi Malik, Vijay Kumar Prajapati, Sankaranarayanan Murugesan
HIV integrase (IN) and reverse transcriptase (RT) are key enzymes for the replication of HIV-1. DNA polymerase and ribonuclease H (RNase H) are the two catalytic domains of HIV-1 RT which are validated as drug targets because of their essence for replication. IN and RNase H domain of RT share the striking structural similarity; it contains conserved DDE triad (two aspartates and one glutamate) and a pair of divalent Mg2+/Mn2+ ions at their catalytic core domain. Therefore, the search of compounds with dual inhibition of IN and RNase H can be the viable and more efficacious approach for the drug development against both wild and drug resistance strains of HIV...
June 15, 2017: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/28640212/synthesis-and-in-vitro-anti-influenza-virus-evaluation-of-novel-sialic-acid-c-5-and-c-9-pentacyclic-triterpene-derivatives
#19
Xu Han, Long-Long Si, Yong-Ying Shi, Zi-Bo Fan, Shou-Xin Wang, Zhen-Yu Tian, Man Li, Jia-Qi Sun, Ping-Xuan Jiao, Fu-Xiang Ran, Yong-Min Zhang, De-Min Zhou, Su-Long Xiao
The emergence of drug resistant variants of the influenza virus has led to a great need to identify novel and effective antiviral agents. In our previous study, a series of sialic acid (C-2 and C-4)-pentacyclic triterpene conjugates have been synthesized, and a five-fold more potent antiviral activity was observed when sialic acid was conjugated with pentacyclic triterpene via C-4 than C-2. It was here that we further reported the synthesis and anti-influenza activity of novel sialic acid (C-5 and C-9)-pentacyclic triterpene conjugates...
June 22, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28638480/mouse-ip-10-gene-delivered-by-folate-modified-chitosan-nanoparticles-and-dendritic-tumor-cells-fusion-vaccine-effectively-inhibit-the-growth-of-hepatocellular-carcinoma-in-mice
#20
Zixi Hu, Jiaojiao Chen, Sufang Zhou, Nuo Yang, Siliang Duan, Zhenghua Zhang, Jing Su, Jian He, Zhiyong Zhang, Xiaoling Lu, Yongxiang Zhao
Dendritic cells (DC) and tumor cell fusion vaccine (DC/tumor cell fusion vaccine) is considered an effective approach in cancer biotherapy. However, its therapeutic effects in early clinical trials have been suboptimal partially due to the immunosuppressive tumor environment. In this study, we used nanoparticles of folate (FA)-modified chitosan, a non-viral vector capable of targeting tumor cells with high expression of FA receptors. FA-chitosan nanoparticles were used as biological carriers for the expression plasmid of the mouse interferon-induced protein-10 (mIP-10) gene, a potent chemoattractant for cytotoxic T cells...
2017: Theranostics
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