大肠肿瘤与细胞凋亡

大肠肿瘤与细胞凋亡孙燕翔１周汉高１谢大业２师英强２１上海市北医院２００４３５２上海市肿瘤医院２０００３２Ｓｕｂｊｅｃｔｈｅａｄｉｎｇｓｃｏｌｏｎｉｃｎｅｏｐｌａｓｍｓ／ｐａｔｈｏｌｏｇｙ；ｒｅｃｔａｌｎｅｏｐｌａｓｍｓ／ｐａｔｈｏｌｏｇｙ；ａｐｏ...     

大肠肿瘤的基因表达及与细胞凋亡的抑制关系

目的探讨 bcl-2和 P53蛋白在大肠肿瘤中的表达及与细胞凋亡关系。方法用免疫组化方法观察了45例大肠腺瘤和61例大肠癌中 bcl-2和 P53蛋白的表达。结果正常大肠粘膜中 bcl-2和 p53均未见表达,而大肠腺瘤及大肠癌阳性率均较正常明显增加(P<0.01)。大肠腺瘤 p53表达随腺瘤大小增加而增加,其中≥20 mm 组阳性率(77.8%)显著高于<10 mm 组(35.0%,P<0.05)。P53蛋白阳性率也随不典型增生程度增加而增高。p53表达与大肠癌分化程度及 Duke 分期有关。大肠癌细胞凋亡指数与 bcl-2阳性表达呈负相关。大肠腺瘤中 bcl-2和 P53蛋白的表达也呈负相关。结论 bcl-2蛋白表达对大肠癌前病变.腺瘤的增殖有一定意义,p53在大肠腺瘤癌变和大肠癌进展中起重要作用,它们是参与细胞凋亡的良好指标。     

细胞凋亡与肿瘤

细胞凋亡（Ａｐｏｐｔｏｓｉｓ）是细胞自然衰老、死亡的一种形式．细胞凋亡规律一旦失常,个体即不能正常发育,或发生畸变或不能存活．１９７２年Ｋｅｒｒｅｔａｌ首先提出这一概念,认为细胞的这种形式的死亡象秋天树叶凋谢一样,其是由基因调控的细胞自我消亡过程,其...     

细胞凋亡与消化道肿瘤研究进展

细胞分化和死亡之间的平衡调节，对于多细胞生物自身稳定与发展是非常必要的。大多数动物细胞在受到严重损伤或机体不再需要时，会激活内在的细胞自杀机制进行自我破坏，这种死亡形式有特征性的形态学和生化变化．即凋亡。细胞凋亡在胚胎发育、精确的细胞数量调节和清除衰老的或潜在的有害细胞方面有极其重要的意义。细胞凋亡的异常参     

细胞凋亡与肿瘤的发生和治疗

细胞凋亡与肿瘤的发生和治疗司斌张世明刘志遐长期以来，癌症研究者一直被肿瘤细胞的无限制繁殖生长所困惑，不断探求造成这种生长失控的原因，寻找解决的办法，但均未能取得满意的结果。随着生物学研究的不断进展，人们发现，在真核多细胞生物中，细胞的数目是通过细胞的...     

细胞凋亡与肿瘤转移在肝癌中的作用

原发性肝癌治愈率很低，是癌症患者最常见的死因。虽然目前肝癌的诊断和治疗取得了很大进展，但其5年生存率仅为7％［1］。肝癌细胞的转移、浸润以及血管再生导致了肝癌的异常增长和过早转移，这都是高致死率的原因。现将肝癌细胞凋亡及转移的研究进展综述如下。     

消化道肿瘤细胞凋亡相关基因治疗研究进展

介绍细胞凋亡的相关基因及其在消化道肿瘤基因治疗中应用和凋亡机制的研究进展。     

消化道肿瘤细胞凋亡相关基因治疗研究进展

介绍细胞凋亡的相关基因及其在消化道肿瘤基因治疗中应用和调亡机制的研究进展。     

大肠腺瘤中细胞凋亡和增殖相关基因的表达与意义

目的：探讨大肠腺瘤中细胞凋亡和增殖相关基因的表达与意义。方法：用脱氧核糖核酸末端转移酶介导的TUNEL法缺口末端标记和免疫组化技术，检测45例大肠腺瘤组织细胞的原位凋亡（AI）、原位增殖（KI）及bcl-2、bax基因表达；并设立20例正常大肠粘膜和40例大肠癌为对照组，探讨细胞凋亡和细胞增殖在大肠癌早期发生中的作用。结果：正常结肠粘膜有少量的bcl-2、bax和ki－67（用KI表示）表达及少量凋亡细胞存在，但无异常表达。大肠腺瘤中bcl-2表达和KI明显增加，与正常组相比P均＜0.05；AI和bax表达轻度增加，与正常相比P＜0.05。bax与AI表达呈正相关（P＜0.01），bcl－2和bax及AI呈负相关。大肠癌中bcl-2表达和KI表达虽增加，但与腺瘤相比无统计学差异P＞0.05；大肠癌组织中AI和bax表达明显增加且与腺瘤组相比P＜0.05。结论：大肠癌发生早期即腺瘤中就有细胞凋亡调控基因及增殖基因的表达异常，且以抗凋亡基因bcl-2和增殖基因表达占主导地位。该基因的表达异常可能是大肠癌发生的一个较早期分子标志；细胞凋亡增加和bax表达异常可能是大肠癌发生的一个相对较早期分子生物学事件。早期检测抗细胞凋亡基因和增殖基因，有助于对大肠癌早期发生的评估。     

细胞凋亡与细胞增殖在胆囊肿瘤形成中的作用

目的 探讨细胞凋亡和细胞增殖在胆囊肿瘤发生发展中的作用。 用原位末端标记法和免疫组织化学染色１、检测２４例胆囊癌和１６例胆囊腺瘤中的凋亡细胞数和ＰＣＮＡ及ｂｃｌ－２癌基因的表达情况。结果 胆囊腺癌中的凋亡细胞数明显低于胆囊癌;分化好的胆囊癌中的凋亡细胞数低于分化差的胆囊腺癌。ＰＣＮＡ和ｂｃｌ－２的阳性表达率在胆囊癌中明显高于胆囊腺瘤。结论胆囊癌不仅有较高的增殖能力,而且有很高的细胞凋亡率。细胞凋亡     

细胞凋亡与肝癌

0 引言 凋亡是遗传和进化方面高保留的重要过程,他与有丝分裂相互协调,参与机体的基因调控、胚胎发育、肿瘤退化、正常组织的更新以及自身反应性淋巴细胞的清除等过程。本文简单介绍有关参与肝癌细胞凋亡的一些特异性(p53,c-myc,Fas,bcl-2/Bax基因等)和非特异性信号在调整细胞生存或细胞死亡平衡中的相互作用,以及某些抗肿瘤治疗的机制。     

细胞凋亡与胃癌及幽门螺杆菌相关胃疾病

0 引言 细胞凋亡对多细胞有机体的发育、内环境的稳定致关重要,他的异常与肿瘤发生密不可分。既往认为胃癌的形成是细胞无限增生所致的细胞集聚,近年发现胃癌中不仅存在细胞增生,同时也存在细胞凋亡,胃癌的发生是细胞凋亡与增生比例失调的结果。细胞凋亡受许多因素(凋亡相关基因、放疗、化疗、细胞因子等)的影响。因此,了解细胞凋亡与胃癌及其癌前疾病,包括幽门螺杆菌(Helicobacter pylori,Hp)相关性胃疾病的关系,有助于揭示胃癌及Hp相关胃疾病的发生机制,同时寻找胃癌治疗的新方法。     

Expression of a novel apoptosis inhibitor-survivin in colorectal carcinoma

AIM: To investigate the role of survivin expression in the pathogenesis of colorectal carcinoma.METHODS: Immunohistochemistry S-P method and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) were used to detect the expression of survivin and apoptotic cell in situ in colorectal cancerous tissues, para-cancerous tissues and normal tissues of 48 cases of colorectal carcinoma.RESULTS: The survivin positive unit (PU) was higher in cancerous tissues (38.76±5.14)than in para-cancerous (25.17±7.26) or normal tissues (0.57±0.03) (P<0.05).The apoptosis index (AI) of para-cancerous tissues was(7.51±2.63%) higher than cancerous tissues (4.65±1.76%).The expression of survivin was associated with pathological grade, lymph node metastasis and Dukes stage of colorectal carcinoma.CONCLUSION: Survivin expression may play an important role in carcinogenesis of colorectal carcinoma and may be associated with malignant biological behaviors of colorectal carcinoma.     

Expression of a novel apoptosis inhibitor-survivin in colorectal carcinoma

AIM: To investigate the role of survivin expression in the pathogenesis of colorectal carcinoma. METHODS: Immunohistochemistry S-P method and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) were used to detect the expression of survivin and apoptotic cell in situ in colorectal cancerous tissues, para-cancerous tissues and normal tissues of 48 cases of colorectal carcinoma. RESULTS: The survivin positive unit (PU) was higher in cancerous tissues (38.76±5.14) than in para-cancerous (25.17±7.26) or normal tissues (0.57±0.03) (P<0.05). The apoptosis index (AI) of para-cancerous tissues was (7.51±2.63%) higher than cancerous tissues (4.65±1.76%). The expression of survivin was associated with pathological grade, lymph node metastasis and Dukes stage of colorectal carcinoma. CONCLUSION: Survivin expression may play an important role in carcinogenesis of colorectal carcinoma and may be associated with malignant biological behaviors of colorectal carcinoma.     

Cell apoptosis and regeneration of hepatocellular carcinoma after transarterial chemoembolization

AIM: To evaluate whether cell apoptosis and regeneration were existed in normal liver cells adjacent to carcinoma after transarterial chemoembolization (TACE). METHODS: Fifty rabbits with hepatic carcinoma were divided into 5 groups at random: group A (control group), groups B and C (TACE treatment groups), groups D and E (partial hepatectomy groups). There were 10 rabbits in each group. Rabbits in groups B-E were treated by transarterial chemoembolization (TACE) and partial hepatectomy (PH) respectively. The changes of S-phase cell fraction (SPF), proliferation index (PI) and cell apoptosis in the normal liver tissue were determined with flow cytometry (FCM) after operations on the first and third days. We determined the mitosis index (MI) with histo-pathological method and the apoptosis index (AI) with TUNEL method at the same time. RESULTS: Twenty-four hours after operations, compared with control group, the rabbits in TACE group had much higher index of SPF, PI and MI (MI: t=4.89, P<0.001; SPF:t=5.27, P<0.001; PI: t=4.87, P<0.001). Moreover, the proliferation of liver cells in TACE group was much weaker than that of the cells treated by partial hepatectomy, and the differences were significant (MI: t=7.02, P<0.001; SPF: t=4.06, P<0.001; PI: t=2.70, P<0.05). Seventy-two h after operations, FCM showed a small sub-G1 peak in TACE group and PH group, compared with the control group, but there was no difference between them (t=0.41, P>0.05). TACE showed that AI in the treated rabbits was higher than that in control group (t=3.07, P<0.05), and there were no differences between TACE group and PH group, either (t=0.93, P>0.05). CONCLUSION: Cell apoptosis and regeneration exist in rabbit liver tissues after TACE in some degree, which may be associated with the selective embolization of iodised oil, chemotherapeutic drug and free radical damage.     

Livin基因沉默对大肠癌细胞凋亡和化疗敏感性的影响

目的 观察沉默Livin基因对大肠癌HT-29细胞凋亡和化疗敏感性的影响.方法 采用脂质体转染技术将化学合成的Livin siRNA转入HT-29细胞,RT-PCR和Western印迹法检测转染效果.选用5-氟尿嘧啶(5-FU)作用于转染和未转染的细胞,MTT检测各组细胞的增殖、流式细胞仪检测细胞的凋亡.结果 si-Livin1转染组Livinα mRNA、Livinβ mRNA和Livin蛋白表达水平较其余干扰组和对照组显著降低(P<0.01).5-FU对HT-29细胞的生长抑制作用强于si-Livin1转染组(P<0.01),而si-Livin1+5-FU组对细胞的生长抑制率显著高于单独si-Livin1转染组和单独5-FU作用组(P<0.01).与空白对照组比较,si-Livin1转染可使细胞出现明显凋亡现象(P<0.01),5-FU对细胞的促凋亡作用强于si-Livin1转染组(P<0.01),si-Livin1+5-FU组的凋亡率显著高于单独si-Livin1转染组和单独5-FU作用组(P<0.01).结论 siRNA沉默Livin基因能够抑制HT-29细胞的生长,促其凋亡,提高5-FU的化疗敏感性.Livin基因有望成为大肠癌治疗的新靶点.     

Cell signalling associated with fibrinolytic ligand binding to human colorectal carcinoma cells

Summary Addition of purified plasmin or plasminogen (0.1 M) to serum-free culture media elevated cellular D-myo-inositol 1,4,5-trisphosphate (InsP ₃) levels in human colorectal carcinoma cells within 1 h to double those of control cells. This was accompanied by decreases in cellular phosphatidylinositol bisphosphate by 40% in cells exposed to fibrinolytic ligands for up to 1 h. The effect was not due to opening of Ca²⁺ channels of the type blocked by 5 M nifedipine, and 100 M EGTA, a Ca²⁺ chelator, did not suppress plasmin's ability to elevate InsP ₃. Binding assays at 4° C with¹²⁵I-labelled plasmin indicated maximum binding within 1 h suggesting that the effects of plasmin may be associated with its cell-binding function. These cells could convert exogenous plasminogen to plasmin with endogenous activation and this was accompanied by a decrease in radioactive phosphatidylinositol well below control levels (13% of control). Our results contribute to evidence for the association of plasmin-binding sites with a signalling system. A cell signalling system indirectly or directly associated with plasmin binding, would permit carcinoma cells to coordinate extracellular fibrinolysis with cell migration and motility through second messengers.Abbreviations InsP ₃ inositol trisphosphate - Ptd phosphatidyl     

Heterocyclic complexes of ruthenium(III) induce apoptosis in colorectal carcinoma cells

Purpose The ruthenium complex salt indazolium trans-[tetrachlorobisindazole-ruthenate(III)] (KP1019) and the analogous sodium salt KP1339 are effective tumor-inhibiting drugs in experimental therapy of autochthonous colorectal carcinomas in rats. This paper examines the cell biological mechanisms underlying their antineoplastic effects.Methods Colorectal tumor cell lines were used to analyze uptake of the ruthenium(III) complexes into the cells and the mechanism as well as the efficacy of their cytotoxic effects.Results KP1019 and KP1339 are efficiently taken up into the cells: 100 µM ruthenium(III) complex in the growth medium led to the uptake of 120–160 ng ruthenium per 10⁶ cells within 30 min. Uptake of KP418 was tenfold lower correlating with its lower cytotoxic efficiency. KP1019 and KP1339 induced apoptosis in SW480 and HT29 cells predominantly by the intrinsic mitochondrial pathway as indicated by loss of mitochondrial membrane potential. Correspondingly sensitivity of the cells paralleled expression of bcl₂ while it was only slightly affected by mutations in Ki-ras.Conclusions Our data demonstrate that trans-[tetrachlorobisindazole-ruthenate(III)] complex salts are promising candidate drugs in the second-line treatment of colorectal cancers resistant to other cytostatic drugs and has been introduced into phase I clinical trials.