Biomedical subjects

Y Chao

Publications and source records attributed to Y Chao.

At least 127 records · Page 7Linked to original sources

PubMed2000

Successful initial treatment with weekly etoposide, epirubicin, cisplatin, 5-fluorouracil and leucovorin chemotherapy in advanced gastric cancer patients with disseminated intravascular coagulation.

BACKGROUND: Acute disseminated intravascular coagulation (DIC) is a rare but severe complication of gastric adenocarcinoma. Conventional treatments, such as fresh frozen plasma, platelet replacement and heparin injections, are disappointing. The only way to correct this fatal condition is to control the underlying cancer promptly by effective chemotherapy. Here the successful initial control of acute DIC in gastric cancer patients with weekly EEPFL chemotherapy is reported. METHODS: Advanced gastric cancer patients complicated with acute DIC were eligible. Patients were treated with weekly EEPFL therapy (etoposide 40, epirubicin 10, cisplatin 25, 5-fluorouracil 2200 and leucovorin 120 mg/m2 ). Response, survival and toxicity were evaluated. RESULTS: From April 1997 to April 1999, six patients were included in this study. All patients received EEPFL chemotherapy. Clinical and laboratory evidence of acute DIC stabilized quickly after starting chemotherapy. Four patients showed a partial response, one stable disease and one progressive disease. The toxicity was mild and well tolerated. Median survival was 28 weeks (12, 14, 26, 30, 30 and 32 weeks). All patients suffered from a relapse of DIC after initial successful control and died within 30 days of clinical and laboratory evidence of acute DIC relapse. CONCLUSION: EEPFL therapy is an effective chemotherapy regimen for patients with advanced gastric cancer associated with acute DIC. The prognosis is poor if the DIC relapses after the initial successful control.

Acute Disease↗

PubMed2000

Salvage surgery for recurrent nasopharyngeal carcinoma.

OBJECTIVE: To evaluate the efficacy of salvage surgery in the treatment of recurrent nasopharyngeal carcinoma (NPC) at the primary site. STUDY DESIGN: A retrospective investigation of the outcome of salvage surgery for 28 patients with recurrent NPC after definite radiation therapy. METHODS: The nasopharynx was approached anteroposteriorly by the transmaxillary approach (maxillary swing, maxillectomy) or inferior approach (midline mandibulotomy or median labiomandibular glossotomy), or laterally by modified facial translocation or transpterygoid approach; intentional ligation of the internal carotid artery was performed after establishment of extracranial-intracranial (EC-IC) bypass in one patient; postoperative irradiation was given to the patients with positive pathological margins. RESULTS: Nine patients lived without disease for 20 to 93 months (mean interval, 52 mo) after surgery; among them, eight patients had T1 tumors that were resected totally by surgery via anteroposterior approaches and the other patient had postoperative irradiation to control the disease. Seven patients had local recurrence 8 to 21 months after treatment. Four patients developed distant metastases, including one patient with a T2b tumor that was totally resected through modified facial translocation approach with ligation of internal carotid artery. Eight patients died of other causes; internal carotid artery blowout was the cause of death in four of these eight patients. CONCLUSIONS: In most cases of recurrence, T1 nasopharyngeal tumors can be resected totally by anteroposterior approaches; for T2 or larger tumors, postoperative irradiation is usually necessary. Otherwise, facial translocation offers a better chance to completely resect the tumors. Internal carotid artery is better ligated if patients have received greater than 70 Gy irradiation or if the artery must be exposed during the surgery. We suggest that EC-IC bypass be used to avoid the possible complications (or cerebral ischemic stroke) caused by ligation of internal carotid artery. The transmaxillary approach is favored in the management of nasopharyngeal tumor recurrence with nasal cavity extension, and midline mandibulotomy is more suitable for resection of posterior margin of nasopharyngeal tumor recurrence. Facial translocation offers the widest operative field and is the most versatile approach for radical resection of nasopharyngeal tumor recurrence, but the surgeon should be skilled in the management of the facial nerves to reduce morbidity.

Adult↗

PubMed2000

Sequential changes in plasma cytokine and endotoxin levels in cirrhotic patients with bacterial infection.

To delineate the clinical roles of plasma cytokine or endotoxin levels in the natural course of infection in patients with decompensated cirrhosis, 66 cirrhotic patients were studied within a 1.5-year period. Plasma levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6, IL-8 and endotoxin were determined on days 1, 4 and 7 after admission when hospital infection was suspected and 4 months later. A total of 24 patients (36.4%) were proven to be infected during hospitalization (group A), while 42 others were not infected (group B). Fever occurred in a very high proportion (22/24) of group A patients. Baseline levels of TNF-alpha (37.7+/-15.2 compared with 8.7+/-1.2 pg/ml; P<0.01) and IL-6 (180.5+/-20.5 compared with 24.6+/-7.5 pg/ml; P<0.0001) were higher in group A patients, while IL-1beta, IL-8 and endotoxin levels were not significantly different between the two groups. For patients with hospital infection, IL-6 levels determined during the episode were significantly higher than baseline levels. Using IL-6 >80 pg/ml as a baseline cut-off level to diagnose bacterial infection, the sensitivity, specificity and accuracy were 87.5, 100 and 95.5% respectively. The one-year cumulative probability of mortality (61.1% compared with 23.7%; P<0.001) and of bacterial re-infection (72.2% compared with 18.4%; P<0.0001) was higher in group A than in group B. Plasma TNF-alpha and IL-6 levels determined at 4 months were not different between the two groups. In conclusion, fever or elevated plasma IL-6 levels in patients with decompensated cirrhosis calls for early antibiotic treatment to prevent life-threatening bacterial infection. Bacterial infection is likely to recur in those patients with increased IL-6 levels, while severe episodes of infection occur in patients with increased TNF-alpha levels.

Aged↗

PubMed2000

[Effects of stress level on the biomechanical behavior of the temporomandibular joint disc in domestic pigs].

This study aimed to examine the responses of the temporomandibular joint (TMJ) disc against compression, to clarify the property of viscoelasticity and permeability of the disc, and to provide experimental data for further analyzing the mechanism of stress dissipation within the TMJ disc. With the use of confined compression mechanics and biphasic theory, creep experiments on eight TMJ discs of four domestic pigs were performed under three stress levels(0.07 MPa, 0.13 MPa and 0.30 MPa). The results showed that at 0.07 stress level, the compressive stiffness at 2 seconds of the anterior band(AB), intermediate zone(IZ) and posterior band(PB) of the disc was 4.48 MPa, 3.93 MPa and 6.31 MPa, respectively; the coefficient K of permeability was 0.272 x 10(-12) m4/NS, 0.30 x 10(-12) m4/NS, and 0.042 x 10(-12) m4/NS. At 0.30 Mpa level, the compressive stiffness increased to 14.07 MPa, 13.68 Mpa and 14.00 MPa; the coefficient K lowered to 0.017 x 10(-12) m4/NS, 0.012 x 10(-12) m4/NS and 0.005 x 10(-12) m4/NS. In conclusion, the TMJ disc has viscoelastic and biobiphasic properties against compression. The stiffness of the disc increases with the increment of stress level but the coefficient of permeability decreases. These findings demonstrate that the modulation of stress and of permeability may be two important factors influencing stress dissipation and shock absorption behavior of the disc during compressive and impact loads.

Animals↗

PubMed2000

[Experiment study on fit of anterior osseointegrated implant frameworks related to the number of fixture abutments].

Good fitness of osseointegrated frameworks was a key factor to protect implant for function. The purpose of this study was to evaluate the fitness of anterior implant fixed bridge in one-piece casting made of Ni-Cr alloy in different numbers of fixture abutments. The specimens were measured by the three-dimensional measurement system (German Opton uMM550). The results demonstrated that there were statistically significant differences in dimensional changes among one, two or three fixture numbers, the space of retention was 50-150 microns, and the flow of retention was 100-250 microns.

Dental Abutments↗

PubMed2000

[Tensile mechanics of mandibular condylar cartilage].

OBJECTIVE: To study the biomechanical properties of the mandibular condyle cartilage and determine its functional importance. METHODS: Eight condyle specimens of the four pig temporomandibular joints were obtained by autopsy and stored in sealed plastic bags at -20 degrees C. These pigs were healthy, aged 1 year +/- 2 months. In the coronal direction, 300 microns wide, rectangular cartilage-bone specimens were prepared on the right condyles using specified knife. In the sagittal direction, rectangular cartilage-bone specimens with the same width were obtained on the left condyles. Standard rectangular testing specimens were prepared from cartilage-bone specimens in a microtome kept at -20 degrees C (300 microns wide and 250 microns thick). The specimens were inserted in a soft-tissue uniaxial tensile test machine and immersed in a bath of Ringer's solution at room temperature. Preconditioning of the specimens was carried out prior to the uniaxial tensile experiment and the specimens were elongated to failure with the constant strain rate (0.05 mm/s). The resulting mean values were curved fitted with Fung's two-parameter (A, B) exponential stress strain equation using a nonlinear regression program. RESULTS: The data obtained showed that a typical nonlinear biomechanical behavior of the condyle cartilage. Toe-region and quasi-linear zone were obvious on the experimental stress strain relation curve. Theoretically fitted parameter A and B were 0.47 and 4.13 (coronally) and 0.60 and 4.70 (sagittally). The sagittal specimens showed greater tensile stress (2.92 MPa), tensile stiffness (9.04 MPa), energy absorption (6.02 N.mm) but less tensile strain (37.34%) than that of the coronal specimens (2.15 MPa, 6.55 MPa, 4.91 N.mm, and 41.12%). The differences were statistically significant (P < 0.05). CONCLUSION: The mandibular condyle cartilage is a kind of biophasic material which shows nonlinear viscoelastic behavior, anistrophic characteristics in biomechanical function and high ability to resist tensile stress in the longitudinal direction.

Animals↗

PubMed2000

[Histological study on the polyhydroxybutyric ester(PHB) membrane used for guided bone regeneration around titanium dental implants].

OBJECTIVE: To evaluate the effects of PHB membrane around dental titanium implants used in guided bone regeneration technique. METHODS: Endosseous cylindrical implants were placed in dogs' mandibles after extraction of all the mandibular premolars and the first molars immediately. Ideal implant placement sites were modified by creating standardized 3 mm x 5 mm facial dehiscent defects. The defects were covered with PHB membrane and titanium membrane respectively, then the membranes were fixed on the periosteum by sutures, and the remainder served as controls. Tissue closure was achieved with mattress and interrupted single sutures, and antibiotic injection was given to the dogs in the following 3 days. The dogs were divided into three groups according to the healing time of 1, 2 and 3 months, then the three groups of dogs were sacrificed. After that, tissue blocks containing the implants and the control ones were removed and studied by gross observation, X-ray radiograph and fluorescence microscope, and the surfaces of the membranes were observed by scanning electron microscope. The specimen used for light microscope study were fixed with 10% formaldehyde for 24 hours, and decalcified with 0.5 mol/L EDTA for 2 weeks. After the titanium implants were carefully removed, the tissue blocks were embedded into the paraffin wax, and the sections were obtained. RESULTS: The PHB membrane degraded slowly and partly 3 months after placement, and the biodegradable property of the PHB membrane deserved a longer period of study; The bone defects covered with PHB and titanium membrane were filled with much more new bone than that of the control group. CONCLUSION: PHB membrane can enhance bone formation and can be used for guided bone regeneration.

Animals↗

PubMed2000

[Study on physical properties of titanium alloy sample fabricated with vacuum-sintered powder metallurgy].

OBJECTIVE: To investigate the physical properties of titanium alloy fabricated with vacuum-sintered powder metallurgy. METHODS: The titanium powders of three different particle sizes(-160mesh, -200 - +300mesh, -300mesh) were selected, and mixed with copper and aluminum powder in different proportions. Two other groups were made up of titanium powder(-200 - +300mesh) plated with copper and tin. The build-up and, condensation method and a double-direction press with a metal mold were used. The green compacts were sintered at 1000 degrees C for 15 minutes in a vacuum furnace at 0.025 Pa. In the double-direction press, the specimens were compacted at the pressure of 100 MPa, 200 MPa and 300 MPa respectively. Then the linear shrinkage ratio and the opening porosity of the sintered compacts were evaluated respectively. RESULTS: 1. The linear shrinkage ratio of specimens decreased with the increased compacted pressure(P < 0.05). There was no significant difference among the linear shrinkage ratios of three different titanium powders at the same compacted pressure(P > 0.05), but that of titanium powder plated with copper and tin was higher than those of other specimens without plating(P < 0.05). 2. The opening porosity of specimens decreased with the increased compacted pressure(P < 0.05). Three different sized particle of titanium powder did not affect the opening porosity at the same compacted pressure(P > 0.05). CONCLUSION: The composition of titanium-based metal powder mixtures and the compacted pressures affect the physical properties of sintered compacts. Titanium powder plated with copper and tin is compacted and sintered easily, and the physical properties of sintered compacts are greatly improved.

Dental Alloys↗

PubMed2000

[Production, partial purification and characterization of methamidophos-degrading enzyme from methylotroph WB-1].

After cultivation for 20 h in the inorganic salt medium with methamidophos as sole carbon and nitrogen source, Methylotroph WB-1 could produce methamidophos-degrading enzyme in larger amounts. The enzyme was partially purified by sonication disruption, Tween-20 extraction, heat treatment(9 min at 60 degrees C), DEAE-cellulose 32 and CM-cellulose32 chromatography with 22.8 times purification and 78.8% recovery. Activity staining showed single violate band corresponding to that of protein staining. Optimum pH of the enzyme was 9.0; poor substrate specificity was showed. It was strongly inhibited by Hg2+, Mn2+ and Cu2+, but not by Co2+ and Zn2+; it also exhibited poor stability.

Aeromonas↗

PubMed2000

[Producing characterization of constitutive-form laccase by Basidiomycete].

A constitutive-laccase-producing fungus was gained from 20 strains of different sources with plate method. Laccase activity reached 0.58 IU/mL when the strain grew on DC medium with shaking cultivation, which was superior to stationary method by 4 times. The enzyme production paralleled with biomass in early 8 days, subsequently activities declined slightly though its biomass continued upward. Tyrosine and tryptone at the concentration of 4 g/L improved the enzyme production, reaching 2.49 and 2.0 IU/mL respectively. Some tested chemical agents seemed not to contribute to the increase of the enzyme production effectively except for syringaldazine and o-tolidine. Heatshock at 40 degrees C for 1 h made 1.3 times more enzyme expression.

Basidiomycota↗

PubMed1999

Inhibition of DNA synthesis by downregulation of cyclin A but not Skp 2 overexpression in human hepatocellular carcinoma cells.

Cyclin A is an S and G2/M phase regulatory protein and associates with Skp 2 in many transformed cells. Our previous results showed that 12 (39%) and 17 (55%) out of 31 hepatocellular carcinoma (HCC) patients exhibited higher protein expression levels of cyclin A and Skp 2, respectively, in their tumorous compared to non-tumorous tissues. In the present study, we used Western blot analysis to show that 3 out of 6 HCC cell lines, HA59T, HA22T and HCC36, exhibited overexpression of cyclin A, among which the HCC36 cell line also expressed a higher Skp 2 protein level. Moreover, we used the antisense oligonucleotide phosphorothioates to down regulate the overexpression of cyclin A and Skp 2 proteins to determine whether or not these two proteins are involved in the mitogenesis of HCC36 cells. After treatment with antisense oligonucleotide phosphorothioates, the gene product of cyclin A or Skp 2 was suppressed dose-dependently as revealed by Western blot analyses. By [3H]thymidine incorporation assay, we found that downregulation of cyclin A but not Skp 2 overexpression could inhibit the DNA synthesis ability of HCC36 cells, suggesting that abnormal Skp 2 expression is not directly correlated with the HCC proliferation.

Carcinoma, Hepatocellular↗

PubMed1999

A multi-centre randomized phase II study of nolatrexed versus doxorubicin in treatment of Chinese patients with advanced hepatocellular carcinoma.

PURPOSE: A multi-centre randomized phase II study of single agent nolatrexed dihydrochloride versus doxorubicin was undertaken in Chinese patients with advanced hepatocellular carcinoma (HCC) to study and compare the clinical efficacy of the two drugs. METHODS: Fifty-four patients with clinical or histological diagnosis of HCC were randomized in a 2:1 ratio to receive nolatrexed or doxorubicin. Nolatrexed 725 mg/m(2)/day was given by continuous infusion via a central venous device for 5 days and doxorubicin 60 mg/m(2) was given as a rapid intravenous infusion every 3 weeks. RESULTS: No objective responses were observed in either treatment arm. Two patients in the nolatrexed arm and none in the doxorubicin arm had >50% decline in serum alpha-fetoprotein. The median survival for the patients in the nolatrexed and doxorubicin arms was 139 days and 104 days, respectively. Moderate toxicities including leukopenia, thrombocytopenia, mucositis and skin rash were observed in both treatment arms. CONCLUSION: Nolatrexed and doxorubicin are minimally active in the treatment of advanced HCC. Given the small sample size, no difference is observed between the two drugs.

Adult↗

PubMed1999

A novel podophyllotoxin-derived compound GL331 is more potent than its congener VP-16 in killing refractory cancer cells.

PURPOSE: GL331 is a new homolog of VP-16, and has demonstrated more efficacious anti-cancer activity in both the in vitro and in vivo lymphoma systems. To extensively explore GL331's clinical value, we furthermore evaluate the cytotoxicity and apoptosis-inducing activity of GL331 in several human cell lines from cancers that are not normally treated with VP-16. METHODS: By MTT and clonogenic survival assays, the cytotoxicities of GL331 and VP-16 were evaluated in a variety of cell lines including nasopharyngeal, hepatocellular, gastric, colon, cervical, and neuroblastoma cancer types. Western blot analysis was performed to detect the MDR-1 level in these cell lines. By Annexin V-staining flow cytometry and detection of DNA ladders, the apoptosis-inducing activities of GL331 and VP-16 were also evaluated. RESULTS: GL331 showed more efficacy than its congener VP-16 in killing cancer cells. The estimated ID50 of GL331 were 2.5 to 17-fold lowerthan those of VP-16. GL331 possessed more cell-killing activity even in MDR-1-overexpressing cell lines such as HCC36 and SW620. Its higher cytotoxicity could be attributed by the elevated ability to induce apoptotic cell death. CONCLUSION: GL331's overriding drug resistance and higher cancer cell-killing activity suggest its superiority in clinical cancer therapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1999

Involvement of Fas (CD95/APO-1) and Fas ligand in apoptosis induced by ganciclovir treatment of tumor cells transduced with herpes simplex virus thymidine kinase.

Transduction of cancer cells with herpes simplex virus thymidine kinase gene (HSVtk) followed by prodrug ganciclovir (GCV) treatment has been shown to induce apoptosis. In this study, four murine tumors including B16F10 melanoma, NG4TL4 sarcoma, H6 hepatoma and 1MEA 7R.1 hepatoma were found to vary in sensitivity to this gene therapy strategy in vitro but, at effective doses of GCV, the HSVtk-transduced cells of all four tumors showed similar kinetics of early rise in p53 protein levels, then cell cycle S-/G2-phase arrest and finally signs of apoptosis. Immunoblot analyses revealed that Fas (CD95/APO-1), Fas ligand (FasL) and two downstream mediators, RIP and caspase-3, (CPP32, YAMA, Apopain) were increased in GCV-treated HSVtk-transduced tumor cells the cell cycle arrest and before apoptosis. Increased expression of FasL could also be observed in vivo in HSVtk-transduced tumors induced to regress by GCV treatment. Enzyme measurements using specific substrate showed that the caspase-3 activation followed kinetically the FasL expression. More than half of the HSVtk/GCV-induced cell death could be abrogated by addition to the cell culture medium of a specific antisense oligonucleotide to block FasL synthesis, a recombinant Fas/Fc chimeric protein to compete with Fas receptor for FasL binding, or cell-permeable specific tetrapeptide inhibitors of caspase-3 or caspase-8.

Animals↗

PubMed1999

Serum levels of cytokines in hepatitis C-related liver disease: a longitudinal study.

BACKGROUND: Elevated serum cytokine levels are found in patients with acute and chronic hepatitis B. However, little is known about the development and progression of cytokines in hepatitis C infection. We conducted this study to evaluate the change and clinical significance of cytokines in the different stages of hepatitis C infection. METHODS: Circulating interleukin-1 beta (IL-1 beta), interleukin-2 receptor (IL-2r), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were measured by enzyme-linked immunosorbent assay in 29 patients with acute hepatitis C (AHC), 43 patients with chronic hepatitis C (CHC), 40 patients with liver cirrhosis (LC) and positive serum anti-hepatitis C antibody (anti-HCV), 36 patients with hepatocellular carcinoma (HCC) and positive anti-HCV and 30 normal controls. A cohort of patients with chronic hepatitis C was monitored for a median of seven years. RESULTS: Serum IL-1 beta, IL-2r, IL-6 and TNF-alpha levels were significantly elevated in all patient groups compared with controls (p < 0.05). The serum IL-1 beta, IL-2r and TNF-alpha levels in patients with LC or HCC were higher than that in patients with AHC or CHC (p < 0.05). In the longitudinal follow-up, 12 patients with chronic hepatitis at enrollment in the study developed liver cirrhosis. For these patients, serum levels of IL-1 alpha, IL-2r and TNF-alpha were higher in liver cirrhosis than in chronic hepatitis (p < 0.05). In addition, the serum concentrations of these cytokines correlated better with indices of hepatic dysfunction (prothrombin time and indocyanine green retention ratio) than with parameters of hepatic inflammation (alanine aminotransferase and aspartate aminotransferase). CONCLUSIONS: Serum IL-1 beta, IL-2r, IL-6 and TNF-alpha levels are elevated in patients with hepatitis C-related liver diseases, especially in LC and HCC patients. These levels reflect hepatic dysfunction better than liver inflammation parameters, which might explain the higher serum concentrations of cytokines in LC patients.

Adult↗

PubMed1999

Characteristics and risk factors of acetaminophen-induced hepatitis in Taiwan.

BACKGROUND: Overdose of acetaminophen may cause hepatic injury and fatal fulminant hepatic failure. Acetaminophen is the most common form of drug-induced hepatic injury in Western countries. However, there is no formal report of this important issue in Taiwan. To assess the clinical characteristics and risk factors of acetaminophen-induced hepatitis in Taiwan, we conducted this study. METHODS: A total of 71 patients who were intoxicated or overdosed with acetaminophen at Veterans General Hospital-Taipei between February, 1991 and June, 1997 were enrolled in this study. Acetaminophen-induced hepatitis was defined according to the Paris international consensus criteria. RESULTS: Suicide attempt was the major cause (67/71) of acetaminophen overdose. Sixty-two of the patients were female. The mean patient age was 24.5 +/- 9.7 years (+/- standard deviation, SD). Nineteen of 71 patients had acetaminophen-induced hepatitis. The peak serum alanine aminotransferase, aspartate aminotransferase and total bilirubin concentrations were 4,181.0 +/- 931.4 IU/l (mean +/- SD), 4,148.0 +/- 1,147.5 IU/l and 2.6 +/- 0.4 mg/dl, respectively. The hepatitis group had higher ingested acetaminophen doses and serum peak acetaminophen levels than did those of the nonhepatitis group (24.9 g vs 12.9 g, p = 0.004; 132.0 mg/l vs 61.7 mg/l, p = 0.013). A higher percentage of alcohol consumption was also noted in the hepatitis group than in the nonhepatitis group (32% vs 12%, p = 0.05). After logistic regression for multivariate analysis, alcohol consumption was the most important risk factor for acetaminophen-induced hepatitis (odds ratio = 8.14, p = 0.018), followed by ingested acetaminophen dose (odds ratio = 1.21, p = 0.001). Most patients received acetylcysteine treatment in time. Two of the 19 patients with hepatitis died. CONCLUSIONS: The majority of acetaminophen-induced hepatitis in Taiwan occurs in young females who attempt suicide. Alcohol consumption and the dose of acetaminophen ingested were the significant risk factors for acetaminophen-induced hepatitis. Alcohol should not be concomitantly used with acetaminophen. Early diagnosis and administration of the antidote are crucial to decrease mortality.

Acetaminophen↗

PubMed1999

Circulating intercellular adhesion molecule-1 in chronic liver disease and hepatocellular carcinoma.

BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) is important in the migration and adhesion of immune cells from the circulation to their targets. A circulating form of ICAM-1 (cICAM-1) is elevated in the serum of patients with hepatitis and various cancers. Our aim was to determine the clinical significance of cICAM-1 in chronic liver diseases and hepatocellular carcinoma (HCC). METHODS: We measured the serum cICAM-1 levels in 91 patients with HCC, 47 with liver cirrhosis, 41 with chronic viral hepatitis and 32 healthy controls using an enzyme-linked immunosorbent assay. Ninety-eight patients had serial follow-up. RESULTS: The cICAM-1 levels in patients with HCC (737 +/- 212 ng/ml) and liver cirrhosis (593 +/- 145 ng/ml) were significantly higher than those in patients with chronic viral hepatitis (488 +/- 127 ng/ml) and controls (318 +/- 64 ng/ml). HCC patients had higher cICAM-1 levels than all the other groups. cICAM-1 levels in patients with chronic viral hepatitis correlated with serum alanine aminotransferase, prothrombin time and indocyanine green retention ratio. In HCC patients, alpha-fetoprotein levels and tumor size paralleled cICAM-1 concentrations. Furthermore, HCC patients with distant metastases had higher cICAM-1 levels than those without distant metastases, and levels of cICAM-1 in patients with stage IV HCC were higher than those in HCC patients with stages I, II or III disease. During a seven-year follow-up, 14 patients with chronic hepatitis developed liver cirrhosis when their cICAM-1 levels increased significantly. In 47 HCC patients, cICAM-1 levels decreased after tumor resection or transcatheter arterial embolization, and increased when the tumor recurred. cICAM-1 levels increased gradually in 14 patients with advanced HCC without specific therapy. CONCLUSIONS: CICAM-1 levels are increased in patients with chronic hepatitis, liver cirrhosis and HCC. This reflects the severity and progression of chronic liver disease and HCC. Sequential measurements of cICAM-1 seem more valuable than a single-point assessment in evaluating the progress of liver disease.

Adult↗

PubMed1999

Gene therapy with tumor vaccine increases the survival of hepatoma-bearing mice.

BACKGROUND: Tumor vaccines combined with cytokine gene therapy and Bacillus Calmette-Guérin (BCG) were tested for prevention and therapeutic effects in the H6 mouse hepatoma model. METHODS: Plasmid DNA of expression vectors carrying cDNA of mouse interleukin (IL)-2 and mouse granulocyte-macrophage colony-stimulating factor (mGM-CSF) were used for transfection to obtain H6 mouse hepatoma cells that secreted IL-2 (H6/IL-2) or GM-CSF (H6/GM-CSF). For tumor prevention, groups of mice were immunized twice with irradiated tumor cells with untransduced H6, H6/IL-2, H6/GM-CSF, or an equal mixture of H6/IL-2 and H6/GM-CSF. Three weeks later, these mice were inoculated subcutaneously with live H6 hepatoma cells, and tumor growth was measured. For therapeutic studies, mice first inoculated with live H6 cells were treated three days later with various irradiated tumor cell vaccines alone or in combination with BCG. Subsequent tumor growth was measured. RESULTS: In tumor prevention studies, significant protection from tumor growth has been observed in animals vaccinated with irradiated cytokine-secreting H6 cells compared with those immunized with irradiated parental H6 cells. In tumor therapy studies, subsequent administration of irradiated H6/GM-CSF cells in combination with BCG impeded the tumorigenicity of preinoculated live H6 hepatoma cells. CONCLUSIONS: These results suggest that cytokine-secreting tumor vaccines have a prophylactic effect and BCG, in combination with irradiated H6/GM-CSF cells, shows a synergistic effect on delaying the growth of H6 mouse hepatomas.

Animals↗