热疗对肿瘤免疫微环境中免疫细胞及免疫相关细胞因子的影响

随着对肿瘤热疗和肿瘤免疫微环境(TIME)的深入研究,近年来热疗对TIME的作用越来越受到学者们的重视。本文就目前国内外研究进展,对热疗与TIME中几类主要免疫细胞和免疫相关细胞因子的影响及作用机制作一综述。全面而透彻的了解热疗对TIME的调控作用,有助于为肿瘤治疗提供新的思路和方法。     

我国大陆恶性高热病例的分析

目的 分析我国大陆恶性高热（MH）病例的临床资料，探讨诊断和治疗中应注意的问题。方法 检索中国生物医学文献数据库，收集1978年1月至2004年3月报道的MH病例34例，分析其流行病学特征、发病特点、临床表现、治疗及转归。结果 我国大陆报道的MH病例以青少年居多，男性多于女性，集中在口腔科手术（尤其是唇腭裂修补术）、骨科手术和小儿外科手术（尤其是先天畸形矫治术），典型的临床表现为突然发生的高碳酸血症、体温急剧升高和骨骼肌僵直等。诊断上主要是根据临床表现，尚未建立骨骼肌体外收缩试验方法，治疗上主要是对症处理，缺乏特效药物（丹曲林）。结论 近几年我国大陆MH病例逐渐增加，应加强对MH发病机制的研究，尽快建立MH的实验诊断标准，增强预防、诊断和治疗MH的能力。     

Modulation of ryanodine-induced contractures in human skeletal muscle pretreated with dantrolene

Dantrolene seems to be the causal therapy in malignant hyperthermia (MH) crisis but the complex mechanisms of MH and dantrolene therapy are still not fully understood. The influence of dantrolene on ryanodine-induced contractures has been reported in animal studies only. In the present study 20 patients from] 7 families were tested for MH using the protocol of the European Malignant Hyperthermia Group. In addition ryanodine-induced contractures were evaluated following bolus application of 10.0 μmol · 1^-1 ryanodine. After pretreatment with 1 μimol · 1^-1 dantrolene ryanodine-provoked contractures developed significantly later in MHS (15.8±1.8 min) and MHN (46.0±4.2 min) muscle specimens than after ryanodine alone (MHS 4.8±0.7 min), (MHN 13.7±0.9 min). They were no longer observed in either group after pretreatment with 5 μimol · 1^-1 dantrolene. We conclude that dantrolene is able to attenuate ryanodine-induced contractures dose-dependendy, and therefore it is speculated that dantrolene could specifically act at the ryanodine receptor binding site.     

三维适形放疗联合肝动脉碘油栓塞化疗并热疗治疗原发性肝癌的疗效研究

目的:探讨原发性肝癌的肝动脉碘油栓塞化疗(TACE)、热疗、三维适形放疗(3DCRT)的综合治疗价值。方法:122例原发性肝癌患者进行前瞻性随机分组研究,综合治疗组64例,行TACE并3DCRT,结合热疗治疗。对照组58例3DCRT治疗,联合TACE。结果:1、2、3年生存率综合治疗组分别为85%、65%、39%,对照组分别为59%、30%、18%(P<0.05)两组毒副作用相似。结论:对于非手术切除的原发性肝癌患者,TA-CE,结合3DCRT并热疗,能明显提高疗效,而毒副作用不增加。     

Cardiac arrest after isoflurane anaesthesia in a patient with Duchenne''s muscular dystrophy

An 8-year-old boy known to have Duchenne's muscular dystrophy suffered a cardiac arrest 10 minutes after he regained consciousness after isoflurane anaesthesia for an orchidopexy procedure. Resuscitation was successful 2 hours after the start of external cardiac compression and after correction of hyperkalaemia and the administration of dantrolene. He later developed myoglobinuria elevated creatine kinase and a metabolic and respiratory acidosis. He demonstrated a delayed increase in rectal temperature.     

Development of an animal model for neuroleptic malignant syndrome: heat-exposed rabbits with haloperidol and atropine administration exhibit increased muscle activity, hyperthermia, and high serum creatine phosphokinase level

The neuroleptic malignant syndrome (NMS) is a life-threatening complication of neuroleptic treatment. To elucidate the pathogenesis of NMS, an animal model has been developed. Experimental rabbits treated with haloperidol (1 mg/kg) by intramuscular injection, were studied for the diagnostic symptoms of increased muscle rigidity, elevated body temperature, and high serum creatine phosphokinase (CPK) level. Administration of haloperidol (1 mg/kg) and atropine (0.4 mg/kg), and exposure to high ambient temperature (35°C) induced a significant increase in electromyographic activity with muscle rigidity similar to that observed in patients with NMS. Such rabbits also showed elevated body temperature and serum CPK value. In addition to the similarity of the signs and symptoms, all parameters measured (muscle rigidity, body temperature, and serum CPK level) were normalized by dantrolene treatment. The effectiveness of dantrolene in the experimental animal partially confirms the validity of this animal model for NMS. This experimental animal model for NMS may be useful to elucidate the pathogenesis of NMS.     

加热及增加细胞内氧自由基水平对恶性胶质瘤细胞生物学特性的影响

本文就加热及同时增加细胞内氧自由基水平对恶性胶质瘤细胞存活、增殖和细胞间隙连结通讯的影响做初步观察。用Ｍ．Ｔ．Ｔ法测定胶质瘤细胞存活率；用Ｋｉ－６７抗增殖细胞核抗原单克隆抗体，通过免疫组织化学ＡＢＣ染色分析胶质瘤细胞的增殖活性；用划痕染料示踪技术观察胶质瘤细胞的细胞间隙连结通讯。结果表明，Ｈ２Ｏ２和３ＡＴ能增强加热对胶质瘤细胞存活与增殖的抑制作用，促进胶质瘤细胞间隙连结通讯的改善，存在着明显的剂量和时间效应。实验结果提示，通过内外源性增加胶质瘤细胞内的氧自由基水平，将有助于强化加热治疗胶质瘤效果，并可以减少加热的剂且，降低副作用。     

加温合并药物治疗Lewis肺癌的实验研究

本实验以荷 Lewis 肺癌的 NIH 小鼠为模型,以肿瘤平均直径倍增时间(MDDT)为终点,进行加温合并抗癌药物的研究。结果表明:①43℃加温25分钟,对 Lewis 肺癌有明显的治疗效果(P<0.05);②喜树碱16mg/kg合并加温25分钟,对 Lewis 肺癌的抑制作用随加热温度升高而加强,在43℃时出现相加作用(P<0.001);③斑蝥素0.45mg/kg,高三尖杉酯碱1.2mg/kg 或消瘤芥0.75mg/kg 合并加温25分钟,对Lewis 肺癌的抑制作用随加热温度升高而增强,其中斑蝥素和消瘤芥在43℃时出现协同作用(P<0.001);①去甲斑蝥酸钠3mg/kg 对 Lewis 肺癌无治疗作用,但合并43℃加温25分钟时有协同作用;⑤鸦胆子油口服乳液8ml/kg,间隔27小时合并43℃加温25分钟,对 Lewis 肺癌的治疗有相加作用,并明显延长了荷瘤动物的生存时间。     

Demonstration of synergistic effects of hyperthermia and photodynamic therapy using the chick chorioallantoic membrane model.

The chick chorioallantoic membrane (CAM) model was used to study vascular effects of photodynamic therapy (PDT) and hyperthermia (HPT) and the synergism of these modalities. The CAM is a convenient medium for monitoring the modifications of the vasculature. It is possible to view the CAM and to examine structural changes of individual blood vessels in real time. Moreover, the CAM is a closed system which lends itself to mathematical modeling of the temporal and spatial temperature profile and in which HPT can be performed quantitatively and to a selected depth, using different lasers. A porphyrin-type photosensitizer solution was applied to areas of the CAM, defined by teflon O-rings placed on the surface. Uptake dynamics of the sensitizer into the CAM was determined by analyzing its fluorescence in vivo. The CAM area was irradiated with a dual-wavelength laser system composed of a dye laser at 644 nm (to induce PDT) and a CO2 laser at 10.6 microns (to bring about HPT). Damage to the CAM vasculature, due to combined PDT+HPT, was compared to the outcome of the separate modalities, and a synergistic effect of about 40% was observed.     

全身热疗法治疗晚期肝脏恶性肿瘤39例报告

目的 探讨全身热疗法（whole body hyperthermia，WBH）治疗肝脏恶性肿瘤的疗效及其对肝功能的影响。方法 采用WBH治疗肝脏恶性肿瘤患者39例，并对治疗前、后患者肝功能指标进行动态观察，分析该疗法对肝脏功能的影响，并通过分析治疗效果，初步评估该疗法的疗效。结果 ①WBH治疗不能手术切除的晚期肝脏恶性肿瘤患者的有效率为61．5％（24／39），60．0％（9／15）的患者AFP有不同程度下降，肿瘤疼痛缓解率达100％；存活期〉2年者占12．8％（5／39），〉1年者占59．0％（23／39），〉6个月者占76．9％（30／39）。②谷丙转氨酶于治疗后1～3d出现明显升高（P〈0．05），7d后下降并接近治疗前水平；谷草转氨酶于治疗后1d明显升高（P〈0．05），3～7d则下降并接近治疗前水平；白蛋白于治疗后1d出现下降（P〈0．05），但3d即已恢复；肝功能正常组总胆红素于治疗后第1～3d出现升高（P〈0．05），而肝功能异常组未观察到同样变化；转肽酶则无明显变化。结论 WBH能改善晚期肝脏恶性肿瘤患者的预后，提高生存质量，延长生存时间，但同时可造成患者肝功能一定程度的可逆性损害。