Database : MEDLINE
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[PMID]: 26403510
[Au] Autor:Hiwatashi N; Hirano S; Suzuki R; Kawai Y; Mizuta M; Kishimoto Y; Tateya I; Kanemaru S; Nakamura T; Dezawa M; Ito J
[Ad] Address:Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan....
[Ti] Title:Comparison of ASCs and BMSCs combined with atelocollagen for vocal fold scar regeneration.
[So] Source:Laryngoscope;126(5):1143-50, 2016 May.
[Is] ISSN:1531-4995
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:OBJECTIVES/HYPOTHESIS: Vocal fold scar remains a therapeutic challenge. Mesenchymal stromal cells (MSCs) are promising tools for regenerative medicine. Nevertheless, few in vivo studies have directly compared various sources of MSCs. The aim of this study was to investigate the therapeutic potential of adipose-derived stromal cells (ASCs) in comparison with bone marrow-derived stromal cells (BMSCs) for vocal fold regeneration. STUDY DESIGN: Prospective animal experiments with controls. METHODS: Two months after stripping of the lamina propria, 18 beagles were divided into four implantation groups: atelocollagen alone (collagen group), atelocollagen with BMSCs (BMSC-collagen), atelocollagen with ASCs (ASC-collagen), or a sham-treated group. One or 6 months after implantation, vibratory and histological examinations were performed. RESULTS: Mucosal vibration was significantly improved in both of the MSC-implanted groups compared with the sham-treated group, whereas only the ASC-collagen group showed a significantly smaller glottal gap than the collagen group. Moreover, in the ASC-collagen group, a significant reduction of collagen density was observed compared to the sham-treated group, and there was a trend for better restoration of hyaluronic acid (HA). Implanted MSCs were detected 1 month postimplantation; however, none survived 6 months postimplantation. CONCLUSIONS: Although implantation of an atelocollagen sponge and ASCs into vocal fold scars induced vibratory recovery comparable to that of BMSCs, ASCs might have more potential in terms of restoration of HA and suppression of excessive collagen deposition. LEVEL OF EVIDENCE: NA Laryngoscope, 126:1143-1150, 2016.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1604
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1002/lary.25667

  2 / 335305 MEDLINE  
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[PMID]: 27057951
[Au] Autor:Perrucci GL; Straino S; Corlianò M; Scopece A; Napolitano M; Berk BC; Lombardi F; Pompilio G; Capogrossi MC; Nigro P
[Ad] Address:Department of Clinical Sciences and Community Health, University of Milan, Via Festa del Perdono 7, 20122 Milan, Italy; Unit of Vascular Biology and Regenerative Medicine, Centro Cardiologico Monzino-IRCCS, Via C. Parea 4, 20138 Milan, Italy....
[Ti] Title:Cyclophilin A modulates bone marrow-derived CD117(+) cells and enhances ischemia-induced angiogenesis via the SDF-1/CXCR4 axis.
[So] Source:Int J Cardiol;212:324-35, 2016 Jun 1.
[Is] ISSN:1874-1754
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:BACKGROUND: Critical limb ischemia (CLI) is a major health problem with no adequate treatment. Since CLI is characterized by insufficient tissue vascularization, efforts have focused on the discovery of novel angiogenic factors. Cyclophilin A (CyPA) is an immunophilin that has been shown to promote angiogenesis in vitro and to enhance bone marrow (BM) cell mobilization in vivo. However, its potential as an angiogenic factor in CLI is still unknown. Thus, this study aimed to evaluate whether CyPA might induce neo-angiogenesis in ischemic tissues. METHODS AND RESULTS: Wild-type C57Bl/6j mice underwent acute hind-limb ischemia (HLI) and received a single intramuscular administration of recombinant CyPA or saline. Limb perfusion, capillary density and arteriole number in adductor muscles were significantly increased after CyPA treatment. Interestingly, BM-derived CD117(+) cell recruitment was significantly higher in ischemic adductor tissue of mice treated with CyPA versus saline. Therefore, the effect of CyPA on isolated BM-derived CD117(+) cells in vitro was evaluated. Low concentrations of CyPA stimulated CD117(+) cell proliferation while high concentrations promoted cell death. Moreover, CyPA enhanced CD117(+) cell adhesion and migration in a dose-dependent manner. Mechanistic studies revealed that CyPA up-regulated CXCR4 in CD117(+) cells and in adductor muscles after ischemia. Additionally, SDF-1/CXCR4 axis inhibition by the CXCR4 antagonist AMD3100 decreased CyPA-mediated CD117(+) cell recruitment in the ischemic limb. CONCLUSION: CyPA induces neo-angiogenesis by recruiting BM-derived CD117(+) cell into ischemic tissues, at least in part, through SDF-1/CXCR4 axis.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1604
[Js] Journal subset:IM
[St] Status:In-Data-Review

  3 / 335305 MEDLINE  
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[PMID]: 26443851
[Au] Autor:Tweats DJ; Johnson GE; Scandale I; Whitwell J; Evans DB
[Ti] Title:Genotoxicity of flubendazole and its metabolites in vitro and the impact of a new formulation on in vivo aneugenicity.
[So] Source:Mutagenesis;31(3):309-21, 2016 May.
[Is] ISSN:1464-3804
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:The anti-parasitic benzimidazole flubendazole has been used for many years to treat intestinal infections in humans and animals. Previous genotoxicity studies have shown that the compound is not a bacterial mutagen and a bone marrow micronucleus test, using a formulation that limited systemic absorption, was negative. The purpose of this study is to explore the genotoxicity of flubendazole and its main metabolites in in vitro micronucleus studies and to test a new oral formulation that improves systemic absorption in an in vivo micronucleus test. The isolated metabolites were also screened using the Ames test for bacterial mutagenicity. It was found that flubendazole, like other chemically related benzimidazoles used in anti-parasitic therapies, is a potent aneugen in vitro The hydrolysed metabolite of flubendazole is negative in these tests, but the reduced metabolite (R- and S-forms) shows both aneugenic and clastogenic activity. However, in vitro micronucleus tests of flubendazole in the presence of rat liver S9 gave almost identical signals for aneugenicity as they did in the absence of S9, suggesting that any clastogenicity from the reduced metabolite is not sufficient to change the overall profile. Like flubendazole itself, both metabolites are negative in the Ames test. Analysis of dose-response curves from the in vitro tests, using recently developed point of departure approaches, demonstrate that the aneugenic potency of flubendazole is very similar to related anti-parasitic benzimidazoles, including albendazole, which is used in mass drug administration programmes to combat endemic filarial diseases. The in vivo micronucleus test of the new formulation of flubendazole also showed evidence of induced aneugenicity. Analysis of the in vivo data allowed a reference dose for aneugenicity to be established which can be compared with therapeutic exposures of flubendazole when this has been established. Analysis of the plasma from the animals used in the in vivo micronucleus test showed that there is increased exposure to flubendazole compared with previously tested formulations, as well as significant formation of the non-genotoxic hydrolysed metabolite of flubendazole and small levels of the reduced metabolite. In conclusion, this study shows that flubendazole is a potent aneugen in vitro with similar potency to chemically related benzimidazoles currently used as anti-parasitic therapies. The reduced metabolite also has aneugenic properties as well as clastogenic properties. Treatment with a new formulation of flubendazole that allows increased systemic exposure, compared with previously used formulations, also results in detectable aneugenicity in vivo. Based on the lack of carcinogenicity of this class of benzimidazoles and the intended short-term dosing, it is unlikely that flubendazole treatment will pose a carcinogenic risk to patients.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1604
[Cu] Class update date: 160423
[Lr] Last revision date:160423
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1093/mutage/gev070

  4 / 335305 MEDLINE  
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[PMID]: 27099644
[Au] Autor:Health Quality Ontario
[Ti] Title:Minimal Residual Disease Evaluation in Childhood Acute Lymphoblastic Leukemia: An Economic Analysis.
[So] Source:Ont Health Technol Assess Ser;16(8):1-83, 2016.
[Is] ISSN:1915-7398
[Cp] Country of publication:Canada
[La] Language:eng
[Ab] Abstract:BACKGROUND: Minimal residual disease (MRD) testing by higher performance techniques such as flow cytometry and polymerase chain reaction (PCR) can be used to detect the proportion of remaining leukemic cells in bone marrow or peripheral blood during and after the first phases of chemotherapy in children with acute lymphoblastic leukemia (ALL). The results of MRD testing are used to reclassify these patients and guide changes in treatment according to their future risk of relapse. We conducted a systematic review of the economic literature, cost-effectiveness analysis, and budget-impact analysis to ascertain the cost-effectiveness and economic impact of MRD testing by flow cytometry for management of childhood precursor B-cell ALL in Ontario. METHODS: A systematic literature search (1998-2014) identified studies that examined the incremental cost-effectiveness of MRD testing by either flow cytometry or PCR. We developed a lifetime state-transition (Markov) microsimulation model to quantify the cost-effectiveness of MRD testing followed by risk-directed therapy to no MRD testing and to estimate its marginal effect on health outcomes and on costs. Model input parameters were based on the literature, expert opinion, and data from the Pediatric Oncology Group of Ontario Networked Information System. Using predictions from our Markov model, we estimated the 1-year cost burden of MRD testing versus no testing and forecasted its economic impact over 3 and 5 years. RESULTS: In a base-case cost-effectiveness analysis, compared with no testing, MRD testing by flow cytometry at the end of induction and consolidation was associated with an increased discounted survival of 0.0958 quality-adjusted life-years (QALYs) and increased discounted costs of $4,180, yielding an incremental cost-effectiveness ratio (ICER) of $43,613/QALY gained. After accounting for parameter uncertainty, incremental cost-effectiveness of MRD testing was associated with an ICER of $50,249/QALY gained. In the budget-impact analysis, the 1-year cost expenditure for MRD testing by flow cytometry in newly diagnosed patients with precursor B-cell ALL was estimated at $340,760. We forecasted that the province would have to pay approximately $1.3 million over 3 years and $2.4 million over 5 years for MRD testing by flow cytometry in this population. CONCLUSIONS: Compared with no testing, MRD testing by flow cytometry in newly diagnosed patients with precursor B-cell ALL represents good value for money at commonly used willingness-to-pay thresholds of $50,000/QALY and $100,000/QALY.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1604
[Cu] Class update date: 160423
[Lr] Last revision date:160423
[Js] Journal subset:IM
[St] Status:In-Data-Review

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[PMID]: 27098268
[Au] Autor:Vasko T; Frobel J; Lubberich R; Goecke TW; Wagner W
[Ad] Address:Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical School, Pauwelsstrasse 20, 52074, Aachen, Germany....
[Ti] Title:iPSC-derived mesenchymal stromal cells are less supportive than primary MSCs for co-culture of hematopoietic progenitor cells.
[So] Source:J Hematol Oncol;9(1):43, 2016.
[Is] ISSN:1756-8722
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:In vitro culture of hematopoietic stem and progenitor cells (HPCs) is supported by a suitable cellular microenvironment, such as mesenchymal stromal cells (MSCs)-but MSCs are heterogeneous and poorly defined. In this study, we analyzed whether MSCs derived from induced pluripotent stem cells (iPS-MSCs) provide a suitable cellular feeder layer too. iPS-MSCs clearly supported proliferation of HPCs, maintenance of a primitive immunophenotype (CD34(+), CD133(+), CD38(-)), and colony-forming unit (CFU) potential of CD34(+) HPCs. However, particularly long-term culture-initiating cell (LTC-IC) frequency was lower with iPS-MSCs as compared to primary MSCs. Relevant genes for cell-cell interaction were overall expressed at similar level in MSCs and iPS-MSCs, whereas VCAM1 was less expressed in the latter. In conclusion, our iPS-MSCs support in vitro culture of HPCs; however, under the current differentiation and culture conditions, they are less suitable than primary MSCs from bone marrow.
[Pt] Publication type:LETTER
[Em] Entry month:1604
[Cu] Class update date: 160423
[Lr] Last revision date:160423
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1186/s13045-016-0273-2

  6 / 335305 MEDLINE  
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[PMID]: 27099737
[Au] Autor:Al-Nabulsi M; Basnet A; Salerno V; Cholankeril M
[Ad] Address:Department of internal medicine Trinitas Regional Medical Center, Seton Hall University school of health and medical sciences Elizabeth New Jersey....
[Ti] Title:A case of mantle cell lymphoma presenting with ascites.
[So] Source:Clin Case Rep;4(4):399-403, 2016 Apr.
[Is] ISSN:2050-0904
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Ascites with the finding of peritoneal carcinomatosis is considered an unusual presentation for mantle cell lymphoma (MCL) and has been rarely described in literature. This case reflects the importance of cytological analysis of peritoneal fluid in a patient with intractable ascites not contributing from other comorbidities. In the event a bone marrow (BM) analysis cannot be made, this may serve as an alternative method for diagnosing MCL taking into consideration the good concordance between peritoneal fluid and BM cytological markers.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1604
[Cu] Class update date: 160423
[Lr] Last revision date:160423
[Da] Date of entry for processing:160421
[St] Status:PubMed-not-MEDLINE
[do] DOI:10.1002/ccr3.533

  7 / 335305 MEDLINE  
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[PMID]: 27078879
[Au] Autor:Savers A; Rasid O; Parlato M; Brock M; Jouvion G; Ryffel B; Cavaillon JM; Eberl G; Ibrahim-Granet O
[Ad] Address:Institut Pasteur, Unité Cytokines & Inflammation, Paris, France....
[Ti] Title:Infection-Mediated Priming of Phagocytes Protects against Lethal Secondary Aspergillus fumigatus Challenge.
[So] Source:PLoS One;11(4):e0153829, 2016.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Phagocytes restrict the germination of Aspergillus fumigatus conidia and prevent the establishment of invasive pulmonary aspergillosis in immunecompetent mice. Here we report that immunecompetent mice recovering from a primary A. fumigatus challenge are protected against a secondary lethal challenge. Using RAGγc knock-out mice we show that this protection is independent of T, B and NK cells. In protected mice, lung phagocytes are recruited more rapidly and are more efficient in conidial phagocytosis and killing. Protection was also associated with an enhanced expression of CXCR2 and Dectin-1 on bone marrow phagocytes. We also show that protective lung cytokine and chemokine responses are induced more rapidly and with enhanced dynamics in protected mice. Our findings support the hypothesis that following a first encounter with a non-lethal dose of A. fumigatus conidia, the innate immune system is primed and can mediate protection against a secondary lethal infection.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1604
[Cu] Class update date: 160423
[Lr] Last revision date:160423
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pone.0153829

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[PMID]: 27074138
[Au] Autor:Ferrell PB; Diggins KE; Polikowsky HG; Mohan SR; Seegmiller AC; Irish JM
[Ad] Address:Department of Medicine, Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America....
[Ti] Title:High-Dimensional Analysis of Acute Myeloid Leukemia Reveals Phenotypic Changes in Persistent Cells during Induction Therapy.
[So] Source:PLoS One;11(4):e0153207, 2016.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The plasticity of AML drives poor clinical outcomes and confounds its longitudinal detection. However, the immediate impact of treatment on the leukemic and non-leukemic cells of the bone marrow and blood remains relatively understudied. Here, we conducted a pilot study of high dimensional longitudinal monitoring of immunophenotype in AML. To characterize changes in cell phenotype before, during, and immediately after induction treatment, we developed a 27-antibody panel for mass cytometry focused on surface diagnostic markers and applied it to 46 samples of blood or bone marrow tissue collected over time from 5 AML patients. Central goals were to determine whether changes in AML phenotype would be captured effectively by cytomic tools and to implement methods for describing the evolving phenotypes of AML cell subsets. Mass cytometry data were analyzed using established computational techniques. Within this pilot study, longitudinal immune monitoring with mass cytometry revealed fundamental changes in leukemia phenotypes that occurred over time during and after induction in the refractory disease setting. Persisting AML blasts became more phenotypically distinct from stem and progenitor cells due to expression of novel marker patterns that differed from pre-treatment AML cells and from all cell types observed in healthy bone marrow. This pilot study of single cell immune monitoring in AML represents a powerful tool for precision characterization and targeting of resistant disease.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1604
[Cu] Class update date: 160423
[Lr] Last revision date:160423
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pone.0153207

  9 / 335305 MEDLINE  
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[PMID]: 27073927
[Au] Autor:El-Badawy A; El-Badri N
[Ad] Address:Center of Excellence for Stem Cells and Regenerative Medicine (CESC), Zewail City of Science and Technology, 6th of October City, Egypt.
[Ti] Title:Clinical Efficacy of Stem Cell Therapy for Diabetes Mellitus: A Meta-Analysis.
[So] Source:PLoS One;11(4):e0151938, 2016.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: Stem cell therapy is a promising therapeutic modality for advanced diabetes mellitus (DM). This study presents a meta-analysis of relevant clinical trials to determine the efficacy of stem cell therapy in DM. We aim to critically evaluate and synthesize clinical evidence on the safety and efficiency of different types of stem cell therapy for both T1DM and T2DM. METHODS AND FINDINGS: We pooled participant-level data from twenty-two eligible clinical trials that satisfied our inclusion criteria, with a total of 524 patients. There were significant differences in the outcome based on the type and source of the infused cells. Out of all T1DM patients who received CD34+ hematopoietic stem cell (HSC) infusion, 58.9% became insulin independent for a mean period of 16 months, whereas the results were uniformly negative in patients who received umbilical cord blood (UCB). Infusion of umbilical cord mesenchymal stem cells (UC-MSCs) provided significantly beneficial outcome in T1DM, when compared to bone-marrow mesenchymal stem cells (BM-MSCs) (P<0.0001 and P = 0.1557). Administration of stem cell therapy early after DM diagnosis was more effective than intervention at later stages (relative risk = 2.0, P = 0.0008). Adverse effects were observed in only 21.72% of both T1DM and T2DM stem cell recipients with no reported mortality. Out of all poor responders, 79.5% were diagnosed with diabetic ketoacidosis. CONCLUSIONS: Stem cell transplantation can represent a safe and effective treatment for selected patients with DM. In this cohort of trials, the best therapeutic outcome was achieved with CD34+ HSC therapy for T1DM, while the poorest outcome was observed with HUCB for T1DM. Diabetic ketoacidosis impedes therapeutic efficacy.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1604
[Cu] Class update date: 160423
[Lr] Last revision date:160423
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pone.0151938

  10 / 335305 MEDLINE  
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[PMID]: 27064901
[Au] Autor:Xiu F; Anipindi VC; Nguyen PV; Boudreau J; Liang H; Wan Y; Snider DP; Kaushic C
[Ad] Address:McMaster Immunology Research Center, Department of Pathology and Molecular Medicine, McMaster University, Michael G. DeGroote Center for Learning and Discovery, Hamilton, Ontario, Canada L8N 3Z5....
[Ti] Title:High Physiological Concentrations of Progesterone Reverse Estradiol-Mediated Changes in Differentiation and Functions of Bone Marrow Derived Dendritic Cells.
[So] Source:PLoS One;11(4):e0153304, 2016.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Female sex steroids, estradiol (E2) and progesterone (P4), play a key role in regulating immune responses in women, including dendritic cell (DC) development, and functions. Although the two hormones co-occur in the body of women throughout the reproductive years, no studies have explored their complex combinatorial effects on DCs, given their ability to regulate each other's actions. We examined murine bone marrow derived dendritic cells (BMDC) differentiation and functions, in the presence of a wide range of physiological concentrations of each hormone, as well as the combination of the two hormones. E2 (10-12 to 10-8M) enhanced the differentiation of CD11b+CD11c+ DCs from BM precursor cells, and promoted the expression of CD40 and MHC Class-II, in a dose-dependent manner. In contrast, P4 (10-9 to 10-5M) inhibited DC differentiation, but only at the highest concentrations. These effects on BMDCs were observed both in the presence or absence of LPS. When both hormones were combined, higher concentrations of P4, at levels seen in pregnancy (10-6M) reversed the E2 effects, regardless of the concentration of E2, especially in the absence of LPS. Functionally, antigen uptake was decreased and pro-inflammatory cytokines, IL-12, IL-1 and IL-6 production by CD11b+CD11c+ DCs, was increased in the presence of E2 and these effects were reversed by high concentrations of P4. Our results demonstrate the distinct effects of E2 and P4 on differentiation and functions of bone marrow myeloid DCs. The dominating effect of higher physiological concentrations of P4 provides insight into how DC functions could be modulated during pregnancy.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1604
[Cu] Class update date: 160423
[Lr] Last revision date:160423
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pone.0153304


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