放疗同步健择与顺铂化疗对大鼠脊髓损伤的实验研究

目的:探讨放射治疗同步顺铂(DDP)和健择(GEM)化疗对大鼠脊髓损伤的影响.方法:观察正常对照组、单纯放疗组、单纯化疗组(健择组、顺铂+健择组)与放疗联合化疗组(健择联合放疗组、顺铂+健择联合放疗组)的光镜和电镜下脊髓的形态学改变.结果:光镜下,单化组灰质出现白质部分脱髓鞘、变性、炎性细胞浸润,灰质结构疏松和血管增多,排列紊乱.单放组白质内神经纤维排列松散紊乱,部分白质出现细胞肿胀、坏死和炎细胞浸润,部分神经元尼氏体消失,神经胶质细胞固缩.化放组白质出现广泛脱髓鞘、炎细胞浸润、灰质血管增多和神经元固缩等改变.电镜下单化组脊髓髓鞘的髓板增厚、扭曲和皱缩;单放组髓鞘的板层结构松解、扭曲;化放组髓鞘轴索皱缩,髓鞘不规则分层且不规则增生,板层结构不明显.结论:不论健择单药还是健择和顺铂联合化疗均可引起大鼠脊髓损伤,放射治疗同步顺铂和健择化疗较单纯放疗加重对大鼠的脊髓损伤.     

放疗同步多西他赛化疗治疗晚期非小细胞肺癌的临床观察

目的:研究放疗同步多西他赛化疗对晚期非小细胞肺癌的疗效及毒副作用。方法:74例Ⅲ期非小细胞肺癌患者被随机分为两组,放疗同步多西他赛化疗组(放化组),单纯放疗组(单放组);两组放疗方法相同,放疗肿瘤量DT60Gy～65Gy,每次2Gy,每周5次,放化组在放疗同时每周予多西他赛40mg化疗一次。结果:放化组和单放组的有效率分别是81.1%和75.7%(P>0.05),两组的完全缓解率是32.4%和10.8%(P<0.05),放射性肺炎及食管炎发生率放化组高于单放组(P<0.05)。结论:放疗同步多西他赛化疗治疗晚期非小细胞肺癌疗效好,副反应虽增加,但能耐受。     

多西他赛和吉西他滨协同放疗增敏对老年非小细胞肺癌近期疗效观察

目的 观察三维适形放疗分别联合多西他赛、吉西他滨治疗老年非小细胞肺癌的疗效及不良反应.方法 将106例经病理学或细胞学证实的老年非小细胞肺癌患者随机分为多西他赛组和吉西他滨组;所有入组患者均先给予2个周期诱导化疗,多西他赛20～25mg/m2,dl、8、15、28大重复;吉西他滨800mg/m2,d1、8、15、28天...     

周剂量多西他赛同步三维适形放疗治疗Ⅲ期非小细胞肺癌临床观察

目的:观察多西他赛每周方案同步三维适形放疗治疗Ⅲ期非小细胞肺癌的疗效及并发症.方法:57例经细胞学或组织学证实的非小细胞肺癌给予多西他赛每周方案化疗同步三维适形放疗,多西他赛35mg/m2,静滴,每周1次,共4次～6次.放疗采用6Mv-X线或15Mv-X线适形累及野照射,常规分割,照射剂量60Gy～64Gy.结果:57例全部完成治疗,全组总有效率为63.2%,其中ⅢA期为66.7%,ⅢB期为57.1%.主要的毒副反应为骨髓抑制.Ⅲ度～Ⅳ度发生率为19.3%,放射性食管炎31.6%,放射性肺炎21.1%等.经过处理后缓解.结论:周剂量多西他赛同步三维适形放疗治疗Ⅲ期非小细胞肺癌,近期疗效满意,毒副反应可耐受.     

低剂量每周一次多西他赛同步放疗治疗食管癌的临床疗效

目的探讨低剂量多西他赛每周一次同步放射治疗食管癌的临床疗效。方法86例食管癌患者随机分为放化组45例和单放组41例。两组均行前程普通放疗加后程适形放疗。前程普通放疗采用三野等中心照射,剂量DT40Gy/20次,后程适形放疗剂量DT26～30Gy/13～15次,总剂量DT66～70Gy/33～35次,6.5～7周完成。放化组在放疗同期行多西他赛化疗,20mg/次,1次/周,总量为120～140mg/6～7次;同时给一定的对症支持治疗等。治疗前及治疗后行上消化道造影、胸部CT,腹部B超等检查,以评价疗效。结果放化组总有效率（CR＋PR）为86.7%,单放组总有效率为68.3%,两组差异具有统计学意义（P〈0.05）;放化组骨髓抑制毒副反应较单放组增加,但经处理后均能顺利完成治疗;两组1年总生存率分别为88.9%和65.8%（P〈0.05）。结论低剂量每周一次多西他赛联合放疗能提高食管癌的近期疗效,毒副反应患者均能耐受。     

脑活素对脊髓的放射防护作用的实验研究

目的 观察脑活素对脊髓的放射防护作用。方法 将Wister品系大白鼠随机分为实验组、对照组、空白组。前两组设脊髓照射野进行~(60)Co—r线外照射,每次400cGy,隔日一次,三次/周,最后一次200cGy,共50Gy/13次。实验组腹腔注射脑活素0.36ml。对照组给予相同量的生理盐水,均于放疗前30分注射。照射后15天,行活体灌注固定,取材,进行光镜及电镜观察。结果 各组动物标本在光镜下改变轻微。电镜下:各组间存在显著差异(P<0.01),实验组放射损伤明显轻于对照组(P<0.05),实验组与空白组间无显著差异。结论 脑活素对脊髓具有明显的放射防护作用。     

吉西他滨和顺铂联合化疗对大鼠脊髓损伤的实验研究

目的观察吉西他滨和顺铂对脊髓损伤的影响,为放化同步治疗减低毒副作用提供理论依据。方法通过大鼠腹腔注射化疗药物,吉西他滨30mg／kg、顺铂5mg／kg,两药间隔时间为30分钟。自然饲养20周。通过光镜、电镜观察脊髓的形态学改变;免疫组化方法检测引起脊髓损伤凋亡基因Bax及caspase-3蛋白的表达。结果吉西他滨或吉西他滨联合顺铂均可引起脊髓的损伤,吉西他滨联合顺铂对脊髓的损伤要重于单用吉西他滨。HE染色表现为白质近中央管处脱髓鞘、变性、炎性细胞浸润,灰质结构疏松、血管增多;超微结构显示白质内部分有髓神经纤维脱髓鞘改变,髓板增厚、扭曲、皱缩。其凋亡基因Bax及caspase-3在脊髓损伤各组均有过表达,且联合治疗组明显高于单药组（P〈0．05）。结论不论吉西他滨单药还是吉西他滨联合顺铂均能引起脊髓损伤,其损伤机制与凋亡相关基因Bax,caspase-3蛋白过表达有关。     

不同剂量X线大分割照射对大鼠小肠的近期生物学效应

目的观察腹部大分割照射后大鼠小肠的形态学变化,并检测细胞凋亡基因Bax、Bcl-2的表达情况。方法将80只大鼠随机分为5组：空白对照组（0 Gy）;4 Gy组（连续照射5次,每天1次）;6 Gy组（照射3次,隔天1次）;8 Gy组（照射2次,一周2次）;12 Gy组（照射1次）;各组于照射后第1、3、5、7天分别断头处死4只,取空肠组织,进行HE染色及免疫组化染色,光镜下观察病理变化,并检测Bax和Bcl-2的表达情况。结果与空白对照组比较,12 Gy、8 Gy照射组大鼠小肠黏膜损伤最重,4 Gy照射组次之,6 Gy照射组损伤较轻;所有照射组小肠Bax和Bcl-2基因表达水平均下降,与空白对照组相比有显著统计学差异（P〈0.001）,而不同照射剂量组间比较无统计学差异（P=0.101）。结论采用等效生物剂量为32 Gy的不同分割方式照射大鼠小肠后,小肠黏膜均出现不同程度损伤,而细胞凋亡基因Bax、Bcl-2表达水平均出现下降。     

康莱特联合多西他赛治疗晚期复发非小细胞肺癌的临床观察

目的观察康莱特联合多西他赛(多西紫杉醇)治疗晚期复发非小细胞肺癌患者的疗效及其对生活质量的影响。方法对82例有病理或细胞学诊断并有可测量病灶、多程化疗后复发的晚期非小细胞肺癌(NSCLC)患者采用完全随机分组的方法,分为康莱特联合多西他赛组41例(康莱特注射液100ml,每日一次静点,连用10～20天,多西他赛35mgm2静脉滴注,第1,8天,21天为1周期,平均2周期),多西他赛单药组41例(多西他赛用法同前)。结果康莱特联合多西他赛组和多西他赛单药组有效率分别为17.1%和12.2%(P>0.05);临床受益率(CR PR SD)康莱特联合多西他赛组高于多西他赛单药组(82.9%vs63.4%),且有显著性差异(P<0.05)。二组的中位生存期分别为10.5个月和9.8个月,无显著性差异。康莱特联合多西他赛组病人化疗时生活质量优于多西他赛单药组,Ⅱ度～Ⅲ度骨髓抑制率下降,P<0.05。结论康莱特联合多西他赛治疗复发晚期非小细胞肺癌能增加疗效,改善病人生活质量,并具有保护骨髓的功能。     

多西他赛与吉西他滨联合放疗治疗老年非小细胞肺癌的疗效比较

目的:观察三维适形放疗分别联合多西他赛、吉西他滨治疗老年非小细胞肺癌的疗效及毒副反应.方法:将106例经病理学或细胞学证实的老年非小细胞肺癌患者随机分为多西他赛组和吉西他滨组,给予单药、周方案诱导化疗2周期.多西他赛20-25mg/m2,d1、8、15,28天重复;吉西他滨800mg/m2,d1、8、15,28天重复.有效者于第三周期化疗第一天开始联合局部三维适形放疗,共接受4周期化疗.结果:多西他赛组总有效率(CR+ PR)为85.2％,腺癌总有效率(CR+ PR)为93.8％;吉西他滨组总有效率(CR+ PR)为86.5％,其中鳞癌总有效率(CR+ PR)为90.9％;两组差异无显著性;多西他赛组3-4级血液毒性发生率1.9％,吉西他滨组为9.6％,两组有显著性差异(P=0.001);多西他赛组1、2、3年生存率分别为79.6％、37.0％、18.5％;吉西他滨组1、2、3、年生存率分别为69.2％、19.2％、17.3％.结论:多西他赛和吉西他滨联合三维适形放疗同步治疗老年非小细胞肺癌安全、有效;但多西他赛对腺癌疗效比吉西他滨更有优势,吉西他滨对鳞癌更有优势;两组1年生存率有显著差异;2、3年生存率无显著差异.     

Radiation tolerance dose of the spinal cord following conventionally fractionated irradiation

409 patients whose spinal cord were irradiated over 30 Gy with conventionally fractionated method were surveyed to study the relation between the dose of spinal cord and the incidence of radiation myelitis. Radiation myelitis was observed in 26 cases including 3 transverse myelitis ones. 5 year incidences of transverse myelitis calculated with life table method were approximately 0% at 40 Gy, 5% at 50 Gy, 10% at 60 Gy and 20% at 70 Gy. The radiation tolerance dose of the spinal cord was considered to be 50 Gy.     

猪下丘脑不同剂量照射后神经内分泌反应

目的　观察幼年猪下丘脑区接受不同剂量单次照射后下丘脑—垂体—睾丸轴反应。方法　(1)20 只幼年雄性小型猪分为5 个组,每组4 只,以蝶鞍上1 cm 为靶点等中心、10 MV 的X 射线、=16 m m 限光筒平行对穿照射,靶区中心吸收剂量分别为5 ,10,15 ,20 Gy;(2) 猪血清睾丸酮测定:照射后每隔4 周采血1 次直至照射后36 周,采用放射免疫分析方法测定猪血清睾丸酮水平;(3)将观察期满40 周的动物处死,取下丘脑组织行电镜和光镜观察,睾丸组织行光镜观察。结果　(1)照射后20 周,15,20 Gy 组动物体重出现降低趋势。(2)5 Gy 组血清睾丸酮水平在照射后曾有一过性降低,于照射后28 周与对照组基本相似;10 Gy 组略低于对照组;15,20 Gy 组持续呈低水平。(3) 光镜观察见下丘脑组织基本正常;电镜观察见10,15 ,20 Gy 组神经细胞浆水肿,髓鞘肿胀、内膜向轴索内突出,血管内皮细胞和胶质细胞增生;光镜下见精原细胞和间质细胞数量减少,细胞体积明显缩小,以20 Gy 组为最明显。结论　幼年猪下丘脑区接受5 Gy 的单次剂量照射就可以发生促性腺激素释放素神经细胞分泌功能的抑制,认为幼年猪的下丘脑区属放射敏感组织;10 Gy 以上单次照射可以导致明显神经内分泌障碍     

High-dose preoperative radiotherapy does not alter the strength of unilaterally irradiated colon anastomoses in rats

PURPOSE: We studied the influence of preoperative radiotherapy on the strength of colon anastomoses in rats. We compared a conventional (2 Gy/fraction; 1 fraction/day; 5 days/week; cumulative doses of 40.0, 60.0, and 80.0 Gy) and a hyperfractionated schedule (1.6 Gy/fraction, 2 fractions/day, 5 days/week, cumulative doses of 41.6, 60.8, and 80.0 Gy). We compared unilaterally with bilaterally irradiated anastomoses for two conventional radiation schedules. METHODS AND MATERIALS: The rectosigmoid was always irradiated. Depending on the experiment, the cecum was irradiated or not. A side-to-side anastomosis between rectosigmoid and cecum was constructed the day following the last irradiation. The strength of the anastomosis was evaluated by means of a bursting pressure (BP) measurement after 10 days. A control group and a sham-treated group were carried out. RESULTS: Compared to controls, the strength of unilaterally irradiated anastomoses was not altered and BP values were independent of the radiation schedule and of the cumulative dose. In case of bilaterally irradiated colon anastomoses, anastomotic strength was significantly reduced at 80 Gy, but not at 40 Gy. CONCLUSIONS: After high doses of preoperative radiotherapy, colon anastomoses in rats can be safely constructed if only one anastomotic segment is irradiated. The strength of bilaterally irradiated colon anastomoses is dose-dependent.     

放化疗治疗后大鼠脊髓p53蛋白表达的研究

目的:探讨放疗、化疗单独及联合应用对脊髓产生的影响。方法:实验共分为4组,即对照组、单纯放疗组、单药化疗组及放化疗联合组。顺铂的剂量各为5mg/kg,单次给予;放射剂量为5Gy/次,采用6MeV的电子线,隔日1次照射大鼠胸段脊髓,总量为40Gy。照射结束后20周,免疫组化检测放疗、化疗及联合治疗时脊髓组织中p53蛋白的表达。结果:空白组、单纯放疗组、顺铂化疗组、顺铂化疗及放疗联合组p53阳性表达率分别为0、36.6%、43.3%和70.0%,联合组与其他3组比较,P<0.05。结论:顺铂加放疗联合组上调脊髓组织p53表达水平,提示放化疗联用可能加重脊髓损伤,对今后设计合理治疗方案有指导意义。     

Intraoperative irradiation in a rat model: histopathological changes in irradiated segments of duodenum

During intraoperative radiation therapy for carcinoma of the head of the pancreas in humans, a portion of duodenum is often at risk for radiation-induced complications because of its fixed anatomical position within the treatment field. This study was undertaken to determine the feasibility of using the rat as a model to determine the radiotolerance of normal mammalian duodenum. The procedures used to exteriorize and irradiate a selected segment of duodenum are described. Histopathologic changes in 5-cm segments of midduodenum were studied 14 and 28 days after 0, 30, 40, or 50 Gy X-radiation. Complete denudation of the epithelium and thickening of the muscularis and serosal layers occurred in all irradiated segments by day 14. By day 28, even though crypt and villus architectures were atypical, large areas of epithelial regeneration were seen in rats receiving 30 Gy. In contrast, complete denudation of the epithelium were still evident along most of the length of the irradiated segments in rats receiving 40 or 50 Gy. Serosal fibrosis was prominent in all irradiated animals, regardless of dose. These results indicate that radiation doses above 30 Gy carry high risks of complications. The rat is considered a suitable animal model.     

The late effects of radiation on the blood brain barrier

Rats were irradiated with 60 to 20 Gy in a single dose focussed to a volume of 0.5 cc in the center of the left hemisphere. Breakdown of the BBB was detected by the presence of spikes on EEG after subcutaneous injection of Bicuculline methiodide, and the presence of staining following Evans Blue dye injection. Breakdown of the BBB (mean and standard deviation) occurred in 38/46 of the 60 Gy rats at 98 +/- 16 days, 7/11 of the 50 Gy rats at 128 +/- 25 days, 11/18 of the 40 Gy rats at 162 +/- 3 days, 5/11 of the 30 Gy rats at 178 +/- 5 days and, 7/12 of the 20 Gy rats at 217 +/- 7 days post irradiation. This study suggests that endothelial damage could be the principle mechanism mediating the late radiation syndrome.     

Radiation injury in the human kidney: a prospective analysis using specific scintigraphic and biochemical endpoints

Renal function was prospectively analyzed in 26 evaluable patients, irradiated to various doses on their kidneys for neoplastic disease. Glomerular function was assessed by 99mTc-DTPA renography, creatinine clearance, and serum beta 2-microglobulin, whereas tubular function was monitored by 99mTc-DMSA scintigraphy, urine beta 2-microglobulin, urine N-acetyl glucosaminidase, and alanine aminopeptidase and a urine concentration test. In the patients given the highest irradiation dose to the entire left kidney, that is, 40 Gy in 5 1/2 weeks, glomerular and tubular functional impairment, as assessed scintigraphically, progressed at a rate of 2.0 +/- 1.0% (+/- 1 SD) and 2.0 +/- 0.5% per month, respectively, down to 30-40% after 3 to 5 years. The overall glomerular function, as assessed by creatinine clearance, decreased by only 20%. In the patients irradiated unilaterally on the upper pole to 40 Gy in 4 weeks, glomerular and tubular function in the left kidney deteriorated at 0.75 +/- 0.33% and 0.75 +/- 0.20% per month in the first 2 years, down to 75-80% at 5 years. This smaller reduction was due to shielding of a part of the left kidney. No changes were observed, thus far, after bilateral whole kidney irradiation to 17-18 Gy in 3 1/2 weeks. The concentration capacity of the kidney after total volume irradiation was not impaired. There was a trend for an increase in diastolic blood pressure in 3 out of 5 patients given the high dose irradiation to the entire left kidney and in 2 out of 7 patients irradiated on the upper pole of the left kidney. The progressive nature of the radiation nephropathy stresses the need for long term follow-up to determine more accurately the "tolerance dose" of the human kidney for irradiation.     

Protective effect of local temporary ischemia depends on applied dose of radiation

The aim of this study was to verify hypothesis that protective effect of local temporary ischemia depends on dose of radiation. 56 male WAG-strain rats were used. Total body irradiation with 3 x 3 and 3 x 5 Gy was performed. Local temporary ischemia was induced by clamping the tail base. The biochemical parameters were the thiobarbituric acid-reactive substances (TBA-RS). In bone marrow smears the polychromatic erythrocyte (PCE) numbers were counted and the numbers of micronucleated PCEs were analyzed. In small intestines the numbers of crypts were calculated. The levels of TBA-RS in the serum of the animals irradiated with a 3 x 3 Gy dose were significantly different (P < 0.002). Also in animals irradiated with a dose of 3 x 3 Gy the numbers of intestinal crypts were different (P < 0.05). In animals irradiated with dose 3 x 5 Gy, for analyzed parameters differences did not achieve statistical significance. Local temporary ischaemia provides general protection against radiation damage for lower dose. This protective effect disappeared after applications of a higher dose of radiation.     

Radiotherapy with concurrent docetaxel for advanced and recurrent breast cancer

BACKGROUND: Docetaxel has shown remarkable radiosensitizing properties in vitro. In this study we investigated whether the addition of docetaxel to radiotherapy enhanced tumor response in patients with advanced or recurrent breast cancer. METHODS: A total of 35 patients were enrolled in this study. Docetaxel was administered concurrently during radiotherapy. Radiation doses were 54 to 69 Gy (median 60 Gy). In those enrolled through January 2000, docetaxel 40 mg/m2 was administered biweekly (once every two weeks), with subsequent dose adjustments based on tolerance and bone marrow and liver function. Beginning in February 2000, a weekly docetaxel schedule was used instead. This new regimen was based on data suggesting reduced myelosuppression with this regimen. The weekly dose rate was 20 mg/m2, with dose reductions for impaired organ function. RESULTS: All patients were evaluated for toxicity and response and a total of 40 irradiated sites were evaluated for local response. The overall response rate of irradiated sites was 95% and the CR rate was 68%. CR and PR were achieved in 40%, 37% of patients, respectively. Acute toxicities were tolerated by most patients: 17% had Grade 3-4 neutropenia, 6% had Grade 3-4 radiation dermatitis, and 3% had Grade 3-4 pneumonitis. CONCLUSION: The combination of docetaxel with radiotherapy is an active and safe regimen in patients with inoperable advanced or recurrent breast cancer. We determined the recommended dose of docetaxel with concomitant radiotherapy to be 20 mg/m2 weekly for a Phase II study. Further study is necessary to assess the impact of this treatment on long-term outcome.     

Enhancement of tumor radioresponse by docetaxel: Involvement of immune system

Docetaxel, a potent chemotherapeutic drug and a strong enhancer of tumor radioresponse, possesses immunomodulating properties. We previously reported that 40% of murine tumors responding to docetaxel by growth delay showed heavy infiltration with macrophages or lymphocytes. The present study explored the effect of whole body irradiation on antitumor action of docetaxel alone or docetaxel plus tumor irradiation. Mice bearing 8-mm MCa-K mammary carcinoma in the leg received 33 mg/kg docetaxel i.v., 5 to 65 Gy tumor irradiation, or both (radiation given 24 h after docetaxel). Docetaxel delayed tumor growth and enhanced the efficacy of radiation: it dramatically reduced TCD50 (radiation dose yielding 50% tumor cure) from the control value of 38.6 Gy to 11.8 Gy, for an enhancement factor of 3.27. In addition to enhancing tumor radioresponse, docetaxel decreased the lung metastatic rate in mice with local tumor control from 26% in mice receiving radiation alone to 11% in mice receiving docetaxel plus radiation. Docetaxel induced heavy infiltration of tumors with lymphocytes, determined 2-4 days after treatment: the percentage of lymphocytes increased from the control value of <2% to 27% in mice that received docetaxel 3 days earlier. This increase was due to the influx of helper/inducer T-lymphocytes and natural killer cells. Immunosuppression of tumor-bearing mice with 6 Gy whole-body irradiation prior to tumor isotransplantation reduced docetaxel-induced lymphocyte infiltration of tumors, antitumor and anti-metastatic action of docetaxel, and docetaxel-induced enhancement of tumor radioresponse. Thus, our results showed that docetaxel stimulates tumor infiltration with immune cells, which then participate in antitumor action of docetaxel alone or when combined with radiotherapy.