Hypoxia-regulated p53 and its effect on radiosensitivity in cancer cells

Purpose: To determine the response of tumor suppressor p53 to hypoxia in different tumor cell lines and the involvement of p53 activity regulation in the effect of hypoxia on tumor cell sensitivity to radiation and hyperthermia.

Materials and methods: Three tumor cell lines with functional p53 were treated with chronic or cyclic hypoxia followed by radiation or hyperthermia to investigate p53 activity and cell survival. Flow cytometry was used to investigate the effect of hypoxia-induced cell cycle arrest on radiosensitivity in KHT-C (mouse fibrosarcoma) cells. Transient transfection was performed to determine the role of altered p53 activity in KHT-C and SCC VII (mouse squamous-cell carcinoma) radiosensitivity.

Results: Aerobic radiosensitivity was decreased in KHT-C and SCC VII cells after in vitro chronic or cyclic hypoxia pretreatment, but in HT1080 cells, it was slightly increased after chronic hypoxia, and was unchanged after acute hypoxia pretreatment. Decreased radiosensitivity in hypoxia-pretreated KHT-C and SCC VII cells was unlikely due to hypoxia-induced cell cycle arrest, but rather seemed to be associated with increased expression of Mdm2 (mouse double minute-2) and decreased p53. Furthermore, hypoxia pretreatment inhibited the activation of p53 by radiation. Similar results were observed in hyperthermia treated KHT-C cells. Finally, decreased radiosensitivity was observed in both KHT-C and SCC VII cells transiently transfected with Mdm2 or anti-sense p53 cDNA.

Conclusion: We demonstrated that hypoxia may decrease tumor cell radiosensitivity through the suppression of p53 activity in some tumor cell lines. These results suggested the response of p53 to hypoxia can be cell type specific and contribute to radiosensitivity of hypoxic cells.     

鼻内镜下或间接喉镜下微波热凝术治疗声带息肉声带小结

目的探讨间接喉镜下或鼻内镜下微波热凝治疗声带息肉或小结的效果。方法对321例在间接喉镜或鼻内镜下微波热凝治疗声带息肉或小结病例资料进行分析。结果321例患者均一次手术成功。术后随诊3个月～一年以上的321例患者,治愈率92%,好转率8%。无效率为0。术中和术后未发生并发症。结论间接喉镜下或鼻内镜下微波热凝治疗声带息肉声带小结,具有操作安全、方便、不出血、快捷、简单、治愈率高等优点。     

胃肠道癌术后腹腔持续热灌注化疗

[目的]探讨腹腔持续热灌注化疗治疗胃肠道癌的近期疗效。[方法]162例住院病人随机分为治疗组及对照组,治疗组病人腹腔持续热灌庄化疗,对照组病人作常规静脉化疗。[结果]治疗组1年生存率为38.9％,对照组为23.6％（P<0.05）。毒副作用以白细胞下降、胃肠道反应及肝肾功能损害为主,治疗组明显低于对照组。[结论]胃肠道癌术后行腹腔持续热灌注化疗副作用小,1年生存率高。     

Predictive factors for skin reactions in patients treated with thermoradiotherapy

In this study we performed univariate analyses to analyse the predictive factors for skin reactions, i.e. erythema, thermal blisters and ulceration, that occur during thermoradiotherapy. One hundred and twenty-six fields in 126 patients were treated with thermoradiotherapy using 915 MHz external microwave hyperthermia. Mean age of patients was 62 years. All but 11 lesions received previous therapy. Prior treatment included surgery (75%), chemotherapy (60%) and/or radiation therapy (51%). The mean previous radiation dose was 54 ± 2 Gy. The concurrent tumour radiation dose was 45 ± 1 Gy, in 16 fractions, over 35 elapsed days (dose per fraction of 1·6–4·8 Gy). The mean number of heat sessions administered was 5·5 ± 0·2 (range 1–14). In 83% of cases hyperthermia was administered biweekly. Forty-two patients were treated without any skin reaction (33%), erythema occurred in 59 fields (47%), transient thermal blisters occurred in 25 fields (20%) and ulceration occurred in 23 fields (18%). In 25 cases, two or more skin reactions (20%) were observed concurrently. Concurrent radiation dose correlated with skin reactions (p = 0·02). The incidence of skin reactions was inversely correlated with previous radiation therapy (p = 0·04) and previous radiation therapy dose (p = 0·04) possibly due to fibrosis. None of the tumour or skin thermal parameters correlated with the reaction rate.     

Thermal therapy of pancreatic tumours using endoluminal ultrasound: Parametric and patient-specific modelling

Purpose: The aim of this study is to investigate endoluminal ultrasound applicator configurations for volumetric thermal ablation and hyperthermia of pancreatic tumours using 3D acoustic and biothermal finite element models. Materials and methods: Parametric studies compared endoluminal heating performance for varying applicator transducer configurations (planar, curvilinear-focused, or radial-diverging), frequencies (1–5 MHz), and anatomical conditions. Patient-specific pancreatic head and body tumour models were used to evaluate feasibility of generating hyperthermia and thermal ablation using an applicator positioned in the duodenal or stomach lumen. Temperature and thermal dose were calculated to define ablation (>?240 EM_43?°C) and moderate hyperthermia (40–45?°C) boundaries, and to assess sparing of sensitive tissues. Proportional-integral control was incorporated to regulate maximum temperature to 70–80?°C for ablation and 45?°C for hyperthermia in target regions.

Results: Parametric studies indicated that 1–3 MHz planar transducers are the most suitable for volumetric ablation, producing 5–8?cm³ lesion volumes for a stationary 5-min sonication. Curvilinear-focused geometries produce more localised ablation to 20–45?mm depth from the GI tract and enhance thermal sparing (T_max?<?42?°C) of the luminal wall. Patient anatomy simulations show feasibility in ablating 60.1–92.9% of head/body tumour volumes (4.3–37.2?cm³) with dose?<?15 EM_43?°C in the luminal wall for 18–48 min treatment durations, using 1–3 applicator placements in GI lumen. For hyperthermia, planar and radial-diverging transducers could maintain up to 8?cm³ and 15?cm³ of tissue, respectively, between 40–45?°C for a single applicator placement. Conclusions: Modelling studies indicate the feasibility of endoluminal ultrasound for volumetric thermal ablation or hyperthermia treatment of pancreatic tumour tissue.     

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.     

Rapid cooling in classic heatstroke: Effect on mortality rates

The case records of 39 patients with classic (non-exertional) heatstroke presenting to an urban emergency department were reviewed. Eight of 39 patients died. Rapid cooling, defined as a rectal temperature of less than or equal to 38.9 degrees C (102 degrees F) within an hour of presentation, was achieved in 27 of 39 patients. Twelve patients had a temperature greater than or equal to 38.9 degrees C (102 degrees F) after one hour of treatment in the emergency department. The rate of mortality in the rapid cooling group was four of 27 (15%), while in the delayed cooling group, the mortality rate was four of 12 (33%) (P = 0.18). Factors such as advanced age, hypotension, altered coagulation status, and the necessity for endotracheal intubation on presentation dictated a poor outcome despite successful cooling measures.     

聚焦热疗联合动脉灌注化疗治疗晚期胰腺癌的临床观察

目的观察聚焦热疗联合动脉灌注化疗治疗晚期胰腺癌的临床疗效。方法将25例晚期胰腺癌患者随机分为治疗组13例和对照组12例。治疗组采用BSD2000相控阵聚焦热疗联合动脉灌注化疗治疗,对照组予单纯动脉灌注化疗治疗。观察2组病灶变化情况,临床受益反应（CBR）、生存率及不良反应情况。结果治疗组肿瘤灶变化总有效率为30．8％高于对照组的16．1％,差异有统计学意义（P〈0．05）。治疗组CBR有效率为53．8％高于对照组的33．3％,差异有统计学意义（P〈0．05）。2组生存率及不良反应差异无统计学意义（P〉0．05）。结论热疗联合动脉灌注化疗治疗晚期胰腺癌能提高近期有效率及患者生活质量,值得临床推广应用。     

中低温度热疗诱导骨肉瘤细胞株凋亡

目的:研究加热诱导成骨肉瘤细胞株(OS-9901)凋亡,为中低温度热疗辅助成骨肉瘤综合治疗提供理论依据. 方法:成骨肉瘤OS-9901细胞株分别经不同温度的热疗作用1 h,用TUNEL法染色及计数、透射电子显微镜观察其对骨肉瘤细胞株的诱导凋亡作用. 同时通过免疫组织化学染色,观察43℃ 1 h热疗对成骨肉瘤细胞株OS-9901的Bcl-2蛋白表达的影响. 结果:43℃作用1 h的成骨肉瘤细胞株继续培养6 h后出现大量异常细胞,透射电镜观察可见有典型的细胞凋亡特征性形态改变. TUNEL法染色后通过计数可见有42%的细胞凋亡比例. 免疫组织化学显示,43℃作用1 h的成骨肉瘤细胞株6 h后Bcl-2蛋白的表达明显减少. 结论:43℃作用1 h可以诱导成骨肉瘤细胞株OS-9901凋亡. 加热后成骨肉瘤细胞Bcl-2表达减少,从而进一步诱导发生细胞凋亡,为热疗诱导肿瘤细胞凋亡的机制提供了部分理论依据.     

高温、亚低温对大鼠脑缺血再灌注损伤的作用及其机制研究

目的：研究轻度高温、亚低温对大鼠脑缺血再灌注损伤组织兴奋性氨基酸（EAA）与氧自由基的相互关系及病理损伤程度的影响。方法：60只Wistar大鼠按不同脑温条件随机分为生化组（n=28）和病理组（n=32)，采用改良Nagasawa局灶脑缺血再灌注模型，观察脑缺血再灌注损伤组织谷氨酸（Glu），超氧化物歧化酶（SOD）、丙二醛（MDA）的变化及光镜，电镜下的病理变化。结果：轻度高温明显加重常温脑缺血再灌注损伤组织Glu、MDA的升高（P＜0．01）及SOD的下降（P＜0．05），加重常温脑缺血再灌注组织病理损伤程度，亚低温的作用则相反，结论：轻度高温可能通过同时促进EAA合成，释放和氧自由基生成系统活化，造成大鼠脑缺血再灌注损组织损伤加重；亚低温可能通过同时抑制EAA合成，释放和氧自由基生成系统活化，减轻大鼠脑缺血再灌注组织损伤程度，对大鼠脑缺血再灌注损伤组织起保护作用。