重组人白细胞介素-6抑制BTT739小鼠膀胱癌生长和转移的实验研究

目的　探讨重组人白细胞介素 6对小鼠膀胱癌BTT739生长和转移的抑制作用。方法将BTT739肿瘤细胞接种于T739近交系小鼠皮下 ( 2 6× 10 5/小鼠 ) ,2 4只小鼠随机分成 3组 ,第 3天始分别给予对照组溶剂 ( 0 9NS) 0 3mL ,治疗组重组人白细胞介素 6( 4× 10 6IU kg) ,日 2次 ,腹腔注射 ,共 2 0天 ,阳性对照组MMC ( 1mg kg)日 1次 ,腹腔注射计 14天。第 2 5天测对照组和治疗组的皮下瘤重及肺转移率 ,分别进行t检验和 χ2 检验。结果　两组皮下瘤重分别为 11 4± 1 9g和 7 4± 0 8g ,重组人白细胞介素 6有明显抑制BTT739肿瘤生长作用 ,抑瘤率 35 1% (P<0 0 5) ,而对肺转移灶数目及转移灶大小的抑制率分别为 61 3%和 2 6 2 % (P值均 <0 0 5) ,有显著性差异。结论　重组人白细胞介素 6可明显抑制BTT739小鼠膀胱癌生长和转移。     

重组人白细胞介素-6抑制BTT_(739)小鼠膀胱癌生长和转移的实验研究

 目的　探讨重组人白细胞介素 6对小鼠膀胱癌BTT739生长和转移的抑制作用。方法将BTT739肿瘤细胞接种于T739近交系小鼠皮下 ( 2 6× 10 5/小鼠 ) ,2 4只小鼠随机分成 3组 ,第 3天始分别给予对照组溶剂 ( 0 9NS) 0 3mL ,治疗组重组人白细胞介素 6( 4× 10 6IU kg) ,日 2次 ,腹腔注射 ,共 2 0天 ,阳性对照组MMC ( 1mg kg)日 1次 ,腹腔注射计 14天。第 2 5天测对照组和治疗组的皮下瘤重及肺转移率 ,分别进行t检验和 χ2 检验。结果　两组皮下瘤重分别为 11 4± 1 9g和 7 4± 0 8g ,重组人白细胞介素 6有明显抑制BTT739肿瘤生长作用 ,抑瘤率 35 1% (P<0 0 5) ,而对肺转移灶数目及转移灶大小的抑制率分别为 61 3%和 2 6 2 % (P值均 <0 0 5) ,有显著性差异。结论　重组人白细胞介素 6可明显抑制BTT739小鼠膀胱癌生长和转移。     

分次照射不同间隔时间对C57BL小鼠Lewis肺癌生长影响的研究

目的 通过对相同照射剂量、不同照射时间的放射对小鼠Lewis肺癌肿瘤生长延迟时间、小鼠生存时间的研究,探讨分次照射不同间隔时间对肿瘤的放射效应的影响.方法 将移植Lewis肺癌种鼠的肿瘤组织制备成1 × 107个/ml肿瘤细胞悬液,选掸48只8-10周雄性C57BL/6J小鼠右后肢外侧小腿腓肠肌处接种0.1 ml,建市移植瘤小鼠模型.肿瘤直径达0.8-1.0 cm时随机分成6个组:空白对照组、18 Gy单次照射组,9 Gy 2次每次间隔30 min组,2.57 Gy 7次每次间隔5 min组、9 Gy 2次每次间隔60 min组、2.57 Gy 7次每次问隔10 min组.隔日测量并记录肿瘤长短直径,观察肿瘤生长曲线、生长延缓时间及小鼠生存时间.结果 不同间隔时间各组生长延缓时间均<18 Gy单次照射组.照射总间隔时间30 min与60 min相比,小鼠肿瘤的生长变缓;而放射总间隔时间相同的各组,小鼠肿瘤生长延缓相似.与18 Gy单次照射组比较,放射总间隔时间延长缩短了小鼠生存时间;放射间隔时间30min和60min对小鼠肿瘤牛长影响相似.结论 小鼠Lewis肺癌模型中,相间照射剂量、放射总间隔时间延长降低了放射疗效,表现为缩短了小鼠肿瘤牛长延缓时间及总生存时间.对小鼠肿瘤生长影响程度与放射间隔时间的长短有关,间隔时间越长对小鼠肿瘤生长影响越大,但间隔30、60 min之间对小鼠生存时间影响差别不大.     

葡萄糖酸锗对小鼠Lewis肺癌放射增敏效应实验研究

采用动物肿瘤模型实验方法探讨葡萄糖酸锗对肿瘤的放射增敏效应。结果显示 :治疗后单药组与对照组肿瘤平均体积比较无显著差异 (P>0 .0 5 ) ,用药加放射 2 0 ,2 5 Gy组肿瘤平均体积分别明显小于单放 2 0 ,2 5 Gy组 (P<0 .0 1) ,当肿瘤体积达到 4 .4 cm3 时 (原照射体积的 4倍 )测得放射增敏比为 1.5 8～ 1.7。说明本药具有放射增敏作用 ,并能使肿瘤放射敏感性提高 5 8%～ 70 %。     

放射线联合人血管内皮生长抑素对HNE1鼻咽癌移植瘤生长抑制作用

目的:研究放射线联合重组人血管内皮生长抑素(Endostatin)对HNE1鼻咽癌移植瘤生长、转移的抑制作用.方法:应用裸鼠建立HNE1移植瘤模型;待瘤体平均体积达627mm3±47mm3,40只裸鼠随机分成治疗组:单独放疗(RT)组,单用Endostatin组,单次20cy照射后+连续使用Endostatin 14天组,连续使用Endostatin 14天后+单次20Gy照射组和空白对照组;绘制肿瘤生长曲线;取瘤体用免疫组化检测乏氧诱导因子-α(HIF-α)和微血管内皮CD34的表达,观察肿瘤乏氧及其微血管密度的变化.结果:与空白对照组比较,照射20GY后+连续Endostatin 14天组,其照射后20天抑瘤率84.79%,而先用Endostatin组+后照射组及单独照射组,单独使用Endostatin(使用完14天以后的第7天)组的抑瘤率分别是83.91%,64.95%,19.47%;其中各放射治疗组的减瘤率分别为44.1%,54.1%和18.1%(P=0.000);使用Endostatin联合放射线及单用Endostatin组,肿瘤新生血管减少,HIF-α表达降低.结论:放射线联合Endostatin的策略,其肿瘤控制率优于单用Endostatin或单用放射线,且能明显抑制HNE1鼻咽癌移植瘤生长和转移.照射后使用Endostatin可以在较短的时间获得较好的局部控制率;而先给予Endostatin再照射具有明显的放射增敏作用,可获得较长的再生长延缓时间,但两者的长期疗效无明显统计学差异(P=0.077).提示采用分割照射方案同时加用Endostatin可能会取得更好的临床疗效.     

高聚生联合化疗腹腔用药治疗恶性腹水140例疗效观察

目的观察高聚生(HASL)联合化疗药物(FEM)腹腔用药治疗消化道恶性肿瘤患者腹水疗效.方法140例消化道肿瘤并恶性腹水患者按随机号分为HASL治疗组(A组)、FEM化疗组(B组)和FEM+HASL治疗组(C组).结果C组有效率(34.5%)显著高于A组(13.3%,P＝0.027),而与B组(20.0%)比较无显著性差异(P＞0.05).以胃癌疗效最高,其次为胰腺癌和结肠癌,肝癌疗效最差.A组副作用最少(22.2%),B组副作用最高(97.5%),C组副作用(56.4%)比B组显著减少(P＜0.001).结论对消化道恶性肿瘤患者腹水的治疗中,HASL联合化疗药物经腹腔途径给药,既可提高化疗药物抗癌疗效,还可以降低化疗药物的毒副作用.     

放射线联合人血管内皮生长抑素对HNE1鼻咽癌移植瘤生长抑制作用

目的研究放射线联合重组人血管内皮生长抑素(Endostatin)对HNE1鼻咽癌移植瘤生长、转移的抑制作用.方法应用裸鼠建立HNE1移植瘤模型;待瘤体平均体积达627mm3±47mm3,40只裸鼠随机分成治疗组单独放疗(RT)组,单用Endostatin组,单次20cy照射后 连续使用Endostatin 14天组,连续使用Endostatin 14天后 单次20Gy照射组和空白对照组;绘制肿瘤生长曲线;取瘤体用免疫组化检测乏氧诱导因子-α(HIF-α)和微血管内皮CD34的表达,观察肿瘤乏氧及其微血管密度的变化.结果与空白对照组比较,照射20GY后 连续Endostatin 14天组,其照射后20天抑瘤率84.79%,而先用Endostatin组 后照射组及单独照射组,单独使用Endostatin(使用完14天以后的第7天)组的抑瘤率分别是83.91%,64.95%,19.47%;其中各放射治疗组的减瘤率分别为44.1%,54.1%和18.1%(P=0.000);使用Endostatin联合放射线及单用Endostatin组,肿瘤新生血管减少,HIF-α表达降低.结论放射线联合Endostatin的策略,其肿瘤控制率优于单用Endostatin或单用放射线,且能明显抑制HNE1鼻咽癌移植瘤生长和转移.照射后使用Endostatin可以在较短的时间获得较好的局部控制率;而先给予Endostatin再照射具有明显的放射增敏作用,可获得较长的再生长延缓时间,但两者的长期疗效无明显统计学差异(P=0.077).提示采用分割照射方案同时加用Endostatin可能会取得更好的临床疗效.     

化瘀解毒抗癌散抗肿瘤作用的实验研究

目的　观察化瘀解毒抗癌散对小鼠实验性肿瘤的抑制作用。方法　采用S3 7肉瘤瘤株 ,EAC瘤株 ,H2 2 瘤株。用昆明种小鼠建立模型 ,化瘀解毒抗癌散 10、5、2 5g/Kg三个剂量组灌胃给药 ,观察该药对小鼠肿瘤的抑制作用。结果　化瘀解毒抗癌散对S3 7小鼠肉瘤的抑瘤率为 2 7 4%～ 5 3 6% ;对EAC实体瘤小鼠的抑瘤率为 2 3 8%～ 42 9;对H2 2 实体瘤小鼠的抑瘤率为 2 7 5 %～ 69 8%。结论　化瘀解毒抗癌散对小鼠实验性肿瘤有明显的抑制作用     

立体定向放射治疗肺癌脑转移疗效分析

目的探讨不同放射治疗方法对肺癌脑转移的疗效.方法176例由病理学证实的肺癌脑转移患者分为4组:单纯全脑放疗(WBRT)组、全脑放疗加立体定向放射外科(WBRT SRS)组、单纯立体定向放射治疗(SRT)组、全脑放疗加立体定向放射治疗(WBRT SRT)组.SRS治疗单次靶区平均周边剂量8～20Gy,总剂量20～32Gy;SRT治疗单次靶区平均周边剂量2～5Gy,总剂量25～60Gy;WBRT1.8～2Gy/次,总剂量30～40Gy.结果四组的局部控制率分别为47.0%、87.7%、86.5%和78.0%;中位生存期分别为5.0,11.0,11.5和10.0个月;局部无进展生存期分别为3.33,8.33,9.33和7.67个月;颅脑无新病灶生存期分别为4.11,8.57,9.03和6.12个月.在死因分析中,WBRT组死于脑转移的比率为57.6%,较其他三组高.而WBRT SRS组的晚期放射反应的发生率为12.2%,较其他组高.结论肺癌单发脑转移瘤患者的最佳治疗方式是单纯立体定向放射治疗,治疗失败后再行挽救性全脑照射或立体定向放疗.对于多发脑转移,全脑放疗加立体定向放射治疗(WBRT SRT)在提高生存率以及减少并发症方面优于其他治疗方法.     

高聚生配合外照射治疗鼻咽癌的临床研究

目的观察高聚生配合外照射治疗鼻咽癌的疗效.方法160例鼻咽癌随机分入放疗加高聚生组(A组)和单纯放疗组(B组).A组高聚生用法放疗前3～5天开始用1000U,肌注,每天1次,直至放疗结束.B组单纯放射治疗,每天2Gy,每周5次.两组放疗方法、剂量相同.结果放疗后3个月检查A、B两组鼻咽部肿瘤完全消退率分别为88.7%和81.3%(P＞0.05).颈部转移淋巴结完全消退率分别为86.3%和73.6%(P＞0.05).3年生存率A、B组分别为76.3%和66.3%(P＞0.05),5年生存率A、B组分别为65.0%和52.5%(P＞0.05);3年鼻咽部肿瘤控制率A、B组分别为76.3%和68.8%(P＞0.05),5年鼻咽部肿瘤控制率A、B组分别为71.3%和58.8%(P＞0.05);3年颈淋巴结转移灶控制率A、B组分别为72.6%和62.5%(P＞0.05),5年颈淋巴结转移灶控制率A、B组分别为61.6%和48.6%(P＞0.05).5年远处转移发生率A、B组分别为28.8%和42.5%(P＜0.05).A组急性毒副反应与B组相似.结论高聚生配合外照射治疗鼻咽癌无明显提高患者的生存率和局部控制率,但有助于降低远处转移的发生.     

小鼠可移植性膀胱移行细胞癌株（BTT739）的建立及实验研究

用化学致癌剂ＢＢＮ诱异Ｔ７３９近交系小鼠膀胱肿瘤，于诱癌２６周时，将其中１只雄性小鼠膀胱癌往同种系小鼠皮下移植获成功。於１９９１年５月２５日建立了我国第一株小鼠可移植性膀胱癌模型，经２年多时间，已移植传代５６代次，其生物学和病理学特征已相对稳定，在同系小鼠移植成功率１００％，无自然消退现象，带瘤小鼠平均存活５４天，病理组织学检查证实ＢＴＴ７３９为低分化小鼠膀胱移行细胞癌，经２０种抗癌药物药敏试验结果表明对其中的１６种显示不同程度敏感。     

依维莫司负调控mTOR信号通路对膀胱癌BTT739细胞增殖和迁移的抑制作用及机制研究

目的:探索mTOR抑制剂依维莫司(RAD001)对膀胱癌BTT739细胞在体外和小鼠体内增殖和迁移的抑制作用及其作用机制,为依维莫司在临床上治疗膀胱癌提供理论依据。方法:体外培养小鼠膀胱癌BTT739细胞,待其生长至对数期后用梯度浓度的RAD001（0 nmol/L、5 nmol/L、10 nmol/L和20 nmol/L）干预24 h,用MTT法检测细胞增殖的变化;Tranwell实验检测RAD001对BTT739细胞迁移的影响;ELISA试剂盒检测细胞分泌蛋白E-钙黏蛋白表达的变化。Western blot检测Akt、mTOR、4EBP和PTEN蛋白的表达,RT-PCR检测mTOR mRNA的表达。将BTT739细胞接种于昆明鼠皮下,待成瘤后,用依维莫司干预14天,取小鼠肿瘤组织检测E-钙黏蛋白及AKT、mTOR、4EBP和PTEN蛋白表达的情况。结果:体外实验显示RAD001可以抑制BTT739细胞的增殖和迁移并与剂量有关（P＜0.05）。还可以增加E-钙黏蛋白的含量,抑制癌细胞的转移。实验证明RAD001在体外抑制Akt、mTOR、4EBP的表达,促进肿瘤抑制因子PTEN的表达（P＜0.05）。将BTT739细胞接种于小鼠皮下后发现,RAD001在小鼠体内亦可以抑制病变情况,促进PTEN和E-钙黏蛋白的表达,抑制Akt、mTOR和4EBP的表达。结论:mTOR抑制剂依维莫司通过抑制mTOR信号通路抑制膀胱癌细胞BTT739的增殖、迁移和侵袭。     

联合应用Ag85A和GM-CSF DNA疫苗对小鼠移植性膀胱癌BTT739细胞瘤免疫治疗的研究

目的:探讨联合应用Ag85A与GM-CSF DNA疫苗对小鼠移植性膀胱癌BTT739细胞瘤免疫治疗的效果。方法:选用小鼠膀胱癌BTT739细胞株,构建T739小鼠移植瘤模型。随机数字表法分为5组:生理盐水组、空载体组、Ag85A组、联合应用组和BCG组。荷瘤后第7天、14天和21天各肌注1次,末次注射后第7天检测各组小鼠脾脏的CD4+和CD8+T细胞亚群数量及CD4+/CD8+比值、血清IFN-γ和肿瘤重量。结果:与生理盐水组对比,单独应用Ag85A和联合应用Ag85A与GM-CSF DNA疫苗均能够升高CD4+和CD8+T细胞的百分比及CD4+/CD8+的比值,提高血清IFN-γ浓度,降低移植瘤重量,差异具有统计学意义(P<0.05)。联合应用的效果要明显优于单独应用组,差异具有统计学意义(P<0.05),但尚不及单纯应用BCG的免疫治疗效果。结论:联合应用Ag85A与GM-CSF DNA疫苗能够提高荷瘤小鼠的免疫功能,从而达到了抑制肿瘤生长的作用,其效果明显优于单独应用Ag85A DNA疫苗,二者联用具有协同增强免疫效应。     

联合应用Ag85A和GM-CSF DNA疫苗对小鼠移植性膀胱癌BTT739细胞瘤免疫治疗的研究

目的：探讨联合应用Ag85A与GM-CSF DNA疫苗对小鼠移植性膀胱癌BTT739细胞瘤免疫治疗的效果。方法：选用小鼠膀胱癌BTT739细胞株,构建T739小鼠移植瘤模型。随机数字表法分为5组：生理盐水组、空载体组、Ag85A组、联合应用组和BCG组。荷瘤后第7天、14天和21天各肌注1次,末次注射后第7天检测各组小鼠脾脏的CD4＋和CD8＋T细胞亚群数量及CD4＋/CD8＋比值、血清IFN-γ和肿瘤重量。结果：与生理盐水组对比,单独应用Ag85A和联合应用Ag85A与GM-CSF DNA疫苗均能够升高CD4＋和CD8＋T细胞的百分比及CD4＋/CD8＋的比值,提高血清IFN-γ浓度,降低移植瘤重量,差异具有统计学意义（P〈0.05）。联合应用的效果要明显优于单独应用组,差异具有统计学意义（P〈0.05）,但尚不及单纯应用BCG的免疫治疗效果。结论：联合应用Ag85A与GM-CSF DNA疫苗能够提高荷瘤小鼠的免疫功能,从而达到了抑制肿瘤生长的作用,其效果明显优于单独应用Ag85A DNA疫苗,二者联用具有协同增强免疫效应。     

A novel immunocompetent murine tumor model for the evaluation of RCAd-enhanced RDAd transduction efficacy

Low gene transfer rate in tumors, high dose-induced acute inflammatory response, and lack of an immunocompetent preclinical animal model to accurately reflect the therapeutic efficacy are prominent reasons for the lack of clinical success of adenoviral (Ad) vectors. In this study, we tested whether human replication-competent adenovirus (RCAd) can replicate in T739 mouse bladder transitional tumor cells (BTT) and lung adenocarcinoma cells (LA795), and whether RCAd can enhance the transduction rate and transgene expression of human replication defective adenoviruses (RDAd) in these tumor cells in vitro and in vivo. We demonstrated that human RCAd exhibited good infectability and cytopathologic effects in mouse BTT and LA795 cells, which was comparable to that in A549 and NCIH460 human tumor cells. In contrast, no infectability and cytopathologic effects were observed in other three mouse tumor cells such as 4T1, B16, and Lewis cells. The combined use of RCAd with RDAd significantly enhanced RDAd transduction efficiency in BTT and LA795 tumor cells in vitro and in vivo. When BTT and LA795 cells were co-infected with RDAd Ad-EGFP and RCAd, a large amount of E1a expression and 2-3 orders of increases in Ad-EGFP genomic DNA were observed. In contrast, the expression of the late gene Hexon is very low, which may explain ineffective packaging of viral particles. In conclusion, our study provided a novel immunocompetent animal model which is useful for evaluating RCAd infectability, cytopathy, and replication. The combined use of RCAd and RDAd provided a new solution for cancer gene therapy.     

Antitumor effects of recombinant human Interleukin-6 on mouse bladder carcinoma through Fas-mediated apoptosis

Purpose

An apoptosis-inducing therapy is gradually becoming a new strategy for cancer treatment. The aim of this study was to investigate the mechanism of growth-inhibitory effects of recombinant human interleukin-6 (rhIL-6) on bladder tumor-bearing T739 mice in vivo.

Methods

Murine bladder transitional carcinoma cells (BTT739) were inoculated subcutaneously into T739 mice as a tumor model for evaluating the antitumor effects of rhIL-6. Then the mice were divided randomly into 5 groups: A, B, C, D and E. Different doses (0, 2, 4, 8 × 10⁶ IU/kg body weight) of rhIL-6 were injected intraperitoneally twice per day and administered for 14 days, and 1 mg/kg/d mitomycin-C(MMC) was used as control. Tumor size was measured and determined as the mean of the largest diameter and the diameter at right angle. Animals were killed by CO₂ inhalation on the 15th day after tumor cell inoculation. Then, tumors were removed, weighed and collected. The tumor growth inhibition rate of rhIL-6 was calculated. The morphological characteristic changes of tumor cells were observed under electron microscope, and cell cycle analysis was determined by flow cytometry. The expressions of Fas, FasL and Bcl-2 protein on tumor cells were qualitatively detected by immunofluorescence cell staining, and their relative contents (rate of positive cells, RPC) were quantitatively determined with flow cytometry.

Results

rhIL-6 could inhibit bladder tumor growth in a dose-dependent manner in vivo. The tumor growth-inhibitory rates of 2, 4, 8 × 10⁶ IU/kg rhIL-6 and 1 mg/kg MMC were 11.8, 39.5, 39.7 and 68.8%, respectively. Flow cytometry results showed that a hypodiploid peak before G1 phase could be found in tumor cells treated with rhIL-6. Moreover, the cells treated with rhIL-6 displayed disappearance of nucleoli, chromatin gathering under the nuclear membrane in mass or ring-shape under transmission electron microscopy. The rates of Fas, FasL protein–positive cells estimated by flow cytometry in rhIL-6-treated mice were (12.57 ± 0.83) and (20.1 ± 0.87) %, respectively, significantly higher than that (4.66 ± 0.17) and (14.1 ± 0.83) % in control mice (P < 0.01). There was no significant difference in the rate of Bcl-2 protein–positive cells between the mice in these two groups (P > 0.05).

Conclusions

rhIL-6 had obvious antitumor effects on mouse bladder carcinoma in vivo, and the Fas signaling pathway might play an important role in rhIL-6-induced bladder carcinoma cell apoptosis.     

Interactions of Radiation and Cancer Chemotherapeutic Drugs in a C3H Mouse Mammary Carcinoma

The interactions of radiation and adriamycin (ADM), bleomycin (BLM), cyclophosphamide (CTX), 5-fluorour-acil (5-FU), methotrexate (MTX), mitomycin C (MM-C), or cis-diamminedichloroplatinum II (cis-DDP) were studied in a spontaneously arisen C3H mouse mammary carcinoma. The tumour response to drugs alone was evaluated by measuring the tumour growth time defined as the time required for a tumour to reach a volume 5 times that of the treatment day. CTX resulted in a marked tumour growth delay whereas the other drugs had a modest or uncertain effect. In the combined treatment experiments, drugs were administered as single doses either 15 min before or 4 hours after graded single doses of irradiation. The end point for each treatment was the radiation dose which on an average was required to achieve local tumour control in 50 per cent of the mice (TCD_So). The dose effect factor (DEF) was 1.16 for ADM and 1.17 for CTX, the enhanced radiation response being independent of administration before or after irradiation. MM-C also decreased the TCD₅₀ for radiation alone, but its effect was more marked 15 min before (DEF 1.32) than 4 hours after irradiation (DEF 1.18). BLM, 5-FU, MTX, and cis-DDP had no effect on the radiation response neither when administered 15 min before nor 4 hours after irradiation.     

转染wt—p53对小鼠移行细胞癌生物学行为影响的研究

为进一步探讨膀胱瘤的治疗途径,方法利用Ｌｉｐｏｆｅｃｔａｍｉｎｅ将外源性野生型ｐ５３基因导入小鼠膀胱移行细胞癌ＢＳＴ７３９细胞中,并行到表达。结果细胞在体外标准条件下,生长增殖率降低。流式细胞计检测：细胞周期分析显示Ｇ０＋Ｇ１细胞比例明显增高,凋亡指数升高,细胞生长速度减低,细胞增殖能力下降,体内接种致瘤性下降。结论增加野生型Ｐ５３基因表达能抑制恶性肿瘤的生长。     

Effect of recombinant human keratinocyte growth factor (rHuKGF, Palifermin) on radiation-induced mouse urinary bladder dysfunction

PURPOSE: To determine the effect of Palifermin (rHuKGF) on acute and late radiation effects in mouse urinary bladder. METHODS AND MATERIALS: Graded radiation doses were applied on day 0. Single subcutaneous injections of Palifermin (15 mg/kg) were given on day -2 or day +2. Changes in bladder function (i.e., a reduction in bladder volume by >or=50% of the individual preirradiation value) were assessed by cystometry. RESULTS: Early changes in mouse bladder after irradiation occur in two phases. In the first early phase, a single injection of Palifermin on day -2 increased the ED(50) (dose associated with a positive bladder response in 50% of the mice) from 20.0 +/- 3.3 Gy to 27.1 +/- 6.9 Gy (p < .0051). Palifermin given on day +2 was not beneficial. No significant effects of Palifermin were seen in the second early phase. However, Palifermin administration before, but not after, irradiation, also modified late radiation effects, with an ED50 of 22.2 +/- 4.8 Gy compared with 16.2 +/- 4.9 Gy in control animals (p < .0187). CONCLUSIONS: Initial early functional changes in the mouse urinary bladder after irradiation as well as late effects can be significantly reduced by a single administration of Palifermin before irradiation.