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Tolerance induction

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https://www.readbyqxmd.com/read/28331050/first-in-human-clinical-trial-of-oral-onc201-in-patients-with-refractory-solid-tumors
#1
Mark N Stein, Joseph R Bertino, Howard L Kaufman, Tina Mayer, Rebecca Moss, Ann Silk, Nancy Chan, Jyoti Malhotra, Lorna Rodriguez-Rodriguez, Joseph Aisner, Robert D Aiken, Bruce G Haffty, Robert S DiPaola, Tracie Saunders, Andrew Zloza, Sherri Damare, Yasmeen Beckett, Bangning Yu, Saltanat Najmi, Christian Gabel, Siobhan Dickerson, Ling Zheng, Wafik S El-Deiry, Joshua Allen, Martin Stogniew, Wolfgang Oster, Janice M Mehnert
Purpose ONC201 is a small molecule selective antagonist of the G protein-coupled receptor DRD2 that is the founding member of the imipridone class of compounds. A first-in-human phase I study of ONC201 was conducted to determine its recommended phase II dose (RP2D). Experimental Design This open-label study treated 10 patients during dose escalation with histologically-confirmed advanced solid tumors. Patients received ONC201 orally once every 3 weeks, defined as one cycle, at doses from 125 to 625 mg using an accelerated titration design...
March 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28329731/feasibility-toxicity-and-response-of-upfront-metaiodobenzylguanidine-therapy-therapy-followed-by-german-pediatric-oncology-group-neuroblastoma-2004-protocol-in-newly-diagnosed-stage-4-neuroblastoma-patients
#2
K C J M Kraal, G M Bleeker, B L F van Eck-Smit, N K A van Eijkelenburg, F Berthold, M M van Noesel, H N Caron, G A M Tytgat
AIM OF THE STUDY: Radiolabelled meta-iodobenzylguanidine (MIBG) is an effective option in treatment of neuroblastoma (NBL) tumours. We studied feasibility, toxicity and efficacy of upfront (131)I-MIBG and induction treatment in stage 4 NBL patients. PATIENTS AND METHODS: Retrospective, multi-centre (AMC and EMC) pilot regimen (1/1/2005-2011). Newly diagnosed stage 4 NBL patients, were treated with 2 courses of (131)I-MIBG, GPOH 2004 NBL protocol, myeloablative therapy (MAT) and autologous stem cell rescue (ASCT)...
March 19, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28328950/repeated-anaesthesia-with-isoflurane-and-medetomidine-midazolam-fentanyl-in-guinea-pigs-and-its-influence-on-physiological-parameters
#3
Sabrina Schmitz, Sabine Tacke, Brian Guth, Julia Henke
Repeated anaesthesia may be required in experimental protocols and in daily veterinary practice, but anaesthesia is known to alter physiological parameters in GPs (Cavia porcellus, GPs). This study investigated the effects of repeated anaesthesia with either medetomidine-midazolam-fentanyl (MMF) or isoflurane (Iso) on physiological parameters in the GP. Twelve GPs were repeatedly administered with MMF or Iso in two anaesthesia sets. One set consisted of six 40-min anaesthesias, performed over 3 weeks (2 per week); the anaesthetic used first was randomized...
2017: PloS One
https://www.readbyqxmd.com/read/28327272/effects-of-electrospun-scaffolds-of-di-o-butyrylchitin-and-poly-%C3%AE%C2%B5-caprolactone-on-wound-healing
#4
Jacek Drobnik, Izabella Krucinska, Agnieszka Komisarczyk, Stanislaw Sporny, Alicja Szczepanowska, Joanna Ciosek
BACKGROUND: We sought to determine the usefulness of electrospun dibutyrylchitin (DBC) or poly (ε-Caprolactone [PCL]), in wound treatment. We investigated the mechanisms of action of these polymers on wound healing. METHODS: We synthesized DBC, a newly identified ester derivative of chitin, using a patented method comprising the substitution of butyryl groups at positions C-3 and C-6 in chitin molecules. We confirmed the double substitution by the butyric groups using infrared spectrometry...
April 1, 2017: Canadian Journal of Surgery. Journal Canadien de Chirurgie
https://www.readbyqxmd.com/read/28326648/changes-in-expression-of-the-cd200-tolerance-signaling-molecule-and-its-receptor-cd200r-by-villus-trophoblasts-during-first-trimester-missed-abortion-and-in-chronic-histiocytic-intervillositis
#5
David A Clark, Jennifer M Dmetrichuk, Elizabeth McCready, Sukhbinder Dhesy-Thind, Jorge L Arredondo
PROBLEM: Expression of CD200 at the feto-maternal interface is associated with successful murine and human pregnancy. CD200 binding to CD200 receptors on lymphomyeloid cells suppresses inflammation and induces Tregs. CD200 receptors are also expressed on mouse and human placental trophoblast cells. What is the expression of CD200 and CD200R in human missed abortions which have preserved Treg levels and in chronic histiocytic intervillositis (CHI) where maternal inflammatory cells cause IUGR? METHODS: Immunohistiochemistry for CD200, CD200R, and Ki67 using human placental sections from missed abortions, term placenta, and CHI...
March 22, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28324270/obinutuzumab-a-review-in-rituximab-refractory-or-relapsed-follicular-lymphoma
#6
REVIEW
Sohita Dhillon
Obinutuzumab (Gazyva(®), Gazyvaro(®)) is a recombinant, monoclonal, humanized and glycoengineered, type II, anti-CD20, IgG1 antibody. It has recently been granted an additional indication for the treatment of patients with follicular lymphoma who relapsed after, or are refractory to, a rituximab-containing regimen. In the primary analysis of the large, phase III GADOLIN study, induction therapy with obinutuzumab plus bendamustine followed by obinutuzumab maintenance prolonged progression-free survival (PFS) to a statistically significant extent relative to induction with bendamustine monotherapy in patients with indolent non-Hodgkin's lymphoma (iNHL)...
March 21, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28324120/-biological-mechanisms-of-radiation-effects
#7
S Gruber, W Dörr
BACKGROUND: Exposure to ionizing radiation for diagnostic purposes is inevitable in modern medicine. The therapeutic application of irradiation is highly effective against cancer; however, this implies exposure of normal tissue structures to significant doses of radiation. Diagnostic or therapeutic exposure to ionizing radiation can result in tissue changes and tumor induction in the long term. Knowledge of the biological mechanisms underlying these effects is essential for individualization of the application...
March 21, 2017: Der Radiologe
https://www.readbyqxmd.com/read/28324001/cyp3a4-induction-by-rifampin-an-alternative-pathway-for-vitamin-d-inactivation-in-patients-with-cyp24a1-mutations
#8
Colin Patrick Hawkes, Dong Li, Hakon Hakonarson, Kevin E Meyers, Kenneth Thummel, Michael A Levine
Context: The P450 enzyme CYP24A1 is the principal inactivator of vitamin D metabolites. Biallelic loss-of-function mutations in CYP24A1 are associated with elevated serum levels of 1,25-dihydroxyvitamin D3 with consequent hypercalcemia and hypercalciuria, and represent the most common form of idiopathic infantile hypercalcemia (IIH). Current management strategies for this condition include a low calcium diet, reduced dietary vitamin D intake and limited sunlight exposure. CYP3A4 is a P450 enzyme that inactivates many drugs and xenobiotics and may represent an alternative pathway for inactivation of vitamin D metabolites...
March 3, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28321218/the-induction-and-maintenance-of-transplant-tolerance-engages-both-regulatory-and-anergic-cd4-t-cells
#9
Alix Besançon, Marije Baas, Tania Goncalves, Fabrice Valette, Herman Waldmann, Lucienne Chatenoud, Sylvaine You
Therapeutic tolerance to self-antigens or foreign antigens is thought to depend on constant vigilance by Foxp3(+) regulatory T cells (Tregs). Previous work using a pancreatic islet allograft model and a short pulse of CD3 antibody therapy has shown that CD8(+) T cells become anergic and use TGFβ and coinhibitory signaling as their contribution to the tolerance process. Here, we examine the role of CD4(+) T cells in tolerization by CD3 antibodies. We show that both Foxp3(+) Tregs and CD4(+) T cell anergy play a role in the induction of tolerance and its maintenance...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28321216/facilitated-peptide-transport-via-the-mucosal-epithelium-impact-on-tolerance-induction
#10
Elisabeth E Kenngott, Jennifer Pfeil, Ute Hoffmann, Uta Lauer, Anja A Kühl, Anne Rigby, Anton Pernthaner, Alf Hamann
A hallmark of autoimmunity is the breakdown of tolerance and generation of effector responses against self-antigens. Re-establishment of tolerance in autoimmune disorders was always the most desired treatment option; however, despite many efforts, clinical trials have been largely unsuccessful. This also applies to the generation of oral tolerance, which seems to be a default response type of the mucosa-associated lymphoid tissues to harmless antigens. In this study, we report improved efficacy of oral tolerance induction by coupling antigen with the newly identified mucosal carrier peptide 13C...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28320288/analysis-of-photoprotection-and-apparent-non-photochemical-quenching-of-chlorophyll-fluorescence-in-tradescantia-leaves-based-on-the-rate-of-irradiance-induced-changes-in-optical-transparence
#11
V V Ptushenko, O S Ptushenko, O P Samoilova, A E Solovchenko
The kinetics of irradiation-induced changes in leaf optical transparence (ΔT) and non-photochemical quenching (NPQ) of chlorophyll fluorescence in Tradescantia fluminensis and T. sillamontana leaves adapted to different irradiance in nature was analyzed. Characteristic times of a photoinduced increase and a dark decline of ΔT in these species were 12 and 20 min, respectively. The ΔT was not confirmed to be the main contributor to the observed middle phase of NPQ relaxation kinetics (τ = 10-28 min). Comparison of rate of photoinduced increase in ΔT and photosystem II quantum yield recovery showed that the former did not affect the tolerance of the photosynthetic apparatus (PSA) to irradiances up to 150 µmol PAR·m(-2)·s(-1)...
January 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28319371/expression-of-heterologous-sigma-factor-expands-the-searchable-space-for-biofuel-tolerance-mechanisms
#12
Timothy A Tomko, Mary J Dunlop
Microorganisms can produce hydrocarbons that can serve as replacements or additions to conventional liquid fuels for use in the transportation sector. However, a common problem in the microbial synthesis of biofuels is that these compounds often have toxic effects on the cell. In this study, we focused on mitigating the toxicity of the bio-jet fuel precursor pinene on Escherichia coli. We used genomic DNA from Pseudomonas putida KT2440, which has innate solvent-tolerance properties, to create transgenic libraries in an E...
March 20, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28315220/ige-epitope-mapping-using-peptide-microarray-immunoassay
#13
Jing Lin, Hugh A Sampson
IgE epitope mapping has the potential to become an additional tool for food allergy diagnosis/prognosis and to lead to a better understanding of the pathogenesis and tolerance induction of food allergy. Due to its ability to screen thousands of targets in parallel using small volumes of sample, peptide microarray has greatly facilitated large-scale IgE epitope mapping. In the past 10 years, we have developed and optimized a reliable and sensitive peptide microarray immunoassay, which has been successfully applied for IgE epitope mapping of many food allergens in our lab...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28314257/treatment-of-hematological-malignancies-with-glycyrrhizic-acid
#14
Bryan J Hostetler, Olga N Uchakina, Hao Ban, Robert J McKallip
The current study examined the effectiveness of glycyrrhizic acid (GA) in reducing cell viability and inducing apoptosis in human chronic myeloid leukemia (CML) in vitro and a mouse lymphoma in vivo. Additionally, we assessed GA as a candidate for combinational therapy in CML along with the current frontline treatment, imatinib (IM). Treatment of K562 CML cells with GA alone resulted in significant induction of apoptosis and loss of cell viability. GA was well tolerated by peripheral blood mononuclear cells (PBMCs) up to 2 mM doses which were subsequently used in combination with IM...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28304331/inverse-association-of-plasma-chromium-levels-with-newly-diagnosed-type-2-diabetes-a-case-control-study
#15
Sijing Chen, Xiaoling Jin, Zhilei Shan, Shuzhen Li, Jiawei Yin, Taoping Sun, Cheng Luo, Wei Yang, Ping Yao, Kaifeng Yu, Yan Zhang, Qian Cheng, Jinquan Cheng, Wei Bao, Liegang Liu
Chromium has long been known as an enhancer of insulin action. However, the role of chromium in the development of type 2 diabetes mellitus (T2DM) in humans remains controversial. The current study aimed to examine the associations of plasma chromium levels with T2DM and pre-diabetes mellitus (pre-DM). We conducted a case-control study involving 1471 patients with newly diagnosed T2DM, 682 individuals with newly diagnosed pre-DM, and 2290 individuals with normal glucose tolerance in a Chinese population from 2009 to 2014...
March 17, 2017: Nutrients
https://www.readbyqxmd.com/read/28302753/erythropoietin-receptor-mediated-molecular-crosstalk-promotes-t-cell-immunoregulation-and-transplant-survival
#16
Carolina Purroy, Robert L Fairchild, Toshiaki Tanaka, William M Baldwin, Joaquin Manrique, Joren C Madsen, Robert B Colvin, Alessandro Alessandrini, Bruce R Blazar, Miguel Fribourg, Chiara Donadei, Umberto Maggiore, Peter S Heeger, Paolo Cravedi
Although spontaneous kidney transplant acceptance/tolerance occurs in mice and occasionally in humans, mechanisms remain unclear. Herein we test the hypothesis that EPO, a hormone predominantly produced by the adult kidney, has immunomodulating properties that are required for spontaneous kidney graft acceptance. In vitro, in a manner dependent on the EPO receptor and CD131 on antigen-presenting cells, EPO induced the secretion of active TGFβ by antigen-presenting cells, which in turn converted naïve CD4(+) T cells into functional Foxp3(+) regulatory T cells (Treg)...
March 16, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28302184/cytokine-free-directed-differentiation-of-human-pluripotent-stem-cells-efficiently-produces-hemogenic-endothelium-with-lymphoid-potential
#17
Yekaterina Galat, Svetlana Dambaeva, Irina Elcheva, Aaruni Khanolkar, Kenneth Beaman, Philip M Iannaccone, Vasiliy Galat
BACKGROUND: The robust generation of human hematopoietic progenitor cells from induced or embryonic pluripotent stem cells would be beneficial for multiple areas of research, including mechanistic studies of hematopoiesis, the development of cellular therapies for autoimmune diseases, induced transplant tolerance, anticancer immunotherapies, disease modeling, and drug/toxicity screening. Over the past years, significant progress has been made in identifying effective protocols for hematopoietic differentiation from pluripotent stem cells and understanding stages of mesodermal, endothelial, and hematopoietic specification...
March 17, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28296255/breg-dependent-islet-transplant-tolerance-is-also-nk-cell-dependent
#18
Christian Schuetz, Kang Mi Lee, Ryan Scott, Lisa Kojima, Laura Washburn, Liye Liu, Wei-Hui Liu, Haley Tector, Ji Lei, Heidi Yeh, James Kim, James F Markmann
Immunologic tolerance to solid organ and islet cell grafts has been achieved in various rodent models using antibodies directed at CD45RB and Tim-1. We have shown that this form of tolerance depends on regulatory B-cells. To elucidate further the mechanism by which Bregs induce tolerance we investigated the requirement of NK and NKT cells in this model. To do so, hyperglycemic B6, μMT, Beige or CD1d(-/-) mice received Balb/c islet grafts and treatment with the tolerance inducing regimen consisting of anti-CD45RB and anti -TIM1...
March 10, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28296027/transitional-b-cells-predominantly-reconstituted-after-a-desensitization-therapy-using-rituximab-before-kidney-transplantation
#19
Masako Ikemiyagi, Toshihito Hirai, Rumi Ishii, Satoshi Miyairi, Masayoshi Okumi, Kazunari Tanabe
The role of B cells in graft rejection and tolerance has aroused great interest. We previously reported that rituximab (RIT) induction prior to kidney transplantation (KTx) reduced the incidence rate of chronic rejection. Here, we performed a cross sectional investigation to determine the characteristics of B cells after RIT induction for KTx. We sampled blood from 29 patients with (N = 16) and without (N = 13) RIT induction 3 to 18 months after KTx. In the RIT group, the majority of repopulating B cells was the transitional type, while memory B cells were scarce...
March 13, 2017: Therapeutic Apheresis and Dialysis
https://www.readbyqxmd.com/read/28295194/anti-leukaemic-activity-of-the-tyk2-selective-inhibitor-ndi-031301-in-t-cell-acute-lymphoblastic-leukaemia
#20
Koshi Akahane, Zhaodong Li, Julia Etchin, Alla Berezovskaya, Evisa Gjini, Craig E Masse, Wenyan Miao, Jennifer Rocnik, Rosana Kapeller, Jeremy R Greenwood, Hong Tiv, Takaomi Sanda, David M Weinstock, A Thomas Look
Activation of tyrosine kinase 2 (TYK2) contributes to the aberrant survival of T-cell acute lymphoblastic leukaemia (T-ALL) cells. Here we demonstrate the anti-leukaemic activity of a novel TYK2 inhibitor, NDI-031301. NDI-031301 is a potent and selective inhibitor of TYK2 that induced robust growth inhibition of human T-ALL cell lines. NDI-031301 treatment of human T-ALL cell lines resulted in induction of apoptosis that was not observed with the JAK inhibitors tofacitinib and baricitinib. Further investigation revealed that NDI-031301 treatment uniquely leads to activation of three mitogen-activated protein kinases (MAPKs), resulting in phosphorylation of ERK, SAPK/JNK and p38 MAPK coincident with PARP cleavage...
March 14, 2017: British Journal of Haematology
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