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Transplantation Induction

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https://www.readbyqxmd.com/read/28820283/n-3-pufas-induce-inflammatory-tolerance-by-formation-of-keap1-containing-sqstm1-p62-bodies-and-activation-of-nfe2l2
#1
Jennifer Mildenberger, Ida Johansson, Ismail Sergin, Eli Kjøbli, Jan Kristian Damås, Babak Razani, Trude Helen Flo, Geir Bjørkøy
Inflammation is crucial in the defense against infections but must be tightly controlled to limit detrimental hyperactivation. Our diet influences inflammatory processes and omega-3 polyunsaturated fatty acids (n-3 PUFAs) have known anti-inflammatory effects. The balance of pro- and anti-inflammatory processes is coordinated by macrophages and macroautophagy/autophagy has recently emerged as a cellular process that dampens inflammation. Here we report that the n-3 PUFA docosahexaenoic acid (DHA) transiently induces cytosolic speckles of the autophagic receptor SQSTM1/p62 (sequestosome 1) (described as SQSTM1/p62-bodies) in macrophages...
August 18, 2017: Autophagy
https://www.readbyqxmd.com/read/28819011/tp53-mutations-identify-younger-mantle-cell-lymphoma-patients-who-do-not-benefit-from-intensive-chemoimmunotherapy
#2
Christian W Eskelund, Christina Dahl, Jakob W Hansen, Maj Westman, Arne Kolstad, Lone B Pedersen, Carmen P Montano-Almendras, Simon Husby, Catja Freiburghaus, Sara Ek, Anja Pedersen, Carsten Niemann, Riikka Räty, Peter Brown, Christian H Geisler, Mette K Andersen, Per Guldberg, Mats Jerkeman, Kirsten Grønbæk
Despite recent advances in lymphoma treatment, mantle cell lymphoma (MCL) remains incurable and we are still unable to identify patients who will not benefit from the current standard-of-care. Here, we explore the prognostic value of recurrent genetic aberrations in diagnostic bone marrow (BM) specimens from 183 younger MCL patients from the Nordic MCL2 and MCL3 trials, which represent current standard-of-care regimens. In the univariate model, mutations of TP53 (11%) and NOTCH1 (4%), and deletions of TP53 (16%) and CDKN2A (20%) were significantly associated with inferior outcomes (together with MIPI, MIPI-c, Blastoid morphology and Ki67>30%); however, in multivariate analyses only TP53 mutations (HR=6...
August 17, 2017: Blood
https://www.readbyqxmd.com/read/28818847/a-french-cohort-study-of-kidney-retransplantation-after-post-transplant-lymphoproliferative-disorders
#3
Sophie Caillard, Etienne Cellot, Jacques Dantal, Olivier Thaunat, François Provot, Bénédicte Janbon, Matthias Buchler, Dany Anglicheau, Pierre Merville, Philippe Lang, Luc Frimat, Charlotte Colosio, Eric Alamartine, Nassim Kamar, Anne Elisabeth Heng, Antoine Durrbach, Valérie Moal, Joseph Rivalan, Isabelle Etienne, Marie Noelle Peraldi, Anne Moreau, Bruno Moulin
BACKGROUND AND OBJECTIVES: Post-transplant lymphoproliferative disorders arising after kidney transplantation portend an increased risk of morbidity and mortality. Retransplantation of patients who had developed post-transplant lymphoproliferative disorder remains questionable owing to the potential risks of recurrence when immunosuppression is reintroduced. Here, we investigated the feasibility of kidney retransplantation after the development of post-transplant lymphoproliferative disorder...
August 17, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28817727/pilot-study-of-lithium-to-restore-intestinal-barrier-function-in-severe-graft-versus-host-disease
#4
Gideon Steinbach, David M Hockenbery, Gerwin Huls, Terry Furlong, David Myerson, Keith R Loeb, Jesse R Fann, Christina Castilla-Llorente, George B McDonald, Paul J Martin
Severe intestinal graft-vs-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT) causes mucosal ulceration and induces innate and adaptive immune responses that amplify and perpetuate GVHD and the associated barrier dysfunction. Pharmacological agents to target mucosal barrier dysfunction in GVHD are needed. We hypothesized that induction of Wnt signaling by lithium, an inhibitor of glycogen synthase kinase (GSK3), would potentiate intestinal crypt proliferation and mucosal repair and that inhibition of GSK3 in inflammatory cells would attenuate the deregulated inflammatory response to mucosal injury...
2017: PloS One
https://www.readbyqxmd.com/read/28815481/gene-delivery-approaches-for-mesenchymal-stem-cell-therapy-strategies-to-increase-efficiency-and-specificity
#5
REVIEW
Gopi Suresh Oggu, Shyama Sasikumar, Nirosha Reddy, Kranthi Kiran Reddy Ella, Ch Mohan Rao, Kiran Kumar Bokara
A significant number of clinical trials have been undertaken to explore the use of mesenchymal stem cells (MSCs) for the treatment of several diseases such as Crohn's disease, diabetes, bone defects, myocardial infarction, stroke etc., Due to their efficiency in homing to the tissue injury sites, their differentiation potential, the capability to secrete a large amount of trophic factors and their immunomodulatory effects, MSCs are becoming increasingly popular and expected to be one of the promising therapeutic approaches...
August 16, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28814236/neuroglial-cell-cryopreservation-in-appropriate-inductive-conditions
#6
Rosa M Gomez, Maria Andrea Dominguez-Sanchez, Magdy M Sanchez, George E Barreto
An ability to store cells (if they cannot be used fresh) reduces cell wastage, thereby increasing the supply of transplantable material. Cell storage is also valuable in scientific research, allowing material to be archived and experiments to be repeated from the same tissue source and facilitating research collaboration by allowing stored samples to be distributed. Cryopreservation is currently considered the most promising and successful, long-term biological conservation method. Its use has led to optimizing survival, improving protocols and stem cell and neuroglia viability, thereby assuring its future use in neuroregeneration and restoration regarding cell therapy...
August 16, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28814164/cpx-351-in-acute-myeloid-leukemia-can-a-new-formulation-maximize-the-efficacy-of-old-compounds
#7
Claudia Brunetti, Luisa Anelli, Antonella Zagaria, Giorgina Specchia, Francesco Albano
The management of Acute Myeloid Leukemia (AML) (with the exception of acute promyelocytic leukemia) has remained largely unchanged over the past 40 years. In particular, patients defined as high-risk, according to the 2017 European Leukemia Net recommendations, represent a subgroup with poor response to current therapies that are frequently associated with high-grade toxicity and potentially fatal complications. Areas covered: Preliminary results from an ongoing phase III clinical trial suggest that CPX-351 could represent an interesting treatment option in both induction and "bridge-to-transplant" settings...
August 17, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28813413/polylox-barcoding-reveals-haematopoietic-stem-cell-fates-realized-in-vivo
#8
Weike Pei, Thorsten B Feyerabend, Jens Rössler, Xi Wang, Daniel Postrach, Katrin Busch, Immanuel Rode, Kay Klapproth, Nikolaus Dietlein, Claudia Quedenau, Wei Chen, Sascha Sauer, Stephan Wolf, Thomas Höfer, Hans-Reimer Rodewald
Developmental deconvolution of complex organs and tissues at the level of individual cells remains challenging. Non-invasive genetic fate mapping has been widely used, but the low number of distinct fluorescent marker proteins limits its resolution. Much higher numbers of cell markers have been generated using viral integration sites, viral barcodes, and strategies based on transposons and CRISPR-Cas9 genome editing; however, temporal and tissue-specific induction of barcodes in situ has not been achieved. Here we report the development of an artificial DNA recombination locus (termed Polylox) that enables broadly applicable endogenous barcoding based on the Cre-loxP recombination system...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28811872/current-and-emerging-treatment-options-for-mantle-cell-lymphoma
#9
REVIEW
Bita Fakhri, Brad Kahl
Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma with typically aggressive behavior. The genetic signature is the chromosomal translocation t(11;14)(q13;q32) resulting in overexpression of cyclin D1. Asymptomatic newly diagnosed MCL patients with low tumor burden can be closely observed, deferring therapy to the time of disease progression. Although MCL classically responds to upfront chemotherapy, it remains incurable with standard approaches. For patients in need of frontline therapy, the initial decision is whether to proceed with an intensive treatment strategy or a non-intensive treatment strategy...
August 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28808225/congestive-preconditioning-by-portal-venous-clamping-a-novel-preventive-concept-for-small-intestinal-congestive-re-outflow-injury
#10
Hironori Hayashi, Hiroyuki Takamura, Ryosuke Gabata, Yoshinao Ohbatake, Shinichi Nakanuma, Tomoharu Miyashita, Hidehiro Tajima, Itasu Ninomiya, Sachio Fushida, Tetsuo Ohta
BACKGROUND Congestion of the small intestine, which induces mucosal damage via apoptosis, is a common pathophysiological change in hepato-biliary-pancreatic surgery, including liver transplantation. Small intestinal mucosal damage can trigger postoperative complications via various pathways. Therefore, we investigated the efficacy of intermittent portal venous clamping, which we named congestive preconditioning (CPC), for decreasing congestive re-outflow injury (CRoI) of the small intestine. MATERIAL AND METHODS Small intestinal CRoI was induced in rats by clamping the portal vein (PV) for 30 min, followed by re-outflow...
August 15, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/28807771/increase-of-intermediate-monocytes-in-gvhd-correlation-with-mdr1-th17-1-levels-and-the-effect-of-prednisolone-and-1%C3%AE-25-dihydroxyvitamin-d3
#11
Katharina Reinhardt-Heller, Insa Hirschberg, Peter Lang, Thomas Vogl, Rupert Handgretinger, Wolfgang A Bethge, Ursula Holzer
Graft-versus-host disease (GvHD) remains one of the major complications after allogeneic hematopoietic stem cell transplantation which is mainly treated with glucocorticoids such as prednisolone. In this study, the influence of monocyte subpopulations, prednisolone and 1α,25-Dihydroxyvitamin D3 on the induction of a pro-inflammatory subset of Th17 cells (MDR(+)Th17.1) characterized by CCR6(+)CXCR3(hi)CCR4(lo)CCR10(-)CD161(+) and stable expression of the multi-drug resistance protein type 1 (MDR1) was investigated...
August 11, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28805292/incidence-and-outcomes-of-primary-central-nervous-system-lymphoma-in-solid-organ-transplant-recipients
#12
Parag Mahale, Meredith S Shiels, Charles F Lynch, Eric A Engels
Primary central nervous system lymphoma (PCNSL) risk is greatly increased in immunosuppressed HIV-infected people. Using data from the United States transplant registry linked with 17 cancer registries (1987-2014), we studied PCNSL and systemic non-Hodgkin lymphoma (NHL) in 288,029 solid organ transplant recipients. Transplant recipients had elevated incidence for PCNSL compared with the general population (standardized incidence ratio=65.1; N=168), and this elevation was stronger than for systemic NHL (standardized incidence ratio=11...
August 14, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28804680/treatment-of-older-patients-with-acute-myeloid-leukemia-aml-revised-canadian-consensus-guidelines
#13
REVIEW
Joseph M Brandwein, Nancy Zhu, Rajat Kumar, Brian Leber, Mitchell Sabloff, Irwindeep Sandhu, Jeannine Kassis, Harold J Olney, Mohamed Elemary, Andre C Schuh
The treatment of acute myeloid leukemia (AML) in older patients is undergoing rapid changes, with a number of important publications in the past five years. Because of this, a group of Canadian leukemia experts has produced an update to the Canadian Consensus Guidelines that were published in 2013, with several new agents recommended, subject to availability. Recent studies have supported the survival benefit of induction chemotherapy for patients under age 80, except those with major co-morbidities or those with adverse risk cytogenetics who are not candidates for allogeneic hematopoietic stem cell transplantation (HSCT)...
2017: American Journal of Blood Research
https://www.readbyqxmd.com/read/28803241/gender-specific-aspects-in-patients-with-multiple-myeloma-undergoing-autologous-stem-cell-transplantation-a-single-center-experience
#14
Doris Posch, Werner Rabitsch, Philipp Wohlfarth, Michael Leiner, Edit Porpaczy, Johannes Drach, Markus Raderer, Wolfgang Lamm
OBJECTIVE: Limited data exist on gender-specific aspects in hematologic malignancies and have been obtained mostly in non-Hodgkin lymphomas. The objective of this study was to investigate gender-specific aspects in patients with multiple myeloma (MM) undergoing autologous stem cell transplantation (ASCT). METHODS: A retrospective data analysis of 191 patients with MM who underwent ASCT was performed. Data collected from clinical records included age, sex, stage, induction therapy, outcome of induction, kind of stem cell mobilization, response to induction therapy and ASCT, cytogenetic aberrations, progression-free survival, and overall survival...
August 12, 2017: Oncology
https://www.readbyqxmd.com/read/28799202/immune-tolerance-induced-by%C3%A2-platelet-targeted-factor-viii-gene-therapy-in-hemophilia-a-mice-is-cd4%C3%A2-t-cell-mediated
#15
Y Chen, X Luo, J A Schroeder, J Chen, C K Baumgartner, J Hu, Q Shi
BACKGROUND: Immune responses are a major concern in gene therapy. Our previous studies demonstrated that platelet-targeted FVIII (2bF8) gene therapy together with in vivo drug-selection of transduced cells can rescue the bleeding diathesis and induce immune tolerance in FVIII(null) mice. OBJECTIVE: To investigate whether non-selectable 2bF8 lentiviral vector (LV) for the induction of platelet-FVIII expression is sufficient to induce immune tolerance and how immune tolerance is induced after 2bF8LV gene therapy...
August 11, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28796244/bet-bromodomain-inhibitors-synergize-with-atr-inhibitors-in-melanoma-in-melanoma
#16
Somsundar Veppil Muralidharan, Berglind Osk Einarsdottir, Joydeep Bhadury, Mattias F Lindberg, Jin Wu, Eric Campeau, Roger Olofsson Bagge, Ulrika Stierner, Lars Ny, Lisa M Nilsson, Jonas A Nilsson
Metastatic malignant melanoma continues to be a challenging disease despite clinical translation of the comprehensive understanding of driver mutations and how melanoma cells evade immune attack. In Myc-driven lymphoma, efficacy of epigenetic inhibitors of the bromodomain and extra-terminal domain (BET) family of bromodomain proteins can be enhanced by combination therapy with inhibitors of the DNA damage response kinase ATR. Whether this combination is active in solid malignancies like melanoma, and how it relates to immune therapy, has not previously investigated...
August 10, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28794968/successful-salvage-chemotherapy-and-allogeneic-transplantation-of-an-acute-myeloid-leukemia-patient-with-disseminated-fusarium-solani-infection
#17
Sheenu Sheela, Sawa Ito, Jeffrey R Strich, Maura Manion, Celina Montemayor-Garcia, Hao-Wei Wang, Karolyn A Oetjen, Kamile A West, Austin J Barrett, Mark Parta, Juan Gea-Banacloche, Steven M Holland, Christopher S Hourigan, Catherine Lai
Disseminated Fusarium infection is associated with high mortality in immunocompromised patients. Patients with acute myeloid leukemia (AML) often have an extended duration of neutropenia during intensive induction chemotherapy, consolidation chemotherapy, and hematopoietic stem cell transplantation (SCT). There is no consensus regarding management of invasive disseminated Fusarium infections in the setting of prolonged neutropenia (Tortorano et al., 2014) [1]. We report a case of disseminated Fusarium in a patient with relapsed AML who underwent successful chemotherapy and haplo-identical allogeneic SCT with administration of granulocyte colony stimulating factor (G-CSF) and granulocyte infusions...
2017: Leukemia Research Reports
https://www.readbyqxmd.com/read/28793875/an-analysis-of-97-previously-diagnosed-de-novo-adult-acute-erythroid-leukemia-patients-following-the-2016-revision-to-world-health-organization-classification
#18
Shaowei Qiu, Erlie Jiang, Hui Wei, Dong Lin, Guangji Zhang, Shuning Wei, Chunlin Zhou, Kaiqi Liu, Ying Wang, Bingcheng Liu, Yuntao Liu, Benfa Gong, Xiaoyuan Gong, Sizhou Feng, Yingchang Mi, Mingzhe Han, Jianxiang Wang
BACKGROUND: The incidence of acute erythroid leukemia subtype (AEL) is rare, accounting for 5% of cases of acute myeloid leukemia (AML), and the outcome is dismal. However, in 2016 revision to the WHO classification, the subcategory of AEL has been removed. Myeloblasts are redefined as the percentage of total marrow cells, not non-erythroid cells. Therefore, the previously diagnosed AEL cases are currently diagnosed as AML or myelodyspalstic syndrome (MDS) according to new criteria. METHODS: We respectively reviewed cases of 97 de novo previously diagnosed AEL and all the patients were diagnosed as AML or MDS according to the new classification scheme, and then the clinical characteristics of these two subtypes were compared...
August 9, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28791576/tolerogenic-nanoparticles-to-treat-islet-autoimmunity
#19
REVIEW
Tobias Neef, Stephen D Miller
PURPOSE OF REVIEW: The current standard therapy for type 1 diabetes (T1D) is insulin replacement. Autoimmune diseases are typically treated with broad immunosuppression, but this has multiple disadvantages. Induction of antigen-specific tolerance is preferable. The application of nanomedicine to the problem of T1D can take different forms, but one promising way is the development of tolerogenic nanoparticles, the aim of which is to mitigate the islet-destroying autoimmunity. We review the topic and highlight recent strategies to produce tolerogenic nanoparticles for the purpose of treating T1D...
August 8, 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28790849/immunotargeting-relapsed-or-refractory-precursor-b-cell-acute-lymphoblastic-leukemia-role-of-blinatumomab
#20
REVIEW
Manon Queudeville, Rupert Handgretinger, Martin Ebinger
Patients with refractory or relapsed (R/R) acute lymphoblastic leukemia (ALL) have a dismal prognosis of around 5% long-term survival when treated with cytotoxic chemotherapy and allogenic stem cell transplantation. T-cell immunobased strategies open up new therapeutic perspectives. Blinatumomab is the first of a new class of antibody constructs that was labeled bispecific T-cell engager (BiTE): it consists of two single chain variable fragment connected with a flexible linker, one side binding CD3, the other CD19...
2017: OncoTargets and Therapy
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