Gene expression of 5-fluorouracil metabolic enzymes in hepatocellular carcinoma and non-tumor tissue

5-fluorouracil (5-FU) is a basic agent used in chemotherapy. The aim of this study is to investigate the gene expression of 5-FU anabolic and catabolic enzymes in hepatocellular carcinoma (HCC) and non-tumor tissue, respectively to increase our knowledge of resistant mechanisms to 5-FU in HCC. The relative mRNA level of orotate phosphoribosyltransferase (OPRT), ribonucleotide reductase (RNR), dihydropyrimidine dehydrogenase (DPD) and target enzyme thymidylate synthase (TS), were analyzed in 30 matched samples of HCC (T) and non-tumor tissue (NT) using quantitative RT-PCR. The expression of OPRT, RNR-M1, RNR-M2 and TS is significantly higher in T compared with in NT (1.3-fold increase, 1.6-fold, 7.1-fold, 1.9-fold, respectively), but that of DPD showed no difference between T and NT. Our results show that HCC should not be treated with 5-FU alone because of its instability in liver.     

Adhesion molecule CD44 expression in non-tumor epithelium adjacent to laryngeal cancer

BACKGROUND: Studies of adjacent non-tumor epithelia (ANTE) of laryngeal cancer have presented contradictory results regarding the expression of the adhesion molecule CD44 and its role as an early event and risk marker for progression to cancer. METHODS: An immunohistochemical study was performed on changes in CD44 expression in the ANTE and tumor tissue of 112 cases of laryngeal cancer, using the anti-CD44 monoclonal antibody DF1485. The aim was to evaluate the importance of these changes as an early event in laryngeal carcinogenesis. RESULTS: The ANTE were histologically hyperplastic in 107 cases (95.5%) and presented epithelial dysplasia in 105 cases (93.7%). A significant association between tumor and epithelial CD44 expression was observed in both hyperplastic (p < 0.001) and dysplastic (p < 0.001) ANTE. There was no significant association between ANTE CD44 expression and clinical or histopathological relevant data. CONCLUSIONS: Loss of CD44 expression in ANTE can be considered an early event in laryngeal carcinogenesis and a marker of major alterations in CD44 expression in the derived tumor tissue.     

Protein expression associated with early intrahepatic recurrence of hepatocellular carcinoma after curative surgery

The poor prognosis of patients with hepatocellular carcinoma (HCC) is attributed to intrahepatic recurrence. To understand the molecular background of early intrahepatic recurrence, we conducted a global protein expression study. We compared the protein expression profiles of the primary HCC tissues of 12 patients who showed intrahepatic recurrence within 6 months post surgery with those of 15 patients who had no recurrence 2 years post surgery. Two-dimensional difference gel electrophoresis identified 23 protein spots, the intensity of which was highly associated with early intrahepatic recurrence. To validate the prediction performance of the identified proteins, we examined additional HCC tissues from 13 HCC patients; six with early intrahepatic recurrence and seven without recurrence. We found that all but one of the 13 patients were grouped according to their recurrence status based on the intensity of the 23 protein spots. Mass spectrometry identified 23 proteins corresponding to the spots. Although 13 of 23 have been previously reported to be correlated with HCC, their association with early intrahepatic recurrence had not been established. The identified proteins are involved in signal transduction pathways, glucose metabolism, cytoskeletal structure, cell adhesion, or function as antioxidants and chaperones. The identified proteins may be candidates for prognostic markers and contribute to the improvement of existing therapeutic strategies.     

Radiation therapy for intrahepatic recurrence after hepatectomy for hepatocellular carcinoma

Background. The intrahepatic recurrence rate after curative hepatectomy for hepatocellular carcinoma (HCC) is high, and management of recurrence is thus important for long-term survival. The use of radiation therapy has been relatively uncommon in the treatment of recurrent HCC.Methods. Eight patients underwent radiation therapy for recurrent HCC 12–98 months after hepatectomy. Five of them were treated with protons (250MeV; 68.8–84.5Gy), and three were treated with X-rays (6MV; 60 or 70Gy). One patient received radiation therapy twice for another lesion with a 79-month interval. The target tumors were 1.2–4.5cm. All patients also underwent transcatheter arterial embolization or other regional therapy.Results. Although transient ascites was found in three patients after radiation therapy, no patient died as a result of the irradiation. Seven patients died 9 months to 4 years (median 1 year 6 months) after radiation therapy. Re-recurrence was observed in the irradiated liver in two patients (local control 78%). Four patients died of lung metastasis after radiation therapy. The median survival time was 3 years 3 months (range 1 year 1 month to 8 years 6 months) after recurrence.Conclusion. Multimodality therapy is necessary for the management of recurrence. Radiation therapy could be beneficial when other therapies present some difficulty regarding application or are performed incompletely. It must be emphasized that radiation therapy should be considered in addition to other regional therapies for the treatment of recurrent or re-recurrent HCC, and that radiation therapy can be repeated in selected patients.     

Transarterial chemoembolization for inoperable hepatocellular carcinoma and postresection intrahepatic recurrence

BACKGROUND AND OBJECTIVES: The role of transarterial chemoembolization (TACE) for inoperable hepatocellular carcinoma (HCC) has remained controversial, and its efficacy for postresection intrahepatic recurrence has not been fully assessed. A study was performed to evaluate the treatment results and prognostic factors of TACE treatment in these patients. METHODS: Clinicopathologic data and treatment results of 384 patients with inoperable HCC and 100 patients with postresection recurrent HCC treated with TACE were collected prospectively and analyzed. RESULTS: TACE was associated with an overall treatment morbidity rate of 23% (112/484) and mortality rate of 4.3% (21/484). A particularly high mortality rate of 20% (9/45) was observed among patients with tumors > 10 cm and pretreatment serum albumin level 35 g/L were independent favorable prognostic factors. TACE in patients with postresection recurrent HCC was associated with less morbidity, mortality, and a better survival outcome compared with patients with primary inoperable HCC, but this was largely related to smaller tumor size and better liver function in the former group at the time of TACE treatment. CONCLUSIONS: TACE in patients with inoperable HCC was associated with significant morbidity and mortality, and the survival benefit was limited. Better patient selection in terms of tumor size and liver function may improve treatment results. Patients who have a tumor > 10 cm and poor liver function (serum albumin 相似文献   

Correlation between CD105 expression and postoperative recurrence and metastasis of hepatocellular carcinoma

Background  

Angiogenesis is one of the mechanisms most critical to the postoperative recurrence and metastasis of hepatocellular carcinoma (HCC). Thus, finding the molecular markers associated with angiogenesis may help identify patients at increased risk for recurrence and metastasis of HCC. This study was designed to investigate whether CD105 or CD34 could serve as a valid prognostic marker in patients with HCC by determining if there is a correlation between CD105 or CD34 expression and postoperative recurrence or metastasis.     

小肝癌患者术后肝内早期复发的生存因素分析

目的:探讨小肝癌术后早期复发的影响因素。方法:回顾性分析2001-01-04-2007-12-31我院收治经病理确诊的原发性小肝癌患者68例,分析宿主情况、肿瘤情况和治疗因素与小肝癌术后早期无瘤生存率的关系。采用SPSS13.0 for windows软件包进行统计学处理,应用Cox回归模型确定影响小肝癌术后复发预后的因素。结果:68例患者中早期肝内复发20例。术后1和2年无瘤生存率分别为82.3%和70.6%。Cox回归模型多因素分析结果表明,肿瘤大小、门脉瘤栓、肿瘤部位和术中输血是影响小肝癌术后早期复发的独立危险因素。结论:小肝癌切除术后患者早期无瘤生存与否取决于宿主情况、肿瘤情况和治疗因素。     

CD44,CD90的表达与肝癌肝移植术后复发转移的关系

目的:探讨CD44,CD90的表达与肝细胞肝癌肝移植患者预后的关系.方法:收集福州总医院2002至2012年行经典原位肝移植治疗的105例原发性肝细胞癌患者的石蜡包埋标本.应用免疫组化染色法检测肿瘤组织中CD90,CD44的表达,并对临床病理特征及术后随访资料进行统计学分析.结果:CD44和CD90的表达相关关系经Spearman相关分析,两者呈正相关(r=0.5,P＜0.001).COX多因素分析显示,患者5年无复发生存率与CD90高表达(HR=2.765,P=0.002)显著相关.Kaplan-Meier分析显示CD90高表达的患者与CD90低表达患者的肝切除术后5年无复发生存率、术后5年总生存率均有显著差异(40.4％ vs57.6％)(P＜0.05)、(12.7％vs 61.1％) (P＜0.001).COX多因素分析显示,患者5年总生存率与肿瘤大小(HR=1.743;P=0.037)、AFP(HR=2.291;P=0.004)、肿瘤分化(HR=0.283;P＜0.001)、CD44(HR=1.977;P =0.029)、CD90(HR=1.883;P=0.041)表达显著相关.Kaplan-Meier分析显示CD44高表达的患者与CD44低表达患者的肝切除术后5年总生存率有显著差异(16.6％vs 62.7％) (P＜0.001),CD44和CD90共同高表达的患者比CD44或CD90低表达患者的术后5年总生存率显著低(10.7％vs 54.5％)(P ＜0.001).结论:CD90与CD44的高表达相关,CD90与肝癌肝移植术后复发转移有关,二者均影响肝癌肝移植患者预后.     

Predictive factors for intrahepatic recurrence of hepatocellular carcinoma after partial hepatectomy.

To establish useful predictors of the intrahepatic recurrence of hepatocellular carcinoma (HCC) after partial hepatectomy, retrospective analyses of clinical and pathologic factors were done in 112 of 206 patients treated by partial hepatectomy. The absence or presence of intrahepatic recurrence was confirmed by a follow-up study. Cancer-free survival rates after 1, 2, 3, and 5 years were 54.8%, 36.7%, 32.5%, and 25.6%, respectively. The significant factors affecting recurrence were tumor size, number of tumors, cancer cell infiltration of the fibrous capsule of the tumor, portal involvement, and stage of the tumor, but the grade of anaplasia according to Edmondson-Steiner's classification and the severity of associated liver cirrhosis did not show a correlation with the incidence of recurrence. According to Akaike's Information Criteria (AIC), tumor number is useful for predicting early prognosis, and capsular infiltration is a good indicator of long-term survival. However, portal involvement gives much prognostic information throughout the entire postoperative period.     

肝细胞癌切除术后肝内复发患者的预后影响因素分析

目的 探讨肝细胞癌(HCC)切除术后肝内复发的预后影响因素以及复发后治疗方式的选择.方法 收集184例HCC切除术后肝内复发患者的临床病理资料,回顾性分析21项临床病理学因素以及复发后治疗方式对HCC患者肝内复发后生存期的影响.结果 单因素分析结果 表明,术前血清甲胎蛋白(AFP)水平较高(>100 ng/ml)、有微血管浸润、首次诊断复发时肿瘤的Child-Pugh分级为B或C级、有多个肝内复发肿瘤以及早期肝内复发(≤12个月)的患者预后不良.Cox多因素分析结果 表明,首次诊断复发时肿瘤的Child-Pugh分级、复发肿瘤的数目和复发时间是影响HCC患者复发后生存期的独立危险因素.69例单个复发肿瘤患者中,经再次肝切除手术和局部消融治疗患者的复发后中位生存期分别为34和23个月,而经肝动脉插管化疗栓塞治疗和未进行治疗患者的复发后中位生存期分别为15和9个月,4种治疗方式患者的生存期差异有统计学意义(P<0.05).结论 首次诊断复发时肿瘤的Child-Pugh分级为A级、单个复发肿瘤、复发时间较晚(>12个月)、经过再次肝癌切除手术或局部消融治疗的HCC肝内复发患者的预后较好.     

High expression of CD44v9 and xCT in chemoresistant hepatocellular carcinoma: Potential targets by sulfasalazine

CD44v9 is expressed in cancer stem cells (CSC) and stabilizes the glutamate‐cystine transporter xCT on the cytoplasmic membrane, thereby decreasing intracellular levels of reactive oxygen species (ROS). This mechanism confers ROS resistance to CSC and CD44v9‐expressing cancer cells. The aims of the present study were to assess: (i) expression status of CD44v9 and xCT in hepatocellular carcinoma (HCC) tissues, including those derived from patients treated with hepatic arterial infusion chemoembolization (HAIC) therapy with cisplatin (CDDP); and (ii) whether combination of CDDP with sulfasalazine (SASP), an inhibitor of xCT, was more effective on tumor cells than CDDP alone by inducing ROS‐mediated apoptosis. Twenty non‐pretreated HCC tissues and 7 HCC tissues administered HAIC therapy with CDDP before surgical resection were subjected to immunohistochemistry analysis of CD44v9 and xCT expression. Human HCC cell lines HAK‐1A and HAK‐1B were used in this study; the latter was also used for xenograft experiments in nude mice to assess in vivo efficacy of combination treatment. CD44v9 positivity was significantly higher in HAIC‐treated tissues (5/7) than in non‐pretreated tissues (2/30), suggesting the involvement of CD44v9 in the resistance to HAIC. xCT was significantly expressed in poorly differentiated HCC tissues. Combination treatment effectively killed the CD44v9‐harboring HAK‐1B cells through ROS‐mediated apoptosis and significantly decreased xenografted tumor growth. In conclusion, the xCT inhibitor SASP augmented ROS‐mediated apoptosis in CDDP‐treated HCC cells, in which the CD44v9‐xCT system functioned. As CD44v9 is typically expressed in HAIC‐resistant HCC cells, combination treatment with SASP with CDDP may overcome such drug resistance.     

Cytokeratin 19 expression in hepatocellular carcinoma predicts early postoperative recurrence

Clinicopathologic features and postoperative outcomes were investigated for patients who underwent curative surgery for biliary marker (CK7 and CK19)-positive hepatocellular carcinoma (HCC). Of 157 HCCs, 93 were CK7(-)CK19(+), 49 were CK7(+)-CK19(-), 1 was CK7(-)CK19(+), and 14 were CK7(+)-CK19(+). Semiquantitative analysis of expression levels demonstrated a significant correlation between CK7 and CK19 expression. Of various clinicopathologic parameters, tumor differentiation exhibited a significant correlation with CK7 and CK19 expression. All 15 patients with CK19-positive HCC also had anti-HBc. Log-rank test revealed that CK7 expression, CK19 expression, high aspartate aminotransferase (AST) activity, low albumin concentration, portal invasion, intrahepatic metastasis, and severe fibrosis (cirrhosis) reduced the tumor-free survival rate. Multivariate analysis demonstrated that CK19 expression, intrahepatic metastasis, and severe fibrosis were independent predictors of postoperative recurrence, while CK7 expression was not. Twelve of 15 patients with CK19-positive HCC had tumor recurrence within 2 years after surgery, a significantly higher incidence of early recurrence than for CK19-negative HCC. The incidence of extrahepatic disease, especially lymph node metastasis, was significantly higher for patients with CK19-positive HCC. These findings indicate that CK19 expression is a predictor of early postoperative recurrence due to increased invasiveness.     

食管癌细胞P-糖蛋白与CD44表达相关性研究

Objective： To investigate the relationship between P-glycoprotein （P-gp） and adhesion molecule CD44 expression as well as their clinical significance in esophageal carcinoma. Methods： To examine the expressed level of P-gp and CD44 by flow cytometry （FCM） in the operated samples of 70 cases with esophageal carcinoma and their normal mucosa of esophageal incision, and to evaluate their relationship with clinicopathological factors. Results： Among the 70 cases with esophageal carcinoma, the expression of P-gp in the 27 cases （38.6%） was negative （positive cells 〈25%）; 11 cases （15.7%） were 25%-40% expression of P-gp positive cells; 14 cases （20%） were 41%-60% expression of P-gp positive cells; 18 cases （25.7%） were the high expression （positive cells 〉60%） of P-gp. Of the cases with the tumor sizes being more than 4 cm, the expression of CD44 showed a significant difference （P〈0.05） in 25 cases with P-gp positive, compared with 19 cases with P-gp negative. Of the cases with high-mild differentiated esophageal carcinoma, the expression of CD44 showed a significant difference （P〈0.05） in 22 cases with P-gp positive, compared with 17 cases with P-gp negative. Of the cases with clinical Ⅲ-Ⅳ stage, the expression of CD44 showed a significant difference （P〈0.05） in 26 cases with P-gp positive, compared with 10 cases with P-gp negative. Of the cases with lymph node metastasis, the CD44 expression showed a significant difference （P=0.050） in 27 cases with P-gp positive, compared with 11 cases with P-gp negative. Of the cases of the patients＇ age being more than 56 years, the expression of CD44 showed a significant difference （P〈0.01） in 27 cases with P-gp positive, compared with 12 cases with P-gp negative. When the P-gp and CD44 expression were positive, the clinical Ⅱ stage and Ⅲ-Ⅳ stage in esophageal carcinoma was showed a significant difference （P〈0.05）. Conclusion： When the CD44 and P-gp both have the positive high expression, it will be significantly associated with the esophageal carcinoma progression and metastasis, so both were a positive expression in esophageal carcinoma, it might suggest a poor and unfavorable prognosis result.     

胃癌患者不同组织CD44v5+细胞表达率的比较

 目的　探讨胃癌患者不同组织CD4 4v5的表达规律。方法　采用流式细胞术对于 39例胃癌患者的癌灶、癌旁组织、淋巴结转移灶和外周血细胞的CD4 4v5表达率进行了检测和对比分析。结果　胃癌患者不同组织的CD4 4v5 +细胞检出率均显著高于正常对照组 (P <0 .0 5或P <0 .0 1)。胃癌患者各种组织CD4 4v5 +细胞表达率大小顺序为癌灶 >癌旁组织 >淋巴结转移灶 >外周血细胞 ,前三者和外周血细胞之间有显著性差异 (P <0 .0 5或P <0 .0 1) ,而前三者之间却无显著性差异 (P >0 .0 5 )。在胃癌患者的各种组织中 ,伴肿瘤转移患者的CD4 4v5 +细胞检出率均显著高于未转移者 (P <0 .0 5或P <0 .0 1)。结论　胃癌患者身体各种组织的CD4 4v5 +细胞表达率显著升高 ,且CD4 4v5 +细胞表达率与肿瘤转移密切相关。     

CD44在肝细胞癌及癌周组织中的表达及其意义

 目的 研究CD44s及CD44v6蛋白在人肝细胞癌组织中表达及其意义。方法 应用免疫组化方法检测42例人肝细胞癌及其癌周组织与10例正常肝组织标本的CD44s及CD44v6表达情况。结果 CD44s及CD44v6在肝癌组织中表达明显高于癌周及正常肝组织，与门静脉内癌栓、包膜浸润及分化程度密切相关（分别为P＜0.01，P＜0.05，P＜0.05）。生存时间2年及2年以上组CD44s及CD44v6阳性表达分别为17.6 %（3／17），5.8 %（1／17），生存时间短于2年分别为52.6 %（10／19），42.2 %（8／19）（P＜0.05）。结论 肝细胞癌组织中CD44的表达与细胞分化、浸润转移密切相关，其阳性表达有助于判断预后。     

肝细胞癌组织CD44v6的检测及其临床意义

目的　探讨原发性肝细胞癌患者术后组织切片中CD44v6的表达及其临床意义。方法　通过免疫组化方法 ,用CD44v6的单克隆抗体 ,以S -P染色法检测CD44v6的表达。结果　CD44v6在癌组织中的表达显著高于癌旁组织 ,有肝外转移的患者其CD44v6的表达也明显高于没有转移的患者 ,而CD44v6的表达在肿瘤大小、分化程度、门静脉癌栓、两年内复发等方面没有显著性差异。结论　CD44v6与肝细胞癌的细胞恶变的发生有关 ,而且CD44v6在有肝外转移患者中的高表达说明它在肝癌发生转移中发挥重要作用。而CD44v6的表达与肿瘤大小、分化程度、门静脉癌栓及两年内复发无关。