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Cytotoxic T cell

Marina T Varela, Maiara M Romaneli, Marta L Lima, Samanta E T Borborema, Andre G Tempone, João P S Fernandes
Chagas' disease and leishmaniasis are parasitic infections enrolled among the neglected tropical diseases, which urge for new treatments. In the search for new chemical entities as prototypes, gibbilimbols A/B have shown antiparasitic activity against Trypanosoma cruzi and Leishmania infantum, and then a set of analogues (LINS03 series) of this natural product were synthesized and evaluated in vitro against the parasites. In the present paper we reported five new compounds with activity against these protozoan parasites, and quite low cytotoxicity...
June 20, 2018: European Journal of Pharmaceutical Sciences
Rindert Missiaen, Massimiliano Mazzone, Gabriele Bergers
Tumor angiogenesis and escape of immunosurveillance are two cancer hallmarks that are tightly linked and reciprocally regulated by paracrine signaling cues of cell constituents from both compartments. Formation and remodeling of new blood vessels in tumors is abnormal and facilitates immune evasion. In turn, immune cells in the tumor, specifically in context with an acidic and hypoxic environment, can promote neovascularization. Immunotherapy has emerged as a major therapeutic modality in cancer but is often hampered by the low influx of activated cytotoxic T-cells...
June 20, 2018: Seminars in Cancer Biology
Suvi Heinimäki, Maria Malm, Timo Vesikari, Vesna Blazevic
Rotavirus (RV) inner capsid VP6 protein is a potential non-live vaccine candidate due to high degree of conservation and immunogenicity, and ability to self-assemble into oligomeric structures, including nanotubes. These VP6 structures induce strong humoral and T cell immunity and protect mice against RV challenge. It has been suggested that intracellular neutralization by IgA antibody and VP6-specific CD4+ T cells mediate protection. We investigated generation of diverse CD4+ T cell subsets by intradermal and intranasal delivery of recombinant VP6 (rVP6) nanotubes in BALB/c mice...
June 20, 2018: Antiviral Research
Julika Pitsch, Julia C Kuehn, Vadym Gnatkovsky, Johannes Alexander Müller, Karen M J van Loo, Marco de Curtis, Hartmut Vatter, Susanne Schoch, Christian E Elger, Albert J Becker
Temporal lobe epilepsy (TLE) represents a devastating neurological condition, in which approximately 4/5 of patients remain refractory for anti-convulsive drugs. Epilepsy surgery biopsies often reveal the damage pattern of "hippocampal sclerosis" (HS) characterized not only by neuronal loss but also pronounced astrogliosis and inflammatory changes. Since TLE shares distinct pathogenetic aspects with multiple sclerosis (MS), we have here scrutinized therapeutic effects in experimental TLE of the immunmodulator fingolimod, which is established in MS therapy...
June 22, 2018: Molecular Neurobiology
Juliana de A Portes, Nathália F B Azeredo, Pedro G T Siqueira, Tatiana Guinancio de Souza, Christiane Fernandes, Adolfo Horn, Dalber R S Candela, Wanderley de Souza, Renato A DaMatta, Sérgio H Seabra
We have previously shown that metallocomplexes can control the growth of Toxoplasma gondii, the agent that causes toxoplasmosis. In order to develop new metallodrugs to treat this disease, we investigated the influence of the coordination of sulfadiazine (SDZ), a drug used to treat toxoplasmosis, on the biological activity of the iron(III) complex [Fe(HBPClNOL)Cl2 ]·H2 O, 1, (H2 BPClNOL=N-(2-hydroxybenzyl)-N-(2-pyridylmethyl)(3-chloro)(2-hydroxy)-propylamine). The new complex [(Cl)(SDZ)Fe(III)(μ-BPClNOL)2 Fe(III)(SDZ)(Cl)]·2H2 O, 2, which was obtained by the reaction between complex 1 and SDZ, was characterized using a range of physico-chemical techniques...
June 22, 2018: Parasitology Research
Saira Sultan, Simone A Osborne, Rama Addepalli, Gabi Netzel, Michael E Netzel, Mary T Fletcher
Indospicine, a non-proteinogenic analogue of arginine, occurs only in Indigofera plant species and accumulates in the tissues of animals grazing on Indigofera. Canine deaths have resulted from the consumption of indospicine-contaminated meat but only limited information is available regarding indospicine toxicity in humans. In this study three human cell lines, Caco-2 (colorectal adenocarcinoma), HT29-MTX-E12 (colorectal adenocarcinoma) and HepG2 (hepatocellular carcinoma), were used to investigate the cytotoxicity of indospicine and its metabolite 2-aminopimelic acid in comparison to arginine...
November 30, 2018: Food Chemistry
David A Clark, Jennifer M Dmetrichuk, Sukhbinder Dhesy-Thind, Mark A Crowther, Jorge L Arredondo
Retrograde menstruation is common and in about 10% of women, endometrial tissues implant at ectopic sites and grow as endometriosis (EM) deposits. To date, there has been no marker to identify which patients have an endometrium that will generate deposits. Both endometrial regulatory T cells (Tregs) and increased stromal cell indoleamine 2,3-dioxygenase (IDO) have been implicated, and may suppress rejection by peritoneal NK cells, neutrophils, and cytotoxic macrophages. CD200 is a tolerance signaling molecule which promotes Tregs, IDO-producing macrophages, and can directly inhibit cytolytic natural killer (NK) cells and neutrophils...
May 21, 2018: Journal of Reproductive Immunology
Jun Lai, Yun Wang, Shan-Shan Wu, Ding Ding, Ze-Yu Sun, Ying Zhang, Jie Zhou, Zhan Zhou, Ying-Chun Xu, Li-Qiang Pan, Shu-Qing Chen
Most tumor-associated proteins are located inside tumor cells and thus are not accessible to current marketed therapeutic monoclonal antibodies or their cytotoxic conjugates. Human leukocyte antigen (HLA) class I can present peptides derived from intracellular tumor-associated proteins and somatically mutated proteins on the cell's surface, forming an HLA/peptide complex as tumor-specific antigens for T cell receptor (TCR) recognition. Therefore, HLA-mediated presentation of intracellular tumor antigen peptides provides a viable way to distinguish tumor cells from normal cells, which is important for broadening antigen selection, especially for antibody-drug conjugates (ADCs) regarding their highly cytotoxic payload...
June 15, 2018: Biomaterials
Tamara Tyrinova, Olga Leplina, Sergey Mishinov, Marina Tikhonova, Anton Kalinovskiy, Sergey Chernov, Evgeniya Dolgova, Vyacheslav Stupak, Evgeniya Voronina, Sergey Bogachev, Ekaterina Shevela, Alexander Ostanin, Elena Chernykh
Besides initiation of tumor-specific T cell immunity, dendritic cells (DCs) are endowed with tumoricidal activity. Previously, we showed that monocyte-derived DCs of high-grade glioma patients generated in the presence of interferon alpha (IFNα) (IFN-DCs) have impaired cytotoxic activity against tumor necrosis factor alpha (TNFα)-sensitive HEp-2 tumor cells. Herein, we demonstrate that decreased transmembrane TNFα (tmTNFα) expression, but not soluble TNFα (sTNFα) production by high-grade glioma patient IFN-DCs, determines the defective tumoricidal activity against TNFα-sensitive HEp-2 cells...
June 22, 2018: Journal of Interferon & Cytokine Research
Giovanni Caprioli, Filippo Maggi, Hamdi Bendif, Mohamed Djamel Miara, Benedetta Cinque, Anna Rita Lizzi, Fabrizia Brisdelli, Giuseppe Celenza
This study aimed to investigate the ethanolic extract of T. lanceolatus, a species native to north-western Algeria, traditionally used as herbal tea, seasoning and a preservative for meat and poultry. HPLC analysis showed the presence of fourteen bioactive compounds, among which rosmarinic acid is by far the most abundant one (15440.9 mg kg-1). Its biological activity on proliferation, viability and ROS protection was investigated towards K562, CaCo-2 and SH-SY5Y human cancer cell lines. Cell proliferation was inhibited in K562 and SH-SY5Y cells in the first 48 h at 500 μg mL-1 but slowly resumed after 72 h...
June 22, 2018: Food & Function
Sonam Puri, Michael Shafique, Jhanelle E Gray
Surgical resection ± chemotherapy ± radiation or stereotactic body radiation therapy (SBRT) are established treatment modalities for resectable stage non-small cell lung cancer (NSCLC), and concurrent chemotherapy with radiation is the therapy of choice for unresectable locally advanced disease. Despite treatment with curative intent, most patients subsequently relapse and develop distant disease. Treatment with checkpoint inhibitors represents a major advancement in the treatment of metastatic NSCLC. Therapy against programed cell death-1/programmed cell death ligand 1 (PD-1/PD-L1) is associated with a significant improvement in overall survival in stage IV disease, and these results have led to a great interest in evaluating these agents in earlier-stage NSCLC...
June 21, 2018: Current Treatment Options in Oncology
Johannes Laengle, Judith Stift, Agnes Bilecz, Brigitte Wolf, Andrea Beer, Balazs Hegedus, Stefan Stremitzer, Patrick Starlinger, Dietmar Tamandl, Dietmar Pils, Michael Bergmann
Preclinical models indicate that DNA damage induces type I interferon (IFN), which is crucial for the induction of an anti-tumor immune response. In human cancers, however, the association between DNA damage and an immunogenic cell death (ICD), including the release and sensing of danger signals, the subsequent ER stress response and a functional IFN system, is less clear. Methods: Neoadjuvant-treated colorectal liver metastases (CLM) patients, undergoing liver resection in with a curative intent, were retrospectively enrolled in this study (n=33)...
2018: Theranostics
Nana H Overgaard, Daniel R Principe, Kyle M Schachtschneider, Jeanne Toft Jakobsen, Laurie A Rund, Paul J Grippo, Lawrence B Schook, Gregers Jungersen
In recent years, immunotherapy has shown considerable promise in the management of several malignancies. However, the majority of preclinical studies have been conducted in rodents, the results of which often translate poorly to patients given the substantial differences between murine and human immunology. As the porcine immune system is far more analogous to that of humans, pigs may serve as a supplementary preclinical model for future testing of such therapies. We have generated the genetically modified Oncopig with inducible tumor formation resulting from concomitant KRASG12D and TP53R167H mutations under control of an adenoviral vector Cre-recombinase (AdCre)...
2018: Frontiers in Immunology
Thibaut Perchet, Maxime Petit, Elena-Gaia Banchi, Sylvain Meunier, Ana Cumano, Rachel Golub
The Notch pathway is one of the canonical signaling pathways implicated in the development of various solid tumors. During carcinogenesis, the Notch pathway dysregulation induces tumor expression of Notch receptor ligands participating to escape the immune surveillance. The Notch pathway conditions both the development and the functional regulation of lymphoid subsets. Its importance on T cell subset polarization has been documented contrary to its action on innate lymphoid cells (ILC). We aim to analyze the effect of the Notch pathway on type 1 ILC polarization and functions after disruption of the RBPJk-dependent Notch signaling cascade...
2018: Frontiers in Immunology
Rachel Walker, Jan Poleszczuk, Shari Pilon-Thomas, Sungjune Kim, Alexander A R A Anderson, Brian J Czerniecki, Louis B Harrison, Eduardo G Moros, Heiko Enderling
Complex interactions occur between tumor and host immune system at each site in the metastatic setting, the outcome of which can determine behavior ranging from dormancy to rapid growth. An additional layer of complexity arises from the understanding that cytotoxic T cells can traffic through the host circulatory system. Coupling mathematical models of local tumor-immune dynamics and systemic T cell trafficking allows us to simulate the evolution of tumor and immune cell populations in anatomically distant sites following local therapy and thus computationally evaluate immune interconnectivity...
June 21, 2018: Scientific Reports
Xiaojie Chu, Yang Li, Weiwei Huang, Xuejun Feng, Pengyan Sun, Yufeng Yao, Xu Yang, Wenjia Sun, Hongmei Bai, Cunbao Liu, Yanbing Ma
Therapeutic vaccine appears to be a potential approach for the treatment of human papillomavirus (HPV)-associated tumours, but its efficacy can be dampened by immunosuppressive factors such as transforming growth factor (TGF)-β1. We sought to investigate whether active immunity against TGF-β1 enhances the anti-tumour immunity elicited by an HPV16 E7-specific vaccine that we developed previously. In this study, virus-like particles of hepatitis B virus core antigen were used as vaccine carriers to deliver either TGF-β1 B cell epitopes or E7 cytotoxic T-lymphocyte epitope...
June 22, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Daniil A Korenkov, Karen L Laurie, Patrick C Reading, Louise A Carolan, Kok Fei Chan, Irina I Isakova-Sivak, Tatiana A Smolonogina, Kanta Subbarao, Ian G Barr, Julie Villanueva, Svetlana Shcherbik, Tatiana Bousse, Larisa G Rudenko
Live attenuated influenza vaccines (LAIVs) are promising tools for the induction of broad protection from influenza due to their ability to stimulate cross-reactive T cells against influenza pathogens. One of the major targets for cytotoxic T-cell immunity is viral nucleoprotein (NP), which is relatively conserved among antigenically distant influenza viruses. Nevertheless, a diversity of epitope composition has been found in the NP protein of different lineages of influenza A viruses. The H2N2 master donor virus which is currently used as a backbone for the LAIV and donor of the six genomic segments encoding the internal proteins, A/Leningrad/134/17/57 (MDV Len/17), was isolated 60 years ago...
June 18, 2018: Infection, Genetics and Evolution
Farnaz Behroozi, Mohammad-Jafar Abdkhodaie, Hamid Sadeghi Abandansari, Leila Satarian, Mohammad Molazem, Khuloud T Al-Jamal, Hossein Baharvand
The oxidation-reduction (redox)-responsive micelle system is based on a diselenide-containing triblock copolymer, poly(ε-caprolactone)-bis(diselenide-methoxy poly(ethylene glycol)/poly(ethylene glycol)-folate) [PCL-(SeSe-mPEG/PEG-FA)2 ]. This has helped in the development of tumor-targeted delivery for hydrophobic anticancer drugs. The diselenide bond, as a redox-sensitive linkage, was designed in such a manner that it is located at the hydrophilic-hydrophobic hinge to allow complete collapse of the micelle and thus efficient drug release in redox environments...
June 18, 2018: Acta Biomaterialia
V P S Jesus, L Raniero, G M Lemes, T T Bhattacharjee, P C Caetano Júnior, M L Castilho
Breast cancer is the most commonly diagnosed cancer and the second leading cause of death related to cancer among women worldwide. Screening and advancements in treatments have improved survival rate of women suffering from this ailment. Novel therapeutic techniques may further reduce cancer related mortality. One of the several emerging therapeutic options is Photodynamic Therapy (PDT) that uses light activated photosensitizer (PS) inducing cell death by apoptosis and/or necrosis. Nanotechnology has made contribution to improve photosensitizer for PDT, increasing the efficiency of therapy using gold and silver nanoparticles...
June 18, 2018: Photodiagnosis and Photodynamic Therapy
Mona S Abdellateif, Sabry M Shaarawy, Eman Z Kandeel, Ahmed H El-Habashy, Mohamed L Salem, Motawa E El-Houseini
Dendritic cells (DCs) have been used in a number of clinical trials for cancer immunotherapy; however, they have achieved limited success in solid tumors. Consequently the aim of the present study was to identify a novel potential immunotherapeutic target for breast cancer patients through in vitro optimization of a viable DC-based vaccine. Immature DCs were primed by viable MCF-7 breast cancer cells and the activity and maturation of DCs were assessed through measuring CD83, CD86 and major histocompatibility complex (MHC)-II expression, in addition to different T cell subpopulations, namely CD4+ T cells, CD8+ T cells, and CD4+ CD25+ forkhead box protein 3 (Foxp3)+ regulatory T cells (Tregs), by flow cytometric analysis...
July 2018: Oncology Letters
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