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Cancer AND Immunology

Thamara Figueiredo Procópio, Leydianne Leite de Siqueira Patriota, Bárbara Rafaela da Silva Barros, Lethícia Maria de Souza Aguiar, Virgínia Maria Barros de Lorena, Patrícia Maria Guedes Paiva, Cristiane Moutinho Lagos de Melo, Thiago Henrique Napoleão
CasuL is a lectin (carbohydrate-binding protein) isolated from the leaf pinnulae of Calliandra surinamensis that is toxic against cancer cells. In this study, the effects of CasuL on the activation of immune cells were evaluated in BALB/c mice splenocytes. Assays measuring the changes in cytosolic calcium concentration ([Ca2+ ]cyt ), mitochondrial membrane potential (ΔΨm), and reactive oxygen species (ROS) levels associated with cell viability, proliferation, and cytokine and nitric oxide production were performed...
August 14, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Kumar Bhaskar Pal, Mukul Mahanti, Xiaoli Huang, Stella Persson, Anders P Sundin, Fredrik R Zetterberg, Stina Oredsson, Hakon Leffler, Ulf J Nilsson
Quinolines, indolizines, and coumarins are well known structural elements in many biologically active molecules. In this report, we have developed straightforward methods to incorporate quinoline, indolizine, and coumarin structures into galactoside derivatives under robust reaction conditions for the discovery of glycomimetic inhibitors of the galectin family of proteins that are involved in immunological and tumor-promoting biological processes. Evaluation of the quinoline, indolizine and coumarin-derivatised galactosides as inhibitors of the human galectin-1, 2, 3, 4N (N-terminal domain), 4C (C-terminal domain), 7, 8N, 8C, 9N, and 9C revealed quinoline derivatives that selectively bound galectin-8N, a galectin with key roles in lymphangiogenesis, tumor progression, and autophagy, with up to nearly 60-fold affinity improvements relative to methyl β-d-galactopyranoside...
August 17, 2018: Organic & Biomolecular Chemistry
Gregory L Beatty, Safi Shahda, Thaddeus Beck, Nikhil Uppal, Steven J Cohen, Ross Donehower, Afshin Eli Gabayan, Albert Assad, Julie Switzky, Huiling Zhen, Daniel D Von Hoff
LESSONS LEARNED: Itacitinib in combination with nab -paclitaxel plus gemcitabine demonstrated an acceptable safety profile with clinical activity in patients with advanced solid tumors including pancreatic cancer.The results support future studies of itacitinib as a component of combination regimens with other immunologic and targeted small molecule anticancer agents. BACKGROUND: Cytokine-mediated signaling via JAK/STAT is central to tumor growth, survival, and systemic inflammation, which is associated with cancer cachexia, particularly in pancreatic cancer...
August 16, 2018: Oncologist
Spencer C Wei, Colm R Duffy, James P Allison
Immune checkpoint blockade is able to induce durable responses across multiple types of cancer, which has enabled the oncology community to begin to envision potentially curative therapeutic approaches. However, the remarkable responses to immunotherapies are currently limited to a minority of patients and indications, highlighting the need for more effective and novel approaches. Indeed, an extraordinary amount of preclinical and clinical investigation is exploring the therapeutic potential of negative and positive costimulatory molecules...
August 16, 2018: Cancer Discovery
Falk Wehrhan, Maike Büttner-Herold, Luitpold Distel, Jutta Ries, Patrick Moebius, Raimund Preidl, Carol I Geppert, Friedrich W Neukam, Marco Kesting, Manuel Weber
BACKGROUND: Neck dissection is standard in surgical management of oral squamous cell carcinomas (oscc). However, the immunologic link between primary tumor and lymph nodes is insufficiently understood. Galectin 3 (Gal3) promotes M2 polarization of macrophages and contributes to immunosuppression. The current study analyzes the association between Gal3 expression in regional lymph nodes of oscc with histomorphologic parameters (T-, N-, L- Pn-stage, grading) of the primary tumor. Additionally, Gal3 expression is correlated with markers of macrophage polarization (M1 vs...
August 16, 2018: BMC Cancer
Stefanie Pektor, Lina Hilscher, Kerstin C Walzer, Isabelle Miederer, Nicole Bausbacher, Carmen Loquai, Mathias Schreckenberger, Ugur Sahin, Mustafa Diken, Matthias Miederer
BACKGROUND: [18 F]Fluoro-2-deoxy-2-D-glucose positron emission tomography (FDG-PET) is commonly used in the clinic for diagnosis of cancer and for follow-up of therapy outcome. Additional to the well-established value in tumor imaging, it bears potential to depict immune processes in modern immunotherapies. T cells enhance their glucose consumption upon activation and are crucial effectors for the success of such novel therapies. In this study, we analyzed the T cell immunity in spleen after antigen-specific stimulation of T cells via highly innovative RNA-based vaccines using FDG-PET/MRI...
August 15, 2018: EJNMMI Research
Saskia J Te Velde, Kristel Lankhorst, Maremka Zwinkels, Olaf Verschuren, Tim Takken, Janke de Groot
BACKGROUND: Little evidence is available about how sports participation influences psychosocial health and quality of life in children and adolescents with a disability or chronic disease. Therefore, the aim of the current study is to assess the association of sports participation with psychosocial health and with quality of life, among children and adolescents with a disability. METHODS: In a cross-sectional study, 195 children and adolescents with physical disabilities or chronic diseases (11% cardiovascular, 5% pulmonary, 8% metabolic, 8% musculoskeletal/orthopaedic, 52% neuromuscular and 9% immunological diseases and 1% with cancer), aged 10-19 years, completed questionnaires to assess sports participation, health-related quality of life (DCGM-37), self-perceptions and global self-worth (SPPC or SPPA) and exercise self-efficacy...
August 15, 2018: Sports Medicine—Open
Jonas Steenbrugge, Koen Breyne, Kristel Demeyere, Olivier De Wever, Niek N Sanders, Wim Van Den Broeck, Cecile Colpaert, Peter Vermeulen, Steven Van Laere, Evelyne Meyer
BACKGROUND: Murine breast cancer models relying on intraductal tumor cell inoculations are attractive because they allow the study of breast cancer from early ductal carcinoma in situ to metastasis. Using a fully immunocompetent 4T1-based intraductal model for triple-negative breast cancer (TNBC) we aimed to investigate the immunological responses that guide such intraductal tumor progression, focusing on the prominent role of macrophages. METHODS: Intraductal inoculations were performed in lactating female mice with luciferase-expressing 4T1 mammary tumor cells either with or without additional RAW264...
August 15, 2018: Journal of Experimental & Clinical Cancer Research: CR
Shailima Rampogu, Saravanan Parameswaran, Mary Rampogu Lemuel, Keun Woo Lee
Fenugreek (Trigonella foenum-graecum) is used as a spice throughout the world. It is known for its medicinal properties such as antidiabetic, anticarcinogenic, and immunological activities. The present study shows the properties and the nutritional quality of fenugreek seed extract and focuses on screening of active compounds in drug designing for type 2 diabetes and breast cancer. Quantitative analysis was used to calculate the percentages of protein, carbohydrates moisture, fatty acid, galactomannan, oil, and amino acid...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
Maysaloun Merhi, Afsheen Raza, Varghese Philipose Inchakalody, Abdulqadir Jeprel Japer Nashwan, Niloofar Allahverdi, Roopesh Krishnankutty, Shahab Uddin, Abdul Rehman Zar Gul, Mohammed Ussama Al Homsi, Said Dermime
Targeting the programmed cell death protein-1 (PD-1)/PD-1 ligand (PD-L1) pathway has been shown to enhance T cell-mediated antitumor immunity. Clinical responses are limited to subgroups of patients. The search for biomarkers of response is a strategy to predict response and outcome of PD-1/PD-L1 checkpoint intervention. The NY-ESO-1 cancer testis antigen has been considered as a biomarker in head and neck squamous cell carcinoma (HNSCC) patients and can induce both specific NY-ESO-1 antibody and T cells responses...
2018: Frontiers in Immunology
Adi Sharbi-Yunger, Mareike Grees, Cafri Gal, David Bassan, Stefan B Eichmüller, Esther Tzehoval, Jochen Utikal, Viktor Umansky, Lea Eisenbach
For many years, clinicians and scientists attempt to develop methods to stimulate the immune system to target malignant cells. Recent data suggest that effective cancer vaccination requires combination immunotherapies to overcome tumor immune evasion. Through presentation of both MHC-I and II molecules, DCs based vaccine platforms are effective in generating detectable CD4 and CD8 T cell responses against tumor associated antigens. Several platforms include DC transfection with mRNA of the desired tumor antigen...
August 14, 2018: International Journal of Cancer. Journal International du Cancer
Cun-Yi Zou, Ge-Fei Guan, Chen Zhu, Tian-Qi Liu, Qing Guo, Wen Cheng, An-Hua Wu
AIMS: Immune checkpoint blockade has made breakthroughs in immunotherapy for glioma. However, current immunotherapy has therapeutic benefits only in a subset of patients and accompanied by immune-related side effects. SLAMF8 is a costimulatory molecule that affects the activation of macrophages in inflammation. The study of SLAMF8 may provide new information for immunological research and treatment of glioma. METHODS: CGGA and TCGA cohorts of 946 patients with RNA sequencing data and full clinical information were analyzed using R language and GraphPad Prism 7...
August 13, 2018: CNS Neuroscience & Therapeutics
Elena Bruzzesi, Irini Sereti
The introduction of combination antiretroviral therapy (cART) in the 1990s has dramatically changed the course of HIV infection, decreasing the risk for both AIDS- and non-AIDS-related events. Cancers, cardiovascular disease (CVD), liver and kidney disease, neurological disorders and frailty have become of great importance lately in the clinical management as they represent the principal cause of death in people living with HIV who receive cART (Kirk et al. in Clin Infect Dis 45(1):103-10, 2007; Strategies for Management of Antiretroviral Therapy Study et al...
August 14, 2018: Current Topics in Microbiology and Immunology
Antoun Al Absi, Hannah Wurzer, Coralie L Guerin, Céline Hoffmann, Flora Moreau, Xianqing Mao, Joshua Brown-Clay, Rémi Petrolli, Carla Pou Casellas, Monika Dieterle, Jean Paul Thiery, Salem Chouaib, Guy Berchem, Bassam Janji, Clement Thomas
Elucidation of the underlying molecular mechanisms of immune evasion in cancer is critical for the development of immunotherapies aimed to restore and stimulate effective antitumor immunity. Here we evaluate the role of the actin cytoskeleton in breast cancer cell resistance to cytotoxic NK cells. A significant fraction of breast cancer cells responded to NK cell attack via a surprisingly rapid and massive accumulation of F-actin near the immunological synapse, a process we termed 'actin response'. Live cell imaging provided direct evidence that the actin response is associated with tumor cell resistance to NK cell-mediated cell death...
August 13, 2018: Cancer Research
Anusha Thadi, Marian Khalili, William F Morano, Scott D Richard, Steven C Katz, Wilbur B Bowne
Peritoneal metastasis (PM) is an advanced stage malignancy largely refractory to modern therapy. Intraperitoneal (IP) immunotherapy offers a novel approach for the control of regional disease of the peritoneal cavity by breaking immune tolerance. These strategies include heightening T-cell response and vaccine induction of anti-cancer memory against tumor-associated antigens. Early investigations with chimeric antigen receptor T cells (CAR-T cells), vaccine-based therapies, dendritic cells (DCs) in combination with pro-inflammatory cytokines and natural killer cells (NKs), adoptive cell transfer, and immune checkpoint inhibitors represent significant advances in the treatment of PM...
August 10, 2018: Vaccines
Lorena Bustamante-Córdova, Edgar A Melgoza-González, Jesús Hernández
The production of recombinant antibodies has had a tremendous impact on several research fields, most prominently in biotechnology, immunology and medicine, enabling enormous advances in each. Thus far, a broad diversity of recombinant antibody (rAb) forms have been designed and expressed using different expression systems. Even though the majority of rAbs approved for clinical use are targeted to humans, advances in veterinary medicine seem promising. The aim of this mini-review is to present an update regarding the rAbs in veterinary medicine reported to date, as well as their potential use in diagnostics, prophylaxis and therapeutics...
2018: Frontiers in Veterinary Science
Jennifer N Saultz, Aharon G Freud, Bethany L Mundy-Bosse
MicroRNAs (miRNAs) are now recognized as important regulators of all cellular processes, including immune function and cancer survival. These evolutionary preserved, single-stranded, non-coding RNA molecules mediate important functional effects primarily through post-transcriptional regulation of protein expression. MiRNAs are known to mediate multiple oncogenic pathways in tumor cells, both tumor promoting and tumor suppressing. In addition to a direct tumor cell effect, miRNAs have also been shown to play a critical role in immune cell development, function and survival...
August 9, 2018: Molecular Immunology
Rachel Bender Ignacio, Lilie L Lin, Lakshmi Rajdev, Elizabeth Chiao
This review highlights current interventional clinical trials for HIV-associated malignancies (HIVAMs), with emphasis on 4 mechanistic areas: immunomodulatory therapies and gene therapies, including immune checkpoint inhibitors; cytotoxic therapies; novel tumor-targeted and virally targeted therapies in both AIDS-defining and non-AIDS-defining cancers (NADC); and other screening or topical/ablative interventions. A search on located 35 trials, including 12 immunomodulatory or gene therapy trials, 6 cytotoxic therapy trials, 10 trials of therapies with tumor or viral molecular targets, and 7 trials evaluating screening interventions or topical or ablative therapies...
August 2018: Journal of the National Comprehensive Cancer Network: JNCCN
Xiao-Hua Luo, Qingda Meng, Martin Rao, Zhenjiang Liu, Georgia Paraschoudi, Ernest Dodoo, Markus Maeurer
Human cytomegalovirus (CMV) is a ubiquitous, persistent beta herpesvirus. CMV infection contributes to the accumulation of functional antigen (Ag)-specific CD8+ T-cell pools with an effector-memory phenotype and enrichment of these immune cells in peripheral organs. We review here this "memory T-cell inflation" phenomenon and associated factors including age and sex. 'Collateral damage' due to CMV-directed immune reactivity may occur in later stages of life - arising from CMV-specific immune responses that were beneficial in earlier life...
August 11, 2018: Immunology
Fanwen Wang, Caoying Xu, Renhao Peng, Bin Li, Xutong Shen, Heng Zheng, Xingzhen Lao
Thymosin α1 (Tα1), a hormone containing 28 amino acids, has been approved in several cancer therapies, but the lack of tumor-targeting hinders its full use in tumor treatment. We designed a new peptide by connecting Tα1 and RGDR, generating a product, Tα1-RGDR, where RGDR is located in the C-end with both tumor-homing and cell internalizing properties (C-end rule peptides, a consensus R/KXXR/K motif). This work aimed to study the antitumor and immunological activities of Tα1-RGDR, and its differences compared with the wild-type Tα1...
August 7, 2018: Biochimie
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