Carcinoma, Hepatocellular ; pathology ; Humans ; Liver Neoplasms ; pathology ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Osteopontin ; Prognosis

Carcinoma, Hepatocellular ; genetics ; pathology ; Gene Expression Profiling ; Genomics ; Humans ; Liver Neoplasms ; genetics ; pathology ; Neoplasm Metastasis ; genetics ; Neoplasm Recurrence, Local ; genetics

OBJECTIVETo study the effect of osteopontin (OPN) expression down-regulated by RNA interference (RNAi) on the invasiveness of hepatocelluar carcinoma cell line HCC-LM3.

METHODSHCC-LM3 cells were transfected with the chemically synthesized small interfering RNA (siRNA) formulated by lipofectamine 2000. Wild type HCC-LM3 and HCC-LM3 cells transfected with non-specific siRNA served as controls. Real-time PCR and Western blotting were used to quantify the mRNA and OPN protein levels. The malignant phenotypes of transfected HCC-LM3 cells including cellular growth rate, colony formation and Matrigel invasion activities were analyzed.

RESULTSSequence-specific siRNAs targeting OPN suppressed OPN RNA expression by 79% and also decreased OPN protein level by 81% in HCC-LM3 cells. The number of formed colonies and migrating numbers in vitro were decreased in HCC-LM3 cells transfected using sequence-specific siRNAs targeting OPN relative to controls (P < 0.05).

CONCLUSIONThis study demonstrated that specific siRNA is able to reduce OPN at both the mRNA and protein levels and significantly diminishes the invasiveness of hepatocellular carcinoma cells.

Carcinoma, Hepatocellular ; genetics ; pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Down-Regulation ; Humans ; Liver Neoplasms ; genetics ; pathology ; Neoplasm Invasiveness ; Osteopontin ; genetics ; RNA Interference ; RNA, Messenger ; biosynthesis ; genetics ; RNA, Small Interfering ; genetics ; Transfection

OBJECTIVEAs our previous comparative proteomics study on high and low metastasis human hepatocellular carcinoma (HCC) cell strains revealed that cytokeratin 19 (CK19) was related to higher metastasis potential, we further investigated the relationship between serum CK19 level in HCC patients and their clinico-pathologic characteristics.

METHODSSerum CK19 levels of 101 normal controls and 108 pathology-proven HCC patients were determined using radioimmunoassay, and the their correlation with clinico-pathologic parameters were studied.

RESULTSThe upper limit of one-side 98% confidence interval of normal serum CK19 level was 2.3 microg/L. Among 108 HCC patients, 24 (22.2%) had increased serum CK19 level, ranging from 2.4 to 45.5 microg/L. There were 12 patients (11.1%) with increased CK19 level but normal AFP level. The percentage of poor differentiated tumor was higher in CK19 increased cases (37.5%, 9/24) than in CK19 normal cases (20.2%, 17/84). Moreover, the presence of portal vein tumor emboli was significantly higher in CK19 increased cases (25.0%, 6/24) than in CK19 normal cases (6.0%, 5/84). (Chi-square = 7.403, P < 0.01) In addition, the percentage of TNM stage III/IV tumor was significantly higher in CK19 increased patients (54.2%, 13/24) than in CK19 normal cases. (chi-square = 13.300, P < 0.005)

CONCLUSIONSome HCC patients do have increased serum CK19 level, which could be related to portal vein tumor emboli, poor tumor differentiation and advanced tumor stages.

Adult ; Aged ; Biomarkers, Tumor ; blood ; Carcinoma, Hepatocellular ; blood ; pathology ; Female ; Humans ; Keratins ; blood ; Liver Neoplasms ; blood ; pathology ; Male ; Middle Aged ; Neoplasm Proteins ; blood ; Peptide Fragments ; blood ; genetics ; Proteome ; analysis

OBJECTIVETo evaluate the usefulness of serum alpha-fetoprotein (AFP) in clinical diagnosis and screening for hepatocellular carcinoma (HCC).

METHODSTotally 290 HCC patients, 48 liver cirrhosis patients, and 49 healthy subjects were enrolled in this study. Serum AFP analysis was performed to investigate the correlation between the serum AFP level in HCC and the clinical or biochemical parameters of the disease, which included the size and number of tumor and the TNM stage. Sensitivities and specificities of AFP in HCC prediction at different cut-off levels were determined.

RESULTSThe serum AFP level was significantly higher in HCC patients than in liver cirrhosis patients (P = 0.0274) and healthy subjects (P = 0.0001). Among 290 HCC patients, 95 patients (32.8%) were AFP-negative (AFP < 20 microg/L), 195 (67.2%) were AFP-positive (AFP > or =20 microg/L). Sensitivity and specificity of AFP at 20 microg/L cut-off was 67.2% and 29.2%, respectively, and the positive and negative predictive value was 85.2% and 12.8%, respectively. Sensitivity of AFP at 400 microg/L cut-off was only 42.8%. Serum AFP levels were significantly different among HCC with different tumor size (P = 0.0009), tumor number (P = 0.0001), and TNM stage [TNM I vs. TNM III-IV (P = 0.0001); TNM II vs. TNM III-IV (P = 0.0003)].

CONCLUSIONSIncreased serum AFP level is highly suggestive in HCC diagnosis. Combined with other imaging examinations, AFP level can be used for the screening of high risk population and for the follow-up of AFP-positive patients.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; blood ; Carcinoma, Hepatocellular ; blood ; diagnosis ; Diagnostic Techniques and Procedures ; Female ; Humans ; Liver Neoplasms ; blood ; diagnosis ; Male ; Middle Aged ; Sensitivity and Specificity ; Young Adult ; alpha-Fetoproteins ; analysis

OBJECTIVETo evaluate the relation between different therapy and survival rate of liver metastasis of colorectal cancer (LMCC).

METHODSClinical data of 669 LMCC patients,collected from Fudan University Zhongshan Hospital from January 2000 to July 2008, were analyzed retrospectively.

RESULTSOf the 669 cases, 379 cases were synchronous liver metastases(SLM) and 290 cases were metachronous liver metastases(MLM). There were no significant differences in age, gender and position of primary tumor between SLM and MLM groups(P>0.05), but as to liver metastasis characteristics(liver lobe involved, focus number and maximal focus diameter) and CEA, CA19-9 before therapy,there were significant differences(P<0.05). Two hundred and fifty-three cases underwent curative hepatic resection, including 123 cases in SLM and 130 cases in MLM. Until October 31, 2008, all the cases were followed up. The median survival time of SLM was(11+/-1) months and of MLM(23+/-2) months(P<0.01). Five-year survival rate of SLM was 6.4% and of MLM 11.4%(P<0.01). As to different treatments, median survival time and 5-year survival rate of curative hepatic resection group were 37 months and 35.6%, and of non-operation groups(i.e. intervention, chemotherapy, radiofrequency therapy and percutaneous ethanol injection) were 5 to 26 months and 0 to 3.6% respectively(P<0.05).

CONCLUSIONSCurative hepatic resection is the first choice of liver metastasis of colorectal cancer, which can improve the survival rate. Resection rate and survival of MLM are better than those of SLM.

Adult ; Aged ; Colorectal Neoplasms ; pathology ; therapy ; Female ; Follow-Up Studies ; Hepatectomy ; Humans ; Liver Neoplasms ; secondary ; therapy ; Male ; Middle Aged ; Neoplasm Metastasis ; Prognosis ; Retrospective Studies ; Survival Rate

OBJECTIVETo evaluate the correlation between different therapies and survival of liver metastasis from colorectal cancer ( LMCC) , and to compare the clinical outcome of synchronous liver metastasis (SLM) with that of metachronous liver metastasis (MLM).

METHODSThe clinical data of 363 patients with LMCC were retrospectively reviewed with focus on the correlation between different therapy and survival.

RESULTSOf these 363 patients, 160 had SLM and 203 had MLM. Between the SLM and MLM group, there was no significant difference in age, or gender or primary cancer site (P > 0. 05 ), but significant differences were observed in condition of liver metastasis including liver lobe involved, focus number, maximum focus diameters and level of serum CEA and CA199 before therapy(P <0. 05). Ninety-one patients underwent curative hepatic resection, 22 of them in the SLM group and 69 in the MLM group. Mortality rate related to operation was 4. 5% (1/22) in SLM group and 2. 9% (2/69) in MLM group( P < 0.05). All patients were followed until 31/6/2005. The 3-year survival rate was 5. 2% with a median survival time of 10 +/- 1 months for the SLM group, and it wasl6. 4% and 17 +/- 1 months for the MLM group (P<0.01). Regarding to the treatment modalities, the 3-year survival rate was 30. 2% with a median survival time of 26 months for curative hepatic resection group, and it was 0% - 16. 7% and 10 - 17 months for non-operation groups treated by intervention, chemotherapy, radiofrequency therapy, percutaneous ethanol injection and Chinese traditional drugs (P <0. 05, P <0. 01 ).

CONCLUSIONCurative hepatic resection is still the first choice for liver metastasis from colorectal cancer improving the survival significantly. Other non-operative methods also can improve phase II resection rate. Metachronous liver metastasis has higher resection rate and better survival than the synchronous liver one.

Antineoplastic Agents, Phytogenic ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; CA-19-9 Antigen ; blood ; Carcinoembryonic Antigen ; blood ; Chemoembolization, Therapeutic ; Colonic Neoplasms ; blood ; pathology ; therapy ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Hepatectomy ; methods ; Humans ; Liver Neoplasms ; blood ; secondary ; therapy ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Phytotherapy ; methods ; Rectal Neoplasms ; blood ; pathology ; therapy ; Retrospective Studies ; Survival Analysis

OBJECTIVETo evaluate the relationship between PAR1 (Protease-Activated Receptor 1) expression and the clinicopathologic features and to investigate the prognostic value of PAR1 expression in hepatocellular carcinoma (HCC) in early stage after curative resection.

METHODSReal-time PCR was used to detect PAR1 expression in 41 pairs of tumors and matched peritumoral samples of HCC in early stage. Prognostic value of PAR1 mRNA expression was evaluated. Meanwhile, another 49 tissue paraffin slices of HCC were tested using immunohistochemistry (Envision) and the prognostic value of PAR1 expression and other clinicopathologic factors were evaluated.

RESULTSPeritumoral PAR1 mRNA expression was significantly increased in HCCs from the patients with tumor recurrence as compared with those without recurrence (P < 0.05). Peritumoral PAR1 protein expression was related to tumor differentiation (P < 0.05). Kaplan-Meier analysis showed that Peritumoral PAR1 protein expression was associated with the overall survival (OS) (P < 0.05) of HCC patients and the time to recurrence (TTR) (P < 0.05). The 1, 3 and 5 -year overall survival time and the cumulative recurrence time in the high PAR1 protein expression group were significantly lower as compared to the low PAR1 expression group in the peritumoral liver tissue.

CONCLUSIONSPeritumoral PAR1 expression is closely associated with the prognosis of early stage HCC patients after curable surgery. PAR1 may be involved in thrombin-mediated invasion process and may be used as a prognostic marker for HCC.

Carcinoma, Hepatocellular ; metabolism ; pathology ; Female ; Humans ; Liver Neoplasms ; metabolism ; pathology ; Male ; Middle Aged ; Postoperative Period ; Prognosis ; Receptor, PAR-1 ; metabolism

OBJECTIVEIn order to seek the functional evidence that there could be metastatsis suppressor gene for liver cancer on human chromosomes, the objective of this study is to establish a method of microcell mediated chromosome transfer (MMCT).

METHODSHuman chromosome 8 randomly marked with neo gene was introduced into highly metastatic rat liver cancer C5F cell line by treating the single human chromosome donor cells with sequential steps of micronucleation, enucleation and microcell fusion. Double selections of G418 and HAT were applied to screen positive microcell hybrids, which were cloned by single cell isolation. Microcell hybrid clones were confirmed by STS-PCR and WCP-FISH.

RESULTSMicrocell hybrids resistant to HAT and G418 were obtained, from which 15 clones were obtained by single-cell isolation cloning. STS-PCR and WCP-FISH proved that human chromosome 8 had been successfully introduced into rat liver cancer cell line C5F. The human chromosome 8 introduced into C5F was found to have random loss of chromosome fragments by STS-PCR and consistent recombination with rat chromosome by WCP-FISH.

CONCLUSIONThe successfulls introduction of human chromosome into highly metastatic rat liver cancer cell line has established the technical basis for functional localization of metastasis suppressor gene(s) for liver cancer on human chromosomes.

Animals ; Cell Line, Tumor ; Chromosome Mapping ; methods ; Chromosomes, Human, Pair 8 ; genetics ; Genes, Tumor Suppressor ; Genetic Techniques ; Humans ; In Situ Hybridization, Fluorescence ; Liver Neoplasms ; genetics ; pathology ; Polymerase Chain Reaction ; Rats

OBJECTIVETo investigate the clinicopathologic features, diagnosis and treatment of hepatic angiomyolipoma (HAML).

METHODSThe clinical, histopathological, treatment and prognosis data of 51 patients treated for HAML from October 1998 to October 2007 were retrospectively analyzed.

RESULTSHAML had a female predilection (female/male = 41/10) and the mean age was 44 years old. The main symptoms were abdominal mass (33 cases) and abdominal pain or discomfort (15 cases), the other 2 cases presented as fever. Histopathologically, HAML was composed of a heterogeneous mixture of blood vessels, smooth muscle, and adipose cells. Immunohistochemical staining showed relatively high positive rate of HMB-45 (50/51), SMA (47/49) and S-100 (39/42). All 51 patients underwent partial hepatectomy. The mean hospital stay was 13.8 days and mean intraoperative blood loss was 263 ml. There was no recurrence or metastasis after a mean follow-up of 55.4 months.

CONCLUSIONSHAML is a rare benign mesenchymal tumor of the liver. Definitive diagnosis of HAML depends on the pathohistological findings and HMB-45 positive myoid cell is an important diagnostic marker. Complete surgical resection is the optimal treatment for HAML with favorable prognosis.

Adolescent ; Adult ; Angiomyolipoma ; diagnosis ; pathology ; surgery ; Female ; Follow-Up Studies ; Humans ; Liver Neoplasms ; diagnosis ; pathology ; surgery ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Treatment Outcome ; Young Adult