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R K Iles

Publications and source records attributed to R K Iles.

59 records · Page 4Linked to original sources

Beta human chorionic gonadotrophin in serum and urine. A marker for metastatic urothelial cancer.

Beta human chorionic gonadotrophin (beta HCG) was measured in 127 urine and 85 serum samples from 175 untreated patients with urothelial cancer. Serum levels of beta HCG were substantially elevated in 16 of 21 patients (76%) with widespread metastases but in only 2 of 64 patients (3%) with disease confined to the pelvis. Urine beta HCG levels were moderately raised in 11 of 25 patients (44%) with locally advanced disease, but greatly elevated in 5 of 7 patients (71%) with metastases. Measurement of serum and/or urine beta HCG appears to be an efficient diagnostic marker for the presence of distant metastases in bladder carcinoma.

Adult↗

Immunochemical analysis of the human chorionic gonadotrophin-like material secreted by 'normal' and neoplastic urothelial cells.

Material with the immunochemical characteristics of human chorionic gonadotrophin (hCG) is produced by bladder tumour cells in vitro and in vivo. In order to characterize this material further, media were collected from 17 cell cultures (three choriocarcinomas, seven bladder carcinomas and seven 'normal' urothelium). The hCG-like material was compared with pregnancy hCG and purified alpha-and beta-subunits by specific radioimmunoassays. Media were also submitted to affinity chromatography and the fractions further analysed by SDS-PAGE and Western blotting. It was shown that both the neoplastic and normal urothelium produced only free beta-subunit-like material. This urothelial 'beta-hCG' has the same molecular weight and electrophoretic mobility as that present in the intact hCG of pregnancy.

Cell Line↗

Amplification or rearrangement of the beta-human chorionic gonadotrophin (beta-hCG)--human LH gene cluster is not responsible for the ectopic production of beta-hCG by bladder tumour cells.

The beta-subunit of human chorionic gonadotrophin (hCG) is coded on chromosome 19 by the beta-hCG-hLH gene cluster. Genomic DNA has been isolated from bladder tumour cell lines which ectopically express beta-hCG. The beta-hCG-hLH gene cluster was probed for possible rearrangement or amplification and cells karyotyped for chromosome 19 abnormalities. No rearrangement or amplification of the gene cluster and no consistent abnormalities of chromosome 19 were found. The expression of beta-hCG by bladder tumours is therefore likely to be the result of altered gene regulation and not a rearrangement or amplification of this gene cluster.

Cell Line↗

Enhancement of ectopic beta-human chorionic gonadotrophin expression by interferon-alpha.

Treatment of three beta-human chorionic gonadotrophin (beta-hCG)-expressing bladder tumour cell lines with interferon-alpha (IFN-alpha) (5000 U/per 10(6) cells) enhanced the rate of beta-hCG secretion from 34.2 +/- 0.9 to 102.5 +/- 0.1 mIU/10(6) cells per 72 h in cell line 5637; 111.15 +/- 11.75 to 261.8 +/- 51.75 mIU/10(6) cells per 72 h in cell line RT112 and 503.25 +/- 28.55 to 1361.65 +/- 110.3 mIU/10(6) cells per 72 h in cell line SCaBER. IFN-gamma had no effect on the rate of beta-hCG secretion. Both interferons reduced the growth rate of the cells: incorporation of radiolabelled thymidine was reduced by 15-45% in the presence of IFN-alpha and by 20-53% with IFN-gamma. Enhancement of beta-hCG secretion by IFN-alpha was dose-dependent over the range 5-50,000 U/10(6) cells. Analysis of cell cycle profiles by flow cytometry showed no increase in the proportion of cells in the G0G1 phase in cultures treated with IFN-alpha. The conceptus of some species produces substances which are either luteotrophic or anti-luteolytic. In sheep, the corpus luteum is maintained by ovine trophoblast protein-I, which has been shown to have structural homology with human IFN-alpha. In primates and a few other higher mammals, early pregnancy is maintained by chorionic gonadotrophin. IFN-alpha is also an early product of the human conceptus. We have now shown that IFN-alpha enhances the ectopic production of the beta-subunit of hCG by bladder tumour cells. This study suggests a direct transcription/translational effect of this cytokine on the expression of a reproductive endocrine gene.

Cell Line↗

In vitro secretion of human chorionic gonadotrophin by bladder tumour cells.

Human chorionic gonadotrophin (hCG) and alphafetoprotein (AFP) were measured in culture media from a panel of 29 cell lines including 9 bladder carcinomas, 5 'normal' bladder epithelia, 10 germ cell tumours, and 5 miscellaneous tumours and 'normal' cell lines. In 7 of the 9 bladder carcinomas and 4 of the 5 'normal' bladder epithelia, the media contained hCG at levels ranging from between 34 and 3,600 IU l(-1). All other cell lines, including the 10 germ cell tumour lines gave negative results for hCG. These findings indicate that in vitro secretion of hCG is a common feature of normal and neoplastic bladder transitional epithelia, and support the hypothesis that parts of the genito-urinary epithelium have a potential for hCG production.

Cell Line↗