Research progress of PD-1/PD-L1 in soft tissue sarcoma / 军事医学

Programmed cell death-1 ( PD-1 ) is a member of the CD28/cytotoxic T lymphocyte-associated protein-4 (CTLA-4) family, expressed on activated T cells, B cells and macrophages.Programmed cell death-ligand 1 (PD-L1) can inhibit T cell proliferation , activation and cytokine secretion , and participate in the negative feedback regulation of T cell receptor signals.In a normal body, PD-1/PD-Ls signaling pathway plays an important role in maintaining immune tolerance,but can inhibit T cell immune response and promote tumor immune escape in case of tumor .The relationships between the expression and prognosis of PD-1/PD-L1 in soft tissue sarcoma ( STS ) and its biological significance , influencing factors of PD-1/PD-L1 expression , and research progress in related drugs and clinical applicability in STS are reviewed.

Clinical analysis and prevention of complications associated with ultrasound-guided percutaneous thick needle biopsy / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the occurrence of complications in US-guided percutaneous biopsy using core (>19G) gauge cutting needle.</p><p><b>METHODS</b>A retrospective analysis of 5366 US-guided thick needle biopsies was conducted to analyze the incidence of complications after biopsy at different positions.</p><p><b>RESULTS</b>The total incidence of complications was 1.08%, including most frequent hemorrhage, pneumothorax, hemotysis and infection.</p><p><b>CONCLUSION</b>Ultrasound-guided automatic biopsy is easy to operate and safe, and strict execution of the procedures can lower the incidence of the complications.</p>

Safety and efficacy of gefitinib for treatment of advanced non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the safety and efficacy of gefitinib as second-line or even third-line treatment for previously treated patients with locally advanced or metastatic non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>156 patients with locally advanced NSCLC which were about to undergo progression after previous chemotherapy were eligible for this study. The regimen was oral intake of gefitinib 250 mg once daily in the morning or afternoon until the disease progression or toxicity has become intolerable. The drug was provided by AstroZeneca Company by its Expanded Access Program.</p><p><b>RESULTS</b>154 such patients were evaluable for response and toxicity assessment. The overall rate of objective response and disease control was 28.6% (44/154) and 89.6% (138/154). The median duration of response was 7. 5 months. The median time to disease progression (TTP) was 5. 1 months and the median overall survival time (OS) 10.0 months. The actuarial 1-year survival was 41. 0%. The response rate in adenocarcinoma was significantly higher than that in squamous carcinoma (P = 0. 026). The risk of disease progression in patients with squamous carcinoma was 1. 7 times as much as that of adenocarcinoma patients ( P = 0. 011) , and the risk of death in male was 2. 0 times as much as that in female ( P = 0. 002). At least one of these adverse events would be observed in 40.9% (63/154) of these patients, which, however was mild and reversible. Conclusion Gefitinib is effective and safe as a second-line or third-line treatment for previously treated patients with locally advanced or metastatic non-small cell lung cancer.</p>

Experimental study of effect of epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 in combination with irinotecan / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To assess the optimal regimen and its mechanism of ZD1839 in combination with SN38, the active metabolite of irinotecan (CPT-11), in the colon cancer cell lines HT-29 and LoVo.</p><p><b>METHODS</b>Chou and Talalay method was used to analyze the combination effects of sequencing of ZD1839 and SN38. Western blotting and immunoprecipitation were used to determine the effects of ZD1839 and/or SN38 on their targeted enzymes and downstream markers. Apoptosis was assayed by analyzing histone-associated DNA fragment.</p><p><b>RESULTS</b>Sequential SN38 followed by ZD1839 produced a synergistic effect. In contrast, SN38 following ZD1839 exhibited an antagonist effect. SN38 markedly inhibited topoisomerase I (Topo-I) activity. ZD1839 did not alter epidermal growth factor receptor (EGFR) expression, but resulted in a complete inhibition of EGFR phosphorylation. Sequential ZD1839 followed by SN38 did not show any enhanced inhibition effect on Topo-I activity, phosphorylation of EGFR and one of its downstream markers MAPK. However, simultaneous SN38 plus ZD1839, and sequential SN38 followed by ZD1839 administrations showed modest inhibition effect on EGFR's another downstream marker AKT. The combination schedules also showed prominent influence on cell cycle distribution. ZD1839 maintained SN38-induced DNA damage and apoptosis.</p><p><b>CONCLUSION</b>Sequential SN38 followed by ZD1839 may be a favorable combination schedule.</p>

Oral immunization of mice with vaccine of attenuated Salmonella typhimurium expressing Helicobacter pylori urease B subunit / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To prepare the live recombinant vaccine of attenuated Salmonella typhimurium SL3261 expressing Helicobacter pylori (H. pylori) B subunit (UreB) and to determine whether it could be used as an oral vaccine against H. pylori infection.</p><p><b>METHODS</b>Using genomic DNA of H. pylori Sydney strain (SSI) as template, the H. pylori UreB gene fragment was amplified by PCR and subcloned into the expression vector pTC01. The recombinant plasmid pTC01-UreB was then transferred into LB5000 to obtain modified forms, and further conversed into the attenuated Salmonella typhimurium SL3261 to obtain recombinant SL3261/pCT01-UreB as an oral immunization reagent, which was then used to orally immunize Balb/c mice twice at a three-week interval. Twelve weeks later, anti-UreB IgA antibodies in intestinal fluid and IgG antibodies in sera were determined by ELISA. The relating data in control groups (including body weight, gastric inflammation, etc.) were also collected.</p><p><b>RESULTS</b>The sequencing analysis showed that the UreB gene fragment amplified by PCR was consistent with the sequence of the H. pylori UreB gene. The restriction enzyme digestion revealed that the correct pTC01-UreB was obtained. SDS-PAGE and Western blot showed that a 61KD protein was expressed in SL3261/pTC01-UreB, which could be recognized by anti-H. pylori UreB antiserum and was absent in the control containing only Salmonella typhimurium SL3261 strain. The multiple oral immunization with SL3261/pTC01-UreB could significantly induce H. pylori specific mucosal IgA response as well as serum IgG responses. IFN-gamma and IL-10 levels were significantly increased in SL3261/pTC01-UreB group, and no obvious side effect and change in gastric inflammation were observed.</p><p><b>CONCLUSION</b>The attenuated vaccine of Salmonella typhimurium expressing H. pylori UreB can be used as an oral vaccine against H. pylori infection.</p>