Relationships between hepatitis B infection status and liver dysfunction after chemotherapy of lung cancer patients in mainland China.

PURPOSE: A preliminary analysis on the risk factors of liver dysfunction was made after the investigation of hepatitis B prevalence and chemotherapy-related hepatic dysfunction occurrence for patients with lung cancer. PATIENTS AND METHODS: Consecutively diagnosed 950 lung cancer patients treated in Huashan Hospital, Fudan University from 1999 to 2009 were enrolled in the study. We investigated hepatitis B (HB) prevalence and analyzed chemotherapy-related hepatic dysfunction occurrence and its influencing factors. Liver dysfunction was considered when alanine transaminase, aspartate aminotransferase, and serum bilirubin levels exceeded at least 1.25-fold of normal levels, and HB statuses were categorized into diagnosed HB, previous HB infection, HB immunity, and no HB infection. RESULTS: Among the 950 lung cancer patients, 632 accepted the HB serum marker tests: 8.4 % (53/632) were HB surface antigen positive, and 37.2 % (235/632) were HB core antibody positive. A number of 281 patients received liver function follow-up examinations after they underwent a total of 774 chemotherapy courses, and 34 liver dysfunctions were detected. A logistic regression analysis showed that younger age at diagnosis (≤60 years; P = 0.029) and abnormal liver function before chemotherapy (P = 0.000) were the risk factors for liver dysfunctions after chemotherapy, but HB status had no influence. CONCLUSIONS: The screening rates for serum HB marker and HB prevalence in patients with lung cancer were high in mainland China. Lung cancer patients with abnormal liver function before chemotherapy and in younger ages had higher risks for liver dysfunctions after chemotherapies, whereas HB status before the first chemotherapy is not an independent impact factor for post-treatment liver dysfunctions.

Effects of deguelin on proliferation and apoptosis of MCF-7 breast cancer cells by phosphatidylinositol 3-kinase/Akt signaling pathway / 中西医结合学报

Objective: To study the effects of deguelin on proliferation and apoptosis of human breast cancer cell line MCF-7 and on phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. Methods: After treatment with 0, 1, 5, 10, 15 and 20 μmol/L of deguelin for 6, 24, 48 and 72 hours, the proliferation inhibition rate of MCF-7 cells was measured by cell counting kit-8 assay. Apoptosis rate of MCF-7 cells was detected with Annexin V-fluorescein isothiocyanate/propidium iodide double staining by flow cytometry and the apoptotic morphology was observed under a transmission electron microscope. After treatment with 0, 1 and 5 μmol/L of deguelin for 6 hours, 5 proteins involved in the PI3K/Akt signaling pathway were examined by Western blot analysis. Results: Deguelin at doses of 5, 10, 15 and 20 μmol/L inhibited the proliferation of MCF-7 cells at 6, 24, 48 and 72 hours. There was a significant difference in each group compared with the control group (P0.05). Deguelin at doses of 5, 10, 15 and 20 μmol/L induced apoptosis of MCF-7 cells at 6 hours. There were significant differences (P<0.01) in the early and late apoptosis rate between the treated groups and the control group. The typical apoptotic MCF-7 cells were observed under the transmission electron microscopy. However, 1 μmol/L of deguelin had no apparent effect in inducing apoptosis of MCF-7 cells at 6 hours. After treatment with 5 μmol/L of deguelin for 6 hours the expression of phosphorylated phosphatase and tensin homologue deleted on chromosome 10 (PTEN) (Ser380), phosphorylated 3-phosphoinositide-dependent protein kinase 1 (PDK1) (Ser241), phosphorylated Akt (Thr308) and phosphorylated glycogen synthase kinase-3β (GSK-3β) (Ser9) proteins were significantly reduced in MCF-7 cells, while there was no significant change in the expression of total Akt protein. However, after treatment with 1 μmol/L of deguelin for 6 hours, there was no apparent change in the expression of these 5 proteins. Conclusion: Deguelin can inhibit the phosphorylation of GSK-3β (Ser9) via inhibition of the phosphorylation of PTEN (Ser380) and PDK1 (Ser241) pathway, thus inducing apoptosis and inhibiting proliferation of MCF-7 cells.

Immunoregulation of galectins in tumor microenvironment / 国际肿瘤学杂志

Galectins can recognize and specifically bind to β-galactosidase,and regulate the transformation and survival of tumor cells,and promote the migration and metastasis of tumor cells,etc.Galectins correlate with tumor diagnosis,progression and prognosis.Galectias also can serve as immunoregulatory molecules to regulate the survival,activation,proliferation and differentiation of immune cells,and are components of tumor immune microenvironment.

Role of dephosphorylation of FOXO1 on apoptosis induced by wortmannin for non-Hodgkin's lymphoma cells.

The aim of this study was to ascertain the relationship between the phosphorylation of FOXO1 and the apoptosis and the proliferation of lymphoma cells so as to further clarify the cellular biology and pathogenesis of the disease. The lymphoma cells Namalwa and Jurkat were treated with PI3K inhibitor wortmannin or etoposide alone or wortmannin plus etoposide with different schedule. The inhibition rates of lymphoma cell growth were examined by XTT assay. Apoptosis were detected by flow cytometry. The expression of p-Akt, p-FOXO1, FOXO1, bim were determined by western blot analysis. Wortmannin induced apoptosis of Jurkat cells and Namalwa cells and inhibited their survival effectively. The rate of growth inhibition and apoptosis of lymphoma cells induced by wortmannin plus etoposide were higher than those induced by etoposide alone. After treated with wortmannin, phosphorylation of FOXO1 remarkably reduced and bim increased. The dephosphorylation of FOXO1 inhibited proliferation of Jurkat cells and Namalwa cells, promoted their apoptosis and sensitized Non-Hodgkin lymphoma cells to etoposide. Bim activated by FOXO1 promoted cells apoptosis.

Positive selection using anti-CD11c magnetic beads for isolation of tumor infiltrating dendritic cells in lung cancer tissues / 中国肿瘤生物治疗杂志

Objective:To establish a method for isolating tumor infiltrating dendritic cells(TIDC)from mice models of Lewis lung cancer by positive selection using anti-CD11c magnetic beads.Methods:A total of 1.0?10~6 Lewis lung cancer cells were subcutaneously injected into a C57BL/6 mice at the lateral abdominal wall to establish the mouse model of lung cancer.TIDC were isolated positively using anti-mouse CD11c magnetic beads;they were labeled by anti-mouse CD11c,and then the purity of the isolated cells was tested by FACScan flow cytometer.The cells were also double labeled by PE-conjugated MHC-ⅡmAb and FITC-conjugated CD83 mAb or FITC-conjugated CD86 mAb to analyze the phenotype of cells by FACScan flow cytometer.Results:The positive selection using anti-CD11 c magnetic beads isolated(1.73?0.31)?10~6 TIDC from each gram of Lewis lung cancer tissue,which accounted for(2.18?0.29)%of the cells in the tumor tissues.The purity of TIDC was 96.49%.Electron microscope showed that the isolated TIDC had the typical character of DC cells.The positive rates of MHC-Ⅱ,CD83 and CD86 molecules in TIDC surface were(51.25?4.21)%, (3.48?0.34)%and(3.07?0.65)%,respectively.Conclusion:The positive selection using anti-CD11c magnetic beads is highly effective,simple,and economic,and is worth popularizing.

The defense-responsive genes showing enhanced and repressed expression after pathogen infection in rice (Oryza sativa L.).

Despite large numbers of studies about defense response, processes involved in the resistance of plants to incompatible pathogens are still largely uncharacterized. The objective of this study was to identify genes involved in defense response by cDNA array analysis and to gain knowledge about the functions of the genes involved in defense response. Approximately 20000 rice cDNA clones were arrayed on nylon filters. RNA samples isolated from different rice lines after infection with incompatible strains or isolates of Xanthomonas oryzae pv. oryzae or Pyricularia grisea, respectively, were used to synthesize cDNA as probes for screening the cDNA arrays. A total of 100 differentially expressed unique sequences were identified from 5 pathogen-host combinations. Fifty-three sequences were detected as showing enhanced expression and 47 sequences were detected as showing repressed expression after pathogen infection. Sequence analysis revealed that most of the 100 sequences had various degrees of homology with genes in databases which encode or putatively encode transcription regulating proteins, translation regulating proteins, transport proteins, kinases, metabolic enzymes, and proteins involved in other functions. Most of the genes have not been previously reported as being involved in the disease resistance response in rice. The results from cDNA arrays, reverse transcription-polymerase chain reaction, and RNA gel blot analysis suggest that activation or repression of most of these genes might occur commonly in the defense response.