Early repair kinetics of intestine and lung in mice, after fast neutron and photon irradiation

Early repair (Elkind repair) kinetics of an early and a late responding tissue after gamma and d(50) + Be neutron irradiation were compared in mice. LD50 at five days after abdominal irradiation and LD50 at 180 days after thoracic irradiation were chosen as biological endpoints to study intestinal and lung tolerance, respectively. Elkind repair is assessed from the additional dose Dr to reach LD50 when a single dose Ds is split into two equal fractions Di separated by time intervals "i" ranging from 0 to 24 hours (Dr = 2Di-Ds). Dr is greater for lung than for intestine after both gamma and neutron irradiations. Our data are consistent with an exponential early repair with an half-life (T 1/2) of 0.5 h for intestine and 1.5 to 2 h for lung.     

老年食管鳞癌淋巴结累及野放射治疗的回顾性资料分析

目的 比较根治性单纯放疗的老年食管鳞癌患者行淋巴结累及野照射(IFI)和预防性照射(ENI)的治疗效果,探讨老年患者单纯放疗行淋巴结累及野照射的可行性.方法 收集分析年龄＞70岁,并经病理证实食管鳞癌且行单纯根治性调强放射治疗的老年患者共79例.其中48例进行IFI放疗,31例进行ENI放疗.中位随访时间为24个月,比较两组的疾病无进展生存率、总生存率、治疗失败模式及肺照射剂量及放射性肺炎发生率.结果 1、2、3年疾病无进展生存率,IFI组为60.4％、34.9％、29.7％,ENI组为64.5％、54.0％、35.0％,两者疾病无进展生存率比较差异无统计学意义(P＞0.05);1、2、3年总生存率IFI组为72.9％、43.4％、31.5％,ENI组为73.0％、53.0％、38.3％,中位生存期两组分别为25和28个月,ENI组有生存提高趋势,但两者差异无统计学意义(P＞0.05).两组的失败模式类似,远处转移、局部复发、非受累野淋巴结复发率IFI组及ENI组分别为22.9％、27.0％、4.2％和25.8％、0％、19.4％,两组比较差异均无统计学意义(P＞0.05).在治疗相关不良反应方面,ENI组中肺V5、V20、肺平均剂量等指标均大于IFI组,比较差异均有统计学意义(=4.66、29.90、15.63,P＜0.05);放射性肺炎的发生率ENI组明显高于IFI组,1～2级分别为22％和13％,3级分别为19％和4％,两组比较差异有统计学意义(x2=4.55、4.77,P＜0.05).结论 在老年食管鳞癌单纯放疗患者中,IFI与ENI的疾病无进展生存率和生存率相似,IFI的肺受照射剂量明显减少,使肺的损伤更小,对老年患者更为适合.     

中子及γ射线照射对小鼠肠道EGF及EGFR表达的影响

目的研究小鼠经中子及γ射线照射后肠组织中EGF和EGFR的表达变化及其意义。方法350只二级雄性BALB／C小鼠，经不同剂量的中子和γ射线照射，于照后6h、12h及1、2、3、4、5、7、10、14、21、28天分批活杀，采用免疫组化法研究EGF和EGFR在肠组织中的变化。结果肠黏膜上皮和隐窝细胞浆内EGF及EGFR表达在2．5Gy中子照后1天内增强，1～2天减少，3～7天增多，5天达高峰，14天后恢复至正常水平；4．0、5．5Gy中子及12Gy γ射线照射后6h增多，12h-4天进行性减少；5．5Gyγ射线照射后3天内增加，3天达高峰，5天后逐渐恢复。结论中子和γ射线照射后肠内源性EGF及EGFR的表达具有不同的变化规律，参与了肠放射损伤及修复的病理过程。     

Split-course neutron and photon irradiation of experimental tumors: the importance of the sequence and interval lengths

In a split course mixed beam experiment we have investigated the influence of the interval and beam-quality on tumour growth delay. Fast growing sarcomas (SaF) in grey CBA-mice were irradiated with different sequences of neutrons (N) and photons (X) varying the length of time interval from 0 up to 300 minutes between two doses. The tumours were treated with isoeffective doses of X-rays and/or neutrons (XX, NN, NX, XN). In order to achieve a homogeneous radiosensitive cell population, tumours were reversibly made hypoxic by clamping ten minutes prior and during irradiation. Tumour growth delay is dependent on the sequence and on the interval. As expected the growth delay in tumours treated with neutrons only was less dependent on the interval than after pure photon irradiation. Beyond an interval of 30 minutes in the mixed beam schedules the one giving neutrons first was more effective than the one giving photons first.     

Studies in the small intestine of mice after fractionated neutron and x-ray irradiation

Several groups of mice received a whole-body irradiation with X-rays and neutrons. The survival and the number of crypts per intestinal circumference was measured after one-time, two-time, three-time, and four-time fractionation. The irradiation interval was 24 hours. Survival rate and number of crypts were compared to one another. There were discrepancies which could be explained by determining the right moments of examination. Thus it seems not recommendable to use the system of small intestine crypts for experiences with fractionated irradiations. The RBE values increased with the rising number of fractions. If Dn-Dl values were calculated, they increased on the one hand with the rising fractionation, on the other hand with the rising total dose. This effect was more marked after X-ray irradiation, less after neutron irradiation. This may be explained by the fact that, contrary to neutron irradiation, the recovery following to sublethal lesion by X-rays had not been exhausted.     

Comparison of intracerebral delivery of carboplatin and photon irradiation with an optimized regimen for boron neutron capture therapy of the F98 rat glioma

In this report we have summarized our studies to optimize the delivery of boronophenylalanine (BPA) and sodium borocaptate (BSH) for boron neutron capture therapy (BNCT) of F98 glioma bearing rats. These results have been compared to a chemoradiotherapeutic approach using the same tumor model. The best survival data from our BNCT studies were obtained using a combination of BPA and sodium borocaptate BSH administered via the internal carotid artery, in combination with blood–brain barrier disruption (BBB-D). This treatment resulted in a mean survival time (MST) of 140 d with a 25% cure rate. The other approach combined intracerebral administration of carboplatin by either convection enhanced delivery (CED) or Alzet pump infusion, followed by external beam photon irradiation. This resulted in MSTs of 83 d and 112 d, respectively, with a cure rate of 40% for the latter. However, a significant problem that must be solved for both BNCT and this new chemoradiotherapeutic approach is how to improve drug uptake and microdistribution within the tumor.     

Effect of roentgen, cyclotron neutron, or mixed neutron-photon fractionated irradiation of mice. LD50/4 day values

Mice were whole-body-irradiated with 5 fractions of roentgen rays in 5 days, 5 fractions of cyclotron neutrons in 5 days, or with mixed neutron-photon fractionated radiation, in the sequence n-n-x-x-x or n-x-x-x-n. The LD50/4 day values were determined. Roentgen rays and neutrons interact in the additive manner in the mixed fractionation schemes: effective dose per fraction is as predicted from the roentgen ray-only and neutron-only experiments. This essentially agrees with HENDRY et coll. (1976). However, no trend was found towards a less-than -additive effect which was observed by those authors and has also been suggested in skin response to mixed schemes (NELSON et coll. 1975).     

中子照射后小鼠骨髓差异表达基因的研究

目的 探讨中子照射后小鼠骨髓差异表达的基因及其意义.方法 二级雄性BALB/c小鼠60只,随机均分为对照组和照射组(n=30).照射组动物采用3.0Gy中子进行全身均匀照射,并分别于照射后6、24、72h活杀,每时间点10只;对照组在相应时间点各处死10只动物.应用HE染色方法观察照射后小鼠骨髓的病理变化.采用小鼠全基因组寡核苷酸芯片技术分析照射后6h小鼠骨髓差异表达的基因谱,并采用RT-PCR对部分结果进行验证.结果 3.0Gy中子照射后,小鼠骨髓腔内造血细胞进行性减少,并有大量出血,至照射后72h,骨髓腔内呈血池状,几乎见不到造血细胞.照射后6h,小鼠骨髓差异表达基因共390个,包括上调和下调基因各195个,功能涉及代谢、生长和发育、细胞信号通路、应激反应、增殖和死亡、免疫应答、细胞连接、物质运输、细胞周期以及功能未知基因等,其中可能与中子辐射损伤密切相关的基因功能涉及细胞周期调控(ccng1、ccne2)、细胞增殖与凋亡调控(bax、bbc3、traf5)、细胞因子合成(psg18、zbtb32、mknkl、cdld1、id4、t2bp)等.RT-PCR验证了部分基因(ccngl、bax、bbc3、ccne2、traf5)的表达情况,其结果与芯片检测结果一致.结论 中子照射后小鼠骨髓出现大量差异表达基因,其中ccng1、bax、bbc3、cene2、traf5和irf4可能为中子辐射致骨髓损伤的敏感靶基因.     

中子辐射致肠道损伤的差异基因筛选研究

目的 筛选中子辐射后小鼠肠道损伤的差异基因.方法 12只二级雄性BALB/c小鼠,3Gy中子照射后6h,取小鼠空肠组织,提取RNA.采用小鼠全基因组寡核苷酸芯片技术分析其基因表达谱的变化,mas系统对差异基因进行分类,RT-PCR验证芯片筛选的部分差异基因.结果 中子照射后6h,在所分析的35 852条目的 基因中,小鼠空肠组织中共有608个差异基因,其中上调的有277个,下调的有331个.mas系统的功能分类结果 显示这些差异基因涉及到代谢、转运、消化、应激、细胞黏附、细胞生长发育和分化、细胞死亡、细胞运动、细胞通讯、细胞周期、DNA代谢和修复、生殖相关基因,另外还有一些未知的功能基因等.与中子辐射肠道损伤密切相关的有应激、细胞生长与死亡、信号转导、细胞周期、DNA损伤与修复等类别的基因.RT-PCR验证了部分结果 ,与芯片一致.结论 中子辐射后,损伤的空肠组织中存在大量差异基因,表明中子辐射对肠道是一种多靶点的损伤;筛选出的差异基因可能为中子辐射肠道损伤的敏感基因和防治靶点.     

252Cf腔内照射治疗食管癌疗效与病变外侵程度的相关性

目的 观察252Cf中子射线内照射治疗食管癌的疗效与食管肿瘤外侵程度及病变长度的关系及对患者预后的影响.方法 对32例食管癌患者进行外照射加252 Cf腔内照射治疗,常规外照射38 Gy/19次(2 Gy/次,1次/日,5次/周)后,开始内外照射同期进行,内照射4 Gy/次,1次/周,共12 Gy/3次,外照射总量为50 Gy.结果 病变长度≤5 cm患者1、3、5年局部控制率及生存率明显高于＞5 cm患者,分别为93.75％、76.70％、65.75％和93.75％、56.25％、43.75％(x2 =7.01,P＜0.05);60.94％、27.08％、27.08％和75.00％、18.75％、12.50％(x2=5.96,P＜0.05).最大浸润深度≤1.5 cm患者1、3、5年局部控制率及生存率明显高于最大浸润深度＞1.5 cm患者,分别为92.31％、73.85％、61.54％和92.31％、61.54％、46.15％(x2=3.87,P＜ 0.05);67.67％、35.45％、35.45％和73.68％、21.05％、15.79％(x2=6.24,P＜0.05).病变长度≤5 cm且浸润深度≤2.0 cm患者与病变长度＞5 cm且浸润深度＞2.0 cm患者比较,局部控制率和生存率差异有统计学意义(x2=10.09、7.97,P＜0.05).结论 食管癌病变长度≤5 cm,CT最大外侵≤1.5 cm,可能是252 Cf中子射线腔内照射的最好适应证.而当病变长度≤5 cm且肿瘤最大浸润深度≤2 cm时也可作为252 Cf中子射线腔内照射的较佳选择.     

The results of a randomised trial of mixed-schedule (neutron/photon) irradiation in the treatment of supratentorial Grade III and Grade IV astrocytoma

A randomised trial is reported of mixed-schedule (neutron/photon) irradiation compared with photon therapy for patients with Grade III or Grade IV astrocytoma. Thirty-one patients were allocated to be treated by the neutron/photon regime and 30 patients by photons. The median survival was 4 months in the mixed-schedule group and 8 months in the photon group. The survival rates were not significantly different. All patients who died had evidence of residual brain tumour. None had signs of radiation-related morbidity.     

rhIL-11对中子照射小鼠肠损伤的治疗作用

目的研究重组人白介素11(rhIL-11)对中子照射小鼠小肠上皮损伤及细胞周期的影响。方法采用裂变中子照射小鼠模型，观察rhIL-11对照射后小鼠小肠上皮形态、隐窝细胞坏死和细胞增生的影响，用流式细胞仪检测小鼠小肠上皮细胞周期的变化。结果rhIL-11治疗和预防给药可通过促进小肠隐窝细胞增殖使肠损伤得到迅速修复。照射后小鼠小肠上皮细胞发生明显的G2期阻滞，rhIL-11治疗可明显提高S期细胞比例。结论rhIL-11对中子照射小鼠小肠损伤具有防护作用，并能够影响细胞周期的变化。     

Fast neutron irradiation effects in PM-355 nuclear track detector.

Samples from sheets of the polymeric material PM-355 have been exposed to neutrons of incident energy in the range 0.8-19.2 MeV. The resultant effect of neutron irradiation on the thermal properties of PM-355 has been investigated using thermo-gravimetric analysis (TGA). The onset temperature of decomposition T(o) and thermal activation energy of decomposition E(a) were calculated, results indicating that the PM-355 detector decomposes in two weight loss stages. The variation of transition temperatures with neutron energy has been determined using differential thermal analysis (DTA). The results indicate the PM-355 thermograms to be characterized by the appearance of an endothermic peak due to melting. Melting temperature was found to be dependent on the neutron energy. In addition, structural property studies using X-ray diffraction and infrared spectroscopy were performed on both non-irradiated PM-355 samples and all of the samples that were irradiated. The results indicate that both the degree of ordering and the absorbance of the PM-355 polymer are dependent on neutron energy.     

重组人白细胞介素-11和姜黄素对中子照射致小鼠肠道损伤的治疗作用

目的 探讨重组人白细胞介素-11(rhIL-11)和姜黄素对中子照射致小鼠肠道损伤的治疗作用。方法 选取二级雄性BALB/c小鼠140只,随机分为健康对照组(20只)、单纯照射组(60只)、IL-11治疗组(30只)和姜黄素治疗组(30只)。单纯照射组小鼠采用3 Gy中子全身均匀照射,两个治疗组于照射后即日分别腹腔注射500μg·kg^-1·d^-1的rhIL-11或200 mg·kg^-1·d^-1的姜黄素,每天1次,连续给药5d。观察各组动物的死亡率。照射后6 h、1、3和5 d分别处死健康对照组和单纯照射组动物,3和5 d分别处死两个治疗组动物。取空肠标本,用HE深色、核仁组成区嗜银蛋白染色、Feulgen氏染色和图像死亡分析等,检测空肠病理形态变化、空肠上皮细胞核内嗜银蛋白含量和DNA含量变化。结果 照后5d,单纯照射组小鼠全部死亡,rhIL-11治疗组存活剩余2只,姜黄素治疗组存活剩余3只。3Gy中子照射后6 h～3 d内,空肠黏膜大面积坏死脱落,3d偶见隐窝细胞再生,5d见较多新生隐窝;IL-11治疗组在照后3d隐窝再生较明显,5d见大量新生绒毛;姜黄素治疗组在照后3d隐窝有部分再生,5d可见新生绒毛,排列结构较IL-11治疗组紊乱,绒毛高度较IL-11治疗组略低。照后5d,两个治疗组小鼠空肠上皮细胞AgNOR含量和DNA含量均高于单纯照射组(F＝0.015～0.035,P<0.05)。结论 3 Gy中子照射引起小鼠空肠明显损伤,rhIL-11和姜黄素治疗可减轻损伤并促进肠道上皮再生修复,对中子辐射肠上皮损伤具有保护作用。     

重组人白细胞介素-11和姜黄素对中子照射致小鼠肠道损伤的治疗作用

Objective To explore the therapeutic effect of recombinant human interleukin(rhIL-11) and curcumin on jejunal damage in mice after neutron irradiation.Methods 140 male BALB/c mice were randomly divided into 4 groups:20 mice in healthy control group,60 mice in mere irradiation group,30 mice in IL-11 treatment group and 30 mice in curcumin treatment group.The mere irradiation group mice were wholly exposed to 3 Gy neutron irradiation.The treatment groups mice were intraperitoneally enterocoelia once a day for 5 d after irradiation.The mortality of the mice were observed.The mice in the control and mere irradiation groups were killed 6 h,1,3,and 6 d post-irradiation,respectively,and the mice of the 2 treatment groups were killed 3 and 6 d post-irradiation,respectively and the samples of jujunum were colleted.HE staining,argyrophilic of nucleaolar organizer regions staining,Feulgen staining,and image analysis were used to observe the pathology and levels of argyrophilic proteins and DNA.Results The mice in the mere irradiation group all died at 5 d post-irradiation,while 2 mice in the IL-11 treatment group and 3 in the curcumin group survived.Large area necrosis and exfoliation were found in the intestinal epithelial mucosa of the mere irradiated group mice since 6 h to 3 d after irradiation.Crypt cell regeneration was seen occasionally found 3 days later and much more 5 days later.Crypt cell regeneration was obviously found in the intestinal epithelial mucosa and lots of new villi were observed 5 d after irradiation in both treatment groups,however,the amounts of crypt cells and new villi of the curcumin treatment group were less than those of the IL-11 treatment group.The contents of AgNOR and DNA in the intestinal epithelial cells 5 days after irradiation of the 2 treatment groups were all significantly higher than those of the mere irradiation group (F = 0.015-0.035,all P ＜ 0.05) but without significant differences between them.Conclusions Jejunal damage in mice could be induced after 3 Gy neutron irradiation.rhIL-11 and curcumin might reduce the damage and promote the regeneration and repair of the intestinal epithelium.