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https://www.readbyqxmd.com/read/28076753/cd25-targeted-therapy-of-chemotherapy-resistant-leukemic-stem-cells-using-dr5-specific-trail-peptide
#1
Jayaprakasam Madhumathi, Surapally Sridevi, Rama Shanker Verma
Chemotherapy resistant leukemic stem cells (LSCs) are being targeted as a modern therapeutic approach to prevent disease relapse. LSCs isolated from methotrexate resistant side population (SP) of leukemic cell lines HL60 and MOLT4 exhibited high levels of CD25 and TRAIL R2/DR5 which are potential targets. Recombinant immunotoxin conjugating IL2α with TRAIL peptide mimetic was constructed for DR5 receptor specific targeting of LSCs and were tested in total cell population and LSCs. IL2-TRAIL peptide induced apoptosis in drug resistant SP cells from cell lines and showed potent cytotoxicity in PBMCs derived from leukemic patients with an efficacy of 81...
January 4, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28056941/neutrophil-lymphocyte-ratio-as-a-predictive-biomarker-for-response-to-high-dose-interleukin-2-in-patients-with-renal-cell-carcinoma
#2
James A Kuzman, David D Stenehjem, Joseph Merriman, Archana M Agarwal, Shiven B Patel, Andrew W Hahn, Anitha Alex, Dan Albertson, David M Gill, Neeraj Agarwal
BACKGROUND: Immunotherapy with high-dose interleukin-2 (HD-IL2) results in long-term survival in some metastatic renal cell carcinoma (mRCC) patients but has significant acute toxicities. Biomarkers predicting response to therapy are needed to better select patients most likely to benefit. NLR (absolute neutrophil count (ANC)/absolute lymphocyte count (ALC)) is a prognostic and predicative biomarker in various malignancies. The goal was to determine whether NLR can predict response to HD-IL2 in this setting...
January 5, 2017: BMC Urology
https://www.readbyqxmd.com/read/27999747/immune-response-and-long-term-clinical-outcome-in-advanced-melanoma-patients-vaccinated-with-tumor-mrna-transfected-dendritic-cells
#3
Jon Amund Kyte, Steinar Aamdal, Svein Dueland, Stein Sæbøe-Larsen, Else Marit Inderberg, Ulf Erik Madsbu, Eva Skovlund, Gustav Gaudernack, Gunnar Kvalheim
The most effective anticancer immune responses are probably directed against patient-specific neoantigens. We have developed a melanoma vaccine targeting this individual mutanome based on dendritic cells (DCs) loaded with autologous tumor-mRNA. Here, we report a phase I/II trial evaluating toxicity, immune response and clinical outcome in 31 metastatic melanoma patients. The first cohort (n = 22) received the vaccine without any adjuvant; the next cohort (n = 9) received adjuvant IL2. Each subject received four weekly intranodal or intradermal injections, followed by optional monthly vaccines...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27992487/changes-in-host-cytokine-patterns-of-tb-patients-with-different-bacterial-loads-detected-using-16s-rrna-analysis
#4
Rhiannon Heslop, Adama L Bojang, Sheikh Jarju, Joseph Mendy, Sarah Mulwa, Ousman Secka, Francis S Mendy, Olumuyiwa Owolabi, Beate Kampmann, Jayne S Sutherland
BACKGROUND: Tuberculosis (TB) has overtaken HIV as the biggest infectious disease killer, with the majority of deaths occurring in sub-Saharan Africa. However it is unknown how differences in bacterial load alter host immune profiles in the sputum and blood of TB patients. METHODS: 16S ribosomal RNA analysis was used to determine bacterial load in sputum samples obtained from 173 patients with active TB (57 pre-treatment and 116 post-treatment). Host analyte concentrations in sputum and Mycobacterium tuberculosis (Mtb) antigen stimulated whole blood assay supernatants were analysed using multiplex cytokine arrays...
2016: PloS One
https://www.readbyqxmd.com/read/27989104/dna-demethylation-of-the-foxp3-enhancer-is-maintained-through-modulation-of-ten-eleven-translocation-and-dna-methyltransferases
#5
Varun Sasidharan Nair, Mi Hye Song, Myunggon Ko, Kwon Ik Oh
Stable expression of Foxp3 is ensured by demethylation of CpG motifs in the Foxp3 intronic element, the conserved non-coding sequence 2 (CNS2), which persists throughout the lifespan of regulatory T cells (Tregs). However, little is known about the mechanisms on how CNS2 demethylation is sustained. In this study, we found that Ten-Eleven-Translocation (Tet) DNA dioxygenase protects the CpG motifs of CNS2 from re-methylation by DNA methyltransferases (Dnmts) and prevents Tregs from losing Foxp3 expression under inflammatory conditions...
December 2016: Molecules and Cells
https://www.readbyqxmd.com/read/27986689/hla-b-57-and-ifnl4-related-polymorphisms-are-associated-with-protection-against-hiv-1-disease-progression-in-controllers
#6
B Dominguez-Molina, L Tarancon-Diez, S Hua, C Abad-Molina, E Rodriguez-Gallego, K Machmach, F Vidal, C Tural, S Moreno, J M Goñi, E Ramírez de Arellano, M Del Val, M F Gonzalez-Escribano, J Del Romero, C Rodriguez, L Capa, P Viciana, J Alcamí, X G Yu, B D Walker, Leal M, M Lichterfeld, E Ruiz-Mateos
BACKGROUND: HIV-1-controllers maintain HIV-1 viremia at low levels (normally <2000 HIV-RNA copies/mL) without antiretroviral treatment. However, some HIV-1-controllers have evidence of immunologic progression with marked CD4(+)T-cell decline. We investigated host genetic factors associated with protection against CD4(+)T-cell loss in HIV-1-controllers. METHODS: We analysed the association of interferon lambda 4 (IFNL4)-related polymorphisms and HLA-B haplotypes within Long Term Non-Progressor HIV-1-controllers ((LTNP-C), defined by maintaining CD4(+)T-cells counts >500 cells/mm(3) for more than 7 years after HIV-1 diagnosis) versus non-LTNP-C, who developed CD4(+)T-cells counts <500 cells/mm(3) Both a Spanish study cohort (n=140) and an international validation cohort (n=914) were examined...
December 16, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/27983725/a-gene-expression-inflammatory-signature-specifically-predicts-multiple-myeloma-evolution-and-patients-survival
#7
C Botta, M T Di Martino, D Ciliberto, M Cucè, P Correale, M Rossi, P Tagliaferri, P Tassone
Multiple myeloma (MM) is closely dependent on cross-talk between malignant plasma cells and cellular components of the inflammatory/immunosuppressive bone marrow milieu, which promotes disease progression, drug resistance, neo-angiogenesis, bone destruction and immune-impairment. We investigated the relevance of inflammatory genes in predicting disease evolution and patient survival. A bioinformatics study by Ingenuity Pathway Analysis on gene expression profiling dataset of monoclonal gammopathy of undetermined significance, smoldering and symptomatic-MM, identified inflammatory and cytokine/chemokine pathways as the most progressively affected during disease evolution...
December 16, 2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27964715/differential-effects-of-palmitoleic-acid-on-human-lymphocyte-proliferation-and-function
#8
M E P Passos, H H O Alves, C M Momesso, F G Faria, G Murata, M F Cury-Boaventura, E Hatanaka, S Massao-Hirabara, R Gorjão
BACKGROUND: Palmitoleic acid (PA) is a n-7 monounsaturated fatty acid (MUFA) secreted by adipose tissue and related to decreased insulin resistance in peripheral tissues. Evidences have been shown that PA also decreased proinflammatory cytokine expression in cultured macrophages. Although studies have shown that other fatty acids (FAs) modulate several lymphocyte functions, the specific effect of PA on these cells is unknown. The aim of the present study was to evaluate the possible influence of PA on activation and differentiation of human lymphocytes in comparison to oleic acid (OA)...
December 13, 2016: Lipids in Health and Disease
https://www.readbyqxmd.com/read/27959627/humanized-mouse-models-of-clinical-disease
#9
Nicole C Walsh, Laurie L Kenney, Sonal Jangalwe, Ken-Edwin Aryee, Dale L Greiner, Michael A Brehm, Leonard D Shultz
Immunodeficient mice engrafted with functional human cells and tissues, that is, humanized mice have become increasingly important as small, preclinical animal models for the study of human diseases. Since the description of immunodeficient mice bearing mutations in the IL2 receptor common gamma chain (IL2rg(null)) in the early 2000s, investigators have been able to engraft murine recipients with human hematopoietic stem cells that develop into functional human immune systems. These mice can also be engrafted with human tissues such as islets, liver, skin, and most solid and hematologic cancers...
December 5, 2016: Annual Review of Pathology
https://www.readbyqxmd.com/read/27941004/optimization-of-peptide-vaccines-to-induce-robust-antitumor-cd4-t-cell-responses
#10
Takumi Kumai, Sujin Lee, Hyun-Il Cho, Hussein Sultan, Hiroya Kobayashi, Yasuaki Harabuchi, Esteban Celis
Substantial evidence indicates that immunotherapy is a feasible and effective approach for the treatment of numerous types of cancer. Among various immunotherapy options, peptide vaccines to generate antitumor T cells appear as promising candidates, because of their cost effectiveness and ease of implementation. Nevertheless, most peptide vaccines are notorious for being weekly immunogenic and, thus, optimization of the vaccination strategy is essential to achieve therapeutic effectiveness. In addition, effective peptide vaccines must stimulate both CD8 cytotoxic and CD4 helper T lymphocytes...
January 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/27938713/cellular-response-markers-and-cytokine-gene-expression-in-the-central-nervous-system-of-cattle-naturally-infected-with-bovine-herpesvirus-5
#11
T C Cardoso, H L Ferreira, L H Okamura, T P Giroto, B R S M Oliveira, C U F Fabri, R Gameiro, E F Flores
The present study reports an investigation on the phenotype of inflammatory and immune cells, cytokine and viral gene expression in the brains of cattle naturally infected with bovine herpesvirus 5 (BHV5). Brain sections of 38 affected animals were analysed for the nature and extent of perivascular cuffs in the Virchow-Robin space and parenchyma. Histopathological changes were severe in the olfactory bulbs (Obs), hippocampus, piriform, frontal, temporal and parietal cortices/lobes and were characterized by inflammatory infiltrates in Virchow-Robin spaces...
December 2016: Veterinary Journal
https://www.readbyqxmd.com/read/27923824/human-dendritic-cells-mitigate-nk-cell-dysfunction-mediated-by-nonselective-jak1-2-blockade
#12
Shane A Curran, Justin A Shyer, Erin T St Angelo, Lillian R Talbot, Sneh Sharma, David J Chung, Glenn Heller, Katharine C Hsu, Brian C Betts, James W Young
Janus kinase (JAK) inhibitors have achieved positive responses in myeloproliferative neoplasms, but at the expense of decreased natural killer (NK) cell numbers and compromised function. Selective JAK2 inhibition may also have a role in preventing and treating graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Although JAK inhibitors can impair monocyte-derived dendritic cell (moDC) activation and function and suppress effector T-cell responses, the effects on NK cells and the relevant mechanisms remain undefined...
December 6, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27910810/production-of-tnf-alpha-ex-vivo-is-predictive-of-an-immune-response-to-flu-vaccination-in-a-frail-elderly-population
#13
Frédéric Bloch, Bénédicte Charmeteau, Michael Tovey, Jean-François Meritet, Corinne Desaint, Odile Launay, Pierre Lebon
OBJECTIVE: To investigate the relationship between the response to influenza vaccination and the ability to produce proinflamatory cytokines in elderly subjects. METHODS: Whole blood samples from 25 elderly subjects collected before influenza vaccination were stimulated with the influenza vaccine in order to evaluate the secretion of five specific cytokines: TNFα, IFNα, IFNγ, IL2 and IL10. The results were correlated with the increased HAI antibody titres two weeks after vaccination...
September 1, 2016: European Cytokine Network
https://www.readbyqxmd.com/read/27903296/factors-affecting-long-term-efficacy-of-t-regulatory-cell-based-therapy-in-type-1-diabetes
#14
Natalia Marek-Trzonkowska, Małgorzata Myśliwiec, Dorota Iwaszkiewicz-Grześ, Mateusz Gliwiński, Ilona Derkowska, Magdalena Żalińska, Maciej Zieliński, Marcelina Grabowska, Hanna Zielińska, Karolina Piekarska, Anna Jaźwińska-Curyłło, Radosław Owczuk, Agnieszka Szadkowska, Krystyna Wyka, Piotr Witkowski, Wojciech Młynarski, Przemysława Jarosz-Chobot, Artur Bossowski, Janusz Siebert, Piotr Trzonkowski
BACKGROUND: Recent studies suggest that immunotherapy using T regulatory cells (Tregs) prolongs remission in type 1 diabetes (T1DM). Here, we report factors that possibly affect the efficacy of this treatment. METHODS: The metabolic and immune background of 12 children with recently diagnosed T1DM, as well as that of untreated subjects, during a 2-year follow-up is presented. Patients were treated with up to 30 × 10(6)/kg b.w. of autologous expanded CD3(+)CD4(+)CD25(high)CD127(-) Tregs...
December 1, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27886209/virus-infection-drives-il-2-antibody-complexes-into-pro-inflammatory-agonists-in-mice
#15
Wendy W L Lee, Teck-Hui Teo, Fok-Moon Lum, Anand K Andiappan, Siti Naqiah Amrun, Laurent Rénia, Olaf Rötzschke, Lisa F P Ng
The use of IL-2/JES6-1 Ab complex (IL-2 Ab Cx) has been considered as a potential therapeutic for inflammatory diseases due to its selective expansion of regulatory T cells (Tregs) in mice. Here, IL-2 Ab Cx was explored as a therapeutic agent to reduce joint inflammation induced by chikungunya virus, an alphavirus causing debilitating joint disease globally. Virus-infected mice treated with IL-2 Ab Cx exhibited exacerbated joint inflammation due to infiltration of highly activated CD4(+) effector T cells (Teffs)...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27884693/design-synthesis-and-characterization-of-rhein-analogs-as-novel-inhibitors-of-scavenger-receptor-a
#16
Yi Zheng, Xia Li, Piyusha P Pagare, Yunyun Yuan, Xiang-Yang Wang, Yan Zhang
Scavenger receptor A (SRA) has been known as an immunosuppressive factor and therefore therapeutic inhibition of SRA may be potentially exploited for cancer immunotherapy. Our previously work suggested that rhein may act as an inhibitor of SRA in reversing immunosuppression of SRA during T cells activation. Herein, three deconstruction analogs of rhein, compound 1, 2, and 3, were further studied as inhibitors of SRA. These three compounds, particularly compound 1, also known as a natural product danthron, enhanced T cells activation, indicated by increased transcriptional activation of interleukin 2 (Il2) gene, production of IL-2 protein, and proliferation of T cells...
January 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27866265/proteomic-analysis-of-fasciola-hepatica-excretory-and-secretory-products-fhesps-involved-in-interacting-with-host-pbmcs-and-cytokines-by-shotgun-lc-ms-ms
#17
Qing Liu, Si-Yang Huang, Dong-Mei Yue, Jin-Lei Wang, Yujian Wang, Xiangrui Li, Xing-Quan Zhu
Fasciola hepatica is a helminth parasite with a worldwide distribution, which can cause chronic liver disease, fasciolosis, leading to economic losses in the livestock and public health in many countries. Control is mostly reliant on the use of drugs, and as a result, drug resistance has now emerged. The identification of F. hepatica genes involved in interaction between the parasite and host immune system is utmost important to elucidate the evasion mechanisms of the parasite and develop more effective strategies against fasciolosis...
November 19, 2016: Parasitology Research
https://www.readbyqxmd.com/read/27852627/co-opting-innate-and-adaptive-immunity-against-cancer
#18
(no author information available yet)
Researchers at the Massachusetts Institute of Technology in Cambridge have devised a way to completely eradicate large, established tumors in mice. Their four-component strategy comprises a tumor-specific antibody and vaccine, along with IL2 and anti-PD-1 therapy, which employs both innate and adaptive immunity for tumor destruction.
January 2017: Cancer Discovery
https://www.readbyqxmd.com/read/27847359/human-asymptomatic-epitopes-identified-from-the-herpes-simplex-virus-tegument-protein-vp13-14-ul47-preferentially-recall-polyfunctional-effector-memory-cd44highcd62llowcd8-tem-cells-and-protect-humanized-hla-a-02-01-transgenic-mice-against-ocular-herpes
#19
Ruchi Srivastava, Arif A Khan, Sumit Garg, Sabrina A Syed, Julie N Furness, Hawa Vahed, Tiffany Pham, Howard T Yu, Anthony B Nesburn, Lbachir BenMohamed
: The herpes simplex virus type 1 (HSV-1) infection is widespread among humans. The HSV-1 virion protein 13/14 (VP13/14), also known as UL47, is a tegument antigen targeted by CD8(+) T cells from HSV-seropositive individuals. However, whether VP13/14-specific CD8(+) T cells play a role in the "natural protection" seen in asymptomatic (ASYMP) individuals (have never had a clinical herpetic disease) has not been elucidated. Using predictive computer-assisted algorithms, we identified 10 potential HLA-A*02:01-restricted CD8(+) T cell epitopes from the 693 amino acids sequence of VP13/14 protein...
November 9, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27820940/activated-phosphorylated-stat1-levels-as-a-biologically-relevant-immune-signal-in-schizophrenia
#20
Rajiv P Sharma, Cherise Rosen, Jennifer K Melbourne, Benjamin Feiner, Kayla A Chase
OBJECTIVE: Activation of STAT1 is directly downstream of the cytokine receptors that signal from specific proinflammatory cytokines known to be dysregulated in schizophrenia (SZ), such as IFNγ, IL6, IL2 and IL10, as well as hypoxia, viral/bacterial infections and peptide growth factors. If the increased cytokine protein levels repeatedly observed in SZ have biological consequences, then the measurement of pSTAT1 is a logical step forward. METHODS: Peripheral blood mononuclear cells (PBMCs) from controls (n = 13) and subjects with SZ (n = 22) were extracted using the Ficoll method...
November 8, 2016: Neuroimmunomodulation
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