p27~(kip1)表达在食管癌放射抗拒中的意义

目的 探讨p27~(kip1)表达与食管癌放射敏感性变化的关系.方法 通过γ射线反复照射人食管鳞癌细胞EC9706(累计放射剂量6 000 cGy),逐步筛选得到具有放射抗拒性的细胞EC9706R.采用克隆形成实验检测两种细胞的放射敏感性,流式细胞仪分析细胞周期特征,免疫细胞化学检测p27~(kip1)的表达.结果 筛选得到的人食管鳞癌细胞EC9706R较亲本细胞显示出明显的放射抗性,EC9706R细胞SF_2=65.71%,D_0=2.20 Gy,D_q=1.61 Gy,N=2.07;EC9706细胞SF_2=46.72%,D_0=1.61 Gy,D_q=0.99 Gy,N=1.85,EC9706R细胞SF_2、D_0、D_q及N值均高于亲本细胞;细胞周期检测显示EC9706R细胞G_1期比例较亲本细胞明显下降,而S期比例明显增加;免疫细胞化学结果 显示具有放射抗性的EC9706R细胞p27~(kip1)表达明显低于亲本细胞.结论 p27~(kip1)表达下调导致细胞周期变化,可能是食管癌细胞产生放射抗拒的机制之一.     

甘氨双唑钠联合放射治疗中晚期鼻咽癌临床研究

目的:观察甘氨双唑钠(sodiumglyci-didazole,CMNa)在中晚期鼻咽癌放射治疗中的作用。方法:60例中晚期鼻咽癌患者随机分观察组(CMNa 放疗)和对照组(单纯放疗组)各30例。CMNa静脉滴入,每次0·75g,每周1、3和5用药,用药后1h内放疗。放疗采用常规外照射方案。结果:鼻咽原发灶CR率在观察组和对照组分别是93%和73%,两组差异有统计学意义,χ2=4·320,P=0·0377。颈淋巴结CR率两组分别是90%和63%,两组差异亦有统计学意义,χ2=5·963,P=0·0146。两组毒副反应如皮肤、黏膜、消化道反应及血白细胞下降等差异无统计学意义,P>0·05。结论:CMNa联合放射治疗可提高鼻咽癌的肿瘤局部控制率,而毒副反应不增加。     

SYNCHRONOUS CHEMOTHERAPY AND RADIOTHERAPY FOR CARCINOMA OF THE ANAL CANAL—AN ALTERNATIVE TO ABDOMINOPERINEAL RESECTION

Five patients with squamous or basaloid carcinoma of the anal canal have been treated with synchronous chemotherapy and external radiotherapy. Three were operable cases, of which one had abdominoperineal resection subsequently, while two had no surgery. The other two had a locally advanced inoperable tumour in one case and pelvic recurrence following abdominoperineal resection in the other. The chemotherapy regimen consisted of mitomycin C given as a single dose of 10 mg m^-2 at commencement of radiotherapy and two i.v. infusions of 5-fluorouracil 1000 mg m^-2/day for 4 consecutive days approximately 4 weeks apart. The radiation dose ranged from 50 Gy to 70 Gy in 25–35 fractions. All patients remain disease free with a median follow up of 14 months. Eradication of tumour at the primary site has been confirmed histologically in the three operable cases. A growing volume of data from the medical literature suggests that patients with operable carcinoma of the anal canal treated with this regimen have a probability of cure at least equal to that of abdominoperineal resection and have the advantage of retaining normal anal function and avoiding permanent colostomy.     

The variation of OER with dose rate

The oxygen enhancement ratio (OER) has been measured as a function of dose rate from 276 Gy/hr to 0.89 Gy/hr for V-79 cells irradiated at 23 degrees C or 37 degrees C. As dose rate is decreased, the OER initially increases, from a value of 3.0, to a maximum value of 3.7 to 4.0, at a dose rate between 20 and 60 Gy/hr. The OER subsequently decreases with further dose rate reduction to a minimum value of 2.4 at the lowest dose rate. Similar experiments conducted with cells in nutrient deprived conditions exhibited a monotonic decrease in OER from 3.0 to 1.7 with dose rate reduction. These experimental findings can be understood in terms of the sublethal damage repair capability of cells under different pO2 and nutrient conditions.     

马蔺子甲素对碳离子放射增敏作用

目的　探讨马蔺子甲素（ Ｑ） 对碳离子的放射增敏作用并与γ射线进行比较。方法　在有氧和乏氧条件下,荷瘤小鼠被随机分为６ 组：对照组;碳离子与γ射线治疗组;碳离子与γ射线加药治疗组;单独用药组。以动脉夹阻断小鼠局部血流以造成肿瘤乏氧２０ ｍｉｎ ,比较在有氧与无氧情况下的增敏作用。结果　此药对乏氧肿瘤的增敏比（ｓｅｎｓｉｔｉｚａｔｉｏｎｅｎｈａｎｃｅｍｅｎｔ ｒａｔｉｏ , Ｓ Ｅ Ｒ） 值明显大于不乏氧肿瘤,且６ Ｇｙ 碳离子的放射增敏作用大于１８ Ｇｙ γ射线的放射增敏作用。结论　马蔺子甲素对小鼠正常皮肤无增敏作用,对小鼠肿瘤乏氧细胞具有选择性地放射增敏的作用     

Growth Inhibition and Radiosensitization of Cultured Glioma Cells by Nitric Oxide Generating Agents

The authors examined the effect of nitric oxide (NO) generating agents on the growth and radiosensitivity of cultured glioma cells. Three glioma, rat C6, and human T98G and U87 cell lines were treated with the NO generating agents, S-nitroso-N-acetyl-penicillamine (SNAP) or sodium nitroprusside (SNP). These agents released NO in the cell culture media and inhibited the growth of the glioma cells. Growth-inhibition was attenuated by hemoglobin, a known inhibitor of NO, suggesting it is mediated by NO. When C6 and T98G cells were irradiated in the presence of SNAP or SNP at 100µM, radiosensitization was observed. SNAP at 100µM exhibited a sensitizer enhancement ratio (SER) of 1.4 for C6 cells and 1.8 for T98G cells. SNP at 100µM only radiosensitized T98G cells with a SER of 1.9. The effect of SNP on radiosensitization of C6 cells was unclear. We conclude that NO generating agents are potential growth inhibitors and radiosensitizers for malignant glioma cells. NO mediated radiosensitization of glioma cells by NO generating agents may offer a new therapeutic approach for malignant glioma.     

Combined gemcitabine and radioimmunotherapy for the treatment of pancreatic cancer.

MAb-PAM4 is an anti-MUC1 antibody that has been shown to be reactive with 85% of pancreatic adenocarcinomas with no reactivity with normal pancreas or other tissues. Initial clinical studies have shown excellent targeting with high tumor/nontumor ratios. Gemcitabine, an analog of deoxycytidine, is currently a frontline treatment for pancreatic cancer. Acting via a number of metabolic pathways, gemcitabine is also a powerful radiosensitizer. Combined-modality, chemo/radiosensitization with gemcitabine and low dose (131)I-PAM4 radioimmunotherapy was performed to determine if a more effective treatment procedure could be developed. Athymic nude mice bearing large (1 cm(3)) CaPan1 human pancreatic tumors were given a single treatment cycle consisting of gemcitabine, 333 mg/m(2) administered on Days 0, 3, 6, 9 and 12 by intraperitoneal injection, along with either 100 or 200 microCi, (131)I-PAM4 administered on Day 0 by intravenous injection. Gemcitabine did not interfere with the biodistribution of radiolabeled antibody. Specific tumor targeting was observed for (131)I-PAM4, with a tumor/blood radiation dose ratio of 2.6 over the first 14 days. Gemcitabine alone and low dose radioimmunotherapy alone, each had no affect upon tumor growth; no statistical differences were noted in comparison to the untreated group. When combined, however, a statistically significant (p = 0.0324), synergistic anti-tumor effect was observed. Median survival time doubled for the combined treatment regimen compared to single modality treatment groups. The combined treatment modality was well tolerated by the mice. Our data show that combined gemcitabine with radioimmunotherapy may provide an improved alternative for the treatment of pancreatic cancer, achieving successful anti-tumor effects with low toxicity.     

肿节风浸膏溶液对鼻咽癌细胞系CNE-2的放射增敏作用

目的：探讨肿节风浸膏对鼻咽癌细胞系CNE-2的细胞毒性作用以及对放射敏感性的影响。方法：应用克隆形成方法,观察不同浓度的肿节风浸膏对CNE-2的细胞杀灭效应,求得IC50,选择合适浓度的肿节风浸膏配合照射和单纯照射对细胞的杀伤作用,计算细胞存活率,用多靶单击数学模型进行曲线拟合作图。结果：与照射配合的肿节风浸膏的合适浓度为10mg／L。单纯照射组D0值为3．096Gy,照射加肿节风浸膏组D0值为2．441Gy,放射增敏比（SER）为1．268（3．096／2．441）。结论：肿节风浸膏具有一定的放射增敏作用。     

沙纳唑对体外培养的小鼠骨髓粒系造血祖细胞的放射增敏作用

目的:本实验旨在研究沙纳唑以及合并γ射线照射对体外培养小鼠骨髓粒系造血祖细胞(CFU-GM)集落形成的影响,分析沙纳唑是否对其有放射增敏作用.方法:从小鼠骨髓分离CFU-CM,在37℃、5%CO2条件下培养,当细胞进入呈指数生长期,分别在培养液中加入一系列浓度纱纳唑(0,1,5,12.5,25,50,100,200,400,800μg/ml)进行孵育,接受60Coγ射线照射(剂量为0,0.5,1,2,3,4Gy),观察细胞集落形成比.为评价沙纳唑对CFU-GM的放射增敏性,将CFU-GM接受沙纳唑和γ射线照射(2Gy)处理以及两者合并处来评价沙纳唑对CFU-GM的放射增敏作用.结果:(1)沙纳唑对体外CFU-GM集落形成明显细胞抑制作用,且随剂量增加作用增大.沙纳唑在低剂量(低于20μg/ml)对CFU-GM集落形成抑制作用呈线性关系(r=0.9987,p<0.01)分别为50和120μg/ml.(2)放射照射对CFU-GM也有明显抑制作用,饱和剂量和Do值分别是2.0和0.72Gy.(3)用沙纳唑联合放射照射处理CFU-GM后,对CFU-GM的抑制作用比单一处理都要强,但经统计学分析沙纳唑与放射照射之间无协同作用.结论:纱纳唑对体外培养小鼠骨髓系造血祖细胞有细胞毒性作用,但在低于IC20剂量下复合放射照射对CFU-GM集落形成无放射增敏作用.