Stathmin在Ⅳ期非小细胞肺癌中表达及紫杉类化疗耐药相关性研究

目的:探讨Ⅳ期非小细胞肺癌（NSCLC ）Stathmin 蛋白表达与紫杉类化疗耐药性关系。方法:回顾性分析2003年10月～2007年10月75例接受以紫杉类化疗的Ⅳ期NSCLC 临床病理资料。免疫组织化学法检测肿瘤标本Stathmin 蛋白表达,并对化疗疗效及生存时间进行分析。结果:Stathmin 阳性表达（≥50% 阳性染色细胞）率为80.00% 60/75）,男性高表达率为81.63% ,女性为76.92% ,P=0.627;鳞癌71.79% ,腺癌88.89% ,P=0.064;≥58岁78.95% ,<58岁81.08% ,P=0.817;化疗有效率（CR+PR）为34.67% ,Stathmin 高表达患者紫杉类化疗有效率低28.33%（17/60）,进展率高21.67%（13/60）,而Stathmin 低表达患者化疗有效率高60.00%（9/15）,进展率低0（0/15）,P=0.021和P=0.047。Stathmin 高表达者有较短的中位OS（12.0 个月）和PFS（8.0 个月）,而Stathmin 低表达患者有较长的中位OS（17.0 个月）和PFS（13.0 个月）,P=0.008 和P=0.008。患者性别、年龄和组织类型与中位OS及PFS 无相关性,P 值均>0.05。结论:Stathmin 高表达NSCLC 患者对紫杉类药物耐药且预后不良。      

放射线联合p53基因及内皮抑素治疗小鼠前列腺癌皮下移植瘤

Objective To test the hypothesis that p53 gene therapy combined with endostatin can enhance tumor response to radiation therapy of RM-1 mouse xenograft prostate cancer and to investigate its mechanism. Methods A mouse prostate cancer model was established. Then mice with xenograft tumor were randomly divided into group A (control), B (radiation), C (radiation and rAdp53), D (radiation and rh-endostatin) and E (radiation and rAdp53 and rh-endostatin). On day 1, rAdp53 was injected intra-tumorously with 1 × 1010 vp per animal to group C and E. From day 1 to 14, rh-endostatin was given 15 mg/kg intraperitoneally daily to group D and E. On day 4 single fraction of 15 Gy was given to tumors in groups B, C, D and E. Normal saline was injected intra-tumorously or intraperitoneaUy accordingly as control. No treatment was done to group A. Tumor volume was measured daily. Samples were collected on Days 5, 10 and 15. Ki67, CD31, p53 and VEGF were detected by means of immunohistochemistry. Results (1) Radiation alone, radiation combined with intra-tumorous injection of Adp53 and/or intraperitoneal injection of rh-endostatin resulted in tumor growth arrest of RM-1 cells in vivo (P = 0.000). Radiation combined with both rAdp53 and rh-endostatin was the most effective treatment (P < 0.05). (2) All the four treatment groups had a decreased expression of mutant type P53 (P = 0.000). The expression of Ki67 in groups B and C were equal (P 0.05) and increasing (P = 0.000), respectively. Group D had a up-down-up curve (P < 0.05), but group E had a up-down one. On day 5 the expresion of VEGF in group E was the lowest (P < 0.05). An increased expression of MVD compared with the control was shown, and MVD in groups C, D and E were always higher than that in the control (P < 0.05). Conclusions The limitation of radiotherapy could be overcome by combination with beth p53 gene therapy and endostatin on the growth of mouse prostate cancer cell. Radiation, rAdp53 and endostatin have their own role but they can be interacted with each other.     

AKR1C3在放疗食管癌患者病理标本检测中的意义

目的 对单纯放疗食管癌患者病理标本进行检测,评估醛固酮类还原酶家族1成员C3(AKR1C3)表达与放疗效果的关系.方法 回顾性分析28例行单纯放疗的局部晚期食管癌患者的临床资料,通过免疫组化检测食管癌患者中AKR1C3的表达情况.结果 AKR1C3在不同分化程度的食管癌患者中表达程度不同,其表达水平与放疗短期疗效呈负相关(P=0.031,95%可信区间 0.151～0.914).结论 AKR1C3有可能成为食管癌放疗疗效判定的敏感性指标.     

寡转移去势抵抗前列腺癌原发灶与转移灶放疗不良反应分析

目的 对寡转移去势抵抗前列腺癌(CRPC)进行原发灶和转移灶放疗的不良反应。方法 2011—2015年收治 20例寡转移CRPC患者,采取影像引导VMAT技术给予前列腺+精囊区76 Gy分38次,盆腔淋巴结防区46 Gy分23次,转移部位中位剂量60(52~66) Gy分23次,分析其临床相关数据及不良反应情况。结果 患者均完成放疗,仅 1例患者出现3级尿路梗阻,须留置导尿。急性期≥2级不良反应中尿路 4例(20%)、直肠 2例(10%)、血液系统 2例(10%)。直 肠V50与直肠急性期≥2级不良反应相关。中位随访时间为24.2个月,无晚期≥2级不良事件发生。20例患者在放疗后均出现PSA下降,中位下降率99%,16例(80%)患者PSA下降率>90%。结论 寡转移CRPC患者对前列腺原发灶及转移灶行根治量放疗安全有效。     

2′-羟基黄烷酮对前列腺癌细胞的放射增敏作用及机制探讨

目的 研究2′-羟基黄烷酮(2′-HF)对前列腺癌细胞的放射增敏作用并初步探讨其机制。方法 应用克隆形成实验、叔丁基过氧化氢(TBHP)氧化损伤实验、Hoechst荧光染色、Annexin V-FITC和PI流式细胞仪凋亡检测实验检测2′-HF对前列腺癌VCaP细胞的放射敏感性影响。应用Western blot方法检测2′-HF对VCaP细胞中AKT、p-AKT、AKR1C3蛋白表达水平影响并初步探讨作用机制。采用t检验和析因方差分析检验结果。结果 克隆形成实验结果提示经2′-HF处理的VCaP细胞在照射后增殖能力明显低于空白对照组(P=0.010),SR=1.19;TBHP氧化损伤实验结果提示经2′-HF处理的VCaP细胞的抗氧化损伤能力明显弱于空白对照组(P=0.015);Hoechst荧光染色、Annexin V-FITC和PI流式凋亡检测实验结果提示2′-HF联合放射线会增加VCaP细胞调亡(P=0.001);Western blot实验结果提示2′-HF可以抑制VCaP细胞中p-AKT、AKR1C3蛋白的表达(P=0.013,P=0.016)。结论 2′-HF可提高前列腺癌细胞的放射敏感性,这可能与其对前列腺癌细胞中AKT通路阻滞或AKR1C3蛋白表达抑制相关。     

分子影像报告基因MMP-2,survivin在食管鳞癌中的表达及意义

目的:为将基质金属蛋白酶2(MMP-2),survivin基因作为分子影像学报告基因应用于食管癌的基因显像研究提供实验数据.方法:对34例食管鳞癌患者的手术离体标本连续取材并进行HE染色,镜下选出癌组织和癌周组织,应用免疫组化法检测MMP-2,survivin基因在其中的表达情况,测量两基因在癌周组织中的阳性表达范围,并分析其与肿瘤分期的关系.结果:①在癌组织中MMP-2基因和survivin基因阳性表达率分别为85%和76%:癌组织阳性表达的标本中癌周亚临床病灶的阳性表达率分别为83%和85%;相邻的正常食管组织中的阳性表达率分别为79%和85%.②在食管大体标本组织中MMP-2基因和survivin基因的阳性表达水平均随标本中肿瘤细胞所占比例的减少而降低,其差异有统计学意义(P值分别为0.002和0.001)且存在线性相关关系.③MMP-2,survivin基因在癌周组织的阳性表达范围随肿瘤分期的进展呈增加趋势,其差异有统计学意义(P值均<0.05).结论:MMP-2,survivin基因可作为对食管癌患者进行分子影像学基因显像研究的2个候选基因.     

容积调强弧形治疗与质子调强放疗在室性心动过速放射消融中的计划对比研究

目的 模拟室性心动过速(VT)患者行立体定向消融体部放疗,探索质子调强放疗(IMPT)的剂量学优势。方法 对资料完整的5例患者的胸部定位CT图像均分别勾画左心室的心尖部、心前壁、间隔壁、下壁、外侧壁心肌全层共25个大体靶体积(GTV)。GTV三维外扩5 mm为ITV,ITV外扩3 mm为PTV。每个靶区均分别设计容积调强弧形治疗(VMAT)与IMPT计划。处方剂量为单次25 Gy (RBE)。比较两种计划靶区及危及器官剂量参数。结果 中位ITV体积45.40cm³(26.72~67.59 cm³),所有计划均达到足够的靶区覆盖(ITV V95%Rx≥99%)。相比VMAT计划,IMPT组全心、心包及靶区外心脏组织Dmean分别降低44.52%、44.91%、60.16%,左前降支D0.03 cm³降低17.58%(P<0.05)。按病灶部位分析后发现,IMPT仍可降低绝大多数危及器官剂量,但当病灶位于前壁及心尖时左前降支D0.03 cm³两者相近,病灶位于前壁或下壁时左回旋支D0.03 cm³也相近(P>0.05)。结论 模拟VT患者立体定向消融体部放疗时,VMAT与IMPT计划均满足临床剂量学要求;而IMPT可降低正常心脏组织受量,具有降低缺血性心脏病、心包炎或心包积液等并发症的潜在获益。     

条件复制腺病毒Ad-MK联合丝裂霉素对膀胱癌细胞的作用

条件复制腺病毒指在正常细胞内无复制或杀伤作用,而在同一机体内的肿瘤细胞中可选择性复制和溶解之,细胞裂解后释放的子代病毒颗粒又感染邻近的肿瘤细胞,如此不断循环反复增殖从而达到杀灭癌细胞的肿瘤特异性增殖型病毒[1].     

食管癌原发肿瘤及亚临床灶MMP-2和Survivin基因表达的初步研究

目的 对食管鳞癌癌周亚临床病灶组织和与之相衔接的分化正常的食管组织中MMP-2基因和Survivin基因的表达情况进行检测,为从分子水平研究食管鳞癌的放疗靶区提供参考.方法 对34例食管鳞癌患者的癌及癌周组织标本进行连续取材并应用免疫组化法检测MMP-2基因和Survivin基因在癌组织和癌周组织的表达情况,测量两基因在癌周食管组织中的阳性表达范围,并对该范围值与肿瘤分期、肿瘤纵向长度的关系进行分析.结果 MMP-2、Survivin基因在癌组织中阳性表达率分别为85%、76%,在阳性表达标本中癌周亚临床病灶的分别为83%、85%,相邻正常食管组织中的分别为79%、85%;亚临床病灶组织中MMP-2、Survivin基因的阳性表达水平明显高于癌周正常食管组织的表达(χ2=6.46,P=0.028;χ2=16.15,P=0.001).食管上、下两端癌阉食管组织中MMP-2基因的阳性表达范围为17.2～70.4 mm和15.0～82.4 mm,其中97%以上患者的表达范围＜70 mm;Survivin基因阳性表达范围为3.7～76.4 am和16.1～56.3 mm,其中96%以上患者的表达范围＜70 mm;两基因在癌周食管组织中的阳性表达范围随肿瘤分期的进展呈增加趋势.随着肿瘤纵向长度的增加两基因在癌周食管组织中的阳性表达纵向范围呈现增加趋势,其中Survivin基因在癌周食管上下端中的阳性表达范围与肿瘤的纵向长度之间存在正相关性(r=0.566、0.416,P=0.003、0.034).结论 MMP-2、Survivin基因在食管癌周组织中存在一定程度和范围阳性表达,其中96%以上患者两基因阳性表达范围＜70 mm且该范围内大小与肿瘤病期进展密切相关,而相邻分化正常食管组织中也存在着阳性表达应给予关注.     

放射线联合p53基因及内皮抑素治疗小鼠前列腺癌皮下移植瘤

Objective To test the hypothesis that p53 gene therapy combined with endostatin can enhance tumor response to radiation therapy of RM-1 mouse xenograft prostate cancer and to investigate its mechanism. Methods A mouse prostate cancer model was established. Then mice with xenograft tumor were randomly divided into group A (control), B (radiation), C (radiation and rAdp53), D (radiation and rh-endostatin) and E (radiation and rAdp53 and rh-endostatin). On day 1, rAdp53 was injected intra-tumorously with 1 × 1010 vp per animal to group C and E. From day 1 to 14, rh-endostatin was given 15 mg/kg intraperitoneally daily to group D and E. On day 4 single fraction of 15 Gy was given to tumors in groups B, C, D and E. Normal saline was injected intra-tumorously or intraperitoneaUy accordingly as control. No treatment was done to group A. Tumor volume was measured daily. Samples were collected on Days 5, 10 and 15. Ki67, CD31, p53 and VEGF were detected by means of immunohistochemistry. Results (1) Radiation alone, radiation combined with intra-tumorous injection of Adp53 and/or intraperitoneal injection of rh-endostatin resulted in tumor growth arrest of RM-1 cells in vivo (P = 0.000). Radiation combined with both rAdp53 and rh-endostatin was the most effective treatment (P < 0.05). (2) All the four treatment groups had a decreased expression of mutant type P53 (P = 0.000). The expression of Ki67 in groups B and C were equal (P 0.05) and increasing (P = 0.000), respectively. Group D had a up-down-up curve (P < 0.05), but group E had a up-down one. On day 5 the expresion of VEGF in group E was the lowest (P < 0.05). An increased expression of MVD compared with the control was shown, and MVD in groups C, D and E were always higher than that in the control (P < 0.05). Conclusions The limitation of radiotherapy could be overcome by combination with beth p53 gene therapy and endostatin on the growth of mouse prostate cancer cell. Radiation, rAdp53 and endostatin have their own role but they can be interacted with each other.