Solid tumor cells show a resistance to immunologic effector cells in vitro[1]. The resistance may be one reason why these tumors withstand immunotherapeutic approaches in humans. Dendritic cells play an important role in the immune response to tumor-associated antigens in humans. Dendritic cells in the periphery capture and process antigens,express lymphocyte costimulatory molecules, migrate to lympoid organs, and secrete cytokines to initiate immune response.

目的：探讨采用体外化学合成的针对表皮生长因子受体（EGFR）设计的双链RNA（double-stranded RNA， dsRNA），是否能诱导肺非小细胞肺癌（NSCLC）细胞出现序列特异性基因沉默，及抑制EGFR基因表达后NSCLC细胞的生物学特征。方法：体外合成EGFR序列特异性dsRNA（dsRNA-EGFR），结合脂质体2000转染肺腺癌SPC2A21细胞，用荧光显微镜及流式细胞仪测定转染细胞的EGFR受体数量;适时定量聚合酶链反应检测其EGFR基因表达水平。采用集落形成试验检测SPC2A21细胞的增殖和集落形成能力。建立裸鼠肿瘤模型，计算肿瘤抑制率。结果：dsRNA2EGFR可使EGFR在蛋白水平表达下降7113%、基因水平表达下降5010%， SPC2A21细胞集落形成下降6618%，并显著抑制在体肿瘤生长，肿瘤抑制率为7510%。结论：dsRNA2EGFR可序列特异性下调NSCLC细胞EGFR在基因及蛋白水平的表达，有效抑制肿瘤生长。

Recently identified suppressors of cytokine signaling (SOCS) have been proposed as negative regulators of cytokine signaling, which have distinct mechanisms of inhibiting JAK-STAT pathway. In this study, using cultures of rat primary pulmonary vascular smooth muscle cells (PASMC), we found that hypoxia induced strongly STAT3 phosphorylation by up to four-fold. At the same time, mRNA for the endogenous cytokine signaling repressor SOCS3, but not SOCS1, was markedly induced in PASMC early as 2 h following hypoxic stimulation. Furthermore, forced expression of SOCS3 gene suppressed tyrosine phosphorylation of STAT3 and transcription of c-myc gene by more than 70% and 60% in PASMC under hypoxic conditions, respectively. Additionally, we showed here that hypoxia enhanced nearly two-fold increase of PASMC proliferation and overexpression SOCS3 gene downregulated hypoxia-induced PASMC proliferation by about 50%. The finding suggest that STAT3-dependent pathway is involved in the activation and proliferation of PASMC stimulated by hypoxia, and SOCS3 is a rapidly hypoxiainducible gene and acts to inhibit activation of cellular signaling pathway in a classical negative feedback loop.

Lung cancer has emerged as a leading cause of cancer death in the world. Non-small cell lung cancer (NSCLC) accounts for 75–80% of all lung cancers. Current therapies are ineffective, thus new approaches are needed to improve the therapeutic ratio. Double stranded RNA (dsRNA) -mediated RNA interference (RNAi) has shown promise in gene silencing, the potential of which in developing new methods for the therapy of NSCLC needs to be tested. We report here RNAi induced effective silencing of the epidermal growth factor receptor (EGFR) gene, which is over expressed in NSCLC. NSCLC cell lines A549 and SPC-A1 were transfected with sequence- specific dsRNA as well as various controls. Immune fluorescent labeling and flow cytometry were used to monitor the reduction in the production of EGFR protein. Quantitative reverse-transcriptase PCR was used to detect the level of EGFR mRNA. Cell count, colony assay, scratch assay, MTT assay in vitro and tumor growth assay in athymic nude mice in vivo were used to assess the functional effects of EGFR silencing on tumor cell growth and proliferation. Our data showed transfection of NSCLC cells with dsRNA resulted in sequence specific silencing of EGFR with 71.31% and 71.78% decreases in EGFR protein production and 37.04% and 54.92% in mRNA transcription in A549 and SPC-A1 cells respectively. The decrease in EGFR protein production caused significant growth inhibition, i.e.: reducing the total cell numbers by 85.0% and 78.3%, and colony forming numbers by 63.3% and 66.8%. These effects greatly retarded the migration of NSCLC cells by more than 80% both at 24 h and at 48h, and enhanced chemo-sensitivity to cisplatin by four-fold in A549 cells and seven-fold in SPC-A1. Furthermore, dsRNA specific for EGFR inhibited tumor growth in vivo both in size by 75.06% and in weight by 73.08%. Our data demonstrate a new therapeutic effect of sequence specific suppression of EGFR gene expression by RNAi, enabling inhibition of tumor proliferation and growth. However, in vivo use of dsRNA for gene transfer to tumor cells would be limited because dsRNA would be quickly degraded once delivered in vivo. We thus tested a new bovine lentiviral vector and showed lentivector-mediated RNAi effects were efficient and specific. Combining RNAi with this gene delivery system may enable us to develop RNAi for silencing EGFR into an effective therapy for NSCLC.

The incidence of the pulmonary complications in patients with acute pancreatitis is up to 60%, from mild hypoxaemia without clinical or radiological abnormalities to severe acute lung injury. Although a number of reviews has described clinical evidence of pancreatitis-associated lung injury (PALI), there is still a lack of information on potential interorgan signalling involved in the development of PALI. The present review discusses the potential factors that have been considered as candidates responsible for interorgan signalling coupling pancreatitis to lung injury. Inflammatory mediators produced from the pancreas, leucocyte system and extrapancreatic organs may directly or indirectly contribute to the high concentration in the circulation, activate circulating leucocytes, initiate the inflammatory responses of pulmonary resident cells or induce acute lung injury. Circulating leucocytes have been suggested to play an important role in interorgan signalling during the development of PALI, by producing the inflammatory mediators, reactive oxygen species and proteinases, interacting with endothelial cells, communicating with pulmonary cells and compromising the lung tissue. Extrapancreatic organ fluid, e.g. liver, PAAF and gut, may also contribute to the interorgan signalling between the pancreas and lungs. There is still a great need to clarify the specificity, sensitivity and repeatability of these candidates for interorgan signalling in PALI.