Interferon alpha-inducible protein 27 (IFI27) is a prognostic marker for pancreatic cancer based on comprehensive bioinformatics analysis.

Accurate biomarkers to predict the genesis and progression of pancreatic adenocarcinoma (PAAD) are needed in the fight against this deadly disease. Here, we combined multiple datasets (GEO, TCGA and GTEx) to conduct a comprehensive analysis of pancreatic cancer. Through an in-depth analysis, we discovered that the expression of the gene encoding interferon alpha-inducible protein 27 (IFI27) was significantly higher in pancreatic cancer tissues than that in normal tissues, and that higher expression of IFI27 was negatively correlated with the overall survival rate of pancreatic cancer patients. The functional annotation of IFI27 demonstrated relationships to cellular immunity and metabolism, especially glycolysis. Analysis of infiltrating immune cells displayed that higher expression of IFI27 expression correlates with decreased CD8 + T cells and increased M2 macrophages in the tumor immune microenvironment (TIME), then biochemical analyses of a mouse model and immunohistochemical (IHC) staining verified that glycolytic enzymes and M2 macrophages increased significantly in pancreatic cancer tissues. We speculate that IFI27 may affect the tumor microenvironment (TME) of PAAD by regulating cellular immunity and metabolism, thereby promoting the progression of pancreatic carcinoma and worsening the prognosis. These findings of our present study are solid evidence that IFI27 is a potential prognostic biomarker of pancreatic cancer and that it affects the tumor immune microenvironment.

Expression of Leukocytic Syncytin-1 in B-Cell Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia Patients.

BACKGROUND: Syncytin-1 is improperly expressed in several cancers. However, its expression profile across leukocytes in leukemia patients has not yet been analyzed. METHODS: A total of 50 AML cases and 14 B-cell ALL patients were consecutively recruited. Bone marrow samples were subjected to flow cytometry. Statistical analysis was applied to compare syncytin-1 expression between B-cell ALL and AML across granulocytes, leukemia cells, and T-lymphocytes (including CD3+, CD4+, and CD8+ subsets thereof) and to correlate syncytin-1 expression to leukemia cells and lymphocytes with the T-cell subset percentages. RESULTS: The syncytin-1-expressing leukemia cell% in AML patients was significantly higher than that in B-cell ALL patients (p < 0.05). The CD8+ T-cell% in AML patients was significantly higher than that in B-cell ALL patients (p < 0.05). The syncytin-1 expression rate on leukemia cells was positively correlated with the CD8+ T-cell percentage (r = 0.289, p < 0.05), while the syncytin-1 expression rate on lymphocytes was negatively correlated with the CD3+, CD4+, and CD8+ T-cell percentages (r = -0.273, -0.450, and -0.307, respectively; p < 0.05). CONCLUSIONS: The percentage of syncytin-1-expressing leukemia cells in AML - due to its positive correlation with the CD8+ suppressor T-cell percentage - shows potential as an indicator of poorer long-term immunity in AML patients.

[Detection and analysis of immune molecules in leukemia cell surfaces of acute promyelocytic leukemia].

Objective To investigate the immunophenotypic characteristics of acute promyelocytic leukemia (APL) and its clinical significance. Methods Immunophenotyping was performed by four-color flow cytometry with CD45/SSC-lin gating for neoplastic cells and was divided into five levels according to the intensity of antigen expression. Results The expression intensity and percentage of typical APL phenotypes were: myeloperoxidase (MPO) and CD33 were consistently expressed (100%); CD38 (82.35%), CD13 (64.71%), CD64 (50%), CD123 (47.06%) and CD117 (44.12%) were partially expressed. HLA-DR (97.06%) and CD34 (99.02%) were negative. Post-chemotherapy remission rate in the Lym+APL patients was significantly lower than that in the Lym-APL patients. Conclusion The typical phenotypic characteristics in APL immunophenotyping were high SSC, CD33+ (grade I), CD38+ (grade I), MPO+ (grade I), CD13+ (grade III), CD64+ (grade I/III), CD117+ (grade II/III/IV), CD123+ (grade III/IV), CD11b-, HLA-DR-, CD34-. Understanding of the immunophenotypic features of APL contributes to rapid diagnosis of APL and the guidance of minimal residual disease (MRD) detection.

Upregulation of Leukocytic Syncytin-1 in Acute Myeloid Leukemia Patients.

BACKGROUND Syncytin-1, a cell membrane-localizing fusogen, is abnormally expressed in several cancers, including endometrial cancer, breast cancer, and leukemia. Although abnormal syncytin-1 expression has been detected in two-thirds of leukemia blood samples, its expression profile in acute leukemia patients has not yet been analyzed. MATERIAL AND METHODS Bone marrow samples from 50 acute myelogenous leukemia (AML) cases and 14 B-cell acute lymphocytic leukemia (B-cell ALL) patients were subjected to flow cytometry to assess leukocyte type distributions and leukocytic syncytin-1 surface expression. RT-PCR was applied to assess leukocytic syncytin-1 mRNA expression. Statistical analysis was applied to compare syncytin-1 expression between AML and B-cell ALL patients across blasts, granulocytes, lymphocytes, and monocytes as well as to determine clinical factors statistically associated with changes in syncytin-1 expression. RESULTS The leukocyte type distributions of the AML and B-cell ALL cohorts highly overlapped, with an observable difference in blast distribution between the 2 cohorts. The AML cohort displayed significantly greater syncytin-1 surface and mRNA expression (p<0.05). Syncytin-1 surface and mRNA expression was significantly increased across all 4 leukocyte types (p<0.05). The percentage of syncytin-1-expressing blasts was significantly greater in AML patients (p<0.05), with blasts showing the largest fold-change in syncytin-1 expression (p<0.05). M5, M5a, and M5b AML patients displayed significantly higher syncytin-1 surface expression relative to all other AML French-American-British (FAB) classifications (p<0.05). CONCLUSIONS These findings suggest leukocytic syncytin-1 expression may play a role in the development and/or maintenance of the AML phenotype and the acute monocytic leukemia phenotype in particular.

Genomic Characterization of a Novel HIV-1 Second-Generation Recombinant Form Originated from CRF01_AE and CRF08_BC in Dali Prefecture of Yunnan Province, China.

Yunnan seems to be a "hot spot" region of HIV-1 recombination. CRF01_AE and subtype CRF08_BC are two main HIV-1 clades circulating in Yunnan. We report here a novel HIV-1 second-generation recombinant form originated from CRF01_AE and CRF08_BC. The strain (12YN10551) was isolated from a HIV-positive male infected through heterosexual contact in Dali prefecture of Yunnan province, China. This is the first report of HIV-1 near full-length genomic sequence in Dali. Recombinant analysis shows that 12YN10551 was composed of two well-established circulating recombinant forms (CRF01_AE and CRF08_BC). Two CRF01_AE recombinant fragments were inserted into the CRF08_BC backbone genome in the pol/vif/vpr/tat/rev and nef gene regions, respectively. The discovery and characterization of this new recombinant indicate that intersubtype recombination is continuously generating new forms of HIV-1. More work is needed to better monitor the genetic diversity of HIV-1 in this region.

A unique MUC1-2-VNTR DNA vaccine suppresses tumor growth and prolongs survival in a murine multiple myeloma model.

Multiple myeloma (MM) is a clonal B-cell malignancy charactered by the aberrant proliferation of malignant plasma cells in the bone marrow. MM is still an incurable malignancy. In this regard, novel treatments are urgently required. MUC1 (mucin 1), a type І transmembrane protein, is overexpressed and aberrantly glycosylated in many carcinomas particularly in MM resulting in an antigenically distinct molecule and may be a potential target for specific immunotherapy. In this study, we first designed a unique DNA vaccine, termed MUC1-2-VNTR (various number tandem repeats) to investigate whether the vaccine could specifically suppress tumor growth in a murine multiple myloma model. Our results showed that the constructed DNA vaccine pcDNA3.1-VNTR elicited both humoral and cellular tumor-specific immune responses in the MM mouse model leading to delay in tumor growth and prolonged survival of the mice. Consequently, our study indicates that this DNA vaccine shows promise to be used as a novel strategy for the treatment of MM.

[Protection of cryopreserved platelets by dimethyl sulfoxide combined with trehalose].

This study was aimed to investigate the protective effects of dimethylsulfoxide (DMSO) combined with trehalose on the cryopreserved platelets. The platelets were preserved at -80 degrees C. The experiments were divided into 5 groups: blank control group composed of apheresis platelet suspension; trehalose group composed of apheresis platelet suspension and 0.25 mol/L trehalose; DMSO group composed of apheresis platelet suspension and 5% DMSO; 5% combined group composed of apheresis platelet suspension, 5% DMSO and 0.25 mol/L trehalose; 2.5% combined group composed of apheresis platelet suspension, 2.5% DMSO and 0.25 mol/L trehalose. All the groups were thawed at 37 degrees C in a waterbath. The recovery rate of platelets and mean platelet volume (MPV) were assayed by using hemocytometer; the ultrastructural changes were examined by electron microscopy; the expressions of CD41, CD42b, CD61 and CD62p on platelets were detected by flow cytometry. The results indicated that single use of trehalose had no strong effect in increasing the recovery rate of platelets, but the morphology of platelets was close to normal. The DMSO showed significant effect in increasing the recovery rate of platelets and maintaining the intact property of platelets, however, the shape of platelets tended to sealing, and partial platelets still displayed heteromorphic changes. The combination of DMSO and trehalose revealed the protective effect on the external morphology and internal structure of platelets to be close to the normal homeostasis, and ensured an ideal recovery rate of the cryopreserved platelets and higher expression levels of CD41, CD42b, CD61 and CD62p in the same time. It is concluded that the combined use of DMSO and trehalose possesses the synergistic protective effect on the cryopreserved platelets, therefore, the combined use of both as the protective agent is hopeful to further raise the effectiveness of clinical infusion of the cryopreserved platelets.

TMVA, a snake C-type lectin-like protein from Trimeresurus mucrosquamatus venom, activates platelet via GPIb.

TMVA is a C-type lectin-like protein with potent platelet activating activity from Trimeresurus mucrosquamatus venom. In the absence of von Willebrand factor (vWF), TMVA dose-dependently induced aggregation of washed platelets. Anti-GP Ib monoclonal antibodies (mAbs), HIP1, specifically inhibited TMVA-induced aggregation in a dose-dependent manner. The aggregation was also inhibited by mAb P2 (an anti-GP IIb mAb). Flow cytometric analysis revealed that FITC-TMVA bound to human formalin-fixed platelets in a saturable manner, and its binding was specifically blocked by HIP1 in a dose-dependent manner. Flow cytometric analysis showed that TMVA did not bind to platelet GPIX, GPIIb, GPIIIa, GPIa, GPIIa and GPIV. Moreover, the platelet aggregation induced by TMVA was partially inhibited when platelet was pretreated with mocarhagin, a snake venom protease that specifically cleaves human GPIb. These results suggest that TMVA is a strong platelet agonist via GPIb and it might have multiple functional binding-sites on GPIb molecule or on other unknown receptor.

[Study on the Polymorphism of Intron 22 (CA)n Repeat within FVIII Gene in Dai, Yi and Han Populations of Yunnan Province]

This study was designed to investigate the polymorphism of intron 22 (CA)n repeat within FVIII gene in Dai, Yi and Han populations of Yunnan province. PCR, DNA sequencing technique and PAGE were used in this study. The results showed that three different alleles corresponding to 24, 25 and 26 dinucleotides were found at this locus and the allele frequency ranged from 1.20% to 57.7% in Dai and from 16.43% to 63.00% in Yi populations. In Han population, five different alleles with 24, 25, 26, 27 and 28 (CA)s were found, the allele frequency ranged from 8.97% to 32.00%. Heterozygotes of intron 22 (CA) repeat within FVIII gene were not found in the three populations. In conclusion, it was obvious that the locus cannot be acted as DNA genetic marker of FVIII gene in the three populations in Yunnan.