National Cancer Institute®
Last Modified: February 1, 2002
UI - 11734333
AU - Qin LF; Ng IO
TI - Induction of apoptosis by cisplatin and its effect on cell cycle-related proteins and cell cycle changes in hepatoma cells.
SO - Cancer Lett 2002 Jan 10;175(1):27-38
AD - Department of Pathology and Centre for the Study of Liver Disease, The University of Hong Kong, Room 127B, University Pathology Building, Queen Mary Hospital, Pokfulam, Hong Kong.
We investigated cisplatin-induced apoptosis and the effects on cell cycle-related proteins and cell cycle changes. Two human hepatoma cell lines, HepG2 (with wild-type p53) and Hep3B (with deleted p53), were treated with different concentrations of cisplatin. Cisplatin induced apoptosis in both cell lines as assessed by cell morphology, DNA fragmentation analysis,TdT-mediated dUTP nick end labeling assay and flow cytometry. HepG2 cells were more sensitive to cisplatin than Hep3B. Low-dose cisplatin induced a transient G(1) arrest, S phase block and upregulation of p53 and p21(WAF1/CIP1) expression in HepG2, but not in Hep3B cells. With cisplatin at a high dose, both cell lines underwent apoptosis that was accompanied by downregulation of p27(KIP1) and Bcl-x(L). In HepG2, upregulation of p53 and p21(WAF1/CIP1) was observed before apoptosis occurred, suggesting that cisplatin-induced apoptosis in HepG2 might be p53-dependent. Expression of Fas was also increased following cisplatin treatment in HepG2. However, there was no induction of p53, p21(WAF1/CIP1) and Fas observed in Hep3B cells. In conclusion, cisplatin induced apoptosis in hepatoma cells via both p53-dependent and -independent pathways.
UI - 11778551
AU - Lu Y; Zhou R
TI - [Mechanism of enhanced invasiveness of human hepatocellular carcinoma by integrin alpha 6 beta 1]
SO - Zhonghua Zhong Liu Za Zhi 2000 Jul;22(4):287-9
AD - Department of Cell Biology, Beijing Medical University, Beijing 100083, China.
OBJECTIVE: To study the mechanism of enhanced invasiveness of human hepatocellular carcinoma (HCC) by laminin (LN) receptor integrin alpha 6 beta 1. METHODS: A stable transfectant of HCC Bel 7402 cell line, the alpha 6 beta 1 receptors of which were replaced by non-functional LN receptor alpha 6 beta 4-TR using dominant negative strategy, was used. Motility of the non-transfected, mock transfected and transfected tumor cells was assessed by the number of cells migrated to an area scratched out of cells on tumor cell monolayer. Tumor cell invasion was examined by cell penetration through a Matrigel layer in Boyden chamber. Matrix metalloproteinases (MMPs) secretion was detected by gelatin zymography. RESULTS: The migration of HCC Bel 7402 cells expressing dominant negative alpha 6 beta 1 was significantly decreased. Their invasive capability was decreased by 46.7%. The secretion of MMP-9 was almost totally inhibited and the activated MMP-2 was decreased by 43.9%. CONCLUSION: The decrease in cell motility, invasiveness and MMPs secretion of HCC cells expressing dominant negative alpha 6 beta 4 TR implies that LN-integrin interaction plays important role in HCC progression.
UI - 11778560
AU - Chen Y; Li H
TI - [Imaging findings of intrahepatic peripheral cholangiocarcinoma]
SO - Zhonghua Zhong Liu Za Zhi 2000 Jul;22(4):318-20
AD - Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, China.
OBJECTIVE: To study the imaging features of intrahepatic peripheral cholangiocarcinoma. METHODS: The imaging features of 11 cases of surgically and pathologically confirmed intrahepatic peripheral cholangiocarcinoma were retrospectively reviewed. B-ultrasonic scanning(BUS) was performed in all patients. CT was done in 8 patients, including conventional unenhanced scanning followed by enhanced scanning in 4 patients, dynamic double-stage scanning in 2 patients, and dynamic double-stage scanning followed by delayed scanning in the other 2 patients. Of the 3 patients received MRI, conventional SE series, T1WI and T2WI were performed in 2 patients, conventional SE series and dynamic scanning in the other one. RESULTS: All lesions were hypo-echoic in BUS, homogeneous or heterogeneous. On unenhanced CT, the lesions were of low density with ill-defined border. On enhanced scanning, moderate enhancement was observed at the edge of the lesions. MRI was of low intensity in T1WI and moderately high intensity in T2WI. Dynamic MRI and double-stage CT scanning showed characteristic enhancement from the periphery toward the center of the lesion. Focal dilatation of the intrahepatic bile ducts around the tumor was seen in 6 cases and retraction of liver capsule in 3 cases. CONCLUSION: To some extent, the imaging features of intrahepatic peripheral cholangiocarcinoma are characteristic. They are useful for differentiating these tumors from other space-occupying lesions in the liver.
UI - 11521784
AU - Emile JF; Azoulay D; Gornet JM; Lopes G; Delvart V; Samuel D; Reynes M;
TI - Bismuth H; Goldwasser F Primary non-Hodgkin's lymphomas of the liver with nodular and diffuse infiltration patterns have different prognoses.
SO - Ann Oncol 2001 Jul;12(7):1005-10
AD - Service d'anatomie pathologique, Hjpital Paul Brousse, UPRES 1596 and IFR 89, Universite Paris Sud, France. email@example.com
BACKGROUND: Primary liver non-Hodgkin's lymphomas have peculiar clinical and biological patterns. This study correlates these patterns with pathology and outcome. PATIENTS AND METHODS: Clinical records and histology of patients with primary liver non-Hodgkin's lymphoma, treated at our institution over a 20-year period, were reviewed. Lymphoproliferations occurring after liver transplantation were excluded. Survival analyses were performed with patients from the other published series (62 patients). RESULTS: Our series included eight patients. Three patients had a nodular liver infiltration, corresponding to a large B-cell lymphoma. Five patients had a diffuse liver infiltration, of whom three had a T-cell lymphoma with predominant sinusoid infiltration, and two had a large B-cell lymphoma. Patients with diffuse liver infiltration presented with hepatomegaly, and two of these also had acute liver failure. Diffuse infiltration had a worse prognosis than nodular infiltration (P = 0.0033). Among these latter patients, those treated with an anthracycline-based chemotherapy had a better outcome (P < 0.0001). CONCLUSIONS: Patients with primary liver lymphomas can be classified in two groups, depending on the type of infiltration. Those with nodular infiltration may benefit from anthracycline-based chemotherapy. Diffuse infiltration has a bad prognosis, and should be suspected in patients presenting with altered liver functions and hepatomegaly.
UI - 11776078
AU - Shao J; Li Y; Li H; Wu Q; Hou J; Liew C
TI - Deletion of chromosomes 9p and 17 associated with abnormal expression of p53, p16/MTS1 and p15/MTS2 gene protein in hepatocellular carcinomas.
SO - Chin Med J (Engl) 2000 Sep;113(9):817-22
AD - Cancer Center, Sun Yat-Sen University of Medical Sciences, Guangzhou 510060, China.
OBJECTIVE: Fifteen loci on chromosome 9p and 17 were analyzed to clarify the involvement of loss of heterozygosity (LOH) in hepatocellular carcinoma (HCC) in Chinese patients positive for hepatitis B (HBV) and/or hepatitis C (HCV) infection. Expression of tumor suppressor genes (TSG) of p53, p16, and p15 gene was found to correlate with a deletion of these genes. METHODS: Immunohistochemistry and PCR-based microsatellite polymorphism analysis techniques were used. RESULTS: A high frequency of LOH was detected on chromosome 9p24 at locus D9S54 (61.8%) and 9p21, concentrated at loci D9S1747 (52.4%) and D9S1752 (51.8%). On chromosome 17, high frequent LOH was concentrated on 17p at the p53 gene locus (53.8%) and locus D17S520 (52.8%). p53 protein expression was increased in HCC, which correlated with p53 gene loss. Expression of p16 and p15 protein decreased in HCC when LOH occurred at locus D9S1752 (p15 gene locus) or at locus D9S1747 and D9S1748 (p16 gene is located between these 2 loci). LOH at the p53 gene and p15 gene loci was closely associated with HBV and HCV co-infection in HCC. No significant relationship between LOH and HCC clinico-pathological outcomes was observed. CONCLUSION: High frequency LOH occurs on chromosomes 9p and 17 in HCC in Chinese patients. Such sites may contain several putative tumor suppressor genes critically involved in the development and/or progression of HCC. Deletion of p53, p16, or p15 tumor suppressor genes may cause abnormal expression of the protein product of these genes. HBV and/or HCV infection may be closely associated with LOH p53 and/or p15 gene expression.
UI - 11776086
AU - Ji Y; Zhu X; Sun H; Tan Y; Ma Z; Ye Q; Sujie A; Tang Z
TI - Hepatocellular adenoma and focal nodular hyperplasia: a series of 24 patients with clinicopathological and radiological correlation.
SO - Chin Med J (Engl) 2000 Sep;113(9):852-7
AD - Department of Pathology, Zhongshan Hospital, Shanghai 200032, China. firstname.lastname@example.org
OBJECTIVE: To investigate two rare benign lesions, hepatocellular adenoma (HCA) and focal nodular hyperplasia (FNH), and evaluate differential diagnosis. METHODS: Twenty-four consecutive patients with presumed HCA and FNH were studied at the Liver Cancer Institute from evaluation, symptoms and laboratory tests. New imaging techniques were prospectively appraised in addition to usual techniques. All had hepatic resections and follow-up. Histologic examination of surgical specimens was obtained in all cases. RESULTS: In every instance, FNH was an incidental finding. FNH consists of nodular aggregates of cytologically normal hepatocytes with foci of intranocular bile duct proliferation. In this series, patients with HCA had larger tumors and more often were symptomatic but the occurrence was unrelated to oral contraceptive steroids (OCS) usage. Intralesional hemorrhage or necrosis is common, and was seen in 75% of cases. The best imaging procedure in the diagnosis of FNH was MRI. Color Doppler US was a useful adjunct, but CT lacked specificity, making histological diagnosis mandatory. All patients underwent tumor resected were tumor--free during the follow-up. CONCLUSIONS: FNH is a distinct histopathologic entity, and is distinguishable from HCA. FNH is a hyperplastic response by the liver parenchyma to a pre-existing arterial malformation. HCA is a liver neoplasia and has the potential of malignant transformation to HCC. Based on these findings, we believe that if the clinical suspicion of HCA or FNH is strong, resection is usually the best approach if technically feasible and histologic diagnosis is mandatory.
UI - 11778272
AU - Zhao X; Wan D; Jiang H
TI - [Analysis on loss of heterozygosity of chromosome 17p13.3 in hepatocellular carcinoma and construction of genomic contig in the deleted region]
SO - Zhonghua Zhong Liu Za Zhi 2000 Sep;22(5):377-80
AD - National Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai 200032, China.
OBJECTIVE: To detect the status of loss of heterozygosity (LOH) on chromosome 17p13.3 in hepatocellular carcinoma (HCC) and determine a minimum region of LOH as well as construct genomic contig in LOH region. METHODS: Variable number tandem repeat (VNTR) and RFLP markers examined by Southern hybridization were used to detect LOH of HCC. Microsatellite markers amplified by PCR were detected for LOH by denatured PAGE. Using microsatellite primers, 3 rounds of PCR amplification were carried out to screen positive genomic clones. The contig was constructed by PCR detecting the reaction between microsatellite markers and individual genomic clone. RESULT: Fifty-four paired HCC samples were analysed with 16 polymorphic markers on chromosome 17p13.3. The data revealed that the region between D17S5 and D17S34 had a high rate of LOH (> 63%), but three markers (proximal to D17S5) toward centromere had low or no LOH. TP53 marker on chromosome 17p13.1 had a LOH rate of 31% which was lower than that on D17S5-D17S34 region. No LOH was found at D17S34, D17S1866 (proximal to telomere) and D17S5, D17S1574 (distal to telomere) in 2 cases of HCC. However, there was LOH between D17S849 and D17S1574 in some cases. In LOH region, genomic clones relative to 18 of markers were obtained. A contig covering 9 markers was constructed. CONCLUSION: Determination of the minimum LOH region on chromosome 17p13.3 in HCC and the construction of genomic clone contig provide basis for further identification of putative new tumor suppressor gene(s) in HCC.
UI - 11676880
AU - Peng G; Pang Z
TI - [In vitro modulation of the invasive and metastatic potentials of human hepatocellular carcinoma by interlukin-2]
SO - Zhonghua Gan Zang Bing Za Zhi 2001 Oct;9(5):303-5
AD - Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
OBJECTIVE: To investigate the effects of interlukin-2 (IL-2) on the in vitro invasiveness and the expression of several cell surface antigens related to invasive and metastatic potentials of human hepatocellular carcinoma (HCC) QGY-7701 cell line. METHODS: QGY-7701 cells were incubated with high concentration of IL-2 or low concentration of IL-2 in different time. The expression of ICAM-1, CD(44) and HLA-I of the tumor cells was determined by fluorescence-activated cell sorter (FACS) analysis The tumor cell binding affinity to extracellular matrix components was measured by cell attachment assay. The degree of homotypic aggregation was quantified by cell aggregation assay. RESULTS: IL-2 treatment exhibited enhanced expression of ICAM-1 (from 8.3% to 20.5% after high concentration of IL-2 treatment and 17.3% after low concentration of IL-2 treatment) and HLA-I (from 9.8% to 25.4% and 22.1%, respectively after high and low concentration of IL-2 treatment), suppression of CD(44) (from 26.4% to 12.5% and 11.6%, respectively) on HCC cell line and decreased binding affinity to type IV collagen (from 23.5% to 12.4%, 32.3% to 13.8%, 45.7% to 19.6% at 20 min, 40 min and 60 min, respectively after high concentration of IL-2 treatment, and 9.6%, 12.5% and 17.9%, respectively after low concentration of IL-2 treatment) and fibronectin (from 18.6% to 14.1%, 31.2% to 18.4%, 44.5% to 20.5% at 20 min, 40 min and 60 min, respectively after high concentration of IL-2 treatment, and 14.6%, 17.1% and 18.9%, respectively after low concentration of IL-2 treatment) and the degree of homotypic aggregation (from 58.3% to 26.5%, 85.4% to 37.6%, 88.6% to 42.3% at 20 min, 40 min and 60 min, respectively after high concentration of IL-2 treatment, and 25.0%, 36.4% and 42.6%, respectively after low concentration of IL-2 treatment)of HCC cells. CONCLUSIONS: IL-2 may directly alter tumor properties associated with invasive and metastatic phenotypes of HCC cells, and can inhibit the invasive and metastatic potentials of HCC cells.
UI - 11776624
AU - Wu P; Li L; Zhang F
TI - [The value of spiral CT in CT arterial portography and CT hepatic arteriography]
SO - Zhonghua Zhong Liu Za Zhi 1999 Nov;21(6):450-2
AD - Cancer Center, Sun Yat-sen University of Medical Sciences, Guangzhou 510060.
OBJECTIVE: To evaluate the usefulness of spiral CT in CT arterial portography (CTAP) and CT hepatic arteriography (CTHA). METHODS: The CTAP and CTHA manifestations in 50 patients with small hepatocellular carcinoma (< 3 cm in diameter) were analyzed and compared with those in bi-phase enhanced CT. RESULTS: The detection rate of CTAP and CTHA was 92.2% and 90.1%, respectively. They could reveal tumors of 0.2 cm-0.5 cm in diameter. Both CTAP and CTHA gave false-positive findings, such as perfusion defects in 13.0% of CTAP and non-pathologic enhancement in 19.1% of CTHA. CONCLUSION: With the use of spiral CT technique, the quantity of contrast material administrated in CTAP and CTHA can be considerably reduced, and the quality of CT images significantly improved. The detection rate of CTAP and CTHA is higher than that of biphase enhanced CT. Simultaneous use of both procedures may help decrease the false-positive rate, and increase the sensitivity of diagnosis for small hepatocellular carcinoma.
UI - 11808941
AU - Yano Y; Yamashita F; Sumie S; Ando E; Fukumori K; Kiyama M; Oyama T;
TI - Kuroki S; Kato O; Yamamoto H; Tanaka M; Sata M Clinical features of hepatocellular carcinoma seronegative for both HBsAg and anti-HCV antibody but positive for anti-HBc antibody in Japan.
SO - Am J Gastroenterol 2002 Jan;97(1):156-61
AD - Saga Social Insurance Hospital, Hyogo-minami, Saga-shi, Japan.
OBJECTIVE: We determined the prevalence of patients with hepatocellular carcinoma (HCC) who were positive for only anti-hepatitis B core (anti-HBc) antibody among 284 Japanese patients and compared their clinical features to those who were hepatitis B surface antigen positive [HBsAg(+)]. METHODS: Serum HBsAg and anti-hepatitis C virus (anti-HCV) antibody were examined for all HCC patients. Testing for anti-HBc antibody was performed in the HBsAg(-)/anti-HCV(-) patients. The clinical factors and the survival rate were compared between the HBsAg(+) patients (HCC-B) and those positive for anti-HBc alone (HCC-PB). RESULTS: There were 19 (6.7%) HBsAg(+), 236 (83.1%) anti-HCV(+), seven (2.5%) HBsAg(+)/anti-HCV(+), and 22 (7.7%) HBsAg(-)/anti-HCV(-) among the 284 patients tested. Sixteen (72.7%) of the 22 HBsAg(-)/anti-HCV(-) patients were assigned to the HCC-PB group. The prevalence of positivity for anti-HBc alone among all 284 HCC patients was 5.6%. Significant differences between the HCC-PB and HCC-B groups were that age at diagnosis was higher in the HCC-PB group (72.1 yr) than in the HCC-B group (56.2 yr) (p < 0.001), the serum alpha-fetoprotein concentrations were lower in the HCC-PB group (8.2 ng/ml) than in the HCC-B group (43 ng/ml) (p = 0.0488), and a higher familial history of liver disease was observed in the HCC-B group (p = 0.0373). However, there was no significant difference in the cumulative survival rate. CONCLUSIONS: Positivity for anti-HBc alone is not rare compared to HBsAg(+), and the clinical features of positivity for anti-HBc alone are similar to those of HBsAg(+). Some differences in the clinical features between the two groups may be explained by differences in the time of first exposure to hepatitis B virus. Therefore, the natural course of acute hepatitis B may be reconsidered.
UI - 11808943
AU - Nair S; Shivakumar KS; Thuluvath PJ
TI - Mortality from hepatocellular and biliary cancers: changing epidemiological trends.
SO - Am J Gastroenterol 2002 Jan;97(1):167-71
AD - Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
OBJECTIVES: The incidence of hepatocellular carcinoma may be rising in the United States. The aim of this study was to determine the epidemiological trends in mortality from hepatocellular carcinoma (HCC) and biliary cancers (BCs) in Maryland during the last 3 decades. METHODS: The number of deaths due to HCC and BCs from 1970 to 1997 were obtained from the Maryland State Department of Health & Hygiene vital statistics database. Malignant neoplasms of the gallbladder and intrahepatic and extrahepatic bile ducts were grouped together as biliary cancers. To determine the trend in mortality, the total time period was divided into seven 4-yr periods. RESULTS: Mortality from HCC increased from 0.94 to 1.84 per 100,000 population (rate ratio = 1.94, CI = 1.87-2.03) and that from BCs increased from 1.28 to 1.7 per 100,000 population (rate ratio = 1.31, CI = 1.26-1.36) over the study period. Although mortality due to HCC doubled in men (1.34 to 2.7 per 100,000) during this period, only a modest increase was observed among women (0.59 to 1.06 per 100,000). Because of a marked increase in the number of deaths among white Americans, the difference in HCC-related mortality between white Americans and African Americans decreased considerably during this period. Mean age at death increased steadily for BCs from 67 to 73 yr, whereas there was no real trend for HCC. Among African Americans, the death from HCC remained stable, but there was a 2-fold increase in BC-related death. CONCLUSIONS: There was a marked increase in deaths from HCC over the past 3 decades in Maryland. This increase was more evident among men and white Americans. Deaths due to BCs increased modestly during the same period of observation. The marked rise in BC-related deaths among African Americans remains unexplained.
UI - 11587244
AU - Anand BS
TI - Drug treatment of the complications of cirrhosis in the older adult.
SO - Drugs Aging 2001;18(8):575-85
AD - Baylor College of Medicine, Houston, Texas, USA. email@example.com
Several age-related changes occur in the structure and functions of the liver. The volume of the liver decreases, despite an increase in the size of hepatocytes, suggesting loss of liver cells. There are decreases in hepatic blood flow, the synthesis of urea and cholesterol, and the metabolism of drugs. Moreover, the regenerative capacity of liver becomes less efficient. Certain caveats are important when treating older patients with liver disease. Strict dietary restrictions, such as a low protein diet, should be avoided in the elderly (unless the patient is encephalopathic) because these patients are often undernourished to start with. Similarly, strict salt restriction should be enforced with caution, since it makes food less palatable and may take away what little desire such patients have to eat. Diuretic doses should be adjusted carefully because of greater risks of azotaemia and electrolyte disturbances in the elderly. Extra vigilance should be exercised in the early detection of infections that are more likely to occur in patients with cirrhosis. For example, spontaneous bacterial peritonitis can be missed in the elderly because of poor systemic (fever, abdominal tenderness) and laboratory responses (leucocytosis). In patients presenting with acute variceal bleeding, it is better to err on the side of underhydration than overhydration because of the risk of congestive heart failure. Vasopressin should be avoided in the elderly, since this drug has a high probability of precipitating an ischaemic event. Older patients do not tolerate beta-blockers as well as younger individuals and may require other treatment strategies for the prevention of variceal rebleeding episodes. Hepatic encephalopathy, especially the milder form, needs careful assessment because it can be easily confused with senile dementia syndromes. Cirrhosis is a premalignant condition and patients are at increased risk of developing hepatocellular carcinoma (HCC), a tumour seen predominantly in the elderly. All patients with cirrhosis should be maintained on a lifelong screening programme consisting of a 6-monthly assessment of alpha-fetoprotein and an imaging study, since early detection provides the only hope for cure of HCC. The only definitive treatment of cirrhosis is liver transplantation. Advanced age is not a contraindication to transplantation, and survival in older patients (aged >60 years) is comparable to that in younger individuals.
UI - 11813698
AU - Wartenberg D; Siegel Scott C
TI - Carcinogenicity of trichloroethylene.
SO - Environ Health Perspect 2002 Jan;110(1):A13-4
UI - 11740693
AU - Kardorff R; Fuchs J; Peuster M; Rodeck B
TI - [Infantile hemangioendothelioma of the liver--sonographic diagnosis and follow-up]
SO - Ultraschall Med 2001 Dec;22(6):258-64
AD - Marien-Hospital Wesel, Klinik fur Kinder- und Jugendmedizin, Germany. firstname.lastname@example.org
OBJECTIVE: Hepatic haemangioendothelioma is the most frequently observed hepatic tumour of early infancy. Lesions may cause life-threatening disease due to av-shunt-related cardiac failure, Kasabach-Merritt syndrome or encroachment on surrounding tissue. In this paper, the value of ultrasonography at initial work-up as well as during follow-up under various management strategies is discussed. METHOD: Retrospective analysis of sonographic and clinical data as well as outcome of 14 patients. RESULTS: The tumours may present initially with a typical sonographic pattern of a roundish solitary lesion consisting predominantly of massively perfused, tortuous cavities. In these cases, histological verification of the diagnosis is not mandatory, provided serological tumour markers are negative. Multifocal haemangioendotheliomata with a solid appearance, however, cannot be reliably distinguished from other entities sonographically. Tumour development - with or without therapy - can be followed up precisely using repeated ultrasound evaluations of tumour volume and sono-morphology as well as Doppler examination of tumour perfusion. CONCLUSIONS: Guidelines for the management of these patients are discussed, based on our experience and a review of the literature. Sonography proves to be of outstanding importance.
UI - 11690710
AU - Kanetaka K; Sakamoto M; Yamamoto Y; Yamasaki S; Lanza F; Kanematsu T;
TI - Hirohashi S Overexpression of tetraspanin CO-029 in hepatocellular carcinoma.
SO - J Hepatol 2001 Nov;35(5):637-42
AD - Pathology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
BACKGROUND/AIMS: The molecules involved in the progression of hepatocellular carcinoma (HCC) are not fully understood. The aim of this study was to elucidate the crucial genes involved in cancer progression and metastasis. METHODS: Selectively expressed genes were screened using differential display analysis, and then further analyzed by real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. RESULTS: Tetraspanin CO-029 was found to be frequently and significantly overexpressed in HCC. Real-time quantitative RT-PCR showed that the CO-029 mRNA level was 1.7 times higher (P=0.030) in cancerous tissues than in non-cancerous tissues. mRNA expression of the other tetraspanins, CD9 and CD82, was downregulated in HCC, especially in tumors with intrahepatic spreading (portal vein invasion and/or intrahepatic metastasis). In contrast, mRNA expression of CO-029 tended to be increased in cancerous tissue showing intrahepatic spreading compared with tumors without such spreading. Immunohistochemical analysis revealed that CO-029 was overexpressed in poorly differentiated HCCs compared with well to moderately differentiated tumors (P<0.001), and in HCCs showing intrahepatic spreading compared with those without spreading (P=0.019). CONCLUSIONS: Our findings suggest that CO-029 has some roles in the promotion of metastasis of HCC.
UI - 11775832
AU - Liu J; Zhou R; Zhang N; Rui J; Jin C
TI - Biological function of a novel gene overexpressed in human hepatocellular carcinoma.
SO - Chin Med J (Engl) 2000 Oct;113(10):881-5
AD - Department of Cell Biology, Beijing Medical University, Beijing 100083, China.
OBJECTIVE: To clone the full-length of a differentially expressed cDNA fragment, LC27, and study its biological function tentatively. METHODS: Northern blot was used to analyze the expression pattern of LC27 in hepatocellular carcinoma, matched nontumor liver tissues, fetal liver and normal adult liver tissues, as well as BEL-7402 hepatocellular carcinoma cell line ESTs splicing and 5' rapid amplification of cDNA ends (5' RACE) were used to clone the full-length of LC27 cDNA. An antisense oligodeoxynucleotide approach was used to investigate the biological role of the gene in the proliferation of BEL-7402 cells. RESULTS: A 2186 bp novel cDNA with an open reading frame encoding a 283 amino acid protein was cloned. Analysis of the deduced amino acid sequence indicated that it is 38% (88/229) identical to human Golgi 4-transmembrane spanning transporter MTP. The gene and the encoded protein was termed hepatocellular carcinoma overexpressed transmembrane protein (hotp) and HOTP, respectively. Hotp mRNA was almost undetectable in normal adult liver and fetal liver tissues. However, it was significantly up-regulated in hepatocellular carcinoma and some matched nontumor liver tissues, as well as BEL-7402 cells. The proliferation of BEL-7402 cells was suppressed by an antisense oligodeoxynucleotide against hotp mRNA at a concentration of 50 micrograms/ml. CONCLUSION: HOTP may be an integral membrane transporter protein. The overexpression of the gene in hepatocellular carcinoma may play an important role in hepatocarcinogenesis and disease progression.
UI - 11775834
AU - Huang J; Shen W; Li B; Luo Y; Liao S; Zhang W; Cheng N
TI - Molecular and immunohistochemical study of the inactivation of the p16 gene in primary hepatocellular carcinoma.
SO - Chin Med J (Engl) 2000 Oct;113(10):889-93
AD - Department of General Surgery, First Affiliated Hospital, Third Military Medical University, Chongqing 400038, China.
OBJECTIVE: To determine whether p16 gene is involved in the genesis of primary hepatocellular carcinoma (HCC). METHODS: Twenty-five HCC tumor samples with corresponding non-tumor liver tissue specimens were examined for p16 gene alterations. The identification of deletion of exon 1 and exon 2 in p16 gene was performed using comparative multiplex polymerase chain reaction (PCR) analysis. The point mutation of exon 2 in p16 gene was investigated by single strand conformational polymorphism (SSCP) analysis, and the status of p16 gene methylation was screened using a PCR based methylation analysis. 35 parafin-embedded specimens of HCC with corresponding non-tumor liver tissues, including the 25 cases described above for screening p16 gene alterations, were investigated for p16 protein expression using immunohistochemical analysis. RESULTS: Among 25 cases, 2 homozygous deletions and 1 hemizygous deletion were found in HCC samples. No point mutation was identified in the remaining 22 tumor samples without p16 gene deletions. Hypermethylation was detected in 24% (6/25) of tumor samples. However, the corresponding non-tumor liver tissue specimens were always unmethylated at the p16 locus. Loss of p16 protein expression occurred in 16 of 35 (45.7%) tumor samples, and all the non-tumor liver tissue specimens showed positive p16 staining. For the 25 cases examined for p16 gene alterations, the loss of p16 protein expression was observed in all tumors with p16 gene alterations and also in 3 tumors without p16 gene alterations. CONCLUSION: Inactivation of the p16 gene may play an important role in the genesis of primary hepatocellular carcinoma.
UI - 11801910
AU - Park MS; Kim KW; Yu JS; Kim MJ; Yoon SW; Chung KW; Lee JT; Yoo HS
TI - Radiologic findings of gastrointestinal tract involvement in hepatocellular carcinoma.
SO - J Comput Assist Tomogr 2002 Jan-Feb;26(1):95-101
AD - Department of Diagnostic Radiology and Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, South Korea.
PURPOSE: The purpose of this work was to evaluate the radiologic findings of gastrointestinal (GI) tract involvement in hepatocellular carcinoma (HCC) and to discuss mechanisms of spread. METHOD: Eighteen patients with histologically proven GI tract metastasis in HCC for 4.5 years underwent CT and five also underwent upper GI (UGI) series. The cases were classified according to the mode of spread, based on the radiologic findings. RESULTS: The involved portion of the GI tract was the stomach (n = 11), duodenum (n = 4), and colon (n = 4). The mode of spread was direct invasion from a contiguous primary tumor (n = 12), hematogenous metastasis (n = 3), peritoneal seeding (n = 1), and undetermined (n = 2). In cases of direct invasion from contiguous primary tumors, CT revealed GI tract invasion directly from bulky hepatic masses (n = 9) or daughter masses at the portion of the bowel wall contiguous to the hepatic masses (n = 3). In cases of hematogenous spread, CT revealed an intramural mass in the stomach and duodenum (n = 2) or a diffuse thickening of the wall of the stomach (n = 1). In the case of peritoneal seeding, CT revealed multiple small nodules in the right paracolic gutter, omentum, and mesentery with invasion to the colon. CONCLUSION: GI tract involvement in HCC shows various radiologic findings according to the mode of spread, but the most common finding is direct invasion of the stomach, duodenum, or colon from contiguous primary tumor.
UI - 11813174
AU - von Schweinitz D; Kraus JA; Albrecht S; Koch A; Fuchs J; Pietsch T
TI - Prognostic impact of molecular genetic alterations in hepatoblastoma.
SO - Med Pediatr Oncol 2002 Feb;38(2):104-8
AD - Department of Pediatric Surgery, University of Basle Childrens' Hospital, Basle, Switzerland. Dietrich.vonSchweinitz@unibas.ch
BACKGROUND: During recent years, we identified characteristic genetic alterations in sporadic hepatoblastoma (HB). These include loss of heterozygosity (LOH) at the chromosomal region 11p15.5, LOH on chromosome arms 1p and 1q, activating mutations in exon 3 of the beta-catenin gene, as well as overexpression of the c-met oncogene, which encodes the hepatocyte growth factor receptor. We now wanted to evaluate the prognostic relevance of these abnormalities concerning the outcome in a large group of patients. PROCEDURE: All but 7 of 56 patients with HB were treated either with primary resection for small tumors, or neo-adjuvant chemotherapy with ifosfamide, cisplatin and doxorubicin (IPA) before delayed surgery in case of extended disease and additional adjuvant IPA therapy in all cases. Seven tumors were primarily resected and adjuvantly treated with different cytotoxic drugs. LOH 11p15.5, LOH 1p, and LOH 1q were detected in tumor tissue in comparison to normal liver and/or peripheral blood leukocytes by PCR based microsatellite analysis. Beta-catenin mutations were analysed with SSCP, deletion screening and direct sequencing. RT-PCR was used for identification of c-met mRNA overexpression. The results were correlated with the tumors' stage, histological type and epithelial differentiation, as well as with the patients' outcome. RESULTS: Overall disease-free survival after median follow-up of 5 years was 43/56 patients (77%). LOH 11p15.5 was found in 15/56, LOH1p in 11/53, LOH1q in 7/53 and beta-catenin mutations in 25/55 HB. 13/23 HB had a c-met overexpression. LOH 11p15.5 and LOH 1p were significantly more often found in embryonal HB, while there was no correlation of other genetic alterations with histological type or differentiation. Furthermore, statistical analysis revealed no correlation of any of these disorders with initial tumor stage, nor with the patients' outcome. CONCLUSION: None of the investigated molecular genetic alterations are suited to serve as a prognostic indicator in HB. Further investigations, especially genetic screening of tumor tissue may reveal prognostic markers for this neoplasm. Copyright 2002 Wiley-Liss, Inc.
UI - 11595469
AU - Lotz G; Kiss A; Novak PK; Sobel G; Schaff Z
TI - Hepatitis viruses and hepatocarcinogenesis.
SO - J Physiol Paris 2001 Jan-Dec;95(1-6):417-22
AD - Second Department of Pathology, Semmelweis University of Budapest, Ulloi street 93, H-1091 Budapest, Hungary.
Hepatocellular carcinoma (HCC) is among the most frequent malignancies worldwide. Hepatitis viruses, such as the hepatitis B virus (HBV) and hepatitis C virus (HCV) are undoubtedly listed in the etiology of HCC. Studies show that, in the near future, viral hepatitis will carry increasing weight in the etiology of HCC. This review briefly discusses the known carcinogenic effects of HBV and HCV in the light of experimental and human studies. The data show that viral proteins may directly interfere with gene products responsible for cell proliferation and cell growth. Many other signal transduction cascades may be affected as well. Direct integration of HBV viral sequences into the host genome increases the genomic instability. The genomic imbalance allows the development and survival of malignant clones bearing defected genomic information. HBV and HCV infection induces indirect and direct mechanisms through cellular damage, increased regeneration and cell proliferation, therefore enhancing the development of HCC.
UI - 11780561
AU - Polakow J; Ladny JR; Janica J; Serwatka W; Walecki J; Puchalski Z
TI - Three-dimensional sonography in the diagnosis of hepatic hemangiomas.
SO - Rocz Akad Med Bialymst 2001;46():182-8
AD - Department of Radiology, Medical Academy of Bialystok, Bialystok, Poland.
The purpose of the study was to compare power 3-D with conventional 2-D sonography with color and power Doppler in assessment of tumor vascularity in small hepatic hemangiomas. The study group comprised 12 patients (7 males and 5 females) aged 28-60, (mean 44) with diagnosed hemangiomas. In all the patients 2-D and 3-D sonography was performed and their results were compared. Both color and power Doppler 2-D sonography failed to detect blood flow in the tumors. Blood flow signals were detected in 3-D power Doppler sonography. 3-D power Doppler is superior to 2-D color and power Doppler imaging in the detection of blood flow signal in hemangiomas.
UI - 11572758
AU - Takeda Y; Nakao K; Nakata K; Kawakami A; Ida H; Ichikawa T; Shigeno M;
TI - Kajiya Y; Hamasaki K; Kato Y; Eguchi K Geranylgeraniol, an intermediate product in mevalonate pathway, induces apoptotic cell death in human hepatoma cells: death receptor-independent activation of caspase-8 with down-regulation of Bcl-xL expression.
SO - Jpn J Cancer Res 2001 Sep;92(9):918-25
AD - The First Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki University, Nagasaki 852-8501, Japan. email@example.com
Geranylgeraniol (GGOH), an intermediate of mevalonate metabolism, is known to induce apoptosis in various lines of cancer cells. The present study was undertaken to clarify the signaling pathways of apoptosis induced by GGOH in human hepatoma cells. HuH-7 human hepatoma cells were incubated in the absence or presence of GGOH. Activation of caspase-8 /-9 /-3 in HuH-7 cells was found after 8 h treatment with GGOH, at which time DNA fragmentation and loss of mitochondrial transmembrane potential (Deltaphim) occurred. HuH-7 cells do not express Bcl-2; however, down-regulation of Bcl-xL expression preceded activation of the caspase cascade in GGOH-treated HuH-7 cells, while Bax expression was not changed by GGOH treatment. Addition of caspase inhibitors restored the decreased cell viability of HuH-7 cells by GGOH, including Deltaphim, to the baseline level, which indicated that caspase triggers mitochondria-dependent apoptotic pathways in GGOH-treated HuH-7 cells. Similarly, GGOH-mediated apoptosis of HuH-7 cells was clearly prevented by coadministration of ursodeoxycholic acid (UDCA), which led to restoration of the level of Bcl-xL expression. Activation of caspase-8 /-9 /-3, as well as Deltaphim, by GGOH treatment was suppressed by addition of UDCA. Our results indicate that activation of the caspase cascade initiating from caspase-8, which could be accelerated by down-regulation of Bcl-xL expression, plays a key role in an apoptotic process induced by GGOH in human hepatoma cells.
UI - 11705869
AU - Parasole R; Izzo F; Perrone F; Pignata S; Galati MG; Leonardi E;
TI - Castiglione F; Orlando R; Castello G; Esposito G; Gallo C; Daniele B Prognostic value of serum biological markers in patients with hepatocellular carcinoma.
SO - Clin Cancer Res 2001 Nov;7(11):3504-9
AD - Division of Clinical Immunology, National Cancer Institute, Via M. Semmola, 80131 Naples, Italy.
PURPOSE: Prognosis of patients with hepatocellular carcinoma (HCC) is assessed by using indexes based on clinical and instrumental parameters. The Cancer of the Liver Italian Program (CLIP) staging system combines the Child-Pugh classification with tumor size, portal invasion, and alpha-fetoprotein and predicts the outcome of HCC patients more precisely than the Okuda staging system. Serum levels of a number of biological variables have been found to be increased in patients with HCC and are associated with different outcomes. Our aims in this study were to test the prognostic role of the serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble interleukin-2 receptor (sIL-2R), interleukin 6 (IL-6), and anti-p53 and to assess whether the addition of any of the above serum markers could further improve the predictive ability of the CLIP score. EXPERIMENTAL DESIGN: Serum levels of sICAM-1, sIL-2R, IL-6, and anti-p53 were assayed in 80 patients with HCC and correlated with their outcomes. Nonparametric procedures were applied to test correlations between serum sICAM-1, sIL-2R, IL-6, anti-p53, and other prognostic factors. For survival analyses, the product-limit method, log-rank test, and Cox proportional hazards model were applied. RESULTS: Only serum levels of sIL-2R correlated with survival, which was longer for patients with lower values (< or =950 units/ml). However, with multivariate analysis sIL-2R did not confirm its predictive role when tested with the CLIP score as a covariate, with a hazard of death of 1.51 (95% confidence interval, 0.76-3.01). CONCLUSIONS: Serum levels of sICAM-1, sIL-2R, IL-6, and anti-p53 are not useful as prognostic factors for HCC in clinical practice. They do not improve the predictive ability of the CLIP score.
UI - 11780342
AU - Cheng J; Leng X; Cai S; Cao Z; Cao G; Peng J; Wang S; Du R
TI - bcl 10 gene mutation in hepatocellular carcinoma.
SO - Chin Med J (Engl) 2001 Jul;114(7):747-51
AD - Department of Surgery, Peking University People's Hospital, Beijing 100044, China.
OBJECTIVE: To detect the mutation frequency of the bcl 10 gene in the early and advanced stages of hepatocellular carcinoma (HCC). METHODS: Genome DNA samples were extracted from 46 cases of fresh HCC tumor tissues and their non-tumor adjacent tissues. Polymerase chain reaction-single strand conformation polymorphism method was used to detect point mutations of the three exons of the bcl 10 gene. For each individual exon, six random samples from those showing abnormal DNA bands were sequenced to verify those mutations. The relationship between serum alpha-fetoprotein (AFP) level and bcl 10 mutation, between the tumor size and bcl 10 mutation was also analyzed. RESULTS: Among the 46 samples, 26 cases (56.5%) were found to have mutations in exon 1, 5 out of the 6 cases were shown to have 5744 C-->G mutation by sequencing; 25 cases (54.3%) were found to have mutations in exon 2, 4 out of the 6 cases were shown to have 11,311 T deletion mutation by sequencing. Twenty-one cases (45.7%) were found to have mutations in exon 3, all of the 6 cases selected for sequencing were shown to have 14,116 C-->T mutation. Statistical analysis showed that neither serum alpha-fetoprotein level nor the size of hepatocellular carcinoma has a significant relationship with bcl 10 mutation. CONCLUSION: The bcl 10 gene has a high mutation frequency in liver cancer.
UI - 11756708
AU - Pauleit D; Textor J; Bachmann R; Conrad R; Flacke S; Layer G; Kreft B;
TI - Schild H Hepatocellular carcinoma: detection with gadolinium- and ferumoxides-enhanced MR imaging of the liver.
SO - Radiology 2002 Jan;222(1):73-80
AD - Department of Radiology, University of Bonn, Germany. firstname.lastname@example.org
PURPOSE: To test the hypothesis that the accuracy of gadolinium- and ferumoxides-enhanced magnetic resonance (MR) imaging is different in small (< or =1.5-cm) and large (>1.5-cm) hepatocellular carcinomas (HCCs). MATERIALS AND METHODS: Forty-three consecutive patients with chronic liver disease were enrolled in this study. The imaging protocol included unenhanced breath-hold T1-weighted fast field-echo sequences, unenhanced respiratory-triggered T2-weighted turbo spin-echo (SE) sequences, dynamic gadolinium-enhanced T1-weighted three-dimensional turbo field-echo sequences, and ferumoxides-enhanced T2-weighted turbo SE sequences. Images of each sequence and two sets of sequences (ferumoxides set and gadolinium set) were reviewed by four observers. The ferumoxides set included unenhanced T1- and T2-weighted images and ferumoxides-enhanced T2-weighted turbo SE MR images. The gadolinium set included unenhanced T1- and T2-weighted images and dynamic gadolinium-enhanced three-dimensional turbo field-echo MR images. In receiver operating characteristic (ROC) curve analysis, the sensitivity and accuracy of the sequences were compared in regard to the detection of all, small, and large HCCs. RESULTS: Imaging performance was different with gadolinium- and ferumoxides-enhanced images in the detection of small and large HCCs. For detection of small HCCs, the sensitivity and accuracy with unenhanced and gadolinium-enhanced imaging (gadolinium set) were significantly (P =.017) superior to those with unenhanced and ferumoxides-enhanced imaging (ferumoxides set). The area under the composite ROC curves, or A(z), for the gadolinium set and the ferumoxides set was 0.97 and 0.81, respectively. For large HCC, the ferumoxides set was superior compared with the gadolinium set, but this difference was not statistically significant. Analysis of all HCCs demonstrated no significant differences for gadolinium- and ferumoxides-enhanced imaging. CONCLUSION: For the detection of early HCC, gadolinium-enhanced MR imaging is preferred to ferumoxides-enhanced MR imaging because the former demonstrated significantly greater accuracy in the detection of small HCCs.
UI - 11756710
AU - Brancatelli G; Federle MP; Grazioli L; Carr BI
TI - Hepatocellular carcinoma in noncirrhotic liver: CT, clinical, and pathologic findings in 39 U.S. residents.
SO - Radiology 2002 Jan;222(1):89-94
AD - Department of Radiology, University of Pittsburgh Medical Center, 200 Lothrop St, Pittsburgh, PA 15213, USA.
PURPOSE: To review clinical, pathologic, and computed tomographic (CT) findings in patients with hepatocellular carcinoma (HCC) in noncirrhotic liver. MATERIALS AND METHODS: Clinical, pathologic, and imaging findings were retrospectively evaluated in 39 patients with HCC in noncirrhotic liver. Helical multiphasic CT scans obtained with 125 mL of contrast medium at a rate of 4 or 5 mL/sec were reviewed for morphologic features such as tumor size, margins, and hemorrhage and degree of enhancement. RESULTS: All patients (25 men, 14 women; mean age, 61 years) were U.S. residents; none had an Asian surname. Twenty-four patients (62%) had no identifiable risk factors; 34 (87%) were symptomatic. HCC was proved and cirrhosis excluded with biopsy in all cases. HCC was moderately (n = 32) or well (n = 6) differentiated in 97% of cases and poorly differentiated in one. Serum alpha-fetoprotein level was elevated in 26 patients. Large tumors (mean diameter, 12.4 cm) were depicted at C