Transcriptome Based System Biology Exploration Reveals Homogeneous Tumorigenicity of Alimentary Tract Malignancy.

Malignancies of alimentary tract include esophageal carcinoma (ESCA), stomach adenocarcinoma (STAD), colon adenocarcinoma (COAD), and rectum adenocarcinoma (READ). Despite of their similarities in cancer development and progression, there are numerous researches concentrating on single tumor but relatively little on their common mechanisms. Our study explored the transcriptomic data of digestive tract cancers from The Cancer Genome Atlas database, yielding their common differentially expressed genes including 1,700 mRNAs, 29 miRNAs, and 362 long non-coding RNAs (lncRNAs). There were 12 mRNAs, 5 miRNAs, and 16 lncRNAs in the core competitive endogenous RNAs network by RNA-RNA interactions, highlighting the prognostic nodes of SERPINE1, hsa-mir-145, and SNHG1. In addition, the weighted gene co-expression network analysis (WGCNA) illustrated 20 gene modules associated with clinical traits. By taking intersections of modules related to the same trait, we got 67 common genes shared by ESCA and READ and screened 5 hub genes, including ADCY6, CXCL3, NPBWR1, TAS2R38, and PTGDR2. In conclusion, the present study found that SERPINE1/has-mir-145/SNHG1 axis acted as promising targets and the hub genes reasoned the similarity between ESCA and READ, which revealed the homogeneous tumorigenicity of digestive tract cancers at the transcriptome level and led to further comprehension and therapeutics for digestive tract cancers.

Effectiveness of advanced nursing care on depression in patients with ovarian cancer: A protocol of systematic review of randomized controlled trial.

BACKGROUND: This systematic review will assess the effectiveness of advanced nursing care (ANC) on depression in patients with ovarian cancer (OC). METHODS: We will identify any relevant randomized controlled trial from Cochrane Library, MEDLINE, Embase, Web of Science, Springer, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure from their inceptions to March 5, 2019. The primary outcome includes depression. The secondary outcomes consist of anxiety, quality of life, and adverse events. Data that meets all the eligibility criteria will be extracted, pooled, and analyzed by using RevMan 5.3 software. Methodological quality for each eligible study will be assessed by using Cochrane risk of bias tool. RESULTS: This study will analyze depression, anxiety, quality of life, and adverse events of ANC on depression in patients with OC. CONCLUSION: The findings of this study will provide the latest evidence for the effectiveness and adverse events of ANC on depression in patients with OC. ETHICS AND DISSEMINATION: No ethic approval is required for this study, because all the data will be extracted from previous published studies. The results of this study will be presented at conference or will be published at a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42019126374.

[Erythropoietin inhibits angiotensin II induced cardiomyocyte hypertrophy in vitro via activating PI3K/Akt-eNOS pathway].

OBJECTIVE: To explore the effect of erythropoietin (EPO) on angiotensin II (AngII) induced neonatal rat cardiomyocyte hypertrophy and the association with PI3K/Akt-eNOS signaling pathway. METHODS: Cardiomyocytes were isolated from new-born Sprague-Dawley rats and stimulated by AngII in vitro. The cell surface area and mRNA expression of atrial natriuretic factor (ANF) of cardiomyocytes were determined in the presence and absence of various concentrations of EPO, phosphatidylinositol 3'-kinase (PI3K) inhibitor LY294002 and nitric oxide synthase (NOS) inhibitor L-NAME. Intracellular signal molecules, such as Akt, phosphorylated Akt, eNOS and phosphorylated eNOS protein expressions were detected by western blot. Nitric oxide (NO) level in the supernatant of cultured cardiomyocytes was assayed by NO assay kit. RESULTS: EPO (20 U/ml) significantly inhibited AngII induced cardiomyocyte hypertrophy as shown by decreased cell surface area and ANF mRNA expression (all P < 0.05). EPO also activated Akt and enhanced the expression of eNOS and its phosphorylation (all P < 0.05), increased the NO production (P < 0.01). These effects could be partially abolished by cotreatment with LY294002 or L-NAME (all P < 0.05). CONCLUSION: EPO attenuates AngII induced cardiomyocytes hypertrophy via activating PI3K-Akt-eNOS pathway and promoting NO production.

Erythropoietin attenuates hypertrophy of neonatal rat cardiac myocytes induced by angiotensin-II in vitro.

OBJECTIVE: Erythropoietin (EPO) is a haematopoietic hormone that has been confirmed as a novel cardioprotective agent. In this study, we test the hypothesis that EPO inhibits angiotensin-II (Ang-II)-induced hypertrophy in cultured neonatal rat cardiomyocytes. MATERIAL AND METHODS: Cultured neonatal rat cardiomyocytes were used to evaluate the effects of EPO on Ang-II-induced hypertrophy in vitro. The surface area and mRNA expression of atrial natriuretic (ANF) myocytes were employed to detect cardiac hypertrophy. A phosphatidylinositol 3'-kinase (PI3K) inhibitor LY294002 and an endothelial nitric oxide synthase (eNOS) inhibitor L-NAME were also employed to detect the underlying mechanism of EPO. Intracellular signal molecules, such as Akt (PKB), phosphorylated Akt, eNOS and transforming growth factor-beta1 (TGF-beta1) protein expression were determined by Western blot. Nitric oxide (NO) levels in the supernatant of cultured cardiomyocytes were assayed using an NO assay kit. RESULTS: The results indicate that EPO significantly attenuates Ang-II-induced hypertrophy shown as inhibition of increases in cell surface area and ANF mRNA levels. NO production was also increased proportionally in the EPO-treated group. EPO enhanced Akt activation and eNOS protein expression, whereas LY294002 or L-NAME partially abolished the anti-hypertrophic effect of EPO, accompanied by a decrease in Akt activation, eNOS protein expression and/or a reduction of NO production. EPO also down-regulated the protein expression of TGF-beta1. CONCLUSION: We conclude that EPO attenuates cardiac hypertrophy via activation of the PI3K-Akt-eNOS-NO pathway and the down-regulation of TGF-beta1.

[Infection status and clinical significance of Epstein-Barr virus in pediatric leukemia---a report of 35 cases].

BACKGROUND & OBJECTIVE: Epstein-Barr virus (EBV) is associated with genesis of many human tumors. This study was to detect EBV infection in pediatric leukemia, and to explore its clinical significance. METHODS: EBV DNA in peripheral blood mononuclear cells in 35 pediatric leukemia patients, including 26 cases of acute lymphoblastic leukemia (ALL) (24 received initial treatment and 2 received retreatment), 8 cases of acute non-lymphocytic leukemia (ANLL) and 1 case of chronic lymphocytic leukemia (CLL), and in 14 healthy children was detected by fluorescent quantitative polymerase chain reaction (FQ-PCR). Its clinical significance was analyzed according to the clinical manifestations, prednisone sensitivity test, and complete remission (CR) rate after induction chemotherapy. RESULTS: EBV DNA was detected in 8 (22.86%) of the 35 pediatric leukemia patients. The positive rate of EBV DNA was 26.92% (7/26) in ALL with quantity of (5.144+/-6.91)x10(5) copies/ml, and 12.5% (1/8) in ANLL patients with quantity of 4.031x10(3) copies/ml. No EBV DNA was detected in CLL patients and healthy controls. The occurrence rates of peripheral leukocytosis and hepatosplenomegaly were significantly higher in the patients with EBV infection than in the patients without EBV infection (P <0.001). In ALL, the rate of no response to prednisone was significantly higher in the patients with EBV infection than in the patients without EBV infection (100% vs. 26.32%, P =0.001); CR rate after induction chemotherapy was significantly lower in the patients with EBV infection than in the patients without EBV infection (28.57% vs. 84.21%, P=0.003). In ANLL, the differences of CR rate and relapse rate were not significant between the patients with and without EBV infection (P=0.5). CONCLUSIONS: Pediatric leukemia patients with EBV infection have higher incidence of peripheral leukocytosis and hepatosplenomegaly. ALL patients with EBV infection have poor prednisone response and low CR rate.

[Expression of the human papillomavirus type 16L/E7 fusion protein in E. coli and observation of its immunogenicity in mice].

BACKGROUND: Many epidemiological and experimental evidences prove that cervical cancers are strongly associated with genital high-risk types of human papillomavirus (HPV). HPV16 is present in 50% of the tumor specimens. Thus, it is important to develop vaccines against HPV16 and cervical cancer. The authors studied the expression of the HPV16 L1DeltaCE7N fusion protein in E. coli and observed its immunogenicity. METHODS: The fragment of HPV16 L1DeltaC gene and the E7N gene were amplified by PCR separately; the fusion gene named L1DeltaCE7N was generated by fusing E7N to the C terminal of L1DeltaC then the chimeric gene was cloned into prokaryotic expression vector pGEX-2T and expressed in E. coli strain JM109. The L1DeltaCE7N protein expressed were detected by Western blot. Finally its immunogenicity was characterized in immunized mice. RESULTS: It was proved that the sequence and open reading frame of fusion gene L1DeltaE7N was correct by sequencing; SDA-PAGE gel analysis showed that HPV16 L1/E7 fusion protein was highly expressed in E. coli; the protein was expressed as soluble form and the molecular weight was about 85 x 10(3). The fusion protein could be purified by affinity chromatography and gel filtration. The ELISA result indicated that L1/E7 could elicit specific antibodies against L1 and E7 in immunized mice. In vivo tumor protection test indicated that tumor formation was retarded or prevented in the mice after vaccination with L1/E7, when C57 BL/6 mice were challenged by syngeneic HVP16E6 and E7 transformed tumor cells. CONCLUSION: HPV16L1/E7 fusion protein was expressed in E. coli, it can be a candidate for prophylactic and therapeutic vaccine for HPV16-associated infection and tumors.

[Analysis of the factors which influence allograft calcification after aorta transplantation of allogenetic rat].

AIM: To explore the factors which influence the calcification of homograft after aorta transplantation of allogenetic rat. METHODS: The research was devided into 2 groups: allogene group and isogenenic group. Allogene group: SD -->Wistar. Isogenenic group: Wistar to Wistar. Aortic valve homograft was heterotopically allografted onto abdominal aorta. The rats were sacrificed in batches at 2, 4, 8, 12 and 16 weeks postoperatively. Blood samples were obtained for accessing the expression of CD25, CD71, and AVH was obtained for accessing the calcium level and the expression of CD40. At the same time, the change of endotheliocyte and smooth muscle cells were observed with transmission electron microscope. RESULTS: (1)Compared with the isogene group, the expression of CD40, CD25 and CD71 in allogene group was much higher at each time point and reached peak at 2-4 weeks after operation. (2)The calcium level in allogene group increased at 4 weeks after operation and reached the peak at 12 weeks after operation. No significant difference in calcium level was found in isogenenic group over 5 different periods. (3)Exfoliation of endotheliacytes as well as necrosis of smooth muscle cells were observed in the graft in allogene group. CONCLUSION: The calcium level of homograft had a relation with immunological rejection. The calcification began at 4 weeks postoperation; the calcium level of homogaft increased gradually and reached the peak at 12 weeks postoperation and then maintained on a stable level.

[Construction and identification of non-replication recombinant vaccinia virus co-expressing human papillomavirus type 16 L1/L2/E6/E7 proteins].

OBJECTIVE: To generate a human papillomavirus (HPV16) prophylactic and therapeutic vaccine candidate for cervical cancer. METHODS: HPV16 major capsid protein L1 gene/minor capsid protein L2 gene and HPV16 early E6/E7 genes were inserted into a vaccinia virus expression vector. A strain of non-recombinant vaccinia virus containing the sequences was obtained through a homologous recombination and identified. RESULTS: DNA hybridization confirmed that the HPV16L1/L2/E6/E7 genes were integrated into vaccinia virus DNA. Western Blot result showed that full-length L1/L2/E6/E7 proteins were co-expressed in CEF cells infected with the recombinant virus. CONCLUSION: NTVJE6E7CKL1L2 could be taken as a candidate of prophylactic and therapeutic vaccine for HPV-associated tumors and their precancerous transformations.

The induction and function study on dendritic cells derived from blasts from patients with acute myelogenous leukemia.

To investigate the induction method and function of dendritic cells (DC) derived from acute myelogenous leukemia (AML) blasts in vitro, cytokine-supplemented suspension cultures of leukemia blasts in 25 AML patients were performed. Mononuclear cells were cultured for 8 to 12 days using recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF), recombinant human interleukin-4 (rhIL-4) and recombinant human tumor necrosis factor-alpha (rhTNF-alpha). Morphology, phenotype, cytogenetics, and function of induced cells were studied. The results showed that after culture for 3 days, cells in 20/25 AML cases demonstrated an increase in size with dendritic morphology. After culture for 8 - 9 days, the percentage of such cells reached peak. When cultured for 12 days, the total number of cells and the number of cells with DC morphology decreased greatly. Phenotypic analyses of cells (11/20 cases) were measured by flow cytometry before and after culture. Before culture, cells did not express CD1a, CD80 and CD83, while expressed CD54, CD86 and HLA-DR with low frequency. After culture, cells upregulated CD1a, CD80, CD83, CD54, CD86 and HLA-DR significantly. A marked increase of the T-cell stimulatory capacity could be generated in Allo-MLRs. FISH confirmed the leukemic origin of generated cells. In conclusion, leukemia-derived DC can be generated from AML blasts using cytokine combination (GM-CSF, IL-4, and TNF-alpha) in vitro.

[Non-replicating recombinant vaccinia virus expressing HPV16 E6 and E7 proteins elicits anti-tumor immunity in mice].

OBJECTIVE: To investigate the anti-tumor immunity of the non-replicating recombinant vaccinia virus expressing HPV16 E6 and E7 proteins. METHODS: C57BL/6 mice were immunized by non-replicating recombinant vaccinia virus (NTVJmE6E7), and then specific CTLs were determined. Immune protection effects were evaluated by challenges of different doses of TC-1 tumor cells. Immunotherapeutic effects in form of recurrence were evaluated on the tumor-removed mice. RESULTS: Mice immunized by NTVJmE6E7 could generate TC-1 cell specific cytotoxic T lymphocyte (CTL). Mice boosted with NTVJmE6E7 could tolerate the challenge of 1 x 10(4) TC-1 cells. NTVJmE6E7 could effectively prevent the tumor recurrence in the tumor-removed mice. CONCLUSION: NTVJmE6E7 can be taken as a candidate of therapeutic vaccine for HPV-associated tumors and their precursor lesions.