目的构建并表征胃癌三维多细胞球体模型,用于评价化疗药物的瘤内穿透。方法将12000个小鼠胃癌MFC细胞系接种于96 U 3D细胞培养板,以构建MFC多细胞肿瘤球体(MFC MCTS);将8000个MFC细胞和4000个小鼠成纤维NIH/3T3细胞系共同接种于96 U 3D...目的构建并表征胃癌三维多细胞球体模型,用于评价化疗药物的瘤内穿透。方法将12000个小鼠胃癌MFC细胞系接种于96 U 3D细胞培养板,以构建MFC多细胞肿瘤球体(MFC MCTS);将8000个MFC细胞和4000个小鼠成纤维NIH/3T3细胞系共同接种于96 U 3D细胞培养板,以构建MFC-NIH/3T3共培养多细胞肿瘤球体(CO MCTS);通过活细胞成像表征球体的直径、圆度、面积和透光率;通过激光共聚焦成像表征球体微环境和化疗药物(LipoDOX,5.0μg/ml)的瘤内穿透。结果培养5 d时,两种球体的透光率最低,圆度>0.90,直径约为530μm,面积约为0.23 mm^(2)。两种球体模型内均检测到3种微环境荧光探针分布。LipoDOX能相对均匀地穿透MFC MCTS,却在CO MCTS内表现出外多内少的不均匀穿透,药物荧光强度降低约58.3%(P<0.01)。结论本研究构建了两种具有良好圆度、高紧实度、适中直径和面积的胃癌三维多细胞球体模型,两种胃癌球体模型均表现出酸性、缺氧和氧化还原微环境,可精准、高效地评价化疗药物的瘤内穿透。展开更多
AIM： To introduce the combination method of radio- chemoembolization for the treatment of selected he- patic metastases. METHODS： Twenty patients with biopsy proven hepat- ic metastases were selected from those who ...AIM： To introduce the combination method of radio- chemoembolization for the treatment of selected he- patic metastases. METHODS： Twenty patients with biopsy proven hepat- ic metastases were selected from those who underwent transarterial radiochemoembolization, a novel combina- tion protocol, between .lanuary 2009 and July 2010. Patients had different sources of liver metastasis. The treatment included transarterial administration of three chemotherapeutic drugs （mitomycin, doxorubicin and cisplatin）, followed by embolization with large （50-150 μm） radioisotope particles of chromic 32R Multiphasic computer tomography or computer tomography stud- ies, with and without contrast medium injections, were performed for all patients for a short-term period before and after the treatment sessions. The short-term effec- tiveness of this procedure was evaluated by modified response evaluation criteria in solid tumors （mRECIST）, which also takes necrosis into account. The subjective percentage of necrosis was also assessed. The re- sponse evaluation methods were based on the changes in size, number, and the enhancement patterns of the lesions between the pre- and post-treatment imaging studies. RESULTS： Patients had liver metastasis from colorectal carcinomas, breast cancer, lung cancer and carcinoid tumors. The response rate based on the mRECIST criteria was 5% for complete response, 60% for par- tial response, 10% for stable disease, and 25% for progressive disease. Regarding the subjective necrosis percentage, 5% of patients had complete response, 50% had partial response, 25% had stable disease, and 20% had progressive disease. Based on traditional RECIST criteria, 3 patients （15%） had partial response, 13 patients （65%） had stable disease, and 4 patients （20%） had disease progression. In most patients, colorectal carcinoma was the source of metastasis （13 patients）. Based on the mRECIST criteria, 8 out of these 13 patients had partial responses, while one remained stable, and 5 showed progressive disease. We also had 5 cases of breast cancer metastasis which mostly remained stable （4 cases）, with only one partial response after the procedure. Six patients had bilobar involvement; three of them received two courses of radiochemoembolization. The follow up imaging study of these patients was performed after the second ses- sion. In the studied patients there was no evidence of extrahepatic occurrence, including pulmonary radioac- tive deposition, which was proven by Bremsstrahlung scintigraphy performed after the treatment sessions. For the short-term follow-ups for the 2 mo after the therapy, no treatment related death was reported. The mostly common side effect was post-embolization syndrome, presented as vomiting, abdominal pain, and fever. Nineteen （95%） patients experienced this syndrome in different severities. Two patient had asci- tes （with pleural effusion in one patient） not related to hepatic failure. Moreover, no cases of acute liver failure, hepatic infarction, hepatic abscess, biliary necrosis, tu- mor rupture, surgical cholecystitis, or non-targeted gut embolization were reported. Systemic toxicities such as alopecia, marrow suppression, renal toxicity, or cardiac failure did not occur in our study group. CONCLUSION： Radiochemoembolization is safe and effective for selected hepatic metastases in a short- term follow-up. Further studies are required to show the long-term effects and possible complications of this approach.展开更多
文摘AIM： To introduce the combination method of radio- chemoembolization for the treatment of selected he- patic metastases. METHODS： Twenty patients with biopsy proven hepat- ic metastases were selected from those who underwent transarterial radiochemoembolization, a novel combina- tion protocol, between .lanuary 2009 and July 2010. Patients had different sources of liver metastasis. The treatment included transarterial administration of three chemotherapeutic drugs （mitomycin, doxorubicin and cisplatin）, followed by embolization with large （50-150 μm） radioisotope particles of chromic 32R Multiphasic computer tomography or computer tomography stud- ies, with and without contrast medium injections, were performed for all patients for a short-term period before and after the treatment sessions. The short-term effec- tiveness of this procedure was evaluated by modified response evaluation criteria in solid tumors （mRECIST）, which also takes necrosis into account. The subjective percentage of necrosis was also assessed. The re- sponse evaluation methods were based on the changes in size, number, and the enhancement patterns of the lesions between the pre- and post-treatment imaging studies. RESULTS： Patients had liver metastasis from colorectal carcinomas, breast cancer, lung cancer and carcinoid tumors. The response rate based on the mRECIST criteria was 5% for complete response, 60% for par- tial response, 10% for stable disease, and 25% for progressive disease. Regarding the subjective necrosis percentage, 5% of patients had complete response, 50% had partial response, 25% had stable disease, and 20% had progressive disease. Based on traditional RECIST criteria, 3 patients （15%） had partial response, 13 patients （65%） had stable disease, and 4 patients （20%） had disease progression. In most patients, colorectal carcinoma was the source of metastasis （13 patients）. Based on the mRECIST criteria, 8 out of these 13 patients had partial responses, while one remained stable, and 5 showed progressive disease. We also had 5 cases of breast cancer metastasis which mostly remained stable （4 cases）, with only one partial response after the procedure. Six patients had bilobar involvement; three of them received two courses of radiochemoembolization. The follow up imaging study of these patients was performed after the second ses- sion. In the studied patients there was no evidence of extrahepatic occurrence, including pulmonary radioac- tive deposition, which was proven by Bremsstrahlung scintigraphy performed after the treatment sessions. For the short-term follow-ups for the 2 mo after the therapy, no treatment related death was reported. The mostly common side effect was post-embolization syndrome, presented as vomiting, abdominal pain, and fever. Nineteen （95%） patients experienced this syndrome in different severities. Two patient had asci- tes （with pleural effusion in one patient） not related to hepatic failure. Moreover, no cases of acute liver failure, hepatic infarction, hepatic abscess, biliary necrosis, tu- mor rupture, surgical cholecystitis, or non-targeted gut embolization were reported. Systemic toxicities such as alopecia, marrow suppression, renal toxicity, or cardiac failure did not occur in our study group. CONCLUSION： Radiochemoembolization is safe and effective for selected hepatic metastases in a short- term follow-up. Further studies are required to show the long-term effects and possible complications of this approach.
