目的构建大鼠程序性细胞死亡因子4(programmed cell death 4,Pdcd4)基因在体干扰模型,为进一步研究该基因的功能提供条件。方法通过给予抗原诱导肺部炎症模型大鼠,鼻腔滴入Pdcd4的干扰质粒,以下调其体内Pdcd4的表达。收集大鼠支气管肺...目的构建大鼠程序性细胞死亡因子4(programmed cell death 4,Pdcd4)基因在体干扰模型,为进一步研究该基因的功能提供条件。方法通过给予抗原诱导肺部炎症模型大鼠,鼻腔滴入Pdcd4的干扰质粒,以下调其体内Pdcd4的表达。收集大鼠支气管肺泡灌洗液细胞,提取总RNA,RT-qPCR检测Pdcd4基因mRNA的表达水平。结果在模型大鼠鼻腔滴入Pdcd4的干扰质粒,大鼠支气管肺泡灌洗液细胞中的Pdcd4的mRNA表达明显下调。结论成功构建了Pdcd4基因的在体干扰大鼠模型,为进一步研究Pdcd4基因的功能和作用机制奠定基础。展开更多
Immune checkpoint inhibitors are increasingly drawing much attention in the therapeutic development for cancer treatment. However, many cancer patients do not respond to treatments with immune checkpoint inhibitors, p...Immune checkpoint inhibitors are increasingly drawing much attention in the therapeutic development for cancer treatment. However, many cancer patients do not respond to treatments with immune checkpoint inhibitors, partly because of the lack of tumor-infiltrating effector T cells. Cancer vaccines may prime patients for treatments with immune checkpoint inhibitors by inducing effector T-cell infiltration into the tumors and immune checkpoint signals. The combination of cancer vaccine and an immune checkpoint inhibitor may function synergistically to induce more effective antitumor immune responses, and clinical trials to test the combination are currently ongoing.展开更多
Different approaches for treating lung cancer have been developed over time, including chemotherapy, radiotherapy and targeted therapies against activating mutations. Lately, better understanding of the role of the im...Different approaches for treating lung cancer have been developed over time, including chemotherapy, radiotherapy and targeted therapies against activating mutations. Lately, better understanding of the role of the immunological system in tumor control has opened multiple doors to implement different strategies to enhance immune response against cancer cells. It is known that tumor cells elude immune response by several mechanisms. The development of monoclonal antibodies against the checkpoint inhibitor programmed cell death protein 1(PD-1) and its ligand(PD-L1), on T cells, has led to high activity in cancer patients with long lasting responses. Nivolumab, an anti PD-1 inhibitor, has been recently approved for the treatment of squamous cell lung cancer patients, given the survival advantage demonstrated in a phase III trial. Pembrolizumab, another anti PD-1 antibody, has received FDA breakthrough therapy designation for treatment of non-small cell lung cancer(NSCLC), supported by data from a phase I trial. Clinical trials with anti PD-1/PD-L1 antibodies in NSCLC have demonstrated very good tolerability and activity, with response rates around 20% and a median duration of response of 18 months.展开更多
文摘目的构建大鼠程序性细胞死亡因子4(programmed cell death 4,Pdcd4)基因在体干扰模型,为进一步研究该基因的功能提供条件。方法通过给予抗原诱导肺部炎症模型大鼠,鼻腔滴入Pdcd4的干扰质粒,以下调其体内Pdcd4的表达。收集大鼠支气管肺泡灌洗液细胞,提取总RNA,RT-qPCR检测Pdcd4基因mRNA的表达水平。结果在模型大鼠鼻腔滴入Pdcd4的干扰质粒,大鼠支气管肺泡灌洗液细胞中的Pdcd4的mRNA表达明显下调。结论成功构建了Pdcd4基因的在体干扰大鼠模型,为进一步研究Pdcd4基因的功能和作用机制奠定基础。
基金supported by the Viragh Foundation(L.Z.)National Institutes of Health(NIH)(Grant No.K23 CA148964,L.Z.)the NCI SPORE in Gastrointestinal Cancers(Grant No.P50 CA062924,L.Z.)
文摘Immune checkpoint inhibitors are increasingly drawing much attention in the therapeutic development for cancer treatment. However, many cancer patients do not respond to treatments with immune checkpoint inhibitors, partly because of the lack of tumor-infiltrating effector T cells. Cancer vaccines may prime patients for treatments with immune checkpoint inhibitors by inducing effector T-cell infiltration into the tumors and immune checkpoint signals. The combination of cancer vaccine and an immune checkpoint inhibitor may function synergistically to induce more effective antitumor immune responses, and clinical trials to test the combination are currently ongoing.
文摘Different approaches for treating lung cancer have been developed over time, including chemotherapy, radiotherapy and targeted therapies against activating mutations. Lately, better understanding of the role of the immunological system in tumor control has opened multiple doors to implement different strategies to enhance immune response against cancer cells. It is known that tumor cells elude immune response by several mechanisms. The development of monoclonal antibodies against the checkpoint inhibitor programmed cell death protein 1(PD-1) and its ligand(PD-L1), on T cells, has led to high activity in cancer patients with long lasting responses. Nivolumab, an anti PD-1 inhibitor, has been recently approved for the treatment of squamous cell lung cancer patients, given the survival advantage demonstrated in a phase III trial. Pembrolizumab, another anti PD-1 antibody, has received FDA breakthrough therapy designation for treatment of non-small cell lung cancer(NSCLC), supported by data from a phase I trial. Clinical trials with anti PD-1/PD-L1 antibodies in NSCLC have demonstrated very good tolerability and activity, with response rates around 20% and a median duration of response of 18 months.