肝细胞癌肝动脉化疗栓塞后增殖细胞核抗原的改变及对预后的影响

增殖细胞核抗原(Ｐｒｏｌｉｆｅｒａｔｉｎｇｃｅｌｌｎｕｃｌｅａｒａｎｔｉｇｅｎ,ＰＣＮＡ)是一种公认的反映细胞增殖状态的指标蛋白,该物质与肿瘤病人的预后有关[1,2]。本文研究,肝细胞癌(肝癌)经肝动脉化疗栓塞(Ｔｒａｎｓｃａｔｈｅｔｅｒａｒｔｅｒｉａｌｃｈｅｍｏｅｍｂｏｌｉｚａｔｉｏｎ,ＴＡＣＥ)后ＰＣＮＡ表达情况的改变,以及对预后的影响,进而指导临床治疗方案的不断改进和完善。材料与方法一、临床资料1992年7月～1995年6月相对病程较晚,不能手术切除的肝癌72例,经ＴＡＣＥ治疗后,又获得二期手术切除,与直接手术切除的肝癌4…     

细胞凋亡与细胞增殖在人肝细胞癌中的表达和意义

目的了解人肝细胞癌中细胞凋亡的形态与分布规律，探索细胞凋亡标记率和增殖标记率与肝细胞癌组织学分级的关系。方法 对２１例人肝细胞癌和１７例慢性肝病分别作ＴＵＮＥＬ标记和ＰＣＮＡ免疫组化检测，采用图像细胞仪作阳性细胞计数。结果 （１）细胞核染色质浓缩，边聚，胞浆嗜酸性变及核周空晕与ＴＵＮＥＬ标记有极好的相关性；（２）凋亡细胞胞多呈弥散分布，以癌坏死区周围多见，包膜浸润处少见；（３）增殖细胞率和凋亡细胞     

经肝动脉化疗栓塞治疗肝细胞癌：使用不同栓塞剂患者生存期的对比

目的：HCC的经动脉化疗栓塞（TACE）最理想的栓塞剂还没有被确定。这项研究报导了使用明胶海绵粉末和聚乙烯醇（PVA）行TACE术治疗肝细胞癌的结果。[第一段]     

细胞凋亡与细胞增殖在人肝细胞癌中的表达和意义

目的：为了解人肝细胞癌中细胞凋的形态与分布规律，探索细胞凋亡标记率和增殖标记率与肝细胞癌组织学分级的关系。方法：对21例人肝细胞癌和17例慢性肝病分别作TUNEL标记和PCNA免疫组化检测，采用图像细胞仪作阳性细胞计数。结果：(1)细胞核染色质浓缩、边聚、胞浆嗜酸性变及核周空晕与TUNEL标记有极好的相关性：(2)凋亡细胞多呈弥散分布，以癌坏死区周围多见，包膜浸润处少见；(3)增殖细胞和凋亡细胞率与肝癌组织学分级呈正相关，Ⅲ级组肝细胞癌中增殖细胞率为278±6．4高于Ⅱ级组141±35(P<0．01)，又高于Ⅰ级组7．4±0．8(P<0.001)，Ⅲ级组肝细胞癌中凋亡细胞率为21±0．97高于Ⅱ级组0.92±O.26(P<0.05)，又高于Ⅰ级组0．45±0.08(P<0．001)(4)包膜浸润和门脉癌栓组凋亡细胞率和增殖细胞率均高于无包膜浸润和门脉癌检组结论：本研究提示细胞凋亡和细胞增殖与肝细胞癌组织学分级、包膜浸润和门脉癌检密切相关。     

CT引导经导管动脉化疗栓塞治疗肝细胞癌

目的探讨CT引导经导管动脉化疗栓塞（transcatheter arerial chemoembolization,TACE）治疗肝细胞癌（hepatocellular carcinoma,HCC）的初步疗效,分析局部复发的危险因素。方法对32例患者的34个HCC病灶进行了CT引导TACE治疗。结果32例中26例实现局部控制,6例出现局部复发。采用Logistic回归分析发现,TACE治疗后中央型HCC病灶是局部复发的危险因素（P=0．0408）。结论CT引导TACE是治疗小HCC的好方法,其局部控制率高、复发率低。中央型HCC是TACE术后局部复发的危险因素。     

经肝动脉化疗栓塞术

经肝动脉灌注化疗栓塞术（TACE）是治疗中、晚期肝癌病人的首选方法.肝癌的主要血液供应来自肝动脉（90%～100%）,通过肝动脉注入化疗药物,可提高肿瘤组织内的药物浓度,并明显减低全身化疗副的作用,TACE以碘化油混悬化疗药物,可使药物高度集中于肿瘤之内（高出一般周围静脉给药或口服给药的10～100倍）并停留数星期甚至数月之久.此外,碘化油还有栓塞肿瘤微细血管的作用,阻断肝肿瘤的血液供应.     

索拉非尼联合肝动脉化疗栓塞术治疗中晚期肝细胞癌疗效观察

目的观察经导管肝动脉化疗栓塞术(TACE)与靶向治疗药相结合治疗中晚期肝细胞癌的疗效和安全性。方法 2008年1月至2012年12月我院收治的中晚期肝细胞癌患者60例,均采用TACE治疗,其中37例术后口服索拉非尼(400 mg,2次/d),根据不良反应调整用量,定期复查腹部CT。根据m RECIST标准进行疗效评价,观察患者的肿瘤进展时间和总生存期,并记录索拉非尼不良反应和TACE前后的肝功能变化。结果 37例应用TACE联合索拉非尼治疗患者的中位生存期为(13±0.98)m,显著长于23例单纯TACE治疗组[(7.3±1.20)m,P=0.001],肿瘤进展时间为(7.5±1.21)m,显著长于单纯TACE治疗组[(5±0.62)m,P=0.001];在随访结束时,联合治疗组疾病控制率为48.6%,显著高于单纯TACE组的17.4%(P0.01);多因素分析显示有无联合应用索拉非尼、有无门脉癌栓、是否抗病毒治疗是显著影响生存时间的风险因素;索拉非尼治疗主要的相关不良反应为手足皮肤反应。结论 TACE联合索拉非尼治疗可延长中晚期肝细胞癌患者的疾病进展时间及总生存期,安全性好。     

经导管肝动脉化疗栓塞术治疗肝细胞癌疗效及复发预测

目的 探讨肝细胞癌(HCC)患者经导管肝动脉化疗栓塞术(TACE)前、术后脱γ-羧基凝血酶原(DCP)、甲胎蛋白异质体(AFP-L3)、甲胎蛋白(AFP)的变化及其与预后关系.方法 纳入96例接受TACE作为初始治疗的HCC患者,分别于术前,术后4～5周及术后6～12个月检测血清DCP、AFP-L3、AFP等水平.根据...     

肝动脉化疗栓塞术对肝细胞癌患者肝功能和血清HBV DNA的影响

目的观察经导管肝动脉化疗栓塞术治疗肝细胞癌患者肝功能和HBV DNA的变化。方法检测64例肝细胞癌患者在肝动脉化疗栓塞术前后HBV DNA定量及肝功能的变化。结果 64例患者在TACE术前HBV DNA阳性42例(65.6%)。术后2例HBV DNA由阴性转为阳性,21例HBV DNA升高10倍以上。TACE术前42例HBV DNA阳性患者HBV DNA定量为4.3±0.5×104copies/ml,术后44例为6.1±0.4×105copies/ml(P0.05)。HBV激活患者术后肝功能出现明显损害。结论肝动脉化疗栓塞术治疗将引起肝细胞癌患者HBV激活,可能加重肝功能损害,应引起高度重视。     

经导管肝动脉化疗栓塞术后原发性肝细胞癌残留状态的增强CT与超声造影比较

背景经导管肝动脉化疗栓塞术(transcatheter arterial chemoembolization, TACE)是通过微导管选择性插入至肿瘤主要供血动脉后,栓塞动脉及注入化疗药物使肿瘤发生缺血坏死,从而发挥灭活肿瘤作用.有效的TACE治疗势必引起肿瘤微循环血流灌注状态改变,而超声造影能准确反映肿瘤组织的血流灌注过程,从而实现对TACE疗效的准确评估.目的探讨运用增强CT(contrast-enhanced CT, CECT)、超声造影(contrast-enhanced ultrasound, CEUS)判定TACE后原发性肝细胞癌(hepatocellular carcinoma, HCC)残留状态的临床应用价值.方法 选取2016-09/2019-03期间,在浙江省肿瘤医院行TA C E术治疗的71例患者作为研究对象,共125个病灶.所有患者TACE术后1 mo均行CEUS、CECT检查,以同期数字减影血管造影(digital subtraction angiography,DSA)检查结果作为"金标准",比较CEUS与CECT在评估TACE疗效中的应用价值.结果 DSA发现病灶残留97个,无残留28个;CEUS判定病灶残留的准确度、灵敏度、特异度分别为96.00%、96.91%、92.86%;CECT判定病灶残留的准确度、灵敏度、特异度分别88.00%、87.63%、89.29%; CEUS判定病灶残留的准确度、灵敏度均高于CECT,差异有统计学意义(P0.05).结论 CEUS能显示TACE术后HCC病灶组织的血流灌注状态,在判定病灶残留方面优于CECT,可为临床评估TACE术后疗效提供新的有效手段.     

Effect of preoperative transcatheter arterial chemoembolization on proliferation of hepatocellular carcinoma cells

AIM To evaluate the effect of preoperative transcatheter arterial chemoembolization (TACE) on proliferation of hepatocellular carcinoma (HCC) cells.METHODS A total of 136 patients with HCC underwent liver resection. Of 136 patients, 79 patients received 1 to 5 courses of TACE prior to liver resection (TACE group),who were further subdivided into four groups Group A (n = 11) who received 1 to 4 courses of chemotherapy alone; Group B (n = 33) who received 1 to 5 courses of chemotherapy combined with iodized oil; Group C (n = 23) who received 1 to 3 courses of chemotherapy combined with iodized oil and gelatin sponge; and Group D (n = 12) who received 1 to 3 courses of chemotherapy combined with iodized oil, ethanol and gelatin sponge.The other 57 patients only received liver resection (nonTACE group). The expressions of Ki-67 and proliferating cell nuclear antigen (PCNA) protein were detected in the liver cancer tissues by immunohistochemical method.RESULTS The Ki-67 protein expression was significantly lower in Groups C and D as compared with non-TACE group (31.35% ± 10.85% vs 44.43% ± 20.70%,30.93% ± 18.10% vs 44.43% ± 20.70%, respectively, P ＜ 0.05). The PCNA protein expression was significantly lower in Groups C and D as compared with non-TACE group (49.61% ± 15.11% vs 62.92% ± 17.21%, 41.16% ± 11.83% vs 62.92% ± 17.21%, respectively, P ＜ 0.05).The Ki-67 protein expression was significantly higher in Group A as compared with non-TACE group (55.44% ± 13.72% vs 44.43% ± 20.70%, P ＜ 0.05). The PCNA protein expression was significantly higher in Groups A and B as compared with non-TACE group (72.22% ± 8.71% vs 62.92% ± 17.21%, 69.91% ± 13.38% vs 62.92% ± 17.21%, respectively, P ＜0.05).CONCLUSION Preoperative multi-material TACE suppresses the proliferation of HCC cells, while a single material embolization and chemotherapy alone enhance the proliferation of HCC cells.     

Role of cell adhesion signal molecules in hepatocellular carcinoma cell apoptosis

AIM: Cell adhesion molecules and their signal molecules play a very important role in carcinogenesis. The aim of this study is to elucidate the role of these molecules and the signal molecules of integrins and E-cadherins, such as (focal adhesion kinase) FAK, (integrin linked kinase) ILK, and p-catenin in hepatocellular carcinoma cell apoptosis. METHODS: We first synthesized the small molecular compound, S-(1,2-dichlorovinyl)-L-cysteine (DCVC), and identified it, by element analysis and 1H NMR. To establish the apoptosis model of the SMMC-7721 hepatocellular carcinoma cell, we treated cells with DCVC in EBSS for different concentrations or for various length times in the presence of 20 μmol/L N,N-diphenyl-p-phenylenediamine, which blocks necrotic cell death and identified this model by flow cytometry and DNA ladder. Then we studied the changes of FAK, ILK, β-catenin, and PKB in this apoptotic model by Western blot. RESULTS: We found that the loss or decrease of cell adhesion signal molecules is an important reason in apoptosis of SMMC-7721 hepatocellular carcinoma cell and the apoptosis of SMMC-7721 cell was preceded by the loss or decrease of FAK, ILK, PKB, and β-catenin or the damage of cell-matrix and cell-cell adhesion. CONCLUSION: Our results suggested that the decrease of adhesion signal molecules, FAK, ILK, PKB, and β-catenin, could induce hepatocellular carcinoma cell apoptosis.     

奥曲肽体外抑制人肝癌细胞株SMMC-7721的增殖及其机制研究

目的研究生长抑素类似物奥曲肽(octreotide)在体外对人肝癌细胞株SMMC-7721的抗增殖作用,并从细胞周期调控的角度探讨其作用机制.方法采用MTT比色法观察octreotidedui对细胞增殖的抑制作用,流式细胞仪分析细胞周期,免疫细胞化学检测cyclin A、增殖细胞核抗原(PCNA)蛋白的表达.结果octreotide能明显地抑制SMMC-7721细胞的增殖,呈剂量依赖性;与对照组比较,octreotide使实验组G0/G1、G2/M期细胞数减少,S期细胞数增加.经octreotide作用72 h后,cyclinA、PCNA蛋白表达水平明显下降(对照组2.833±0.074,4.851±0.059;octreotide组1.674±0.043,3.257±0.036).结论octreotide能影响细胞周期的进程,通过下调S期细胞周期素A、PCNA蛋白的表达来干扰SMMC-7721细胞增殖环节,可能是其发挥抑制肝癌细胞增殖的机制之一.     

黄芩甙对肝癌细胞BEL-7402抗黏附作用中细胞凋亡和细胞周期的改变

目的:研究黄芩甙对人肝癌BEL-7402细胞系黏附、细胞凋亡及细胞周期的影响,探讨三者之间的关系.方法:应用细胞培养技术培养BEL-7402细胞,不同浓度黄芩甙处理肝癌细胞,通过Boyden小室模型测定其黏附力,同时观察细胞形态,流式细胞术测定肝癌细胞integrinβ_1、E-cd表达的改变及细胞凋亡率.结果:5,10,20mg/L黄芩甙处理组细胞黏附力与对照组相比均有显著降低(52.38±3.83,35.63±2.32,26.58±1.13 vs 84.32±6.74.p<0.05).对照组表现出纤维母细胞样形态,伸出形态各异的伪足.而黄芩甙组细胞形态较圆,伪足数目相对较少,电镜下显示细胞微绒毛明显减少,甚至消失.5,10,20mg/L黄芩甙组细胞integrinβ_1表达较对照组降低(354.07±18.17,319.44±15.21,291.49±12.88 vs 407.54±20.58:P<0.05),E-cd的表达则增加(335.5±20.18,376.4±22.36,393.8±25.68 vs 251.72±12.34,P<0.05).黄芩甙作用后,随黄芩甙浓度增加肝癌细胞G_0/G_1,期比例逐步增高,S期细胞减少,同时细胞凋亡率增加.结论:黄芩甙对肝癌BEL-7402细胞发挥抗黏附作用,其机制可能与抑制黏附分子E-cd的表达,促进integrinβ_1表达有关.在抗黏附的同时细胞周期发生改变,细胞凋亡增多.     

Expression of fragile histidine triad in primary hepatocellular carcinoma and its relation with cell proliferation and apoptosis

AIM: To evaluate the expression of fragile histidine triad (FHIT) gene protein, product of a candidate tumor suppressor, and to investigate the relationship between FHIT, cell apoptosis and proliferation, and pathological features of primary hepatocellular carcinoma (HCC). METHODS: Forty-seven HCC and ten normal liver specimens were collected during surgical operation between 2001 and 2003. FHIT and proliferating cell nuclear antigen (PCNA) expression were detected by immunohistochemistry, and apoptotic level was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay on the tissue sections. RESULTS: All normal liver tissues showed a strong expression of FHIT, whereas 28 of 47 (59.6%) carcinomas showed a significant loss or absence of FHIT expression (P= 0.001). The proportion of reduced FHIT expression in those carcinomas at stages Ⅲ-Ⅳ (70.6%) and in those with extrahepatic metastasis (86.7%) showed an increasing trend compared with those at stages HI (30.8%, P= 0.013) and those without metastasis (46.9%, P = 0.010) respectively. Apoptotic incidence in advanced TNM stage carcinoma and those with positive FHIT expression was higher than that in early stage carcinoma (P=0.030) and in those with negative FHIT expression (P=0.044) respectively. The proliferating potential of hepatocellular carcinoma was associated with FHIT expression (P= 0.016) and the aggressive feature (P = 0.019). Kaplan-Meier analysis demonstrated that the survival time of these 47 patients correlated with TNM stage, FHIT expression and metastasis. CONCLUSION: There is marked loss or absence of FHIT expression, as well as abnormal apoptosis-prdiferation balance in HCC. FHIT may play an important role in carcinogenesis and development of HCC.     

Effect of preoperative transcatheter arterial chemoembolization on angiogenesis of hepatocellular carcinoma cells

AIM： To evaluate the effects of four types of preoperative transcatheter arterial chemoembolization （TACE） on angiogenesis of hepatocellular carcinoma （HCC） ceils. METHODS： A total of 136 patients with HCC underwent liver resection. One to five courses of TACE prior to liver resection were performed in 79 patients （TACE group）, in which one to four courses of chemotherapy alone were performed in 11 patients （group A）; one to five courses of chemotherapy combined with iodized oil were performed in 33 patients （group B）; one to three courses of chemotherapy combined with iodized oil and gelatin sponge were performed in 23 patients （group C）, one to three courses of chemotherapy combined with iodized oil, ethanol and gelatin sponge were performed in 12 patients （group D）. The other 57 patients only received liver resection （non-TACE group）. The microvessels were marked by CD31. The expression of CD31 and vascular endothelial growth factor （VEGF） protein were detected by immunohistochemical methods. RESULTS： The mean microvessel density （MVD） in HCC cells was significantly higher in groups A, B, C and D than in the nonACE group （P 〈 0.05）. The expression of VEGF protein in HCC cells were significantly higher in groups A, B, C and D than in the non-TACE group （P 〈 0.05）. MVD and the expression of VEGF protein were positively correlated. Mean MVD and the expression of VEGF protein were closely related to the number of courses of TACE and the interval of TACE. CONCLUSION： Four different types of preoperative TACE regimens enhanced angiogenesis in HCC cells by up-regulating the expression of VEGF protein. It is necessary to repress angiogenesis of liver cancer after TACE.     

肝动脉化疗栓塞联合射频消融治疗大肝癌的疗效评价

目的探讨经导管肝动脉化疗栓塞（transcatheter arterial chemoembolization,TACE）联合射频消融（radiofrequency ablation,RFA）治疗大肝癌的临床应用价值。方法回顾性分析我院2006年4月至2008年7月收治的66例肝细胞癌患者的治疗结果,根据治疗方法分为TACE＋RFA组、TACE组及RFA组,其中19例行RFA联合TACE治疗（TACE＋RFA组）,24例单纯TACE治疗（TACE组）,23例单纯RFA治疗（RFA组）。结果 TACE＋RFA组的肿瘤坏死率达73.68%,明显高于单纯TACE组及单纯RFA组（分别为50.00%,52.17%,P〈0.01,P〈0.05）。局部复发率分别为26.32%、37.50%和30.43%,三组间无显著统计学差异（P〉0.05）。TACE＋RFA组的平均生存期为28.3个月,显著高于TACE组的13.6个月（P〈0.01）和单纯RFA组的21.7个月（P〈0.05）。结论 TACE联合RFA治疗大肝癌与单纯TACE和单纯RFA治疗效果相比,可提高肿瘤坏死率,延长患者生存期。     

Cerebral lipiodol embolism following transcatheter arterial chemoembolization for hepatocellular carcinoma

Cerebral lipiodol embolism (CLE) is an extremely rare complication of transcatheter arterial chemoembolization for hepatocellular carcinoma (HCC). The authors present a case of CLE that occurred after the second hepatic arterial chemoembolization for HCC, and attempt to introduce several plausible mechanisms of CLE, after reporting the clinical and radiological findings and reviewing the medical literature.     

The radiological prognostic factors of transcatheter arterial chemoembolization to hepatocellular carcinoma

Transcatheter arterial chemoembolization (TACE) is the recommended treatment modality for intermediate stage hepatocellular carcinoma (HCC). The aim of this study was to determine the HCC radiological characteristics associated with prognosis of patients with intermediate stage HCC receiving TACE. Patients with HCC BCLC stage B from January 2005 to December 2009 were collected. According to mRECIST criteria, patients with complete response and partial response were assigned to the objective response (OR) group, while those with stable disease and progressive disease were assigned to the nonobjective response (non-OR) group. Among a total of 128 enrolled patients, there were 66 (51.6%) and 62 (48.4%) patients in the OR group and non-OR group, respectively. The clinical parameters in the two groups were similar, although HCC size was smaller in the OR group. Logistic analysis found combined radiological characteristics including complete lipiodol retention, tumor feeding artery blockage, and no residual tumor blush were significant correlated with achievement of OR (odds ratio 2.46, 95% CI 1.08–5.61, P = .032). However, no radiological characteristics had significant strength to predict overall survival. Patients with OR after TACE had significantly longer survival time than those with non-OR. Combined characteristics of complete lipiodol retention, tumor feeding artery blockage, and no residual tumor blush had a positive impact on OR in TACE. In patients receiving TACE, those who achieved OR had a better overall survival.