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https://www.readbyqxmd.com/read/28441526/it-s-t-time-for-normal-blood-vessels
#1
Bernard Thienpont, Diether Lambrechts
In a new report in Nature, Tian and colleagues (2017) describe that T cell activation in tumors induces blood vessel normalization. Because abnormal vasculature in tumors is known to reduce chemotherapy effectiveness and T lymphocyte infiltration and to increase metastasis, this suggests an exciting novel angle for checkpoint immunotherapy.
April 24, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28440968/the-effects-of-active-hexose-correlated-compound-ahcc-on-levels-of-cd4-and-cd8-in-patients-with-epithelial-ovarian-cancer-or-peritoneal-cancer-receiving-platinum-based-chemotherapy
#2
Wineeya Suknikhom, Ruangsak Lertkhachonsuk, Tarinee Manchana
Background: Adjuvant chemotherapy is a required treatment for most patients with epithelial ovarian cancer (EOC) or peritoneal cancer. However, it has many adverse events which may affect oncologic outcomes. Active hexose correlated compound (AHCC) has been reported to be an immunoenhancer to decrease adverse events of chemotherapy. Materials and Methods: Patients were randomized and allocated to receive either AHCC three grams/day (500mg/ capsule) or placebo. These drugs were administrated as two capsules orally three times a day throughout six cycles of chemotherapy...
March 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28440659/alleviation-of-multiple-asthmatic-pathologic-features-with-orally-available-and-subtype-selective-gabaa-receptor-modulators
#3
Gloria S Forkuo, Amanda N Nieman, Nina Y Yuan, Revathi Kodali, Olivia B Yu, Nicolas M Zahn, Rajwana Jahan, Guanguan Li, Michael Rajesh Stephen, Margaret L Guthrie, Michael M Poe, Benjamin D Hartzler, Ted William Harris, Gene T Yocum, Charles W Emala, Douglas A Steeber, Douglas C Stafford, James M Cook, Leggy A Arnold
We describe pharmacokinetic and pharmacodynamic properties of two novel oral drug candidates for asthma. Phenolic α4β3γ2 GABAAR selective compound 1 and acidic α5β3γ2 selective GABAAR positive allosteric modulator compound 2 relaxed airway smooth muscle ex vivo and attenuated airway hyperresponsiveness (AHR) in a murine model of asthma. Importantly, compound 2 relaxed acetylcholine contracted human tracheal airway smooth muscle strips. Oral treatment of compound 1 and 2 decreased eosinophils in bronchoalveolar lavage fluid in ovalbumin sensitized and challenged mice, thus exhibiting anti-inflammatory properties...
April 25, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28440511/simultaneously-increased-expression-of-glucocorticoid%C3%A2-induced-tumor-necrosis-factor-receptor-and-its-ligand-contributes-to-increased-interleukin%C3%A2-5-13%C3%A2-producing-group-2-innate-lymphocytes-in-murine-asthma
#4
Mengying Zhang, Jie Wan, Yunyun Xu, Danyi Zhang, Jingjing Peng, Chen Qi, Qi Guo, Sheng Xia, Zhaoliang Su, Shengjun Wang, Huaxi Xu
Glucocorticoid‑induced tumor necrosis factor receptor (GITR) is expressed at high levels on CD4+CD25+ regulatory T cells (Tregs). Following activation by its ligand (GITRL), GITR influences the activity of effector T cells and Tregs and participates in the development of numerous autoimmune and inflammatory diseases, including asthma. However, the GITR/GITRL expression level in lung tissue and its influence on group 2 innate lymphocytes (ILC2s) in asthma remains unclear. The present study detected the number of ILC2s and the expression levels of GITR and GITRL in the lung tissues of asthmatic mice by flow cytometry analysis, immunofluorescence staining and reverse transcription quantitative polymerase chain reaction...
April 21, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28440453/scrg1-suppresses-lps-induced-ccl22-production-through-erk1-2-activation-in-mouse-macrophage-raw264-7-cells
#5
Manabu Inoue, Junko Yamada, Emiko Aomatsu-Kikuchi, Kazuro Satoh, Hisatomo Kondo, Akira Ishisaki, Naoyuki Chosa
Recently, we identified the scrapie responsive gene 1 (SCRG1) secreted from mesenchymal stem cells (MSCs) and its receptor bone marrow stromal cell antigen 1 (BST1) as positive regulators of stem cell qualities such as self‑renewal, migration abilities, and osteogenic differentiation potential. Here, we examined the effect of the paracrine activity of SCRG1 in macrophages. The mouse macrophage‑like cell line Raw264.7 expressed BST1/β1 or BST1/β2 integrin as possible SCRG1 receptors. Unexpectedly, recombinant SCRG1 did not enhance cell proliferation, migration, or adhesion in these macrophages...
April 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28440449/preoperative-tim%C3%A2-3-expression-on-peripheral-nk-cells-is-correlated-with-pathologic-tnm-staging-in-colorectal-cancer
#6
Yang Wang, Jintang Sun, Wenjuan Gao, Bingfeng Song, Qianqian Shao, Lei Zhao, Yun Zhang, Qingjie Wang, Yun Zhang, Xun Qu
Previous research has indicated that T cell immunoglobulin and mucin domain 3 (Tim-3) serves an important regulatory role in lymphocytes and in several cancers. However, the association between Tim‑3 expression on various lymphocyte subsets and human colorectal cancer (CRC) has not been elucidated. The present study aimed to characterize Tim‑3 expression on peripheral lymphocytes, including cluster of differentiation CD3+CD56‑ T cells, CD3‑CD56+ natural killer (NK) cells and CD3+CD56+ natural killer T (NKT) cells, in patients with CRC...
April 19, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28440200/effect-of-halofuginone-on-the-pathogenesis-of-autoimmune-thyroid-disease-in-different-mice-models
#7
Xin Hou, Jin Zhou, Rong Yang, Shanshan Liu, Mei Bi, Tong Liu, Chenling Fan, Haixia Guan, Yushu Li, Zhongyan Shan, Weiping Teng
OBJECTIVE: Our objectives were to investigate the therapeutic effect of halofuginone (HF) in the treatment of autoimmune thyroid diseases (AITDs) and explore its underlying mechanism of action. METHODS: The Graves' disease (GD) model was generated by immunizing female BALB/c mice with adenovirus expressing the TSH receptor A subunit (Ad-TSHR289). The Ad-TSHRA+HF and Ad-TSHRA+DMSO groups were injected intraperitoneally with HF or the vehicle control (DMSO), respectively...
April 23, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/28439898/optimizing-autologous-nonmobilized-mononuclear-cell-collections-for-cellular-therapy-in-pediatric-patients-with-high-risk-leukemia
#8
Ehud Even-Or, Maria Di Mola, Muhammad Ali, Sarah Courtney, Elizabeth McDougall, Sarah Alexander, Tal Schechter, James A Whitlock, Christoph Licht, Joerg Krueger
BACKGROUND: The manufacturing of cellular products for immunotherapy, such as chimeric antigen receptor T cells, requires successful collection of mononuclear cells. Collections from children with high-risk leukemia present a challenge, especially because the established COBE Spectra apheresis device is being replaced by the novel Spectra Optia device (Optia) in many institutions. Published experience for mononuclear cell collections in children with Optia is lacking. Our aim was to compare the two collection devices and describe modified settings on the Optia to optimize mononuclear cell collections...
April 25, 2017: Transfusion
https://www.readbyqxmd.com/read/28439892/cerebrospinal-fluid-cyto-chemokine-profile-during-acute-herpes-simplex-virus-induced-anti-n-methyl-d-aspartate-receptor-encephalitis-and-in-chronic-neurological-sequelae
#9
Kavitha Kothur, Deepak Gill, Melanie Wong, Shekeeb S Mohammad, Sushil Bandodkar, Susan Arbunckle, Louise Wienholt, Russell C Dale
AIM: To examine the cytokine/chemokine profile of cerebrospinal fluid (CSF) during acute herpes simplex virus-induced N-methyl-d-aspartate receptor (NMDAR) autoimmunity and in chronic/relapsing post-herpes simplex virus encephalitis (HSE) neurological syndromes. METHOD: We measured longitudinal serial CSF cyto-/chemokines (n=34) and a glial marker (calcium-binding astroglial protein, S100B) in one patient during acute HSE and subsequent anti-NMDAR encephalitis, and compared the results with those from two patients with anti-NMDAR encephalitis without preceding HSE...
April 25, 2017: Developmental Medicine and Child Neurology
https://www.readbyqxmd.com/read/28439500/chronic-toxoplasma-gondii-infection-exacerbates-secondary-polymicrobial-sepsis
#10
Maria C Souza, Denise M Fonseca, Alexandre Kanashiro, Luciana Benevides, Tiago S Medina, Murilo S Dias, Warrison A Andrade, Giuliano Bonfá, Marcondes A B Silva, Aline Gozzi, Marcos C Borges, Ricardo T Gazzinelli, José C Alves-Filho, Fernando Q Cunha, João S Silva
Sepsis is a severe syndrome that arises when the host response to an insult is exacerbated, leading to organ failure and frequently to death. How a chronic infection that causes a prolonged Th1 expansion affects the course of sepsis is unknown. In this study, we showed that mice chronically infected with Toxoplasma gondii were more susceptible to sepsis induced by cecal ligation and puncture (CLP). Although T. gondii-infected mice exhibited efficient control of the bacterial burden, they showed increased mortality compared to the control groups...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28439019/type-i-interferons-induced-by-endogenous-or-exogenous-viral-infections-promote-metastasis-and-relapse-of-leishmaniasis
#11
Matteo Rossi, Patrik Castiglioni, Mary-Anne Hartley, Remzi Onur Eren, Florence Prével, Chantal Desponds, Daniel T Utzschneider, Dietmar Zehn, Maria G Cusi, F Matthew Kuhlmann, Stephen M Beverley, Catherine Ronet, Nicolas Fasel
The presence of the endogenous Leishmania RNA virus 1 (LRV1) replicating stably within some parasite species has been associated with the development of more severe forms of leishmaniasis and relapses after drug treatment in humans. Here, we show that the disease-exacerbatory role of LRV1 relies on type I IFN (type I IFNs) production by macrophages and signaling in vivo. Moreover, infecting mice with the LRV1-cured Leishmania guyanensis (LgyLRV1(-) ) strain of parasites followed by type I IFN treatment increased lesion size and parasite burden, quantitatively reproducing the LRV1-bearing (LgyLRV1(+) ) infection phenotype...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28438973/pulmonary-il-17-lymphocytes-increase-during-pneumocystis-murina-infection-but-are-not-required-for-clearance-of-pneumocystis
#12
Chiara Ripamonti, Lisa R Bishop, Joseph A Kovacs
Pneumocystis remains an important pathogen of immunosuppressed patients, causing a potentially life-threatening pneumonia. Despite its medical importance, the immune responses required to control infection, including the role of IL-17, which is important in controlling other fungal infections, have not been clearly defined. Using flow cytometry and intracellular cytokine staining following stimulation with PMA and ionomycin, we examined interferon-γ, IL-4, IL-5, and IL-17 production by lung lymphocytes in immunocompetent C57BL/6 mice over time following infection with P...
April 24, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28438900/definition-of-the-nature-and-hapten-threshold-of-the-%C3%AE-lactam-antigen-required-for-t-cell-activation-in-vitro-and-in-patients
#13
Xiaoli Meng, Zaid Al-Attar, Fiazia S Yaseen, Rosalind Jenkins, Caroline Earnshaw, Paul Whitaker, Daniel Peckham, Neil S French, Dean J Naisbitt, B Kevin Park
Covalent modification of protein by drugs may disrupt self-tolerance, leading to lymphocyte activation. Until now, determination of the threshold required for this process has not been possible. Therefore, we performed quantitative mass spectrometric analyses to define the epitopes formed in tolerant and hypersensitive patients taking the β-lactam antibiotic piperacillin and the threshold required for T cell activation. A hydrolyzed piperacillin hapten was detected on four lysine residues of human serum albumin (HSA) isolated from tolerant patients...
April 24, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28438506/diacylglycerol-kinase-%C3%AE-limits-cytokine-dependent-expansion-of-cd8-t-cells-with-broad-antitumor-capacity
#14
Elena Andrada, Rosa Liébana, Isabel Merida
Interleukin-2 and -15 drive expansion/differentiation of cytotoxic CD8(+) T cells that eliminate targets via antigen-independent killing. This property is clinically relevant for the improvement of T cell-based antitumor therapies. Diacylglycerol kinase α and ζ (DGKα/ζ) metabolize the diacylglycerol generated following antigen recognition by T lymphocytes. Enhanced expression of these two lipid kinases in tumor-infiltrating CD8(+) T cells promotes a hyporesponsive state that contributes to tumor immune escape...
April 14, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28437437/use-of-short-interfering-rna-delivered-by-cationic-liposomes-to-enable-efficient-down-regulation-of-ptpn22-gene-in-human-t-lymphocytes
#15
Valentina Perri, Marsha Pellegrino, Francesca Ceccacci, Anita Scipioni, Stefania Petrini, Elena Gianchecchi, Anna Lo Russo, Serena De Santis, Giovanna Mancini, Alessandra Fierabracci
Type 1 diabetes and thyroid disease are T cell-dependent autoimmune endocrinopathies. The standard substitutive administration of the deficient hormones does not halt the autoimmune process; therefore, development of immunotherapies aiming to preserve the residual hormonal cells, is of crucial importance. PTPN22 C1858T mutation encoding for the R620W lymphoid tyrosine phosphatase variant, plays a potential pathophysiological role in autoimmunity. The PTPN22 encoded protein Lyp is a negative regulator of T cell antigen receptor signaling; R620W variant, leading to a gain of function with paradoxical reduced T cell activation, may represent a valid therapeutic target...
2017: PloS One
https://www.readbyqxmd.com/read/28437174/more-than-fever-thermoregulatory-responses-to-immunological-stimulation-and-consequences-of-thermoregulatory-strategy-on-innate-immunity-in-gopher-tortoises-gopherus-polyphemus
#16
Jeffrey M Goessling, Craig Guyer, Mary T Mendonça
Organisms possess a range of thermoregulatory strategies that may vary in response to sickness, thereby driving important life-history consequences. Because the immune system is vital to maintaining organism function, understanding the suite of immune responses to infection indicates basic costs and benefits of physiological strategies. Here, we assessed consequences of thermoregulation and seasonality on immune function in both immunologically stimulated and nonstimulated gopher tortoises (Gopherus polyphemus)...
July 2017: Physiological and Biochemical Zoology: PBZ
https://www.readbyqxmd.com/read/28436934/biopolymers-codelivering-engineered-t-cells-and-sting-agonists-can-eliminate-heterogeneous-tumors
#17
Tyrel T Smith, Howell F Moffett, Sirkka B Stephan, Cary F Opel, Amy G Dumigan, Xiuyun Jiang, Venu G Pillarisetty, Smitha P S Pillai, K Dane Wittrup, Matthias T Stephan
Therapies using T cells that are programmed to express chimeric antigen receptors (CAR T cells) consistently produce positive results in patients with hematologic malignancies. However, CAR T cell treatments are less effective in solid tumors for several reasons. First, lymphocytes do not efficiently target CAR T cells; second, solid tumors create an immunosuppressive microenvironment that inactivates T cell responses; and third, solid cancers are typified by phenotypic diversity and thus include cells that do not express proteins targeted by the engineered receptors, enabling the formation of escape variants that elude CAR T cell targeting...
April 24, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28436605/digeorge-like-syndrome-in-a-child-with-a-3p12-3-deletion-involving-mir4273-gene-born-to-a-mother-with-gestational-diabetes-mellitus
#18
Emilia Cirillo, Giuliana Giardino, Vera Gallo, Giovanni Galasso, Roberta Romano, Roberta D'Assante, Giulia Scalia, Luigi Del Vecchio, Lucio Nitsch, Rita Genesio, Claudio Pignata
Chromosome 22q11.2 deletion is the most common chromosomal alteration associated with DiGeorge syndrome (DGS), even though this is not the only underlying cause of DGS. In rare patients, mutations in a single gene, TBX1, have been described resulting in a DGS phenotype. Recently, it has been reported that at least part of the TBX1 mutant phenotype is due to excessive bone morphogenetic proteins (BMP) signaling. Evidence suggests that miRNA may modulate the expression of critical T-box transcriptional regulators during midface development and Bmp-signaling...
April 24, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28436481/fusions-of-tumor-derived-endothelial-cells-with-dendritic-cells-induces-antitumor-immunity
#19
Yingying Huang, Qiqi Mao, Jian He, Jing Su, Yi Peng, Wei Liang, Zixi Hu, Sufang Zhou, Xiaoling Lu, Yongxiang Zhao
To explore dendritic cells/tumor-derived endothelial cells (DC/EC) fusion cells are potent stimulators of T cells to impact tumor progression. ECs were isolated from mice hepatoma cell line (H22) Xenograft, and dendritic cells were isolated from bone marrow of BALB/c mice, then the isolated ECs were cultured and detected the endothelial surface expression of CD105 by flow cytometry. The endothelial characteristics of ECs were detected by tube formation assay and Dil-Ac-LDL uptake assay. After the fusion with polyethylene glycol (PEG), we used DCs, ECs, DCs mixed ECs as the control groups, DC/EC fusion cells as the experimental group, Secretion of IFN-α and IFN-γ was evaluated, T lymphocyte proliferation and cytotoxic T lymphocytes (CTL) were detected in vitro...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28436295/treatment-response-to-dimethyl-fumarate-is-characterized-by-disproportionate-cd8-t-cell-reduction-in-ms
#20
Vinzenz Fleischer, Michaela Friedrich, Ayman Rezk, Ulrike Bühler, Esther Witsch, Timo Uphaus, Stefan Bittner, Sergiu Groppa, Björn Tackenberg, Amit Bar-Or, Frauke Zipp, Felix Luessi
BACKGROUND: The effect of dimethyl fumarate (DMF) on circulating lymphocyte subsets and their contribution as predictors of clinical efficacy have not yet been investigated in multiple sclerosis (MS). OBJECTIVE: To evaluate lymphocytes and lymphocyte subsets (analyzed 6 months after DMF start) in MS patients with and without disease activity after 1 year of treatment in a retrospective study. METHODS: Peripheral blood lymphocyte subsets were analyzed by flow cytometry...
April 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
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