Vascular targeted photochemotherapy(VTP) holds promise as a novel strategy of the focal treatment of localised prostate cancer(LPCa). It is convenient to perform, minimally invasive and can be conduct in ambulatory co...Vascular targeted photochemotherapy(VTP) holds promise as a novel strategy of the focal treatment of localised prostate cancer(LPCa). It is convenient to perform, minimally invasive and can be conduct in ambulatory conditions. In this review, methodologic aspects of padoporfin- and padeliporfin-mediated VTP and its clinical application in focal treatment of LPCa as well as future perspective of this method were presented. Physicochemical and pharmacokinetic parameters of padoporphin and padeliporfin using as VTP photosensitizers were described, as well as methodologic question of radiation delivery and dosimetry, and oxygen monitoring in cancer tissue in context of VTP safety and efficiency of LPCa focal therapy were discussed. The results of clinical trials concerning application of padoporfin- and padeliporfin-mediated VTP in LPCa were also presented. The future of VTP is development of protocols, founded on the realtime feedback and rules-based approach to make this strategy a standard procedure in LPCa treatment. To evaluate clinical potential of this procedure, a costeffectiveness analysis is also necessary.展开更多
目的光敏剂8-甲氧基补骨脂素(8-Methoxsalen,8-MOP)联合长波紫外线(ultraviolet radiation A,UVA)作用(UVAP)诱导小鼠黑色素瘤细胞B16铁死亡效果及免疫原性变化研究,并分析处理后对后续免疫激活的影响。方法1)培养小鼠黑色素瘤B16细胞,...目的光敏剂8-甲氧基补骨脂素(8-Methoxsalen,8-MOP)联合长波紫外线(ultraviolet radiation A,UVA)作用(UVAP)诱导小鼠黑色素瘤细胞B16铁死亡效果及免疫原性变化研究,并分析处理后对后续免疫激活的影响。方法1)培养小鼠黑色素瘤B16细胞,使用8-MOP(100 ng/mL)和UVA(4 J/cm^(2))处理B16细胞,照射后于恒温培养箱(37℃,5%CO_(2))培养24 h。2)用CCK8(细胞增殖和毒性)检测试剂盒检测肿瘤细胞的死亡率。3)LPO(脂质过氧化物)、GSH(谷胱甘肽)检测试剂盒检测肿瘤细胞氧化损伤程度;用共聚焦显微镜对肿瘤细胞内的Fe^(2+)、线粒体膜电位(JC-1)、BODIPY 581/591 C11(脂质过氧化检测试剂盒)变化进行检测;WB检测GPX4、SLC7A11和NCOA4,以确定肿瘤细胞是否发生铁死亡。4)ELISA试剂盒检测肿瘤细胞培养上清液中的HMGB1(高迁移率族蛋白1)、ATP、CRT(钙网蛋白)表达,评价肿瘤细胞免疫原性变化。5)将1×10^(5)个B16细胞以100μL皮下注射小鼠后背颈部皮肤构建小鼠黑色素瘤模型,提取荷瘤小鼠脾脏单个核细胞并立即与照射后的肿瘤细胞共培养48 h,通过MHC-Ⅱ、CD11c、CD80、CD83流式检测DC成熟度的变化。结果UVAP后,B16细胞存活率明显下降(61.39±6.823 vs 84.81±7.026 vs 100.0±3.996,P<0.0001,P<0.01);且UVAP后确实会诱导B16细胞发生铁死亡,LPO、C11脂质过氧化程度增强,GSH耗竭,Fe^(2+)沉积和线粒体膜破坏,并且GPX4、SLC7A11蛋白表达下降,NCOA4表达升高,均符合铁死亡趋势。B16细胞免疫原性增强,ATP、CRT、HMGB1表达上升,DC成熟度增加(CD80:31.92±4.071 vs 19.77±3.177;CD83:21.40±4.787 vs 12.19±1.487,P<0.001,P<0.01)。结论8-MOP和UVA联合作用会诱导B16肿瘤细胞发生铁死亡,并且增强肿瘤细胞的免疫原性,释放更多肿瘤抗原,以促进DC的成熟,并更好地进行抗原递呈,实现后续免疫活化。展开更多
文摘Vascular targeted photochemotherapy(VTP) holds promise as a novel strategy of the focal treatment of localised prostate cancer(LPCa). It is convenient to perform, minimally invasive and can be conduct in ambulatory conditions. In this review, methodologic aspects of padoporfin- and padeliporfin-mediated VTP and its clinical application in focal treatment of LPCa as well as future perspective of this method were presented. Physicochemical and pharmacokinetic parameters of padoporphin and padeliporfin using as VTP photosensitizers were described, as well as methodologic question of radiation delivery and dosimetry, and oxygen monitoring in cancer tissue in context of VTP safety and efficiency of LPCa focal therapy were discussed. The results of clinical trials concerning application of padoporfin- and padeliporfin-mediated VTP in LPCa were also presented. The future of VTP is development of protocols, founded on the realtime feedback and rules-based approach to make this strategy a standard procedure in LPCa treatment. To evaluate clinical potential of this procedure, a costeffectiveness analysis is also necessary.
文摘目的光敏剂8-甲氧基补骨脂素(8-Methoxsalen,8-MOP)联合长波紫外线(ultraviolet radiation A,UVA)作用(UVAP)诱导小鼠黑色素瘤细胞B16铁死亡效果及免疫原性变化研究,并分析处理后对后续免疫激活的影响。方法1)培养小鼠黑色素瘤B16细胞,使用8-MOP(100 ng/mL)和UVA(4 J/cm^(2))处理B16细胞,照射后于恒温培养箱(37℃,5%CO_(2))培养24 h。2)用CCK8(细胞增殖和毒性)检测试剂盒检测肿瘤细胞的死亡率。3)LPO(脂质过氧化物)、GSH(谷胱甘肽)检测试剂盒检测肿瘤细胞氧化损伤程度;用共聚焦显微镜对肿瘤细胞内的Fe^(2+)、线粒体膜电位(JC-1)、BODIPY 581/591 C11(脂质过氧化检测试剂盒)变化进行检测;WB检测GPX4、SLC7A11和NCOA4,以确定肿瘤细胞是否发生铁死亡。4)ELISA试剂盒检测肿瘤细胞培养上清液中的HMGB1(高迁移率族蛋白1)、ATP、CRT(钙网蛋白)表达,评价肿瘤细胞免疫原性变化。5)将1×10^(5)个B16细胞以100μL皮下注射小鼠后背颈部皮肤构建小鼠黑色素瘤模型,提取荷瘤小鼠脾脏单个核细胞并立即与照射后的肿瘤细胞共培养48 h,通过MHC-Ⅱ、CD11c、CD80、CD83流式检测DC成熟度的变化。结果UVAP后,B16细胞存活率明显下降(61.39±6.823 vs 84.81±7.026 vs 100.0±3.996,P<0.0001,P<0.01);且UVAP后确实会诱导B16细胞发生铁死亡,LPO、C11脂质过氧化程度增强,GSH耗竭,Fe^(2+)沉积和线粒体膜破坏,并且GPX4、SLC7A11蛋白表达下降,NCOA4表达升高,均符合铁死亡趋势。B16细胞免疫原性增强,ATP、CRT、HMGB1表达上升,DC成熟度增加(CD80:31.92±4.071 vs 19.77±3.177;CD83:21.40±4.787 vs 12.19±1.487,P<0.001,P<0.01)。结论8-MOP和UVA联合作用会诱导B16肿瘤细胞发生铁死亡,并且增强肿瘤细胞的免疫原性,释放更多肿瘤抗原,以促进DC的成熟,并更好地进行抗原递呈,实现后续免疫活化。
