TECIA法体外放射敏感性实验对原发性肺鳞癌放疗个体化方案选择的意义

目的:建立人原发性肺鳞癌的组织培养放疗敏感性检测法,快速确定人原发性肺鳞癌组织的辐射敏感性的个体差异,用于筛选放疗方案及指导临床肿瘤个体化放疗方案.方法:采用TECIA法检测不同个体原发性肺鳞癌组织在不同剂量、不同分次放疗方案照射后不同时间的细胞凋亡水平.比较不同剂量、不同分次放疗方案照射后不同时间的细胞凋亡水平的差异.结果:TECIA法发现,照射前人原发性肺鳞癌组织细胞凋亡指数较低,放疗后出现较高的细胞凋亡指数,与放疗剂量呈正相关.结论:肿瘤放射敏感性实验对指导患者的个体化治疗具有重要的价值.     

重离子治疗肿瘤的两大优势

目的观察两种人恶性肿瘤细胞-人肝癌细胞SMMC-7721和人黑色素瘤细胞A375对高LET12C6+离子和γ射线照射的敏感性及分次效应,观察重离子治疗肿瘤的可行性及优势。方法以两种体外培养的来源于人体不同组织的具有高辐射抗性的恶性肿瘤细胞为实验对象,分别进行12C6+和γ射线0~6Gy内不同剂量点的单次和分次照射,采用克隆存活法统计细胞的存活分数。结果无论是单次还是分次照射,12C6+照射后两种细胞的存活分数均明显低于γ射线照射的细胞,而且重离子的分次效应明显降低。结论结果显示重离子在肿瘤治疗中的两个重要优势,即具有高的肿瘤杀伤力和低的分次效应,显示重离子照射引发的低修复现象,可使肿瘤放疗具有更高的效率。     

头颈部鳞癌调强放疗最佳分割方案的理论分析北大核心CSCD

目的理论分析头颈部鳞癌调强放疗时最佳的剂量分割模式。方法分别用目前常用的33次分割、保证物理剂量为70 Gy、用生物等效剂量(BED)84 Gy10和延长总治疗时间(1~7天)的剂量分割方案的前提下模拟不同分次剂量和分次数,用线性二次模型公式分别通过理论计算肿瘤、早反应组织(黏膜)、晚反应组织BED和肿瘤杀伤对数级,比较分析调强放疗最佳的剂量分割方案。结果在33次每天一次的分割方案中分次剂量从2.12 Gy提升到2.30 Gy时,照射的总物理剂量相应从70.0 Gy提升到75.9 Gy,肿瘤、早反应组织和晚反应组织分别为69.6~78.2Gy10、55.5~64.1Gy10和119.4~129.5Gy3,肿瘤杀伤对数级为10.6~11.9。当总保持照射剂量分为70 Gy或84 Gy10的前提下而改变分次剂量和分次数目,分次剂量为2.0~2.80 Gy,照射次数为25~35次,总治疗时间为32~46天,肿瘤、早反应组织和晚反应组织分别为67.5~82.3Gy10、53.1~69.8Gy10和113.5~119.8 Gy3,肿瘤杀伤对数级为10.3~12.5。综合比较肿瘤、早反应组织BED、晚反应组织BED和肿瘤杀伤对数级4个参数提示30次的分割方案中肿瘤控制和不良反应相对得到较好的平衡。总治疗时间每延长一天肿瘤BED降低1.4%(0.8Gy10),肿瘤杀伤对数级降低0.1。结论理论上头颈部鳞癌IMRT的最佳剂量分割总治疗时间为6周的30次分割方案,总治疗时间延长导致肿瘤BED降低。     

放射线诱导人鼻咽癌细胞系凋亡的研究

目的 研究Ｘ线诱导两种人鼻咽癌细胞系凋亡的情况。材料与方法 应用ＤＮＡ特异荧光染料Ｈｏｅｃｈｓｔ ３３４２观察凋亡细胞，细胞的照射应用直线加速器。结果 给一固定剂量照射后，ＣＮＥ细胞系凋亡指数与时间和剂量相关性，于照射后４８小时达到平台期。在分次放疗中，ＣＮＥ细胞系总剂量１０Ｇｙ，照射５次／５天组的凋亡指数较对照２次／５天和对照１次／１天组高，分别为３７．８％、３４．５％和２２．８％、２Ｇｙ照射后     

99mTc-HYNIC-annexinⅤ活体检测单次放疗后肿瘤细胞凋亡

  目的   本研究旨在采用99mTc-HYNIC-annexinⅤ活体检测放疗后肿瘤的凋亡情况,并初步探讨凋亡与照射剂量及肿瘤敏感性的关系。   方法   将EL₄淋巴瘤和S180肉瘤细胞株分别接种于实验小鼠右腋下10 d,随机分成显像组和观察组。显像组不同剂量照射后尾静脉注射99mTc-HYNIC-annexinⅤ,2 h后SPECT显像,取组织称重后分别测量放射性计数,计算每克组织百分注射剂量率（%ID/g）及T/B、T/M放射性比值,应用TUNEL法检测肿瘤凋亡细胞数。观察组照射后观察2周。   结果   EL₄淋巴瘤随照射剂量增加显影逐渐清晰,凋亡细胞数增多,且与%ID/g呈正相关（r=0.892,P < 0.001）;S180肉瘤不明显。相同剂量（0 Gy或8 Gy）照射,EL₄淋巴瘤放射性分布及凋亡细胞数明显高于S180肉瘤。8 Gy照射后,S180肉瘤仅缩小0.1 cm,EL₄淋巴瘤完全消退。   结论   99mTc-HYNIC-annexinⅤ可早期活体检测放疗诱导的肿瘤凋亡。放射诱导的凋亡与疗效呈正相关,检测凋亡有助于判断其对放疗的敏感性,可以作为预后的指标。      

电离辐射对小鼠腹腔积液型S180细胞凋亡的影响

目的：观察电离辐射诱导小鼠Ｓ１８０细胞凋亡与辐射剂量、照射方式、抑瘤作用及生存期的。方法：将Ｓ１８０荷瘤鼠分为对照组,不同剂量组,以医用直线加速器Ｘ线单次照射和分次照射。采用光镜、电镜、ＤＮＡ琼脂糖凝胶电泳法、以及流式细胞法观察Ｓ１８０细胞凋亡的形态学和生化学特征,并观察不同处理组的小鼠抑瘤情况及生存期。结果：（１）单次照射、分次照射的均能导出典型的凋亡特征。（２）分次照射凋亡率高于次单次照射。     

NP方案联合不同间隔时间放疗对乳腺癌MCF-7细胞作用研究

目的:研究化疗方案顺铂(DDP) 盖诺(NVB)联合不同间隔时间放射治疗对人乳腺癌MCF-7细胞辐射敏感性影响。方法:采用细胞集落形成方法观察DDP NVB方案联合不同间隔时间放疗对细胞的杀伤作用,流式细胞仪对各组周期分布和凋亡情况进行分析比较,并观察凋亡形态特征。结果:MCF-7细胞化放疗间隔不同时间后细胞SF值差异随照射剂量增加而逐渐明显,8Gy时12小时组最低,0小时组居中,48、72小时组最高。化放疗间隔时间不同引起MCF-7细胞SF值不同与NP作用后不同间隔时间G2/M期阻滞比例不同有一定相关性,NP化疗可诱导细胞凋亡,而且随时间增加呈不可逆转增加,但化疗后不同时间凋亡差异同SF值差异间并未呈现相关性。结论:NP不同时机顺序联合放疗对MCF-7细胞辐射敏感性有一定影响,这种差异同NP作用后不同时间细胞周期分布、凋亡等作用有关。     

"彗星"分析法检测人癌裸鼠移植瘤的放射敏感性

目的　探讨“彗星”分析法应用于人实体肿瘤放射敏感性检测的可能性。方法　应用“彗星”分析法 ,以尾力距之比 (RTM)作为终指标 ,检测人肺腺癌、人食管鳞癌和人鼻咽鳞癌等 3种人癌裸小鼠移植瘤的放射敏感性。裸小鼠移植瘤组织被消化并稀释成细胞浓度为 4× 10 4ml的单细胞悬液后 ,分成对照组 (0Gy)和不同剂量照射组 ,照射组分别给予 2、5、10和 15Gy的 6MVX射线的冰上照射 ,照射后立即进行“彗星”分析。结果　 3种人癌裸小鼠移植瘤细胞未照射时 (0Gy)的尾力矩 (TM)差异有显著性意义 (F =9.11,P <0 .0 1)。不同剂量 (2、5、10和 15Gy)照射后 ,3种人癌裸小鼠移植瘤细胞未做校正时的TM所反映放射敏感性由高到低的变化趋势依次为 :肺腺癌 >食管鳞癌 >鼻咽鳞癌 ,显然与临床一般印象不符 ;而经与对照组进行“本底”校正后的RTM所反映放射敏感性由高到低的变化趋势依次为 :食管鳞癌 >鼻咽鳞癌 >肺腺癌 ,则符合临床一般印象。结论　①应用“彗星”分析法检测实体肿瘤的放射敏感性 ,尾力矩必须进行“本底”校正 ,即扣除对照组本底误差后的尾力矩才能很好地反映实体肿瘤的放射敏感性差异。②“彗星”分析法可用于检测人体肿瘤组织的放射敏感性。     

放疗联合化疗对乳腺癌MCF-7细胞凋亡及周期分布的影响

[目的]研究放射治疗联合乳腺癌化疗方案NP(NVB+DDP)对人乳腺癌MCF-7细胞凋亡及细胞周期分布的影响.[方法]通过形态学和流式细胞术对MCF-7细胞的凋亡诱导效应进行定性及定量观察,并对细胞周期分布进行分析.[结果]单纯放疗组可诱导MCF-7细胞阻滞在G2/M期.单纯放疗组和单纯化疗组的凋亡指数随时间延长而增加.放化组照射后24h,在4Gy、6Gy和8Gy不同照射剂量下,4Gy出现凋亡峰值,凋亡指数4Gy＞6Gy＞8Gy,表现为低剂量辐射联合化疗有较好的凋亡诱导效应.[结论]放疗联合化疗对乳腺癌的凋亡诱导效应明显,并呈一定的时间一剂量选择性.     

24例原发性肝癌患者的肿瘤药敏结果分析

目的通过测定原发性肝癌患者对5-氟脲嘧啶(5-Fu)、顺铂(DDP)、阿霉素(ADM)、丝裂霉素(MMC)、氨甲喋呤(MTX)、长春新碱(VCR)6种化疗药物的体外敏感性试验,探讨肿瘤药敏试验对原发性肝癌个体化疗的应用价值。方法采用组织块培养-终点染色-计算机图像分析法(TECIA)。结果24例原发性肝癌细胞对6种化疗药物的敏感性由高到低依次为5-Fu、MMC、DDP、ADM、MTX、VCR。结论TECIA法的体外肿瘤药敏试验在原发性肝癌的临床用药及个体化化疗方面具有重要的指导意义。     

TECIA法体外药敏试验对肺癌术后化疗个体化方案选择的研究

目的：研究新鲜肿瘤组织块体外药敏试验和化疗方案以及生存期的关系,指导肺癌术后化疗方案的选择,实现肺癌个体化药物治疗。方法：采用TECIA法对126例肺癌肿瘤新鲜组织标本进行体外培养,选用临床常用的8种化疗药物进行肿瘤药物敏感性试验,根据试验结果选用化疗方案进行术后辅助化疗,并随访观察生存期。结果：126例标本对常见化疗药高度敏感占1.19%,中度敏感占60.71%;根据药敏结果选用中、高度敏感药物进行术后化疗,其5年生存期延长。结论：根据肿瘤药物敏感试验选用化疗药物能延长生存期,对指导患者的个体化治疗具有一定的指导意义。     

Fractionated irradiation of five human lung cancer cell lines and prediction of survival according to a radiobiology model

BACKGROUND: This study evaluates a predictive radiobiology model by measurements of surviving fraction (SF) by the clonogenic assay or the extrapolation method and the proliferation rate in vitro. It is hypothesized that incorporating proliferation to intrinsic radiosensitivity, measured by SF, to predict radiation responsiveness after fractionated irradiation adds to the model's accuracy. Materials and Methods. Five lung cancer cell lines with known SF after 1 Gy (SF1), and also SF2 and SF5, were irradiated with three different fractionation regimes; 10 × 1 Gy, 5 × 2 Gy or 2 × 5 Gy during the same total time to achieve empirical SF. In addition, the SF1, SF2 and SF5 after fractionated irradiation was calculated for each cell line based on the already known single fraction SF and with or without a proliferation factor. The results were compared to the empirical data. Results and Discussion: By using the clonogenic assay to measure radiosensitivity, prediction of radiosensitivity was improved after fractionated radiotherapy when proliferation was used in the radiobiology model. However, this was not the case in the cell lines where the extrapolation method was used to calculate SF. Thus, a radiobiology model including intrinsic radiosensitivity, measured by the clonogenic assay, as well as proliferation, is better at predicting survival after fractionated radiotherapy, compared to the use of intrinsic radiosensitivity alone.     

Ⅱ、Ⅲ期乳腺癌术后三种放疗方式的比较研究

目的：探讨Ⅱ、Ⅲ期乳腺癌术后适宜的胸壁和锁骨上区照射方式。方法：156例患者随机分成A、B、C三组,给予不同放疗方式。A组锁骨上区和胸壁给予常规电子线照射,2Gy/次,1次/d,5d/周,总量至50Gy。B、C组电子线放疗至32Gy后,分别改用4野调强和三维适形切线放疗,剂量均为DT18Gy分9次11d完成。比较三组不良反应和疗效。结果：三组放射性皮肤反应发生率、胸壁复发率无差异（P〉0.05）;放射性肺损伤发生率分别为32.7%、10.4%、22.6%（P〈0.05）,B组最低,A组最高;远处转移率分别为36.3%、8.3%、37.7%（P〈0.01）,B组最低,A、C两组无差异。结论：三种放疗方式在皮肤反应和局部控制率上无差别;电子线＋4野调强能减少放射性肺损伤发生,而对控制远处转移发生的作用尚需进一步研究。     

三维适形加量放射治疗非小细胞肺癌

目的：探讨三维适形加量放射治疗非小细胞肺癌（NSCLC）的优势。方法：21例非小细胞肺癌，CT模拟机定位，输入TPS（Pinnacle^3 7．4／7．6），勾画GTV1，先常规或三维适形放疗30Gy／15F～50Gy／25F，第2次CT定位，勾画GTV2，予三维适形放射治疗至66Gy／33F～70Gy／35F。结果：GTV2与GTVl相比，平均缩小比例39．5％，13例大于40％。近期疗效：CR19．0％，PR71．4％，NC9．5％，总有效率（CR＋PR）90．5％，1年生存率85．7％。早期放射性肺损伤：1级13例（61．9％），2级6例（28．6％），3级2例（9．5％）。放射性食管炎：1级15例（71．4％），2级6例（28．6％）。后期放射肺纤维化：0级2例（9．5％），1级15例（71．4％），2级4例（19．0％）。结论：三维适形加量放射治疗NSCLC过程中，肿瘤平均退缩比例为39．5％，再次重新勾画GTV并加量，可以有效地减少治疗范围，提高靶区剂量，降低放射治疗副反应。     

The increment of micronucleus frequency in cervical carcinoma during irradiation in vivo and its prognostic value for tumour radiocurability.

A potential usefulness of micronucleus assay for prediction of tumour radiosensitivity has been tested in 64 patients with advanced stage (II B-IV B) cervical carcinoma treated by radiotherapy. The study of cellular radiosensitivity in vitro was conducted in parallel with the study of cellular damage after tumour irradiation in vivo. Radiosensitivity of in vitro cultured primary cells isolated from tumour biopsies taken before radiotherapy was evaluated using cytokinesis-block micronucleus assay. Frequency of micronuclei per binucleated cell (MN/BNC) at 2 Gy was used as a measure of radiosensitivity. Radiation sensitivity in vivo was expressed as per cent increment of micronucleus frequency in cells isolated from biopsy taken after 20 Gy (external irradiation, 10 x 2 Gy) over the pre-treatment spontaneous micronucleus level and was called MN20. Very low correlation (r = 0.324) was observed between micronucleus frequency in vitro and in vivo. Although micronucleus frequency at 2 Gy differed widely between tumours evaluated (mean MN/BNC was 0.224; range 0.08-0.416), no significant correlation was observed between this parameter and clinical outcome. The average increment of micronucleus frequency after 20 Gy amounted to 193% of spontaneous level (range 60-610%) and was independent of spontaneous micronucleation before radiotherapy. In contrast to in vitro results, these from in vivo assay seem to have a predictive value for radiotherapy of cervix cancer. The micronucleus increment in vivo that reached at least 117.5% of pretreatment value (first quartile for MN20 data set) correlated significantly with better tumour local control (P < 0.008) and overall survival (P < 0.045). Our results suggest that evaluation of increment of micronucleus frequency during radiotherapy (after fixed tested dose of 20 Gy) offers a potentially valuable approach to predicting individual radioresponsiveness and may be helpful for individualization of treatment strategy in advanced stage cervical cancer.     

Individual radiosensitivity measured with lymphocytes may predict the risk of acute reaction after radiotherapy

PURPOSE: We tested whether the chromosomal radiosensitivity of in vitro irradiated lymphocytes could be used to predict the risk of acute reactions after radiotherapy. METHODS AND MATERIALS: Two prospective studies were performed: study A with 51 patients included different tumor sites and study B included 87 breast cancer patients. Acute reaction was assessed using the Radiation Therapy Oncology Group score. In both studies, patients were treated with curative radiotherapy, and the mean tumor dose applied was 55 Gy (40-65) +/- boost with 11 Gy (6-31) in study A and 50.4 Gy +/- boost with 10 Gy in study B. Individual radiosensitivity was determined with lymphocytes irradiated in vitro with X-ray doses of either 3 or 6 Gy and scoring the number of chromosomal deletions. RESULTS: Acute reactions displayed a typical spectrum with 57% in study A and 53% in study B showing an acute reaction of Grade 2-3. Individual radiosensitivity in both studies was characterized by a substantial variation and the fraction of patients with Grade 2-3 reaction was found to increase with increasing individual radiosensitivity measured at 6 Gy (study A, p = 0.238; study B, p = 0.023). For study B, this fraction increased with breast volume, and the impact of individual radiosensitivity on acute reaction was especially pronounced (p = 0.00025) for lower breast volume. No such clear association with acute reaction was observed when individual radiosensitivity was assessed at 3 Gy. CONCLUSION: Individual radiosensitivity determined at 6 Gy seems to be a good predictor for risk of acute effects after curative radiotherapy.     

局部晚期宫颈癌CT图像引导下适形调强后程推量的临床研究

目的：观察利用三维适形调强技术（Intensity modulated radiotherapy,IMRT）、采用5Gy×5f分割模式对于局部晚期宫颈癌患者盆腔外照射后残留病灶局部推量的治疗效果及并发症发生。方法：33例局部晚期宫颈癌患者在完成盆腔外照射及同期DDP化疗后,行CT模拟定位扫描,定位前及每次治疗前均进行膀胱灌注以控制膀胱的充盈程度,勾画子宫颈、宫旁及阴道侵犯区域以及2cm阴道组织、子宫体下段2/3为CTV-boost,CTV-boost加5、15mm为PTV-boost,设计并执行7野三维适形调强计划,处方剂量为5Gy/f×5f,2f/w。结果：1年总生存率、无病生存率、盆腔控制率分别为82%、76%、79%,其中15mm PTV边界组的1年盆腔控制率为90%。结论：对于不能进行腔内后装治疗的部分局部晚期宫颈癌患者,采用5Gy×5f分割模式的三维适形调强技术进行后程推量可达到根治效果,1年内未见严重直肠、膀胱并发症出现,远期疗效及并发症正在进一步观察中。     

In vitro radiosensitivity of skin fibroblasts can identify a group of patients with complications in various health tissues after radiotherapy]

PURPOSE: A retrospective study of the in vitro radiosensitivity of skin fibroblasts derived from two groups of patients treated by definitive radiotherapy for a variety of tumors who either displayed or did not display severe complications. PATIENTS AND METHODS: Seven radiotherapy patients were selected: three were treated for head and neck, prostate and non-Hodgkin lymphoma tumors, and did not develop any significant complications (control group); four patients were treated for bladder, thyroid, head and neck and anal canal tumors and developed serious acute and especially late reactions (hypersensitive group). Primary cell cultures of skin fibroblasts were established and their radiosensitivity studied by the clonogenic assay after exposing to single radiation doses ranging between 1 and 8 Gy. RESULTS: The survival fraction at 2 Gy (SF2) ranged from 0.27 to 0.38, with a mean of 0.33 for the control group, and from 0.10 to 0.20 with a mean of 0.17 for the hypersensitive group. The Mann-Whitney non-parametric test showed that the difference between the two means was statistically significant (p = 0.03). CONCLUSION: The data are in favor of a correlation between the radiosensitivity of patients' fibroblasts and the reactions of different normal tissues to radiotherapy. This association supports the use of the clonogenic survival, or a surrogate test, as a predictive assay. The multiplicity of normal tissues and organs implicated in this association suggests the existence of genetic factors that determine, at least in part, the radiosensitivity of target cells involved in the expression of normal tissues complications following radiotherapy.     

Radiotherapy of brain metastases

The effect of radiotherapy in 254 cases of brain metastases, treated between 1977 and 1984, were studied. The cases included 141 of lung cancer, 28 of mammary cancer, and 85 of other primary sites. The percentages of patients with improvement in clinical symptoms were 8, 39, and 66, respectively. These were groups of patients irradiated with less than 30 Gy, 30 Gy to 50 Gy, and more than 50 Gy. The 50% survival periods from the start of irradiation for the last group were as follows: for radiotherapy only, 4.1 months, radiotherapy and surgery, 4.2 months, radiotherapy and chemotherapy combined, 6.9 months, radiotherapy, surgery and chemotherapy combined, 12.1 months. The intervals between the initial diagnosis and brain metastases were different in lung cancer and mammary cancer, but the prognosis after brain metastases showed little difference between them.     

体部伽玛刀治疗原发性大肝癌163例疗效分析

目的：探讨全身γ刀立体定向放射治疗原发性大肝癌的临床可行性及疗效。方法：采用超级γ刀（SGS-I型）立体定向放射治疗原发性大肝癌163例,根据肿瘤的位置、临床靶体积、病人的身体状况与治疗目的,制定放射治疗计划及调整剂量分布。肿瘤体积56.9-2697.0cm3,等剂量曲线50%-60%,周边照射总剂量33-40Gy,分割处方剂量3.3-5.0Gy,重复治疗8-12次,5次/周。结果：治疗前肝区胀痛不适等98例,治疗结束后1-3个月,症状完全消失59例（60.20%）,部分缓解30例（30.61%）,9例无效（9.18%）,症状改善有效率为90.82%;163例病人治疗后2-3个月复查CT或MR,肿瘤CR 17例（10.43%）,PR 79例（48.47%）,NC57例（34.97%）,PD 10例（6.13%）,总有效率93.87%。6个月和1年生存率分别为71.17%和58.90%。结论：全身γ刀立体定向放射治疗原发性大肝癌临床效果确切,副反应较轻。