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https://www.readbyqxmd.com/read/28732312/drug-eluting-scaffold-inhibited-in-vivo-pancreatic-tumorigenesis-by-engaging-murine-ccr4-cd8-t-cells
#1
Qian Zhan, Baiyong Shen, Yuan Fang, Xiaxing Deng, Hao Chen, Jiabin Jin, Chenghong Peng, Hongwei Li
CCL17 is well known for its ability to engage CCR4(+)CD8(+) T cells, which have been shown to play a critical role in preventing tumorigenesis. In this study, we attempted to inhibit in vivo pancreatic tumorigenesis by engaging murine CCR4(+)CD8(+) T cells through a drug-eluting scaffold with a payload of CCL17. The drug-eluting scaffold was fabricated by electrospinning polyglyconate and porcine gelatin. The electrospun scaffold featured randomly distributed non-woven fibers with diameters ranging from 1μm to 4μm...
July 10, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28731372/exploring-the-effect-of-vitamin-d3-supplementation-on-the-anti-ebv-antibody-response-in-relapsing-remitting-multiple-sclerosis
#2
Linda Rolf, Anne-Hilde Muris, Amandine Mathias, Renaud Du Pasquier, Inga Koneczny, Giulio Disanto, Jens Kuhle, Sreeram Ramagopalan, Jan Damoiseaux, Joost Smolders, Raymond Hupperts
BACKGROUND: Epstein-Barr virus (EBV) infection and vitamin D insufficiency are potentially interacting risk factors for multiple sclerosis (MS). OBJECTIVES: To investigate the effect of high-dose vitamin D3 supplements on antibody levels against the EBV nuclear antigen-1 (EBNA-1) in patients with relapsing-remitting multiple sclerosis (RRMS) and to explore any underlying mechanism affecting anti-EBNA-1 antibody levels. METHODS: This study utilized blood samples from a randomized controlled trial in RRMS patients receiving either vitamin D3 (14,000 IU/day; n = 30) or placebo ( n = 23) over 48 weeks...
July 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28730140/current-advances-in-checkpoint-inhibitors-lessons-from-non-central-nervous-system-cancers-and-potential-for-glioblastoma
#3
REVIEW
Natasha Lakin, Robert Rulach, Stefan Nowicki, Kathreena M Kurian
The adaptive immune system depends on the sequence of antigen presentation, activation, and then inhibition to mount a proportionate response to a threat. Tumors evade the immune response partly by suppressing T-cell activity using immune checkpoints. The use of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PD-L1) antibodies counteract this suppression, thereby enhancing the antitumor activity of the immune system. This approach has proven efficacy in melanoma, renal cancer, and lung cancer...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28729866/cytokine-induced-killer-cells-as-pharmacological-tools-for-cancer-immunotherapy
#4
REVIEW
Xingchun Gao, Yajing Mi, Na Guo, Hao Xu, Lixian Xu, Xingchun Gou, Weilin Jin
Cytokine-induced killer (CIK) cells are a heterogeneous population of effector CD3(+)CD56(+) natural killer T cells, which can be easily expanded in vitro from peripheral blood mononuclear cells. CIK cells work as pharmacological tools for cancer immunotherapy as they exhibit MHC-unrestricted, safe, and effective antitumor activity. Much effort has been made to improve CIK cells cytotoxicity and treatments of CIK cells combined with other antitumor therapies are applied. This review summarizes some strategies, including the combination of CIK with additional cytokines, dendritic cells, check point inhibitors, antibodies, chemotherapeutic agents, nanomedicines, and engineering CIK cells with a chimeric antigen receptor...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28729689/metal-nanoclusters-with-synergistically-engineered-optical-and-buffering-activity-of-intracellular-reactive-oxygen-species-by-compositional-and-supramolecular-design
#5
B Santiago-Gonzalez, A Monguzzi, M Caputo, C Villa, M Prato, C Santambrogio, Y Torrente, F Meinardi, S Brovelli
Metal nanoclusters featuring tunable luminescence and high biocompatibility are receiving attention as fluorescent markers for cellular imaging. The recently discovered ability of gold clusters to scavenge cytotoxic reactive oxygen species (ROS) from the intracellular environment extends their applicability to biomedical theranostics and provides a novel platform for realizing multifunctional luminescent probes with engineered anti-cytotoxic activity for applications in bio-diagnostics and conceivably cellular therapy...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729358/targeting-c-type-lectin-receptors-a-high-carbohydrate-diet-for-dendritic-cells-to-improve-cancer-vaccines
#6
REVIEW
Dieke van Dinther, Dorian A Stolk, Rieneke van de Ven, Yvette van Kooyk, Tanja D de Gruijl, Joke M M den Haan
There is a growing understanding of why certain patients do or do not respond to checkpoint inhibition therapy. This opens new opportunities to reconsider and redevelop vaccine strategies to prime an anticancer immune response. Combination of such vaccines with checkpoint inhibitors will both provide the fuel and release the brake for an efficient anticancer response. Here, we discuss vaccine strategies that use C-type lectin receptor (CLR) targeting of APCs, such as dendritic cells and macrophages. APCs are a necessity for the priming of antigen-specific cytotoxic and helper T cells...
July 20, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28728794/myeloid-suppressor-cells-in-cancer-and-autoimmunity
#7
REVIEW
Antonio Sica, Marco Massarotti
A bottleneck for immunotherapy of cancer is the immunosuppressive microenvironment in which the tumor cells proliferate. Cancers harness the immune regulatory mechanism that prevents autoimmunity from evading immunosurveillance and promoting immune destruction. Regulatory T cells, myeloid suppressor cells, inhibitory cytokines and immune checkpoint receptors are the major components of the immune system acting in concert with cancer cells and causing the subversion of anti-tumor immunity. This redundant immunosuppressive network poses an impediment to efficacious immunotherapy by facilitating tumor progression...
July 17, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28726787/alkbh7-drives-a-tissue-and-sex-specific-necrotic-cell-death-response-following-alkylation-induced-damage
#8
Jennifer J Jordan, Sophea Chhim, Carrie M Margulies, Mariacarmela Allocca, Roderick T Bronson, Arne Klungland, Leona D Samson, Dragony Fu
Regulated necrosis has emerged as a major cell death mechanism in response to different forms of physiological and pharmacological stress. The AlkB homolog 7 (ALKBH7) protein is required for regulated cellular necrosis in response to chemotherapeutic alkylating agents but its role within a whole organism is unknown. Here, we show that ALKBH7 modulates alkylation-induced cellular death through a tissue and sex-specific mechanism. At the whole-animal level, we find that ALKBH7 deficiency confers increased resistance to MMS-induced toxicity in male but not female mice...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28726761/a-cell-adhesive-plasma-polymerized-allylamine-coating-reduces-the-in-vivo-inflammatory-response-induced-by-ti6al4v-modified-with-plasma-immersion-ion-implantation-of-copper
#9
Uwe Walschus, Andreas Hoene, Maciej Patrzyk, Silke Lucke, Birgit Finke, Martin Polak, Gerold Lukowski, Rainer Bader, Carmen Zietz, Andreas Podbielski, J Barbara Nebe, Michael Schlosser
Copper (Cu) could be suitable to create anti-infective implants based on Titanium (Ti), for example by incorporating Cu into the implant surface using plasma immersion ion implantation (Cu-PIII). The cytotoxicity of Cu might be circumvented by an additional cell-adhesive plasma polymerized allylamine film (PPAAm). Thus, this study aimed to examine in vivo local inflammatory reactions for Ti6Al4V implants treated with Cu-PIII (Ti-Cu), alone or with an additional PPAAm film (Ti-Cu-PPAAm), compared to untreated implants (Ti)...
July 20, 2017: Journal of Functional Biomaterials
https://www.readbyqxmd.com/read/28726600/age-and-sex-associated-differences-in-phenotypic-and-functional-characteristics-of-peripheral-blood-lymphocytes-in-chimpanzees-pan-troglodytes
#10
Pramod Nehete, Elizabeth Magden, Bharti Nehete, Lawrence Williams, Christian Abee, K Sastry
Chimpanzees are the closest phylogenetic relatives to humans, sharing more than 98% genetic sequence identity. Thesegenetic similarities prompted the belief that chimpanzees can serve as an ideal model for human disease conditions andvaccine development. However, in light of the recent NIH decision to phase out biomedical research in chimpanzees and retire NIH-supported chimpanzees, data from the present study will continue to provide value for the care of aged and sick chimpanzees located in zoos, sanctuaries, and primate centers...
July 19, 2017: Journal of the American Association for Laboratory Animal Science: JAALAS
https://www.readbyqxmd.com/read/28726521/polymer-donors-of-nitric-oxide-improve-the-treatment-of-experimental-solid-tumours-with-nanosized-polymer-therapeutics
#11
Milada Šírová, Veronika Horková, Tomáš Etrych, Petr Chytil, Blanka Říhová, Martin Studenovský
Polymer carriers based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers with incorporated organic nitrates as nitric oxide (NO) donors were designed with the aim to localize NO generation in solid tumours, thus highly increasing the enhanced permeability and retention (EPR) effect. The NO donors were coupled to the polymer carrier either through a stable bond or through a hydrolytically degradable, pH sensitive, bond. In vivo, the co-administration of the polymer NO donor and HPMA copolymer-bound cytotoxic drug (doxorubicin; Dox) resulted in an improvement in the treatment of murine EL4 T-cell lymphoma...
July 20, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28726519/cancer-stem-cells-cd133-inhibition-and-cytotoxicity-of-certain-3-phenylthiazolo-3-2-a-benzimidazoles-design-direct-synthesis-crystal-study-and-in-vitro-biological-evaluation
#12
Ghada H Al-Ansary, Wagdy M Eldehna, Hazem A Ghabbour, Sara T A Al-Rashood, Khalid A Al-Rashood, Radwa A Eladwy, Abdullah Al-Dhfyan, Maha M Kabil, Hatem A Abdel-Aziz
Cancer stem cells (CSCs) have been objects of intensive study since their identification in 1994. Adopting a structural rigidification approach, a novel series of 3-phenylthiazolo[3,2-a]benzimidazoles 4a-d was designed and synthesised, in an attempt to develop potent anticancer agent that can target the bulk of tumour cells and CSCs. The anti-proliferative activity of the synthesised compounds was evaluated against two cell lines, namely; colon cancer HT-29 and triple negative breast cancer MDA-MB-468 cell lines...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28725433/macrophage-type-2-differentiation-in-a-patient-with-laryngeal-squamous-cell-carcinoma-and-metastatic-prostate-adenocarcinoma-to-the-cervical-lymph-nodes
#13
Michael C Topf, Madalina Tuluc, Larry A Harshyne, Adam Luginbuhl
BACKGROUND: The tumor microenvironment often polarizes infiltrating macrophages towards a type 2, or M2 phenotype, that is characterized by expression of various cysteine-rich, scavenger receptors, including CD163. The primary function of M2 macrophages is to facilitate wound healing. As such, they are capable of providing metabolic support to a growing tumor, neovascularization, as well as protection from cytotoxic T cells. The tumor microenvironment contains a milieu of secreted factors and vesicles, which in certain circumstances can gain access to lymphatic vessels that drain to local lymph nodes...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28725220/a-novel-derivative-of-mycousnine-produced-by-the-endophytic-fungus-mycosphaerella-nawae-exhibits-high-and-selective-immunosuppressive-activity-on-t-cells
#14
Li-Wei Wang, Jin-Liang Wang, Jing Chen, Jia-Jie Chen, Jia-Wei Shen, Xiao-Xiao Feng, Christian P Kubicek, Fu-Cheng Lin, Chu-Long Zhang, Feng-Yang Chen
An endophytic fungus, Mycosphaerella nawae ZJLQ129, was isolated from the leaves of the traditional Chinese medicine Smilax china. From the fermentation broth and mycelium, a dibenzofurane compound (-)mycousnine (1) was isolated. Chemical modification of it to the amide derivative (-)mycousnine enamine (2), which is new to science, was found to have high and selective immunosuppressive activity: similar to cyclosporin A, (-)mycousnine enamine (2) selectively inhibited T cell proliferation, suppressed the expression of the surface activation antigens CD25 and CD69 and the formation and expression of the cytokines interleukin-2 as well as interferon γ in activated T cells, but did not show any effect on the proliferation of B cells and cancer cells (PANC-1 and A549) and the activation of macrophages...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28725044/cord-blood-nk-cells-engineered-to-express-il-15-and-a-cd19-targeted-car-show-long-term-persistence-and-potent-anti-tumor-activity
#15
E Liu, Y Tong, G Dotti, H Shaim, B Savoldo, M Mukherjee, J Orange, X Wan, X Lu, A Reynolds, M Gagea, P Banerjee, R Cai, M H Bdaiwi, R Basar, M Muftuoglu, L Li, D Marin, W Wierda, M Keating, R Champlin, E Shpall, K Rezvani
Chimeric antigen receptors (CARs) have been used to redirect the specificity of autologous T-cells against leukemia and lymphoma with promising clinical results.(1-3) Extending this approach to allogeneic T-cells is problematic as they carry a significant risk of graft-versus-host disease (GVHD). Natural killer (NK) cells are highly cytotoxic effectors, killing their targets in a non-antigen specific manner without causing GVHD. Cord blood (CB) offers an attractive, allogeneic, off-the-self source of NK cells for immunotherapy...
July 20, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28724801/tcr-ligand-dissociation-rate-is-a-robust-and-stable-biomarker-of-cd8-t-cell-potency
#16
Mathilde Allard, Barbara Couturaud, Laura Carretero-Iglesia, Minh Ngoc Duong, Julien Schmidt, Gwennaëlle C Monnot, Pedro Romero, Daniel E Speiser, Michael Hebeisen, Nathalie Rufer
Despite influencing many aspects of T cell biology, the kinetics of T cell receptor (TCR) binding to peptide-major histocompatibility molecules (pMHC) remain infrequently determined in patient monitoring or for adoptive T cell therapy. Using specifically designed reversible fluorescent pMHC multimeric complexes, we performed a comprehensive study of TCR-pMHC off-rates combined with various functional assays on large libraries of self/tumor- and virus-specific CD8+ T cell clones from melanoma patients and healthy donors...
July 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28724766/a-unique-t-cell-receptor-amino-acid-sequence-selected-by-htlv-i-tax301-309-specific-cytotoxic-t-cells-in-hla-a24-02-asymptomatic-carriers-and-adult-t-cell-leukemia-lymphoma-patients
#17
Yuko Ishihara, Yukie Tanaka, Seiichiro Kobayashi, Koji Kawamura, Hideki Nakasone, Ayumi Gomyo, Jin Hayakawa, Masaharu Tamaki, Yu Akahoshi, Naonori Harada, Machiko Kusuda, Kazuaki Kameda, Tomotaka Ugai, Hidenori Wada, Kana Sakamoto, Miki Sato, Kiriko Terasako-Saito, Misato Kikuchi, Shun-Ichi Kimura, Aki Tanihara, Shinichi Kako, Kaoru Uchimaru, Yoshinobu Kanda
We previously reported that the T-cell receptor (TCR) repertoire of HTLV-I Tax301-309-specific CD8(+) cytotoxic T-cells (Tax-CTLs) was highly restricted and a particular amino acid sequence motif, "PDR", was conserved among HLA-A*24:02(+) ATL patients who have undergone allogeneic hematopoietic cell transplantation (allo-HSCT). Furthermore, we found that donor-derived PDR+CTLs selectively expanded in ATL long-term HSCT survivors with strong CTL activity against HTLV-I. On the other hand, the TCR repertoires in Tax-CTL of asymptomatic HTLV-I carriers (ACs) remain unclear...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28724188/bisindole-oxadiazole-hybrids-t3p-%C3%A2-mediated-synthesis-and-appraisal-of-their-apoptotic-antimetastatic-and-computational-bcl-2-binding-potential
#18
Pooja R Kamath, Manu M Joseph, Abdul Ajees Abdul Salam, Sreelekha T Therakathinal, Dhanya Sunil, Subhankar Biswas, Karkala Sreedhara Ranganath Pai
In the pursuit of novel anticancer leads, new bisindole-oxadiazoles were synthesized using propyl phosphonic anhydride as a mild and efficient reagent. The molecule, 3-[5-(1H-indol-3-ylmethyl)-1,3,4-oxadiazol-2-yl]-1H-indole (3a) exhibited selective cytotoxicity to MCF-7 cells with a cell cycle arrest in the G1 phase. The mechanism of cytotoxicity of 3a involved caspase-2-dependent apoptotic pathway with characteristic apoptotic morphological alterations as observed in acridine orange/ethidium bromide and Hoechst staining...
July 19, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28723659/data-driven-analysis-of-immune-infiltrate-in-a-large-cohort-of-breast-cancer-and-its-association-with-disease-progression-er-activity-and-genomic-complexity
#19
Ruth Dannenfelser, Marianne Nome, Andliena Tahiri, Josie Ursini-Siegel, Hans Kristian Moen Vollan, Vilde D Haakensen, Åslaug Helland, Bjørn Naume, Carlos Caldas, Anne-Lise Børresen-Dale, Vessela N Kristensen, Olga G Troyanskaya
The tumor microenvironment is now widely recognized for its role in tumor progression, treatment response, and clinical outcome. The intratumoral immunological landscape, in particular, has been shown to exert both pro-tumorigenic and anti-tumorigenic effects. Identifying immunologically active or silent tumors may be an important indication for administration of therapy, and detecting early infiltration patterns may uncover factors that contribute to early risk. Thus far, direct detailed studies of the cell composition of tumor infiltration have been limited; with some studies giving approximate quantifications using immunohistochemistry and other small studies obtaining detailed measurements by isolating cells from excised tumors and sorting them using flow cytometry...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723561/crosstalk-between-regulatory-t-cells-and-tumor-associated-dendritic-cells-negates-anti-tumor-immunity-in-pancreatic-cancer
#20
Jung-Eun Jang, Cristina H Hajdu, Caroline Liot, George Miller, Michael L Dustin, Dafna Bar-Sagi
Regulatory T (Treg) cell infiltration constitutes a prominent feature of pancreatic ductal adenocarcinoma (PDA). However, the immunomodulatory function of Treg cells in PDA is poorly understood. Here, we demonstrate that Treg cell ablation is sufficient to evoke effective anti-tumor immune response in early and advanced pancreatic tumorigenesis in mice. This response is dependent on interferon-γ (IFN-γ)-producing cytotoxic CD8(+) T cells. We show that Treg cells engage in extended interactions with tumor-associated CD11c(+) dendritic cells (DCs) and restrain their immunogenic function by suppressing the expression of costimulatory ligands necessary for CD8(+) T cell activation...
July 18, 2017: Cell Reports
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