白细胞介素12早期干预对急性放射病小鼠的治疗作用

目的:研究重组鼠白细胞介素12(rmIL-12)早期干预对γ射线急性放射病小鼠的治疗作用,并与重组鼠血小板生成素(rmTPO)的辐射防护作用进行比较。方法:42只BALB/c小鼠均给予60Coγ射线6.0Gy一次全身照射后随机分为照射对照(对照)、rmIL-12治疗和rmTPO治疗3组。rmIL-12治疗组小鼠于照射后1h及此后每3d一次分别腹腔注射rmIL-12 20μg/(kg.d),共5次;rmTPO治疗组小鼠于照射后0.5和24h分别皮下注射rmTPO 15μg/kg;对照组给予等体积的无菌PBS。2次/d观察小鼠一般情况,3d检测1次外周血细胞数,分别于照射后14d和28d收集骨髓细胞进行集落培养。结果:rmIL-12治疗组小鼠一般情况较对照组改善,外周血中血小板(PLT)下降速度明显慢于对照组,PLT恢复时间较对照组明显提前(11d vs 14d),且PLT最低值明显高于对照组(18.9%vs 8.1%,P<0.05)。rmIL-12治疗组PLT恢复速度稍快于rmTPO治疗组,但差异无统计学意义(P>0.05)。照射后14和28d骨髓有核细胞集落培养结果提示rmIL-12治疗组CFU-Mix明显高于对照组(P<0.01),与rmTPO治疗组差异无统计学意义(P>0.05)。结论:rmIL-12可明显促进急性放射病小鼠造血功能恢复,对巨核系的恢复作用与rmTPO相当,有望开发成安全有效的新型辐射防治药物。     

BALB／c小鼠重度骨髓型急性放射病模型的建立

 目的　建立BALB／c小鼠重度骨髓型急性放射病模型,为重度骨髓型急性放射病的实验研究提供依据。方法　BALB／c小鼠给予60Coγ射线6.0 Gy一次全身照射。观察小鼠照射后一般临床表现、外周血细胞计数、股骨病理组织学及骨髓细胞集落生成情况。结果　小鼠照射后第3天活动量即有不同程度的减少,但均无呕吐、稀便,照射后第11天白细胞降至最低值（基础水平的3.0 %）,照射后第28天恢复至基础水平的53.7 %;照射后第14天血小板降至最低值（基础水平的8.1 %）,照射后第28天恢复至基础水平的60.4 %;照射后第14天骨髓病理示骨髓腔呈空虚状态,骨髓有核细胞集落培养亦提示粒细胞-巨噬细胞集落形成单位（CFU-GM）、混合集落形成单位（CFU-Mix）明显下降;照射后第28天骨髓病理、CFU-GM及CFU-Mix未完全恢复;照射后2个月全部小鼠存活。结论　6.0 Gy 60Coγ射线一次全身照射BALB／c小鼠可成功构建重度骨髓型急性放射病模型,可用于骨髓型急性放射病的实验研究。     

小鼠白介素-12真核表达质粒的构建及其表达

目的:构建能在真核细胞内稳定表达小鼠白介素-12(mIL-12)的质粒,为进一步研究mIL-12的免疫调节机制及其抗肿瘤作用奠定基础。方法:通过聚合酶链反应(PCR)扩增质粒pORF-mIL-12(Elas-ti),双酶切后将目的片段mIL-12连接到真核表达载体pcDNA3.1( )质粒上,mIL-12受pcDNA3.1( )中mCMV启动子驱动,将mIL-12全长转录至同一mRNA上,对重组质粒进行鉴定后将其转染小鼠Lewis肺癌细胞(LLC)测其表达。结果:PCR成功扩增出mIL-12片段,PCR鉴定、酶切鉴定及测序均证实pcDNA3.1( )-mIL-12质粒构建成功,RT-PCR及ELISA证实重组质粒在mRNA及蛋白质水平均高表达mIL-12。结论:pcDNA3.1( )-mIL-12真核表达质粒构建成功并能在LLC细胞中稳定表达。     

白介素12重组腺病毒载体的构建及其抗肿瘤作用初步观察

[目的]构建携带小鼠白细胞介素12腺病毒载体(AdCMVmIL-12),并观察其对H22肿瘤的抑瘤效果。[方法]构建重组质粒pdlE1SP1BmIL-12,并用该质粒与质粒pJM17共转染293细胞后包装而成AdCMVmIL-12,并进行酶切法鉴定。同时制备肿瘤动物,通过肿瘤内局部注射AdCMVmIL-12,观察其抗肿瘤作用。[结果]酶切鉴定显示构建正确,其病毒滴度为1.3×109pfu/ml;当病毒滴度为100MOI时,mIL-12浓度达到3417ng/1×106细胞/24h。动物实验表明,注射AdCMVmIL-12的小鼠,肿瘤体积明显小于对照组(P<0.01),生存期显著延长。[结论]构建AdCMVmIL-12成功,肿瘤内局部注射可发挥抗肿瘤作用。     

人IL-12重组质粒对S-180荷瘤小鼠的治疗作用

目的：探讨人白细胞介素（imerleukin,IL）-12重组质粒对荷瘤小鼠的基因治疗作用．并进行初步的安全性评价。方法：建立肉瘤细胞（8-180）荷瘤小鼠模型,随机分为3组,每组10只,分别于注射瘤细胞后的第4、7、10、14和17天给予人IL-12重组质粒（pcDNA6-p70,100μg／只）、环磷酰胺（40mg／kg）及生理盐水（100μL／只）瘤体内注射。观察小鼠的存活时间;于致瘤后第21天处死小鼠,测肿瘤大小及质量,计算脾和胸腺指数;乳酸脱氢酶法检测NK杀伤活性;MTT法检测脾淋巴细胞增殖反应;ELISA法检测小鼠血清IFN-γ水平。对pcDNA6p70小鼠体内运用进行初步的安全性评价。结果：与生理盐水组相比．pcDNA6-p70瘤体内注射可显著延长荷瘤小鼠存活时间,P=0．03;缩小肿瘤体积,抑瘤率为30％,生理盐水组为0;增加脾（P=0．04）及胸腺（P=0．019）指数．增强其NK活性（P=0．001）及淋巴细胞增生反应（P=0．000）,提高荷瘤血清IFN-γ水平（P=0．000）。安全性检测结果显示,pcDNA6p70在小鼠体内应用无明显毒副作用．P=0．58。结论：人IL-12重组质粒可通过增强机体的细胞免疫功能发挥对肿瘤的基因治疗作用。     

表达白细胞介素-12质粒DNA抗小鼠肝癌皮下移植瘤的作用

目的 探讨瘤内注射mIL-12质粒DNA抗小鼠肝癌皮下移植瘤的作用。方法：构建真核表达质粒载体pDC511mIL-12，ELISA方法检测质粒载体在真核细胞中的表达，淋巴母细胞增殖法检测mIL-12的生物学活性；分别于小鼠肝癌H22皮下移植瘤内直接注射质粒DNA，观察各组小鼠存活时间、肿瘤体积变化及各组小鼠脾脏细胞毒T淋巴细胞(CTL)的活性：注射质粒DNA后1月进行瘤体组织病理学观察：结果：mIL-12基因治疗组与空载体对照组相比，肿瘤生长显著受抑制(F=4．10，P=0．03)，小鼠存活期显著延长(X^2=4．48，P=0．03)．并且小鼠脾细胞CTL杀伤活性增强。质粒DNA瘤内注射1月后，pDC511mIL-12组肿瘤病灶炎性细胞浸润明显，病灶内肿瘤细胞广泛坏死。结论：瘤内注射mIL-12表达质粒DNA可抑制小鼠肝癌皮下移植瘤生长，能提高机体抗肿瘤免疫应答。     

可诱导表达的白细胞介素12基因治疗小鼠原位移植性肝癌

目的 评估RU486系统诱导表达的白细胞介素12(IL-12)基因对小鼠原位移植性肝癌的治疗效果.方法 小鼠肝脏接种H22肝癌细胞,制备原位移植性肝癌模型.采用水流动力学注射法,将含有RU486调控系统的小鼠IL-12表达质粒pRS22注射到小鼠体内,腹腔注射RU486(250μg/kg)诱导质粒表达,检测血清中IL-12、干扰素γ(IFN-γ)和一氧化氮(NO)的表达水平.采用HE染色和免疫组织化学方法检测瘤细胞增殖活性和肿瘤血管生成情况.结果 注射生理盐水+RU486组、pRS-LacZ+RU486组、pRS22+芝麻油组和pRS22+RU486组小鼠肝脏肿瘤体积分别为(409.90±137.03)mm3、(271.80±182.63)mm3、(251.00±76.55)mm3和(46.48±47.19)mm3,肿瘤细胞增殖细胞核抗原(PCNA)阳性率分别为(82.10±4.62)%、(83.45±2.34)%、(77.46±2.99)%和(50.67±8.09)%,肿瘤组织微血管密度分别为(74.58±18.47)个/400倍视野、(63.60±13.36)个/400倍视野、(53.52±11.74)个/400倍视野和(25.38±10.87)个/400倍视野.与注射生理盐水+RU486组、pRS-LacZ+RU486组和pRS22+芝麻油组相比,pRS22+RU486组小鼠生存期明显延长(接种瘤细胞后第50天仍然有1只小鼠存活),血清中IL-12、IFN-γ和NO的表达水平分别为(11.52±7.46)ng/ml、(2.68±0.32)ng/ml和(5.10±3.27)μmol/L.结论 RU486系统能有效地调控IL-12基因的表达,可诱导的IL-12能够有效地抑制小鼠原位移植性肝癌的生长,延长小鼠的生存期.     

重组白介素-12治疗小鼠Lewis肺癌的实验研究

背景与目的:白介素-12(interleukin-12,IL-12)是具有抗瘤活性的细胞因子,本研究建立稳定表达小鼠IL-12(murineinterleukin-12,mIL-12)的小鼠Lewis肺癌(Lewislungcarcinoma,LLC)细胞系LLC/mIL-12,评估mIL-12重组质粒及LLC/mIL-12瘤苗治疗小鼠Lewis肺癌移植瘤的疗效。方法:脂质体转染LLC获得LLC/mIL-12瘤苗。于C57BL/6小鼠皮下接种LLC细胞2×106个,成瘤后将小鼠随机分成4组(n=10),第1、4、7天瘤内注射质粒或瘤苗,第14天处死小鼠,观察肿瘤生长曲线、脾细胞中CTL细胞和NK细胞活性以及肿瘤浸润淋巴细胞。结果:LLC/mIL-12瘤苗组和pcDNA3.1( )-mIL-12质粒组肿瘤体积显著缩小,mIL-12能增强NK细胞和CTL细胞活性,两者均以LLC/mIL-12治疗组更显著,LLC/mIL-12和pcDNA3.1( )-mIL-12治疗组有大量CD4 、CD8 淋巴细胞浸润。结论:mIL-12基因能增强NK细胞和CTL活性,LLC/mIL-12及pcDNA3.1( )-mIL-12均能产生抗瘤免疫反应,且前者作用更强。     

硫普罗宁对放疗所致小鼠白细胞减少的预防及治疗作用

为观察硫普罗宁 (Tiopronin ,MPG)对放疗所致小鼠白细胞减少的预防和治疗作用。方法　采用60 Co -γ射线造成外周血白细胞减少的动物模型进行试验 ,观察MPG防治由放疗所致白细胞减少的作用。结果　预先用MPG不同剂量对小鼠经口灌胃 (ig)或腹腔注射 (ip)用药 5天 ,给动物一次60 Co -γ射线全身照射 480Rad/ 3min ,及先给动物进行一次60 Co -γ射线全身照射 480Rad/ 3min后 ,用MPG不同剂量对小鼠ig或ip进行治疗。然后均于放疗后第 3天、第 5天计数白细胞总数 ,与单用放疗组相比具有显著性差异。结论　MPG具有明显的预防和治疗由60 Co -γ射线所致的小鼠白细胞减少的作用。     

三联菌苗对小鼠肉瘤180的抑制作用

背景与目的:据报道,肿瘤患者在急性感染后可出现肿瘤症状显著改善、肿瘤完全消退的现象.链球菌OK-432菌苗对多种动物肿瘤有显著抑制作用,并已试用于临床肿瘤治疗,除有发热与白细胞数升高外,无其他副作用.本研究旨在探讨三联菌苗对荷肉瘤180(S180)小鼠血清白介素12p70(IL-12 p70)含量的变化及S180生长的影响,以及血清IL-12(p70)含量的变化与S180生长的关系.方法:所有实验小鼠接种S180后,按完全随机设计分成5组(即金黄色葡萄球菌菌苗组,A组、鼠伤寒沙门氏菌菌苗组,B组、草分枝杆菌菌苗组,C组、由前3种菌组成的三联菌苗组,D组、空白对照组,E组)进行实验.称重法检测各菌苗对小鼠S180的抑瘤率,ELISA法检测菌苗对S180小鼠血清IL-12(p70)的含量.结果:A、B、C组小鼠平均S180瘤重分别为1.39、1.50、1.36 g,而D组小鼠的平均瘤重最低(0.62 g),E组平均瘤重最高(2.40 g).各组小鼠S180重量的差异有非常显著性(F=66.73,P＜0.001);A、B、C、D组的平均瘤重均比E组低,D组比A、B、C组的低,差异均有显著性(q检验,P＜0.001).胸腺、脾脏重量在各组间的差异无显著性(F=2.36,P＞0.05;F=1.89,P＞0.05).A、B、C组的抑瘤率分别为42.08%、37.50%、43.33%,D组抑瘤率为74.17%.D组小鼠血清IL-12(p70)的平均含量最高(19.44 pg/ml),A、B、C组IL-12(p70)的平均含量分别为11.88、10.35、11.68 pg/ml,E组的最低(4.45 pg/ml);各组小鼠血清IL-12(p70)含量的差异有显著性(F=15.76,P＜0.0001);A、B、C组小鼠血清IL-12(p70)含量的差异无显著性(q检验,P＞0.05),而其余任何两组均数比较,差异均有显著性(q检验,P＜0.01).结论:实验所选用的菌苗能诱导小鼠产生IL-12(p70)、抑制小鼠S180的增长,三联菌苗比单价菌苗的效果更好.     

Therapeutic index by combination of adriamycin and docetaxel depends on dosing time in mice

Although the combination of adriamycin and docetaxel showed a better cure rate against metastatic breast cancer, severe myelosuppression and cardiotoxicity were dose-limiting factors. The purpose of this study was to establish a suitable dosing schedule, based on a chronopharmacologic approach, to relieve severe adverse effects. In experiment 1, adriamycin or docetaxel was injected i.p. at 2, 6, 10, 14, 18, or 22 hours after light onset (HALO) to estimate toxicities. In experiment 2, the dosing time dependency of toxicity and pharmacokinetics were assessed in the combination of adriamycin and docetaxel. In addition, G2-M phase in myelocyte cells was determined in nontreated mice. Adverse effects caused by adriamycin were shown to be the worst at 2 HALO and the best at 14 HALO. On the other hand, docetaxel-induced adverse effects were more severe at 14 HALO than at 2 HALO. In the combination study, the D(2)-A(1)4 group, in which docetaxel was administered at 2 HALO followed by adriamycin at 14 HALO, showed the most toxicity relief of all the treated groups. In the pharmacokinetic study, the dosing time dependency of toxicities was not related to the daily variation of pharmacokinetics of adriamycin and docetaxel. A significant 24-hour rhythm of G2-M phase distribution was found in myelocyte cells of nontreated mice. The daily variation of leukopenia caused by docetaxel corresponded to the 24-hour rhythm of G2-M phase distribution. These findings reveal that the therapeutic index of the combined chemotherapy can be improved by administering adriamycin and docetaxel at the time when the most adverse effects are relieved in each drug.     

Comparison of acute toxicity and mortality after two different dosing regimens of high-dose interleukin-2 for patients with metastatic melanoma

We compared acute toxicity, drug exposure, in-hospital mortality, and inpatient length of stay between two currently recommended dosing protocols (from the National Comprehensive Cancer Network Guidelines) of high-dose interleukin-2 (IL-2) treatment for patients with metastatic melanoma. Patients with metastatic melanoma who received high-dose IL-2 treatment between 2003 and 2010 were identified. Chemotherapy orders, electronic medical records, paper medical charts, and patient discharge summaries were reviewed retrospectively. We identified 13 patients who had received 600,000 units/kilogram (kg)/dose and 15 patients who had received 720,000 units/kg/dose. Patients in the 720,000 units/kg/dose group had a higher rate of grade 3 and 4 bilirubin elevations (34 vs. 12 %), weight gain (any grade, 96 vs. 89 %), and thrombocytopenia (any grade, 75 vs. 65 %). Patients receiving the higher dose also experienced more dose-limiting neurotoxicity (45 vs. 23 %), large-volume diarrhea (15 vs. 0 %), and hepatotoxicity (7 vs. 0 %). There was no in-hospital mortality during treatment in either group. The average length of stay was similar between both groups (5 days, SD?=?1 for both groups), and the median cumulative IL-2 exposure was similar between both groups for the first course (10.1 vs.10.5 million units/kg) and for all courses (approximately 11–12 million units/kg). Both high-dose IL-2 protocols had comparable in-hospital mortality and cumulative IL-2 exposure. The 720,000 units/kg/dose dosing scheme did not shorten the length of stay but did lead to greater acute toxicity. Therefore, as a result, we recommend 600,000 units/kg/dose when deciding between the two regimens.     

不同方案治疗急性早幼粒细胞白血病169例疗效分析

 目的 探讨不同治疗方案对急性早幼粒细胞白血病（APL）的治疗效果。方法 对不同治疗方案的APL疗效进行回础性分析比较。结果 采用全反式维A酸（ATRA）+三氧化二砷（As2O3）或者两者交替组获得CR中位时间分别为34,35.5 d,与单用ATRA的62 d比较,差异有统计学意义（P＜0.05）。ATRA+As2O3组或两者交替组,3年无病生存率分别为78 %和80 %,与单用ATRA组比较,差异有统计学意义（P＜0.05）。15例行造血干细胞移植（HSCT）者,仅2例复发,其余13例中位无病生存时间（DFS）为11.5年, 该13例PCR检测PML-RARα融合基因转阴性。结论 应用ATRA+As2O3或两者交替加化疗治疗APL获得CR时间明显缩短,而且3年无病生存率相对较高。缓解后6个月进行HSCT者,DFS可进一步延长。     

Peritoneal plasmacytomagenesis in mice: comparison of different pristane dose regimens

Plasmacytomas were induced in inbred BALB/c pi mice by the ip injection of pristane with 4 different dose schedules. Three 0.5-ml doses (1.5 ml) given at 2-month intervals gave an average yield of 61% plasmacytomas in 6 experimental groups with a range from 51 to 71%; a single 1-ml dose gave an average yield of 42% plasmacytomas in 5 experimental groups with a range from 37 to 45%; and a single 0.5-ml dose gave an average of 22% from 3 experiments involving young mice with a range from 14 to 26%. Two 0.5-ml doses given at various intervals from 14 to 300 days gave yields of plasmacytomas that usually but not always were greater than that obtained with a single 0.5-ml dose of pristane. When the second injection of pristane was delayed as long as 180 days, a strong additive effect over that observed with 0.5 ml alone was obtained. The plasmacytomas developed in mice given the second dose 180 days after the first, with virtually the same latent period as observed with a single 1-ml dose. No plasmacytomas were found in 200 BALB/c pi mice inoculated with corn oil, aluminum hydroxide, or very small doses of pristane (i.e., 0.05 ml). The minimal latent period for plasmacytoma development is about 120 days. The median latent period ranged from 180 to 250 days in the groups of mice that received 3 0.5-ml injections of pristane. In a single experiment pristane freed of UV-absorbing materials was as potent as commercial grade pristane in inducing plasmacytomas.     

剂量分割模式照射人肺腺癌移植瘤后基因表达谱差异的初步研究

目的 研究总相同照射剂量、不同剂量分割方案对BALB/c-nu裸鼠移植瘤(人肺腺癌细胞系Anip973)基因表达的差异.方法 将移植瘤种鼠的肿瘤组织制备成肿瘤组织块,选择裸鼠右后肢外侧小腿腓肠肌处接种,建立移植瘤裸鼠模型.待肿瘤直径达1.0 cm时将48只裸鼠分成4个组:未照射空白对照组、2 Gy30次常规照射组(2 Gy组)、6 Gy10次大分割组(6 Gy组)、10 Gy6次大分割组(10 Gy组).大分割组均在2周内完成,所有照射完成后继续观察裸鼠1个半月.采用基因谱芯片技术检测4个组移植瘤细胞的基因表达差异,并进行实时PCR验证.结果 6、10 Gy组较2 Gy组上调了抑制细胞增殖和诱导凋亡的基因如Bax和BCL2L10,下调了促进细胞增殖基因如c-myc和EGF、抗凋亡基因以及XRCCA、RAD21、RAD23B等DNA损伤修复基因.PCR证实6 Gy10次组c-myc基因表达丰度明显低于2 Gy30次组和10 Cy6次组,分别为2.9%、5.6%、4.8%(P=0.000;P=0.002);10 Gy6次组c-myc基因水平相对于2 Gy30次组也有下降(P=0.069).结论 两个大分割方案较常规分割方案对BALB/c-nu裸鼠移植瘤(人肺腺癌细胞系Xnip973)在基因水平上生长抑制显著,6 Gy10次分割方案较10 Gy6次分割方案有更强的生长抑制作用.     

Bleomycin lung: the effect of different chemotherapeutic regimens

Summary A review of hard-copy computed tomography (CT) images of patients who had undergone chemotherapy for testicular teratoma revealed that the incidence of lung toxicity appeared to be lower in those who had received bleomycin by slow infusion [EBCi (3) regimen, etoposide/bleomycin/cisplatin] rather than by intravenous bolus [PVB regimen, cisplatin/vinblastine/bleomycin; BEP (5) regimen, bleomycin/etoposide/cisplatin]. This difference reached statistical significance only for PVB vs EBCi (3) (t=2.63,P<0.01). Nevertheless, in view of continuing reports of mortality resulting from bleomycin-induced pulmonary fibrosis in patients receiving the drug by i. v. bolus, further exploration of these results is clearly justified.     

Therapeutic effect of adriamycin encapsulated in long-circulating liposomes on meth-a-sarcoma-bearing mice

Long-circulating liposomes modified with a uronic-acid derivative, palmityl-D-glucuronide (PGIcUA), have been developed previously for the passive targeting of liposomes to tumor tissues. In this study, we examined the therapeutic effect of adriamycin (ADM) encapsulated in PGIcUA liposomes composed of dipalmitoylphosphatidylcholine (DPPC), cholesterol (Chol) and PGIcUA (molar ratio, 40/40/10) since this amount of PGIcUA was enough to endow liposomes with long-circulating activity. Long-circulating activity was also observed with palmityl-D-galacturonide (PGalUA) modified liposomes, suggesting that uronic acid plays an important role in preventing liposomes from being trapped in the reticuloendothelial system (RES). ADM was loaded in liposomes by a remote-loading method. Free or liposomal ADM was injected i.v. into BALB/c mice bearing s.c.-implanted Meth-A sarcoma. The liposomal formulation was efficient for reducing tumors, prolonging survival time and curing the animals, especially in the case of large tumors where free ADM was not. Furthermore, PGIcUA liposomes were more effective than conventional liposomes containing dipalmitoylphosphatidylglycerol (DPPG) instead of PGIcUA for prolonging survival time in mire. It might therefore be appropriate to use PGIcUA liposomes as the carriers of anticancer drugs.     

脑胶质瘤不同照射方案生物效应的实验研究

目的 通过对人脑多形性胶质母细胞瘤(BT325细胞系)裸小鼠移植瘤不同分割模式照射后生物效应的实验研究,加深对人脑胶质瘤放射反应生物学特性认识,为临床设计照射计划、制定合理分次治疗方案提供实验依据.方法 对BT325细胞系裸小鼠移植瘤进行单次10、20、30、40、60 Gy照射和2 Gy每周5次每天照射、3 Gy每周3次隔天照射、3 Gy每周5次每天照射、4 Gy每周3次隔天照射,总剂量分别为125、114、126、112 Gy.用肿瘤生长曲线评价剂量效应关系并测定肿瘤体积倍增时间.取贴壁生长的指数生长期BT325细胞,用生长曲线测定细胞倍增时间,细胞克隆形成分析法绘制细胞存活曲线(照射剂量为0、1、2、4、6、8、10 Gy)计算曲线参数值,彗星分析法测定DNA单链断裂半修复时间(T1/2).结果 单次照射各剂量点均不能有效控制肿瘤.2 Gy5次/周和3 Gy3次/周治疗方案对人脑胶质瘤实体瘤也无明显治疗效果.增加分次剂量可使脑胶质瘤实体肿瘤有较明显的消退,其中4 Gy3次/周方案好于其他方案但仍未能达到治愈肿瘤的效果.表明对肿瘤干细胞的控制不理想.各项生物学参数的测定结果:BT325细胞倍增时间为30.16 h,裸小鼠移植瘤肿瘤倍增时间为43 d;细胞存活曲线LQ模型拟合的α=0.360 Gy-1、β=0.057 Gy-2,多靶单击模型拟合的D0=1.394 Gy、Dq=2.127 Gy、SF2=0.714;5 Gy照射DNA单链断裂的T1/2=9.999 min.结论 本实验从实证实验角度印证了临床上脑胶质瘤是一种放射耐受性较高的肿瘤的看法.研究结果提示增高分割剂量有可能提高肿瘤的近期疗效(使肿瘤消退率增加),但如何提高对肿瘤干细胞的控制还需进一步深入研究.各项生物学参数测定结果提示脑胶质瘤细胞内在放射敏感性较差.