肝癌介入性热化疗的研究进展

目前,介入性热化疗作为一种新的综合治疗手段已经应用于临床,但在抗癌机制及治疗方案等方面仍未有定论,本文就近年来肝癌介入性热化疗的温度及时间、灌注液的总量及流速、常用药物及热化疗方案等方面的研究情况作一综述,并指出了介入性热化疗存在的问题和发展方向。     

Thermal enhancement of melphalan and oxaliplatin cytotoxicity in vitro

It has been established that hyperthermia can enhance cytotoxicity of some chemotherapeutic agents. This has led to various clinical trials of thermochemotherapy, although many questions remain unanswered. The effects of various agents have been studied on animal tumours with different histopathology at elevated temperatures. These studies indicated that alkylating agents were most effective to all tumours at a moderately elevated temperature. Cisplatin was also effective to all tumours, but its effectiveness at 41.5°C was less than that of alkylating agents. To quantitatively study these findings, the magnitude of thermal enhancement of melphalan, an alkylating agent, and that of oxaliplatin, a new platinum compound, were studied at 37-44.5°C by the colony formation assay. The dose of each agent was kept constant, and cell survival was determined as a function of treatment time. The cell survival curve was exponentially related with treatment time at all test temperatures, and the T 0 (the time to reduce survival from 1 to 0.37) decreased with an increasing temperature. These results suggested that the cytotoxic effect of these agents occurred with a constant rate at 37°C, and the rate was facilitated with an increasing temperature. This suggests that heat can accelerate the cytotoxic chemical reaction, leading to substantial thermal enhancement. The thermal enhancement ratio (TER, the ratio of the T 0 at 37°C to the T 0 at an elevated temperature) increased with an increase in the temperature. The activation energy for melphalan at moderately elevated temperatures was largest among the agents tested in the laboratory and that for oxaliplatin was approximately half of the melphalan activation energy. This suggests that the thermal enhancement for the cytotoxicity of melphalan or alkylating agents might be the greatest. Potential mechanisms of thermal enhancement of cytotoxicity were discussed.     

经胃左动脉灌注热化疗药物对家兔胃壁超微结构影响的实验研究

 目的　通过观察经胃左动脉热灌注化疗药物对正常胃组织超微结构的影响研究其安全性。方法　家兔 30只 ,随机分为 6组 ,手术经胃左动脉插入 0 .0 38英寸导管 ,分别以不同温度灌注化疗药物 ,取胃组织做病理和电镜检查。结果　 5 3℃组出现可恢复性细胞损伤 ,5 6℃组出现细胞凋亡及坏死等不可恢复性损伤。结论　 5 3℃组胃壁组织的温度达到了 4 3℃左右的治疗温度 ,损伤是可恢复性的。 5 6℃以上会造成胃壁正常细胞不可恢复损伤。     

温热与羟基喜树碱（OPT）联合对胃腺癌（SGC－7901）细胞的作用

以体外长期培养胃低分化腺癌细胞系（ＳＧＣ－７９０１）细胞为模型，采用水浴加温法对细胞的生长抑制规律进行了观察。表明：１）温热、ＯＰＴ对ＳＧＣ－７９０１细胞均有一定的抑制增殖和直接杀伤作用；温热与药物联合应用具有协同抑制增殖和杀伤细胞的作用。２）温热和ＯＰＴ联合对ＳＧＣ７９０１细胞的杀伤和生长抑制作用均较温热或药物单独作用强，但序贯方面以热药同时为佳。３）温热、ＯＰＴ都可使ＳＧＣ－７９０１细胞结构发生变化，单用以细胞变性为主，联合组多为不可逆性损伤。４）温热４０℃作用后细胞爆发性生长，表明单纯加热低于４２℃是不适宜的。     

局部热化疗对鼠胶质瘤PCNA和VEGF蛋白表达的影响

目的研究局部热化疗对鼠胶质瘤PCNA和VEGF蛋白表达的影响,探讨其作为胶质瘤辅助治疗的可行性。方法将传代培养的C6细胞接种于大鼠背部皮下,肿瘤生长至1.5～2cm直径时,分组进行局部热疗、化疗、热化疗。测量肿瘤体积和重量;用免疫组化S-P法检测PCNA、VEGF蛋白表达,光镜观察肿瘤增殖状况。结果热疗、化疗、热化疗与对照组比较:瘤体缩小、瘤重减轻,PCNA和VEGF蛋白表达减低(P<0.01),且热化疗较单纯热疗和化疗减低更明显(P<0.01)。结论①热疗、化疗、热化疗能抑制肿瘤生长,且热化疗有协同作用;②热化疗一方面抑制PCNA合成与表达,抑制肿瘤增殖;另一方面抑制VEGF合成与分泌,抑制肿瘤血管再生,达到抗瘤作用。     

局部热化疗对鼠胶质细胞移植瘤细胞增殖及其蛋白表达的影响

目的　研究局部热化疗对鼠胶质细胞移植瘤细胞增殖及PCNA、IGF I表达的作用 ,探讨其作为胶质瘤辅助治疗的可行性。方法　将传代培养的C6细胞接种于大鼠背部皮下 ,肿瘤生长至直径为 1.5～2 .0cm时 ,分组进行局部热疗、化疗和热化疗。继续观察皮下肿瘤生长情况 ,测量瘤体体积和重量 ;用免疫组化S P法检测PCNA、IGF I蛋白表达 ;用HE染色法、电镜观察肿瘤增殖状况。结果　热疗、化疗、热化疗与对照组比较 ,瘤体缩小 ,瘤重减轻 (分别为 2 .95 ,1.95 ,1.86和 1.0 9g ,P值均 <0 .0 1) ;PCNA蛋白和IGF I蛋白表达降低 (P <0 .0 1) ,且热化疗较单纯热疗和化疗降低更明显 (P <0 .0 1)。出现核染色质凝聚 ,凋亡小体 ,细胞增殖明显受抑制。结论　①热疗、化疗、热化疗能抑制肿瘤增殖 ,且热化疗有协同作用。②热疗、化疗、热化疗能减低PCNA、IGF I蛋白表达。③热化疗抑制胶质瘤的PCNA合成与表达 ,抑制IGF I的合成与分泌 ,是其治疗肿瘤的机制之一。     

热化疗对人胆管癌细胞增殖和凋亡的影响

目的探讨表阿霉素(EADM)热化疗对人胆管癌细胞(QBC939)的增殖和凋亡的作用。方法以体外培养的人胆管癌细胞株为研究对象,采用水浴加热法进行体外细胞毒实验(MTT)、透射电镜观察及流式细胞仪检测,观察热疗、化疗、热化疗对人胆管癌细胞的生长抑制和凋亡的影响。结果42℃以上单纯热疗对QBC939细胞有明显杀伤作用(P<0.01),42℃以上热化疗对QBC939细胞有明显的协同或相加作用(P<0.01)。透射电镜和流式细胞术均观察到热疗、化疗、热化疗诱导细胞凋亡的作用(P<0.01);热化疗有协同作用(P<0.01)。结论热疗、化疗、热化疗均抑制QBC939细胞增殖;热疗、化疗、热化疗诱导细胞凋亡为其抗癌机制之一;热疗提高化疗药物的细胞毒作用。     

The effect of various chemotherapeutic agents given with mild hyperthermia on different types of tumours

It has been shown that hyperthermia can enhance the cytotoxicity of some chemotherapeutics. However, the most effective agent(s) at elevated temperatures have yet to be determined. A previous study suggests that the drug of choice at elevated temperatures may be different from that at the physiological temperature, and that the alkylating agents may be most effective at elevated temperatures. To further investigate these possibilities, the effect of chemotherapeutic agents were compared. These agents were cyclophosphamide, ifosfamide, melphalan, cis-diamminedichloroplatinum (II), 5-fluorouracil, mitomycin C and bleomycin. Three tumours (mammary carcinoma, osteosarcoma and squamous cell carcinoma) were used. They were transplanted into the feet of C3H/He mice. When tumours reached 65 mm 3 , a test agent was injected intraperitoneally. Tumours were immediately heated at 41.5°C for 30 min, and the tumour growth (TG) time was studied for each tumour. Using the TG times, the TG-50 (the time required for one-half of the total number of the treated tumours to reach the volume of 800 mm 3 from 65 mm 3 ) was calculated. Subsequently, the tumour growth delay time (GDT) and the thermal enhancement ratio (TER) were obtained. The GDT was the difference between the TG-50 of treated tumours and that of non-treated control tumours. The TER was the ratio of the GDT of a group treated with an agent at 41.5°C to that of a group treated with the agent at room temperature. Results showed that the top three effective agents tested at 41.5°C were solely alkylating agents--CY, IFO and L-PAM--for each kind of tumour. A GDT of cisplatin was smaller than those of the alkylating agents. The smallest TER, 1.1, was observed for 5-fluorouracil, which was given for mammary carcinoma, and for mitomycin C, which was given for squamous cell carcinoma. It could be concluded that the alkylating agents at elevated temperatures might be the drugs of choice for many types of tumours. The possible mechanisms of thermal enhancement associated with these agents are discussed.     

阿霉素加热化疗对人肝癌细胞耐药模型-7721/Adm多药耐药性的影响

目的 探讨阿霉素（ＡＤＭ）化疗与４３℃加热化疗对人肝癌细胞－７７２１（以下简称７７２１细胞）和耐药人肝癌细胞模型－７７２１／Ａｄｍ（以下简称７７２１／Ａｄｍ细胞）的细胞毒作用。方法 以体外培养的人肝癌细胞－７７２１和我们培养建立的人肝癌细胞模型－７７２１／Ａｄｍ为研究对象,采用水浴加温法,体外细胞毒试验（ＭＴＴ法）,观察ＡＤＭ化疗与加热化疗对细胞的生长抑制规律的影响;采用流式细胞技术检测加热对７７２１细胞和７７２１／Ａｄｍ细胞内阿霉素浓度的影响。结果 （１）７７２１／Ａｄｍ细胞对阿霉素的敏感性明显低于７７２１细胞;（２）加热可以明显提高两种细胞对阿霉素的敏感性;（３）流式细胞检测显示加热可明显提高这两种细胞内的阿霉素的浓度,尤其是７７２１／Ａｄｍ细胞内的阿霉素浓度。结论 加热可以显提高人肝癌细胞－７７２１和耐     

热化疗对唇癌患者T淋巴细胞免疫功能的影响

目的　探讨热化疗对唇癌患者 T淋巴细胞免疫功能的影响 ,为临床热化疗治疗唇癌提供理论依据。方法　 2 0例唇癌患者给予静脉推注平阳霉素 (8mg)、甲氨蝶呤 (2 0 m g)后 ,给予 (4 2 .5± 0 .2 )℃、4 0 min微波热疗。每周两次 ,10次为一疗程。分别于第 1次热化疗前和第 10次热化疗后取患者静脉血 ,并采用 3H-胸腺嘧啶核苷 (3H-Td R)掺入法和流式细胞术分别检测热化疗前后 T淋巴细胞转化指数和 CD4 + 、CD8+ T细胞亚群的变化。结果　热化疗一个疗程结束后 ,2 0例患者肿瘤全部消退 ,皮肤、粘膜形态恢复。治疗后 T淋巴细胞转化指数高于治疗前(P<0 .0 1)。治疗后 CD4 + T细胞和 CD4 + / CD8+ 比值高于治疗前 (P<0 .0 5 ) ;CD8+ T细胞治疗后低于治疗前 ,但在统计学上无显著性差异 (P>0 .0 5 )。结论　热化疗可以增强唇癌患者 T淋巴细胞抗肿瘤免疫能力 ,这在热化疗治疗唇癌的机制中可能发挥重要作用