CD44 V6和VEGF在肝癌组织中的表达及其预后价值的研究

目的探讨CD44 V6和VEGF在肝细胞癌(HCC)中的表达及其在临床预后中的价值。方法对随访的40例原发性肝癌临床病理学资料进行回顾性分析分类,并按照1年内有无复发和转移分组,然后进行常规HE染色及CD44 V6、VEGF的免疫组化染色(S_P法)。结果结果CD44 V6和VEGF主要定位于癌细胞的胞膜,部分胞质同时出现阳性表达;在40例肝癌组织中,CD44 V6和VEGF的阳性表达率分别为75%(30/40)和77.5%(31/40);CD44 V6、VEGF在复发和转移组的表达均高达88.9%(16/18,16/18),明显高于未复发和转移组,和肿瘤侵袭转移的发生有相关性(P<0.05),癌组织中的表达均明显高于癌旁组织,而在肿瘤大小及组织学分级间未见明显差异。结论资料提示肝癌组织中CD44 V6和VEGF过表达分析,有助于肝癌侵袭、转移预测和肝癌预后判断。     

肝细胞癌CD44v6和p16基因蛋白的表达及其意义

目的探讨CD44v6和p16基因蛋白表达与肝细胞癌(HCC)转移和预后的关系。方法应用免疫组织化学方法,检测分析110例HCC组织中CD44v6及p116蛋白表达,结合随访资料分析。结果在HCC中,CD44v6和p16阳性表达率分别为42.7%和34.5%。CD44v6阳性表达的HCC转移率高(P<0.05),分化程度和患者>5年生存率低(P<0.05);p16阳性表达的HCC转移率低(P<0.05),分化程度和患者>5年生存率高(P<0.05)。CD44v6与p16表达呈负相关(r=-0.59,P<0.005)。结论CD44v6和p16表达与HCC转移和患者生存期密切相关,检测CD44v6和p16蛋白的表达可作为判断HCC预后的参考指标。     

经肝动脉化疗栓塞治疗原发性肝癌56例

2005年2月-2006年2月,我院采用经导管肝动脉化疗栓塞术（TACE）治疗原发性肝癌56例,取得满意疗效。现报告如下。     

肝细胞癌患者经导管动脉化疗栓塞术前后血清HIF-1α、VEGF水平变化及其意义

目的 观察肝细胞癌(HCC)患者经导管动脉化疗栓塞术(TACE)前后血清缺氧诱导因子1α(HIF-1α)、血管内皮生长因子(VEGF)水平变化,并探讨其临床意义。方法 选择HCC患者142例,均接受TACE治疗。TACE治疗后随访3年,死亡40例(死亡组)、存活102例(存活组)。分别于TACE治疗前和治疗后3天,采集HCC患者空腹肘静脉血,离心留取血清,采用ELISA法检测血清HIF-1α、VEGF,计算治疗前后血清HIF-1α、VEGF水平变化(ΔHIF-1α、ΔVEGF)。收集所有研究对象的临床资料,包括性别、年龄、BMI、肿瘤数量、肿瘤最大径、TNM分期、ECOG评分、肝功能Child-Pugh分级,是否合并血管侵犯、转移、静脉癌栓、门静脉高压和腹水以及ΔHIF-1α、ΔVEGF,采用多因素Cox回归模型分析影响HCC患者TACE治疗后3年死亡的危险因素。以血清ΔHIF-1α、ΔVEGF水平的中位数为临界值,将HCC患者分为血清ΔHIF-1α高水平者与低水平者、血清ΔVEGF高水平者与低水平者,比较不同ΔHIF-1α、ΔVEGF水平者TACE治疗后3年累积存活率。结果 死亡组血...     

TACE后残存肝癌组织中VEGF及MVD表达变化及意义

目的观察肝动脉栓塞化疗（TACE）后残存肝癌组织中VEGF与MVD表达变化及意义。方法取21例一期手术切除的原发性肝细胞癌手术切除标本为对照组,19例TACE后二期切除的原发性肝细胞癌手术切除标本为观察组。采用免疫组化法测算两组VEGF阳性表达率与MVD值。结果对照组VEGF阳性表达率为38.1%,MVD值为（90.9±45.3）条/HP,均明显低于观察组的78.9%和（171.6±68.1）条/HP,P均〈0.01。结论 TACE治疗后残存癌组织的VEGF与MVD表达明显增多,可增加转移复发的机会。对于TACE后有手术指征的患者应尽早手术。     

肝癌组织骨桥蛋白及CD44v6的表达与肝癌肝移植术患者预后的意义研究

目的研究骨桥蛋白(OPN)、CD44v6预测肝细胞癌肝移植患者预后效能,为寻求新的受体选择标准提供理论依据。方法收集2002年8月至2006年7月期间在西安交通大学医学院第一附属医院行经典原位肝移植术,且病理确诊为肝细胞癌的病例共30例。应用组化染色法,检测OPN、CD44v6的表达,进行统计分析。结果 30例肝细胞肝癌组织中OPN和CD44v6表达正相关。肝移植术后肿瘤复发转移与符合米兰标准情况显著负相关(P<0.01),与OPN、CD44v6的表达正相关(P<0.05)。在超出米兰标准的患者中,肿瘤复发与OPN、CD44v6阳性表达的相关性更强(P<0.01)。随访期内OPN或CD44v6染色阳性患者的生存率明显低于阴性患者(P=0.001),双阳性患者的生存率最低。对于超米兰标准的肝移植患者更为显著(P=0.004)。结论 OPN、CD44v6可以作为预测肝细胞癌肝移植患者预后的预测标签,联合检测OPN、CD44v6能够更好地反映超米兰标准的肝移植患者预后,检测OPN、CD44v6可以纳入受体选择标准。     

肝细胞癌患者肝动脉化疗栓塞术前后血清TGFβ1、VEGF、bFGF浓度变化

目的：观察肝细胞癌患者肝动脉化疗栓塞术（TACE）前后血清转化生长因子（TGFβ1）、血管内皮生长因子（VEGF）和碱性成纤维细胞生长因子（bFGF）的浓度变化。方法：随机选择64例经病理确诊的肝细胞癌（HCC）患者,按照单纯随机抽样法均分为实验组和对照组,两组患者治疗药物相同,实验组患者行TACE术,对照组患者静脉注射化疗药物。用双抗体夹心酶联免疫吸附试验法检测两组患者TACE术前3天和术后两周血清TGFβ1、VEGF、bFGF浓度。结果：治疗后两周患者血清TGFβ1、VEGF、bFGF浓度均升高;与治疗前比较,差异有显著性意义（P〈0.05）。结论：TACE的远期疗效欠佳,可能是其引起HCC患者血清TGFβ1、VEGF、bFGF过表达,导致肿瘤血管增生、侧枝循环形成以及机体的免疫反应被抑制。     

VEGF、CD44v6及p27在胃癌组织中的表达及其临床意义

目的探讨血管内皮细胞生长因子(VEGF)、CD44v6及p27在胃癌中的表达并判断其与胃癌发生的关系。方法应用S-P法,对63例胃癌组织及相应的癌旁组织、28例正常胃组织进行VEGF、CD44v6及p27蛋白检测,并研究其与病理分期的相关性。结果胃癌组织中p27阳性表达率显著下降,VEGF、CD44v6阳性表达率显著升高(P0.05);胃癌组织中,分化程度低、侵及浆膜、有淋巴结转移及TNM分期高者,p27阳性表达率显著下降,VEGF、CD44v6阳性表达率显著升高(P0.05);胃癌中VEGF表达与p27表达呈负相关(r=-0.614 P0.05);与CD44v6表达呈正相关(r=0.614 P0.05);p27的表达与CD44v6表达呈负相关(r=-0.745 P0.05)。结论 VEGF、CD44v6及p27表达与胃癌发生发展、浸润、转移有关,预示这三种蛋白的表达可能与胃癌的治疗和预后具有显著关系,为临床治疗胃癌提供新的思路。     

胃癌组织中MMP-9、CD44v6和VEGF的表达变化及意义

目的观察胃癌组织中基质金属蛋白酶9（MMP-9）、黏附分子CD44拼接变异体v6（CD44v6）和血管内皮生长因子（VEGF）表达变化,并探讨其临床意义。方法采用免疫组化法检测80例胃癌组织及癌旁组织中MMP-9、CD44v6和VEGF。结果胃癌组织中MMP-9、CD44v6和VEGF表达显著高于癌旁组织,且有淋巴结转移者均高于无淋巴结转移者,Ⅲ～Ⅳ期者高于Ⅰ～Ⅱ期（P均〈0.05）;胃癌组织中MMP-9、CD44v6与VEGF的表达呈正相关（r=0.331、0.421,P均〈0.05）。结论胃癌组织中MMP-9、CD44v6、VEGF表达水平明显上调,其表达与胃癌淋巴结转移和临床分期有关;三者在胃癌的发生发展过程中可能起协同作用。     

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.     

Combined treatment of hepatocellular carcinoma with partial splenic embolization and transcatheter hepatic arterial chemoembolization

AIM: To prospectively evaluate the effi cacy and safety of partial splenic embolization (PSE) combined with transcatheter hepatic arterial chemoembolization (TACE) in treatment of hepatocellular carcinoma (HCC). METHODS: Fifty patients suffering from primary HCC associated with hypersplenism caused by cirrhosis were randomly assigned to 2 groups: group A receiving PSE combined with TACE (n = 26) and group B receiving TACE alone (n = 24). Follow-up examinations included calculation of peripheral blood cells (leukcytes, platelets and red blood cells) and treatment-associated complications. RESULTS: Prior to treatment, there was no signifi cant difference in sex, age, Child-Pugh grade, tumor diameter, mass pathology type and peripheral blood cell counts between the 2 groups. After treatment, leukocyte and platelet counts were significantly higher in group A during the 3-mo follow-up period (P < 0.05), but lower in group B (P < 0.05). Severe complications occurred in 3 patients (11.5%) of group A and in 19 patients (79.2%) of group B (P < 0.05), and there was no significant difference in symptoms of post-embolization syndrome, including abdominal pain, fever, mild nausea and vomiting between the 2 groups (P > 0.05). CONCLUSION: PSE combined with TACE is more effective and safe than TACE alone for patients with HCC associated with hypersplenism caused by cirrhosis.     

Cerebral and pulmonary embolisms after transcatheter arterial chemoembolization for hepatocellular carcinoma

A cerebral lipiodol embolism is an extremely rare complication of transcatheter arterial chemoembolization for hepatocellular carcinoma. We present a case of cerebral lipiodol embolism that occurred after the third arterial chemoembolization, report the clinical and radiological findings, and review the medical literature.     

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...     

明胶酶、CD44v6在结直肠癌中的表达及意义

目的探讨明胶酶在结直肠癌中的表达及其CD44v6在结直肠癌侵袭转移过程中的关系。方法采用明胶酶谱（gel zymography）和S-P免疫组化对50例结直肠癌癌组织和相应正常组织中的明胶酶、CD44v6进行检测。结果明胶酶在结直肠癌中的表达水平显著高于正常组织（P〈0．05）；明胶酶与结直肠癌的Duke’s分期呈同步的正相关（P〈0．05）；明胶酶在CD44v6强阳性组中表达量升高显著（P〈0．05）。结论明胶酶与结直肠癌的侵袭转移性有着密切的关系，不仅在癌细胞的酶解，而且在癌细胞的黏附、运动过程中有可能发挥着重要作用。     

Fever after transcatheter arterial chemoembolization for hepatocellular carcinoma: incidence and risk factor analysis

Objective. Post-treatment fever frequently occurs in hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE), but its incidence and clinical significance are unclear. The aim of this study was to identify the incidence and risk factors for fever after TACE in HCC patients. Material and methods. Forty-one consecutive HCC patients undergoing 73 sessions of TACE were included in the study. The incidence and possible risk factors associated with post-TACE fever were analyzed. Results. Forty-nine (67%) episodes of fever developed in 30 (73%) HCC patients after TACE, but none of the patients developed bacterial infection after TACE. Patients who developed fever were of younger age, had larger tumors, a higher dose of chemoembolization agents and a higher embolized volume compared with those without fever. Multivariate logistic regression disclosed that a dosage of doxorubicin plus iodized oil >23 during chemoembolization and tumor size >3 cm were significant predictors associated with the development of post-TACE fever (odds ratio: 3.749, 95% CI: 1.188–11.830, p=0.024 and odds ratio: 3.599, 95% CI: 1.107–11.706, p=0.033, respectively). Conclusions. Fever after TACE is common, but infectious complications are rare. Chemoembolization dosage and tumor size are predictive of fever after transcatheter arterial chemoembolization and may be of help in the prevention and care of this distressing complication.     

Balloon-occluded transcatheter arterial chemoembolization for hepatocellular carcinoma

Transcatheter arterial chemoembolization(TACE) is widely accepted as a treatment for patients with hepatocellular carcinoma(HCC) in the intermediate stage according to the Barcelona Clinic Liver Cancer(BCLC) guidelines. Recently, balloon-occluded TACE(B-TACE) was developed in Japan. Despite the lack of a clear definition, B-TACE is generally defined as the infusion of emulsion of chemotherapeutic agents with lipiodol followed by gelatin particles under the occlusion of feeding arteries by a microballoon catheter, which leads to the dense lipiodol emulsion(LE) accumulation in HCC nodules. This phenomenon cannot be explained only by the prevention of proximal migration and leakage of embolization materials; it further involves causing local changes in the hemodynamics of the surrounding occlusion artery and targeted HCC nodules. Balloon-occluded arterial stump pressure plays an important role in the dense LE accumulation in targeted HCC nodules. Although randomized controlled trials comparing the therapeutic effect and the prognosis of B-TACE to those of the other TACE procedures, such as conventional-TACE and drug-eluting beads TACE, are still lacking, B-TACE is thought to be a promising treatment. The purpose of this review is to summarize the mechanism, therapeutic effect, indication, prognosis and complications of BTACE.     

Expression of vascular endothelial growth factor in surgical specimens of hepatocellular carcinoma

Purpose: Vascular endothelial growth factor (VEGF) has been reported to play an important role in angiogenesis in hepatocellular carcinoma (HCC). However, there is great variation in reports on the distribution of VEGF expression, especially in non-carcinoma liver cells. Furthermore, some reports have mentioned that endothelial cells were positive for VEGF antibody but have not evaluated its significance. In this study, we focused our attention to these problems and try to solve them. We also analyzed the factors influencing VEGF expression and evaluated the prognostic potential of VEGF protein in HCC. Methods: We examined the VEGF expression in specimens surgically removed from 46 HCC patients and 3 patients with liver cancer metastatic from the colon, and in 4 specimens of liver tissue with benign disease, by immunohistochemical methods. Results/conclusions: VEGF was expressed in HCC cells and hepatocytes and on vascular endothelial cells. Our finding that about seven times more endothelial cells were positive for VEGF antibody in carcinoma areas than in non-carcinoma areas (P < 0.001) suggests that VEGF is a very important angiogenesis factor for HCC growth. VEGF expression in HCC cells and non-carcinoma liver cells and on endothelial cells did not closely correlate with the disease recurrence rate (P > 0.05), suggesting that VEGF expression may not be useful as an individual factor for estimating the prognosis of HCC. A statistical analysis of the relationships between VEGF expression and clinicopathological variables revealed the following: preoperative transcatheter arterial embolization enhanced VEGF expression in both HCC cells and non-carcinoma liver cells. The histological grade of HCC and the level of alanine aminotransferase was related to VEGF expression in non-carcinoma liver cells and on endothelial cells in HCC areas. Tumor size and the histological status of the accompanying chronic hepatitis also influenced the VEGF expression on endothelial cells. Our findings concerning not only HCC but also the surrounding liver and endothelial cells may provide useful information for further research on the role of VEGF expression in HCC patients. Received: 29 July 1999 / Accepted: 11 October 1999     

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。