National Cancer Institute®
Last Modified: September 1, 2002
UI - 11866295
AU - Miyakawa H; Fujikawa H; Kikuchi K; Kitazawa E; Kawashima Y
TI - Irregular regeneration of hepatocytes and development of hepatocellular carcinoma in primary biliary cirrhosis.
SO - Am J Gastroenterol 2002 Feb;97(2):488
UI - 12154346
AU - Bruno R; Sacchi P; Filice C; Puoti M; Filice G
TI - Hepatocellular carcinoma in HIV-infected patients with chronic hepatitis: an emerging issue.
SO - J Acquir Immune Defic Syndr 2002 Aug 15;30(5):535-6
UI - 11943598
AU - Zhou H; Zheng C; Zou G; Tao D; Gong J
TI - G(1)-phase specific apoptosis in liver carcinoma cell line induced by copper-1,10-phenanthroline.
SO - Int J Biochem Cell Biol 2002 Jun;34(6):678-84
AD - College of Life Sciences, Wuhan University, 430072, Wuhan, PR China.
Reactive oxygen species play an important role in the mediation of cell killing. But the mechanistic links between reactive oxygen species (ROS) and cell death remains unclear. There was a speculation that ROS, especially hydroxyl radicals can induce necrosis but not apoptosis in cells treated with copper-1,10-phenanthroline, IICu(OP)(2). In this paper, liver carcinoma cell line (Bel-7402) was treated with IICu(OP)(2) and its effect was examined by several means. Cells were found to undergo changes characteristic of apoptosis. Hoechst staining showed apoptotic body appeared in the cells induced by IICu(OP)(2). When DNA extracted from the cells treated with IICu(OP)(2) was analyzed by agarose gel electrophoresis it generated 'ladder' pattern of discontinuous DNA fragments. Sub-G(1) peak was detected in treated cells. Furthermore, two different flow cytometric methods were used, each allowing us to relate the apoptotic cells to the position the cell-cycle position. Apoptosis induced by IICu(OP)(2) was limited to G(1)-phase cells. Using cyclin analysis, the expression of cyclin E in G(1) was blocked. Thus, it was concluded that IICu(OP)(2) can induce G(1)-phase specific apoptosis in Bel-7402.
UI - 11959293
AU - Jimenez C; Rodriguez D; Marques E; Loinaz C; Alonso O; Hernandez-Vallejo
TI - G; Marin L; Rodriguez F; Garcia I; Moreno E De novo tumors after orthotopic liver transplantation.
SO - Transplant Proc 2002 Feb;34(1):297-8
AD - Department of General and Digestive Surgery and Abdominal Organ Transplantation, Hospital Universitario Doce de Octubre, Madrid, Spain.
UI - 12110732
AU - Saito Y; Kanai Y; Sakamoto M; Saito H; Ishii H; Hirohashi S
TI - Overexpression of a splice variant of DNA methyltransferase 3b, DNMT3b4, associated with DNA hypomethylation on pericentromeric satellite regions during human hepatocarcinogenesis.
SO - Proc Natl Acad Sci U S A 2002 Jul 23;99(15):10060-5
AD - Pathology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
DNA hypomethylation on pericentromeric satellite regions is an early and frequent event associated with heterochromatin instability during human hepatocarcinogenesis. A DNA methyltransferase, DNMT3b, is required for methylation on pericentromeric satellite regions during mouse development. To clarify the molecular mechanism underlying DNA hypomethylation on pericentromeric satellite regions during human hepatocarcinogenesis, we examined mutations of the DNMT3b gene and mRNA expression levels of splice variants of DNMT3b in noncancerous liver tissues showing chronic hepatitis and cirrhosis, which are considered to be precancerous conditions, and in hepatocellular carcinomas (HCCs). Mutation of the DNMT3b gene was not found in HCCs. Overexpression of DNMT3b4, a splice variant of DNMT3b lacking conserved methyltransferase motifs IX and X, significantly correlated with DNA hypomethylation on pericentromeric satellite regions in precancerous conditions and HCCs (P = 0.0001). In particular, the ratio of expression of DNMT3b4 to that of DNMT3b3, which is the major splice variant in normal liver tissues and retains conserved methyltransferase motifs I, IV, VI, IX, and X, showed significant correlation with DNA hypomethylation (P = 0.009). Transfection of human epithelial 293 cells with DNMT3b4 cDNA induced DNA demethylation on satellite 2 in pericentromeric heterochromatin DNA. These results suggest that overexpression of DNMT3b4, which may lack DNA methyltransferase activity and compete with DNMT3b3 for targeting to pericentromeric satellite regions, results in DNA hypomethylation on these regions, even in precancerous stages, and plays a critical role in human hepatocarcinogenesis by inducing chromosomal instability.
UI - 12185596
AU - Masutomi K; Kaneko S; Yasukawa M; Arai K; Murakami S; Kobayashi K
TI - Identification of serum anti-human telomerase reverse transcriptase (hTERT) auto-antibodies during progression to hepatocellular carcinoma.
SO - Oncogene 2002 Aug 29;21(38):5946-50
AD - Department of Gastroenterology, Kanazawa University Graduate School of Medicine, Takara-Machi 13-1, Japan.
Human telomerase reverse transcriptase, hTERT, is the catalytic component of human telomerase. Expression of hTERT confers telomerase activity, indicating that hTERT is the rate-limiting component of human telomerase. Here we report the detection of anti-hTERT auto-antibodies in the sera derived patients with hepatocellular carcinoma using recombinant, purified hTERT as an antigen in an enzyme linked immunosorbent assay (ELISA). The levels of anti-hTERT antibodies in serum correlated with progression to hepatocellular carcinoma. In contrast, we detected only low levels of anti-hTERT auto-antibodies in the sera derived from 18 normal volunteers. The observation of hTERT auto-antibodies in the sera derived from cancer patients suggests that such auto-antibodies constitute novel and specific tumor marker.
UI - 11998568
AU - Motohara T; Semelka RC; Nagase L
TI - MR imaging of benign hepatic tumors.
SO - Magn Reson Imaging Clin N Am 2002 Feb;10(1):1-14
AD - Department of Radiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
Use of a state-of-the-art pattern recognition approach and the combination of various MR sequences and contrast enhancement techniques makes it possible to diagnose most benign hepatic tumors with confidence.
UI - 11998574
AU - Hussain SM; Semelka RC; Mitchell DG
TI - MR imaging of hepatocellular carcinoma.
SO - Magn Reson Imaging Clin N Am 2002 Feb;10(1):31-52, v
AD - Department of Radiology, Erasmus University Medical Center, Rotterdam, The Netherlands. email@example.com
In this article, MR imaging features of hepatocellular carcinoma (HCC) are described. To better understand the MR imaging features of HCC, recent progress regarding its etiology, treatment, carcinogenesis, histology, and gross pathology will be described. Currently, T2-weighted fast spin-echo with fat saturation, and multiphasic dynamic gadolinium-enhanced two-dimensional and three-dimensional T1-weighted gradient echo imaging provides excellent results for detection and characterization of HCC.
UI - 11998575
AU - Braga L; Semelka RC; Pedro MS; de Barros N
TI - Post-treatment malignant liver lesions. MR imaging.
SO - Magn Reson Imaging Clin N Am 2002 Feb;10(1):53-73
AD - Department of Radiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
MR imaging is very accurate in the diagnosis and staging of tumors and in surgical planning. MR imaging is also an excellent method for evaluation of the liver after surgical resection, systemic or local tumor therapies, and liver transplantation. It permits early recognition of complications and the presence of recurrent tumor, providing an opportunity to repeat treatment or use alternative treatment. Surgical resection remains the standard therapy for treating liver metastases. The relatively small number of patients who are candidates for curative resection have provided impetus for the implementation and improvement of other techniques. The variety of techniques and the sensitivity for contrast enhancement have made MR imaging an ideal method to follow the response of tumors to various treatment approaches. The appearance of tumor recurrence and the response to treatment are relatively consistently shown on MR images; however, the time course of change in lesion appearance has not been fully elucidated, particularly in the setting of chemotherapy. Evaluating the response to chemotherapy is rendered complex because of the longer duration of the therapy, the types of response that various chemotherapeutic agents engender, the method of action of this therapy and the time of imaging in relation to therapy. The various local therapies share some general principles of action, and many have similar MR imaging findings. Some local therapies are effective only with certain malignancies (e.g., alcohol therapy and HCC), whereas other therapies are more limited because of the size of the tumor kill zone (e.g., interstitial laser therapy). We are in the early stages of using MR imaging to guide local therapies and to monitor response during treatment in real time. This appears to be an important future direction for MR imaging. The role of MR imaging in liver transplantation involves pre- and postoperative investigation of both donors (in the case of living-related transplantation) and recipients. These issues are described further in the section on MR imaging of liver transplantation.
UI - 12149612
AU - Thorgeirsson SS; Grisham JW
TI - Molecular pathogenesis of human hepatocellular carcinoma.
SO - Nat Genet 2002 Aug;31(4):339-46
AD - Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. firstname.lastname@example.org
Hepatocarcinogenesis is a slow process during which genomic changes progressively alter the hepatocellular phenotype to produce cellular intermediates that evolve into hepatocellular carcinoma. During the long preneoplastic stage, in which the liver is often the site of chronic hepatitis, cirrhosis, or both, hepatocyte cycling is accelerated by upregulation of mitogenic pathways, in part through epigenetic mechanisms. This leads to the production of monoclonal populations of aberrant and dysplastic hepatocytes that have telomere erosion and telomerase re-expression, sometimes microsatellite instability, and occasionally structural aberrations in genes and chromosomes. Development of dysplastic hepatocytes in foci and nodules and emergence of hepatocellular carcinoma are associated with the accumulation of irreversible structural alterations in genes and chromosomes, but the genomic basis of the malignant phenotype is heterogeneous. The malignant hepatocyte phenotype may be produced by the disruption of a number of genes that function in different regulatory pathways, producing several molecular variants of hepatocellular carcinoma. New strategies should enable these variants to be characterized.
UI - 9672372
AU - Tanaka K; Shibuya A; Naitoh M; Komatsu T; Amaki S; Shibata M; Miyakawa H
TI - Hepatocellular carcinoma arising from primary biliary cirrhosis in Japan.
SO - Am J Gastroenterol 1998 Jul;93(7):1190-1
UI - 9695391
AU - Dhir V; Mohandas KM
TI - Epidemiology of digestive tract cancers in India. III. Liver.
SO - Indian J Gastroenterol 1998 Jul-Sep;17(3):100-3
AD - Division of Digestive Diseases and Clinical Nutrition, Tata Memorial Hospital, Mumbai.
Liver cancer or hepatocellular carcinoma (HCC) is the fourth commonest cause of cancer deaths in the world. The condition is extremely common in Southeast Asia and Africa. In this report the available data on the epidemiology of HCC from India are summarized. We estimate that 12,750 new patients will be diagnosed to have HCC in India in the year 2001; this will comprise 1.6% of all incident cancers. Published studies from India and those involving Indian immigrants to other countries suggest that the prevalence of HCC is relatively lower in Indians than in most parts of the world. This contrasts with the widespread contamination of foods with aflatoxin and the moderately high prevalence of hepatitis B (HBV) and hepatitis C (HCV) virus-related chronic liver disease in India. There are no studies available to explain this observation. There are several articles on HBV and HCC in India but there is a paucity of analytical epidemiological data on HCV and HCC from India. Published studies indicate HBV to be the single most important etiologic association, with HCV playing a lesser but important role. About 80% of Indian patients with HCC have hepatitis virus-associated liver disease. Multicenter epidemiological studies are needed to solve some of the enigmas and observations peculiar to India.
UI - 10903620
AU - Morales KH; Ryan L; Kuo TL; Wu MM; Chen CJ
TI - Risk of internal cancers from arsenic in drinking water.
SO - Environ Health Perspect 2000 Jul;108(7):655-61
AD - Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA.
The U.S. Environmental Protection Agency is under a congressional mandate to revise its current standard for arsenic in drinking water. We present a risk assessment for cancers of the bladder, liver, and lung from exposure to arsenic in water, based on data from 42 villages in an arseniasis-endemic region of Taiwan. We calculate excess lifetime risk estimates for several variations of the generalized linear model and for the multistage-Weibull model. Risk estimates are sensitive to the model choice, to whether or not a comparison population is used to define the unexposed disease mortality rates, and to whether the comparison population is all of Taiwan or just the southwestern region. Some factors that may affect risk could not be evaluated quantitatively: the ecologic nature of the data, the nutritional status of the study population, and the dietary intake of arsenic. Despite all of these sources of uncertainty, however, our analysis suggests that the current standard of 50 microg/L is associated with a substantial increased risk of cancer and is not sufficiently protective of public health.
UI - 11283811
AU - Cacoub P; Geffray L; Rosenthal E; Perronne C; Veyssier P; Raguin G;
TI - Joint Study Group on Hepatitis C Virus of the French National Society of Internal Medicine and the French Society of Infectious Diseases (GERMVIC Study Group) Mortality among human immunodeficiency virus-infected patients with cirrhosis or hepatocellular carcinoma due to hepatitis C virus in French Departments of Internal Medicine/Infectious Diseases, in 1995 and 1997.
SO - Clin Infect Dis 2001 Apr 15;32(8):1207-14
AD - Dept of Internal Medicine, Hopital La Pitie-Salpetriere, Paris, France. email@example.com
Several studies have suggested that the progression of hepatitis C virus (HCV) infection is more severe in patients infected by the human immunodeficiency virus (HIV). Two national retrospective multicenter cohort surveys were performed in France that included 17,487 HIV-infected patients during 1995 and 26,497 during 1997. The following data was evaluated: total number of deaths; number of deaths linked to AIDS, cirrhosis, or hepatocellular carcinoma (HCC); and number of deaths related to other (non-HCV--linked) causes. In 1995, the causes of death were as follows: AIDS, 1307 (7.47%); cirrhosis or HCC, 21 (0.12%); and other (non-HCV--linked) causes, 99 (0.56%). In 1997, the causes of deaths were as follows: AIDS, 459 (1.73%); cirrhosis or HCC 36 (0.13%); and other (non-HCV--linked) causes, 48 (0.18%). Comparative results between the 1995 and 1997 surveys showed a dramatic decrease in AIDS-related mortality rates (7.47% vs. 1.73%; P<.001) but not in HCV-related mortality rates (0.06% vs. 0.07%; P=.79). In France, despite the high prevalence of HCV infection in HIV-positive patients, the mortality rate in 1995 and 1997 caused by HCV-related cirrhosis or HCC was low.
UI - 11554170
AU - Vega F; Medeiros LJ; Bueso-Ramos C; Jones D; Lai R; Luthra R; Abruzzo LV
TI - Hepatosplenic gamma/delta T-cell lymphoma in bone marrow. A sinusoidal neoplasm with blastic cytologic features.
SO - Am J Clin Pathol 2001 Sep;116(3):410-9
AD - Dept of Hematopathology, Box 72, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
We report 8 cases of hepatosplenic T-cell lymphoma (HSTCL) involving bone marrow and correlate histologic findings with disease progression. Immunophenotypic analysis demonstrated mature, aberrant gamma/delta T-cell immunophenotypes. Isochromosome 7q was identified in 4 cases; 1 case showed the t(7;14)(q34;q13). Seven of 7 cases tested had monoclonal TCR gamma gene rearrangements. The initial diagnostic bone marrow biopsy specimens were hypercellular with a frequently subtle, predominantly sinusoidal infiltrate of atypical small to medium-sized lymphoid cells. In all cases, aspirate smears at diagnosis and in subsequent specimens contained malignant cells that resembled blasts, some with fine cytoplasmic granules. With progression, the pattern of HSTCL in bone marrow biopsy specimens became increasingly interstitial, and the neoplastic cells became larger. In aspirate smears, the proportion of blasts increased. Seven patients died; 1 was lost to follow-up. Autopsy performed on 1 patient demonstrated malignant cells within vascular channels in all organs sampled, with relatively little tumor formation, resembling intravascular lymphoma at these sites. HSTCL often can be recognized in bone marrow by its unique combination of a sinusoidal pattern in core biopsy specimens and blastic cytology in aspirate smears.
UI - 11933585
AU - Mortele KJ; Ros PR
TI - Benign liver neoplasms.
SO - Clin Liver Dis 2002 Feb;6(1):119-45
AD - Department of Radiology, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. firstname.lastname@example.org
A variety of benign focal liver lesions are easily characterized with currently available imaging techniques and contrast agents. The most common benign liver lesions, such as hemangioma, bile duct cyst, and FNH, reveal characteristic cross-sectional imaging features that allow an accurate diagnosis. For atypical variants and more uncommon lesions, including HCA, angiomyelioma, infantile hemagioendothelioma, and mesenchymal hamartoma, integration of clinical data can often help in the interpretation of imaging studies. Finally, for the remaining lesions, such as hepatic adenomatosis, the imaging findings may not be specific enough to negate the need for a tissue biopsy.
UI - 11933586
AU - Levy AD
TI - Malignant liver tumors.
SO - Clin Liver Dis 2002 Feb;6(1):147-64
AD - Department of Radiologic Pathology, Armed Forces Institute of Pathology, Washington, DC, USA. email@example.com
The primary hepatic malignancies are a diverse group of neoplasms with distinctive clinical and pathologic features. Imaging of the primary hepatic malignancies continues to be challenging. Ultrasonography, CT scanning, and MR imaging play complementary roles in the evaluation of these patients. Many [figure: see text] of these neoplasms have distinctive imaging features that may permit diagnosis. In most instances, however, biopsy is required for definitive diagnosis and treatment planning.
UI - 12015043
AU - Liang P; Dong B; Yu A; Cao B; Yu X; Yu D; Su L
TI - [Ultrasonography in the diagnosis of hepatic malignant cystic tumors]
SO - Zhonghua Zhong Liu Za Zhi 2002 Mar;24(2):178-80
AD - Department of Ultrasound, PLA General Hospital, Beijing 100853, China.
OBJECTIVE: To evaluate the clinical application of gray scale and color Doppler sonography in the diagnosis of hepatic malignant cystic tumors. METHODS: Characteristics of gray scale and color Doppler sonography were studied in 16 cases of malignant hepatic tumors confirmed by pathology. Tumor size, shape, number of lesion, thickness of cystic wall and echogenecity of the lesion were observed with gray scale sonography. Blood supply of the tumor and its velocity were observed with Color Doppler sonography. RESULTS: One single lesion was common in primary malignancy while multiple lesions signified metastasis. Sonographic findings revealed that the shape of the tumor was spheroid in 8 cases, irregular in 5 and leaf-shaped in 3, with the diameter varying from 1.9 cm to 13.6 cm. Sonography showed malignant cystic tumor with irregular thick wall in 15 cases, multiple septa in 7 cases and papillary projections in 6 on gray scale. Color Doppler flow signal was detected in the irregular thick wall, multiple septa or papillary projections in 14 cases, of which the arterial blood flow signals were demonstrated in 13. CONCLUSION: Color Doppler is able to clearly detect the blood flow signals in the irregular thick wall, multiple septa or papillary projections, providing an important sign for the diagnosis of hepatic malignant cystic tumors.
UI - 12117890
AU - Tannapfel A; Busse C; Geissler F; Witzigmann H; Hauss J; Wittekind C
TI - INK4a-ARF alterations in liver cell adenoma.
SO - Gut 2002 Aug;51(2):253-8
AD - Institute of Pathology, University of Leipzig, Liebigstr 26, 04103 Leipzig, Germany. firstname.lastname@example.org
BACKGROUND: The INK4a-ARF (CDKN2A) locus on chromosome 9p21 encodes two tumour suppressor proteins, p16(INK4a) and p14(ARF), whose functions are inactivated in many human cancers. AIMS: To evaluate p14(ARF) and p16(INK4a) alterations in liver cell adenoma. METHODS: After microdissection, DNA from 25 liver cell adenomas and corresponding normal liver tissue were analysed for INK4-ARF inactivation by DNA sequence analysis, methylation specific polymerase chain reaction, restriction enzyme related-polymerase chain reaction (RE-PCR), mRNA expression, microsatellite analysis, and immunohistochemistry. In addition, microdeletion of p14(ARF) and p16(INK4a) were assessed by differential PCR. RESULTS: Methylation of p14(ARF) was found in 3/25 cases (12%) and alterations in p16(INK4a) occurred in 6/25 liver cell adenomas (24%) which correlated with loss of mRNA transcription. We failed to detect microdeletions or specific mutations of both exons. p16(INK4a) methylation appeared in the context of an unmethylated p14(ARF) promoter in six cases. In normal liver tissue, p14(ARF) or p16(INK4a) alterations were not observed. CONCLUSIONS: Our data suggest that p14(ARF) methylation occurs independently of p16(INK4a) alterations in liver cell adenomas. Furthermore, methylation of p14(ARF) and p16(INK4a) may be a result of cell cycle deregulation and does not seem to be a prerequisite of malignancy.
UI - 12133332
AU - Zhao W; Ma Z; Zhou X; Feng Y; Fang B
TI - [Prognostic value of CLIP score system for patients with resection of hepatocellular carcinoma]
SO - Zhonghua Wai Ke Za Zhi 2002 May;40(5):321-5
AD - Department of Oncosurgery, First Affiliated Hospital, Medical College, Zhejiang University, Hangzhou 310003, China.
OBJECTIVE: To evaluate the prognostic value of CLIP score system for patients with resection of HCC. METHODS: A retrospective survey was carried out in 174 patients undergoing resection of HCC from January followed up for at least three years. Disease-free survival rate was defined as the time relapsed from the date of image diagnosis and either the date of death or the date of the latest follow-up visit, with final evaluation at June 30, 2001. Recurrences were classified into early (= 3 year) and late (> 3 year) recurrence. Risk factors for recurrences and prognostic factors for survival in each group were analyzed by the chi-square test, the Kalain-Meier estimation and the COX proportional hazards model respectively. RESULTS: The 1-, 3-, 5-, 7-, and 10-year cumulative disease free survival rates were 57.2%, 28.3%, 23.5%, 18.8% and 17.8%, respectively. The associated factors with early recurrence were as fellows: tumor size > 5 cm, microsatellite, venous invasion, tumor morphology, tumor extension, advanced TNM stages, CLIP scores, radical resection, and resection margin, respectively. But both CLIP scores and Child stage were associated with late recurrence. Univariate survival curves analysis expressed that Child grades, radical resection, resection margin, tumor size, microsatellite, venous invasion, tumor morphology, tumor extension, TNM stages, and CLIP scores were associated with prognosis. The multivariate analysis by COX proportional hazards model, the independent prognostic factors for survival were radical resection, resection margin, and TNM stages. CONCLUSIONS: CLIP score, which takes into account both liver function and tumor extension, has displayed a unique superiority in predicting the tumor early and late recurrence and prognosis. It could be an useful tool in predicting the patient recurrence and prognosis with resection of HCC. Meanwhile, it may help physicians to decide the more appropriate management in advance for patients with HCC.
UI - 12133336
AU - Yin X; Lu M; Liang L; Lai Y; Huang J; Li Z
TI - [Infiltration of dendritic cells and lymphocytes in hepatocellular carcinoma tissue]
SO - Zhonghua Wai Ke Za Zhi 2002 May;40(5):336-43
AD - Department of Hepatobiliary Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China. email@example.com
OBJECTIVE: To explore the clinical significances of dendritic cells and lymphocytes infiltration in hepatocellular carcinoma (HCC) tissue. METHODS: Clinicopathological data were collected from 44 patients with HCC who had under/gone curative tumor resection in our hospital. Immunohistochemical staining was used to detect the infiltration of dendritic cells in the tumor tissue, and lymphocytes infiltration was assessed simultaneously. The correlation between the infiltration of dendritic cells and lymphocytes and postoperative tumor recurrence and survival rate was analyzed. RESULTS: Tumor recurrence was markedly late in patients with dendritic cells count >/= 20 and positive lymphocytes infiltration (group A, n = 17) as compared with those who did not meet both criteria simultaneously (group B, n = 27), with a median interval of 21.6 months for group A and 4.1 months for group B (U value = 105.5, P = 0.009). The 1-, 3-, 4-year survival rates were significantly greater in group A than in group B; they were 83.5% vs. 42.2%, 61.8% vs. 28.4% and 48.7% vs. 23.0%, respectively (Log rank = 7.68, P < 0.01). CONCLUSION: The infiltration of dendritic cells and lymphocytes in HCC tissue, as an independent prognostic factor, was closely related to postoperative prognosis.
UI - 12150730
AU - Lu J; Leng X; Peng J; Mou D; Pang X; Shang X; Chen W
TI - Induction of cytotoxic T lymphocytes from the peripheral blood of a hepatocellular carcinoma patient using melanoma antigen-1 (MAGE-1) peptide.
SO - Chin Med J (Engl) 2002 Jul;115(7):1002-5
AD - Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing 100044, China.
OBJECTIVE: To investigate the possibility of using melanoma antigen-1 (MAGE-1) peptide as a tumor vaccine to treat hepatocellular carcinoma (HCC). METHODS: The expressions of MAGE-1 in 8 HCC cell lines and in liver cancer tissue from a patient were detected using RT-PCR. The type of human leucocyte antigen I(HLA I) of both 8 HCC cell lines and peripheral blood mononuclear cells of the patient was detected using a microcytotoxicity method to screen out target cell lines for the cytotoxicity assay. Peripheral blood mononuclear cells from the HCC patient pulsed with an MAGE-1 peptide (NYKCRFPEI) were used as antigen presenting cells. Autogenous peripheral blood mononuclear cells were stimulated with antigen presenting cells every 7 days for 4 times to elicit cytotoxic T lymphocytes. The phenotype of effector cells was analyzed using flow cytometry. The cytotoxicity of effector cells was detected with a lactate dehydrogenase releasing assay. RESULTS: The expressions of both MAGE-1 and HLA-A24 were detected in BEL7405 cell line which were used as the positive target cell line in the cytotoxicity assay. The expression of MAGE-1 alone was detected in HLE, BEL7402, BEL7404, QGY7703 and SMMC7721 cell lines, and the expression of neither MAGE-1 nor HLA-A24 was shown in QGY 7701 and HpG2 cell lines. The last 7 cell lines could be used as negative target cell lines in the cytotoxicity assay. Peripheral blood mononuclear cells expanded 32 folds during 28-day culture. The ratio of CD3(+) T cells increased by 16% (from 54% to 70%), and the ratio of CD8(+) T cells increased by 20% (from 36% to 56%) during 28-day culture. When the ratio of effector cells to target cells was 10:1, effector cells exhibited 62.5% cytotoxicity against autogenous lymphoblasts pulsed with the peptide (NYKCRFPEI) of MAGE-1 antigen, 40.25% cytotoxicity against BEL7405 cells, compared with 17.88% cytolysis observed against autogenous lymphoblasts, 19.55% against HLE cells, and 1.6% against QGY7701 cells. When the ratio of effector cells to target cells was 3.3:1, the cytotoxicity of effector cells against the peptide pulsed autogenous lymphoblasts was 53.6%, which was much higher against autogenous lymphoblasts, HLE cells and QGY7701 cells at 15.6%, 13% and 1%, respectively. CONCLUSION: The results demonstrate that cytotoxic T lymphocytes with the ability to specifically lyse target cells expressing both MAGE-1 and HLA-A24 could be successfully induced by the MAGE-1 peptide NYKCRFPEI in vitro. This indicates that a good result might be anticipated if this peptide is used as a tumor vaccine to treat HLA-A24 HCC patients.
UI - 12185056
AU - Kim SK; Kim SH; Lee WJ; Kim H; Seo JW; Choi D; Lim HK; Lee SJ; Lim JH
TI - Preoperative detection of hepatocellular carcinoma: ferumoxides-enhanced versus mangafodipir trisodium-enhanced MR imaging.
SO - AJR Am J Roentgenol 2002 Sep;179(3):741-50
AD - Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50, Ilwon-Dong, Kangnam-Ku, Seoul 135-710, Korea.
OBJECTIVE: The purpose of our study was to compare the diagnostic accuracy and lesion conspicuity of ferumoxides-enhanced MR imaging with those of mangafodipir trisodium-enhanced MR imaging for the preoperative detection of hepatocellular carcinoma. SUBJECTS AND METHODS: Twenty-one patients with 39 hepatocellular carcinomas underwent ferumoxides-enhanced and mangafodipir trisodium-enhanced MR imaging. The diagnosis was established by pathologic examination after surgical resection in all patients. Five MR sequences were obtained 30 min after ferumoxides administration, and two MR sequences were obtained before and 15 min after mangafodipir trisodium administration. Three observers independently interpreted both MR images of all sequences on a segment-by-segment basis. The diagnostic accuracy of MR imaging was assessed using receiver operating characterizing analysis. Lesion (hepatocellular carcinoma > 10 mm in diameter)-to-liver contrast-to-noise ratio was calculated on MR images. RESULTS: Ferumoxides-enhanced MR imaging (A(z) = 0.971) was significantly more accurate (p < 0.05) than mangafodipir trisodium-enhanced MR imaging (A(z) = 0.950). The mean sensitivity of ferumoxides-enhanced MR imaging (86%) was significantly greater (p < 0.05) than that of mangafodipir trisodium-enhanced MR imaging (44%) in lesions smaller than 10 mm. The mean lesion-to-liver contrast-to-noise ratio of hepatocellular carcinoma on ferumoxides-enhanced MR imaging (13.7 +/- 8.8) was significantly greater than on mangafodipir trisodium-enhanced MR imaging (5.4 +/- 5.1) (p < 0.01). CONCLUSION: Ferumoxides-enhanced MR imaging has superior diagnostic accuracy in lesions smaller than 10 mm and superior lesion conspicuity compared with mangafodipir trisodium-enhanced MR imaging for the preoperative detection of hepatocellular carcinoma.
UI - 12185057
AU - Ichikawa T; Kitamura T; Nakajima H; Sou H; Tsukamoto T; Ikenaga S; Araki
TI - T Hypervascular hepatocellular carcinoma: can double arterial phase imaging with multidetector CT improve tumor depiction in the cirrhotic liver?
SO - AJR Am J Roentgenol 2002 Sep;179(3):751-8
AD - Department of Radiology, Yamanashi Medical University, 1110 Shimokato, Tamaho, Nakakoma, Yamanashi 409-3815, Japan.
OBJECTIVE: We assessed the efficacy of double arterial phase CT with multidetector CT for the detection of hypervascular hepatocellular carcinoma in the cirrhotic liver. MATERIALS AND METHODS: Double arterial phase images with multidetector CT were evaluated using quantitative, qualitative, and receiver operating characteristic analyses for 59 patients with 78 hepatocellular carcinomas. Early and late arterial phase (double arterial phase) CT scans were obtained at a fixed time of 25 and 40 sec, respectively, after administration of contrast material. Total dose and injection rate of contrast material were 100 mL and 3 mL/sec, respectively. RESULTS: On the basis of the receiver operating characteristic curves, the mean area under the curve values of the late (0.98) and combined arterial phase CT scans (0.98) were equivalent, and both were significantly greater than the mean of the early arterial phase CT scans (0.842) for detecting hepatocellular carcinoma (p < 0.05). The mean relative sensitivity values obtained with the late (69/78, 88%) and combined arterial phase CT scans (70/78, 90%) were also equivalent and were significantly greater than those obtained with the early arterial phase CT scans (52/78, 67%; p < 0.001). CONCLUSION: Double arterial phase CT with multidetector CT showed no significant improvement in effectiveness compared with single late arterial phase CT used alone for detecting hypervascular hepatocellular carcinoma in the cirrhotic liver.
UI - 12154039
AU - Yeh SH; Chang CF; Shau WY; Chen YW; Hsu HC; Lee PH; Chen DS; Chen PJ
TI - Dominance of functional androgen receptor allele with longer CAG repeat in hepatitis B virus-related female hepatocarcinogenesis.
SO - Cancer Res 2002 Aug 1;62(15):4346-51
AD - Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
The CAG polymorphism in exon 1 of the androgen receptor (AR) gene has been shown associated with the development of human male hepatocellular carcinoma (HCC) with the shorter AR alleles conferring a higher risk. However, the significance of AR-CAG repeats in female hepatocarcinogenesis remains to be addressed. In this study, seventy-six pairs of female HCCs and corresponding nontumorous tissues were collected, and 180 cirrhotic nodules were microdissected from 7 cirrhotic livers. The clonality status, functional AR alleles, and CAG repeat number of each sample were determined by AR methylation analysis. In a total of 44 monoclonal HCCs, the mean of CAG repeats in the active alleles was significantly longer than that in the inactive alleles (22.0 +/- 2.8 versus 20.7 +/- 3.6; P = 0.047). When we divided HCCs into hepatitis B virus-positive [HBV(+)] and HBV(-) subgroups, the long AR allele dominance was found only in HBV(+) ones (P = 0.006 versus P = 0.923). Notably, the preference of long CAG repeat has also been found in the 100 monoclonal nodules (P = 0.013). For comparison of monoclonal nodules obtained from the same individual, a dominant long AR allele was found in 6 patients. The proportion of monoclonal cirrhotic nodules and HCCs expressing longer AR allele, 69 and 68%, are both significantly higher than 50%, the assumed value in normal liver (P < 0.001 for cirrhotic nodules and P = 0.005 for HCC). The dominance is again only prominent in HBV-infected HCCs [85% for HBV(+) HCC; P < 0.001 but 54% for HBV(-) HCC; P = 0.27]. The results indicated that in female hepatocarcinogenesis, hepatocytes expressing the longer AR allele seem to be favorably selected for autonomous growth and transformation, especially in synergy with HBV infection.
UI - 12174931
AU - Ito Y; Miyoshi E; Takeda T; Nagano H; Sakon M; Noda K; Tsujimoto M;
TI - Monden M; Matsuura N Linkage of elevated ets-2 expression to hepatocarcinogenesis.
SO - Anticancer Res 2002 Jul-Aug;22(4):2385-9
AD - Department of Surgery, Kuma Hospital, Kobe, Japan. firstname.lastname@example.org
BACKGROUND: Previous studies have shown that ets-2, a transcription factor, is linked to carcinoma progression. In the present study, we investigated the expression and clinical significance of ets-2 in hepatocellular carcinoma (HCC) and malignant transformation of the liver. MATERIALS AND METHODS: The expression of ets-2 was immunohistochemically investigated with 91 HCC, 46 noncancerous lesions, 8 atypical adenomatous hyperplasias and 14 normal liver controls. RESULTS: The ets-2 labeling index (LI) in normal liver was significantly lower than in noncancerous lesion (p<0.0001). The LI in atypical adenomatous hyperplasia tended to be higher than in noncancerous lesion (p=.0779). In HCC, the LI was significantly lower (p<0.0001) than that in noncancerous lesion and atypical adenomatous hyperplasia. In HCC, the ets-2 expression level was significantly lower in cases with advanced stage (p=0.0085), large size (p=0.0441), high proliferating activity (p<0.0001), poor differentiation (p=0.0005), the presence of portal invasion (p=0.0009) and intrahepatic metastasis (p=0.0236) and shorter disease-free survival (p=0.0372). CONCLUSION: These findings suggest that ets-2 plays an important role predominantly in malignant transformation of the liver.
UI - 12000592
AU - Omata M; Dan Y; Daniele B; Plentz R; Rudolph KL; Manns M; Piratvisuth T;
TI - Chen DS; Tateishi R; Chutaputti A Clinical features, etiology, and survival of hepatocellular carcinoma among different countries.
SO - J Gastroenterol Hepatol 2002 Feb;17 Suppl():S40-9
AD - Department of Gastroenterology, University of Tokyo Graduate School of Medicine, Japan. OMATAemail@example.com
UI - 12008038
AU - Holub MC; Hegyesi H; Igaz P; Polgar A; Toth S; Falus A
TI - Soluble interleukin-6 receptor enhanced by oncostatin M induces major changes in gene expression profile of human hepatoma cells.
SO - Immunol Lett 2002 Jun 3;82(1-2):79-84
AD - Department of Genetics, Cell- and Immunobiology, Semmelweis University of Medicine, Budapest, Hungary.
Interleukin-6 (IL-6) binds to a receptor complex consisting of an 80 kDa binding unit (IL-6R) and gp130 responsible for signal transduction. Due to alternative splicing and/or proteolytic digestion IL-6R occurs in soluble form (sIL-6R), as well. Soluble IL-6R is able to bind to gp130 expressing on nucleated cells, thus sIL-6R makes most cells responsive to IL-6. In this study we found that oncostatin M (OSM), an other gp130 dependent cytokine with proliferation inhibitory potential, increases the expression of both membrane-bound IL-6R and sIL-6R generated by alternative splicing in hepatic and mammary carcinoma cell lines. Furthermore, we studied the functional relevance of the presence and binding of soluble IL-6R to HepG2 cells. Using a cDNA expression array, mRNA levels of about 580 human genes were tested by differential display analysis. Our findings suggest, that elevation of surface density of IL-6R by attachment of sIL-6R induces major modulation in gene expression profile of the hepatoma cells. Soluble IL-6R alone has minor effect, it rather decreases expression of some genes, while incubation with IL-6 and sIL-6R together induces major changes in the mRNA pattern of HepG2 cells. These data strongly suggest that presence and binding of soluble cytokine receptors are important elements of inter-cytokine cross talk and affects actual gene expression profile of responding cells.
UI - 12053775
AU - Mejia-Arangure JM; Beutelspacher-Vazquez O; Juarez-Ocana S;
TI - Vazquez-Langle J; Martinez-Garcia Mdel C; Fajardo-Gutierrez A [Trends in the incidence of hepatic tumors in childhood]
SO - Salud Publica Mex 2002 Mar-Apr;44(2):100-7
AD - Unidad de Investigacion Medica en Epidemiologia Clinica, Hospital de Pediatria, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico, D.F., Mexico. firstname.lastname@example.org
OBJECTIVE: To evaluate the incidence trends of hepatic tumors among children living in Mexico City. MATERIAL AND METHODS: A cross-sectional hospital survey was conducted to yield two databases. The first database contains the registry of all the cases of hepatic tumors occurring during the period 1982-1991, in public hospitals of Mexico City. The second database contains all hepatic tumor cases found between 1996 and 1999 in Hospital de Pediatria del Centro Medico Nacional "Siglo XXI" and in Hospital General del Centro Medico La Raza, both hospitals pertaining to Instituto Mexicano del Seguro Social (Mexican Institute of Social Security). The average annual incidence rates (AAIR) were calculated for each type of hepatic tumor. The rates were standardized with the direct method, using as standard the world population under 15 years of age. The trends were evaluated with the annual incidence rates and the average rate of change assuming a Poisson distribution. RESULTS: The AAIR for hepatoblastoma during the period 1982-1991 was three times higher for men than for women, with a value of 0.6 x 10(6). The group of 1-4 years of age was the most affected. For hepatocarcinomas the AAIR was two-fold for women (0.14) as compared to men. Between 1996-1999 the AAIR for hepatoblastoma was 5.11 in women and 1.85 in men. The age group with the highest rate was women under one year of age. The AAIR for hepatocarcinoma was 0.64 for males and 1.23 for females. The most affected age group was males aged 10 to 14 years. No significant upward or downward trend was found in the incidence of hepatoblastomas. A non-significant change rate of 10% was found for hepatocarcinoma. CONCLUSIONS: No significant trends were observed in the incidence of hepatic tumors in children of Mexico City aged under 15 years, during the periods 1982-1991 and 1996-1999. The English version of this paper is available at: http://www.insp.mx/salud/index.html.
UI - 12048165
AU - Chang J; Kim NG; Piao Z; Park C; Park KS; Paik YK; Lee WJ; Kim BR; Kim H
TI - Assessment of chromosomal losses and gains in hepatocellular carcinoma.
SO - Cancer Lett 2002 Aug 28;182(2):193-202
AD - Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
We examined the chromosomal changes of 22 hepatocellular carcinomas (HCCs) by comparative genomic hybridization (CGH) analysis and compared the results with that of allelotype by polymerase chain reaction based loss of heterozygosity (PCR-LOH) analysis. By CGH analysis, frequent chromosomal losses were noted in the chromosomal region of 4q (59%), 8p (77%), and 16q (50%), whereas gains were noted in 1q (86%) and 8q (77%). All of these chromosomal arms were revealed to have frequent allelic imbalances by PCR-LOH analysis, however, 9% of chromosomal aberrations were detected only by CGH analysis and 2% were detected only by PCR-LOH analysis. Our results suggest that CGH analysis gives more precise results for the screening of chromosomal aberrations in HCCs than that of PCR-LOH analysis with randomly selected microsatellite markers.
UI - 12188451
AU - Rerknimitr R; Attasaranya S; Kladchareon N; Mahachai V; Kullavanijaya P
TI - Feasibility and complications of endoscopic biliary drainage in patients with malignant biliary obstruction at King Chulalongkorn Memorial Hospital.
SO - J Med Assoc Thai 2002 Jun;85 Suppl 1():S48-53
AD - Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Currently the best curative therapy for primary malignant biliary tumor is surgery. Unfortunately, many patients present at a very late stage and only