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https://www.readbyqxmd.com/read/29036539/immune-cells-and-autoantibodies-in-pulmonary-arterial-hypertension
#1
Cheng Li, Pingping Liu, Rong Song, Yiqing Zhang, S Lei, Shangjie Wu
Analyses of immunity in pulmonary arterial hypertension (PAH) support the notion that maladaptation of the immune response exists. Altered immunity is an increasingly recognized feature of PAH. Indeed, a delicate balance between immunity and tolerance exists and any disturbance may result in chronic inflammation or autoimmunity. This is suggested by infiltration of various immune cells (e.g. macrophages, T and B lymphocytes) in remodeled pulmonary vessels. In addition, several types of autoantibodies directed against antinuclear antigens, endothelial cells (ECs) and fibroblasts have been found in idiopathic and systemic sclerosis-associated PAH...
September 27, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29036189/inhibition-of-cug-binding-protein-1-and-activation-of-caspases-are-critically-involved-in-piperazine-derivative-bk10007s-induced-apoptosis-in-hepatocellular-carcinoma-cells
#2
Ju-Ha Kim, Hee Young Kwon, Dong Hoon Ryu, Min-Ho Nam, Bum Sang Shim, Jin Han Kim, Jae Yeol Lee, Sung-Hoon Kim
Though piperazine derivative BK10007S was known to induce apoptosis in pancreatic cancer xenograft model as a T-type CaV3.1 a1G isoform calcium channel blocker, its underlying antitumor mechanism still remains unclear so far. Thus, in the present study, the antitumor mechanism of BK10007S was elucidated in hepatocellular carcinoma cells (HCCs). Herein, BK10007S showed significant cytotoxicity by 3-[4,5-2-yl]-2,5-diphenyltetra-zolium bromide (MTT) assay and anti-proliferative effects by colony formation assay in HepG2 and SK-Hep1 cells...
2017: PloS One
https://www.readbyqxmd.com/read/29035366/cytoplasmic-p53-couples-oncogene-driven-glucose-metabolism-to-apoptosis-and-is-a-therapeutic-target-in-glioblastoma
#3
Wilson X Mai, Laura Gosa, Veerle W Daniels, Lisa Ta, Jonathan E Tsang, Brian Higgins, W Blake Gilmore, Nicholas A Bayley, Mitra Dehghan Harati, Jason T Lee, William H Yong, Harley I Kornblum, Steven J Bensinger, Paul S Mischel, P Nagesh Rao, Peter M Clark, Timothy F Cloughesy, Anthony Letai, David A Nathanson
Cross-talk among oncogenic signaling and metabolic pathways may create opportunities for new therapeutic strategies in cancer. Here we show that although acute inhibition of EGFR-driven glucose metabolism induces only minimal cell death, it lowers the apoptotic threshold in a subset of patient-derived glioblastoma (GBM) cells. Mechanistic studies revealed that after attenuated glucose consumption, Bcl-xL blocks cytoplasmic p53 from triggering intrinsic apoptosis. Consequently, targeting of EGFR-driven glucose metabolism in combination with pharmacological stabilization of p53 with the brain-penetrant small molecule idasanutlin resulted in synthetic lethality in orthotopic glioblastoma xenograft models...
October 9, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29033940/pi3k%C3%AE-inhibition-enhances-the-antitumor-fitness-of-adoptively-transferred-cd8-t-cells
#4
Jacob S Bowers, Kinga Majchrzak, Michelle H Nelson, Bulent Arman Aksoy, Megan M Wyatt, Aubrey S Smith, Stefanie R Bailey, Lillian R Neal, Jeffrey E Hammerbacher, Chrystal M Paulos
Phosphatidylinositol-3-kinase p110δ (PI3Kδ) inhibition by Idelalisib (CAL-101) in hematological malignancies directly induces apoptosis in cancer cells and disrupts immunological tolerance by depleting regulatory T cells. Yet, little is known about the direct impact of PI3Kδ blockade on effector T cells from CAL-101 therapy. Herein, we demonstrate a direct effect of p110δ inactivation via CAL-101 on murine and human CD8(+) T cells that promotes a strong undifferentiated phenotype (elevated CD62L/CCR7, CD127, and Tcf7)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29033371/a-small-molecule-inhibitor-of-the-%C3%AE-catenin-tcf4-interaction-suppresses-colorectal-cancer-growth-in-vitro-and-in-vivo
#5
Seung Ho Shin, Do Young Lim, Kanamata Reddy, Margarita Malakhova, Fangfang Liu, Ting Wang, Mengqiu Song, Hanyong Chen, Ki Beom Bae, Joohyun Ryu, Kangdong Liu, Mee-Hyun Lee, Ann M Bode, Zigang Dong
Colorectal cancer is associated with aberrant activation of the Wnt pathway. β-Catenin plays essential roles in the Wnt pathway by interacting with T-cell factor 4 (TCF4) to transcribe oncogenes. We synthesized a small molecule, referred to as HI-B1, and evaluated signaling changes and biological consequences induced by the compound. HI-B1 inhibited β-catenin/TCF4 luciferase activity and preferentially caused apoptosis of cancer cells in which the survival is dependent on β-catenin. The formation of the β-catenin/TCF4 complex was disrupted by HI-B1 due to the direct interaction of HI-B1 with β-catenin...
September 27, 2017: EBioMedicine
https://www.readbyqxmd.com/read/29031499/micrornas-15a-and-16-1-activate-signaling-pathways-that-mediate-chemotaxis-of-immune-regulatory-b-cells-to-colorectal-tumors
#6
Ronghua Liu, Zhou Lu, Jie Gu, Jiajing Liu, Enyu Huang, Xiaoming Liu, Luman Wang, Jiao Yang, Yuting Deng, Jiawen Qian, Feifei Luo, Zhiming Wang, Hushan Zhang, Xuechao Jiang, Dan Zhang, Jing Qian, Guangwei Liu, Hongguang Zhu, Youcun Qian, Zhanju Liu, Yiwei Chu
BACKGROUND & AIMS: B cells infiltrate tumors but little is known about how they affect tumor growth and progression. microRNA15A (MIR15A or miRNA15A) and microRNA16-1 (MIR16-1 or miRNA16-1) regulate cell proliferation, apoptosis and drug resistance. We investigated their involvement in B cell-mediated immune suppression by colorectal tumors. METHODS: Mice with disruptions of the gene cluster that encodes MIR15A and MIR16-1 (KO mice), and control (C57BL/B6) mice were given azoxymethane with dextran sodium sulfate (AD) to induce formation of colorectal tumors...
October 11, 2017: Gastroenterology
https://www.readbyqxmd.com/read/29031078/structural-design-synthesis-and-pharmacological-evaluation-of-thiazoles-against-trypanosoma-cruzi
#7
Gevanio Bezerra de Oliveira Filho, Marcos Veríssimo de Oliveira Cardoso, José Wanderlan Pontes Espíndola, Dayane Albuquerque Oliveira E Silva, Rafaela Salgado Ferreira, Pollyanne Lacerda Coelho, Pâmela Silva Dos Anjos, Emanuelle de Souza Santos, Cássio Santana Meira, Diogo Rodrigo Magalhaes Moreira, Milena Botelho Pereira Soares, Ana Cristina Lima Leite
Chagas disease is one of the most significant health problems in the American continent. benznidazole (BDZ) and nifurtimox (NFX) are the only drugs approved for treatment and exhibit strong side effects and ineffectiveness in the chronic stage, besides different susceptibility among T. cruzi DTUs (Discrete Typing Units). Therefore, new drugs to treat this disease are necessary. Thiazole compounds have been described as potent trypanocidal agents. Here we report the structural planning, synthesis and anti-T...
September 22, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29030391/the-effect-of-plasma-auto-iggs-on-cd4-t-cell-apoptosis-and-recovery-in-hiv-infected-patients-under-antiretroviral-therapy
#8
Zhenwu Luo, Zejun Zhou, Elizabeth Ogunrinde, Tao Zhang, Zhen Li, Lisa Martin, Zhuang Wan, Hao Wu, Zhiqiang Qin, Tongwen Ou, Jiafeng Zhang, Lei Ma, Guoyang Liao, Sonya Heath, Lei Huang, Wei Jiang
Although effective antiretroviral therapy (ART) suppresses HIV viral replication, prevents AIDS-related complications, and prolongs life, a proportion of patients fails to restore the patients' CD4(+) T cell number to the level of healthy individuals. Increased mortality and morbidity have been observed in these patients. In the current study, we have investigated the role of auto-IgGs in CD4(+) T cell apoptosis and recovery in a cross-sectional study. All HIV(+) subjects were on viral-suppressive ART treatment with a different degree of CD4(+) T cell reconstitution...
October 13, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29029943/bcg-immune-activation-reduces-growth-and-angiogenesis-in-an-in-vitro-model-of-head-and-neck-squamous-cell-carcinoma
#9
Carolina Sánchez-Rodríguez, Keyliz Peraza Cruces, Juan Riestra Ayora, Eduardo Martín-Sanz, Ricardo Sanz-Fernández
Head and neck squamous cell carcinoma (HNSCC) is one of the most frequent cancers worldwide and is associated with poor survival and significant treatment morbidity. The immune profile in patients with HNSCC is immunosuppressive and presents cytokine-mediated adaptive immune responses, triggered apoptosis of T cells, and alterations in antigen processing machinery. Bacille Calmette-Guerin (BCG) immunotherapy has been used successfully as a treatment for several types of cancer. In the present study, we sought to determine the antitumor effect of soluble mediators from peripheral blood mononuclear immune cells (PBMCs) activated with BCG vaccine in a three-dimensional coculture model of HNSCC growth using FaDu hypopharynx carcinoma squamous cells...
October 10, 2017: Vaccine
https://www.readbyqxmd.com/read/29029511/mesenchymal-stromal-cells-promote-b-cell-lymphoma-in-lacrimal-glands-by-inducing-immunosuppressive-microenvironment
#10
Min Joung Lee, Se Yeon Park, Jung Hwa Ko, Hyun Ju Lee, Jin Suk Ryu, Jong Woo Park, Sang In Khwarg, Sun-Ok Yoon, Joo Youn Oh
Mesenchymal stromal cells (MSCs) have therapeutic potential for various diseases because of their anti-inflammatory and immunosuppressive properties. However, the immunosuppressive microenvironment allows tumor cells to evade immune surveillance, whereas maintenance of inflammation is required for tumor development and progression. Hence, MSCs may promote or suppress tumors in a context-dependent manner. We here investigated the effects of bone marrow-derived MSCs in a murine model of lacrimal gland B-cell lymphoma...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29028088/antitumor-effect-of-mir-27b-3p-on-lung-cancer-cells-via-targeting-fzd7
#11
Y Sun, T Xu, Y-W Cao, X-Q Ding
OBJECTIVE:   Lung cancer is the most common malignancy with the highest mortality rate among cancers. microRNAs (miRNAs) have been confirmed to be closely related to the physiological disorder, especially the tumor process. This study aimed to investigate the effect of miR-27b-3p on lung tumor cells. MATERIALS AND METHODS: The expressions of miR-27b-3p in lung tumors and adjacent non-tumors lung tissues were compared. We test the bonding effect of miR-27b-3p on the Fzd7 promoter, and miR-27b-3p effects on the Fzd7 expression in both NCI-H446 and A549 cells...
September 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29027218/cell-death-and-immunity-in-cancer-from-danger-signals-to-mimicry-of-pathogen-defense-responses
#12
REVIEW
Abhishek D Garg, Patrizia Agostinis
The immunogenicity of cancer cells is an emerging determinant of anti-cancer immunotherapy. Beyond developing immunostimulatory regimens like dendritic cell-based vaccines, immune-checkpoint blockers, and adoptive T-cell transfer, investigators are beginning to focus on the immunobiology of dying cancer cells and its relevance for the success of anticancer immunotherapies. It is currently accepted that cancer cells may die in response to anti-cancer therapies through regulated cell death programs, which may either repress or increase their immunogenic potential...
November 2017: Immunological Reviews
https://www.readbyqxmd.com/read/29025092/heat-stress-induces-autophagy-in-pig-ovaries-during-follicular-development
#13
Benjamin J Hale, Candice L Hager, Jacob T Seibert, Joshua T Selsby, Lance H Baumgard, Aileen F Keating, Jason W Ross
Hyperthermia or heat stress (HS) occurs when heat dissipation mechanisms are overwhelmed by external and internal heat production. Hyperthermia negatively affects reproduction and potentially compromises oocyte integrity and reduces developmental competence of ensuing embryos. Autophagy is the process by which cells recycle energy through the reutilization of cellular components and is activated by a variety of stressors. Study objectives were to characterize autophagy-related proteins in the ovary following cyclical HS during the follicular phase...
August 28, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29023933/mir-15a-16-1-suppresses-ahr-dependent-il-22-secretion-in-cd4-t-cells-and-contributes-to-immune-mediated-organ-injury
#14
Zhou Lu, Jiajing Liu, Xiaoming Liu, Enyu Huang, Jiao Yang, Jiawen Qian, Dan Zhang, Ronghua Liu, Yiwei Chu
Interleukin-22 (IL-22), as a link between leukocytic and non-leukocytic cells, has gained increasing attention for its pronounced tissue-protective properties. MicroRNAs (miRNAs), emerging as crucial immune modulators, have been reported to be involved in the production and action of various cytokines. However, the precise control of IL-22 by miRNAs and its subsequent actions remained to be elucidated. In this study, we found a negative correlation between the expression of miR-15a/16-1 and IL-22 in the model of concanavalinA (ConA)-induced immune-mediated liver injury...
October 10, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29023577/sevoflurane-protects-rat-brain-endothelial-barrier-structure-and-function-after-hypoxia-reoxygenation-injury
#15
Tanja Restin, Marie-Elisabeth Kajdi, Martin Schläpfer, Birgit Roth Z'graggen, Christa Booy, Claudia Dumrese, Beatrice Beck-Schimmer
BACKGROUND: After cerebral injury blood-brain barrier disruption significantly impairs brain homeostasis. Volatile anesthetics have been shown to be protective in ischemia-reperfusion injury scenarios. Their impact on brain endothelial cells after hypoxia-reoxygenation (H/R) has not yet been studied in detail. METHODS: Rat brain endothelial cells (RBE4) were exposed to severe hypoxia and reoxygenated in air in the presence or absence of sevoflurane. Changes in dextran permeability and architecture of the cellular junctional proteins ZO-1 and β-catenin were measured...
2017: PloS One
https://www.readbyqxmd.com/read/29023354/effects-of-hypercapnia-on-acute-cellular-rejection-after-lung-transplantation-in-rats
#16
Jing Tan, Yanhong Liu, Tao Jiang, Ling Wang, Can Zhao, Dongfang Shen, Xiaoguang Cui
BACKGROUND: Hypercapnia alleviates pulmonary ischemia-reperfusion injury, regulates T lymphocytes, and inhibits immune reaction. This study aimed to evaluate the effect of hypercapnia on acute cellular rejection in a rat lung transplantation model. METHODS: Recipient rats in sham-operated (Wistar), isograft (Wistar to Wistar), and allograft (Sprague-Dawley to Wistar) groups were ventilated with 50% oxygen, whereas rats in the hypercapnia (Sprague-Dawley to Wistar) group were administered 50% oxygen and 8% carbon dioxide for 90 min during reperfusion (n = 8)...
October 12, 2017: Anesthesiology
https://www.readbyqxmd.com/read/29022489/adar1-expression-is-associated-with-tumour-infiltrating-lymphocytes-in-triple-negative-breast-cancer
#17
In Hye Song, Young-Ae Kim, Sun-Hee Heo, In Ah Park, Miseon Lee, Won Seon Bang, Hye Seon Park, Gyungyub Gong, Hee Jin Lee
Tumours with a high mutation burden exhibit considerable neoantigens and tumour-infiltrating lymphocytes. RNA editing by ADAR1 is a source of changes in epitope. However, ADAR1 expression in cancer cells and tumour-infiltrating lymphocyte levels in triple-negative breast cancer have not been well evaluated. We immunohistochemically examined ADAR1 expression in 681 triple-negative breast cancer patients and analysed their clinicopathological characteristics. We also analysed basal-like tumours using The Cancer Genome Atlas data...
October 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29021794/cd95-fas-non-apoptotic-signaling-pathways-and-kinases
#18
REVIEW
Matthieu Le Gallo, Amanda Poissonnier, Patrick Blanco, Patrick Legembre
Endothelial cells lining new blood vessels that develop during inflammatory disorders or cancers act as doors that either allow or block access to the tumor or inflamed organ. Recent data show that these endothelial cells in cancer tissues and inflamed tissues of lupus patients overexpress CD95L, the biological role of which is a subject of debate. The receptor CD95 (also named Fas or apoptosis antigen 1) belongs to the tumor necrosis factor (TNF) receptor superfamily. Its cognate ligand, CD95L, is implicated in immune homeostasis and immune surveillance...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29021786/a-new-role-for-helicobacter-pylori-urease-contributions-to-angiogenesis
#19
Deiber Olivera-Severo, Augusto F Uberti, Miguel S Marques, Marta T Pinto, Maria Gomez-Lazaro, Céu Figueiredo, Marina Leite, Célia R Carlini
Helicobacter pylori is a pathogen involved in gastric diseases such as ulcers and carcinomas. H. pylori's urease is an important virulence factor produced in large amounts by this bacterium. In previous studies, we have shown that this protein is able to activate several cell types like neutrophils, monocytes, platelets, endothelial cells, and gastric epithelial cells. Angiogenesis is a physiological process implicated in growth, invasion and metastization of tumors. Here, we have analyzed the angiogenic potential of H...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29018243/6e11-a-highly-selective-inhibitor-of-receptor-interacting-protein-kinase-1-protects-cells-against-cold-hypoxia-reoxygenation-injury
#20
C Delehouzé, S Leverrier-Penna, F Le Cann, A Comte, M Jacquard-Fevai, O Delalande, N Desban, B Baratte, I Gallais, F Faurez, M C Bonnet, M Hauteville, P G Goekjian, R Thuillier, F Favreau, P Vandenabeele, T Hauet, M T Dimanche-Boitrel, S Bach
Necroptosis is a programmed cell death pathway that has been shown to be of central pathophysiological relevance in multiple disorders (hepatitis, brain and cardiac ischemia, pancreatitis, viral infection and inflammatory diseases). Necroptosis is driven by two serine threonine kinases, RIPK1 (Receptor Interacting Protein Kinase 1) and RIPK3, and a pseudo-kinase MLKL (Mixed Lineage Kinase domain-Like) associated in a multi-protein complex called necrosome. In order to find new inhibitors for use in human therapy, a chemical library containing highly diverse chemical structures was screened using a cell-based assay...
October 10, 2017: Scientific Reports
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