Impaired upregulation of keratinocyte growth factor in injured lungs induced by Pseudomonas aeruginosa in immunosuppressed rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The number of immunosuppressed patients has increased in the past decades. Among them Pseudomonas aeruginosa (P. aeruginosa) is one of the leading bacteria for pneumonia that are associated with poor prognosis. However, the pathogenesis of P. aeruginosa pneumonia in immunosuppressed patients is not understood completely. Previous reports showed keratinocyte growth factor (KGF) is associated with lung injury in immunocompetent hosts. In this study, we investigated the different reactions of lung injury, lung pathology and KGF expressions in P. aeruginosa pneumonia between immunosuppressed and immunocompetent rats.</p><p><b>METHODS</b>Immunosuppression of male rats was induced by injecting immunosuppressive subcutaneously. Pneumonia was established by instilling P. aeruginous tracheally. The immunocompetent rats were the control group. Survival rate, lung histopathology, pulmonary permeability and oedema, KGF mRNA and protein expressions in lungs of both groups were investigated.</p><p><b>RESULTS</b>The survival rate of immunosuppressed group was lower than that of immunocompetent group (33.3% vs 83.3%). After exposure to bacteria, pulmonary permeability and wet/dry ratio in immunosuppressed group were higher than those in immunocompetent group. Pulmonary congestion and haemorrhage were more intensive in immunosuppressed group compared to immunocompetent group. Apoptosis and necrosis were also observed in infected lungs of immunosuppressed rats. Although we detected KGF expressions in lungs of both groups after infection, the expressions of KGF protein and mRNA gene in immunosuppressed group were much lower than in immunocompetent group.</p><p><b>CONCLUSIONS</b>Compared with immunocompetent group, there was more intensive lung injury in immunosuppressed group. Severe lung injury may contribute to the poor prognosis of pneumonia. KGF expressions of pneumonia in immunosuppressed rats were less than those in immunocompetent ones.</p>

Suicidal cancer vaccine enhances anti-tumor immunotherapeutic effect and its safety in the treatment of ovarian cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the anti-tumor immunotherapeutic effect induced by the suicidalcancer vaccine FC/TK, and to evaluate the safety of this vaccine.</p><p><b>METHODS</b>The suicidal cancer vaccine, named FC/TK, was prepared by fusion of suicide gene (HSVI,-TK gene) -modified ovarian carcinoma NuTu-19 cells with rat bone marrow-derived dendritic cells (DCs). The morphology of FC/TK was evaluated by scanning electron microscopy. The stimulatory effect of FC/TK on T cells was determined by T cell proliferation assay. In immunotherapeutic studies in vivo, Fischer344 rats were injected subcutaneously with NuTu-19 cells, followed by treatment of FC/TK on days 7 and 14, compared to controls treated with irradiated FC/TK, FC or PBS, respectively. Tumor incidence and volume were measured in 90 days after challenge. To determine the killing effect of FC/TK in vivo, TUNEL assays were applied to detect apoptotic cell death in spleen of vaccinated rats with prodrug ganciclovir administration.</p><p><b>RESULTS</b>FC/TK cells were of irregular shape with surface membrane processes. Compared to the control groups, FC/TK significantly promoted T cell proliferation (P <0.01). The rats vaccinated with FC/TK and FC significantly inhibited the tumor growth compared to rats vaccinated with irradiated FC/TK (P <0.05) or with PBS ( P <0.01). The immunotherapeutic effect induced by FC/TK was similar to that using FC. Fluorescence microscopy showed that fluorescein-stained FC/TK cells migrated into spleen also showed to be TUNEL-positive, suggesting that the FC/TK cells were killed by ganciclovir in vivo.</p><p><b>CONCLUSION</b>Our data indicate that suicidal cancer vaccine is an effective and safe therapy for ovarian carcinoma and may serve as a broadly applicable approach for other cancer vaccines in the future.</p>

Downregulation of Duffy antigen receptor for chemokine (DARC) is associated with lymph node metastasis in human breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the relationship between Duffy antigen receptor for chemokines (DARC) and the metastasis potential in human breast cancer. METHODS Breast cancer tissue sections from 75 patients, grouped according to the local lymph node status were examined immunohistochemically for protein level of DARC. Microvessel density (MVD) was counted by endothelial cells immunostained using anti-CD34 antibody.</p><p><b>RESULTS</b>Strong positive DARC immunostaining in lymph node negative and positive groups was detected in 31 cases (81.6%) and 18 cases (48.6%), respectively (P < 0.01). MVD was (35.67 +/- 17.96)/HP and (53.38 +/- 20.29)/HP in DARC strong positive and less positive cases (P < 0.01). In those patients with lung, bone, hepatic distant metastasis (13 cases), 9 cases (69.2%) were DARC less positive, 4 cases (30.8%) were DARC strong positive. The correlation coefficient was -0.412 between DARC expression and MVD and the corresponding value was -0.346 between DARC expression and lymph node status and -0.333 between DARC expression and distant metastasis in breast cancer.</p><p><b>CONCLUSION</b>DARC may play a negative role in the process of neoangiogenesis, and probably has an association with the lymph node status.</p>