信号转导及转录激活因子3(signal transducers and activators of transcription 3,STAT3)是一种细胞内重要的转录因子,在体内可被其最常见的上游激酶JAK激酶(Janus kinase)磷酸化激活。众所周知,异常激活的STAT3促进肿瘤的发生发展,因...信号转导及转录激活因子3(signal transducers and activators of transcription 3,STAT3)是一种细胞内重要的转录因子,在体内可被其最常见的上游激酶JAK激酶(Janus kinase)磷酸化激活。众所周知,异常激活的STAT3促进肿瘤的发生发展,因此研究人员一直致力于研究一类靶向JAK/STAT3信号通路的抗肿瘤药物。笔者收集了近年来文献中报道的靶向JAK/STAT3信号通路的抑制剂研究及临床试验进展,对于部分抑制剂已经报道的靶点、作用机制和药效活性进行总结。展开更多
A novel self-delivered prodrug system was fabricated for tumor-targeting therapy. In this nanosystem, the Arg-Gly-Asp-Ser （RGDS） tetrapeptide was used to improve the therapeutic index to integrin-overexpressing tumo...A novel self-delivered prodrug system was fabricated for tumor-targeting therapy. In this nanosystem, the Arg-Gly-Asp-Ser （RGDS） tetrapeptide was used to improve the therapeutic index to integrin-overexpressing tumor cells. The antitumorous drug camptothecin was further appended to the ε-amino group of lysine by 20-O-succinyl linkage and controllably released via hydrolytic cleavage. Prodrug molecules self-assembled into fibrillar nano-architectures and achieved the capability of self-delivery after being injected subcutaneously into mice. Introduction of hydrophobic myristic add favored the self-assembly and enhanced the cellular internalization of the prodrugs. In vitro and in vivo studies demonstrated that the self-assembled nanofibers could effectively target integrin- overexpressing tumorous cells and inhibit tumor growth via RGD-mediated specific targeting. Therefore, the traditional idea that fibrillar structures hold low therapeutic efficacy due to poor cell uptake can be challenged.展开更多
文摘信号转导及转录激活因子3(signal transducers and activators of transcription 3,STAT3)是一种细胞内重要的转录因子,在体内可被其最常见的上游激酶JAK激酶(Janus kinase)磷酸化激活。众所周知,异常激活的STAT3促进肿瘤的发生发展,因此研究人员一直致力于研究一类靶向JAK/STAT3信号通路的抗肿瘤药物。笔者收集了近年来文献中报道的靶向JAK/STAT3信号通路的抑制剂研究及临床试验进展,对于部分抑制剂已经报道的靶点、作用机制和药效活性进行总结。
基金This work was supported by the National Natural Science Foundation of China （Nos. 51125014, 51503227 and 51233003） and Natural Science Foundation of Hubei Province of China （Nos. 2014CFB696 and 2013CFA003）.
文摘A novel self-delivered prodrug system was fabricated for tumor-targeting therapy. In this nanosystem, the Arg-Gly-Asp-Ser （RGDS） tetrapeptide was used to improve the therapeutic index to integrin-overexpressing tumor cells. The antitumorous drug camptothecin was further appended to the ε-amino group of lysine by 20-O-succinyl linkage and controllably released via hydrolytic cleavage. Prodrug molecules self-assembled into fibrillar nano-architectures and achieved the capability of self-delivery after being injected subcutaneously into mice. Introduction of hydrophobic myristic add favored the self-assembly and enhanced the cellular internalization of the prodrugs. In vitro and in vivo studies demonstrated that the self-assembled nanofibers could effectively target integrin- overexpressing tumorous cells and inhibit tumor growth via RGD-mediated specific targeting. Therefore, the traditional idea that fibrillar structures hold low therapeutic efficacy due to poor cell uptake can be challenged.
