阿霉素化疗与热化疗对兔毛细胞白血病VX—2细胞体外作用的比较

目的 观察比较热疗,化疗,热职对体外兔ＶＸ－２细胞的生长抑制规律的影响。为临床介入性热化疗提供实验数据。方法 以体外长期培养的兔ＶＸ－２细胞为靶细胞,采用水浴加温法,进行体外细胞毒试验（ＭＴＴ法）观察单纯热疗,单纯化疗及热疗与化疗结合对兔ＶＸ－２细胞的生长抑制规律的影响及差别。结果 （１）温热和阿霉素对ＶＸ－２均有一定的抑制和杀伤作用,两者一定方式的联合具有协同或相加作用;（２）热化疗加热温度以４     

阿霉素热化疗对肝癌细胞增殖和凋亡的影响

目的：探讨阿霉素（ADM）加热化疗对人肝癌细胞HHCC及HepG2的增殖抑制和凋亡诱导作用。方法：以体外培养的人肝癌细胞HHCC和HepG2为研究对象,采用水浴加温法,观察单纯热疗,ADM化疗和热化疗对细胞增殖和凋亡的影响。MTT法确定阿霉素的工作浓度并检测细胞增殖的抑制作用,流式细胞术检测细胞凋亡。结果：热化疗组细胞的抑制率显著高于单纯热疗、单纯化疗组[HHCC细胞：（65.77±2.54）%vs（23.18±0.81）%、（38.35±2.23）%,P〈0.05。HepG2细胞：（74.25±1.53）%vs（1 7.1 2±2.8 6）%、（30.35±5.90）%,P〈0.05]。热化疗组细胞凋亡率显著高于单纯热疗组、单纯化疗组[HHCC细胞：（76.1±2.33）%vs（23.83±1.76）%、（45.57±2.81）%,P〈0.05。HepG2细胞：（76.9±2.79）%vs（19.7±7.63）%、（37.43±1.88）%,P〈0.05]。结论：加热能增强ADM对HHCC及HepG2的增殖抑制和诱导凋亡作用。     

全身热疗联合化疗治疗晚期非小细胞肺癌

目的：观察全身热疗联合化疗治疗晚期非小细胞肺癌的疗效及安全性。方法：将１５４例病理确诊的患者随机分为全身热疗联合化疗组和单用化疗组。全身热疗联合化疗组在深度镇静或全身麻醉成功后,放置食管、直肠测温探头,动态监测温度。当食管温度升到３９℃时,输注顺铂６０ｍｇ／ｍ^２;达到４１℃时,输注伊立替康５０ｍｇ／ｍ^２。热疗后第８天、第１５天继续给予伊立替康５０ｍｇ／ｍ^２化疗。单纯化疗组仅用相同方案化疗。２８天为１个周期,３周期后按ＷＨＯ标准评价疗效。结果：治疗组总有效率（ＣＲ＋ＰＲ）为６１.０４％（４７／７７）。对照组总有效率为４０.２６％（３１／７７）,两组疗效有明显差异（Ｐ＝０.０１５６）。结论：全身热疗联合化疗对晚期非小细胞肺癌有明显疗效。在深度镇静或全身麻醉下可以安全进行全身热疗。     

温热与卡铂联合对胃腺癌（SGC－7901）细胞的作用

本实验以体外培养人胃腺癌（ＳＧＣ－７９０１）细胞为实验模型，选择卡铂（ＣＢＤＣＡ）与温热４０℃、４２℃联合应用，采用先药后热、热药同时、先热后药３种方案，对细胞的生长抑制及杀伤规律进行了观察。表明：１．温热与ＣＢＤＣＡ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对细胞具有协同抑制增殖和杀伤作用。２．温热和ＣＢＤＣＡ的联合对ＳＧＣ－７９０１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４Ｏ℃作用后细胞“爆发性生长”，表明单纯加热低于４２℃是不适宜的。     

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。     

热、化疗联合治疗晚期非小细胞肺癌的疗效观察

目的：观察异长春花碱（NVB），顺铂（DDP）静脉化疗与热疗联合治疗晚期非小细胞肺癌的疗效。方法：44例晚期非小细胞肺癌患者随机分为两组，单纯化疗组（22例）仅予常规NP方案化疗，28天为一周期，完成2周期，热化疗组22例使用NP方案化疗联合射频热疗，每周热疗2次，共12次。结果：热化疗组PR9例，有效率41％，单纯化疗组PR6例，有效率27％，两组生活质量改善情况差异有显著性（P〈0．05），毒副反应相似，主要毒性为骨髓抑制以及胃肠道反应。结论：NP方案联合热疗治疗晚期非小细胞肺癌方便、安全，近期疗效较好。     

热化疗对小鼠移植性Ｓ１８０肉瘤细胞凋亡、增殖及血管生成的影响

目的　探讨热疗联合化疗对小鼠Ｓ１８０肉瘤模型细胞凋亡、增殖及血管生成的影响。方法　建立荷瘤小鼠模型,随机分为对照组、化疗组、热疗组和热化疗组,化疗组予以平阳霉素０.２ｍｇ／只,热疗组予以（４３±０.２）℃水浴１ｈ,热化疗组同时予以化疗＋热疗,每４天１次,重复３次。治疗结束后,取瘤体,测瘤重,计算抑瘤率,流式细胞仪测定肿瘤细胞周期、凋亡率及增殖细胞核抗原（ＰＣＮＡ）蛋白含量,ＲＴ-ＰＣＲ检测血管内皮生长因子（ＶＥＧＦ）ｍＲＮＡ、ＰＣＮＡｍＲＮＡ,免疫组化法检测ＶＥＧＦ蛋白,计数微血管密度（ＭＶＤ）值。结果　Ｓ期细胞对热疗最敏感。化疗组、热疗组和热化疗组均可抑制小鼠Ｓ１８０肉瘤的生长,细胞凋亡率均较对照组高（Ｐ＜０.０５）,ＰＣＮＡ、ＶＥＧＦ蛋白表达和ＭＶＤ均较对照组降低（Ｐ＜０.０５）,其中热化疗组变化最显著（Ｐ＜０.０５）。ＲＴ-ＰＣＲ检测ＶＥＧＦｍＲＮＡ、ＰＣＮＡｍＲＮＡ亦得到上述同样结果。直线相关性分析示,ＶＥＧＦ蛋白表达与ＭＶＤ呈正相关（ｒ＝０.９１５,Ｐ＜０.０１）。结论　热疗可以诱导Ｓ１８０细胞凋亡,抑制ＰＣＮＡ、ＶＥＧＦ表达,使ＭＶＤ下降。热疗与化疗联合具有协同作用,显著提高对Ｓ１８０肉瘤的疗效。     

高剂量化疗对小细胞肺癌治疗的分析（附6例长期随访的结果）

目的：研究病理明确诊断的小细胞肺癌采用自体外周血干血细胞移植支持下的高剂量化疗的疗效。方法：６例患者选自常用化疗达到ＣＲ、ＰＲ或手术切除原发灶的小细胞肺癌，对其采用自体外周血干细胞移植支持下的高剂量环磷酰胺（ＣＴＸ）、足叶乙甙（ＶＰ－１６）、卡铂（ＣＢＰ）的化疗（ＣＴＸ ６０００ｍｇ／ｍ＾２，ＶＰ－１６１２００ｍｇ／ｍ＾２，ＣＢＰ １２００ｍｇ／ｍ＾２），其中５例进行了化疗后的局部放疗，并进行了长     

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ＳＧＣ－７９０１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     

多西紫杉醇用于肿瘤热化疗的体外研究

目的：研究不同剂量的多烯紫杉醇（docetaxel，DTX）联合不同温度的热疗对两种肝癌细胞（HepG2、BEL-7402）的体外毒性，探讨热疗对化疗是否具有协同增敏效应，为肝肿瘤的热化疗提供理论依据。方法：CCK-8法测定不同浓度DTX对细胞的毒性作用，SPSS17．0软件分析DTX作用于两种细胞的Ic50值，并进一步研究温度对两种细胞IC50值的影响，Veleriote法分析该药物浓度下的热化疗是否存在协同增敏效应。结果iDTX对HepG2和BEL-7402的IC50值分别为0．152ug／ml和0．563ug／ml。热疗可有效抑制两种细胞的生存率，热化疗联合处理可显著降低两种细胞的存活率，且该综合治疗方法在一定温度下存在协同增敏效应。结论：HepG2和BEL-7402两种细胞对DTX均很敏感，其IC50值的不同提示了临床上个性化治疗的重要性。热疗联合DTX的综合治疗明显优于单一治疗，热化疗的协同增敏效应呈温度依赖性。     

ADYNAMIC STUDY OF THE CYTOTOXICEFFECTS OF HYPERTHERMIA COMBINED WITH CIS－DIAMINE DICHLOROLPLATINUM（DDP） ON HUMAN GASTRIC CANC

ＡＤＹＮＡＭＩＣＳＴＵＤＹＯＦＴＨＥＣＹＴＯＴＯＸＩＣＥＦＦＥＣＴＳＯＦＨＹＰＥＲＴＨＥＲＭＩＡＣＯＭＢＩＮＥＤＷＩＴＨＣＩＳ－ＤＩＡＭＩＮＥＤＩＣＨＬＯＲＯＬＰＬＡＴＩＮＵＭ（ＤＤＰ）ＯＮＨＵＭＡＮＧＡＳＴＲＩＣＣＡＮＣＥＲＣＥＬＬＬＩＮＥＳＭＫＮ...     

阿霉素加热化疗对抗人肝癌耐药细胞多药耐药性的实验研究

 目的　观察比较阿霉素 ( ADM)化疗与 43℃加热化疗对耐药人肝癌细胞模型 - 772 1 /Adm(以下简称 772 1 /Adm细胞 )的敏感性及细胞内药物浓度的影响。方法　以人肝癌细胞模型 -772 1 /Adm为研究对象 ,采用水浴加温法、体外细胞毒试验 ( MTT法 )、流式细胞技术 ,观察阿霉素( ADM)化疗与加热化疗后细胞的存活率及细胞内阿霉素浓度的变化。结果　 ( 1 )阿霉素化疗、加热化疗 30、60 min后 772 1 /Adm细胞存活率分别为 70 .2 %、40 .8%和 60 .2 %、37.4% ;( 2 )流式细胞仪检测显示阿霉素化疗、加热化疗 30 min后细胞内阿霉素浓度分别为 41 .3%、92 .0 %。结论　加热可以显著对抗 772 1 /Adm的耐药性 ,提高其对阿霉素的敏感性 ,这与加热提高了细胞内药物浓度有关。     

热疗联合足叶乙甙对K562 体外抑制效应及bcl-2 的表达

 目的 观察热疗联合足叶乙甙增强对K562的体外增殖的抑制作用及对其凋亡、bcl-2表达的影响。方法 采用MTT法测定确定VP16的工作浓度，以该浓度进行化疗或与热疗的联合，选择温度40℃、42℃，体外作用于K562。48小时及作用前均采用台盼蓝拒染法检测肿瘤细胞的存活率；MTT法检测对肿瘤细胞增殖的抑制作用；流式细胞仪检测作用后肿瘤细胞的凋亡及bcl-2的表达。观察热疗联合足叶乙甙的抗肿瘤作用。结果 以作用48小时IC50的值作为实验的工作浓度。单纯40℃、42℃热疗60分钟在48小时对K562细胞系有抑制作用（P〈0．01），并随温度增高而增强；单纯化疗对K562细胞系也有明显抑制作用（P〈0．01）；热化疗组在40℃、42℃温度下，对K562均有显著的抑制作用（P〈0．01），随着温度的增高而增强。热疗组、化疗组、热化疗组细胞凋亡率均较对照组显著升高，各组之间均有显著性差异（P〈0．01）；bcl-2蛋白的表达下降，各组之间也有显著性差异（P〈0．01）。结论 热疗联合足叶乙甙能增强对K562细胞的体外抑制作用；热化疗联合应用可以提高肿瘤细胞的凋亡率，下调bcl-2的表达。     

局部热化疗对鼠胶质瘤肿瘤细胞凋亡及其耐药的研究

 目的　探讨局部热化疗对大鼠胶质瘤凋亡、耐药和肿瘤微血管的作用。方法　将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、化疗和热化疗。观察皮下肿瘤生长情况 ;用S P免疫组化法检测bax、bcl 2和 p gp蛋白表达 ;用HE染色法、电镜、TUNWL法观察凋亡 ;电镜观察肿瘤微血管的变化。结果　热疗、化疗、热化疗组较对照组瘤体缩小 ,瘤重减轻 (P <0 .0 0 1 ) ;bax蛋白表达增强 (P <0 .0 0 1 ) ,且热化疗组较单纯热疗和化疗组均增强 (P <0 .0 0 1 ) ;bcl 2蛋白表达改变不明显 (P >0 .0 5 ) ;化疗组 p gp表达增强 (P <0 .0 0 1 ) ,热疗和热化疗组 p gp表达减弱 (P <0 .0 0 1 ) ;细胞凋亡指数增大 (P<0 .0 0 1 ) ;热化疗组出现核染色质凝聚 ,凋亡小体 ;肿瘤微血管外径变小 ,管壁变厚 ,血管减少 ,有的血管甚至只能发现完整的基膜而缺乏内皮细胞。结论　 (1 )热疗化疗、热化疗能抑制肿瘤增殖 ,促进bax蛋白表达 ,使bcl 2 /bax减小 ,诱导细胞凋亡 ,且热...     

Optimizing the factors which modify thermal enhancement of melphalan in a spontaneous murine tumor

Background: Hyperthermia enhances the cytotoxicity of some chemotherapeutic agents. Both clinical and laboratory studies suggest melphalan may be an important drug when hyperthermia is added to chemotherapy treatments. Factors that may modify the thermal enhancement of melphalan were studied to optimize its clinical use with hyperthermia. Methods: The tumor studied was an early-generation isotransplant of a spontaneous C3Hf/Sed mouse fibrosarcoma, Fsa-II. All studies were performed under supervision of the Animal Care and Use Committee. Hyperthermia was administered by immersing the tumor-bearing foot into a constant temperature water bath. Four factors were studied: duration of hyperthermia, sequencing of hyperthermia and melphalan, intensity of hyperthermia, and tumor size. To study duration of hyperthermia tumors were treated at 41.5°C for 30 or 90 min immediately after intraperitoneal administration of melphalan. For sequencing of hyperthermia and melphalan, animals received hyperthermia treatment of tumors for 30 min at 41.5°C immediately after drug administration, both immediately and 3 h after administration of drug or only at 3 h after administration of drug. Intensity of hyperthermia was studied using heat treatment of tumors for 30 min at 41.5 or 43.5°C immediately following drug administration. Effect of tumor size was studied by delaying experiments until three times the tumor volume (113 mm³) was observed. Treatment of tumors was for 30 min at 41.5°C immediately following drug administration. Tumor response was studied by the mean tumor growth time. Results: Hyperthermia in the absence of melphalan had a small but significant effect on tumor growth time at 43.5°C but not at 41.5°C. Hyperthermia at 41.5°C immediately after melphalan administration doubled mean tumor growth time at 30 min and caused a threefold increase at 90 min (P=0.0002) when compared to tumors treated with melphalan alone at room temperature. Application of hyperthermia for one-half hour immediately following drug administration was the most effective in delaying tumor growth. No significant difference in mean tumor growth time was observed with an increase in temperature from 41.5 to 43.5°C. For large tumors heat alone and melphalan alone caused a moderate increase in tumor growth delay. These effects in large tumors were greatly increased by a combination of chemotherapy and hyperthermia. Conclusions: From our data it would appear that the administration of intraperitoneal melphalan immediately prior to 90 min of heat at 41.5°C may optimize anti-neoplastic activity. These data may be useful in formulating clinical protocols in which melphalan and heat are combined.     

In vitro and in vivo responses of doxorubicin ion exchange microspheres to hyperthermia.

The utility of microspheres as targeted drug delivery agents is addressed with reference to using heat during formulation and to administration in combination with hyperthermia. It was demonstrated that rate of loading of the drug doxorubicin onto resin microspheres is enhanced under conditions of elevated temperature but this was shown to increase the incidence of microsphere aggregation. Total amount of drug loaded was related to time rather than temperature such that low temperature loading for up to 24 h produced optimum quality injectates. However, release of doxorubicin from microspheres was significantly increased during elevations of temperature to 43 degrees C. Thus, during hyperthermia doxorubicin release can be increased to provide periods of high drug availability targeted to tumour tissue for concomitant thermochemotherapy with microspheres. The therapeutic benefit derived from this combined therapy was assessed in 20 rabbits with VX2 carcinoma implanted in the liver. Hyperthermia was delivered by 2450 MHz microwave applicator to the exteriorized liver at 43 degrees C for 30 min, while chemotherapy was administered by intratumoural injection of doxorubicin microspheres (2.3 mg) into each tumour. Both hyperthermia and chemotherapy alone significantly reduced the size of tumours 10 days following treatment (p less than 0.01). However, in animals treated with both modalities, the size of tumours was significantly less than either treatment alone (p less than 0.05). These results provide a strong rationale for combining hyperthermia with targeted chemotherapy using microspheres.     

The selective inhibitory effect of hyperthermia on the metabolism and growth of malignant cells

Hyperthermia (42° C.) exerted an inhibitory effect on the O₂ uptake of rabbit VX2 carcinoma cells in vitro, and led to a decrease in viability and growth potential of the cells, as measured by their ability to produce tumours in rabbits. Anaerobic glycolysis of the tumour cells was unaltered by hyperthermia. Respiration and anaerobic glycolysis of normal rabbit liver, kidney and red blood cells were unaffected by the elevated temperature. Local heat was applied to established VX2 tumours in vivo, with a subsequent reduction in tumour size in all cases, the most effective therapy regime being 3 one-hour applications of heat within the mean cell generation time of the tumour. Following heating there was rapid and widespread tumour cell necrosis and lysis, with subsequent replacement of the tumour architecture by connective tissue. There was a prolongation of survival time in 50% of the treated animals, which are still alive 18 months after therapy; all the control animals died within 10 weeks. The selective inhibitory effects of hyperthermia on cancer cells, and its application to human neoplasms, are discussed.     

Reversing adriamycin resistance of human breast cancer cells by hyperthermia combined with Interferon alpha and Verapamil

One of the major obstacles related to chemotherapy is resistance against anticancer drugs, including Adriamycin (ADM). The purpose of the present work is to investigate the reversal effects on ADM resistance by hyperthermia (42.5 degrees C) combined with two reversal agents (Interferon alpha and Verapamil) in MCF-7/ADR (ADM-resistant MCF-7 breast cancer cell line), and its relevant molecular mechanism of action. The cell survival rate and ADM IC50 of different experiment groups were measured by MTT test. The quantitative expression of MDR1 gene in cells was detected by Real-time PCR, and the expression of P-glycoprotein (P-gp) on the cells surface and the intracellular ADM accumulation was detected by flow cytometry (FCM). The ADM IC50 of the MCF-7/ADR cells decreased 830-fold after combined with Interferon alpha (IFN-alpha) and Verapamil (VRP). Although there was no distinction in the mRNA expression of MDR1, the P-gp on the MCF-7/ADR cell membrane was significantly reduced and the cellular ADM uptake increased markedly as compared to pretreatment. Our results suggeste that hyperthermia induces a considerably reversal activity against ADM resistance synergizing other reversal agents (IFN-alpha and VRP). The reversal mechanism needs further study. However, these features of hyperthermia may be exploited in clinical cancer chemotherapy.     

Cytotoxicity of perillyl alcohol against cancer cells is potentiated by hyperthermia

PURPOSE: Perillyl alcohol (POH) (4-isopropenyl-cyclohexenecarbinol) is a member of the monoterpenes, which are present in various fruits and vegetables. POH has been demonstrated to be cytotoxic against a variety of experimental cancer cells in vitro and in vivo. Phase I clinical trials have indicated that POH may be useful for human tumor treatment. The purpose of our study was to reveal whether the anticancer effect of POH could be enhanced by hyperthermia. METHODS AND MATERIALS: SCK mammary carcinoma cells of A/J mice were used. The effects of POH or hyperthermia alone were studied by incubating the cells during exponential growth phase in culture with 0.25-1.0 mM of POH at 37 degrees C for varying lengths of time or heating cells at 41-43 degrees C for varying lengths of time. The combined effect of POH and hyperthermia was investigated by heating the cells with 1 mM of POH at 41-43 degrees C for varying lengths of time. The effects of the treatments were evaluated using the clonogenic cell survival assay and three types of apoptosis assays. RESULTS: An incubation of SCK cells with 1 mM of POH at 37 degrees C for 60 min or hyperthermia at 43 degrees C for 1 h decreased clonogenic cell survival to 40% and 60%, respectively. When the cells were heated at 43 degrees C for 1 h in the presence of 1 mM of POH, clonogenic cell survival decreased to 0.2%, indicating that hyperthermia potentiated the effect of POH to cause clonogenic cell death. Hyperthermia also markedly increased the degree of POH-induced apoptosis. CONCLUSION: Hyperthermia synergistically potentiates the cytotoxicity of naturally occurring POH against cancer cells.     

高温联合顺铂及多西他赛对肺腺癌A549细胞体外作用的研究

目的：研究高温联合顺铂（DDP）及多西他赛（TXT）对肺腺癌细胞株A549的体外作用。方法：不同处理因素作用于A549细胞后,应用四氮唑盐比色法（MTT法）测定细胞增殖情况,根据Veleriote法判断高温联合化疗药的作用效果;通过两药相互作用指数判断药物联合作用效果;流式细胞仪检测不同处理后细胞凋亡情况;光学显微镜及荧光显微镜观察细胞形态学变化。结果：高温和化疗药单独作用均对A549有生长抑制作用（P〈0．05）;化疗药有剂量依赖关系;高温有温度依赖关系;高温与药物联合对细胞生长抑制作用强于单独高温组或单独化疗组（P〈0．01）;DDP与高温联合为协同作用;TXT与高温联合为次加作用;DDP和rr）（T联合作用对细胞生长抑制为协同作用;42℃、DDP2μg/ml和TXT1IXg／ml三者联合凋亡率明显高于其他处理组（P〈0．01）;普通光镜和荧光显微镜下42％、DDP2μg/ml和TXT1μg/ml三者联合凋亡细胞数较对照组和42℃组明显增多,细胞形态学变化明显。结论：DDP、TXT、高温三者体外联合作用对A549有明显的生长抑制和诱导凋亡作用。