Database : MEDLINE
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[PMID]: 25066812
[Au] Autor:Kanaji S; Fahs SA; Ware J; Montgomery RR; Shi Q
[Ad] Address:Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI, USA; The Scripps Research Institute, La Jolla, CA, USA.
[Ti] Title:Non-myeloablative conditioning with busulfan before hematopoietic stem cell transplantation leads to phenotypic correction of murine Bernard-Soulier syndrome.
[So] Source:J Thromb Haemost;12(10):1726-32, 2014 Oct.
[Is] ISSN:1538-7836
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: Bernard-Soulier syndrome (BSS) is an inherited bleeding disorder characterized by macrothrombocytopenia. Platelet transfusion is used for the management of bleeding, but repeated transfusion often results in alloimmunization. We have recently shown phenotypic correction of murine BSS (GPIbα(null) ) using lethal radiation conditioning followed by hematopoietic lentivirus-mediated gene transfer. OBJECTIVES: For application of gene therapy to treatment of human patients, it is important to minimize treatment-related side effects. The objective of this study is to model a clinically relevant non-myeloablative hematopoietic stem cell (HSC) transplantation strategy. METHODS: Using transplantation of bone marrow (BM) HSCs from transgenic mice that express hGPIbα (hGPIbα(tg+/+) ), we sought to (i) determine the percentage of hGPIbα(tg+/+) HSCs required for therapeutic benefit, (ii) evaluate the efficacy of non-myeloablative conditioning using busulfan, and (iii) test the ability of anti-thymocyte globulin (ATG) to prevent/reduce undesirable immune responses. RESULTS: Transplantation of 10-20% hGPIbα(tg+/+) BM HSCs mixed with GPIbα(null) BM HSCs into irradiated GPIbα(null) mice was sufficient to correct bleeding time (n=5). Transplantation of hGPIbα(tg+/+) BM HSCs into busulfan-conditioned GPIbα(null) mice corrected bleeding time in 21 of 27 recipients. Antibody response to hGPIbα and immune-mediated thrombocytopenia was documented in eight of 27 recipients, suggesting immunogenicity of hGPIbα in busulfan-conditioned GPIbα(null) mice. However, these antibodies disappeared without treatment within 30weeks after transplantation. A combination of busulfan plus ATG conditioning successfully prevented antibody development and significantly increased therapeutic engraftment. CONCLUSION: A conditioning regimen of busulfan in combination with ATG could potentially be used in non-myeloablative autologous gene therapy in human BSS.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1111/jth.12673

  2 / 312217 MEDLINE  
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[PMID]: 25263552
[Au] Autor:Roccaro AM; Sacco A; Purschke WG; Moschetta M; Buchner K; Maasch C; Zboralski D; Zllner S; Vonhoff S; Mishima Y; Maiso P; Reagan MR; Lonardi S; Ungari M; Facchetti F; Eulberg D; Kruschinski A; Vater A; Rossi G; Klussmann S; Ghobrial IM
[Ad] Address:Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA....
[Ti] Title:SDF-1 Inhibition Targets the Bone Marrow Niche for Cancer Therapy.
[So] Source:Cell Rep;9(1):118-28, 2014 Oct 9.
[Is] ISSN:2211-1247
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Bone marrow (BM) metastasis remains one of the main causes of death associated with solid tumors as well as multiple myeloma (MM). Targeting the BM niche to prevent or modulate metastasis has not been successful to date. Here, we show that stromal cell-derived factor-1 (SDF-1/CXCL12) is highly expressed in active MM, as well as in BM sites of tumor metastasis and report on the discovery of the high-affinity anti-SDF-1 PEGylated mirror-image l-oligonucleotide (olaptesed-pegol). Invivo confocal imaging showed that SDF-1 levels are increased within MM cell-colonized BM areas. Using invivo murine and xenograft mouse models, we document that invivo SDF-1 neutralization within BM niches leads to a microenvironment that is less receptive for MM cells and reduces MM cell homing and growth, thereby inhibiting MM disease progression. Targeting of SDF-1 represents a valid strategy for preventing or disrupting colonization of the BM by MM cells.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Js] Journal subset:IM
[St] Status:In-Data-Review

  3 / 312217 MEDLINE  
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[PMID]: 25064747
[Au] Autor:Ballen KK; Joffe S; Brazauskas R; Wang Z; Aljurf MD; Akpek G; Dandoy C; Frangoul HA; Freytes CO; Khera N; Lazarus HM; LeMaistre CF; Mehta P; Parsons SK; Szwajcer D; Ustun C; Wood WA; Majhail NS
[Ad] Address:Department of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts....
[Ti] Title:Hospital Length of Stay in the First 100Days after Allogeneic Hematopoietic Cell Transplantation for Acute Leukemia in Remission: Comparison among Alternative Graft Sources.
[So] Source:Biol Blood Marrow Transplant;20(11):1819-27, 2014 Nov.
[Is] ISSN:1523-6536
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Several studies have shown comparable survival outcomes with different graft sources, but the relative resource needs of hematopoietic cell transplantation (HCT) by graft source have not been well studied. We compared total hospital length of stay in the first 100days after HCT in 1577 patients with acute leukemia in remission who underwent HCT with an umbilical cord blood (UCB), matched unrelated donor (MUD), or mismatched unrelated donor (MMUD) graft between 2008 and 2011. To ensure a relatively homogenous study population, the analysis was limited to patients with acute myelogenous leukemia and acute lymphoblastic leukemia in first or second complete remission who underwent HCT in the United States. To account for early deaths, we compared the number of days alive and out of the hospital in the first 100days post-transplantation. For children who received myeloablative conditioning, the median time alive and out of the hospital in the first 100days was 50days for single UCB recipients, 54days for double UCB recipients, and 60days for MUD bone marrow (BM) recipients. In multivariate analysis, use of UCB was significantly associated with fewer days alive and out of the hospital compared with MUD BM. For adults who received myeloablative conditioning, the median time alive and out of the hospital in first 100days was 52days for single UCB recipients, 55days for double UCB recipients, 69days for MUD BM recipients, 75days for MUD peripheral blood stem cell (PBSC) recipients, 63days for MMUD BM recipients, and 67days for MMUD PBSC recipients. In multivariate analysis, UCB and MMUD BM recipients had fewer days alive and out of the hospital compared with recipients of other graft sources. For adults who received a reduced-intensity preparative regimen, the median time alive and out of the hospital during the first 100days was 65days for single UCB recipients, 63days for double UCB recipients, 79days for MUD PBSC recipients, and 79days for MMUD PBSC recipients. Similar to the other 2 groups, receipt of UCB was associated with a fewer days alive and out of the hospital. In conclusion, length of stay in the first 100days post-transplantation varies by graft source and is longer for UCB HCT recipients. These data provide insight into the resource needs of patients who undergo HCT with these various graft sources.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Js] Journal subset:IM
[St] Status:In-Data-Review

  4 / 312217 MEDLINE  
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[PMID]: 25042734
[Au] Autor:Ringdn O; Brazauskas R; Wang Z; Ahmed I; Atsuta Y; Buchbinder D; Burns LJ; Cahn JY; Duncan C; Hale GA; Halter J; Hayashi RJ; Hsu JW; Jacobsohn DA; Kamble RT; Kamani NR; Kasow KA; Khera N; Lazarus HM; Loren AW; Marks DI; Myers KC; Ramanathan M; Saber W; Savani BN; Schouten HC; Socie G; Sorror ML; Steinberg A; Popat U; Wingard JR; Mattsson J; Majhail NS
[Ad] Address:Center for Allogeneic Stem Cell Transplantation, Karolinka University Hospital, Stockholm, Sweden....
[Ti] Title:Second solid cancers after allogeneic hematopoietic cell transplantation using reduced-intensity conditioning.
[So] Source:Biol Blood Marrow Transplant;20(11):1777-84, 2014 Nov.
[Is] ISSN:1523-6536
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:We examined risk of second solid cancers after allogeneic hematopoietic cell transplantation (AHCT) using reduced-intensity/nonmyeloablative conditioning (RIC/NMC). RIC/NMC recipients with leukemia/myelodysplastic syndrome (MDS) (n=2833) and lymphoma (n=1436) between 1995 and 2006 were included. In addition, RIC/NMC recipients 40 to 60years of age (n=2138) were compared with patients of the same age receiving myeloablative conditioning (MAC, n=6428). The cumulative incidence of solid cancers was 3.35% at 10years. There was no increase in overall cancer risk compared with the general population (leukemia/MDS: standardized incidence ratio [SIR] .99, P=1.00; lymphoma: SIR .92, P=.75). However, risks were significantly increased in leukemia/MDS patients for cancers of lip (SIR 14.28), tonsil (SIR 8.66), oropharynx (SIR 46.70), bone (SIR 23.53), soft tissue (SIR 12.92), and vulva (SIR 18.55) and skin melanoma (SIR 3.04). Lymphoma patients had significantly higher risks of oropharyngeal cancer (SIR 67.35) and skin melanoma (SIR 3.52). Among RIC/NMC recipients, age >50years was the only independent risk factor for solid cancers (hazard ratio [HR] 3.02, P<.001). Among patients ages 40 to 60years, when adjusted for other factors, there was no difference in cancer risks between RIC/NMC and MAC in leukemia/MDS patients (HR .98, P=.905). In lymphoma patients, risks were lower after RIC/NMC (HR .51, P=.047). In conclusion, the overall risks of second solid cancers in RIC/NMC recipients are similar to the general population, although there is an increased risk of cancer at some sites. Studies with longer follow-up are needed to realize the complete risks of solid cancers after RIC/NMC AHCT.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Js] Journal subset:IM
[St] Status:In-Data-Review

  5 / 312217 MEDLINE  
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[PMID]: 25298091
[Au] Autor:Lee DK; Yi T; Park KE; Lee HJ; Cho YK; Lee SJ; Lee J; Park JH; Lee MY; Song SU; Kwon SW
[Ad] Address:1] College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea [2]....
[Ti] Title:Non-invasive characterization of the adipogenic differentiation of human bone marrow-derived mesenchymal stromal cells by HS-SPME/GC-MS.
[So] Source:Sci Rep;4:6550, 2014.
[Is] ISSN:2045-2322
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:A non-invasive method to characterize human mesenchymal stromal cells during adipogenic differentiation was developed for the first time. Seven fatty acid methyl esters (FAMEs), including methyl laurate, methyl myristate, methyl palmitate, methyl linoleate, methyl oleate, methyl elaidate and methyl stearate, were used for characterizing adipogenic differentiation using headspace solid-phase microextraction (HS-SPME) which is a very simple and non-invasive method for the extraction of volatile compounds. Glassware was used for culturing mesenchymal stromal cells rather than the common plasticware to minimize contamination by volatile impurities. The optimal SPME fiber was selected by comparing diverse fibers containing two pure liquid polymers (PDMS and PA) and two porous solids (PDMS/DVB and CAR/PDMS). Using optimized procedures, we discovered that seven FAMEs were only detected in adipogenic differentiated mesenchymal stromal cells and not in the mesenchymal stromal cells before differentiation. These data could support the quality control of clinical mesenchymal stromal cell culture in the pharmaceutical industry in addition to the development of many clinical applications using mesenchymal stromal cells.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1038/srep06550

  6 / 312217 MEDLINE  
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[PMID]: 25295996
[Au] Autor:Skrnjug I; Guzmn CA; Ruecker C
[Ad] Address:Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
[Ti] Title:Cyclic GMP-AMP Displays Mucosal Adjuvant Activity in Mice.
[So] Source:PLoS One;9(10):e110150, 2014.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The recently discovered mammalian enzyme cyclic GMP-AMP synthase produces cyclic GMP-AMP (cGAMP) after being activated by pathogen-derived cytosolic double stranded DNA. The product can stimulate STING-dependent interferon type I signaling. Here, we explore the efficacy of cGAMP as a mucosal adjuvant in mice. We show that cGAMP can enhance the adaptive immune response to the model antigen ovalbumin. It promotes antigen specific IgG and a balanced Th1/Th2 lymphocyte response in immunized mice. A characteristic of the cGAMP-induced immune response is the slightly reduced induction of interleukin-17 as a hallmark of Th17 activity - a distinct feature that is not observed with other cyclic di-nucleotide adjuvants. We further characterize the innate immune stimulation activity in vitro on murine bone marrow-derived dendritic cells and human dendritic cells. The observed results suggest the consideration of cGAMP as a candidate mucosal adjuvant for human vaccines.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pone.0110150

  7 / 312217 MEDLINE  
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[PMID]: 25185127
[Au] Autor:Mark L; Henke N; Park JK; Spallek B; Qadri F; Balogh A; Apel IJ; Oravecz-Wilson KI; Choi M; Przybyl L; Binger KJ; Haase N; Wilck N; Heuser A; Fokuhl V; Ruland J; Lucas PC; McAllister-Lucas LM; Luft FC; Dechend R; Mller DN
[Ad] Address:From the Experimental and Clinical Research Center, a joint cooperation between the Charit Medical Faculty and the Max-Delbrck Center for Molecular Medicine, Berlin, Germany (L.M., B.S., F.Q., A.B., M.C., L.P., K.J.B., N.H., N.W., V.F., F.C.L., R.D., D.N.M.); Department of Internal Medicine/Cardio...
[Ti] Title:Bcl10 Mediates Angiotensin II-Induced Cardiac Damage and Electrical Remodeling.
[So] Source:Hypertension;64(5):1032-9, 2014 Nov.
[Is] ISSN:1524-4563
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Angiotensin (Ang) II is a potent mediator of both hypertension and cardiac damage; however, the mechanisms by which this occur remain unclear. B-cell lymphoma/leukemia 10 (Bcl10) is a member of the CBM signalosome, which links Ang II and nuclear factor-κB signaling. We hypothesized that Bcl10 is pivotal in the pathogenesis of Ang II-induced cardiac damage. Ang II infusion in mice lacking Bcl10 resulted in reduced cardiac fibrosis, less cellular infiltration, and improved arrhythmogenic electric remodeling, despite a similar degree of hypertension or cardiac hypertrophy. Adoptive transfer of bone marrow (BM), whereby Bcl10 knockout or wildtype BM was transferred to their opposite genotype recipients, revealed the dual importance of Bcl10 within both cardiac and immune cells. Loss of Bcl10 in cardiac cells resulted in reduced expression of genes important for the adhesion and recruitment of immune cells. In vitro experiments demonstrated that adhesion of monocytes to Ang II-treated endothelial cells also required Bcl10. Additionally, Bcl10 deficiency in macrophages reduced their intrinsic migratory ability. To address the role of BM-derived fibroblasts in the formation of cardiac fibrosis, we explored whether Bcl10 is also important for the infiltration of BM-derived (myo)fibroblasts into the heart. The transfer of green fluorescent protein positive wildtype BM into Bcl10 knockout recipient mice revealed a reduced number of noncardiac (myo)fibroblasts compared with those wildtype recipients. Our results demonstrate the significant role of Bcl10 in multiple cell types important for the generation of Ang II-induced cardiac damage and electric remodeling and may provide a new avenue for therapeutic intervention.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1161/HYPERTENSIONAHA.114.03900

  8 / 312217 MEDLINE  
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[PMID]: 25298750
[Au] Autor:Yang X; Li Z; Ma Y; Gao J; Liu S; Gao Y; Wang G
[Ad] Address:Blood Transfusion Department, The Bethune International Peace Hospital, Shijiazhuang, 050082 Hebei P R. China....
[Ti] Title:Human umbilical cord mesenchymal stem cells promote carcinoma growth and lymph node metastasis when co-injected with esophageal carcinoma cells in nude mice.
[So] Source:Cancer Cell Int;14(1):93, 2014.
[Is] ISSN:1475-2867
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: Human umbilical cord blood derived-mesenchymal stem cells (hUCMSCs) offer an attractive alternative to bone marrow-derived MSCs (BMMSCs) for cell-based therapy as it is a less invasive source of biological material. However, limited studies have been conducted with hUCMSCs as compared to BMMSCs. The present study was conducted to evaluate the effects of hUCMSCs in esophageal carcinoma (EC). METHODS: hUCMSCs together with EC cells were transplanted subcutaneously into BALB/c nude mice to observe the effects of hUCMSCs on tumor establishment. hUCMSCs injected through the caudal vein to the mice with pre-established EC to observe the effects of hUCMSCs on tumor outgrowth. In order to elucidate the underlying mechanisms, we also performed in vitro experiments including directly co-culture, transwell assay, proliferation assay and western blotting analysis. RESULTS: hUCMSCs promoted EC formation in nude mice. In the in vivo model of pre-established EC, intravenously injected hUCMSCs potently promoted tumor growth. When in vitro co-cultured with hUCMSCs, EC cells proliferation increased. After co-cultured with hUCMSCs through transwell system, EC cells showed increased proliferation. Through transwell assay, we also observed that EC cells recruited MSCs, and MSCs promoted EC cells migration and invasion. Western blotting data showed that the expressions of proliferation related proteins Bcl-2, survivin and metastasis related proteins MMP-2 and MMP-9 were up-regulated in the EC cells transwell co-cultured with hUCMSCs. CONCLUSIONS: Our results indicated that hUCMSCs could favor tumor growth in vivo and in vitro. Thus, the exploitation of hUCMSCs in new therapeutic strategies should be cautious under the malignant conditions.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Cu] Class update date: 141011
[Lr] Last revision date:141011
[Da] Date of entry for processing:141009
[St] Status:PubMed-not-MEDLINE
[do] DOI:10.1186/s12935-014-0093-9

  9 / 312217 MEDLINE  
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[PMID]: 25290916
[Au] Autor:Mead B; Logan A; Berry M; Leadbeater W; Scheven BA
[Ad] Address:Neurotrauma Research Group, Neurobiology Section, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, United Kingdom; School of Dentistry, University of Birmingham, Birmingham, United Kingdom....
[Ti] Title:Paracrine-mediated neuroprotection and neuritogenesis of axotomised retinal ganglion cells by human dental pulp stem cells: comparison with human bone marrow and adipose-derived mesenchymal stem cells.
[So] Source:PLoS One;9(10):e109305, 2014.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:We have investigated and compared the neurotrophic activity of human dental pulp stem cells (hDPSC), human bone marrow-derived mesenchymal stem cells (hBMSC) and human adipose-derived stem cells (hAMSC) on axotomised adult rat retinal ganglion cells (RGC) in vitro in order to evaluate their therapeutic potential for neurodegenerative conditions of RGC. Using the transwell system, RGC survival and length/number of neurites were quantified in coculture with stem cells in the presence or absence of specific Fc-receptor inhibitors to determine the role of NGF, BDNF, NT-3, VEGF, GDNF, PDGF-AA and PDGF-AB/BB in stem cell-mediated RGC neuroprotection and neuritogenesis. Conditioned media, collected from cultured hDPSC/hBMSC/hAMSC, were assayed for the secreted growth factors detailed above using ELISA. PCR array determined the hDPSC, hBMSC and hAMSC expression of genes encoding 84 growth factors and receptors. The results demonstrated that hDPSC promoted significantly more neuroprotection and neuritogenesis of axotomised RGC than either hBMSC or hAMSC, an effect that was neutralized after the addition of specific Fc-receptor inhibitors. hDPSC secreted greater levels of various growth factors including NGF, BDNF and VEGF compared with hBMSC/hAMSC. The PCR array confirmed these findings and identified VGF as a novel potentially therapeutic hDPSC-derived neurotrophic factor (NTF) with significant RGC neuroprotective properties after coculture with axotomised RGC. In conclusion, hDPSC promoted significant multi-factorial paracrine-mediated RGC survival and neurite outgrowth and may be considered a potent and advantageous cell therapy for retinal nerve repair.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pone.0109305

  10 / 312217 MEDLINE  
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[PMID]: 25290447
[Au] Autor:Ha CT; Li XH; Fu D; Moroni M; Fisher C; Arnott R; Srinivasan V; Xiao M
[Ad] Address:Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America....
[Ti] Title:Circulating Interleukin-18 as a Biomarker of Total-Body Radiation Exposure in Mice, Minipigs, and Nonhuman Primates (NHP).
[So] Source:PLoS One;9(10):e109249, 2014.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:We aim to develop a rapid, easy-to-use, inexpensive and accurate radiation dose-assessment assay that tests easily obtained samples (e.g., blood) to triage and track radiological casualties, and to evaluate the radioprotective and therapeutic effects of radiation countermeasures. In the present study, we evaluated the interleukin (IL)-1 family of cytokines, IL-1, IL-18 and IL-33, as well as their secondary cytokines' expression and secretion in CD2F1 mouse bone marrow (BM), spleen, thymus and serum in response to γ-radiation from sublethal to lethal doses (5, 7, 8, 9, 10, or 12 Gy) at different time points using the enzyme-linked immune sorbent assay (ELISA), immunoblotting, and cytokine antibody array. Our data identified increases of IL-1, IL-18, and/or IL-33 in mouse thymus, spleen and BM cells after total-body irradiation (TBI). However, levels of these cytokines varied in different tissues. Interestingly, IL-18 but not IL-1 or IL-33 increased significantly (2.5-24 fold) and stably in mouse serum from day 1 after TBI up to 13 days in a radiation dose-dependent manner. We further confirmed our finding in total-body γ-irradiated nonhuman primates (NHPs) and minipigs, and demonstrated that radiation significantly enhanced IL-18 in serum from NHPs 2-4 days post-irradiation and in minipig plasma 1-3 days post-irradiation. Finally, we compared circulating IL-18 with the well known hematological radiation biomarkers lymphocyte and neutrophil counts in blood of mouse, minipigs and NHPs and demonstrated close correlations between these biomarkers in response to radiation. Our results suggest that the elevated levels of circulating IL-18 after radiation proportionally reflect radiation dose and severity of radiation injury and may be used both as a potential biomarker for triage and also to track casualties after radiological accidents as well as for therapeutic radiation exposure.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pone.0109249


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