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https://www.readbyqxmd.com/read/28723974/alginate-hydrogels-allow-for-bioactive-and-sustained-release-of-vegf-c-and-vegf-d-for-lymphangiogenic-therapeutic-applications
#1
Kevin T Campbell, Dustin J Hadley, David L Kukis, Eduardo A Silva
Lymphatic dysfunction is associated with the progression of many cardiovascular disorders due to their role in maintaining tissue fluid homeostasis. Promoting new lymphatic vessels (lymphangiogenesis) is a promising strategy to reverse these cardiovascular disorders via restoring lymphatic function. Vascular endothelial growth factor (VEGF) members VEGF-C and VEGF-D are both potent candidates for stimulating lymphangiogenesis, though maintaining spatial and temporal control of these factors represents a challenge to developing efficient therapeutic lymphangiogenic applications...
2017: PloS One
https://www.readbyqxmd.com/read/28723860/higher-thioguanine-nucleotide-metabolite-levels-are-associated-with-better-long-term-outcomes-in-patients-with-inflammatory-bowel-diseases
#2
Andres J Yarur, Bilal Gondal, Ayal Hirsch, Britt Christensen, Russell D Cohen, David T Rubin
GOALS: The aim of this study was to assess whether sustained 6-thioguaninenucleotide (6-TGN) levels were associated with improved long-term outcomes in patients with inflammatory bowel diseases (IBD). BACKGROUND: Cross-sectional data have shown that thiopurine metabolites are correlated with clinical efficacy in patient receiving thiopurines for IBD but the role for serial measurements through treatment course is unclear. STUDY: We conducted a retrospective cohort study including patients with IBD on thiopurine monotherapy and had serial 6-TGN levels measured...
July 18, 2017: Journal of Clinical Gastroenterology
https://www.readbyqxmd.com/read/28723685/downregulation-of-macrophage-derived-t-ucr-uc-306-associates-with-poor-prognosis-in-hepatocellular-carcinoma
#3
Hong-Lin Luo, Jie Chen, Tao Luo, Fei-Xiang Wu, Jun-Jie Liu, Hui-Feng Wang, Miao Chen, Le-Qun Li, Hang Li
BACKGROUND/AIMS: Increasing evidence suggests that T-UCRs are involved in the development of cancer. In this study, we evaluated the role of a macrophage-derived T-UCR, uc.306, in the prognosis of hepatitis B (HBV)-related hepatocellular carcinoma (HCC). METHODS: The uc.306 was obtained by screening microassay data obtained during the polarization of U937 cells from the M2 to M1 phenotype. Uc.306 and macrophage molecule markers were detected by qPCR. Immunohistochemical (IHC) assays were used to examine the M1/M2 status of 90 paired HCC tissues...
July 19, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28723564/the-lysine-acetyltransferase-gcn5-is-required-for-inkt-cell-development-through-egr2-acetylation
#4
Yajun Wang, Chawon Yun, Beixue Gao, Yuanming Xu, Yana Zhang, Yiming Wang, Qingfei Kong, Fang Zhao, Chyung-Ru Wang, Sharon Y R Dent, Jian Wang, Xiangping Xu, Hua-Bin Li, Deyu Fang
The development of CD1d-restricted invariant natural killer T (iNKT) cells, a population that is critical for both innate and adaptive immunity, is regulated by multiple transcription factors, but the molecular mechanisms underlying how the transcriptional activation of these factors are regulated during iNKT development remain largely unknown. We found that the histone acetyltransferase general control non-derepressible 5 (GCN5) is essential for iNKT cell development during the maturation stage. GCN5 deficiency blocked iNKT cell development in a cell-intrinsic manner...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28723547/the-p2x7-receptor-in-infection-and-inflammation
#5
REVIEW
Francesco Di Virgilio, Diego Dal Ben, Alba Clara Sarti, Anna Lisa Giuliani, Simonetta Falzoni
Adenosine triphosphate (ATP) accumulates at sites of tissue injury and inflammation. Effects of extracellular ATP are mediated by plasma membrane receptors named P2 receptors (P2Rs). The P2R most involved in inflammation and immunity is the P2X7 receptor (P2X7R), expressed by virtually all cells of innate and adaptive immunity. P2X7R mediates NLRP3 inflammasome activation, cytokine and chemokine release, T lymphocyte survival and differentiation, transcription factor activation, and cell death. Ten human P2RX7 gene splice variants and several SNPs that produce complex haplotypes are known...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28723546/local-modulation-of-antigen-presenting-cell-development-after-resolution-of-pneumonia-induces-long-term-susceptibility-to-secondary-infections
#6
Antoine Roquilly, Hamish E G McWilliam, Cedric Jacqueline, Zehua Tian, Raphael Cinotti, Marie Rimbert, Linda Wakim, Irina Caminschi, Mireille H Lahoud, Gabrielle T Belz, Axel Kallies, Justine D Mintern, Karim Asehnoune, Jose A Villadangos
Lung infections cause prolonged immune alterations and elevated susceptibility to secondary pneumonia. We found that, after resolution of primary viral or bacterial pneumonia, dendritic cells (DC), and macrophages exhibited poor antigen-presentation capacity and secretion of immunogenic cytokines. Development of these "paralyzed" DCs and macrophages depended on the immunosuppressive microenvironment established upon resolution of primary infection, which involved regulatory T (Treg) cells and the cytokine TGF-β...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28723504/active-surveillance-for-small-renal-masses-when-less-is-more
#7
REVIEW
Benjamin T Ristau, Alexander Kutikov, Robert G Uzzo, Marc C Smaldone
CONTEXT: A marked increase in incidentally detected small renal masses (SRMs) has occurred over the past decade. Active surveillance (AS) has emerged as an initial management option for these patients. OBJECTIVE: (1) To determine selection criteria, assess appropriate imaging modalities and surveillance frequencies, and define triggers for delayed intervention (DI) for patients on AS. (2) To describe oncologic outcomes for patients on AS protocols. EVIDENCE ACQUISITION: The PubMed database was queried for English language articles using the keywords "surveillance" and "renal mass" or "renal cell carcinoma" or "kidney cancer...
December 15, 2016: European Urology Focus
https://www.readbyqxmd.com/read/28723489/immunotherapy-for-renal-cancer-sequencing-and-combinations
#8
REVIEW
Grant D Stewart, Maria De Santis, Bernard Escudier, Thomas Powles, Guru Sonpavde
CONTEXT: Current therapy for renal cell carcinoma (RCC) generally consists of the sequential administration of single agent therapy. Given the advent of T-cell checkpoint inhibitors, the role of combinations including these agents is being intensely interrogated. OBJECTIVE: To evaluate ongoing trials of combinations including immunotherapy and sequencing of agents to treat RCC. EVIDENCE ACQUISITION: Recent data and ongoing trials were analyzed to evaluate the direction of research in this arena...
December 15, 2016: European Urology Focus
https://www.readbyqxmd.com/read/28722681/the-role-of-toll-like-receptor-4-in-tumor-microenvironment
#9
REVIEW
Jing Li, Fan Yang, Feng Wei, Xiubao Ren
Tumors are closely related to chronic inflammation, during which there are various changes in inflammatory sites, such as immune cells infiltration, pro-inflammation cytokines production, and interaction between immune cells and tissue cells. Besides, substances, released from both tissue cells attacked by exogenous etiologies, also act on local cells. These changes induce a dynamic and complex microenvironment favorable for tumor growth, invasion, and metastasis. The toll-like receptor 4 (TLR4) is the first identified member of the toll-like receptor family that can recognize pathogen-associated molecular patterns (PAMPs) and damage-associated molecular pattern (DAMPs)...
July 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28722319/immunophenotypic-aberrancies-in-acute-lymphoblastic-leukemia-from-282-iraqi-patients
#10
S D Jalal, N A S Al-Allawi, A A S Al Doski
INTRODUCTION: The identification of aberrancies in leukemia-associated immunophenotype (LAIP) of acute lymphoblastic leukemia (ALL) is quite important in the assessment of minimal residual disease (MRD). This study, the first from Iraq, aimed to assess the frequency and patterns of LAIP among Iraqi patients with ALL, to establish future strategies for evaluating MRD. METHODS: A total of 282 newly diagnosed Iraqi ALL cases were analyzed with six-parameter flow cytometry using a panel of 29 monoclonal antibodies...
July 18, 2017: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/28722206/alcohol-consumption-and-risk-of-urothelial-cell-bladder-cancer-in-the-european-prospective-investigation-into-cancer-and-nutrition-cohort
#11
E Botteri, P Ferrari, N Roswall, A Tjønneland, A Hjartåker, J M Huerta, R T Fortner, A Trichopoulou, A Karakatsani, C La Vecchia, V Pala, A Perez-Cornago, E Sonestedt, F Liedberg, K Overvad, M J Sánchez, I T Gram, M Stepien, L Trijsburg, L Börje, M Johansson, T Kühn, S Panico, R Tumino, H B Bueno-de-Mesquita, E Weiderpass
Findings on the association between alcohol consumption and bladder cancer are inconsistent. We investigated that association in the European Prospective Investigation into Cancer and Nutrition cohort. We included 476,160 individuals mostly aged 35-70 years, enrolled in ten countries and followed for 13.9 years on average. Hazard ratios (HR) for developing urothelial cell carcinoma (UCC; 1,802 incident cases) were calculated using Cox proportional hazards models. Alcohol consumption at baseline and over the life course was analyzed, as well as different types of beverages (beer, wine, spirits)...
July 19, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28722017/the-role-of-age-related-t-cell-differentiation-in-patients-with-renal-replacement-therapy
#12
Matthias Schaier, Angele Leick, Lorenz Uhlmann, Florian Kälble, Volker Eckstein, Anthony Ho, Stefan Meuer, Karsten Mahnke, Claudia Sommerer, Martin Zeier, Andrea Steinborn
Dialysis patients have deficiencies regarding the generation of immune responses and show an increased susceptibility for infections. Persisting uremic conditions are made responsible for the increased aging of their immune system. In this study, we analyzed whether age-related differences in the differentiation of both recent-thymic-emigrant-(RTE)-regulatory (Tregs) and RTE-responder T cells (Tresps) into CD31(-)-memory Tregs/Tresps led to differences in the suppressive activity of naïve and memory Tregs on autologous Tresps between healthy volunteers and dialysis patients...
July 19, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28721731/self-assembled-injectable-peptide-hydrogels-capable-of-triggering-antitumor-immune-response
#13
Ruirui Xing, Shukun Li, Ning Zhang, Guizhi Shen, Helmuth Möhwald, Xuehai Yan
Self-assembled peptide hydrogels are particularly appealing for drug delivery, tissue engineering, and anti-tumor therapy due to various advantageous features including excellent biocompatibility and biodegradability, defined molecular and higher organized structures and easy availability. However, the poor mechanical and rheological properties of assembled peptide hydrogels cause difficulties in injection, thus limiting further applications. Herein, injectable peptide-based hydrogels with tunable mechanical and rheological properties were obtained by combination with a positively charged poly-peptide (poly-L-lysine, PLL)...
July 19, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28721499/treg-protected-donor-lymphocyte-infusions-a-new-tool-to-address-the-graft-versus-leukemia-effect-in-the-absence-of-graft-versus-host-disease-in-patients-relapsed-after-hsct
#14
Mauro Di Ianni, Paola Olioso, Raffaella Giancola, Stella Santarone, Annalisa Natale, Gabriele Papalinetti, Ida Villanova, Stefano Baldoni, Ambra Di Tommaso, Tiziana Bonfini, Patrizia Accorsi, Paolo Di Bartolomeo
In high-risk acute leukemia patients undergoing haploidentical hematopoietic stem cell transplantation (HSCT), adoptive immunotherapy with T regulatory cells (Tregs) and T conventional cells (Tcons) prevented acute and chronic graft-versus-host disease (GvHD), favored post-transplant immunological reconstitution and was associated with a powerful graft-versus-leukemia (GvL) effect. With a particularly innovative approach, we developed a treatment with a Treg-protected donor lymphocyte infusion (DLI) for patients with early relapse after HSCT and we report here the results obtained in the first patient with APL (M3v) relapsed after a second matched allogeneic HSCT (15% blasts and 75% of donor cells in bone marrow)...
July 18, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28721397/hivis-dna-or-hivisopt-dna-priming-followed-by-cmdr-vaccinia-based-boosts-induce-both-humoral-and-cellular-murine-immune-responses-to-hiv
#15
J Hinkula, S Petkov, K Ljungberg, D Hallengärd, A Bråve, M Isaguliants, T Falkeborn, S Sharma, V Liakina, M Robb, M Eller, B Moss, G Biberfeld, E Sandström, C Nilsson, K Markland, P Blomberg, B Wahren
BACKGROUND: In order to develop a more effective prophylactic HIV-1 vaccine it is important optimize the components, improve Envelope glycoprotein immunogenicity as well as to explore prime-boost immunization schedules. It is also valuable to include several HIV-1 subtype antigens representing the world-wide epidemic. METHODS: HIVIS-DNA plasmids which include Env genes of subtypes A, B and C together with Gag subtypes A and B and RTmut/Rev of subtype B were modified as follows: the Envelope sequences were shortened, codon optimized, provided with an FT4 sequence and an immunodominant region mutated...
June 2017: Heliyon
https://www.readbyqxmd.com/read/28720665/targeted-exome-sequencing-of-krebs-cycle-genes-reveals-candidate-cancer-predisposing-mutations-in-pheochromocytomas-and-paragangliomas
#16
Laura Remacha, Iñaki Comino-Méndez, Susan Richter, Laura Contreras, Maria Currás-Freixes, Guillermo Pita, Rocío Letón, Antonio Galarreta, Rafael Torres-Pérez, Emiliano Honrado, Scherezade Jiménez, Lorena Maestre, Sebastian Moran, Manel Esteller, Jorgina Satrústegui, Graeme Eisenhofer, Mercedes Robledo, Alberto Cascon
Purpose: Mutations in Krebs cycle genes are frequently found in patients with pheochromocytomas/paragangliomas. Disruption of SDH, FH or MDH2 enzymatic activities lead to accumulation of specific metabolites, which give rise to epigenetic changes in the genome that cause a characteristic hypermethylated phenotype. Tumors showing this phenotype, but no alterations in the known predisposing genes, could harbor mutations in other Krebs cycle genes. <p>Experimental Design: We used downregulation and methylation of RBP1, as a marker of a hypermethylation phenotype, to select eleven pheochromocytomas and paragangliomas for targeted exome sequencing of a panel of Krebs cycle-related genes...
July 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28720505/chemically-generated-igg2-bispecific-antibodies-through-disulfide-bridging
#17
James T Patterson, Edwige Gros, Heyue Zhou, Ghazi Atassi, Lisa Kerwin, Lisa Carmody, Tong Zhu, Bryan Jones, Yanwen Fu, Gunnar F Kaufmann
Bispecific antibodies (BsAbs) are designed to engage two antigens simultaneously, thus, effectively expanding the ability of antibody-based therapeutics to target multiple pathways within the same cell, engage two separate soluble antigens, bind the same antigen with distinct paratopes, or crosslink two different cell types. Many recombinant BsAb formats have emerged, however, expression and purification of such constructs can often be challenging. To this end, we have developed a chemical strategy for generating BsAbs using native IgG2 architecture...
July 8, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28720483/left-right-patterning-breaking-symmetry-to-asymmetric-morphogenesis
#18
REVIEW
Daniel T Grimes, Rebecca D Burdine
Vertebrates exhibit striking left-right (L-R) asymmetries in the structure and position of the internal organs. Symmetry is broken by motile cilia-generated asymmetric fluid flow, resulting in a signaling cascade - the Nodal-Pitx2 pathway - being robustly established within mesodermal tissue on the left side only. This pathway impinges upon various organ primordia to instruct their side-specific development. Recently, progress has been made in understanding both the breaking of embryonic L-R symmetry and how the Nodal-Pitx2 pathway controls lateralized cell differentiation, migration, and other aspects of cell behavior, as well as tissue-level mechanisms, that drive asymmetries in organ formation...
July 15, 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28720467/intradermal-immunization-with-raav1-vector-induces-robust-memory-cd8-t-cell-responses-independently-of-transgene-expression-in-dcs
#19
Alexandre Ghenassia, David-Alexandre Gross, Stéphanie Lorain, Fabiola Tros, Dominique Urbain, Sofia Benkhelifa-Ziyyat, Alain Charbit, Jean Davoust, Pascal Chappert
Recombinant adeno-associated viral (rAAV) vectors exhibit interesting properties as vaccine carriers for their ability to induce long-lasting antibody responses. However, rAAV-based vaccines have been suggested to trigger functionally impaired long-term memory CD8(+) T cell responses, in part due to poor dendritic cell (DC) transduction. Such results, albeit limited to intramuscular immunization, undermined the use of rAAV as vaccine vehicles against intracellular pathogens. We report here that intradermal immunization with a model rAAV2/1-based vaccine drives the development of bona fide long-term memory CD8(+) T cell responses...
July 15, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28720430/oncogenic-pathways-that-affect-antitumor-immune-response-and-immune-checkpoint-blockade-therapy
#20
REVIEW
Xianda Zhao, Subbaya Subramanian
Mechanistic insights of cancer immunology have led to the development of immune checkpoint blockade therapy (ICBT), which has elicited a remarkable clinical response in some cancer patients. Increasing evidence suggests that activation of oncogenic pathways, such as RAS/RAF/MAPK and PI3K signaling, impairs the antitumor immune response. Such oncogenic signaling, in turn, activates many inhibitory factors, including expression of immune checkpoint genes-allowing active infiltration of immunosuppressive cells into the tumor environment and inducing resistance against T-cell killing...
July 15, 2017: Pharmacology & Therapeutics
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