keyword
MENU ▼
Read by QxMD icon Read
search

Inhibitor tolerance induction

keyword
https://www.readbyqxmd.com/read/29330325/cutting-edge-plasmodium-falciparum-induces-trained-innate-immunity
#1
Jacob E Schrum, Juliet N Crabtree, Katherine R Dobbs, Michael C Kiritsy, George W Reed, Ricardo T Gazzinelli, Mihai G Netea, James W Kazura, Arlene E Dent, Katherine A Fitzgerald, Douglas T Golenbock
Malarial infection in naive individuals induces a robust innate immune response. In the recently described model of innate immune memory, an initial stimulus primes the innate immune system to either hyperrespond (termed training) or hyporespond (tolerance) to subsequent immune challenge. Previous work in both mice and humans demonstrated that infection with malaria can both serve as a priming stimulus and promote tolerance to subsequent infection. In this study, we demonstrate that initial stimulation with Plasmodium falciparum-infected RBCs or the malaria crystal hemozoin induced human adherent PBMCs to hyperrespond to subsequent ligation of TLR2...
January 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29314558/neutrophil-derived-csf1-induces-macrophage-polarization-and-promotes-transplantation-tolerance
#2
Mounia S Braza, Patricia Conde, Mercedes Garcia, Isabel Cortegano, Manisha Brahmachary, Venu Pothula, Francois Fay, Peter Boros, Sherry A Werner, Florent Ginhoux, Willem J M Mulder, Jordi Ochando
The colony-stimulating factor 1 (CSF1) regulates the differentiation and function of tissue macrophages and determines the outcome of the immune response. The molecular mechanisms behind CSF1-mediated macrophage development remain to be elucidated. Here we demonstrate that neutrophil-derived CSF1 controls macrophage polarization and proliferation, which is necessary for the induction of tolerance. Inhibiting neutrophil production of CSF1 or preventing macrophage proliferation, using targeted nanoparticles loaded with the cell cycle inhibitor simvastatin, abrogates the induction of tolerance...
January 4, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29304833/a-phase-i-study-of-selinexor-in-combination-with-high-dose-cytarabine-and-mitoxantrone-for-remission-induction-in-patients-with-acute-myeloid-leukemia
#3
Amy Y Wang, Howard Weiner, Margaret Green, Hua Chang, Noreen Fulton, Richard A Larson, Olatoyosi Odenike, Andrew S Artz, Michael R Bishop, Lucy A Godley, Michael J Thirman, Satyajit Kosuri, Jane E Churpek, Emily Curran, Kristen Pettit, Wendy Stock, Hongtao Liu
BACKGROUND: Novel therapies for patients with acute myeloid leukemia (AML) are imperative, particularly for those with high-risk features. Selinexor, an exportin 1 (XPO1/CRM1) inhibitor, has demonstrated anti-leukemia activity as a single agent, as well as in combination with anthracyclines and/or DNA-damaging agents. METHODS: We report the findings of a phase I dose escalation trial with cohort expansion in 20 patients with newly diagnosed or relapsed/refractory AML that combined selinexor with age-adjusted high-dose cytarabine and mitoxantrone (HiDAC/Mito)...
January 5, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29288671/prolonged-skin-grafts-survival-time-by-ifn-%C3%AE-in-allogeneic-skin-transplantation-model-during-acute-rejection-through-ifn-%C3%AE-stat3-ido-pathway-in-epidermal-layer
#4
Yijie Zhang, Yunchuan Wang, Gaofeng Wu, Wei Zhang, Xujie Wang, Weixia Cai, Julei Zhang, Shichao Han, Yan Li, Xiaozhi Bai, Jihong Shi, Linlin Su, Dahai Hu
Allogeneic skin transplantation is the life-saving therapy for multiple diseases, including extensive burn, large-scale trauma and certain post-surgical complications. However, acute rejection impedes clinical application of allogeneic skin transplantation. Although a lot of novel immunosuppressant drugs have been developed, there is still great need for ideal therapy with less complication and more therapeutic effects. Here, we found interferon gamma (IFN-γ) as an immunomodulatory cytokine prolonged the survival time of allografts from (8...
December 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29285240/molecular-basis-for-the-dna-damage-induction-and-anticancer-activity-of-asymmetrically-substituted-anthrapyridazone-pdz-7
#5
Majus Misiak, Mateusz Heldt, Marlena Szeligowska, Stefania Mazzini, Leonardo Scaglioni, Grzegorz J Grabe, Marcin Serocki, Jan Lica, Marta Switalska, Joanna Wietrzyk, Giovanni L Beretta, Paola Perego, Dominik Zietkowski, Maciej Baginski, Edward Borowski, Andrzej Skladanowski
Anthrapyridazones, imino analogues of anthraquinone, constitute a family of compounds with remarkable anti-cancer activity. To date, over 20 derivatives were studied, of which most displayed nanomolar cytotoxicity towards broad spectrum of cancer cells, including breast, prostate and leukemic ones. BS-154, the most potent derivative, had IC50 values close to 1 nM, however, it was toxic in animal studies. Here, we characterize another anthrapyridazone, PDZ-7, which retains high cytotoxicity while being well tolerated in mice...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29239193/-checkpoint-inhibitors-in-the-treatment-of-upper-gastrointestinal-tract-tumors
#6
R Obermannova
Chemotherapy prolongs overall survival (OS) in esophageal (EC) and gastric cancer (GC). Unsatisfactory results of systemic therapy initiated a search for new treatment options. In metastatic disease, a number of targeted drugs were tested; however, several phase III studies assessing receptor tyrosin kinase-related signaling pathways, such as EGFR, MET/HGF or mTOR, failed. Trastuzumab remains the only targeted drug with a known molecular predictor, which extended the OS in metastatic gastric adenocarcinoma and adenocarcinoma of esophago-gastric junction...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/29225598/innovative-approaches-for-immune-tolerance-to-factor-viii-in-the-treatment-of-hemophilia-a
#7
REVIEW
Alexandra Sherman, Moanaro Biswas, Roland W Herzog
Hemophilia A (coagulation factor VIII deficiency) is a debilitating genetic disorder that is primarily treated with intravenous replacement therapy. Despite a variety of factor VIII protein formulations available, the risk of developing anti-dug antibodies ("inhibitors") remains. Overall, 20-30% of patients with severe disease develop inhibitors. Current clinical immune tolerance induction protocols to eliminate inhibitors are not effective in all patients, and there are no prophylactic protocols to prevent the immune response...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29207601/dissecting-the-mechanisms-involved-in-anti-human-t-lymphocyte-immunoglobulin-atg-induced-tolerance-in-the-setting-of-allogeneic-stem-cell-transplantation-potential-implications-for-graft-versus-host-disease
#8
Katia Beider, David Naor, Valeria Voevoda, Olga Ostrovsky, Hanna Bitner, Evgenia Rosenberg, Nira Varda-Bloom, Victoria Marcu-Malina, Jonathan Canaani, Ivetta Danilesko, Avichai Shimoni, Arnon Nagler
Polyclonal anti-human thymocyte globulins (ATG) have been recently shown to significantly reduce the incidence of graft versus host disease (GVHD) post allogeneic stem cell transplantation (HSCT) from both sibling and unrelated donors. Induction of regulatory T cells has been suggested as one of the possible mechanisms. The aim of current study was to further characterize the T cell populations induced by ATG treatment and to delineate the mechanisms involved in ATG-induced tolerance. Phenotypic characterization revealed a significant increase in the expression of FoxP3, GITR, CD95, PD-1 and ICOS as well as the complement inhibitory molecules CD55, CD58 and CD59 on CD4+CD25+ T cells upon ATG treatment...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29201050/the-role-of-ache-in-swimming-behavior-of-daphnia-magna-correlation-analysis-of-both-parameters-affected-by-deltamethrin-and-methomyl-exposure
#9
Qing Ren, Ruibin Zhao, Cheng Wang, Shangge Li, Tingting Zhang, Zongming Ren, Meiyi Yang, Hongwei Pan, Shiguo Xu, Jianping Zhu, Xun Wang
The unpredictable toxicity of insecticides may cause behavior disorder of biological organisms. In order to assess the role of acetylcholinesterase (AChE) in swimming behavior of Daphnia magna, a correlation analysis of both parameters in 24 h exposure of deltamethrin (DM) and methomyl (MT) was investigated. The behavior responses of D. magna in DM (13.36 μg/L and 33.40 μg/L) and MT (19.66 μg/L and 49.15 μg/L) suggested that recovery behavior in the adjustment phase was crucial, and behavior homeostasis provided them with an optimal way to achieve a wider tolerance against environmental stress...
2017: Journal of Toxicology
https://www.readbyqxmd.com/read/29184126/genetic-and-pharmacological-inhibition-of-microrna-92a-maintains-podocyte-cell-cycle-quiescence-and-limits-crescentic-glomerulonephritis
#10
Carole Henique, Guillaume Bollée, Xavier Loyer, Florian Grahammer, Neeraj Dhaun, Marine Camus, Julien Vernerey, Léa Guyonnet, François Gaillard, Hélène Lazareth, Charlotte Meyer, Imane Bensaada, Luc Legrès, Takashi Satoh, Shizuo Akira, Patrick Bruneval, Stefanie Dimmeler, Alain Tedgui, Alexandre Karras, Eric Thervet, Dominique Nochy, Tobias B Huber, Laurent Mesnard, Olivia Lenoir, Pierre-Louis Tharaux
Crescentic rapidly progressive glomerulonephritis (RPGN) represents the most aggressive form of acquired glomerular disease. While most therapeutic approaches involve potentially toxic immunosuppressive strategies, the pathophysiology remains incompletely understood. Podocytes are glomerular epithelial cells that are normally growth-arrested because of the expression of cyclin-dependent kinase (CDK) inhibitors. An exception is in RPGN where podocytes undergo a deregulation of their differentiated phenotype and proliferate...
November 28, 2017: Nature Communications
https://www.readbyqxmd.com/read/29173475/mechanism-of-insulin-like-effect-of-chromium-iii-ions-on-glucose-uptake-in-c2c12-mouse-myotubes-involves-ros-formation
#11
Maciej Lipko, Bogdan Debski
Chromium is considered a trace element which improves glucose tolerance, but mechanism accounting for this insulin-like action is not recognized. The main purpose of this study was to examine the role of reactive oxygen species (ROS) in chromium and insulin stimulated glucose transport using antioxidants. Effect of chromium ions on phosphatases, enzymes involved in inhibition of insulin signaling was also investigated. Experiments were performed in vitro on C2C12 mouse myotubes. ROS level was measured with the use of confocal microscope and 2',7' dichlorodihydrofluorescein diacetate (DCFH-DA)...
January 2018: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/29170896/modern-treatments-of-haemophilia-review-of-cost-effectiveness-analyses-and-future-directions
#12
REVIEW
Paolo A Cortesi, Lucia S D'Angiolella, Alessandra Lafranconi, Mariangela Micale, Giancarlo Cesana, Lorenzo G Mantovani
BACKGROUND: Cost is currently one of the most important aspects in haemophilia care. Factor concentrates absorb more than 90% of healthcare direct costs of haemophilia care, and the debate regarding the high cost of haemophilia treatments and their different use across different countries is increasing. OBJECTIVE: The objective of this study was to review cost-effectiveness analyses conducted on treatment options in haemophilia, focusing on their results and their strengths and limitations; to highlight the possible issues associated with economic evaluations of new treatment options...
November 23, 2017: PharmacoEconomics
https://www.readbyqxmd.com/read/29165070/bortezomib-in-kidney-transplant-current-use-and-perspectives
#13
Lucio R Requião-Moura, Taina V de Sandes-Freitas, Gessika Marcelo-Gomes, Erika B Rangel
BACKGROUND: Despite major advances in transplant medicine, antibody-mediated rejection (AMR) continues to have severe clinical implications and adversely affect graft survival. Therefore, the search for alternative drugs to treat AMR is widely pursued. The first-in-class proteasome inhibitor bortezomib (BZ) is a selective inhibitor of the 26S proteasome, which was initially approved for the treatment of malignant plasma cell disorders. METHODS: This review encompasses how our understanding of inhibiting proteasome pathway created the basis of BZ research and important milestones accomplished in AMR treatment in the transplant setting...
November 20, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/29139135/phase-1-study-of-quizartinib-in-combination-with-induction-and-consolidation-chemotherapy-in-patients-with-newly-diagnosed-acute-myeloid-leukemia
#14
Jessica K Altman, James M Foran, Keith W Pratz, Denise Trone, Jorge E Cortes, Martin S Tallman
Novel therapies have potential to improve outcomes in patients with acute myeloid leukemia (AML) harboring FLT3-ITD mutations that have high risk of relapse and poor survival following standard of care (SOC) cytarabine/anthracycline-based induction/consolidation chemotherapy. Quizartinib is a selective and highly potent FLT3 inhibitor that has shown strong single-agent activity in relapsed or refractory (R/R) AML. This phase 1, open-label, sequential group dose-escalation trial (NCT 01390337) is the first evaluating safety and tolerability of quizartinib in combination with SOC chemotherapy in newly diagnosed AML (ndAML)...
November 15, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29111717/discovery-of-a-novel-and-selective-indoleamine-2-3-dioxygenase-ido-1-inhibitor-3-5-fluoro-1h-indol-3-yl-pyrrolidine-2-5-dione-eos200271-pf-06840003-and-its-characterization-as-a-potential-clinical-candidate
#15
Stefano Crosignani, Patrick Bingham, Pauline Bottemanne, Hélène Cannelle, Sandra Cauwenberghs, Marie Cordonnier, Deepak Dalvie, Frederik Deroose, Jun Li Feng, Bruno Gomes, Samantha Greasley, Stephen E Kaiser, Manfred Kraus, Michel Négrerie, Karen Maegley, Nichol Miller, Brion W Murray, Manfred Schneider, James Soloweij, Albert E Stewart, Joseph Tumang, Vince R Torti, Benoit Van Den Eynde, Martin Wythes
Tumors use tryptophan-catabolizing enzymes such as indoleamine 2,3-dioxygenase (IDO-1) to induce an immunosuppressive environment. IDO-1 is induced in response to inflammatory stimuli and promotes immune tolerance through effector T-cell anergy and enhanced Treg function. As such, IDO-1 is a nexus for the induction of a key immunosuppressive mechanism and represents an important immunotherapeutic target in oncology. Starting from HTS hit 5, IDO-1 inhibitor 6 (EOS200271/PF-06840003) has been developed. The structure-activity relationship around 6 is described and rationalized using the X-ray crystal structure of 6 bound to human IDO-1, which shows that 6, differently from most of the IDO-1 inhibitors described so far, does not bind to the heme iron atom and has a novel binding mode...
December 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29106782/expression-and-assembly-of-largest-foreign-protein-in-chloroplasts-oral-delivery-of-human-fviii-made-in-lettuce-chloroplasts-robustly-suppresses-inhibitor-formation-in-hemophilia-a-mice
#16
Kwang-Chul Kwon, Alexandra Sherman, Wan-Jung Chang, Aditya Kamesh, Moanaro Biswas, Roland W Herzog, Henry Daniell
Inhibitor formation is a serious complication of factor VIII (FVIII) replacement therapy for the X-linked bleeding disorder hemophilia A and occurs in 20-30% of patients. No prophylactic tolerance protocol currently exists. Although we reported oral tolerance induction using FVIII domains expressed in tobacco chloroplasts, significant challenges in clinical advancement include expression of the full-length CTB-FVIII sequence to cover the entire patient population, regardless of individual CD4(+) T cell epitope responses...
November 6, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/29094008/total-joint-replacement-in-inhibitor-positive-haemophilia-long-term-outcome-analysis-in-fifteen-patients
#17
Heidi Danielson, Riitta Lassila, Pekka Ylinen, Timo Yrjönen
AIM: To collect data from joint replacement in inhibitor patients, evaluate haemostatic and patient outcomes, and analyse the costs. METHODS: We report our 21-year, single-centre cumulative experience of 15 joint arthroplasties in six inhibitor patients. RESULTS: Two low responder inhibitor patients were in the early days treated with FVIII, whereas bypassing agents were used in the rest of the high responder patients. The primary haemostatic outcome was good in 8/15, fair in 4/15 and poor in 3/15 operations...
October 18, 2017: World Journal of Orthopedics
https://www.readbyqxmd.com/read/29081190/-immune-tolerance-induction-in-a-case-of-hemophilia-b-with-inhibitor-with-prothrombin-complex-concentrate-and-rituximab
#18
F Xue, W Liu, Y F Cheng, X F Liu, Y T Huang, R F Fu, L Zhang, R C Yang
Objective: To explore the immune tolerance induction (ITI) in a case of severe hemophilia B patient with inhibitor. Methods: The F Ⅸ∶C was detected using a one-stage method and FIX inhibitor was assayed using Bethesda method. ITI was performed with prothrombin complex concentrates (PCC) in combination with rituximab. Results: His past exposure days (ED) with PCC were 20 ED and his peak FⅨ inhibitor titer was 56 BU/ml. When his FIX inhibitor titer decreased to 10.4 BU/ml in Nov. 2015 and after receiving the informed consent from his parents, ITI was started...
September 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29054599/indoleamine-2-3-dioxygenase-expression-in-primary-cutaneous-melanoma-correlates-with-breslow-thickness-and-is-of-significant-prognostic-value-for-progression-free-survival
#19
Felicia Rubel, Johannes S Kern, Kristin Technau-Hafsi, Sibylle Uhrich, Kaethe Thoma, Georg Häcker, Nikolas von Bubnoff, Frank Meiss, Dagmar von Bubnoff
The enzyme indoleamine 2,3-dioxygenase (IDO) is emerging as a facilitator of cancer development through its effects on cancer-associated inflammation. Recent studies report a significant improvement of the response rates in melanoma patients to PD-1 antibodies when IDO-inhibitors were added to the regimen. Data on IDO-expression in primary human melanomas are however incomplete and conflicting. Here, we show that the level of IDO-expression in primary human melanoma cells significantly correlates with Breslow thickness (p = 0...
October 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29038460/a-novel-immunohistochemical-score-to-predict-early-mortality-in-acute-myeloid-leukemia-patients-based-on-indoleamine-2-3-dioxygenase-expression
#20
Abhishek Mangaonkar, Ashis Kumar Mondal, Sadanand Fulzule, Chetan Pundkar, Eun Jeong Park, Anand Jillella, Vamsi Kota, Hongyan Xu, Natasha M Savage, Huidong Shi, David Munn, Ravindra Kolhe
Indoleamine 2,3 dioxygenase-1 (IDO-1) is an enzyme in the kynurenine pathway which augments tumor-induced immune tolerance. Previous studies in childhood acute myeloid leukemia (AML) have shown a negative correlation of IDO-1 mRNA expression with outcomes. The aim of our study was to develop a practical and objective immunohistochemical technique to quantify IDO-1 expression on diagnostic bone marrow biopsies of AML patients in order to facilitate its use in routine clinical practice. IDO-1 mRNA was extracted from diagnostic bone marrow specimens from 29 AML patients...
October 16, 2017: Scientific Reports
keyword
keyword
4858
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"