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Xiaodan Luo, Lihua Xu, Yangqiu Li, Huo Tan
Graft-versus-host disease (GVHD) induced by host antigen-presenting cells (APCs) and donor-derived T cells remains the major limitation of allogeneic bone marrow transplantation (allo-BMT). Notch signaling pathway is a highly conserved cell-cell communication that is important in T cell development. Recently, Notch signaling pathway is reported to be involved in regulating GVHD. To investigate the role of Notch inhibition in modulating GVHD, we established MHC-mismatched murine allo-BMT model. We found that inhibition of Notch signaling pathway by γ-secretase inhibitor in vivo could reduce aGVHD, which was shown by the onset time of aGVHD, body weight, clinical aGVHD scores, pathology aGVHD scores, and survival...
October 21, 2016: Cell Biology and Toxicology
Sofia Morfopoulou, Edward T Mee, Sarah M Connaughton, Julianne R Brown, Kimberly Gilmour, W K 'Kling' Chong, W Paul Duprex, Deborah Ferguson, Mike Hubank, Ciaran Hutchinson, Marios Kaliakatsos, Stephen McQuaid, Simon Paine, Vincent Plagnol, Christopher Ruis, Alex Virasami, Hong Zhan, Thomas S Jacques, Silke Schepelmann, Waseem Qasim, Judith Breuer
Routine childhood vaccination against measles, mumps and rubella has virtually abolished virus-related morbidity and mortality. Notwithstanding this, we describe here devastating neurological complications associated with the detection of live-attenuated mumps virus Jeryl Lynn (MuV(JL5)) in the brain of a child who had undergone successful allogeneic transplantation for severe combined immunodeficiency (SCID). This is the first confirmed report of MuV(JL5) associated with chronic encephalitis and highlights the need to exclude immunodeficient individuals from immunisation with live-attenuated vaccines...
October 21, 2016: Acta Neuropathologica
Min-Min Shi, Yuan Kong, Yang Song, Yu-Qian Sun, Yu Wang, Xiao-Hui Zhang, Lan-Ping Xu, Kai-Yan Liu, Xiao-Jun Huang
Poor graft function (PGF) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Murine studies suggest that endothelial progenitor cells (EPCs) are preferential supporting cells for hematopoietic stem cells (HSCs) in the bone marrow (BM) microenvironment. Our previous work found that a reduced number of BM EPCs was an independent risk factor for the occurrence of PGF after allo-HSCT. However, little is known about the functional role of BM EPCs and how to improve impaired BM EPCs in PGF...
October 21, 2016: Blood
Serdar Sivgin, Sinan Nazlim, Gokmen Zararsiz, Osman Baspinar, Leylagul Kaynar, Kemal Deniz, Mustafa Cetin, Ali Unal, Bulent Eser
BACKGROUND: Iron overload is one of the most significant problems as a leading cause of death in patients with leukemia and those who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT). METHODS: In the current study, we retrospectively evaluated the bone marrow iron scores (BMIS) in patients who underwent alloHSCT (n = 125). The first available bone marrow biopsy specimens prior to the alloHSCT procedure or date of hospitalization (control group) were assessed in a blinded fashion using a standardized scoring system...
October 2016: Clinical Lymphoma, Myeloma & Leukemia
Margarida Ferreira-Teixeira, Daniela Paiva-Oliveira, Belmiro Parada, Vera Alves, Vitor Sousa, Obinna Chijioke, Christian Münz, Flávio Reis, Paulo Rodrigues-Santos, Célia Gomes
BACKGROUND: High-grade non-muscle invasive bladder cancer (NMIBC) has a high risk of recurrence and progression to muscle-invasive forms, which seems to be largely related to the presence of tumorigenic stem-like cell populations that are refractory to conventional therapies. Here, we evaluated the therapeutic potential of Natural Killer (NK) cell-based adoptive immunotherapy against chemoresistant bladder cancer stem-like cells (CSCs) in a pre-clinical relevant model, using NK cells from healthy donors and NMIBC patients...
October 21, 2016: BMC Medicine
S J Lang, D Böhringer, G Geerling, T Reinhard
AimThe objective of the study was to evaluate the long-term results of allogenic penetrating limbo-keratoplasy. This method allows simultaneous transplantation of a corneal graft and limbal stem cells of the donor by means of eccentric trephination of the donor button.MethodThe data of 192 consecutive cases of allogenic penetrating limbo-keratoplasty from 1995 to 2015 were reviewed. These had been performed exclusively in eyes with complete failure of the limbal stem cells, in combination with deep corneal scarring...
October 21, 2016: Eye
Emmanuelle Ginoux, Diane Kottler, Bruno Anglaret, Brigitte Balme, Claude-Eric Bulabois, François Skowron
No abstract text is available yet for this article.
September 2016: JAAD Case Reports
Janet Ayello, Jessica Hochberg, Allyson Flower, Yaya Chu, Laxmi V Baxi, William Quish, Carmella van de Ven, Mitchell S Cairo
NK cells play a significant role in reducing relapse in patients with hematological malignancies following allogeneic stem cell transplantation but NK cell number and naturally occurring inhibitory signals limit their capability. IL-15 and 4-1BBL are important modulators of NK expansion and functional activation. With an aim to overcome these limitations, cord blood (CB) mononuclear cells (MNC) were ex-vivo expanded (EvE) for 7 days with genetically modified K562-mbIL15-41BBL (MODK562) or wildtype K562 (WTK562)...
October 17, 2016: Experimental Hematology
Mª Carmen Herrero-Sánchez, Concepción Rodríguez-Serrano, Julia Almeida, Laura San Segundo, Susana Inogés, Ángel Santos-Briz, Jesús García-Briñón, Luis Antonio Corchete, Jesús F San Miguel, Consuelo Del Cañizo, Belén Blanco
BACKGROUND: Graft-versus-host disease (GvHD) remains the major obstacle to successful allogeneic hematopoietic stem cell transplantation, despite of the immunosuppressive regimens administered to control T cell alloreactivity. PI3K/AKT/mTOR pathway is crucial in T cell activation and function and, therefore, represents an attractive therapeutic target to prevent GvHD development. Recently, numerous PI3K inhibitors have been developed for cancer therapy. However, few studies have explored their immunosuppressive effect...
October 20, 2016: Journal of Hematology & Oncology
Jana Jakubikova, Danka Cholujova, Teru Hideshima, Paulina Gronesova, Andrea Soltysova, Takeshi Harada, Jungnam Joo, Sun-Young Kong, Raphael E Szalat, Paul G Richardson, Nikhil C Munshi, David M Dorfman, Kenneth C Anderson
Specific niches within the tumor bone marrow (BM) microenvironment afford a sanctuary for multiple myeloma (MM) clones due to stromal cell-tumor cell interactions, which confer survival advantage and drug resistance. Defining the sequelae of tumor cell interactions within the MM niches on an individualized basis may provide the rationale for personalized therapies. To mimic the MM niche, we here describe a new 3D co-culture ex-vivo model in which primary MM patient BM cells are co-cultured with mesenchymal stem cells (MSC) in a hydrogel 3D system...
October 13, 2016: Oncotarget
Arpit Bhargava, Dinesh K Mishra, Subodh K Jain, Rupesh K Srivastava, Nirmal K Lohiya, Pradyumna K Mishra
We aimed to identify an optimum nano-carrier system to deliver tumor antigen to dendritic cells (DCs) for efficient targeting of tumor reinitiating cells (TRICs) in gynecological malignancies. Different lipid based nano-carrier systems i.e. liposomes, ethosomes and solid lipid nanoparticles (SLNPs) were examined for their ability to activate DCs in allogeneic settings. Out of these three, the most optimized formulation was subjected for cationic and mannosylated surface modification and pulsed with DCs for specific targeting of tumor cells...
October 17, 2016: Molecular Immunology
Lauren Brasile, Nicholas Henry, Bart Stubenitsky
BACKGROUND: We have previously reported on a novel organ-specific immunomodifying therapy that provides protection from early allograft rejection in the absence of systemic immunosuppressive drugs. This novel therapy is a nano-barrier membrane called ImmunoCloak, consisting of a matrix of laminin, proteoglycans, fibronectin and collagens. The membrane "immunocloaks" the luminal surfaces within the renal vasculature by covering the point of contact between donor vascular endothelial cells and the recipient's immune cells; without adversely affecting renal function...
October 19, 2016: Transplantation
Hannah K Choe, Usama Gergis, Sebastian A Mayer, Himanshu Nagar, Adrienne A Phillips, Tsiporah B Shore, Michael J Smith, Koen van Besien
BACKGROUND: Preliminary evidence indicates that the addition of low dose TBI (2-4 Gy) to reduced intensity conditioning may reduce the rate of relapse in allogeneic stem cell transplants. In very high risk patients receiving combination haploidentical-single unit cord blood transplants, we have added 4 Gy TBI to the widely used fludarabine, melphalan conditioning regimen, in hopes of reducing relapse and decreasing graft rejection. METHODS: We retrospectively reviewed the posttransplant outcomes of patients who underwent haplo-cord SCT between May 2013 and March 2015 and who received fludarabine 30mg/m2 D-7 to -3, melphalan 140mg/m2 D-2, and 2 Gy TBI D-4 and -3...
October 19, 2016: Transplantation
Vincent Ronfard, Alain Vertes, Michael May, Anne Dupraz, Mark van Dyke, Yves Bayon
"Evaluating the Past & Present of Regenerative Medicine (RM)" was the first part of an Industry Symposium dedicated to the subject during the 2015 World TERMIS Congress in Boston. This working session presented a critical review of the current RM landscape in Europe and North America with possible projections for the future. Interestingly, the RM development cycle seems to obey the Gartner hype cycle, now at the enlightenment phase, after past exaggerated expectations and discouragements, as suggested by increasing numbers of clinical trials and recent market approvals of RM solutions in both Europe (Glybera & Holoclar® from Chiesi Pharma and Strimvelis® from GSK) and Japan (Remestemcel-L from Mesoblast® )...
October 20, 2016: Tissue Engineering. Part B, Reviews
Takeshi Kimura, Akihiro Yamashita, Keiichi Ozono, Noriyuki Tsumaki
Articular cartilage damage does not spontaneously heal and could ultimately result in a loss of joint function. Damaged cartilage can be repaired with cell/tissue sources that are transplanted, however, autologous chondrocytes are limited in number as a cell source. Induced pluripotent stem cells (iPSCs) are a relatively new and abundant cell source and can be made from the patient, but at considerable cost. Because cartilage is immunoprivileged tissue, allogeneic cartilages have been transplanted effectively without matching for human leukocyte antigen (HLA), but are difficult to acquire due to scarcity of donors...
October 20, 2016: Tissue Engineering. Part A
Animesh Pardanani
: Disease overview:Systemic mastocytosis (SM) results from a clonal proliferation of abnormal mast cells (MC) in one or more extra-cutaneous organs. DIAGNOSIS: The major criterion is presence of multifocal clusters of morphologically abnormal MC in the bone marrow. Minor diagnostic criteria include elevated serum tryptase level, abnormal MC expression of CD25 and/or CD2, and presence of KITD816V. Risk stratification: The 2008 World Health Organization (WHO) classification of SM has been shown to be prognostically relevant...
November 2016: American Journal of Hematology
Nirali N Shah, Theresa M Watson, Bonnie Yates, David J Liewehr, Seth M Steinberg, David Jacobsohn, Terry J Fry
BACKGROUND: Diagnosis of engraftment syndrome (ES) following allogeneic hematopoietic stem cell transplantation (HSCT) can be a challenge due to the systemic presentation and alternative etiologies. With a goal of establishing biomarkers to more accurately distinguish ES, we prospectively analyzed levels of cytokines during HSCT. PROCEDURES: We performed a prospective study of children ≤21 years who underwent allogeneic HSCT. Blood samples for interleukin (IL)-6, IL-8, IL-10, IL-1b, IL-12p70, interferon-γ, tumor necrosis factor alpha (TNF-α) and procalcitonin were obtained from each subject prior to conditioning, at day 0, and then biweekly through engraftment and at days 30, 60 and 100...
October 20, 2016: Pediatric Blood & Cancer
Katsuto Takenaka, Kazuya Shimoda, Naoyuki Uchida, Taizo Shimomura, Koji Nagafuji, Tadakazu Kondo, Hirohiko Shibayama, Takehiko Mori, Kensuke Usuki, Taichi Azuma, Yutaka Tsutsumi, Junji Tanaka, Hitomi Dairaku, Keitaro Matsuo, Keiya Ozawa, Mineo Kurokawa, Shunya Arai, Koichi Akashi
We conducted a 17-year nationwide survey (1999-2015) to elucidate the clinical outcomes of patients with primary myelofibrosis (PMF) in Japan. Questionnaires were sent annually to approximately 500 hematology departments. Newly diagnosed patients with PMF were enrolled in this study, and were followed up annually to collect prognostic information. Approximately 50 patients were enrolled per year, yielding a total of 780 patients with PMF included in this study. The median age at diagnosis was 66 years. At the time of analysis, the median survival duration was 47 months, and the 3-year overall survival rate was 59 %...
October 19, 2016: International Journal of Hematology
Corinna La Rosa, Jeff Longmate, Joy Martinez, Qiao Zhou, Teodora I Kaltcheva, Weimin Tsai, Jennifer Drake, Mary Carroll, Felix Wussow, Flavia Chiuppesi, Nicola Hardwick, Sanjeet Dadwal, Ibrahim Aldoss, Ryotaro Nakamura, John A Zaia, Don J Diamond
Attenuated poxvirus Modified vaccinia Ankara (MVA) is a useful viral-based vaccine for clinical investigation, because of its excellent safety profile and property of inducing potent immune responses against recombinant (r) antigens. We developed Triplex by constructing an rMVA encoding three immunodominant CMV antigens which stimulates a host anti-viral response: UL83 (pp65), UL123 (IE1-exon4), and UL122 (IE2-exon5). We completed the first clinical evaluation of the Triplex vaccine in 24 healthy adults, with or without immunity to CMV and vaccinia virus (previous DryVax smallpox vaccination)...
October 19, 2016: Blood
Hidekazu Nishikii, Byung-Su Kim, Yasuhisa Yokoyama, Yan Chen, Jeanette Baker, Antonio Pierini, Maite Alvarez, Melissa Mavers, Kristina Maas-Bauer, Yuqiong Pan, Shigeru Chiba, Robert S Negrin
CD4(+)Foxp3(+) regulatory T cells (Treg) are a subpopulation of T cells, which regulate the immune system and enhance immune tolerance after transplantation. Donor-derived Treg prevent the development of lethal acute graft versus host disease (GVHD) in murine models of allogeneic hematopoietic stem cell transplantation (HCT). We recently demonstrated that a single treatment of the agonistic antibody to DR3 (Death receptor 3, αDR3) to donor mice resulted in the expansion of donor derived Treg and prevented acute GVHD, although the precise role of DR3 signaling in GVHD has not been elucidated...
October 19, 2016: Blood
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