• breast cancer
• etiology
• risk factors
• second primary cancer
• thyroid cancer
• treatment

• S100P
• cell migration
• metastasis
• microtubule
• peptides
• tubulin

• Animals
• COS Cells
• Calcium-Binding Proteins/biosynthesis
• Calcium-Binding Proteins/chemistry
• Calcium-Binding Proteins/genetics
• Cell Adhesion/physiology
• Cell Movement/physiology
• Chlorocebus aethiops
• HeLa Cells
• Humans
• Neoplasm Proteins/biosynthesis
• Neoplasm Proteins/chemistry
• Neoplasm Proteins/genetics
• Protein Binding/physiology
• Protein Structure, Secondary
• Tubulin/biosynthesis
• Tubulin/chemistry
• Tubulin/genetics

• G0801447 Medical Research Council

Esophageal cancer is one of the most common malignant tumors of the digestive system, and China has the highest morbidity and mortality rates of esophageal cancer in the world. Currently, main therapies for esophageal cancer include endoscopy, surgery, chemotherapy, and radiotherapy. These traditional treatments have appreciated clinical effects, but the prognosis of this malignancy is still poor. There is accumulating evidence that tumor immune microenvironment plays a key role in the development and progression of esophageal cancer. Recent clinical investigations and ongoing studies indicate that immunotherapy might have a great potential in the treatment of patients with esophageal cancer. Future studies will identify treatment strategies that can maximize therapeutic benefits by combining immunotherapies with existing and novel treatment modalities.

• Esophageal cancer
• Tumor immune microenvironment
• Immunotherapy

AIM: To evaluate the efficacy of telomerase activity assay and peritoneal lavage cytology (PLC) examination in peritoneal lavage fluid for the prediction of peritoneal metastasis in gastric cancer patients, and to explore the relationship between telomerase activity and proliferating cell nuclear antigen expression.

METHODS: Telomeric repeated amplification protocol (TRAP)-enzyme-linked immunosorbent assay (ELISA) was performed to measure the telomerase activity in 60 patients with gastric cancer and 50 with peptic ulcer. PLC analysis of the 60 patients with gastric cancer was used for comparison. The proliferating cell nuclear antigen (PCNA) in gastric carcinoma was immunohistochemically examined.

RESULTS: The telomerase activity and PLC positive rate in peritoneal lavage fluid from patients with gastric cancer was 41.7% (25/60), and 25.0% (15/60), respectively. The positive rate of telomerase activity was significantly higher than that of PLC in the group of pT₄ (15/16 vs 9/16, P < 0.05), P_1-3 (13/13 vs 9/13, P < 0.05) and diffuse type (22/42 vs 13/42, P < 0.05). The patients with positive telomerase activity, peritoneal metastasis, and serosal invasion had significantly higher levels of average PCNA proliferation index (PI), (55.00 ± 6.59 vs 27.43 ± 7.72, 57.26 ± 10.18 vs 29.15 ± 8.31, and 49.82 ± 6.74 vs 24.65 ± 7.33, respectively, P < 0.05).

CONCLUSION: The TRAP assay for telomerase activity is a useful adjunct for cytologic method in the diagnosis of peritoneal micrometastasis and well related to higher proliferating activity of gastric cancer. The results of this study also suggest a promising future therapeutic strategy for treating peritoneal dissemination based on telomerase inhibition.

• Gastric cancer
• Telomerase activity
• Peritoneal lavage cytology
• Peritoneal metastasis
• Proliferating cell nuclear antigen

• Adenocarcinoma/diagnosis
• Adenocarcinoma/enzymology
• Adenocarcinoma/secondary
• Adult
• Aged
• Ascitic Fluid/enzymology
• Biomarkers, Tumor/metabolism
• Cell Proliferation
• Enzyme-Linked Immunosorbent Assay
• Female
• Humans
• Immunohistochemistry
• Male
• Middle Aged
• Nucleic Acid Amplification Techniques
• Peptic Ulcer/enzymology
• Peritoneal Lavage/methods
• Peritoneal Neoplasms/diagnosis
• Peritoneal Neoplasms/enzymology
• Peritoneal Neoplasms/secondary
• Predictive Value of Tests
• Proliferating Cell Nuclear Antigen/metabolism
• Stomach Neoplasms/enzymology
• Stomach Neoplasms/pathology
• Telomerase/analysis
• Telomerase/metabolism

AIM: To explore the capability of a monoclonal antibody (mAb) against murine endoglin to inhibit tumor angiogenesis and suppression of hepatoma growth in murine models.

METHODS: A monoclonal antibody against murine endoglin was purified by affinity chromatography and passively transfused through tail veins in two murine hepatoma models. Tumor volume and survival time were observed at three-day intervals for 48 d. Microvessels in tumor tissues were detected by immunohistochemistry against CD31, and angiogenesis in vivo was determined by alginate encapsulated assay. In addition, tumor cell apoptosis was detected by TUNEL assay.

RESULTS: Passive immunotherapy with anti-endoglin mAb could effectively suppress tumor growth, and prolonged the survival time of hepatoma-bearing mice. Angiogenesis was apparently inhibited within the tumor tissues, and the vascularization of alginate beads was also reduced in the mice passively transfused with anti-endoglin mAb. In addition, increased apoptotic cells were observed within the tumor tissues from the mice passively transfused with anti-endoglin mAb.

CONCLUSION: Passive immunotherapy with anti-endoglin mAb effectively inhibits tumor growth via inhibiting tumor angiogenesis and increasing tumor cell apoptosis, which may be highly correlated with the blockage of endoglin-related signal pathway induced by anti-endoglin mAb.

• Monoclonal antibody
• Endoglin
• Passive immunotherapy
• Tumor angiogenesis
• Apoptosis

• Alginates
• Animals
• Antibodies, Monoclonal/immunology
• Antibodies, Monoclonal/therapeutic use
• Apoptosis/drug effects
• Cell Line, Tumor
• Disease Models, Animal
• Endoglin
• Glucuronic Acid
• Hexuronic Acids
• Immunization, Passive/methods
• Intracellular Signaling Peptides and Proteins/immunology
• Liver Neoplasms, Experimental/blood supply
• Liver Neoplasms, Experimental/drug therapy
• Liver Neoplasms, Experimental/immunology
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Nude
• Microspheres
• Neovascularization, Pathologic/drug therapy
• Random Allocation
• Signal Transduction/drug effects
• Survival Rate

AIM: To examine the presence of human papillomavirus (HPV) in esophageal squamous cell carcinoma (ESCC) specimens collected from Colombia and Chile located in the northern and southern ends of the continent, respectively.

METHODS: We examined 47 and 26 formalin-fixed and paraffin-embedded ESCC specimens from Colombia and Chile, respectively. HPV was detected using GP5+/GP6+ primer pair for PCR, and confirmed by Southern blot analysis. Sequencing analysis of L1 region fragment was used to identify HPV genotype. In addition, P16^INK4A protein immunostaining of all the specimens was conducted.

RESULTS: HPV was detected in 21 ESCC specimens (29%). Sequencing analysis of L1 region fragment identified HPV-16 genome in 6 Colombian cases (13%) and in 5 Chilean cases (19%). HPV-18 was detected in 10 cases (21%) in Colombia but not in any Chilean case. Since Chilean ESCC cases had a higher prevalence of HPV-16 (without statistical significance), but a significantly lower prevalence of HPV-18 than in Colombian cases (P = 0.011) even though the two countries have similar ESCC incidence rates, the frequency of HPV-related ESCC may not be strongly affected by risk factors affecting the incidence of ESCC. HPV-16 genome was more frequently detected in p16 positive carcinomas, although the difference was not statistically significant. HPV-18 detection rate did not show any association with p16 expression. Well-differentiated tumors tended to have either HPV-16 or HPV-18 but the association was not statistically significant. HPV genotypes other than HPV-16 or 18 were not detected in either country.

CONCLUSION: HPV-16 and HPV-18 genotypes can be found in ESCC specimens collected from two South American countries. Further studies on the relationship between HPV-16 presence and p16 expression in ESCC would aid understanding of the mechanism underlying the presence of HPV in ESCC.

• Human papillomavirus
• Esophageal squamous cell cancer
• Colombia
• Chile

• Aged
• Aged, 80 and over
• Carcinoma, Squamous Cell/genetics
• Carcinoma, Squamous Cell/virology
• Chile/epidemiology
• Colombia/epidemiology
• Esophageal Neoplasms/genetics
• Esophageal Neoplasms/virology
• Female
• Gene Expression Regulation, Neoplastic
• Genes, p16
• Human papillomavirus 16/genetics
• Human papillomavirus 18/genetics
• Humans
• Male
• Middle Aged
• Papillomavirus Infections/epidemiology
• Papillomavirus Infections/genetics

• nucleoporin 88
• hepatitis b and c virus
• hepatocellular carcinogenesis

• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/mortality
• Carcinoma, Hepatocellular/pathology
• Cell Line, Tumor
• Cells, Cultured
• Gene Expression Regulation
• Gene Expression Regulation, Neoplastic/genetics
• Hepatitis B/genetics
• Hepatitis B/metabolism
• Hepatitis B/pathology
• Hepatitis B Core Antigens/genetics
• Hepatitis B Core Antigens/metabolism
• Hepatitis C/genetics
• Hepatitis C/metabolism
• Hepatitis C/pathology
• Humans
• Liver/metabolism
• Liver/pathology
• Liver Neoplasms/genetics
• Liver Neoplasms/metabolism
• Liver Neoplasms/pathology
• Nuclear Pore Complex Proteins/genetics
• Nuclear Pore Complex Proteins/metabolism

• Carcinoma, Squamous Cell/ethnology
• Carcinoma, Squamous Cell/etiology
• Carcinoma, Squamous Cell/pathology
• Diet
• Esophageal Neoplasms/ethnology
• Esophageal Neoplasms/etiology
• Esophageal Neoplasms/pathology
• Esophagus/pathology
• Exons
• Genes, p53
• Humans
• India/ethnology
• Middle Aged
• Mutation
• Risk Factors

• real-time rt-pcr
• peritoneal washes
• gastric cancer
• carcinoembryonic antigen

• Adult
• Aged
• Ascitic Fluid/chemistry
• Ascitic Fluid/pathology
• Carcinoembryonic Antigen/genetics
• Female
• Humans
• Male
• Middle Aged
• Neoplasm Metastasis
• Neoplasm Staging
• Peritoneal Lavage
• Peritoneal Neoplasms/chemistry
• Peritoneal Neoplasms/genetics
• Peritoneal Neoplasms/pathology
• RNA, Messenger/analysis
• Reverse Transcriptase Polymerase Chain Reaction
• Sensitivity and Specificity
• Stomach Neoplasms/chemistry
• Stomach Neoplasms/genetics
• Stomach Neoplasms/pathology

AIM: To explore the preliminary identification of serum protein pattern models that may be novel potential biomarkers in the detection of gastric cancer.

METHODS: A total of 130 serum samples, including 70 from patients with gastric cancer and 60 from healthy adults, were detected by surface-enhanced laser desorption and ionization time-of-flight mass spectrometry (SELDI-TOF-MS). The data of spectra were analyzed by Biomarker Patterns Software (BPS). Thirty serum samples of gastric cancer patients and 30 serum samples of healthy adults were grouped into the training group to build models, and the other 70 samples were used to test and evaluate the models. The samples of the test group were judged only with their peaks’ height and were separated into cancer group or healthy control group by BPS automatically and the judgments were checked with the histopathologic diagnosis of the samples.

RESULTS: Sixteen mass peaks were found to be potential biomarkers with a significant level of P<0.01. Among them, nine mass peaks showed increased expression in patients with gastric cancer. Analyzed by BPS, two peaks were chosen to build the model for gastric cancer detection. The sensitivity, specificity, and accuracy of the model were 90%, 36/40, 86.7%, 26/30, and 88.6%, 62/70, respectively, which were greatly higher than those of clinically used serum biomarkers CEA (carcinoembryonic antigen), CA19-9 and CA72-4. Stage I/II gastric cancer samples of the test group were all judged correctly.

CONCLUSION: The novel biomarkers in serum and the established model could be potentially used in the detection of gastric cancer. However, large-scale studies should be carried on to further explore the clinical impact on the model.

• SELDI-TOF-MS
• Serum
• Gastric cancer

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor/metabolism
• Humans
• Mass Spectrometry/methods
• Middle Aged
• Proteomics
• Software
• Stomach Neoplasms/metabolism
• Stomach Neoplasms/pathology

AIM: Gene expression profiling provides an unique opportunity to gain insight into the development of different types of gastric cancer. Tumor sample heterogeneity is thought to decrease the sensitivity and tumor specificity of microarray analysis. Thus, microdissection and preamp-lification of RNA is frequently performed. However, this technique may also induce considerable changes to the expression profile. To assess the effect of gastric tumor heterogeneity on expression profiling results, we measured the variation in gene expression within the same gastric cancer sample by performing a gene chip analysis with two RNA preparations extracted from the same tumor specimen.

METHODS: Tumor samples from six intestinal T2 gastric tumors were dissected under liquid nitrogen and RNA was prepared from two separate tumor fragments. Each extraction was individually processed and hybridized to an Affymetrix U133A gene chip covering approximately 18 000 human gene transcripts. Expression profiles were analyzed using Microarray Suite 5.0 (Affymetrix) and GeneSpring 6.0 (Silicon Genetics).

RESULTS: All gastric cancers showed little variance in expression profiles between different regions of the same tumor sample. In this case, gene chips displayed mean pair wise correlation coefficients of 0.94±0.02 (mean±SD), compared to values of 0.61±0.1 for different tumor samples. Expression of the variance between the two expression profiles as a percentage of "Total change "(Affymetrix) revealed a remarkably low average value of 1.18±0.78 for comparing fragments of the same tumor sample. In contrast, comparison of fragments from different tumors revealed a percentage of 24.4±4.5.

CONCLUSION: Our study indicates a low degree of expression profile variability within gastric tumor samples isolated from one patient. These data suggest that tumor tissue heterogeneity is not a dominant source of error for microarray analysis of larger tumor samples, making total RNA extraction an appropriate strategy for performing gene chip expression profiling of gastric cancer.

• Gastric cancer
• Microarray analysis
• Tissue heterogeneity

• Aged
• Aged, 80 and over
• Analysis of Variance
• Female
• Gene Expression Profiling/statistics & numerical data
• Humans
• Male
• Oligonucleotide Array Sequence Analysis/statistics & numerical data
• RNA, Neoplasm/genetics
• RNA, Neoplasm/isolation & purification
• Stomach Neoplasms/genetics

• hydroxycamptothecin
• transcatheter arterial embolization
• portal venous embolization
• hepatocellular carcinoma

• Adult
• Aged
• Antimetabolites, Antineoplastic/administration & dosage
• Antineoplastic Agents/administration & dosage
• Antineoplastic Agents, Phytogenic/administration & dosage
• Antineoplastic Agents, Phytogenic/therapeutic use
• Antineoplastic Combined Chemotherapy Protocols/administration & dosage
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Camptothecin/administration & dosage
• Camptothecin/analogs & derivatives
• Camptothecin/therapeutic use
• Carcinoma, Hepatocellular/therapy
• Chemoembolization, Therapeutic
• Cisplatin/administration & dosage
• Drug Administration Schedule
• Female
• Fluorouracil/administration & dosage
• Hepatic Artery
• Humans
• Liver Neoplasms/therapy
• Male
• Middle Aged
• Portal Vein
• Treatment Outcome

AIM: To determine whether any changes have occurred on the patterns of colorectal cancer in China.

METHODS: Data from 21 Chinese articles published from 1980 to 1999, were used to analyze the time trend of colorectal cancer according to the patients’ age at diagnosis, sex, the site of the tumor, stage, and the pathology.

RESULTS: From 1980s to 1990s, the mean age of the colorectal cancer patients has increased. The percentage of the female patients rose. The distribution of colorectal carcinoma shows a predominance of rectal cancer. However, the proportion of proximal colon cancer (including transverse and ascending colon) increased significantly accompanied by a decline in the percentage of rectal cancer. Similarity in the percentage of distal colon cancer between two decades was revealed. In the 1990s, statistically more Stage B patients were found than those in 1980s. In addition, databases show a significant decrease in the Stage D cases. The proportion of adenocarcinoma increased, but the mucinous adenocarcinoma decreased during two decades.

CONCLUSION: These findings indicate that the pattern of colorectal cancer in China has been changing. Especially, a proximal shift due to the increasing proportion of ascending and transverse colon cancer has occurred in China.

• Colorectal carcinoma
• Time trends
• Age
• Sex
• Subsite
• Pathology

• China/epidemiology
• Colonic Neoplasms/epidemiology
• Colorectal Neoplasms/epidemiology
• Colorectal Neoplasms/pathology
• Female
• Humans
• Male
• Middle Aged
• Rectal Neoplasms/epidemiology
• Sex Distribution
• Time Factors

AIM: To evaluate the relationship of expression of paxillin, syndecan-1 and EMMPRIN proteins with clinicopathological features in hepatocellular carcinoma (HCC).

METHODS: Fifty-one patients who underwent HCC resection were recruited in the study. Paxillin, syndecan-1 and EMMPRIN proteins in HCC tissues were detected with immunohistochemical staining.

RESULTS: Of 51 cases of HCC, 23 (45%) exhibited paxillin protein positive expression. Of 42 cases of adjacent non-tumor liver tissues, 24 (57%) exhibited positive expression. Positive paxillin protein expression was associated with low differentiation (r = 0.406, P = 0.004), with the presence of portal vein thrombosis (r = 0.325, P = 0.021), with extra-hepatic metastasis (r = 0.346, P = 0.014). Of 51 cases of HCC, 28 (55%) exhibited syndecan-1 protein positive expression. Of 42 cases of adjacent non-tumor liver tissues, 23 (55%) exhibited positive expression. Positive snydecan-1 protein expression was associated with well differentiation (r = 0.491, P = 0.001), with no extra-hepatic metastasis (r = 0.346, P = 0.014). Of 51 cases of HCC, 28 (55%) exhibited EMMPRIN protein positive expression. Of 42 cases of adjacent non-tumor liver tissues, 21 (50%) exhibited positive expression. Expression of EMMPRIN protein was not associated with serum AFP level, HBsAg status, presence of microsatellite nodule, tumor size, presence of cirrhosis and necrosis, differentiation, presence of portal vein thrombosis, extra-hepatic metastasis, disease-free survival and overall survival (P>0.05). Expression of paxillin protein was correlated conversely with the expression of syndecan-1 protein in HCC (r = -0.366, P = 0.010).

CONCLUSION: Expression of paxillin and syndecan-1 proteins in HCC may affect its invasive and metastatic ability of the tumor. There may be a converse correlation between the expression of paxillin and syndecan-1 protein in HCC. Expression of EMMPRIN protein may be detected in HCC, but it may play little role in the invasion and metastasis of HCC.

• Hepatocellular carcinoma
• Paxillin
• Syndecan-1
• EMMPRIN
• Immunohistochemistry

• Adult
• Aged
• Antigens, CD/metabolism
• Basigin
• Carcinoma, Hepatocellular/metabolism
• Carcinoma, Hepatocellular/pathology
• Cytoskeletal Proteins/metabolism
• Female
• Humans
• Liver Neoplasms/metabolism
• Liver Neoplasms/pathology
• Male
• Membrane Glycoproteins/metabolism
• Middle Aged
• Paxillin
• Phosphoproteins/metabolism
• Proteoglycans/metabolism
• Syndecan-1
• Syndecans

AIM: To investigate the effects of thalidomide on angiogenesis, tumor growth and metastasis of hepatocellular carcinoma in nude mice.

METHODS: Twenty-four nude mice were randomly divided into therapy group and control group, 12 mice in each group. Thalidomide dissolved in 0.5% sodium carboxyl methyl cellulose (CMC) suspension was administered intraperitoneally once a day at the dose of 200 mg/kg in therapy group, and an equivalent volume of 0.5% CMC in control group. Mice were sacrificed on the 30^th d, tumor size and weight and metastases in liver and lungs were measured. CD34 and VEGF mRNA in tumor tissue were detected by immunohistochemistry and semi-quantitative RT-PCR respectively and microvessel density (MVD) was counted. Serum concentrations of TNF-α and ALT and AFP were also tested.

RESULTS: MVD and VEGF mRNA in therapy group were less than those in control group (31.08±16.23 vessels/HP vs 80.00±26.27 vessels/HP, 0.0538±0.0165 vs 0.7373±0.1297, respectively, P<0.05). No statistical difference was observed in tumor size and weight and metastases in liver and lungs. TNF-α was significantly lower in therapy group than in control group (28.64±4.64 ng/L vs 42.69±6.99 ng/L, P<0.05). No statistical difference in ALT and AFP was observed between groups.

CONCLUSION: Thalidomide can significantly inhibit angiogenesis and metastasis of hepatocellular carcinoma. It also has inhibitory effects on circulating TNF-α.

• Hepatocellular carcinoma
• Thalidomide
• Angiogenesis
• Neoplasm metastasis

• Angiogenesis Inhibitors/pharmacology
• Animals
• Base Sequence
• Carcinoma, Hepatocellular/blood supply
• Carcinoma, Hepatocellular/pathology
• Cell Division
• DNA Primers
• Humans
• Liver Neoplasms/blood supply
• Liver Neoplasms/pathology
• Mice
• Mice, Nude
• Neoplasm Metastasis
• Neovascularization, Pathologic/prevention & control
• Polymerase Chain Reaction
• Thalidomide/pharmacology
• Transplantation, Heterologous
• Vascular Endothelial Growth Factor A/genetics

AIM: To establish a nude mice model of human hepatocellular carcinoma (HCC) via orthotopic implantation of histologically intact tissue, in order to study biologic features of HCC in vivo and to direct clinical treatment respectively.

METHODS: Histologically intact fresh specimens of HCC were orthotopically implanted in nude mice (BALB/c, nu/nu). Survival rate and growth curve were investigated with B-ultrasound. Morphological characteristics of pathology and spontaneous metastatic rates were detected with microscopy. Expression of multidrug resistance genes studied with immunohistochemical method and RT-PCR, and other biologic features of implanted tumor were observed and compared with human HCC specimens.

RESULTS: Out of the specimens from two patients with HCC, only one specimen survived in nude mice. The orthotopic implantation tumor survival rate, spontaneous intrahepatic metastatic rate, pulmonary metastatic rate and bone metastases rate were 100%, 75.0%, 37.5% and 37.5% respectively in the first passage. AFP was kept on secreting and increasing with the size of the tumor. The morphological characteristics and biologic features were similar to the donor’s, the protein and mRNA of MDR1 and LRP were expressed in tumors of the model and the donor, and there was no significant difference between them (P > 0.05).

CONCLUTION: The model of nude mice with orthotopic implantation of histologically intact HCC tissue is an ideal model to study biologic features of HCC in vivo and to direct clinical treatment.

• ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics
• Animals
• Biomarkers, Tumor/genetics
• Bone Neoplasms/secondary
• Carcinoma, Hepatocellular/secondary
• Disease Models, Animal
• Humans
• Liver Neoplasms/secondary
• Lung Neoplasms/secondary
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Transplantation/methods

AIM: To study the epidemiology of gastric malignancies in Jordan as a model for Middle East countries where such data is scarce.

METHODS: Pertinent epidemiological and clinicopathological data for 201 patients with gastric malignancy in north of Jordan between 1991 and 2001 were analyzed.

RESULTS: Male: female ratio was 1.8:1. The mean age was 61.2 years, and 8.5% of the patients were younger than 40 years of age. The overall age- adjusted incidence was 5.82/100 000 population/year. The age specific incidence for males raised from 1.48 in those aged 30-39 years to 72.4 in those aged 70-79 years. Adenocarcinomas, gastric lymphomas, malignant stromal tumors, and carcinoids were found in 87.5%, 8%, 2.5%, and 2% respectively. There was an average of 10.1-month delay between the initial symptoms and the diagnosis. Only 82 patients underwent “curative” gastrectomy. Among adenocarcinoma groups, Lauren intestinal type was the commonest (72.2%) and the distal third was the most common localization (48.9%). The mean follow up for patients with gastric adenocarcinoma was 25.1 mo (range 1 mo -132 mo) . The 5-year survival rates for stages I (n = 15), II (n = 41), III (n = 59), and IV (n = 53) were 67.3%, 41.3%, 5.7%, and 0% respectively (P = 0.0001). The overall 5 year survival was 21.1%.

CONCLUSION: Despite low incidence, some epidemiological features of gastric cancer in Jordan mimic those of high-risk areas. Patients are detected and treated after a relatively long delay. No justification in favor of a possible gastric cancer screening effort in Jordan is supported by our study; rather, the need of an earlier diagnosis and subsequent better care.

• Adolescent
• Adult
• Age Distribution
• Aged
• Aged, 80 and over
• Child
• Child, Preschool
• Female
• Gastrectomy/statistics & numerical data
• Humans
• Incidence
• Infant
• Infant, Newborn
• Jordan/epidemiology
• Male
• Middle Aged
• Sex Distribution
• Stomach Neoplasms/epidemiology
• Stomach Neoplasms/surgery
• Survival Analysis

AIM: To establish a novel human hepatocellular carcinoma (HCC) cell line FHCC-98 from HCC tissue and to provide a suitable model for studying HCC occurrence, progress and metastasis.

METHODS: Serially passaged cells were cultured and their morphologies were observed under light and electron microscope. Cytogenetic study was conducted by using flow cytometry and chromosome analysis. Expressions of tumor markers such as α-fetoprotein (AFP), cytokeratin (CK) and hepatoma metastasis-associated factor HAb18G/CD147 on the FHCC-98 cells were detected by immunocytochemistry or Western blotting. Lactic dehydrogenase (LDH) isoenzymes were detected by polyacrylamide gel electrophoresis (PAGE). Xenograft was performed by inoculating FHCC-98 cells into the flanks of nude mice.

RESULTS: Morphology of FHCC-98 cells was the same as that of other malignant cells. The expressions of the cells were positive for HAb18G/CD147 and CK, and negative for AFP. Its population doubling time was 21.4 h. The cell DNA was tetraploid and the major chromosomes were triploid by cytogenetics analysis. The tumorigenicity in nude mice was 100%. PAGE showed four bands representing LDH₂, LDH₃, LDH₄ and LDH₅.

CONCLUSION: FHCC-98 is a novel HCC cell line and an ideal cell model for further exploring the mechanism of hepatocellular carcinoma invasion and metastasis.

• Adult
• Animals
• Biomarkers, Tumor
• Carcinoma, Hepatocellular/metabolism
• Carcinoma, Hepatocellular/pathology
• Cell Culture Techniques/methods
• Cell Line, Tumor/cytology
• Cell Line, Tumor/metabolism
• Cell Shape
• Humans
• Liver Neoplasms/metabolism
• Liver Neoplasms/pathology
• Male
• Mice
• Mice, Nude
• Neoplasm Transplantation
• Transplantation, Heterologous

AIM: Transcatheter arterial embolization (TAE) of the hepatic artery has been accepted as an effective treatment for unresectable hepatocellular carcinoma (HCC). However, embolized vessel recanalization and collateral circulation formation are the main factors of HCC growth and recurrence and metastasis after TAE. Vascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis. This study was to explore the inhibitory effect of VEGF antisense oligodeoxynucleotides (ODNs) on VEGF expression in cultured Walker-256 cells and to observe the anti-tumor effect of intra-arterial infusion of antisense ODNs mixed with lipiodol on rat liver cancer.

METHODS: VEGF antisense ODNs and sense ODNs were added to the media of non-serum cultured Walker-256 cells. Forty-eight hours later, VEGF concentrations of supernatants were detected by ELISA. Endothelial cell line ECV-304 cells were cultured in the supernatants. Seventy-two hours later, growth of ECV-304 cells was analyzed by MTT method. Thirty Walker-256 cell implanted rat liver tumor models were divided into 3 groups. 0.2 mL lipiodol (LP group, n = 10), 3OD antisense ODNs mixed with 0.2 mL lipiodol (LP+ODNs group, n = 10) and 0.2 mL normal saline (control group, n = 10) were infused into the hepatic artery. Volumes of tumors were measured by MRI before and 7 d after the treatment. VEGF mRNA in cancerous and peri-cancerous tissues was detected by RT-PCR. Microvessel density (MVD) and VEGF expression were observed by immunohistochemistry.

RESULTS: Antisense ODNs inhibited Walker-256 cells’ VEGF expression. The tumor growth rate was significantly lower in LP+ODNs group than that in LP and control groups (140.1 ± 33. 8%, 177. 9 ± 64. 9% and 403.9 ± 69.4% respectively, F = 60.019, P < 0.01). VEGF mRNAs in cancerous and peri-cancerous tissues were expressed highest in LP group and lowest in LP+ODNs group. The VEGF positive rates showed no significant difference among LP, control and LP+ODNs groups (90%, 70% and 50%, H = 3.731, P>0.05). The MVD in LP+ODNs group (53.1 ± 18.4) was significantly less than that in control group (73.2 ± 20.4) and LP group (80.3 ± 18.5) (F = 5.44, P < 0.05)

CONCLUSION: VEGF antisense ODNs can inhibit VEGF expression of Walker-256 cells. It maybe an antiangiogenesis therapy agent for malignant tumors. VEGF antisense ODNs mixed with lipiodol embolizing liver cancer is better in inhibiting liver cancer growth, VEGF expression and microvessel density than lipiodol alone.

• Animals
• Arteries
• Cell Line, Tumor
• Embolization, Therapeutic
• Iodized Oil/therapeutic use
• Liver Neoplasms/blood supply
• Oligonucleotides, Antisense/therapeutic use
• Rats
• Vascular Endothelial Growth Factor A/antagonists & inhibitors
• Vascular Endothelial Growth Factor A/genetics

AIM: Ets1 proto-oncogene is a transcription factor involved in the activation of several genes of tumor invasion and metastasis. We aimed to determine the relationship between the extent and intensity of Ets1 expression and patients’ clinicopathological factors in gastric carcinoma.

METHODS: Immunohistochemical analysis was performed for gastric tumor paraffin-embedded sections, followed by image analysis.

RESULTS: Ets1 was not expressed in the normal gastric epithelium and its surrounding cells. The percentage of Ets1 expressing cells detected increased significantly in both epithelial tumor and stromal cells from high T classification, lymph node metastasis positive, clinical advanced-stage groups (P < 0.001). The level of Ets1 staining in epithelial tumor cells also reflected the degree of cell differentiation. The percentage of epithelial and stromal cells expressing Ets1 was significantly correlated with the presence of lymph node metastasis (P = 0.014 and P < 0.001 respectively). Ets1 expression was not observed in tissue samples from patients with benign gastric ulcers.

CONCLUSION: Ets1 protein expression in epithelial tumor cells reflects the degree of differentiation, and the percentage of Ets1 positive tumor and stromal cells correlates with lymph node metastasis. Thus Ets1 is a valuable marker of malignant potential in terms of invasiveness and metastasis of gastric carcinoma. It is also possible that inhibition of Ets1 is a potential avenue for therapy in gastric cancer.

• Adenocarcinoma/metabolism
• Adenocarcinoma/secondary
• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor/metabolism
• Carcinoma/metabolism
• Carcinoma/secondary
• Carcinoma, Signet Ring Cell/metabolism
• Carcinoma, Signet Ring Cell/secondary
• Female
• Humans
• Lymphatic Metastasis
• Male
• Middle Aged
• Proto-Oncogene Mas
• Proto-Oncogene Protein c-ets-1
• Proto-Oncogene Proteins/metabolism
• Proto-Oncogene Proteins c-ets
• Stomach Neoplasms/metabolism
• Stomach Neoplasms/pathology
• Transcription Factors/metabolism

AIM: To study the immunoprotective effect of liver cancer vaccine with co-transfected IL-2 and B7-1 genes on hepatocarcinogenesis in mice.

METHODS: The murine liver cancer cell line Hepal-6 was transfected with IL-2 and/or B7-1 gene via recombinant adenoviral vectors and the liver cancer vaccines were prepared. C57BL/6 mice were immunized with these vaccines and challenged with the parental Hepal-6 cells afterwards. The immunoprotection was investigated and the reactive T cell line was assayed.

RESULTS: The immunoprotection of the tumor vaccine was demonstrated. The effect of IL-2 and B7-1 genes co-transfected Hepal-6 liver cancer vaccine (Hep6-IL2/B7 vaccine) on the onset of tumor formation was the strongest. When attacked with wild Hepal-6 cells, the median survival period of the mice immunized with Hep6-IL2/B7 vaccine was the longest (68 d, χ² = 7.70-11.69, P < 0.05) and the implanted tumor was the smallest (z = 3.20-44.10, P < 0.05). The effect of single IL-2 or B7-1 gene-transfected vaccine was next to the IL2/B7 gene co-transfected group, and the mean survival periods were 59 and 54 d, respectively. The mean survival periods of wild or enhanced green fluorescence protein gene modified vaccine immunized group were 51 and 48 d, respectively. The mice in control group all died within 38 d and the implanted tumor was the largest (z = 3.20-40.21, P < 0.05). The cellular immunofunction test and cytotoxicity study showed that the natural killer (NK) cell, lymphokine activated killer (LAK) cell and cytotoxic T lymphocyte (CTL) activities were significantly increased in mice immunized with the Hep6-IL2/B7 vaccine, (29.5% ± 2.5%, 65.0% ± 2.9%, 83.1% ± 1.5% respectively, compared with other groups, P < 0.05).

CONCLUSION: The Hep6-IL2/B7 liver cancer vaccines can induce the mice to produce activated and specific CTL against the parental tumor cells, and demonstrate stronger effect on the hepatocarcinogenesis than single gene modified or the regular tumor vaccine. Therefore, the vaccines may become a novel potential therapy for recurrence and metastasis of HCC.

• Animals
• B7-1 Antigen/genetics
• Cancer Vaccines/genetics
• Carcinoma, Hepatocellular/immunology
• Carcinoma, Hepatocellular/prevention & control
• Cell Line, Tumor
• Female
• Flow Cytometry
• Gene Expression
• Genetic Therapy
• Interleukin-2/genetics
• Killer Cells, Natural/immunology
• Liver Neoplasms, Experimental/immunology
• Liver Neoplasms, Experimental/prevention & control
• Lymphocyte Activation
• Mice
• Mice, Inbred C57BL
• Spleen/cytology
• Transfection

AIM: To describe the mortality rate of pancreatic cancer and its distribution in China during the period of 1991-2000.

METHODS: Based on the data of demography and death collected through China’s Disease Surveillance Point System (DSPS) over the period of 1991-2000, the distribution of death rate of pancreatic cancer was described in terms of age group, gender, calendar year, rural/urban residence and administrative district.

RESULTS: A total of 1619 death cases attributed to pancreatic cancer (975 men and 644 women) were reported by DSPS during 1991-2000. The reported, adjusted and age-standardized mortality rates increased from 1.46, 1.75, and 2.18 per 100000 populations in 1991 to 2.38, 3.06, and 3.26 per 100000 populations in 2000. The majority (69.62%) of the deaths of pancreatic cancer were seen in the age group of 60 years and older. The mortality rate was higher in men than in women, but the male to female death rate ratios decreased during the 10 years. Our data also showed that the death rate of pancreatic cancer in urban areas was about 2-4 fold higher than that in rural areas, and in Northeast and East China, the death rates were higher than those in the other 5 administrative districts.

CONCLUSION: The death rate due to pancreatic cancer was rising during the period of 1991-2000 and the peak mortality of pancreatic cancer might arrive in China.

• Age Distribution
• China/epidemiology
• Female
• Humans
• Male
• Middle Aged
• Pancreatic Neoplasms/mortality
• Rural Population/statistics & numerical data
• Sex Distribution
• Urban Population/statistics & numerical data

AIM: To evaluate the value of right trisectionectomy, previously named right trisegmentectomy, in the treatment of primary liver cancer by summarizing our 13-year experience for this procedure.

METHODS: Thirty three primary liver cancer patients undergoing right trisectionectomy from Apr. 1987 to Dec. 1999 were investigated retrospectively. The impacts in survival of patients by cancerous biological behavior, such as tumor thrombi and satellite nodules, were discussed respectively. All right trisectionectomies were performed under normothermic interruption of porta hepatis at single time. Ultrasonic dissector (CUSA system 200) was used in dissection of hepatic parenchyma from Nov. 1992, instead of finger fracture.

RESULTS: 1-, 3- and 5-year survival rates were 71.9%, 40.6% and 34.4%, respectively. The longest survival term with free cancer was 150 months (alive). There were no significant differences in survival curves between cases with and without tumor thrombi (right branch of portal vein) and satellite nodules. Operative mortality was 3.0% (1/33). Main surgical complications occurred in 5 cases.

CONCLUSION: Right trisectionectomy should be regarded as an effective and safe procedure for huge primary liver cancers and is worth using more widely.

• Adult
• Female
• Follow-Up Studies
• Hepatectomy/methods
• Hepatectomy/mortality
• Humans
• Liver Neoplasms/mortality
• Liver Neoplasms/pathology
• Liver Neoplasms/surgery
• Lymphatic Metastasis
• Male
• Middle Aged
• Postoperative Complications/epidemiology
• Retrospective Studies
• Survival Rate
• Time Factors

AIM: To establish an ideal implantable rat liver tumor model for interventional therapy study and examine its angiographic signs and MRI, CT features before and after embolization.

METHODS: Forty male Wistar rats were implanted with Walker-256 tumor in the left lateral lobe of liver. Digital subtraction angiography (DSA) and transarterial chemoembolization were performed on day 14 after implantation. Native computer tomography (CT, n = 8) and native magnetic resonance (MR, n = 40) were performed between the day 8 and day 21 after implantation. The radiological morphological characteristics were correlated with histological findings.

RESULTS: Successful implantation was achieved in all forty rats, which was confirmed by CT and MRI. MR allowed tumor visualization from day 8 while CT from day 11 after implantation. The tumors were hypodensity on CT, hypointense on MR T1-weighted and hyperintense on T2-weighted. The model closely resembled human hepatocarcinoma in growth pattern and the lesions were rich in vasculature on angiography and got its filling mainly from the hepatic artery. Before therapy, tumor size was 211.9 ± 48.7 mm³. No ascites, satellite liver nodules or lung metastasis were found. One week after therapy, tumor size was 963.6 ± 214.8 mm³ in the control group and 356.5 ± 78.4 mm³ in TACE group. Ascites (4/40), satellite liver nodules (7/40) or lung metastasis (3/40) could be seen on day 21.

CONCLUSION: Walker-256 tumor rat model is suitable for the interventional experiment. CT and MRI are helpful in animal optioning and evaluating experimental results.

• Animals
• Carcinoma 256, Walker/pathology
• Carcinoma 256, Walker/therapy
• Chemoembolization, Therapeutic
• Disease Models, Animal
• Hepatic Artery
• Liver Neoplasms/pathology
• Liver Neoplasms/therapy
• Magnetic Resonance Imaging
• Male
• Neoplasm Transplantation
• Rats
• Rats, Wistar
• Tumor Cells, Cultured

AIM: The widespread use of antibacterial therapy has been suggested to be the cause for the decline in the prevalence of Helicobacter pylori infection. This study examine the serial changes of urea breath test results in a group of hospitalized patients who were given antibacterial therapy for non-gastric infections.

METHODS: Thirty-five hospitalized patients who were given antibacterial therapy for clinical infections, predominantly chest and urinary infections, were studied. Most (91%) patients were given single antibiotic of either a penicillin or cephalosporin group. Serial ¹³C-urea breath tests were performed within 24 h of initiation of antibiotics, at one-week and at six-week post-therapy. H. pylori infection was diagnosed when one or more urea breath tests was positive.

RESULTS: All 35 patients completed three serial urea breath tests and 26 (74%) were H. pylori-positive. Ten (38%) H. pylori-infected patients had at least one negative breath test results during the study period. The medium delta ¹³C values were significantly lower at baseline (8.8) than at one-week (20.3) and six-week (24.5) post-treatment in H. pylori-positive individuals (P = 0.022). Clearance of H. pylori at six-week was only seen in one patient who had received anti-helicobacter therapy from another source.

CONCLUSION: Our results suggested that one-third of H. pylori-infected individuals had transient false-negative urea breath test results during treatment with antibacterial agent. However, clearance of H. pylori infection by regular antibiotic consumption is rare.

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Anti-Bacterial Agents/administration & dosage
• Breath Tests
• Child
• Child, Preschool
• False Negative Reactions
• Female
• Helicobacter Infections/diagnosis
• Helicobacter Infections/drug therapy
• Helicobacter pylori
• Humans
• Male
• Middle Aged
• Urea/metabolism

AIM: To confirm if p53 mutation could be a routine predictive marker for the prognosis of hepatocellular carcinoma (HCC) patients.

METHODS: Two hundreds and forty-four formalin-fixed paraffin-embedded tumor samples of the patients with HCC receiving liver resection were detected for nuclear accumulation of p53. The percent of p53 immunoreactive tumor cells was scored as 0 to 3 + in p53 positive region (< 10% -, 10%-30% +, 31%-50% ++, > 50% +++). Proliferating cell nuclear antigen (PCNA) and some clinicopathological characteristics, including patients’ sex, preoperative serum AFP level, tumor size, capsule, vascular invasion (both visual and microscopic), and Edmondson grade were also evaluated.

RESULTS: In univariate COX harzard regression model analysis, tumor size, capsule status, vascular invasion, and p53 expression were independent factors that were closely related to the overall survival (OS) rates of HCC patients. The survival rates of patients with 3+ for p53 expression were much lower than those with 2+ or + for p53 expression. Only vascular invasion (P < 0.05) and capsule (P < 0.01) were closely related to the disease-free survival (DFS) of HCC patients. In multivariate analysis, p53 overexpression (RI 0.5456, P < 0.01) was the most significant factor associated with the OS rates of patients after HCC resection, while tumor size (RI 0.5209, P < 0.01), vascular invasion (RI 0.5271, P < 0.01) and capsule (RI 0.8691, P < 0.01) were also related to the OS. However, only tumor capsular status was an independent predictive factor (P < 0.05) for the DFS. No significant prognostic value was found in PCNA-LI, Edmondson’s grade, patients’ sex and preoperative serum AFP level.

CONCLUSION: Accumulation of p53 expression, as well as tumor size, capsule and vascular invasion, could be valuable markers for predicting the prognosis of HCC patients after resection. The quantitative immunohistochemical scoring for p53 nuclear accumulation might be more valuable for predicting prognosis of patients after HCC resection than the common qualitative analysis.

• Adolescent
• Adult
• Aged
• Biomarkers, Tumor/metabolism
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/metabolism
• Carcinoma, Hepatocellular/surgery
• Female
• Genes, p53
• Humans
• Immunohistochemistry
• Liver Neoplasms/genetics
• Liver Neoplasms/metabolism
• Liver Neoplasms/surgery
• Male
• Middle Aged
• Mutation
• Prognosis
• Tumor Suppressor Protein p53/metabolism

The prognosis of patients with HCC still remains dismal. The life expectancy of HCC patients is hard to predict because of the high possibility of postoperative recurrence. Many factors, such as patient's general conditions, macroscopic tumor morphology, as well as tumor hitopathology features, have been proven of prognostic significance. Female HCC patient often has a better prognosis than male patient, which might be due to the receptor of sex hormones. Younger patients often have tumors with higher invasiveness and metastatic potentials, and their survival and prognosis are worse than the older ones. Co-existing hepatitis status and hepatic functional reserve have been confirmed as risk factors for recurrence. Serum alpha-fetoprotein (AFP) is useful not only for diagnosis, but also as a prognostic indicator for HCC patients. AFP mRNA has been proposed as a predictive marker of HCC cells disseminated into the circulation and for metastatic recurrence. Many pathologic features, such as tumor size, number, capsule state, cell differentiation, venous invasion, intrahepatic spreading, and advanced pTNM stage, are the best-established risk factors for recurrence and important aspects affecting the prognosis of patients with HCC. Marked inflammatory cell infiltration in the tumor could predict a better prognosis. Clinical stage is still the most important factor influencing on the prognosis. Extratumor spreading and lymph nodal metastasis are independent predictors for poor outcome. Some new predictive systems have recently been proposed. Different strategies of treatment might have significant different effects on the patients' prognosis. To date, surgical resection is still the only potentially curative treatment for HCC, including localized postoperative recurrences. Extent of resection, blood transfusion, occlusion of porta hepatis, and blood loss affect the survival and prognosis of HCC patients. Regional therapies provide alternative ways to improve the prognosis of HCC patients who have no opportunity to receive surgical treatment or postoperative recurrence. The combination of these treatment modalities is hopeful to further improve the prognosis. The efficacies of neoadjuvant (preoperative) or adjuvant (postoperative) chemotherapy or chemoembolization in preventing recurrence and on the HCC prognosis still remain great controversy, and deserves further evaluation. Biotherapy, including IFN-alpha therapy, will play more important role in preventing recurrence and metastasis of HCC after operation.

• Age Factors
• Carcinoma, Hepatocellular/diagnosis
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/physiopathology
• Carcinoma, Hepatocellular/therapy
• Hepatitis/physiopathology
• Humans
• Liver Cirrhosis/physiopathology
• Liver Neoplasms/diagnosis
• Liver Neoplasms/pathology
• Liver Neoplasms/physiopathology
• Liver Neoplasms/therapy
• Neoplasm Staging
• Prognosis
• Recurrence
• Sex Factors
• alpha-Fetoproteins/metabolism

Metastatic human HCC model is needed for the studies on mechanism and interven tion of metastatic recurrence. By using orthotopic implantation of histologically intact tissues of 30 surgical specimens, a patient-like metastatic model of hu man HCC in nude mice (LCI-D20) and a low metastatic model of human HCC in nude mice (LCI-D35) have been established. All mice with transplanted LCI-D20 tumors exhibited extremely high metastatic ability including spontaneous metasta sis to liver, lungs, lymph nodes and peritoneal seeding. Remarkable difference was also found in expression of some of the invasiveness related genes and growth factors between the LCI-D20 and LCI-D35 tumors. PAI-1 increased gradually following tumor progression in LCI-D20 model, and correlated with tumor size and AFP level. Phasic expression of tissue intercellular adhesio nmolecule-1 in this model was also observed. Using corneal micropocket model, it was demonstrated that the vascular response induced by LCI-D20 tumor was stronger than that induced by LCI-D35 tumor. Similar report on metastatic human HCC model in nude mice and human HCC cell line with metastatic potential was rarely found in the literature. This LCI-D20 model has been widely used for the studies on intervention of metastasis, including anti-angiogenesis, antisense approach, metallopro teinase inhibitor, differentiation inducer, etc. It is concluded that the establ ishment of metastatic human HCC model in nude mice and human HCC cell line with metastatic potential will provide important models for the in vivo and in vitro study of HCC invasiveness, angiogenesis as well as intervention of HCC recurrence.

• hepatocellular carcinoma
• metastasis
• metastatic model
• nude mice
• cell line
• experimental intervention
• angiogenesis

• Animals
• Carcinoma, Hepatocellular/secondary
• Disease Models, Animal
• Humans
• Liver Neoplasms, Experimental/secondary
• Mice
• Mice, Nude
• Tumor Cells, Cultured

AIM: To establish clone cells with different metastatic potential for the study of metastasis-related mechanisms.

METHODS: Cloning procedure was performed on parental hepatocellular carcinoma (HCC) cell line MHCC97, and biological characteristics of the target clones selected by in vivo screening were studied.

RESULTS: Two clones with high (MHCC97-H) and low (MHCC97-L) metastatic potential were isolated from the parent cell line. Compared with MHCC97-L, MHCC97-H had smaller cell size (average cell diameter 43 μm vs 50 μm) and faster in vitro and in vivo growth rate (tumor cell doubling time was 34.2 h vs 60.0 h). The main ranges of chromosomes were 55-58 in MHCC97-H and 57-62 in MHCC97-L. Boyden chamber in vitro invasion assay demonstrated that the number of penetrating cells through the artificial basement membrane was (37.5 ± 11.0) cells/field for MHCC97-H vs (17.7 ± 6.3)/field for MHCC97-L. The proportions of cells in G0-G1 phase, S phase, and G2-M phase for MHCC97-H/MHCC97-L were 0.56/0.65, 0.28/0.25 and 0.16/0.10, respectively, as measured by flow cytometry. The serum AFP levels in nude mice 5 wk after orthotopic implantation of tumor tissue were (246 ± 66) μg•L¯¹ for MHCC97-H and (91 ± 66) μg•L¯¹ for MHCC97-L. The pulmonary metastatic rate was 100% (10/10) vs 40% (4/10).

CONCLUSION: Two clones of the same genetic background but with different biological behaviors were established, which could be valuable models for investigation on HCC metastasis.

• hepatocellular carcinoma
• clone cells
• metastasis

• Albumins/analysis
• Animals
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/secondary
• Cell Division
• Chromosomes
• Clone Cells
• Flow Cytometry
• Hepatitis B/pathology
• Hepatitis B Surface Antigens/analysis
• Hepatitis B virus/isolation & purification
• Humans
• Keratins/analysis
• Liver/pathology
• Liver Neoplasms, Experimental/genetics
• Liver Neoplasms, Experimental/secondary
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Invasiveness
• Tumor Cells, Cultured/chemistry
• Tumor Cells, Cultured/cytology
• Tumor Cells, Cultured/virology
• Virus Integration
• alpha-Fetoproteins/analysis

• carcinoma, hepatocellular/etiology
• carcinoma, hepatocellular/surgery
• carcinoma, hepatocellular/drug therapy
• liver neoplasms/etiology
• liver neoplasms/surgery
• liver neoplasms/drug therapy
• human
• review

• Animals
• Carcinoma, Hepatocellular/etiology
• Carcinoma, Hepatocellular/secondary
• Carcinoma, Hepatocellular/therapy
• Humans
• Liver Neoplasms/etiology
• Liver Neoplasms/secondary
• Liver Neoplasms/therapy

• carcinoma, hepatocellular
• liver neoplasms
• survival/rate
• australia