蛋珍油对家兔放射性食管损伤防治作用的实验研究

目的:用家兔放射性食管损伤的模型来评价中药制剂蛋珍油对放射性食管炎的防治作用.方法:24只雄性家兔按随机抽签法分为单纯照射(R)组、蛋珍油给药(D)组、思密达给药(S)组和正常对照(C)组,每组6只.家兔清醒状态下,用直线加速器对R组、D组和S组家兔全胸部照射,照射剂量单次15Gy,源皮距(SSD)为100cm,照射面积7cm×3cm,照射剂量率200cGy/min.C组未行照射.蛋珍油给药量,7ml/次,思密达药量3g/次.每天分3次经口腔缓慢地给药,连续给药5天后立即统一处死家兔.取材切片,行苏木精一伊红(HE)染色,在光镜下观察食管组织病理学改变,用Western-bloting和RT-PCR技术分别检测IL-8和TGF-β1蛋白及mRNA表达水平.结果:D组家兔食管组织于照射后第5天放射性食管损伤比照射组明显减轻.D组IL-8和TGF-β1蛋白相对含量(0.589±0.053,0.511±0.022)较R组(0.744±0.026,0.686±0.091)明显减弱(P<0.01),与S组(0.547±0.062,0.496±0.066)差异无统计学意义(P>0.05).RT-PCR结果显示,R组的IL-8和TGF-β1mRNA相对含量(0.697±0.076,0.626±0.071)较D组(0.149±0.056,0.162±0.022),S组(0.332±0.081,0.396±0.018)和C组(0.126±0.092,0.108±0.058)差异均有统计学意义(P<0.01),D组IL-8和TGF-β1mRNA相对含量低于S组(P<0.05).结论:成功地复制了放射性食管损伤急性期动物模型,并发现蛋珍油能明显减轻辐射所引起食管损伤的病理改变,抑制放射性食管损伤中IL-8和TGFβ1蛋白表达及mRNA表达,对家兔急性放射性食管炎具有一定防治作用.     

γ-IFN对于兔盆腔常规分割照射后输尿管放射性损伤及纤维化的影响

目的:探讨γ-IFN对兔盆腔常规分割照射后输尿管放射性损伤及纤维化的影响.方法:建立兔放射性输尿管损伤的动物模型,52只新西兰兔随机分为常规照射组、组及正常对照组,除正常对照组外其余兔盆腔均接受6MV-X线照射.γ-IFN组从照射后第5天给予γ-IFN250,000U·kg-1,肌注每周1次,共5次.常规照射组给予5ml·kg-1的生理盐水.照射后4周,8周,12周,16周处死实验兔,取其照射范围内的输尿管组织.用HE染色,原位杂交染色及免疫组化方法分析γ-IFN对于放射性输尿管损伤及纤维化影响.结果:HE染色观察放射线导致输尿管损伤的组织结构变化,γ-IFN组与单纯照射组比较,照射后4,8,12周其损伤程度均有显著性差异(P<0.05),16周则无显著性差异(P>0.05);TGF-β1 mRNA原位杂交实验,γ-IFN组输尿管黏膜的TGF-β1 mRNA表达在照射后4,8,12,16周低于常规照射组,有显著性差异(P<0.05),与正常对照组比较也有显著性差异(P<0.05);Ⅲ型胶原免疫组化结果显示γ-IFN组与单纯照射组均存在显著性差异(P<0.05),较正常对照组差异有显著性(P<0.05).结论:γ-IFN能够减轻实验兔放射性输尿管损伤,抑制放射后输尿管黏膜TGF-β1 mRNA的升高,降低Ⅲ型胶原的表达,减轻放射性输尿管损伤及纤维化的形成.     

丹参酮ⅡA对放射性肺纤维化防治作用的实验研究

目的探讨丹参酮ⅡA对分次照射放射性肺纤维化的防治效果及机制。方法雌性Wistar大鼠,6 MV X线右胸照射,3 Gy/次,5次/周,总量30 Gy。每次照射前1 h腹腔注射丹参酮ⅡA磺酸钠15 mg/kg。照射后5个月取大鼠肺组织进行HE染色、Masson染色、转化生长因子-β1(TGF-β1)免疫组化染色、羟脯氨酸含量及实时荧光定量RT-PCR检测TGF-β1 mRNA的表达变化。结果每克湿肺羟脯胺酸含量在对照组、照射组与丹参酮加照射组分别为(21.99±3.96)、(38.25±7.18)(、28.94±4.29)μg/g。照射组较对照组肺泡炎、纤维化病变加重,羟脯氨酸含量、TGF-β1蛋白及mRNA的表达升高;丹参酮加照射组较照射组肺泡炎、纤维化病变减轻,羟脯氨酸含量、TGF-β1表达下降。结论丹参酮ⅡA能增加肺组织对放射性损伤的耐受,其机制可能通过抑制TGF-β1表达,使炎症及纤维化病变减轻。     

IFN-γ对兔盆腔术中照射后直肠组织TGF-β1 mRNA表达的影响

目的:通过观察手术中一次性大剂量照射后不同时相兔直肠组织的病理变化和转化生长因子-β1(TGF-β1)含量的动态变化,以及IFN-γ早期干预的影响,探讨IFN-γ防治兔直肠组织大剂量照射后损伤的作用和机理.方法: 雌性新西兰大白兔54只,体重(2000±200)g,随机分为单纯照射组(R组,25只),药物干预组(I组,25只),空白对照组(C组,4只).手术中直视下用直线加速器给予R组和I组全盆腔一次性大剂量照射(20Gy),于术中照射后当天开始每隔4天给予I组肌注IFN-γ 250000U/kg/f,共5次;R组、I组于术中照射后第4周,8周,12周,16周,20周分别处死5只兔(经耳缘静脉空气栓塞致死),C组于实验完成时处死,取直肠组织切片行原位杂交法测TGF-β1 mRNA比较不同时相各组直肠组织TGF-β1 mRNA的表达水平.结果: R组TGF-β1 mRNA于照射后第4 周增高,第20周含量最多; I组与R组比较差异有显著性(P<0.05).结论: 给予一次性大剂量术中照射后,兔直肠组织TGF-β1 mRNA的表达随时间的推移而增多,而早期应用IFN-γ干预可明显抑制TGF-β1的表达,可减轻早期放射性炎症反应及后期放射性纤维化的程度.     

大鼠急性放射性肝损伤及其保护的实验研究

目的:探讨活性氧自由基(ROS)、一氧化氮(NO)和TGF-β1在大鼠急性放射性肝损伤中的机制及细胞保护剂安福定对大鼠急性放射性肝损伤的保护作用.方法:健康雄性SD大鼠48只,随机分成正常对照组(C组)、安福定组(A组)、单纯照射组(X组)3组各16例.正常对照组不予照射.其余两组给予一次性全肝照射,照射剂量20Gy.安福定组于照射前30 min腹腔内注射安福定200mg/kg;单纯照射组则照射前腹腔注射等容量的生理盐水.结果:照射后第4、8、14天的血ALT、AST、肝组织光镜未出现明显变化.电镜下明显的超微结构改变.单纯放射组大鼠血浆ROS活性明显高于正常对照组(P<0.05).安福定组血浆MDA含量显著低于正常对照组,而SOD活性则高于正常对照组.单纯放射组大鼠血浆NO含量明显高于正常对照组和安福定组(P<0.05).照射后第14天单纯放射组大鼠血浆TGF-131含量明显高于正常对照组和安福定组(P<0.05).结论:ROS、NO和TGF-β1都参与了急性放射性肝损伤.NO和TGF-β1则分别作为炎症介质和炎性细胞因子在损伤的进程中起关键作用.安福定对放射性肝损伤有保护作用.测定血MDA含量及SOD活性、NO和TGF-β1比血ALT、AST更早提示放射性肝损伤.     

放射性肺损伤形成过程中一氧化氮与转化生长因子-β1的协同作用研究

目的:观察一氧化氮(NO)与转化生长因子-β1(TGF-β1)在放射性肺损伤形成过程中的协同作用。方法:实验兔分为对照组和L-NAME组,采用6MVX线对左全肺进行照射,25Gy,1次。将2组动物再各自随机分为3组,分别于照射后1、3和6个月各自处死一组动物,照射前及处死前进行双肺血流同位素扫描及左肺肺泡灌洗。进行灌洗液NO及TGF-β1测定及肺组织病理分期。结果:在照射后1个月,对照组及L-NAME组的NO含量分别为(0.48±0.26)和(0.30±0.11)μmol/L,均明显高于放疗前水平,L-NAME组的升高幅度低于对照组。在照射后1、3和6个月,对照组的TGF-β1含量分别为(0.58±0.15)、(0.30±0.10)和(0.59±0.28)ng/mL,均明显高于放疗前水平,L-NAME组TGF-β1的升高幅度低于对照组。放疗后肺血流呈持续下降趋势。对照组放射性肺炎发生率(5/5)高于L-NAME组(2/5)。结论:NO在放疗早期的明显升高放疗后肺血流的持续下降是放射性肺损伤的发病机制之一;NO与TGF-β1在放射性肺损伤的形成过程中具有协同作用。     

γ-IFN对于兔盆腔常规分割照射后输尿管放射性损伤及纤维化的影响

目的：探讨γ-IFN对兔盆腔常规分割照射后输尿管放射性损伤及纤维化的影响.方法：建立兔放射性输尿管损伤的动物模型,52只新西兰兔随机分为常规照射组、组及正常对照组,除正常对照组外其余兔盆腔均接受6MV-X线照射.γ-IFN组从照射后第5天给予γ-IFN250,000U·kg-1,肌注每周1次,共5次.常规照射组给予5ml·kg-1的生理盐水.照射后4周,8周,12周,16周处死实验兔,取其照射范围内的输尿管组织.用HE染色,原位杂交染色及免疫组化方法分析γ-IFN对于放射性输尿管损伤及纤维化影响.结果：HE染色观察放射线导致输尿管损伤的组织结构变化,γ-IFN组与单纯照射组比较,照射后4,8,12周其损伤程度均有显著性差异（P〈0.05）,16周则无显著性差异（P〉0.05）;TGF-β1 mRNA原位杂交实验,γ-IFN组输尿管黏膜的TGF-β1 mRNA表达在照射后4,8,12,16周低于常规照射组,有显著性差异（P〈0.05）,与正常对照组比较也有显著性差异（P〈0.05）;Ⅲ型胶原免疫组化结果显示γ-IFN组与单纯照射组均存在显著性差异（P〈0.05）,较正常对照组差异有显著性（P〈0.05）.结论：γ-IFN能够减轻实验兔放射性输尿管损伤,抑制放射后输尿管黏膜TGF-β1 mRNA的升高,降低Ⅲ型胶原的表达,减轻放射性输尿管损伤及纤维化的形成.     

阿米福汀对单次肺照射的保护作用及TGF-β1活性的影响

目的用大鼠放射性肺损伤模式评价阿米福汀对单次肺照射的放射性肺损伤保护作用和对TGFβ1活性变化的影响。方法34只150～160g的Fish344雌性大鼠随机进入照射加药(11只)、单纯照射(11只)、单用药(6只)和正常对照(6只)实验组。用4MVX射线单次28Gy照射右全肺,照射前30min腹腔内注射阿米福汀150mg/kg。每2周观测呼吸频率和血浆转化生长因子(TGFβ1)水平,在6个月后终止观察。肺组织进行羟脯胺酸、胶原蛋白含量、总TGFβ1与活性TGFβ1水平、TGFβ1蛋白表达和巨噬细胞量等检测。结果单纯照射组呼吸频率于第8周发生改变、达(185±13)次/min,3只因呼吸困难终止观察,7只有胸腔积液;照射加药组于第14周开始增加,仅为(125±5)次/min,无呼吸困难和胸腔积液发生。单纯照射组的肺组织结构消失纤维化,照射加药组也有纤维化,但保持大部分肺泡结构。血浆TGFβ1水平呈双峰改变,单纯照射组12周时为(3.2±0.5)ng/ml,较照射加药组(1.3±0.3)ng/ml明显增高(P=0.004);肺组织活性TGFβ1与总TGFβ1含量之比分别为3.9%±0.2%与3.1%±0.2%,单纯照射明显高于照射加药组(P<0.05)。结论阿米福汀不仅能增加肺组织对放射性损伤的耐受,同时也能减少TGFβ1的含量与表达,也许同时能减少TGFβ1的活性表达。     

β-榄香烯对肝癌细胞SK-hep-1的迁移和侵袭力的影响

目的:观察β-榄香烯对肝癌SK-hep-1细胞的侵袭、转移等生物学行为的影响,探讨其对MMP2基因的调节.方法:将SK-hep-1细胞分为3组:control组、β-榄香烯(80μg/ml)组、TGF-β1(transforming growth factor β1,TGF-β1)(10μg/ml)组,RT-PCR检测各组细胞的MMP2(matrix metalloproteinase-2,MMP2)mRNA表达;通过划痕试验及transwell细胞侵袭试验进一步对β-榄香烯作用的肝癌细胞迁移和侵袭能力进行分析.结果:β-榄香烯作用肝癌细胞中MMP2mRNA表达低于control组和TGF-β1组(P<0.05).β-榄香烯组穿膜细胞数(50±10)少于control组(150±16)及TGF-β1组(300±13),(P<0.05).β-榄香烯组细胞的迁移数(92±8)明显低于control组(180±14)及TGF-β组(300±20),差异具有统计学意义(P<0.05).结论:β-榄香烯能下调肝癌细胞SK-hep-1的MMP2mRNA表达,降低肝癌细胞的侵袭、迁移能力.     

益气活血中药对放射损伤大鼠肺组织TGF-β1和Ⅰ、Ⅲ型胶原合成的影响

目的:观察小剂量重复照射下不同时相大鼠肺组织转化生长因子-β1(TGF-β1)的表达和Ⅰ、Ⅲ型胶原纤维的动态变化,以及益气活血中药干预的影响,探讨益气活血中药防治放射性肺损伤的作用及机理.方法:96只Wistar种雌性大鼠随机分为照射加中药组(A组)30只、照射加氨溴索组(B组)30只、单纯照射组(C组)30只、正常对照组(D组)6只.用直线加速器对前3组大鼠右肺进行分次照射(5Gy/次,1次/w,累积剂量为30Gy),于照射开始后第4、6、8、12、26w 5个时间点分别处死3组大鼠各6只,取肺组织切片行TGF-β1和Ⅰ、Ⅲ型胶原纤维免疫组化检测,观察各组大鼠肺组织不同时相TGF-β1的表达和胶原纤维含量的改变.结果:单纯照射组大鼠肺组织TGF-β1于照射第4w增高,第12w达到高峰;胶原纤维合成在第4w开始,第12w明显增快,至26w达到高峰.中药干预组各时相大鼠肺组织TGF-β1表达及Ⅰ、Ⅲ型胶原纤维增生程度均明显低于单纯照射组(P<0.05);各时相值与照射加氨溴索组近似,相比无统计学差异(P>0.05).结论:在小剂量重复照射过程中,组织TGF-β1表达与组织胶原纤维合成有明显的同步性,而早期应用益气活血中药可抑制TGF-β1的表达,并减轻早期放射性肺炎的炎症反应和后期放射性肺纤维化的程度,因而对放射性肺损伤具有防治作用.     

APRIL在大肠癌组织中的表达及化疗药物对大肠癌SW480细胞APRIL表达的影响

背景与目的:增殖诱导配体(a proliferation-inducing ligand,APRIL)是最近发现的肿瘤坏死因子家族新成员,有促进肿瘤生成和增殖的能力。本实验通过研究APRIL在大肠癌组织中的表达,并对比氟尿嘧啶和顺铂对大肠癌细胞株SW480表达APRIL水平的影响,探讨抗癌药对APRIL在大肠癌组织中表达的影响。方法:采用免疫组化法和荧光定量PCR检测56例大肠癌患者癌组织和配对癌旁相对正常组织及大肠癌细胞株SW480上APRIL的表达。将不同终浓度的氟尿嘧啶和顺铂加入培养中的SW480细胞,用荧光定量PCR检测加入药物后24h、48h和72hSW480细胞表达APRIL mRNA的水平。结果:大肠癌组织表达APRIL的阳性率为76.8%,mRNA水平为0.71±0.08,高于癌旁相对正常组织的16.1%和0.16±0.05(P<0.001)。SW480细胞上有明显的APRIL表达,加入不同浓度的氟尿嘧啶后,SW480细胞APRIL的mRNA水平逐渐升高,至72h表达最高,25、50、100、200μg/mL4个药物浓度作用72h后细胞APRIL mRNA水平分别为0.85±0.10、0.81±0.09、0.83±0.11和0.90±0.12,与空白对照(0.57±0.06)相比差异有统计学意义(P<0.001);而加入不同浓度的顺铂后,细胞APRILmRNA水平与空白对照相比差异无统计学意义(P>0.05),仅在10、20μg/mL浓度作用72h后细胞的APRIL mRNA水平(分别为0.44±0.05,0.40±0.07)低于空白对照(P<0.05)。结论:APRIL在大肠癌的进展过程中可能起到一定程度的促进作用;氟尿嘧啶可能具有对抗APRIL功能的潜在作用。     

乳腺癌淋巴化疗与静脉化疗后腋窝淋巴结药物浓度的比较

背景和目的:淋巴结状态是乳腺癌重要的预后因素之一,区域淋巴组织靶向化疗是近几年出现的针对高淋巴转移倾向肿瘤的治疗方法。本研究检测乳腺癌患者淋巴化疗(lymphaticchemotherapy,LC)后腋窝淋巴结内的药物浓度,并与静脉化疗(intravenouschemotherapy,VC)作对比,以确定LC能否有效提高区域淋巴结内抗癌药物的聚积。方法:60例乳腺癌患者随机分为LC组和VC组,每组30例,所有患者均于术前穿刺活检明确诊断。LC组在癌灶周围皮下注射卡铂鄄活性炭混悬液5mg/ml,VC组给予同等剂量卡铂水溶液静脉化疗。给药后1、12、24、36、48h分别行乳腺癌改良根治术,每组每个时间点各6例患者。术中常规清扫腋窝淋巴结并送病理检查,原子吸收光谱法(AAS)测定淋巴结内卡铂浓度。结果:术中共切除淋巴结275枚,其中LC组154枚,VC组121枚。共有23例(38.3%)患者的146枚(53.1%)淋巴结发现癌转移。LC组给药后1、12、24、36、48h腋窝淋巴结中卡铂浓度分别为(11.82±3.50)、(23.58±7.34)、(18.22±4.93)、(16.70±5.15)、(14.62±4.29)μg/g,VC组在给药后1、12、24、36h分别为(0.06±0.02)、(0.11±0.05)、(0.10±0.02)、(0.05±0.02)μg/g,给药后48h淋巴结内未检测出卡铂,两组间差异有极显著性(P<0.001)。淋巴结药物浓度与癌转移之间无明显     

Histopathologic amelioration of fibroproliferative change in rat irradiated lung using soluble transforming growth factor-beta (TGF-beta) receptor mediated by adenoviral vector

PURPOSE: To investigate whether an adenoviral-mediated soluble transforming growth factor-beta (TGF-beta) type II receptor could ameliorate fibroproliferative change in rat irradiated lung. METHODS AND MATERIALS: We used an adenoviral vector expressing a soluble TGF-beta receptor (AdT beta-ExR), which adsorbs TGF-beta and inhibits the function of the wild-type receptor as a dominant-negative mutant. Rats were i.v. injected with either 0.5 mL of AdT beta-ExR (1.0 x 10(9) plaque-forming units/mL) or AdLacZ (1.0 x 10(9) plaque-forming units/mL), a control adenovirus expressing bacterial beta-galactosidase, or saline, then 3 days later they received 4-MV X-ray irradiation of 30 Gy in a single fraction to the right lung. Eight weeks after irradiation, the rats were killed, and their right lungs were examined histopathologically. The respiratory rates of all rats were observed with a charge-coupled device video system before the rats were irradiated and killed. RESULTS: A significant increase in breathing rates was observed in the saline- or AdLacZ-infected rats. The respiratory rate of the AdT beta-ExR-treated rats was significantly lower than that in the saline- or AdLacZ-infected rats. Fibroproliferative change in the irradiated lung was markedly reduced in the AdT beta-ExR-treated rats in comparison with the saline- or AdLacZ-infected rats. With respect to active TGF-beta 1 expression, myofibroblast proliferation, and macrophage/monocyte infiltration, the findings were identical to those for fibroproliferative change. CONCLUSIONS: Our results indicate that TGF-beta plays a critical role in radiation-induced fibroproliferation of the lung and suggest that the adenoviral-mediated soluble TGF-beta receptor may have potential for use in the amelioration of this intractable pulmonary damage.     

Elevated serum levels of transforming growth factor-beta1 in patients with colorectal carcinoma: its association with tumor progression and its significant decrease after curative surgical resection

BACKGROUND: Transforming growth factor-beta1 (TGF-beta1) acts as a potent inhibitor of cell growth and tumor progression but loss of this negative regulation can contribute to tumor development. Some studies have reported an association between disease progression and TGF-beta1 expression in patients with colorectal carcinoma, but their results were not always consistent. METHODS: Serum levels of TGF-beta1 were measured using an enzyme-linked immunoadsorbent assay in 121 consecutive patients with colorectal carcinoma and compared with TGF-beta1 serum levels in 31 healthy volunteers. Serum levels of TGF-beta1 also were measured in 50 patients who underwent curative surgical resection (part of the 121 preoperative patients) to compare their levels with preoperative serum levels of TGF-beta1. RESULTS: Serum levels of TGF-beta1 in patients with colorectal carcinoma (45+/-15 ng/mL) (mean+/-the standard deviation) were significantly higher than those in the healthy control group (32+/-4 ng/mL) (P = 0.001). Serum levels of TGF-beta1 increased with increasing tumor stage (P < 0.01). Serum levels of TGF-beta1 were correlated significantly with depth of tumor invasion, lymph node metastasis, distant metastasis, and serum levels of carcinoembryonic antigen (CEA). Serum levels of TGF-beta1 tended to increase with increasing CEA (correlation coefficient = 0.21; P < 0.05). The mean serum level of TGF-beta1 in patients with colorectal carcinoma before surgery (45+/-14 ng/mL) (n = 50) significantly decreased to 34+/-7 ng/mL, which was within the normal range (32+/-4 ng/mL), after curative surgical resection of the tumor (P = 0.0000). Serum levels of TGF-beta1 after tumor resection decreased more significantly in patients with higher preoperative levels of TGF-beta1 (from 53+/-12 ng/mL to 36+/-6 ng/mL) (n = 30). CONCLUSIONS: The results of the current study suggest that serum levels of TGF-beta1 in colorectal carcinoma patients may be associated with disease progression and may be used as a biomarker in the management of colorectal carcinoma patients. The authors believe further studies with a large number of patients for a longer follow-up period are necessary to conclude whether serum levels of TGF-beta1 carry significant clinical relevance.     

Early alteration in TGF-beta mRNA expression in irradiated rat liver

PURPOSE: Radiation of the liver results in hepatic fibrosis as a late complication. TGF-beta has been implicated in the pathogenesis of fibrosis. The purpose of this study was to determine if there is early alteration in TGF-beta expression before hepatic fibrosis is evident. METHODS AND MATERIALS: Male Sprague-Dawley rats weighing 150-175 g were used. A partial volume of liver as large as a 2 cm x 1 cm rectangle was given a single dose of 25 Gy gamma radiation. Animals were sequentially sacrificed from day 0 to day 28. Appearance of hepatic fibrosis was tested by trichrome stain. Levels of mRNA expression of TGF-beta1 and TGF-beta3 were measured by Northern blot hybridization. Change in the level of mRNA expression was analyzed by densitometry. The expression of TGF-betas was also analyzed in tissue with immunohistochemical staining. RESULTS: In trichrome-stained liver tissues obtained through 28 days after irradiation, there was no evidence of hepatic fibrosis. The expression of mRNAs of TGF-beta1 and TGF-beta3 showed different features; The level of TGF-beta1 mRNA showed a gradual increase to the peak level of 3.6-fold at day 28, the last analyzed time. In contrast, TGF-beta3 mRNA showed an early peak of 4.8-fold at day 7 followed by a decrease to the lowest level of 1.6-fold at the last analyzed time. The expression of TGF-betas was also analyzed in tissue with immunohistochemical staining. At day 28 after radiation, increased positive staining for TGF-beta1 was observed around the central vein. Positive staining appeared mainly in nonhepatocytic cells. For TGF-beta3, the same pattern of positive staining was observed at day 7. CONCLUSION: The results of this study suggest that the alteration in mRNA expression of TGF-beta1 and TGF-beta3 occurs very early after radiation. The contrasting difference in the mRNA expression pattern of TGF-beta1 and TGF-beta3 suggests that interaction of the TGF-betas may be involved in fibrogenesis of irradiated liver, with TGF-beta1 as a positive regulator and TGF-beta3 as a negative regulator.     

Major hepatic resection may suppress the growth of tumours remaining in the residual liver

Little is known as to how hepatectomy is associated with the growth of hepatic tumours, which may reside in the remaining liver after curative resection for hepatocellular carcinoma. Using an intra-hepatic tumour implantation model in rats, the effects of hepatectomy on tumour growth in the remaining liver were investigated. On post-operative day 7, the tumour weight in the remaining liver following 30% hepatectomy was 0.321+/-0.058 g (mean +/- SD) which was significantly greater than that (0.245+/-0.040 g) in sham operations (P<0.05). However, the tumour weight (0.156+/-0.067 g) in the remaining liver following 60% hepatectomy was significantly lower than that in sham animals (P< 0.005). The number of TdT-mediated dUTP nick-end labelling (TUNEL) positive tumour cells was significantly increased in 60% hepatectomy as compared with the sham and 30% hepatectomy group. The mRNA expression of TGF-beta1, TNF-alpha and Fas in the tumour portion of 60% hepatectomy, was higher than that in 30% hepatectomy group. Plasma levels of TGF-beta1 were inversely correlated with intra-hepatic tumour weights. These results suggest that major hepatic resection may lead to an increased induction of apoptosis for the remaining hepatic tumour.     

X线照射后肺癌细胞肿瘤坏死因子mRNA的表达

目的探讨X线诱导和调节肺癌细胞株NCI-H596和A549肿瘤坏死因子(TNF-α)mRNA的表达作用及其临床意义。方法应用实时荧光定量RT-PCR技术,定量检测NCI-H596和A549细胞株照射前和接受不同剂量(2,5,10,20,30和40Gy)的X线照射后,以及受照30Gy后不同时间TNF-αmRNA的表达。同时进行集落形成试验,检测NCI-H596和A549细胞株的放射敏感性。结果集落形成试验结果显示,未照射的NCI-H596细胞株集落形成率为0.12～0.24;A549细胞株集落形成率为0.37～0.45。照射后,A549细胞的存活分数(SF)在2Gy时为47.3%±9.0%,4Gy时为18.0%±3.0%,6Gy时为6.0%±2.0%,8Gy时为1.4%±0.3%;NCI-H596细胞的SF在2Gy时为55.2%±51.0%,4Gy时为15.9%±9.2%,6Gy时为3.5%±1.7%;8Gy时为0.9%±0.6%;二者SF差异无统计学意义,二者的D0值和Dq值差异亦无统计学意义(P>0.05)。实时荧光定量RT-PCR检测显示,NCI2H596细胞受照后TNF-αmRNA表达逐渐升高,照射剂量达40Gy时,TNF-αmRNA表达水平达高峰,为对照组的83倍;受照后,1hTNF-αmRNA表达逐渐升高,6h达高峰,为对照组的568倍。A549细胞受照后,1hTNF-αmRNA表达即达高峰,为对照组的136倍。结论X线可诱导肺癌细胞株A549和NCI2H596产生TNF-α,且呈剂量、时间依赖性,可提高肺癌放射治疗的疗效,也可对正常组织和     

Anti-inflammatory effects of low-dose radiotherapy in an experimental model of systemic inflammation in mice

PURPOSE: The aim of this study was to determine the effects of low-dose radiotherapy (LD-RT) on the inflammatory response and to characterize the potential mechanisms underlying these effects. METHODS AND MATERIALS: Mice were irradiated with 0.1, 0.3, 0.6 Gy, or sham radiation before lipopolysaccharide (LPS) challenge. Leukocyte-endothelial cell interactions in intestinal venules were assessed using intravital microscopy. Intercellular adhesion molecule-1 (ICAM-1) expression was determined using radiolabeled antibodies 5 h after irradiation. Production of transforming growth factor-beta1 (TGF-beta1) was measured by enzyme-linked immunosorbent assay and its in vivo functional relevance by immunoneutralization. RESULTS: Compared with vehicle treated animals, LPS induced a marked increase in leukocyte adhesion (0.13+/-0.59 vs. 5.89+/-1.03, p<0.0001) in intestinal venules. The number of adherent leukocytes was significantly reduced by the 3 doses of LD-RT tested; the highest inhibition was observed with 0.3 Gy (0.66+/-1.96, p<0.0001). LPS-induced ICAM-1 upregulation was not modified by LD-RT. Circulating levels of TGF-beta1 were significantly increased in response to LD-RT in controls and LPS challenged animals. Neutralization of TGF-beta1 partially restored LPS-induced adhesion (4.83+/-1.41, p<0.05). CONCLUSIONS: LD-RT has a significant anti-inflammatory effect, inhibiting leukocyte recruitment, which is maximal at 0.3 Gy. This effect results in part from increased TGF-beta1 production and is not related to modulation of ICAM-1 expression.