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NCI CANCERLIT^® Search: Diagnosis-Histopathology-Pathogenesis of Liver Cancer - October 2002

National Cancer Institute^®

Activation of nuclear factor kappaB in hepatitis C virus infection: implications for pathogenesis and hepatocarcinogenesis.
[Immunohistochemical study of hepatitis C virus core antigen and HBxAg in liver cirrhosis and hepatocellular carcinoma tissues]
[Study of fungus polysaccharides compounds (FPC) in inducing the apoptosis of liver cancer cell Bel-7402]
Frequent impairment of the spindle assembly checkpoint in hepatocellular carcinoma.
Analysis of alterations of WFDC1, a new putative tumour suppressor gene, in hepatocellular carcinoma.
EGFR is a transducer of the urokinase receptor initiated signal that is required for in vivo growth of a human carcinoma.
Discovery and analysis of hepatocellular carcinoma genes using cDNA microarrays.
Integrin gene expression profiles of human hepatocellular carcinoma.
Overexpression of p28/gankyrin in human hepatocellular carcinoma and its clinical significance.
HLA class I expression in primary hepatocellular carcinoma.
Role and limitation of FMPSPGR dynamic contrast scanning in the follow-up of patients with hepatocellular carcinoma treated by TACE.
[Towards early screening and treatment of hepatocellular carcinoma cirrhosis?]
[Practical screening and early treatment of hepatocellular carcinoma. Results of a French survey]
Increased chromosomal alterations and micronuclei formation in human hepatoma HepG2 cells transfected with the hepatitis B virus HBX gene.
Risk factors for morbidity following liver surgery.
Chromosomal analysis of hepatic adenoma and focal nodular hyperplasia by comparative genomic hybridization.
Aortic and hepatic enhancement and tumor-to-liver contrast: analysis of the effect of different concentrations of contrast material at
Oral contraceptives use and liver tumours: a review.
Hepatic incidentaloma: a modern problem.
Prevalence of antibody against the core protein of hepatitis C virus in patients with hepatocellular carcinoma.
The risk of liver neoplasia in relation to combined oral contraceptive use.
Hepatic adenoma and focal nodular hyperplasia.
Hepatocellular carcinoma: risk factors other than HBV.
Hepatic cavernous haemangioma: a 10 year review.
Parity and primary liver cancer among young women.
Birth control pills, cigarettes, alcohol linked to liver cancer.
The interrelationship between HBV-markers and HIV antibodies in patients with hepatocellular carcinoma.
Prevalence of hepatocellular carcinoma in patients with alcoholic cirrhosis and prior exposure to hepatitis C.
Female hormone utilisation and risk of hepatocellular carcinoma.
Liver cancer and oral contraceptives.
[Quantitative morphological investigations in livers and liver tumors after taking contraceptives (author's transl)]
[Benign hepatic tumours and oral contraception. Pathophysiology (author's transl)]
[Oral contraceptives and liver tumors]
Studies on the role of oral contraceptive use in the etiology of benign and malignant liver tumors.
[The liver and the "pill". 2. Liver tumors]
Oral contraceptives and hepatic tumors.
Clinical and pathological comparison of young adult women with hepatocellular carcinoma with and without exposure to oral
Hepatocellular carcinoma in women: probable lack of etiologic association with oral contraceptive steroids.
Increased UDP-glucuronyltransferase in putative preneoplastic foci of human liver after long-term use of oral contraceptives.
Liver tumours associated with contraceptive hormonal treatment.
Human liver tumors in relation to steroidal usage.
Hepatocellular carcinoma and oral contraceptives.
Systemic effects of oral contraceptives.
Hepatocellular carcinoma in the non-cirrhotic liver: a comparison with that complicating cirrhosis.
[Hepatocellular carcinoma]
Oral contraceptives and primary liver cancer.
Oral contraceptive use and liver cancer.
Liver tumours.
p53 mutations in hepatocellular carcinoma related to oral contraceptive use.
Hepatitis C virus and HIV antibodies in patients with hepatocellular carcinoma in Zimbabwe: a pilot study.
A case-control study of hepatitis B and C virus infection as risk factors for hepatocellular carcinoma in Henan, China.
Alcohol consumption as a major risk factor for the rise in liver cancer mortality rates in Japanese men.
The European approach to hepatocellular carcinoma.
Methods and related drawbacks in the estimation of surgical risks in cirrhotic patients undergoing hepatectomy.
Ultrasound-guided liver resections for hepatocellular carcinoma.
Early diagnosis of hepatocellular carcinoma using a sensitive assay for serum des-gamma-carboxy prothrombin: a prospective study.
Resection of hepatocellular carcinoma: a European experience on 328 cases.
Liver transplantation for hepatocellular carcinoma.
[Localization and distribution of Kupffer cells in hepatocellular carcinoma]
Improved sonographic imaging of hepatic hemangioma with contrast-enhanced coded harmonic angiography: comparison with MR
Modern treatment of childhood hepatoblastoma: what do clinicians and pathologists have to say to each other?
Hepatoblastoma: assessment of criteria for histologic classification.
Chemotherapy for suspected hepatoblastoma without efforts at surgical resection is a bad practice.
Hepatoblastoma with cholangioblastic features ('cholangioblastic hepatoblastoma') and other liver tumors with bimodal differentiation in
Pediatric liver tumors and hepatic ontogenesis: common and distinctive pathways.
Stem-like cells in hepatoblastoma.
Hepatoblastoma and low birth weight: a trend or chance observation?
Adult type vs. Childhood hepatocellular carcinoma--are they the same or different lesions? Biology, natural history, prognosis, and treatment.
Hemangioma of the liver in children: proliferating vascular tumor or congenital vascular malformation?
Genetic alterations in hepatoblastoma and hepatocellular carcinoma: common and distinctive aspects.
Fluorescent in situ hybridization (FISH) reveals frequent and recurrent numerical and structural abnormalities in hepatoblastoma with no
Discussion and epilogue.
Expression of HLA class I molecules and the transporter associated with antigen processing in hepatocellular carcinoma.
Autoantibody responses in Chinese hepatocellular carcinoma.
Evaluation of the effect of age on functioning hepatocyte mass and liver blood flow using liver scintigraphy in preoperative estimations for
The value of Tc-99m red blood cell SPECT in differentiating giant cavernous hemangioma of the liver from other liver solid masses.
Detection of malignant hepatic lesions before orthotopic liver transplantation: accuracy of ferumoxides-enhanced MR imaging.
Extrahepatic recurrence and second malignancies after treatment of hepatocellular carcinoma: spectrum of imaging findings.
High viral loads, serum alanine aminotransferase and gender are predictive factors for the development of hepatocellular carcinoma from
N-Acetylglucosaminyltransferase V as a possible aid for the evaluation of tumor invasiveness in patients with hepatocellular carcinoma.
Comparison of clinicopathological features of patients with hepatocellular carcinoma seropositive for alpha-fetoprotein alone and
Copper resistant human hepatoblastoma mutant cell lines without metallothionein induction overexpress ATP7B.
Pedunculated hepatocellular carcinoma: clinicopathologic study of 18 surgically resected cases.
[Malignant primary tumors of the liver in childhood]
B and C hepatitis viruses, HLA-DQ1 and -DR3 alleles and autoimmunity in patients with hepatocellular carcinoma.
Yes, hepatocellular cancer does occur in primary biliary cirrhosis.
Rising prevalence of hepatitis C virus infection among patients recently diagnosed with hepatocellular carcinoma in the United States.
P53 gene and Wnt signaling in benign neoplasms: beta-catenin mutations in hepatic adenoma but not in focal nodular hyperplasia.
Clinicopathologic features of patients with hepatocellular carcinoma seropositive for alpha-fetoprotein-L3 and seronegative for
Hepatic nodules with early enhancement during computed tomography portography: report of six cases.
Occult hepatitis B virus infection.
Apoptosis induced by ceramide in hepatocellular carcinoma Bel7402 cells.
Anti-hepatoma activity of taxol in vitro.
Effects of ascorbic acid and DL-alpha-tocopherol on human hepatoma cell proliferation and redifferentiation.
Differentiation-inducing action of 10-hydroxycamptothecin on human hepatoma Hep G2 cells.
Hepatocellular carcinoma: global epidemiology.
Interactions between metabolic disorders (diabetes, gallstones, and dyslipidaemia) and the progression of chronic hepatitis C virus
Is insulin resistance a pathogenic co-factor in hepatitis C virus-related disease and hepatocellular carcinoma?
The rise and fall in primary liver cancer mortality in Italy.
Intravenous contrast-enhanced Doppler sonography and intra-arterial carbon dioxide-enhanced sonography in the assessment of hepatocellular
Role of Rel/NF-kappaB transcription factors in apoptosis of human hepatocellular carcinoma cells.
Primary non-Hodgkin's lymphomas of the liver with nodular and diffuse infiltration patterns have different prognoses.
Detection and differential diagnosis of hepatic masses using pulse inversion harmonic imaging during the liver-specific late phase of
Variation of hepatitis C virus load, hypervariable region 1 quasispecies and CD81 hepatocyte expression in hepatocellular carcinoma and adjacent

1
UI - 10706556
AU - Tai DI; Tsai SL; Chen YM; Chuang YL; Peng CY; Sheen IS; Yeh CT; Chang
TI - KS; Huang SN; Kuo GC; Liaw YF Activation of nuclear factor kappaB in hepatitis C virus infection: implications for pathogenesis and hepatocarcinogenesis.
SO - Hepatology 2000 Mar;31(3):656-64
AD - Graduate Institute of Clinical Medicine, Chang Gung University College of Medicine, Taipei, Taiwan.
The hepatitis C virus (HCV) core protein is a multifunctional protein. It may bind to the death domain of tumor necrosis factor receptor 1 (TNFR1) and to the cytoplasmic tail of lymphotoxin-beta receptor, implying that it may be involved in the apoptosis and anti-apoptosis signaling pathways. In vitro studies have been inconclusive regarding its ability to inhibit or enhance TNF-alpha-induced apoptosis. To address this issue, electrophoretic mobility shift assay (EMSA) and immunohistochemical studies were used to show the activation of nuclear factor kappaB (NF-kappaB) in HCV-infected liver tissues and in HCV core-transfected cells. The activation of NF-kappaB was correlated with the apoptosis assays. The results showed that NF-kappaB activation could be shown in HCV-infected livers and HCV core-transfected cells. The data of EMSA correlated with those of immunohistochemical studies, which revealed a higher frequency of NF-kappaB nuclear staining in HCV-infected than in normal livers. NF-kappaB activation conferred resistance to TNF-alpha-induced apoptosis in HCV core-transfected cells. Inhibition of NF-kappaB activation by pyrrolidine dithiocarbamate sensitized them to TNF-alpha-induced apoptosis. These findings suggest that HCV infection may cause anti-apoptosis by activation of NF-kappaB and implicate a mechanism by which HCV may evade the host's immune surveillance leading to viral persistence and possibly to hepatocarcinogenesis.

2
UI - 10743066
AU - Wang C; Wang W; Lu H
TI - [Immunohistochemical study of hepatitis C virus core antigen and HBxAg in liver cirrhosis and hepatocellular carcinoma tissues]
SO - Zhonghua Zhong Liu Za Zhi 1997 Mar;19(2):85-8
AD - Department of Pathology, Fourth Military Medical University, Xi'an.
OBJECTIVE: To study the distribution and significance of hepatitis C virus core antigen in liver cirrhosis and hepatocellular carcinoma tissues. METHODS: Hepatitis C virus antigen and HBx-Ag were detected in liver cirrhosis (LC) and hepatocellular carcinoma (HCC) tissues with immunohistochemical methods. RESULTS: In some cases, not only was HCV core antigen positive stain distributed in the liver cells and nuclei of the cancer cell but it was also found in the cytoplasm. In different cases, it may be predominantly cytoplasm positive or nuclear positive or both. In liver cancer tissues, the HCV core antigen cytoplasmic positive cells were focally distributed and whereas the nuclear positive cells were diffusely distributed. The HCV core antigen nuclei positive cells were often observed in HCC tissues, but the cytoplasmic positive cells were often observed in the pericancerous liver tissue. The detection rates of HCV core antigen in LC, HCC and pericancerous liver tissues were 67.3% (66/98), 75.0% (78/104) and 48.1% (25/52), respectively. Statistical analysis suggested that: HCV core antigen nuclei positive rate in HCC be much higher than that in LC and pericancerous liver tissues (P < 0.01) and HCV core antigen nuclei positive rate be much higher than the cytoplasm positive rate in HCC tissues (P < 0.01). CONCLUSION: HCV, of which the infection being very common in LC and HCC of our country, may play an important role in the development of LC and HCC except HBV infection.

3
UI - 11255762
AU - Liu C; Gao P; Sun M; Yan W
TI - [Study of fungus polysaccharides compounds (FPC) in inducing the apoptosis of liver cancer cell Bel-7402]
SO - Wei Sheng Yan Jiu 2001 Jan;30(1):40-3
AD - Institute of Food Safety Control and Inspection, Ministry of Health, Beijing 100021, China.
To observe the influence of fungus polysaccharides compounds (FPC) in inducing human liver cancer cell Bel-7402 apoptosis in cell cultivating in vitro, the authors analyzed tumor inhibitive gene P53 expression in Bel-7402 apoptosis by applying double immuno-marker. The result showed that the multilevel of FPC could all apparently induce Bel-7402 apoptosis. With the enhancement of FPC concentration, the authors observed chromatin condensation in some phases companying with the characteristic apoptosis. In the meantime, it could also greatly reduce the G1 and S, with obviously dose-response relationship. The percentage of cell apoptosis increased with the enhancing of concentration. In the high-level group the authors found typical DNA ladder eletrophoresis stripe. The result showed that the mechanism of the FPC antineoplastic effect had an intimate relation with its induction to apoptosis and that the result of FPC inducing tumor cell apoptosis had the character of P53 independence.

4
UI - 11932908
AU - Saeki A; Tamura S; Ito N; Kiso S; Matsuda Y; Yabuuchi I; Kawata S;
TI - Matsuzawa Y Frequent impairment of the spindle assembly checkpoint in hepatocellular carcinoma.
SO - Cancer 2002 Apr 1;94(7):2047-54
AD - Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, 2-2 B-5 Yamadaoka, Suita, Osaka 565-0871, Japan.
BACKGROUND: Chromosomal instability (CI) leading to aneuploidy is one form of genetic instability, a characteristic feature of various types of cancers. Recent work has suggested that CI can be induced by a spindle assembly checkpoint defect. The aim of the current study was to determine the frequency of a defect of the checkpoint in hepatocellular carcinoma (HCC) and to establish whether alterations of genes encoding the checkpoint were associated with CI in HCC. METHODS: Aneuploidy and the function of the spindle assembly checkpoint were examined using DNA flow cytometry and morphologic analysis with microtubule disrupting drugs. To explore the molecular basis, the authors examined the expression and alterations of the mitotic checkpoint gene, BUB1, using Northern hybridization and direct sequencing in 8 HCC cell lines and 50 HCC specimens. Furthermore, the authors examined the alterations of other mitotic checkpoint genes, BUBR1, BUB3, MAD2B, and CDC20, using direct sequencing in HCC cell lines with aneuploidy. RESULTS: An impaired spindle assembly checkpoint was found in five (62.5%) of the eight aneuploid cell lines. Transcriptional expressions of the BUB1 gene appeared in all cell lines. While some polymorphic base changes were noted in BUB1, BUBR1, and CDC20, no mutations responsible for impairment of the mitotic checkpoint were found in either the HCC cell lines or HCC specimens, which suggests that these genes did not seem to be involved in tumor development in HCC. CONCLUSIONS: The loss of spindle assembly checkpoint occurred with a high frequency in HCC with CI. However, other mechanisms might also contribute to CI in HCC. Copyright 2002 American Cancer Society.

5
UI - 12032731
AU - Saffroy R; Riou P; Soler G; Azoulay D; Emile JF; Debuire B; Lemoine A
TI - Analysis of alterations of WFDC1, a new putative tumour suppressor gene, in hepatocellular carcinoma.
SO - Eur J Hum Genet 2002 Apr;10(4):239-44
AD - Service de Biochimie et Biologie moleculaire, Hopital Universitaire Paul Brousse, UPRES 1596-Faculte de Medecine Paris-Sud, 14 avenue Paul Vaillant Couturier 94804 Villejuif Cedex, France. raphael.saffroy@pbr.ap-hop-paris.fr
WFDC1 is a recently isolated human gene identified as a tumour suppressor gene candidate. It is not known whether alterations in this gene are associated with human cancers. The WFDC1 gene maps in human chromosome 16q24, an area of frequent loss of heterozygosity (LOH) in several tumour types, in particular in hepatocellular carcinoma (HCC). We investigated its role in 46 European HCC by means of the detection of LOH at the WFDC1 locus. We describe here an assay for the detection of loss of heterozygosity at this locus using two dinucleotide repeat polymorphisms identified in WFDC1 introns, with a combined informativity of 86%. LOH was observed in 4/40 informative HCC samples. We further investigated the role of WFDC1 as a tumour suppressor gene candidate in five hepatocellular cell lines and in tumours exhibiting LOH by means of mutation, promoter methylation and gene expression analysis. In HCC samples showing LOH, no mutation of the remaining allele was observed. No significant up or down gene expression was observed in tumour samples comparatively to normal liver and gene expression did not seem related to promoter methylation. These results suggest a minor role, if any, of WFDC1 in hepatocarcinogenesis. However, this approach might be useful for investigating the role of this candidate tumour suppressor gene in other tumour types.

6
UI - 12124174
AU - Liu D; Aguirre Ghiso J; Estrada Y; Ossowski L
TI - EGFR is a transducer of the urokinase receptor initiated signal that is required for in vivo growth of a human carcinoma.
SO - Cancer Cell 2002 Jun;1(5):445-57
AD - Department of Medicine, Division of Medical Oncology, Mount Sinai School of Medicine, New York, New York 10029, USA.
Urokinase plasminogen activator receptor (uPAR) activates alpha5beta1 integrin and ERK signaling, inducing in vivo proliferation of HEp3 human carcinoma. Here we demonstrate that EGFR mediates the uPAR/integrin/fibronectin (FN) induced growth pathway. Its activation is ligand-independent and does not require high EGFR, but does require high uPAR expression. Only when uPAR level is constitutively elevated does EGFR become alpha5beta1-associated and activated. Domain 1 of uPAR is crucial for EGFR activation, and FAK links integrin and EGFR signaling. Inhibition of EGFR kinase blocks uPAR induced signal to ERK, implicating EGFR as an important effector of the pathway. Disruption of uPAR or EGFR signaling reduces HEp3 proliferation in vivo. These findings unveil a mechanism whereby uPAR subverts ligand-regulated EGFR signaling, providing cancer cells with proliferative advantage.

7
UI - 12136251
AU - Li Y; Li Y; Tang R; Xu H; Qiu M; Chen Q; Chen J; Fu Z; Ying K; Xie Y;
TI - Mao Y Discovery and analysis of hepatocellular carcinoma genes using cDNA microarrays.
SO - J Cancer Res Clin Oncol 2002 Jul;128(7):369-79
AD - State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai 200433, People's Republic of China. yaoliff@yahoo.com
PURPOSE: Microarray analysis on a genomic scale was used to profile changes in gene expression accompanying hepatocellular carcinoma. METHODS: Gene expression profiles of liver tissues from twelve hepatocellular carcinoma samples relative to the gene expression profile of the normal liver tissue were analyzed using 4096 chips and 12800 chips. The results of microarray experiments were verified by the Northern blot technique. RESULTS: A group of 1,820 genes with altered expression were identified in more than 50% of the patients examined. This highly concordant expression profile included human genes encoding proteins involved in the function of peroxisomes, serum control, polycyclic aromatic hydrocarbon carcinogenesis, cell growth and differentiation, metastasis, the function of the immune system, apoptosis, and remodeling of the cytoskeleton. CONCLUSIONS: The newly identified genes afford a quantitative view of the changes that accompany liver cancer at the genomic level, enable deeper insights into the molecular basis of disease, and provide an extensive list of potential early-onset molecular markers for improved diagnosis.

8
UI - 12174369
AU - Liu LX; Jiang HC; Liu ZH; Zhou J; Zhang WH; Zhu AL; Wang XQ; Wu M
TI - Integrin gene expression profiles of human hepatocellular carcinoma.
SO - World J Gastroenterol 2002 Aug;8(4):631-7
AD - National Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Science Peking Union Medical College, Panjiayuan, Chaoyang District, Beijing 100021, China.
AIM: To investigate gene expression profiles of integrin genes in hepatocellular carcinoma (HCC) through the usage of Atlas Human Cancer Array membranes, semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and Northern blot. METHODS: Hybridization of cDNA array membrane was performed with alpha(32)P-labeled cDNA probes synthesized from RNA isolated from hepatocellular carcinoma and adjacent non-cirrhotic liver. AtlasImage, which is a software specific to array, was used to analyze the result. RT-PCR of 24 pairs specimen and Northern blot of 4 pairs specimen were used to confirm the expression pattern of some integrin genes identified by Atlas arrays hybridization. RESULTS: Among 588 genes spotted in membrane, 17 genes were related to integrin. Four genes were up-regulated, such as integrin alpha8, beta1, beta7 and beta8 in HCC. Whereas there were no genes down-regulated in HCC. RT-PCR and Northern blot analysis of integrin beta1 gene gave results consistent with cDNA array findings. CONCLUSION: Investigation of these integrin genes should help to disclose the molecular mechanism of the cell adhesion, invasive and metastasis of HCC. A few genes are reported to have changed in HCC for the first time. The quick and high-throughout method of profiling gene expression by cDNA array provides us overview of key factors that may involved in HCC, and may find the clue of the study of HCC metastasis and molecular targets of anti-metastasis therapy. The precise relationship between the altered genes and HCC is a matter of further investigation.

10
UI - 12174373
AU - Huang J; Cai MY; Wei DP
TI - HLA class I expression in primary hepatocellular carcinoma.
SO - World J Gastroenterol 2002 Aug;8(4):654-7
AD - Bioinfo Tech Incorporated Company, 10F Zhuangsen No.8 Dongsheng Street, Chengdu 610015, Sichuan Province,China. huangjian@bioinfochina.com
AIM: To investigate whether CTL vaccine therapy is suitable for primary hepatocellular carcinoma (HCC) from the viewpoint of HLA class I antigens expression. METHODS: The immunocytochemistry, image analysis, flow cytometry, and labeled streptavidin biotin (LSAB) method of immunohistochemistry were applied respectively to study 4 HCC cell lines (e.g. Alexander, HepG2, SMMC-7721, and QGY-7703) cultured in vitro and 6 frozen tissue specimens of HCC. RESULTS: The positive control cell line Raji had very strong positive staining. Most mitotic and nonmitotic cells of the 4 HCC cell lines had various intensity of HLA class I antigens expression. The negative control cell K562 and the control slides of all the cell lines had no positive staining. In the 6 HCC specimens immunohistochemically studied, histological normal hepatocytes had no or very weak positive staining and the liver sinus had very strong positive staining. Most HCC cells in the sections from the 6 HCC specimens had strong positive HLA classIantigens staining. The positive staining was located in the cytoplasm, the perinuclear area, and at the cell membrane of the liver cancer cells. Flow cytometry also revealed that Raji and those 4 HCC cell lines had strong HLA classIantigens expression, which was confirmed quantitatively by the image analysis. It showed that the objective grayscale values of Raji and those 4 HCC cell lines were significantly different from that of K562 (Raji 114.04+/-10.94, Alexander 165.97+/-5.35, HepG2 167.02+/-12.60, QGY-7703 161.46+/-7.13, SMMC-7721 165.93+/-5.21, K562 244.89+/-4.60, P<0.01). Significant differences were also found between Raji and the 4 HCC cell lines. CONCLUSION: HCC cells express HLA class I antigens strongly. From this point of view, the active specific immunotherapy of CTL vaccine is suitable and practicable for HCC.

11
UI - 12174374
AU - Yan FH; Zhou KR; Cheng JM; Wang JH; Yan ZP; Da RR; Fan J; Ji Y
TI - Role and limitation of FMPSPGR dynamic contrast scanning in the follow-up of patients with hepatocellular carcinoma treated by TACE.
SO - World J Gastroenterol 2002 Aug;8(4):658-62
AD - Zhongshan Hospital, Fudan University, 180 Fenglin Road,Shanghai 200032, China. yanfuhua@yahoo.com
AIM: To evaluate the role and limitation of fast multiplanar spoiled gradient-recalled (FMPSPGR) MR dynamic contrast scanning in the follow-up of patients with HCC treated by transarterial chemoembolization (TACE). METHODS: Twenty-two patients with 24 HCC lesions confirmed by biopsy or surgical resection underwent MR imaging in 4-9wks after TACE with a superconducting 1.5 T MR scanner, including SE T(1)WI, T(2)WI and FMPSPGR dynamic contrast scanning. The signal intensities of all lesions on SE T(1)WI,T(2)WI and the enhancement patterns on FMPSPGR dynamic contrast scanning were observed, and the comparison was made between MRI findings and pathological results in all the cases. RESULTS: Of the 24 lesions, the signal intensities were various on SE T(1)WI and T(2)WI. On T(1)WI, 13 lesions appeared as hyperintense, 4 lesions were isointense and the other 7 lesions were hypointensese. Histologically, hyperintense lesions showed on T(1)WI were viable tumor or hemorrhage; isointensities were coagulative necrosis or inflammatory infiltration; hypointensities were tumor, liquified necrosis, coagulative necrosis or inflammatory infiltration. On T(2)WI, 15 lesions appeared as hyperintense, 3 lesions were isointense and the other 6 lesions were hypointensese. Hyperintense lesions showed on T(2)WI were residuals of viable tumor, hemorrhage, liquefied necrosis or inflammatory infiltration; isointense lesions were residuals of viable tumor or inflammatory infiltration; hypointense lesions were coagulative necrosis. On FMPSPGR dynamic contrast scanning, 18 of the 24 lesions enhanced on early-phase dynamic scanning corresponding to residuals of viable tumor and the other 6 lesions had no enhancement at this phase because complete necrosis were seen in the histologic examination. On delayed-phase dynamic scanning, 6 lesions had permanent enhancement appeared as inhomogeneous hyperintensity and both residuals of viable tumor and inflammatory infiltration were found by histologic examination. 18 lesions were hypointense at this phase and 8 of them coexisted with peripheral ring-like enhancement of the lesions resulting from viable tumors or inflammatory infiltration. CONCLUSION: FMPSPGR MR dynamic contrast scanning can reflect the pathologic changes of HCC treated by TACE. Especially, early-phase dynamic scanning can evaluate accurately residuals of viable tumor and necrosis in HCC lesions. FMPSPGR dynamic contrast scanning is useful in the follow-up of patients with HCC treated by TACE combined with SE T(1)WI and T(2)WI, but it is difficult to differentiate peripheral viable tumors from inflammatory infiltration.

12
UI - 12193853
AU - Roudot-Thoraval F; Dhumeaux D
TI - [Towards early screening and treatment of hepatocellular carcinoma cirrhosis?]
SO - Gastroenterol Clin Biol 2002 Jun-Jul;26(6-7):559-60

13
UI - 12193855
AU - Ganne-Carrie N; Chevret S; Barbare JC; Chaffaud C; Grando V; Vogt AM;
TI - Beaugrand M; Trinchet JC; et l'Association Francaise pour l'Etude du Foie (2) et l'Association Nationale des Gastroenterologues des Hopitaux generaux [Practical screening and early treatment of hepatocellular carcinoma. Results of a French survey]
SO - Gastroenterol Clin Biol 2002 Jun-Jul;26(6-7):570-7
AD - Service d'Hepato-Gastroenterologie, Hopital Jean Verdier (AP-HP, Universite Paris 13), Bondy 93140, France. nathalie.ganne@jvr.ap-hop-paris.fr
AIM: To describe French practices for screening hepatocellular carcinoma. METHODS: A standardized questionnaire was mailed to all out of 623 practitioners responded (66%). 394 (96%) routinely screen hepatocellular carcinoma, mainly with ultrasound (98%) and mainly at 6-month intervals (77%). Screening was performed in cirrhosis (100%) or extensive fibrosis (54%), independent of the etiology (21%) or the Child-Pugh score of the chronic liver disease (41%), but based on age and treatment feasibility. If of a small hypoechogenic nodule was detected in a young patient with compensated HCV-cirrhosis, 59% of practitioners performed a histological examination. In case of non biopsy-proven hepatocellular carcinoma, a second biopsy (49%), treatment (either percutaneous alcohol injection, resection or transplantation) (24%) or an ultrasonographic follow-up (23%) was proposed. In case of biopsy-proven hepatocellular carcinoma, resection (49%), transplantation (30%) or percutaneous alcohol injection (16%) was proposed. CONCLUSION: Almost all French specialists routinely screen cirrhotic patients for hepatocellular carcinoma, but use somewhat different modalities. In case of small HCC without contraindications to curative treatment, surgical resection is performed in half the patients.

14
UI - 12175906
AU - Livezey KW; Negorev D; Simon D
TI - Increased chromosomal alterations and micronuclei formation in human hepatoma HepG2 cells transfected with the hepatitis B virus HBX gene.
SO - Mutat Res 2002 Aug 29;505(1-2):63-74
AD - Department of Pathology and Laboratory Medicine, MCP Hahnemann School of Medicine, Broad and Vine, Philadelphia, PA 19102, USA. kristin1@gen-probe.com
The protein encoded by the hepatitis B virus (HBV)-X gene, HBX, has been implicated to be involved in the development of HBV-associated liver cancer. HBX is a multifunctional regulatory protein that has been identified as a potential oncogene but its exact function remains unclear. HBX was documented to interact with several factors involved in cellular DNA repair as well as compromise the cell's ability to repair damaged DNA. We previously documented an accumulation of genetic alterations in two HepG2 cell lines independently transfected with HBV. In this report, we investigate the effect of the HBV-X gene (HBX) on the stability of the host genome using HepG2 stable transfectants (HepG2-HBX) and vector controls (HepG2-neo). We document that all HepG2-HBX clones analyzed contain HBX gene integrated and HBX transcript. Our data demonstrate that HepG2-HBX cells have an increased number of chromosome alterations and micronuclei formation compared to vector controls. A total of 10 de novo chromosomal rearrangements involving nine different chromosomes were detected in the HepG2-HBX clones, while no new rearrangements were found in vector controls. Each HepG2-HBX clone contained independently occurring de novo alterations not found in other HBX or vector clones. A three-fold increase of micronuclei formation was detected in HepG2-HBX cells compared to vector controls. Micronuclei originated from all chromosomes, however, preliminary data indicated that micronuclei originating from chromosomes 2, 3, 7, 18 and 20 were found in a greater amount in cells expressing the HBX gene. Interestingly, chromosomes 2, 18 and 20 were three of the chromosomes found rearranged in HepG2-HBX clones. These data provide evidence that genomic integrity was affected in cells expressing the HBX gene. De novo cytogenetic alterations identified in HepG2-HBX clones implicate the involvement of HBX in the process and support the hypothesis that HBX may interfere with normal cellular processes responsible for genomic integrity, increasing the risk for acquiring genetic mutations in infected hepatocytes.

15
UI - 12211740
AU - Szubert A; Sarzynski J; Biejat Z; Uryzek M; Grous A; Kowalik I; Polanski
TI - JA Risk factors for morbidity following liver surgery.
SO - Med Sci Monit 2001 May;7 Suppl 1():294-7
AD - 3rd Department of Surgery, 2nd Faculty of Medicine, Medical University in Warsaw, ul. Stepinska 19/25, Warsaw, Poland.
The aim of this study is to define risk factors for severe complications following anatomical liver resections. The study material consists of the first 50 patients (26 women, 24 men, at mean age 50.6 years) treated at 3rd Department of Surgery 2nd Faculty of Medicine, Medical University in Warsaw. The indications for resection included benign neoplasm in 19 cases and malignancy in 31 cases. All the patients underwent anatomical liver resection in accordance with Couinaund's segmental division. In order to define prognostic factors for severe postoperative complications, a multi-factor statistical analysis was conducted. The following parameters were analysed: patient's age, the levels of bilirubin, total protein, albumin, prothrombin time, kaolin-kephalin time, range of resection and blood loss during operation. Eleven patients (22%) died in postoperative period. In 8 cases the death was caused by liver failure. Statistical analysis showed that blood loss, albumin level on fifth postoperative day and kaolin-kephalin time before and after surgery are independent risk factors predisposing to the development of complications.

16
UI - 12203777
AU - Chen YJ; Chen PJ; Lee MC; Yeh SH; Hsu MT; Lin CH
TI - Chromosomal analysis of hepatic adenoma and focal nodular hyperplasia by comparative genomic hybridization.
SO - Genes Chromosomes Cancer 2002 Oct;35(2):138-43
AD - Center for General Education, National Yang-Ming University, Taipei, Taiwan.
Hepatic adenoma (HA) and focal nodular hyperplasia (FNH) are two common non-malignant tumors of the liver. Genomic analysis on these benign lesions may shed light on the genetic mechanism underlying liver carcinogenesis. We used comparative genomic hybridization (CGH) to evaluate genomic changes in eight cases of HA and six cases of FNH, obtained by surgical procedures; the resulting chromosomal aberration profiles were analyzed together with their pathological and clinical manifestations. We found consistent chromosomal lesions associated with both non-malignant hepatic tumors. The overall genomic abnormalities in HA and FNH were much less obvious than those in hepatocellular carcinoma (HCC). Among these limited changes, frequent gains were located on chromosomal arms 1q (50%), 17q (50%), 1p (38%), and 11q (38%) in HA, and on 11q (50%), 9q (33%), 17q (33%), and 22q (33%) in FNH. Gains outnumbered losses, and HA contained more CGH abnormalities than did FNH. Interestingly, CGH alteration hotspots found in HA, but not in FNH, appeared largely to coincide with common genomic lesions of cancerous HCC, suggesting an interesting relationship along the tumorigenesis pathway of HA and HCC. Copyright 2002 Wiley-Liss, Inc.

17
UI - 12202710
AU - Awai K; Takada K; Onishi H; Hori S
TI - Aortic and hepatic enhancement and tumor-to-liver contrast: analysis of the effect of different concentrations of contrast material at multi-detector row helical CT.
SO - Radiology 2002 Sep;224(3):757-63
AD - Department of Radiology, Rinku General Medical Center, 2-23 Rinkuorai-kita, Izumisano City, Osaka 598-8577, Japan.
PURPOSE: To investigate the effect of different iodine concentrations of contrast material on aortic and hepatic enhancement and the detectability of hypervascular hepatocellular carcinoma (HCC) with multi-detector row computed tomography (CT) and a uniphasic contrast material injection technique. MATERIALS AND METHODS: Two hundred one patients with known or who were suspected of having HCC underwent multi-detector row CT; 58 patients with hypervascular HCC were identified. First-, second-, and third-phase scanning was started with the aortic arrival times plus 15 seconds, plus 30 seconds, and plus 105 seconds, respectively. All patients were assigned randomly into two groups. Patients in groups A and B received iopamidol with an iodine concentration of 300 mg/mL and 370 mg/mL, respectively, with the same total iodine load per patient per body weight. The liver and aorta enhancement and tumor-to-liver contrast (TLC) were measured. Depiction of hepatic arteries was evaluated visually by two radiologists. RESULTS: During the first phase, aortic enhancement was significantly (P <.01) higher in group B, with no significant difference in hepatic enhancement between the two groups. During the second phase, aortic enhancement was significantly (P <.01) higher in group A, with no significant difference in hepatic enhancement. The TLC was significantly (P <.01) higher in group B during the first phase, but there was no significant difference between the two groups during the second phase. There was no significant difference in any parameters between the two groups during the third phase. Depiction of the hepatic arteries in group B was significantly (P <.05) superior to that in group A. CONCLUSION: In the arterial phase, administration of a higher concentration of contrast material is effective for a significantly higher TLC. Copyright RSNA, 2002

18
UI - 2191857
AU - Kenya PR
TI - Oral contraceptives use and liver tumours: a review.
SO - East Afr Med J 1990 Mar;67(3):146-53
AD - Kenya Medical Research Institute, Medical Research Centre, Nairobi.
Of the nine epidemiologic controlled studies reporting on the relationship between oral contraceptives use and hepatic tumours, three have findings specifically on the association of oral contraceptives use and hepatocellular adenomas. The strength of this association is reported to be dependent more on long-term oral contraceptive use. Three other studies have reported similar relationships of oral contraceptives use with hepatocellular carcinoma, whereas the remaining three other studies have reported no association between oral contraceptives use and hepatocellular carcinoma. There is however, an increased risk of hepatocellular carcinoma as the duration of oral contraceptives use increases. The risk of developing hepatocellular adenomas is higher in oral contraceptives users over 30 years of age than in the younger age groups. These tumours occur more often in oral contraceptive users taking pills with high doses of estrogens and progestogens; while they are not only associated with oral contraceptives containing mestranol, but also those containing ethinylestradiol.

19
UI - 2166378
AU - Little JM; Kenny J; Hollands MJ
TI - Hepatic incidentaloma: a modern problem.
SO - World J Surg 1990 Jul-Aug;14(4):448-51
AD - Department of Surgery, Westmead Hospital, New South Wales, Australia.
As clinical skills give way to increased reliance on organ imaging, a new clinical problem is identified--the hepatic "incidentaloma." This may be defined as an unexpected solid filling defect in the liver of a well patient. Thirty-six such lesions have been seen in one practice over a period of 36 months. Twenty-nine (81%) were benign: 24 (67%) nonneoplastic conditions 5 (14%) benign tumors. The remaining 7 (19%) were malignant: 5 secondary tumors and 2 primary tumors. Patients with physical signs of liver mass or enlargement were more likely to harbor malignancies. An elevated serum alkaline phosphatase (SAP) was suggestive of malignancy. Hepatic hemangioma was the most common single diagnosis (20 patients, 56%). We propose a regimen of investigation which should allow diagnosis to be reached in about one-half of these patients without admission to the hospital. The rest will need at least a short hospital admission for angiography and fine-needle aspiration biopsy.

20
UI - 1710205
AU - Watanabe Y; Harada S; Saito I; Miyamura T
TI - Prevalence of antibody against the core protein of hepatitis C virus in patients with hepatocellular carcinoma.
SO - Int J Cancer 1991 May 30;48(3):340-3
AD - Department of Enteroviruses, National Institute of Health, Tokyo, Japan.
We have cloned the whole structural region of the hepatitis C virus (HCV) genome and transiently expressed the nucleocapsid protein in animal cells. Since the nucleotide sequences of this region of the HCV genome has been shown to be highly conserved among different HCV isolates, the assay detecting the antibody to this expressed protein is useful for studying the pathogenicity of HCV. In this work, we investigated the presence of antibodies to HCV nucleocapsid protein (p22) in patients with hepatocellular carcinoma (HCC) and compared its frequency with that of antibody to HCV non-structural protein (C-100), which is presently applied for blood screening for transfusion and diagnosis for chronic hepatitis C. By a sensitive Western blot analysis, 85 of 102 (83.3%) sera of hepatitis B virus surface antigen (HBsAg)-negative HCC patients were positive for the antibody to p22 (anti-p22), whereas 68 of the same 102 cases (66.7%) were positive for the anti-C100 by ELISA. The prevalence of anti-p22 in 23 HBV carrier HCC patients, 56 patients with non-HCC cancer and 100 healthy blood donors were 4.3, 12.5 and 1.0%, respectively. Thus, high prevalence of anti-p22 in non-B HCC confirmed that HCV infection is closely related to the development of HCC. Furthermore, the anti-p22 assay can detect HCV-infected patients who could not previously be identified as such by the present anti-C100 assay.

21
UI - 1651205
AU - Rosenberg L
TI - The risk of liver neoplasia in relation to combined oral contraceptive use.
SO - Contraception 1991 Jun;43(6):643-52
AD - Slone Epidemiology Unit, Boston University School of Medicine, Brookline, MA 02146.
Benign liver tumors occurring in young women were rarely reported in the medical literature before the introduction of oral contraceptives in the early 1960s. Subsequently, there were numerous case reports from the U.S. and other countries of liver tumors in women who used combined oral contraceptives. These reports, coupled with data from two U.S. case-control studies, indicate that the risk of hepatocellular adenoma increases sharply with increasing duration of oral contraceptive use. Case reports suggest that there may be a similar effect on the risk of focal nodular hyperplasia, but this is not established because there have been no case-control studies of the lesion. The incidence of benign liver disease attributable to oral contraceptive use in the U.S. is small because of the very low incidence of the disease. There have also been numerous case reports of malignant liver tumors in young women who used oral contraceptives. Seven case-control studies have been conducted--two in Great Britain, two in the U.S., one in Italy, one in several developing countries (conducted by the World Health Organization (WHO)), and one in South Africa. Data from the first five studies, all conducted in low risk populations, indicated an association of hepatocellular carcinoma (largely in the absence of liver cirrhosis) with oral contraceptive use. Because of small numbers estimates were unstable, but the risk did not appear to be increased appreciably for durations of use less than about five years. For longer durations, the risk appeared increased by five- to tenfold or more. There was little evidence of hepatitis B infection in the cases, but systematic determinations were not carried out. An increased risk of cholangiocarcinoma was not established, but few of these lesions were studied. Because the incidence of primary liver cancer in Northern Europe and the U.S. is low, the incidence attributable to oral contraceptive use is also likely to be low. The WHO study was carried out in eight countries, most of which have a high incidence of liver cancer and a high prevalence of a predisposing factor, hepatitis B infection. Similarly, the South African study was carried out among black women, and virtually all of the cases had serological evidence of hepatitis B infection. Both studies indicated no association of short-term oral contraceptive use with risk of hepatocellular carcinoma, and the WHO study indicated a lack of association with cholangiocarcinoma.

22
UI - 1658955
AU - Shortell CK; Schwartz SI
TI - Hepatic adenoma and focal nodular hyperplasia.
SO - Surg Gynecol Obstet 1991 Nov;173(5):426-31
AD - Department of Surgery, University of Rochester Medical Center, New York 14642.
Hepatic adenoma and focal nodular hyperplasia are benign lesions of the liver. The incidence of these conditions has been increasing since 1970. Hepatic adenoma primarily affects young women of childbearing age who have a long history of using oral contraceptives, while focal nodular hyperplasia has a wider age distribution and is not associated with the use of oral contraceptives. The most extensive complication of hepatic adenoma is intratumoral or intraperitoneal hemorrhage, which occurs in 50 to 60 per cent of patients. Patients with focal nodular hyperplasia are usually asymptomatic and rarely experience complications. Hepatic adenoma is distinct from focal nodular hyperplasia both in its clinical behavior and its pathologic features; the two can usually be differentiated radiographically using a combination of radionuclide scanning and angiography. There is a proved association between the use of oral contraceptives and the development of hepatic adenoma; the longer the duration of oral contraceptive use, the more the risk of having hepatic adenoma develop. In addition, users of oral contraceptives who have hepatic adenoma develop are likely to have larger tumors and higher rates of bleeding and rupture than nonusers who have hepatic adenoma develop. Although hepatic adenomas may regress after discontinuation of oral contraceptive use, this is not a consistent finding. In addition, it has now been demonstrated that hepatic adenomas do undergo malignant transformation and that this can be detected by measuring the alpha-fetoprotein level. Focal nodular hyperplasia may be a precursor for fibrolamellar hepatocellular carcinoma. Elective resection of hepatic adenoma has a mortality rate of less than 1 per cent, while the mortality rate with free rupture is 5 to 10 per cent. Because of the relative safety of elective versus emergency resection and the potential for malignant change, the treatment of choice for hepatic adenoma is surgical resection.

23
UI - 1660333
AU - Villa E; Melegari M; Scaglioni PP; Trande P; Cesaro P; Manenti F
TI - Hepatocellular carcinoma: risk factors other than HBV.
SO - Ital J Gastroenterol 1991 Sep-Oct;23(7):457-60
AD - Cattedra di Gastroenterologia, Universita di Modena, Italy.
The putative risk factors for hepatocellular carcinoma (HCC) are several, even in countries endemic for hepatitis B virus (HBV) infection. Cirrhosis characterizes more than 90% of HCC cases. The phases of inflammation, necrosis and regeneration, present for long periods in cirrhosis, might be most relevant in hepatocarcinogenesis. It is not clear what role is played by sex hormones while alcohol probably has a promoter role. Aflatoxins are known carcinogenins in the experimental animal: however it is difficult to evaluate the impact in human carcinogenesis due to the lack of reliable methods of measuring aflatoxin exposure in population studies. In conclusion, the aetiology of HCC is multifactorial and the main risk factor resides in the presence of underlying chronic li

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