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Biomedical subjects

M Kew

Publications and source records attributed to M Kew.

34 records · Page 2Linked to original sources
PubMed1990

Polymerase chain reaction to detect hepatitis B virus DNA and RNA sequences in primary liver cancers from patients negative for hepatitis B surface antigen.

BACKGROUND AND METHODS: The role of hepatitis B virus (HBV) in the course of patients with primary liver cancer who are negative for hepatitis B surface antigen has been debated. We used the polymerase chain reaction to evaluate 28 such patients for the presence of DNA and RNA sequences of the virus; 22 of these patients had associated cirrhosis. The patients were from areas with different prevalences of HBV infection (South Africa, Italy, France, and Japan). RESULTS: Antibodies to the surface and core antigens of HBV were detected in 10 of the 23 patients tested. HBV DNA sequences were detected in 17 of the 28 patients, including 8 of the 10 with HBV antibodies and 6 of 13 without HBV serologic markers. HBV RNA molecules were found in four of five tumors tested. CONCLUSIONS: Our investigation indicates that transcriptionally active HBV genomes are present in various geographic areas among patients with liver cancer who are negative for hepatitis B surface antigen. This observation is consistent with an etiologic role for the virus in the development of these tumors.

Adult↗
PubMed1989

Loss of heterozygosity suggests tumor suppressor gene responsible for primary hepatocellular carcinoma.

Primary hepatocellular carcinoma (PHC), epidemiologically associated with chronic hepatitis B virus (HBV) infection, has historically been felt to be caused by the activation or introduction of an oncogene. However, transforming sequences from human PHC have not been reproducibly isolated. In this paper, evidence is presented that suggests PHC may result instead from the loss of an anti-oncogene. Seven of 12 human primary liver tumors tested against a panel of restriction fragment length polymorphisms (RFLPs) demonstrated loss of constitutional heterozygosity for markers on chromosome 4. Tumor and nontumor liver tissue were typed for 11 chromosome 4 RFLPs. In addition, at least one RFLP on nine other chromosomes (1, 2, 6, 7, 9, 11, 13, 14, and 17) was tested for allelic loss. Seven of nine tumors constitutionally heterozygous for chromosome 4q markers showed allele loss in tumor tissue. Six of the seven samples were jointly informative for both 4p and 4q markers. Five of the six demonstrated loss for only 4q RFLPs. In one individual, in which two samples were taken from distant locations within the same tumor, both samples showed loss of the same alleles. Among the other chromosomes informative for allele loss, one tumor showed changes on 13q. No other changes were observed in RFLPs located on the eight other chromosomes tested. These results indicate that an anti-oncogene may be located on 4q and suggest a mechanism for PHC and other cancers seroepidemiologically related to virus infection. Liver cancer caused by chronic HBV infection or other environmental agents may be linked through genetic events responsible for the loss of a tumor suppressor locus (anti-oncogene) located on chromosome 4.

Carcinoma, Hepatocellular↗
PubMed1988

Cell-surface changes associated with transformation of human hepatocytes to the malignant phenotype.

Hepatocellular carcinoma is one of the leading causes of cancer death in the world. To understand the cellular changes associated with transformation of hepatocytes to the malignant state, we have made several libraries of monoclonal antibodies against the hepatocellular carcinoma cell line FOCUS and have found six antibodies (AF-20, SF-25, SF-31, SF-90, XF-4, and XF-8) that recognize antigens expressed at consistently higher levels on hepatoma cells. We have studied malignant and nontransformed liver tissue from the same individual by using direct 125I-labeled antibody binding and immunoperoxidase staining techniques. For each of these antibodies, we found striking increases in antigen expression on the transformed tissues. These antigens were found to be expressed throughout the tumor and on distant metastases, with little, if any, expression on the nontransformed adjacent liver. These antibodies demonstrate that hepatic transformation may be accompanied by stereotyped and predictable antigenic changes. The uniformity of such antigenic changes suggests an association between these cell-surface alterations and the malignant transformation process.

Antibodies, Monoclonal↗
PubMed1987

Combination chemotherapy of hepatocellular cancer. Comparison of adriamycin + VM 26 + 5-fluorouracil with mAMSA + VM 26 + 5-fluorouracil.

Forty-seven patients with hepatocellular cancer were treated in a randomised trial comparing adriamycin + VM 26 + 5-Fluorouracil (5-FU) to mAMSA + VM 26 + 5-FU. Thirteen patients had a partial response to treatment (28%) and another 6 (13%) showed disease stabilisation. There were no significant differences in the response rates between the two treatment regimens. Patients who responded to treatment showed significant prolongation of survival (48 weeks) when compared to non-responders (5 weeks).

Adult↗
PubMed1985

Deletion in chromosome 11p associated with a hepatitis B integration site in hepatocellular carcinoma.

Hepatitis B virus (HBV), a virus with known carcinogenic potential, integrates into cellular DNA during long-term persistent infection in man. Hepatocellular carcinomas isolated from viral carriers often contain clonally propagated viral DNA integrations. As small chromosomal deletions are associated with several types of carcinomas, the occurrence of chromosomal deletions in association with HBV integration in hepatocellular carcinoma was studied. HBV integration was accompanied by a deletion of at least 13.5 kilobases of cellular sequences in a human hepatocellular carcinoma. The viral DNA integration and deletion of cellular sequences occurred on the short arm of chromosome 11 at location 11p13-11p14. The cellular sequences that were deleted at the site of HBV integration were lost from the tumor cells, leaving only a single copy of the remaining cellular allele.

Animals↗
PubMed1983

Lymphocyte subtypes in patients with atopic eczema, protein calorie malnutrition, SLE and liver disease.

Peripheral blood lymphocytes from patients with protein calorie malnutrition, atopic eczema, systemic lupus erythematosus and in three groups of patients with liver disease, were characterized by reactivity with monoclonal antibodies to the surface antigens of helper-inducer (OKT4) and suppressor-cytotoxic (OKT8) T cell subsets and to a common T cell antigen (OKT3). The protein calorie malnutrition group showed a considerable decrease in all subsets while patients with atopic eczema displayed an increase in the total number of OKT3+ cells, attributable primarily to an increase in the OKT4+ cell population with the OKT8+ cells remaining within normal values. In the SLE group, only 3 of the 16 patients had OKT8+ numbers below that of normal controls, whereas the mean number of OKT4+ cells in the group was less than normal controls. The striking feature of patients with liver disease, was the altered ratio of OKT4+ to OKT8+ cells in the hepatocellular carcinoma and amebic liver abscess groups due primarily to decreased OKT4+ and raised OKT8+ cell subpopulations.

Antibodies, Monoclonal↗
PubMed1982

Depressed natural killer cell activity in patients with hepatocellular carcinoma. In vitro effects of interferon and levamisole.

Enriched lymphocytes from patients with primary hepatocellular carcinoma showed considerably reduced natural cytotoxicity against two established hepatoma cell lines and against the myelogenous derived cell line K562, as compared to lymphocytes from normal volunteers or from patients with various nonmalignant liver diseases. The serum of hepatoma patients did not effect normal or patient NK cell activity. When lymphocytes from patients or controls were treated for three hours with human leukocyte interferon, NK cell cell activity was significantly improved. Levamisole did not produce a significant increase in normal NK cytotoxicity but did improve the killing of lymphocytes from patients with hepatocellular carcinoma.

Adult↗
PubMed1978

Serum somatomedin and insulin levels in tumor hypoglycemia.

Serum concentrations of somatomedin and immunoreactive insulin were measured during the hypoglycemic phase of 3 patients with tumor hypoglycemia. Normal amounts of somatomedin were detected in their fasting sera, but they may have been inappropriate (or associated with enhanced insulin-like activity) considering the degree of hypoglycemia. Fasting serum insulin levels were consistently depressed, and in two of the cases remained low even after an oral glucose load. Nevertheless, the blood glucose concentrations of these two patients fell to hypoglycemic levels again by 3 hours; the mechanism of this reactive hypoglycemia remains unclear.

Adult↗
PubMed1976

57-cobalt-bleomycin as a tumor scanning agent in primary hepatocellular cancer.

57Co-bleomycin and 99mTc-sulfur colloid scans were performed in 13 southern African black patients with primary hepatocellular cancer (PHC) and 3 patients with other space-occupying hepatic lesions. Selective concentration of 57Co-bleomycin in the defect or defects seen on the 99mTc-sulfur colloid scan occurred in only 4 of the 13 (31%) patients with PHC. In the remaining PHC patients, as well as in the 2 patients with metastatic liver disease and the 1 patient with an amebic liver abscess, the 57 Co-bleomycin and 99mTc-sulfur colloid scans were identical. 57Co-bleomycin appears to have only a limited place as a tumor-seeking agent in the diagnosis of PHC in southern African blacks.

Bleomycin↗
PubMedDate not supplied

Recombinant leukocyte interferon treatment of chronic hepatitis B.

We have investigated the efficacy of a relatively prolonged course of recombinant leukocyte interferon treatment in 14 chronic HBsAg-, HBeAg-, hepatitis B virus DNA- and DNA polymerase-positive carriers. alpha-Interferon was administered for 9 weeks. Six of 14 treated carriers have a sustained loss of HBeAg, hepatitis B virus DNA and DNA polymerase. Four subsequently lost HBsAg (28.5%). Elevated pretreatment SGPT concentrations, histologic chronic active hepatitis, an exacerbation of chronic hepatitis with an increase in SGPT concentrations in the last weeks of treatment and possibly recent onset of the carrier state was associated with complete inhibition of viral replication. None of 11 matched, untreated HBsAg-, HBeAg-, hepatitis B virus DNA- and DNA polymerase-positive carriers monitored during the same period lost HBsAg. The effect of recombinant leukocyte interferon may require an appropriate host-immune response. The efficacy of recombinant leukocyte interferon therapy is restricted, but it may be of benefit in a proportion of carriers, if these carriers can be precisely identified.

Adult↗
PubMedDate not supplied

c-fos and c-myc oncoprotein expression in human hepatocellular carcinomas.

Amounts of the proteins encoded by the two oncogenes c-myc and c-fos have been compared in seven specimens of hepatocellular carcinoma and two normal liver samples using a Western blot procedure. It was found that with the exception of one tumour, the amount of these proteins was markedly increased in the tumours when compared to the normal specimens. Furthermore, there appeared to be elevated c-myc and c-fos mRNA concentrations in the tumours which correlated with the protein levels. This is the first report of such a correlation in human hepatocellular carcinoma. We propose that transactivation of these oncogenes may in part be responsible for transformation in hepatocellular carcinoma.

Blotting, Western↗
PubMedDate not supplied

Expression of c-erbA in human hepatocellular carcinomas.

The expression of the oncogene c-erbA was studied in six hepatocellular carcinoma specimens and normal hepatic tissue. Total RNA isolated from these samples was analysed by Northern as well as slot blot hybridisation to a radioactive c-erbA probe. When compared to normal tissue, expression in the tumour and tissue adjacent to tumour was markedly elevated. These results suggest that overexpression of c-erbA is related to hepatocarcinogenesis. Southern blot analysis of DNA from the tumours gave no evidence of c-erbA rearrangements.

Blotting, Northern↗