ABSTRACT
Objective: To investigate the therapeutic effect and mechanism of lenvatinib on regorafenib-resistant hepatocellular carcinoma cells. Methods: CCK-8 and clone formation assay were used to observe the inhibitory effect of lenvatinib on the growth of hepatocellular carcinoma cells. Flow cytometry was used to detect the apoptosis of regorafenib-resistant hepatocellular carcinoma cells treated with lenvatinib. The expression levels of related proteins were detected by western blot and immunohistochemical staining. The inhibitory effect of lenvatinib on the tumor formation ability of regorafenib-resistant hepatocellular carcinoma cells in vivo was observed by subcutaneous tumor formation experiment in mice. Results: CCK-8 and clone formation assay showed that lenvatinib could inhibit the proliferation of regorafenib-resistant hepatocellular carcinoma cells. The number of clones of HepG2, SMMC7721 and regorafenib-resistant HepG2, SMMC7721 cells in lenvatinib group (120.67±11.06, 53.00±11.14, 55.00±9.54, 78.67±14.64) were all lower than those in control group (478.00±24.52, 566.00±27.87, 333.67±7.02, 210.00±12.77, all P<0.05). Flow cytometry showed that lenvatinib could promote apoptosis of regorafenib-resistant hepatocellular carcinoma cells, the apoptosis rates of HepG2, SMMC7721 and regorafenib-resistant HepG2, SMMC7721 cells in lenvatinib group [(12.30±0.70)%, (9.83±0.38)%, (15.90±1.32)%, (10.60±0.00)%] were all higher than those in control group [(7.50±0.87)%, (5.00±1.21)%, (8.10±1.61)%, (7.05±0.78)%, all P<0.05]. The apoptosis-related protein levels suggested that apoptosis was increased in the treatment of lenvatinib. The animal study showed that lenvatinib can inhibit the growth of regorafenib-resistant cells in vivo. Immunohistochemistry and western blot results showed that lenvatinib could down-regulate the abnormally activated IGF1R/Mek/Erk signaling pathway in regorafenib-resistant cells. Conclusion: Lenvatinib can reverse regorafenib resistance in hepatocellular carcinoma, possibly by down-regulating IGF1R/Mek/Erk signaling pathway.
Subject(s)
Animals , Mice , Humans , Apoptosis , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Proliferation , Liver Neoplasms/pathology , Signal TransductionABSTRACT
Objective: To investigate the influence of HBsAg expression in peritumoral tissue of hepatocellular carcinoma (HCC) patients on their postoperative recurrence. Methods: The HCC patients treated in Shanghai Eastern Hepatobiliary Surgery Hospital from October 2009 to August 2010 were selected. The clinicopathological data and adjacent tissues of 718 patients were collected, and dextran polymer immunohistochemical staining was used to detect the expression of HBsAg in adjacent tissues. According to the expression of HBsAg in adjacent tissues, the tissues were divided into HBsAg positive group and HBsAg negative group. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox regression model was used for multivariate analysis. Results: Among the 718 patients in the whole group, 153 were HBsAg negative and 565 were HBsAg positive. There was a statistically significant difference in serum HBV DNA level between HBsAg-positive and HBsAg-negative patients (P<0.001). The number of patients with serum DNA≥2 000 IU/ml and<2 000 IU/ml in HBsAg negative group were 52 and 93, while the patients in HBsAg positive group were 325 and 205. The cumulative recurrence rates of all patients at 1, 3, and 5 years after surgery were 30.2%, 54.3%, and 62.7%, respectively. The expression of HBsAg was related to the recurrence (P=0.038). Multivariate analysis showed that γ-GT, PT, multiple tumors, tumor length, and portal vein invasion were independent risk factors for recurrence of HCC (P<0.05). In HBeAg-negative patients with low viral load (HBV DNA <2 000 IU/ml) and without cirrhosis, the recurrence rates of HBsAg-positive patients were 14.3% and 31.0% at 3 and 5 years, respectively, compared with HBsAg negative patients (all 0), the difference was statistically significant (P=0.021). Conclusion: The positive expression of HBsAg in peritumoral tissue increases the postoperative recurrence risk of HCC patients.
Subject(s)
Humans , Carcinoma, Hepatocellular/pathology , China , DNA, Viral/analysis , Hepatitis B Surface Antigens , Hepatitis B virus/metabolism , Liver Neoplasms/pathologyABSTRACT
Objective: To investigate the urinary small molecular metabolites and their metabolic characteristics of patients with hepatocellular carcinoma (HCC). Methods: High throughput ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was used to detect the small molecular metabolites in urine of healthy control (n=10), patients with hepatic hemangioma (n=10) and patients with HCC (n=10). The orthogonal projections to latent structures-discriminant analysis (OPLS-DA), hierarchical cluster analysis of multivariate analysis and univariate analysis were used to analyze the differential metabolites of the three groups. Results: The metabolic profiles of the three groups showed that the total of 381 differential metabolites were identified and divided into 96 up-regulated metabolites and 285 down-regulated metabolites. There were 55 urinary metabolites specifically related to HCC. Twenty-one of them were significantly up-regulated, including Acetyl-DL-Leucine, Ala Asp, HoPhe-Gly-OH, while 34 were significantly down-regulated, including Selenocystathionine, Met Trp Met Cys, Valsartan acid and so on. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the differential metabolites were mainly enriched in glutamine/glutamate metabolism, lysine biosynthesis, tricarboxylic acid cycle and purine metabolism. Conclusions: The occurrence of HCC is accompanied by the abnormalities of multiple metabolites and metabolic pathways. The analysis of the characteristic metabolic profile of urine in patients with HCC is helpful to find metabolic markers and potential therapeutic targets for liver cancer.
Subject(s)
Humans , Carcinoma, Hepatocellular/metabolism , Chromatography, High Pressure Liquid/methods , Liver Neoplasms/metabolism , Mass Spectrometry/methods , Metabolomics/methodsABSTRACT
Purpose To investigate the correlation and clinical value of HBO1 and Ki-67 expression in patients with hepatocelluar carcinoma ( HCC). Methods The expression of HBO1 and Ki-67 in 142 cases of hepatocellular carcinoma tis-sues and corresponding adjacent tissues was detected by immu-nohistochemical EnVision. The correlation of clinical pathologic characteristics and prognosis between them was analyzed. Re-sults The positive rates of HBO1 and Ki-67 in HCC were 69. 0% (98/142) and 55. 6% (79/142), respectively, which was obviously higher than that in para-carcinoma tissues (24.6%,19.7%) with statistically significance (P＜0.05). The expressions of HBO1 and Ki-67 were positively correlated. The expressions of HBO1 and Ki-67 were both related to the tumor size, degree of differentiation, TNM staging and portal thrombosis ( P ＜0. 05 ). Kaplan-Meier univariate statistical a-nalysis showed that the survival time of patients with high HBO1 and Ki-67 expression group was significantly shorter than that of the low expression group (P＜0. 05). Cox multivariate analysis showed that high expression of HBO1 and Ki-67, TNM staging and portal thrombosis were significantly correlated to the progno-sis of patients ( P ＜0. 05 ). Conclusion The expressions of HBO1 and Ki-67 are related to the development of HCC and prognosis. Combined detection of HBO1 and Ki-67 may helpful to judge the malignant degree and prognosis of HCC.
ABSTRACT
Objective:To investigate the level and prognostic significance of RNF87 in human hepatocellular carcinoma.Methods:Detected the expression of RNF87 in 98 HCC tissues by immunohistochemistry and Western Blot.According to the clinical data of the patients,we analyzed the relationship between RNF87 level and the prognosis of the HCC patients.Results:The level of RNF87 in HCC tissues is down-regulated,compared with the adjacent tissues.And the expression of RNF87 was significantly related to the prognosis of HCC patients.Besides,the lower level of RNF87 was also obviously related with microvascular invasion.Conclusions:The down-regulated level of RNF87 may be one of the risk factors of human hepatocellular carcinoma progression;RNF87 maybe one of potential tumor suppressors;the level of RNF87 can be used as an indicator to predict the prognosis of HCC patients.
ABSTRACT
Purpose To evaluate the expression of miR-21 in the tissues and cell lines of hepatocellular carcinoma,and to try to find its possible target genes.Methods The expression profile of miR-21 was detected in hepatocellular carcinoma tissues and cell lines.Mter miR-21 inhibitor was used,the alterations in the vitality and invasion of hepatocellular carcinoma cells were observed.The possible target gene of miR-21 was predicted by bioinformatics analysis.The influence of miR-21 inhibitors on the target gene activity was evaluated by dual luciferase reporting gene system.Results The expression level of miR-21 was significantly higher in hepatocellular carcinoma tissues than that in the adjacent ones (P ＜0.05).The expression level of miR-21 in hepatocellular carcinoma cells was significantly higher than that in the hepatic cells (P ＜0.01).After inhibiting miR-21,the viability and invasion ability of hepatocellular carcinoma cells were decreased (P ＜ 0.01).The expression level of programmed cell death 4 (PDCD4) in hepatocellular carcinoma tissues was significantly lower than that in the adjacent tissues (P ＜ 0.01).Its expression level in hepatocellular carcinoma cells was significantly lower than that in the hepatic cells (P ＜ 0.01).After interfering with PDCD4,the vitality and invasion ability of liver cancer cells were increased (P ＜ 0.05).Dual luciferase reporter gene assay indicated that by inhibiting miR-21,the expression level of PDCD4 was up-regulated (P ＜ 0.01).The vitality and invasion ability of liver cancer cells were reduced (P ＜ 0.001).Conclusion MiR-21 can regulate the growth and invasion of liver cancer cells through targeting PDCD4.
ABSTRACT
Purpose To investigate the expression of Dkk3 and Cyclin D1 protein in human hepatocellular carcinoma (HCC) and clinical significance.Methods Immunohistochemistry was used to detect Dkk-3 and Cyclin D1 protein expression level in 80 cases of hepatocellular carcinoma and corresponding para-cancer tissue.Results The expression of Dkk-3 in hepatocellular carcinoma was significantly lower than those in corresponding para-cancer tissue (P ＜ 0.05) and the expression of Cyclin D1 in hepatocellular carcinoma was significantly higher than those in CoTesponding para-cancer tissue (P ＜ 0.05).The up-regulation of Cyclin D1 and the down-regulation of Dkk-3 proteins were correlated with pathologic differentiation degree (P ＜0.05).There was a significant inverse correlation between Dkk3 and Cyclin D1 expression (P =0.044,rs =-0.226).Conclusion The abnormal expression of Dkk-3 and Cyclin D1 gene in human hepatocellular carcinoma suggest that Dkk-3 and Cyclin D1 gene may play an important role in the development and progression of the cancer.The combination deteetion of the two biomarkers may provide valuable data for diagnosis and prognosis estimation of HCC.
ABSTRACT
Hepatocellular carcinoma is one of the most common malignancies in the worldwide.Selected patients with hepatocellular carcinoma are candidates for curative resection,but nevertheless there is a high risk of tumor recurrence.Microvascular invasion (MVI) is an aggressive biological behavior and has repeatedly been identified as a risk factor for prognosis after curative treatment,meanwhile,it is now becoming increasingly concerned.It would be of great significance to distinguish MVI in an early stage and choose an appropriate treatment timely to get a definite improvement for the long-term survival in patients with hepatocellular carcinoma after curative treatment.This review focuses on some certain issues of MVI.
ABSTRACT
Objective@#To analyze the quantitative expression and prognostic significance of tumor neo-vessels, macrophages and fibroblasts in tumor microenvironment of hepatocellular carcinoma (HCC).@*Methods@#The clinic-pathological features and tissue samples for 101 HCC cases were collected. Immunohistochemistry was used to stain the tumor neo-vessels, macrophages and fibroblasts on tumor tissue. The distribution results and quantitative data of above key components were acquired by inverted microscopy equipped with CRi Nuance multispectral analysis system. The number of tumor neo-vessels and macrophages on HCC tissue were counted and the thickness of cancer stroma based on the expression of fibroblasts was measured. The clinic-pathological characteristics and overall survival were analyzed.@*Results@#The median disease free survival (DFS) of 101 HCC cases was 5 month. The quantitative analysis of tumor neo-vessels, macrophages and fibroblasts showed that the expression range was 51-429 with median 218, 110-555 with median 259, 35.61-555.35 with median 246.98, respectively. To take the median as cutoff, all the cases could be classified into high and low expression group. The survival analysis demonstrated that the high density group of macrophages (P=0.022) and fibroblasts (P<0.001) has shorter DFS than low density group, with statistical significance. The high tumor neo-vessels group has shorter DFS with median 5 month than low density group with median 7 month. However, there was no statistical significance between these two group (P=0.197). Combined with above the three stromal components, all the cases could be classified into low, middle and high group. The survival analysis demonstrated that the high density group of stromal components has shorter DFS than the other two groups with median 3 month (P=0.001). Multivariate analysis by Cox regression indicated that cirrhosis, metastasis status, macrophages and fibroblasts density were the independent prognostic factors.@*Conclusion@#The key elements in tumor microenvironment including tumor neo-vessels, macrophages and fibroblasts were heterogenic in HCC tissues and played significant roles in HCC invasion and metastasis.
ABSTRACT
Objective:To investigate the role of Notch signaling pathway in the migration of hepatocellular carcinoma cells and its related mechanisms.Methods:HepG2 was cultured in vitro,which was HL-7702,Huh-7.The migration ability of Transwell cells was detected,Notch,Snail,Westernblot to detect the expression of E-cadherin protein.1 mol/L DAPT and 5 mol/L DAPT were used to block the Notch signaling pathway,and compared the effects of different concentrations on cell migration and the expression of Snail and E-cadherin protein in hepatocellular carcinoma cells.Results:The invasion and migration ability of HCC cell lines was significantly higher than that of normal non neoplastic liver cells (P＜0.05).The invasion and migration ability of HepG2 was slightly higher than that of Huh-7,but the difference was not statistically significant (P＞0.05).Used Western blot method to detect protein imprinting cells Notch,SnaiI,E-cadherin protein expression,results showed that the expression of Notch and Snail in liver cancer cells than normal cells,the expression of E-cadherin was significantly lower than that of normal cells.Blocking the Notch signaling pathway by 1 mol/L DAPT and 5 mol/L DAPT results showed that compared with the control group,the expression of 1 mol/L DAPT and 5 mol/L DAPT can significantly reduce Snail,increased the expression of E-cadherin,and with the increase of the concentration of strengthening effect (P＜0.05).Conclusion:Notch signaling pathway plays an important role in the invasion and migration of hepatocellular carcinoma cells.It is believed that the expression of Snail and E-cadherin may be related to the expression.
ABSTRACT
Objective:To investigate the role of Notch signaling pathway in the migration of hepatocellular carcinoma cells and its related mechanisms.Methods:HepG2 was cultured in vitro,which was HL-7702,Huh-7.The migration ability of Transwell cells was detected,Notch,Snail,Westernblot to detect the expression of E-cadherin protein.1 mol/L DAPT and 5 mol/L DAPT were used to block the Notch signaling pathway,and compared the effects of different concentrations on cell migration and the expression of Snail and E-cadherin protein in hepatocellular carcinoma cells.Results:The invasion and migration ability of HCC cell lines was significantly higher than that of normal non neoplastic liver cells (P＜0.05).The invasion and migration ability of HepG2 was slightly higher than that of Huh-7,but the difference was not statistically significant (P＞0.05).Used Western blot method to detect protein imprinting cells Notch,SnaiI,E-cadherin protein expression,results showed that the expression of Notch and Snail in liver cancer cells than normal cells,the expression of E-cadherin was significantly lower than that of normal cells.Blocking the Notch signaling pathway by 1 mol/L DAPT and 5 mol/L DAPT results showed that compared with the control group,the expression of 1 mol/L DAPT and 5 mol/L DAPT can significantly reduce Snail,increased the expression of E-cadherin,and with the increase of the concentration of strengthening effect (P＜0.05).Conclusion:Notch signaling pathway plays an important role in the invasion and migration of hepatocellular carcinoma cells.It is believed that the expression of Snail and E-cadherin may be related to the expression.
ABSTRACT
Objective To investigate the risk factors resulting in the perioperative liver failure and death for the HBV-associated hepatocellular carcinoma (HCC) patients with or without cirrhosis.Methods The method of retrospective case-control study was performed.The clinicopathological data of 1 083 HCC patients with positive HBsAg who received curative liver resection at the Southwest Hospital from January 2008 to December 2012 were collected.According to the absence or presence of cirrhosis,the HCC patients with positive HBsAg were divided into the 2 groups,including the cirrhosis group (633 patients) and the non-cirrhosis group (450patients).The intraoperative conditions (operation time,volume of intraoperative blood loss,rate of blood transfusion,rate of pringle maneuver) and postoperative conditions (incidence of perioperative complications,duration of postoperative hospital stay,perioperative mortality) of HCC patients were observed.The gender,age,alanine transaminase (ALT),aspartate transaminase (AST),albumin (Alb),total bilirubin (TBil),platelet (PLT),Child-Pugh classification,operation time,volume of intraoperative blood loss,blood transfusion,pringle maneuver,extent of liver resection,number of tumors,tumor diameter,tumor thrombus and liver cirrhosis were enrolled and prognostic factors resulting in perioperative liver failure and death for the HCC patients were explored.Measurement data with skewed distribution were presented as M (range) and comparison between the 2 groups was analyzed using Mann-Whitney U test.Count data were presented as counts (percentage) and comparison between the 2 groups was analyzed using chi-square test or Fisher exact probability.Univariate analysis was performed by chi-square test and multivariate analysis was performed by Logistic regression model (forward).Results (1) The intraoperative conditions:the volume of intraoperative blood loss were 500 mL (range,30-7 000 mL) in the cirrhosis group and 400 mL (range,50-8 000 mL) in the non-cirrhosis group,with a statistically significant difference between the 2 groups (Z =-2.209,P ＜ 0.05).The operation time,rate of blood transfusion and rate of pringle maneuver were 250 minutes (range,82-715 minutes),29.86％ (189/633),62.24％ (394/633) in the cirrhosis group and 242 minutes (range,85-738 minutes),27.11％ (122/450),66.67％ (300/450) in the non-cirrhosis group,respectively,with no statistical differences between the 2 groups (Z =-1.212,x2 =0.969,2.236,P ＞0.05).(2) The postoperative conditions:the incidence of perioperative complications was 30.49％(193/633) in the cirrhosis group and 21.11％ (95/450) in the non-cirrhosis group,with a statistically significant difference between the 2 groups (x2 =11.851,P ＜ 0.05).The incidence of lung infection,abdominal infection and liver failure were 6.48％ (41/633),2.69％ (17/633),5.53％ (35/633) in the cirrhosis group and 3.56％ (16/450),0.89％ (4/450),1.33％ (6/450) in the non-cirrhosis group,respectively,with statistically significant differences between the 2 groups (x2 =4.502,4.465,12.713,P ＜ 0.05).The duration of postoperative hospital stay was 15 days (range,0-70 days) in the cirrhosis group and 14 days (range,0-71 days) in the non-cirrhosis group,with a statistically significant difference between the 2 groups (Z =-3.448,P ＜ 0.05).The perioperative mortality was 5.85％ (37/633) in the cirrhosis group and 2.44％ (11/450) in the non-cirrhosis group,with a statistically significant difference between the 2 groups (x2=7.181,P ＜ 0.05).(3)Results of risk factors affecting perioperative liver failure:①results of univariate analysis showed that age,AST,Alb,Child-Pugh classification,operation time,volume of intraoperative blood loss,blood transfusion,extent of liver resection,tumor diameter,liver cirrhosis with positive HBsAg were associated with perioperative liver failure in HCC patients (x2=5.013,7.979,8.855,16.968,14.148,9.764,18.511,11.749,5.534,12.713,P＜0.05);age,AST,Alb,Child-Pugh classification,operation time,blood transfusion,extent of liver resection and tumor diameter were associated with perioperative liver failure in the cirrhosis group (x2=5.877,5.380,11.087,13.672,8.849,13.170,12.418,5.805,P ＜ 0.05);volume of intraoperative blood loss was associated with perioperative liver failure in the non-cirrhosis group (P ＜ 0.05).②Results of multivariate analysis showed that age≥60 years,Child-Pugh class B,operation time ＞ 360 minutes,blood transfusion,extent of liver resection ≥3 segments and liver cirrhosis were independent risk factors affecting perioperative liver failure in HCC patients with positive HBsAg [OR =2.285,2.716,2.315,2.159,2.459,4.322;95％ confidence interval (CI):1.081-4.831,1.100-6.706,1.064-5.038,1.068-4.362,1.264-9.786,1.763-10.598,P＜0.05];Alb ＜38 g/L,Child-Pugh class B,blood transfusion and extent of liver resection ≥ 3 segments were independent risk factors affecting perioperative liver failure in the cirrhosis group (OR =2.231,2.857,2.186,2.927,95％ CI:1.038-4.795,1.095-7.451,1.045-4.576,1.426-6.008,P ＜ 0.05);volume of intraoperative blood loss ＞ 1 200 mL was an independent risk factor affecting perioperative liver failure in the non-cirrhosis group (OR =15.077,95％CI:2.695-84.353,P ＜ 0.05).(4) Risk factors affecting perioperative death:①results of univariate analysis showed that gender,Alb,TBil,Child-Pugh classification,blood transfusion,extent of liver resection,tumor diameter,tumor thrombus and liver cirrhosis were associated with perioperative death in HCC patients with positive H BsAg (x2=4.462,8.783,4.212,4.869,7.189,11.745,6.837,4.323,7.181,P ＜0.05);Alb,extent of liver resection and tumor diameter were associated with perioperative death in the cirrhosis group (x2=12.173,12.793,10.981,P ＜ 0.05);blood transfusion and tumor thrombus were associated with perioperative death in the non-cirrhosis group (x2 =5.836,6.417,P ＜ 0.05).② Results of multivariate analysis showed that Alb ＜38 g/L,extent of liver resection ≥ 3 segments and liver cirrhosis were independent risk factors affecting perioperative death in HCC patients with positive HBsAg (OR =2.560,2.657,2.567,95％ CI:1.382-4.742,1.471-4.800,1.283-5.134,P ＜ 0.05);Alb ＜ 38 g/L,extent of liver resection ≥ 3 segments and tumor diameter≥5 cm were independent risk factors affecting perioperative death in the cirrhosis group (OR =3.003,2.533,3.060,95％ CI:1.495-6.034,1.251-5.128,1.135-8.251,P＜0.05);blood transfusion and tumor thrombus were independent risk factors affecting perioperative death in the non-cirrhosis group (OR =3.755,4.036,95％ CI:1.047-13.467,1.126-14.469,P ＜ 0.05).Conclusions Liver cirrhosis is an independent risk factor for perioperative liver failure and death in HCC patients with positive HBsAg.The risk of perioperative liver failure and death in HCC patients with cirrhosis is significantly higher than that in HCC patients without cirrhosis,and there is a difference in the risk factors for perioperative liver failure and death.
ABSTRACT
Objective To study the feasibility of defining the internal gross tumor volume (IGTV) of hepatocellular carcinoma applying the enhanced four-dimensional computed tomography (4DCT) images with deformable registration technology.Methods Ten HCC patients who accepted radiation therapy were selected in this study.The 4DCT in free breathing,non-enhanced 3DCT and arterial phase enhanced 3DCT in end inspiration breath holding associated with active breathing coordinator were acquired sequentially.4DCT were sorted into ten series CT images according to breath phase,and named CT00,CT10..…CT90.Gross tumor volume (GTV) were contoured on different CT series and the IGTV1 was merged by ten phases GTVs of 4DCT.The GTV of enhanced 3DCT was registered to different CT series of 4DCT and the IGTVDR was obtained by merging the GTVs after deformable registration.The target volumes differences were compared by paired t-test.Results The edge of tumor was difficult to define on 4DCT and non-enhanced 3DCT images.The enhanced 3DCT image showed clearer tumor edge,and the GTV increased by mean 37.99％ compared to GTV on 4DCT different series images and non-enhanced 3DCT image (P =0.002).The GTV after deformable registration on 4DCT different phase images increased by mean 36.34％ (P =0.011),which were similar to GTV on enhanced 3DCT image (P =0.632).The IGTVDR increased by 19.91％ (P =0.017),compared to IGTV1.Conclusions The contrast-enhanced 4DCT image which was obtained by combining enhanced 3DCT and 4DCT images with deformable registration technology could raise the position precision of the HCC IGTV effectively.
ABSTRACT
Objective To study the dose characteristics of Body γ Knife and Tomotherapy treatment plans for hepatocellular carcinoma,and compare their differences between organs at risk (OAR) dose and the range of low dose.Methods CT simulation images of twelve patients with hepatocellular carcinoma were selected,the target volume and OAR were drew by doctor.Body γ Knife and Tomotherapy treatment plans were optimized with their own planning station.The dosimetric characteristics were evaluated by dose volume histograms and were compared.To analyze the difference between the two techniques,the paired t-test was applied.Results The Dmax and Dmean of target with Body γ Knife were higher than Tomotherapy (P =0.002,0.000),but the conformal index of PTV of Tomotherapy was superior to the Body γ Knife (P =0.001).The Dmax of spinal cord and left kidney with Body γ Knife was lower than Tomotherapy (P =0.013,0.012),and it was also in the Dean of stomach and left kidney (P =0.010,0.023).In the volume dose comparison,the V40,V35,V30,V25 and V20 of normal tissue (all Body-PTV) and liver (all liver-GTV) with Body γ Knife were higher than Tomotherapy (P =0.001,0.001,0.001,0.007,0.029),but the V10 and V5 were lower (P =0.019,0.031),the Dmax of stomach,Dmean of right kidney and liver were no statistical difference (P =0.247,0.308,0.401).Conclusions Both treatment plans could meet the clinical dosimetric need,by the same prescription dose,Dmax and Dmean of target of Body γ Knife were higher than Tomotherapy.Tomotherapy had excellent dose-target conformal and could reduce the range of V25-V40 of OAR and normal tissue,but the range of V5-V10 was increased obviously.
ABSTRACT
Purpose To investigate the expression and clinical significance of miR-100 in hepatocellular carcinoma ( HCC) . Methods LNA-modified miR-100 fluorescent probe was used to detect the formalin-fixed and paraffin-embedded tissues of 29 cases of HCC, while 10 cases of normal human liver tissues were used as the control group. Results Analysis of fluorescence in situ hybridization ( FISH) showed that, in all normal tissues miR-100 expression were positive, fluorescence signal located in the cytoplasm, while only 11 cases of HCC were positive, and there was a significant difference between both positive rates (100% vs 37. 9%, P<0. 01). In addition, with the degree of differentiation of HCC decreased, the expression of miR-100 showed a decreasing trend, positive rate of the well differentiation group and moderate differentiation group was significantly higher than the poor differentiation group ( P<0. 05 ) . Conclusion Detection of miR-100 expression in HCC tissue might be helpful to evaluate the pathologic grade of the tumors.
ABSTRACT
The recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) has a major impact on outcome, while the guide of treatment of it is lacked until now. so this review will attempt to sum-marize how best to manage recurrent HCC after LT in detail.
ABSTRACT
Objective:To prepare and identify monoclonal antibody specifically targeting epidermal growth factor receptor(EGFR) and(or) epidermal growth factor receptor vⅢ(EGFRvⅢ),and to investigate its inhibitory effects on human hepatocellular carcinoma Huh7-EGFRvⅢ cell-and epidermal carcinoma A431 cell-implanted tumors in nude mice.Methods: BALB/c mice were immunized with 3T3 cells stably transfected with EGFRvⅢ(3T3-EGFRvⅢ).Immunized spleen cells were fused with myeloma SP2/0 cells,and anti-EGFRvⅢ monoclonal antibody positive hybridoma cells(named 9B9 antibody and 9B9 cells,respectively) were selected and identified by ELISA.The specific interaction between 9B9 antibody and EGFRvⅢ/EGFR antigen was detected by Western blotting and immunofluorescence assay.Huh7-EGFRvⅢ cell-(human hepatocellular carcinoma Huh7 cells stably transfected with EGFRvⅢ) and epidermal cell carcinoma A431 cell-bearing mouse models were established and were divided into PBS group,Cetuximab group and 9B9 antibody group.Then,anti-tumor effect of 9B9 antibody was examined and compared with those of PBS and Cetuximab.Results: A monoclonal antibody,named 9B9 antibody,was obtained by hybridoma technique and it reacted with both EGFRvⅢ antigen and EGFR antigen as detected by Western blotting and immunofluorescence.The inhibitory rates of Cetuximab and 9B9 antibody against Huh7-EGFRvⅢ cells-implanted tumors were 42% and 46%,respectively,and those against A431 cells-implanted tumors were 85% and 86%,respectively.Conclusion: 9B9 monoclonal antibody can effectively inhibit the growth of human hepatocellular carcinoma cell-and epidermal cell carcinoma cell-implanted tumors,and the effects resemble that of Cetuximab.
ABSTRACT
Objective:To investigate the inhibitory effect of antisense human telomerase RNA(hTR) gene on implanted hepatocellular carcinoma in nude mice.Methods: HepG2 cells were subcutaneously inoculated into BALB/c nude mice at the axilla to establish implanted hepatocellular carcinoma model.The retrovirus plasmid containing antisense telomerse RNA(PLXSN-hTR-BamHⅠ) was injected into the tumor(0.2 ml every time,5 times).Retrovirus plasmid containing sense telomerase RNA(PLXSN-hTR-EcoRⅠ) and normal saline were inoculated as control groups.Tumor volume was determined and the inhibitory rate was calculated.Tumor necrosis was observed by histological analysis and cell apoptosis was analyzed by terminal transferase dUTP nick end labeling(TUNEL).Results: Tumor growth in antisense hTR group was significantly inhibited compared with the two control groups.The tumor inhibitory rate(26.78%) of antisense hTR group was significantly higher than that of sense hTR group(1.93%,P
ABSTRACT
We have cloned full-length MDR1 cDNA from human normal liver tissue in previous study. Using this MDR1 cDNA as probe, we observed the MDR1 gene expression in human hepatocellular carcinoma treated with and without chemotherapy by Northern blot. The results showed that expression of MDR1 gene in hepatocellular carcinoma tissues was higher than that in their adjacent normal liver tissues; and enhanced MDR1 gene expression was also observed in hepatocellular carcinoma treated with chemotherapic agents. We also explored a method for quantitative analysis of MDR1 gene expression in hepatocellular carcinoma by polymerase chain reaction. This study suggests that overexpression of MDR1 gene may be responsible for the intrinsic and acquired drug resistance of human hepatocellular carcinoma, and PCR is a preferable method for quantitative analysis of MDR1 gene expression in hepatocellular carcinoma.