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https://www.readbyqxmd.com/read/28922786/relapse-free-survival-as-a-surrogate-for-overall-survival-in-the-evaluation-of-stage-ii-iii-melanoma-adjuvant-therapy
#1
Stefan Suciu, Alexander M M Eggermont, Paul Lorigan, John M Kirkwood, Svetomir N Markovic, Claus Garbe, David Cameron, Srividya Kotapati, Tai-Tsang Chen, Keith Wheatley, Natalie Ives, Gaetan de Schaetzen, Achmad Efendi, Marc Buyse
Background: We assessed whether relapse-free survival (RFS; time until recurrence/death) is a valid surrogate for overall survival (OS) among resected stage II-III melanoma patients through a meta-analysis of randomized controlled trials. Methods: Individual patient data (IPD) on RFS and OS were collected from 5826 patients enrolled in 11 randomized adjuvant trials comparing interferon (IFN) to observation. In addition, IPD from two studies comparing IFN and vaccination in 989 patients were included...
January 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28922589/higher-baseline-proinflammatory-cytokines-mark-poor-antidepressant-response-in-bipolar-disorder
#2
Francesco Benedetti, Sara Poletti, Thomas A Hoogenboezem, Clara Locatelli, Harm de Wit, Annemarie J M Wijkhuijs, Cristina Colombo, Hemmo A Drexhage
BACKGROUND: The clinical relevance of raised levels of circulating cytokines in bipolar disorder is still unclear. Cytokines influence neurotransmitters, neuroplasticity, and white matter integrity. An inconsistent literature suggests that higher cytokine levels could hamper antidepressant response. Total sleep deprivation (TSD) and light therapy (LT) prompt a rapid antidepressant response and can provide a model treatment to study predictors of response. METHODS: We studied at baseline 15 immune-regulating compounds in 37 consecutively admitted inpatients with a major depressive episode in the course of bipolar disorder (DSM-5 criteria) and in 24 controls...
September 12, 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/28922104/interleukin-2-interferon-gamma-gene-polymorphisms-in-recurrent-aphthous-stomatitis
#3
Shamsolmoulouk Najafi, Hila Yousefi, Mahsa Mohammadzadeh, Alireza Zare Bidoki, Elham Farhadi, Nima Rezaei
Recurrent aphthous stomatitis (RAS) is the most common oral ulcerative inflammatory disease with unknown etiology. IL-2 and IFN-γ are secreted by Th1 cells and the elevated levels of them have been reported in RAS. Single nucleotide polymorphisms (SNPs) of IL-2 and IFN-γ genes could alter the cytokine production. The aim of this study was to investigate frequencies of IL-2 and IFN-γ alleles and genotypes in a group of patients with minor-RAS (MiRAS). PCR-SSP method used to type genomic DNA of 64 Iranian patients with MiRAS for IL-2 gene (G -330 T) and (G +166 T) and IFN-γ gene at position UTR5644 (A/T)...
2017: Prague Medical Report
https://www.readbyqxmd.com/read/28921877/analysis-of-infantile-fibrosarcoma-reveals-extensive-t-cell-responses-within-tumors-implications-for-immunotherapy
#4
Hua Zhu, Song Gu, Minzhi Yin, Min Shi, Chao Xin, Jianmin Zhu, Jing Wang, Siqi Huang, Chenjie Xie, Jing Ma, Ci Pan, Jingyan Tang, Min Xu, Xue-Feng Bai
BACKGROUND: Infantile fibrosarcoma (IFS) is a rare pediatric malignancy with relatively good prognosis, but the risk of progression or recurrence after therapy exists. To understand the immune microenvironment of IFS and determine if immunotherapy is a potential treatment, we analyzed T-cell responses in IFS tumors. PROCEDURE: IFS tumors were analyzed by immunohistochemistry and multicolor flow cytometry to characterize immune cell infiltration and function. Tumor infiltrating lymphocytes (TILs) were expanded in vitro and evaluated for recognition of autologous tumor cells...
September 17, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28921595/the-interplay-of-type-i-and-type-ii-interferons-in-murine-autoimmune-cholangitis-as-a-basis-for-sex-biased-autoimmunity
#5
Heekyong R Bae, Deborah L Hodge, Guo-Xiang Yang, Patrick S C Leung, Sathi Babu Chodisetti, Julio C Valencia, Michael Sanford, John M Fenimore, Ziaur S M Rahman, Koichi Tsuneyama, Gary L Norman, M Eric Gershwin, Howard A Young
We have reported a murine model of autoimmune cholangitis, generated by altering the AU rich element by deletion of the IFN-γ 3'UTR region (coined ARE-Del(-/-) ), that has striking similarities to human primary biliary cholangitis (PBC) with female predominance. Previously, we suggested that the gender bias of autoimmune cholangitis was secondary to intense and sustained type I and II IFN signaling. Based on this thesis, and to define the mechanisms that lead to portal inflammation, we specifically addressed the hypothesis that type I IFNs are the driver of this disease...
September 16, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28921566/pegylation-of-cationic-liposomes-encapsulating-soluble-leishmania-antigens-sla-reduces-the-adjuvant-efficacy-of-liposomes-in-murine-model
#6
Hadi Naseri, Faezeh Eskandari, Mahmoud Reza Jaafari, Ali Khamesipour, Azam Abbasi, Ali Badiee
Although there have been several attempts to develop a vaccine against leishmaniasis; no vaccine in human has been developed yet. Liposomes consisting of 1, 2-dioleoyl-3-trimethylammonium-propane (DOTAP) encapsulating soluble Leishmania antigens (SLA) enhance protective immunity of SLA against L. major infection in mice. However, they immobilized at the injection site because of their positive charge. To overcome the problem, shielding the surface charge with polyethylene glycol (PEGylation) was chosen in this study...
September 16, 2017: Parasite Immunology
https://www.readbyqxmd.com/read/28921473/the-development-and-diversity-of-ilcs-nk-cells-and-their-relevance-in-health-and-diseases
#7
Yuxia Zhang, Bing Huang
Next to T and B cells, natural killer (NK) cells are the third largest lymphocyte population. They are recently re-categorized as innate lymphocytes (ILCs), which also include ILC1, ILC2, ILC3, and the lymphoid tissue inducer (LTi) cells. Both NK cells and ILC1 cells are designated as group 1 ILCs because they secrete interferon-γ (IFN-γ) and tumor necrosis factor (TNF). However, in contrast to ILC1 and all other ILCs, NK cells possess potent cytolytic functions that resemble cytotoxic T lymphocytes (CTL)...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28921470/cgas-sting-activation-in-the-tumor-microenvironment-and-its-role-in-cancer-immunity
#8
Geneviève Pépin, Michael P Gantier
Stimulator of interferon (IFN) genes (STING) is a key mediator in the immune response to cytoplasmic DNA sensed by cyclic GMP-AMP (cGAMP) synthase (cGAS). After synthesis by cGAS, cGAMP acts as a second messenger activating STING in the cell harboring cytoplasmic DNA but also in adjacent cells through gap junction transfer. While the role of the cGAS-STING pathway in pathogen detection is now well established, its importance in cancer immunity has only recently started to emerge. Nonetheless, STING appears to be an essential component in the recruitment of immune cells to the tumor microenvironment, which is paramount to immune clearance of the tumor...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28921466/roles-of-hdacs-in-the-responses-of-innate-immune-cells-and-as-targets-in-inflammatory-diseases
#9
Yiqun Hu, Bandar Ali Suliman
Histone deacetylases (HDACs) are an emerging class of molecules involved in the epigenetic regulation of innate immune responses through Toll-like receptor (TLR) and interferon (IFN) signaling pathways. HDACs are also key drivers of inflammatory diseases via epigenetic regulation through chromatin DNA and histone modification by methylation and acetylation, among other mechanisms, which control innate immune cell gene expression. Importantly, these epigenetic changes are reversible, and HDACs may also be targeted by small-molecule HDAC inhibitors, which have been used in clinical settings for cancer therapy...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28919989/cyclophosphamide-treatment-regulates-the-balance-of-functional-exhausted-tumor-specific-cd8-t-cells
#10
Aurélie Hanoteau, Coralie Henin, David Svec, Charlotte Bisilliat Donnet, Sébastien Denanglaire, Didier Colau, Pedro Romero, Oberdan Leo, Benoit Van den Eynde, Muriel Moser
An important question is how chemotherapy may (re-)activate tumor-specific immunity. In this study, we provide a phenotypic, functional and genomic analysis of tumor-specific CD8(+) T cells in tumor (P815)-bearing mice, treated or not with cyclophosphamide. Our data show that chemotherapy favors the development of effector-type lymphocytes in tumor bed, characterized by higher KLRG-1 expression, lower PD-1 expression and increased cytotoxicity. This suggests re-engagement of T lymphocytes into the effector program...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919791/pegylated-interferon-plus-ribavirin-treatment-does-not-alter-the-prevalence-of-resistance-associated-substitutions-to-direct-acting-antivirals-in-hcv-genotype-1a-patients
#11
Zhi-Wei Chen, Xi-Chen Pang, Zhao Li, Hong Ren, Peng Hu
BACKGROUND: Direct-acting antiviral (DAA) resistance-associated substitutions (RASs) can jeopardize the effectiveness of DAAs in patients with hepatitis C virus (HCV). The selection pressure by pegylated-interferon (Peg-IFN) plus ribavirin (P/R) treatment may enhance HCV genome variation. However, whether P/R treatment alters the rate of change of RASs is still unclear. MATERIALS AND METHODS: We retrieved the genomic sequences of HCV genotype (GT) 1a patients from GenBank, which included patients naïve to P/R (pre-IFN group) and those previously treated with P/R (post-IFN group)...
2017: Infection and Drug Resistance
https://www.readbyqxmd.com/read/28919584/reduced-ifn-%C3%AE-production-in-chronic-brucellosis-patients
#12
Ehsanollah Ghaznavi Rad, Khadijeh Khosravi, Nader Zarinfar, Ghasem Mosayebi
BACKGROUND: Brucella is a well-known intracellular bacterium entailing acute and chronic illnesses in humans and domestic animals. The infection chronicity may be affected by the cell-mediated immunity and cytokine patterns. OBJECTIVE: To evaluate the patterns of T-helper cytokines in patients suffering from chronic and acute brucellosis. METHODS: In this cross-sectional study, 22 individuals with acute brucellosis, 21 individuals with chronic brucellosis, and 21 healthy individuals with the same genetic background were recruited from October 2015 to April 2016...
September 2017: Iranian Journal of Immunology: IJI
https://www.readbyqxmd.com/read/28919581/antitumor-response-to-a-codon-optimized-hpv-16-e7-hsp70-fusion-antigen-dna-vaccine
#13
Hoorieh Soleimanjahi, Hadi Razavinikoo, Fatemeh Fotouhi, Abdollah Ardebili
BACKGROUND: Vaccines based on virus-like particles are effective against Human Papilloma Virus (HPV) infection; however, they have not shown a therapeutic effect against HPV-associated diseases. New immunotherapy strategies based on immune responses against tumor antigens can positively affect the clearance of HPV-associated lesions. OBJECTIVE: To generate two therapeutic fusion DNA vaccines (optimizedE7/mouseHSP70 and wildE7/mouseHSP70) to induce antitumor specific responses in mice models...
September 2017: Iranian Journal of Immunology: IJI
https://www.readbyqxmd.com/read/28919514/hz-6d-targeted-herc5-to-regulate-p53-isgylation-in-human-hepatocellular-carcinoma
#14
Yang Wang, Qi Ding, Tao Xu, Chang-Yao Li, Dan-Dan Zhou, Lei Zhang
Manipulating the posttranslational modulator of p53 is central in the regulation of its activity and function. ISGylated p53 can be degraded by the 20S proteasome. During this process, HERC5/Ceb1, an IFN-induced HECT-type E3 ligase, mediated p53 ISGylation. In this study, we indicated that HERC5 was over-expressed in both HCC tissue samples and cell lines. Knockdown of HERC5 significantly induced the expression of p53, p21 and Bax/Bcl-2 in HCC cells, resulting in apoptosis augment. Whereas, opposite results were obtained by using HERC5 over-expression...
September 14, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28919454/a-robust-immune-system-conditions-the-response-to-abagovomab-anti-idiotypic-monoclonal-antibody-mimicking-the-ca125-protein-vaccination-in-ovarian-cancer-patients
#15
Alessandra Battaglia, Marco Fossati, Alexia Buzzonetti, Giovanni Scambia, Andrea Fattorossi
INTRODUCTION: Despite encouraging phase I and II study results, vaccination of ovarian cancer patients with abagovomab - an anti-idiotypic mAb that mimics the ovarian cancer CA125 protein - failed to demonstrate efficacy in the phase III trial named MIMOSA (NCT00418574). We postulated that in this trial patients with a more robust immune system did respond to abagovomab but went undetected among a larger number of non-responders. We also postulated that assessment of the immune system status ahead of abagovomab administration might predict patients' propensity to respond to abagovomab...
September 14, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28919446/increased-interferon-mediated-immunity-following-in-vitro-and-in-vivo-modafinil-treatment-on-peripheral-immune-cells
#16
Adriano Zager, Wesley Nogueira Brandão, Rafael Oliveira Margatho, Daniel Sanzio Gimenes Cruz, Jean Pierre Peron, Sergio Tufik, Monica Levy Andersen, Monica Moresco, Fabio Pizza, Giuseppe Plazzi, Birgitte Rahbek Kornum, João Palermo-Neto
The wake-promoting drug Modafinil has been used for treatment of sleep disorders, such as Narcolepsy, excessive daytime sleepiness and sleep apnea, due to its stimulant action. Despite the known effect of Modafinil on brain neurochemistry, particularly on brain dopamine system, recent evidence support an immunomodulatory role for Modafinil treatment in neuroinflammatory models. Here, we aimed to study the effects of in vitro and in vivo Modafinil treatment on activation, proliferation, cell viability, and cytokine production by immune cells in splenocytes culture from mice...
September 15, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28919362/a-homozygote-trex1-mutation-in-two-siblings-with-different-phenotypes-chilblains-and-cerebral-vasculitis
#17
Rabia Miray Kisla Ekinci, Sibel Balci, Atil Bisgin, Derya Ufuk Altintas, Mustafa Yılmaz
Three prime repair exonuclease 1 degrades single and double stranded DNA with 3'-5' nuclease activity and its mutations are related to type 1 IFN mediated autoinflammation due to accumulated intracellular nucleic acids. To date, several cases of systemic lupus erythematosus, Aicardi-Goutieres syndrome, familial chilblain lupus, retinal vasculopathy-cerebral leukodystrophy have been reported with TREX1 mutations. Chilblain lupus is a skin disease characterized by blue-reddish coloring, swelling or ulcers on acral regions of body such as fingertips, heels, nose and auricles...
September 12, 2017: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/28919361/molecular-characterisation-ontogeny-and-expression-analysis-of-melanoma-differentiation-associated-factor-5-mda5-from-asian-seabass-lates-calcarifer
#18
Anutosh Paria, M Makesh, Aparna Chaudhari, C S Purushothaman, K V Rajendran
MDA5 is the pivotal member of the retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) and is reported to play a crucial role in type I IFN-mediated responses against pathogen-associated molecular patterns (PAMPs), especially nucleic acids. In this study, we have identified and cloned the full-length cDNA sequence of MDA5, which comprises 3398 nucleotides and encodes for a putative protein of 978 AA length, in Asian seabass, Lates calcarifer. From the putative amino acid sequence of AsMDA5, four different conserved domains could be predicted: two N-terminal CARD domains, a DExDc domain, a HELICc domain and a C-terminal RIG-1_C-RD domain...
September 15, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28919298/mxra5-is-decreased-in-preeclampsia-and-affects-trophoblast-cell-invasion-through-the-mapk-pathway
#19
Lan Ding, Shaocong Li, Yanshang Zhang, Junfeng Gai, Jianfang Kou
Preeclampsia causes gestational failure in a significant number of women annually. Insufficient trophoblast cell invasion plays an essential role in preeclampsia pathogenesis. Matrix-remodeling associated 5 (MXRA5) is a proteoglycan involved in adhesion and matrix remodeling. This study sought to explore the role of MXRA5 in trophoblast cell invasion. Preeclamptic villi were obtained for the delineation of MXRA5 expression. Specific MXRA5 siRNA and pcDNA3.1/MXRA5 were used to manipulate MXRA5 expression in HTR-8/SVneo...
September 14, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28919109/long-term-measurements-of-human-inflammatory-cytokines-reveal-complex-baseline-variations-between-individuals
#20
Danlu Wu, Trinh L Dinh, Bruce P Bausk, David R Walt
Comprehensive characterization of the healthy human proteome baseline is essential for personalized medicine. Baseline data are necessary to understand the variation between individuals as well as longitudinal variation within individuals. Many important protein biomarkers, such as cytokines, exist at extremely low or undetectable levels in the healthy state. This paper describes results from a 14-week study of healthy human subjects using ultrasensitive single molecule array (Simoa) assays to measure both intra and intersubject variation of 15 cytokines...
September 14, 2017: American Journal of Pathology
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