المؤلفون: Qiu JG; Liver Cancer Institute and Department of Liver Surgery, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan, Shanghai 200032, China., Fan J, Liu YK, Zhou J, Dai Z, Huang C, Tang ZY

المصدر: Journal of cancer research and clinical oncology [J Cancer Res Clin Oncol] 2008 Mar; Vol. 134 (3), pp. 299-305. Date of Electronic Publication: 2007 Sep 08.

نوع المنشور: Comparative Study; Journal Article

بيانات الدورية: Publisher: Springer-Verlag Country of Publication: Germany NLM ID: 7902060 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-1335 (Electronic) Linking ISSN: 01715216 NLM ISO Abbreviation: J Cancer Res Clin Oncol Subsets: MEDLINE

مواضيع طبية MeSH: Portal Vein*, Biomarkers, Tumor/*blood , Blood Proteins/*analysis , Carcinoma, Hepatocellular/*diagnosis , Liver Neoplasms/*diagnosis , Thrombosis/*diagnosis, Amino Acid Sequence ; Electrophoresis, Gel, Two-Dimensional ; Electrophoresis, Polyacrylamide Gel ; Female ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Molecular Weight ; Neoplastic Cells, Circulating/metabolism

مستخلص: Purpose: Serum low molecular weight protein biomarkers might be important in relation to portal vein tumor thrombi (PVTT) in hepatocellular carcinoma (HCC). This study aimed to screen and to detect these biomarkers.
Methods: We selected sera of 3 groups from 12 healthy volunteers, 12 HCC patients without PVTT and 12 HCC patients with PVTT, respectively. By using two-dimensional gel electrophoresis (2-DE) in which the first dimension was 16% SDS-PAGE, serum protein images of 3 groups were analyzed by Image Master Software. The differential protein spots were further identified by MALDI-TOF MS/MS.
Results: Compared with 12.5% SDS-PAGE gel, there were more protein bands between 3 and 20 kDa in 16% SDS-PAGE gel and low molecular weight (MW) protein spots (< 20 kDa) were clearly shown. Fifteen differential protein spots representing five proteins were found in the three groups by inter-class comparison and were then identified. Compared with the healthy group, apolipoprotein A-I, lipoprotein CIII, transthyretin and DNA topoisomerase II were down regulated in HCC groups while haptoglobin-2 was over expressed. All the five proteins were less in PVTT group than in non-PVTT group.
Conclusion: The expression of low MW serum protein changes obviously in the beginning and progressive stage of HCC, and differentially expressed low MW proteins might be the potential biomarkers in early prognostication and surveillance of treatment for HCC and PVTT.

المؤلفون: Zhang H; Liver Cancer Institute and Zhongshan Hospital, Institutes of Biomedical Science, Fudan University, 180 Feng Lin Road, Shanghai, 200032, China., Ye QH, Ren N, Zhao L, Wang YF, Wu X, Sun HC, Wang L, Zhang BH, Liu YK, Tang ZY, Qin LX

المصدر: Journal of cancer research and clinical oncology [J Cancer Res Clin Oncol] 2006 Nov; Vol. 132 (11), pp. 709-17. Date of Electronic Publication: 2006 Jun 20.

نوع المنشور: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: Springer-Verlag Country of Publication: Germany NLM ID: 7902060 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0171-5216 (Print) Linking ISSN: 01715216 NLM ISO Abbreviation: J Cancer Res Clin Oncol Subsets: MEDLINE

مواضيع طبية MeSH: Biomarkers, Tumor/*blood , Carcinoma, Hepatocellular/*blood , Liver Neoplasms/*blood , Osteopontin/*blood, Adult ; Aged ; Aged, 80 and over ; Carcinoma, Hepatocellular/pathology ; Carcinoma, Hepatocellular/surgery ; Case-Control Studies ; Enzyme-Linked Immunosorbent Assay ; Female ; Hepatectomy ; Humans ; Immunoenzyme Techniques ; Liver Neoplasms/pathology ; Liver Neoplasms/surgery ; Lung Neoplasms/blood ; Lung Neoplasms/secondary ; Lung Neoplasms/surgery ; Male ; Middle Aged ; Neoplasm Invasiveness/pathology ; Neoplasm Recurrence, Local/blood ; Neoplasm Staging ; Prognosis ; Survival Rate

مستخلص: We aimed to evaluate the prognostic value of preoperative plasma osteopontin (OPN) levels in 101 patients with hepatocellular carcinoma (HCC) who underwent liver resection. Plasma OPN levels were detected by ELISA. The association of plasma OPN levels of patients with clinicopathological characteristics, tumor recurrence, and survival was analyzed. The median plasma OPN level of patients was 176.90 ng/ml (range 13.73-780.00 ng/ml), which was significantly higher than that of 24 healthy volunteers (63.74 ng/ml, range 12.20-122.32 ng/ml). Plasma OPN levels were significantly different in patients with different numbers of tumor nodules (168.18 and 217.11 ng/ml for single and multiple nodules, respectively; P = 0.002), different Edmondson's grades (201.24, 168.36, and 503.58 ng/ml for grades I, II, and III/IV, respectively; P = 0.015), and different TNM stages (168.16, 167.54, and 216.18 ng/ml for stages I, II, and III/IV, respectively; P = 0.016). Significantly higher plasma OPN levels were found in patients with a recurrence of HCC after resection, compared with those without recurrence (213.55 versus 153.70 ng/ml; P = 0.0013). A higher plasma OPN level was a leading independent prognostic factor for both overall survival (OS) and disease-free survival (DFS) in univariate and multivariate Cox models. This suggests that the preoperative plasma OPN level can be used as a predictive marker for HCC recurrence and may be helpful to assess the prognosis of patients with HCC after surgery.

المؤلفون: Li Y; Department of Oncology, Zhongnan Hospital of Wuhan University and Cancer Center of Wuhan University, No. 169 Donghu Road, Wuhan, 430071, China. liyansd@hotmail.com, Tang ZY, Tian B, Ye SL, Qin LX, Xue Q, Sun RX

المصدر: Journal of cancer research and clinical oncology [J Cancer Res Clin Oncol] 2006 Aug; Vol. 132 (8), pp. 515-20. Date of Electronic Publication: 2006 May 19.

نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: Springer-Verlag Country of Publication: Germany NLM ID: 7902060 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0171-5216 (Print) Linking ISSN: 01715216 NLM ISO Abbreviation: J Cancer Res Clin Oncol Subsets: MEDLINE

مواضيع طبية MeSH: Antigens, Neoplasm/*blood , Biomarkers, Tumor/*blood , Carcinoma, Hepatocellular/*blood , Keratins/*blood , Liver Neoplasms/*blood , Lung Neoplasms/*blood, Adult ; Aged ; Animals ; Carcinoma, Hepatocellular/secondary ; Female ; Humans ; Keratin-19/blood ; Liver Neoplasms/pathology ; Lung Neoplasms/secondary ; Male ; Mice ; Mice, Nude ; Middle Aged ; Neoplasm Staging ; Neoplastic Cells, Circulating ; Portal Vein ; Random Allocation

مستخلص: Our previous proteomics study on human hepatocellular carcinoma (HCC) cell strains revealed that cytokeratin 19 (CK19) was expressed in cells with high metastasis potential; we further studied serum CK19 fragment CYFRA 21-1 level in HCC patients and nude mice model of HCC metastasis. HCC cell line HCCLM3 was injected subcutaneously into 30 nude mice which were then randomized into 6 groups of 5 mice each. The murine serum CYFRA 21-1 and pulmonary metastases were determined 2, 3, 4, 5, 6, and 7 weeks after injection. Serum CYFRA 21-1 levels of 101 normal controls and 108 HCC patients were also determined. In nude mice model, CYFRA 21-1 level increased significantly when pulmonary metastases occurred. Among 108 HCC patients, 24 (22.2%) had increased serum CYFRA 21-1 level. The presence of portal vein tumor emboli was significantly higher in CYFRA 21-1 increased cases (33.3%, 6/24) than in CYFRA 21-1 normal cases (6.0%, 5/84) (x2=7.403, P < 0.01). In addition, the percentage of TNM stage III/IV tumor was significantly higher in CYFRA 21-1 increased patients (54.2%, 13/24) than in CYFRA 21-1 normal cases (21.4%, 18/84) (x2=9.776, P < 0.005). These results suggest that CK19 may play an important role in HCC metastasis.

المؤلفون: Song HY; Liver Cancer Institute, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Road, 200032 Shanghai, People's Republic of China., Liu YK, Feng JT, Cui JF, Dai Z, Zhang LJ, Feng JX, Shen HL, Tang ZY

المصدر: Journal of cancer research and clinical oncology [J Cancer Res Clin Oncol] 2006 Feb; Vol. 132 (2), pp. 92-8. Date of Electronic Publication: 2005 Nov 01.

نوع المنشور: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: Springer-Verlag Country of Publication: Germany NLM ID: 7902060 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0171-5216 (Print) Linking ISSN: 01715216 NLM ISO Abbreviation: J Cancer Res Clin Oncol Subsets: MEDLINE

مواضيع طبية MeSH: Biomarkers, Tumor/*analysis , Carcinoma, Hepatocellular/*chemistry , Heat-Shock Proteins/*analysis , Liver Neoplasms/*chemistry , Neoplasm Proteins/*analysis, Actins/analysis ; Blotting, Western ; Electrophoresis, Gel, Two-Dimensional ; Gene Expression Regulation, Neoplastic ; HSP27 Heat-Shock Proteins ; Humans ; Immunohistochemistry ; Mass Spectrometry ; Molecular Chaperones ; Reverse Transcriptase Polymerase Chain Reaction ; Up-Regulation

مستخلص: Purpose: A comparative proteomic approach was used to identify and analyze proteins related to metastasis of hepatocellular carcinoma (HCC).
Methods: Proteins extracted from 12 HCC tissue specimens (six with metastases and six without) were separated by two-dimensional gel electrophoresis (2-DE). The protein spots exhibiting statistical alternations between the two groups through computerized image analysis were then identified by mass spectrometry. In addition immunohistochemistry (IHC), Western blotting and RT-PCR were performed to verify the expression of certain candidate proteins.
Results: 16 proteins including HSP27, S100A11, CK18 were annotated by mass spectrometry, relevant to chaperone function, cell mobility, cytoskeletal architecture, respectively. Most were previously unconnected with metastasis of HCC. Of these HSP27 was found overexpressed consistently in 2-DE patterns of all metastatic HCC tissues compared with nonmetastatic ones. IHC and Western blotting of HCC tissues confirmed this difference while RT-PCR did not.
Conclusion: There are various proteins joined together in HCC metastasis. The overexpression of HSP27 may serve as a biomarker for early detection and therapeutic targets unique to the metastatic phenotype of HCC.

المؤلفون: Qin LX; Liver Cancer Institute and Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Road, 200032 Shanghai, P.R. China., Tang ZY

المصدر: Journal of cancer research and clinical oncology [J Cancer Res Clin Oncol] 2004 Sep; Vol. 130 (9), pp. 497-513. Date of Electronic Publication: 2004 Jun 17.

نوع المنشور: Journal Article; Review

بيانات الدورية: Publisher: Springer-Verlag Country of Publication: Germany NLM ID: 7902060 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0171-5216 (Print) Linking ISSN: 01715216 NLM ISO Abbreviation: J Cancer Res Clin Oncol Subsets: MEDLINE

مواضيع طبية MeSH: Genetic Markers*, Biomarkers, Tumor/*analysis , Carcinoma, Hepatocellular/*chemistry , Carcinoma, Hepatocellular/*diagnosis , Liver Neoplasms/*chemistry , Liver Neoplasms/*diagnosis, Angiogenesis Inducing Agents/analysis ; Antigens, Neoplasm/analysis ; Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/secondary ; Cell Adhesion Molecules/analysis ; Cell Cycle Proteins/analysis ; Chromosome Aberrations ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor ; Humans ; Liver Neoplasms/genetics ; Liver Neoplasms/pathology ; Oncogenes ; Predictive Value of Tests ; Telomerase/metabolism

مستخلص: Molecular markers (biomarkers) for hepatocellular carcinoma (HCC) metastasis and recurrence could provide additional information to that gained from traditional histopathological features. A large number of biomarkers have been shown to have potential predictive significance. One important aspect of this is to detect the transcripts of tumor-associated antigens (such as AFP, MAGEs, and CK19), which are proposed as predictive markers of HCC cells disseminated into the circulation and for metastatic recurrence. Another important aspect is to analyze the molecular markers for cellular malignancy phenotype, including DNA ploidy, cellular proliferation index, cell cycle regulators, oncogenes, and tumor suppressors (especially p53 gene), as well as telomerase activity. Molecular factors involved in the process of HCC invasion and metastasis, including adhesion molecules (E-cadherin, catenins, ICAM-1, laminin-5, CD44 variants, osteopontin), proteinases responsible for the degradation of extracellular matrix (MMPs, uPA system), as well as angiogenesis regulators (such as VEGF, intratumor MVD), have also been shown to be potential predictors for HCC metastatic recurrence and clinical outcomes. One important new trend is to widely delineate biomarkers with genomic and proteomic expression with reference to predicting metastatic recurrence, molecular diagnosis, and classification, which has been drawing more attention recently. Body fluid (particularly blood and urine) testing for biomarkers is easily accessible and more useful in clinical patients. The prognostic significance of circulating DNA in plasma or serum and its genetic alterations is another important direction. More attention should be paid to these areas in the future. As understanding of tumor biology deepens, more and more new biomarkers with high sensitivity and specificity for HCC metastatic recurrence could be found and routinely used in clinical assays. However, the combination of the pathological features and some of the biomarkers mentioned above seems to be more practical up to now.