Objective:To investigate the inducing effects of sunitinib malate on expression of NKG2D ligands in nasopharyngeal carcinoma cell ABCG2high CNE2/DDP.Methods:ABCG2highCNE2/DDP cells and Allo-NK cells were isolated by magnetic activated cell sorting(MACS).Flow cytometry was used to evaluate the purity of isolated cells and the expression of NKG2D-ligands on target cells before and after incubation with sunitinib malate.Then the cytotoxic sensitivity of treated and un-treated ABCG2high CNE2/DDP cells to Allo-NK cells were measured by LDH releasing assay.Results:The positive rate of ABCG2 in ABCG2highCNE2/DDP cells was(91.40?2.32)%.More than 90% of isolated Allo-NK cells were proven to be CD3-CD16+CD56+ cells.The expression of MICA,MICB,ULBP1,ULBP2 and ULBP3 on ABCG2high CNE2/DDP cells incubated with sunitinib malate increased from(2.92?0.33)%,(4.27?0.33)%,(5.80?0.62)%,(11.10?3.15)%,and(7.75?1.14)% to(89.12?4.56)%,(66.10?2.22)%,(67.56?4.19)%,(69.37?8.83)%,and(63.28?3.31)%,respectively.At the E ∶T ratios of 10 ∶1 and 20 ∶1,the cytotoxic sensitivities of ABCG2high CNE2/DDP cells to Allo-NK cells increased from(15.32?13.86)% and(27.26?6.81)% to(41.12?4.12)% and(57.25?2.37)%,respectively,after treatment with sunitinib malate,with significantly difference found in the cytotoxic sensitivities of target cells in each group before and after sunitinib malate treatment(F=15.58,P=0.000).Conclusion:Sunitinib malate can up-regulate expression of NKG2D-ligands(MICA/B,ULBP1-3)in ABCG2high nasopharyngeal carcinoma cells,which results in higher cytotoxic sensitivity to Allo-NK cells.

Objective To investigate the mechanisms and effects of Sorafenib on cytotoxic sensitivity of allo-reactive natural killer(Allo-NK) cells against human multi-drug resistant nasopharyngeal carcinoma CNE2/DDP cells which expressing highly ATP-binding cassette superfamily G member 2(ABCG2)(abbr.as ABCG2HighCNE2/DDP cells).Methods ABCG2HighCNE2/DDP and Allo-NK cells were isolated by magnetic bead technique.The target cells were divided into 3 groups: a) treated group(ABCG2HighCNE2/DDP cells incubated with 10 ng/ml sorafenib for 4h);b) untreated group(conventionally cultured ABCG2HighCNE2/DDP cells);and c) control group(conventionally cultured K562 cells).Expression rates of ABCG2 in treated and untreated groups,and of five NKG2D-ligands(MICA,MICB,ULBP1,ULBP2,ULBP3) were evaluated by flow cytometry.The cytotoxic effects of NK cells against different groups of target cells were detected with LDH releasing assay.Results Expression rate of ABCG2 in isolated CNE2/DDP cells was 91.40%?2.32%.The purity of sorted CD3-CD16+CD56+ Allo-NK cells was 90% and higher.The expression rates of NKG2D-ligands(MICA,MICB,ULBP1,ULBP2 and ULBP3) in untreated group were 2.92%?0.33%,4.27%?0.33%,5.80%?0.62%,11.10%?3.15% and 7.75%?1.14%,respectively,which were remarkablely higher than that in treated group(10.38%?1.23%,10.68%?1.26%,11.62%?1.22%,43.24%?4.42% and 11.91%?0.88%,respectively,P

OBJECTIVETo observe the influence of decreasing conditioning regimen intensity on the engraftment of HLA haplotype peripheral blood stem cell transplantation.

METHODTwelve patients with leukemia, including 4 in complete remission, whose HLAs were full matched with donors, and 8 with refractory leukemia, whose HLAs were mismatched, were transplanted with G-CSF mobilized allogeneic peripheral blood stem cells after conditioned with a regimen consisting of fludarabine (30 mg/m(2) x 6 days), busulfan (4 mg/kg x 2 days) and cyclophosphamide (30 approximately 60 mg/kg x 2 days) (FBC). Donor lymphocytes were infused at day + 30, + 60 and + 90 after transplantation, respectively. Hematopoietic reconstitution was observed. Engraftment was documented by the analysis of short tandem repeats with polymerase chain reaction (STR-PCR).

RESULTPatients in HLA haplotype group received a mean number of 4.87 x 10(8)/kg donor mononuclear cells (MNC), with CD(34)(+) cells of 4.58 x 10(6)/kg and patients in HLA identical group a mean number of 4.85 x 10(8)/kg MNC with CD(34)(+) cells of 4.47 x 10(6)/kg. The mean time of white blood cell count more than 1.0 x 10(9)/L was 14 (10 approximately 18) days in HLA matched patients and 29 (11 approximately 90) days in HLA haplotype group. One three locus mismatched patient failed to engraft, but auto-hematopoiesis was recovered on day + 50. Full donor chimerism was observed in all patients except one with mixed chimera. The mixed chimera was converted into full donor chimera after three times donor lymphocyte infusion. One each died from severe acute GVHD, severe VOD and severe chronic GVHD in HLA haplotype group, and one from chronic GVHD in HLA identical group.

CONCLUSIONPatients survived engraftment was not influenced by decreasing conditioning intensity as in this regimen. Haplotype stem cells could be engrafted durable in recipients by this regimen combined with donor lymphocyte infusion.

Adolescent ; Adult ; Busulfan ; therapeutic use ; Cyclophosphamide ; therapeutic use ; Female ; Graft Survival ; drug effects ; Graft vs Host Disease ; prevention & control ; Hematopoietic Stem Cell Transplantation ; Histocompatibility Testing ; Humans ; Immunosuppressive Agents ; therapeutic use ; Leukemia ; therapy ; Male ; Middle Aged ; Transplantation Conditioning ; Transplantation Tolerance ; drug effects ; Vidarabine ; analogs & derivatives ; therapeutic use

Heart failure is a clinical syndrome caused by various causes of myocardial damage and cardi-ac function decrease that cannot meet the body's metabolic needs.The proinflammatory cytokines play an im-portant role in the process of occurrence and development of heart failure.The Notch1/Jagged1 signaling path-way is related to the proinflammatory cytokines,inflammatory responses and immune responses.This paper discusses the involvement of the Notch1/Jagged1 signaling pathway in the development and development of chronic heart failure by modulating immune inflammation.

Objective: To analyze the prognostic factors on multidisciplinary team patients for diagnosis, and treatment of hepatocellular carcinoma. Methods: This retrospective study enrolled 132 HBsAg positive patients with HCC. MDT diagnostic approach was conducted at our hospital between 1 January 2015 and 31 December 2015, and all patients were followed up to 31 December 2017. Groups were arranged according to variables such as Barcelona stage, MDT compliance, and multidisciplinary combination therapy. TTP and OS were statistically analyzed. Results: The survival of the MDT compliance group was better than the non-compliance group. The difference in survival curves was statistically significant (χ² = 4.062, P < 0.05). The 1- and 2-year survival rates of the former group were 72.0%, 60.9%, and the latter was 64.3%, 40.3%. The survival of the combined treatment group was better than the non-combination group. The survival curves of the two groups were statistically significant (χ² = 9.502, P < 0.05), and they were independent influencing factors of survival (HR = 0.451, 95% CI, 0.210-0.968). The 1- and 2-year survival rates of the former group were 82.2% and 75.4%, and the latter was 63.1% and 44.6%. The median survival time of the follow-up group was 29.4 months, and the non-compliance and the uncombined group were 17.0 months. The difference was statistically significant (χ² = 13.336, P < 0.001). The median tumor progression time was 15.7 months in the combination group and 10.1 months in the non-compliance group (χ² = 7.263, P < 0.05). Conclusion An advanced MDT compliance with implementation of multidisciplinary combination therapy may help to improve the prognosis of MDT patients with liver cancer.