Reduction of bladder cancer cell growth in response to hCGbeta CTP37 vaccinated mouse serum.

The free beta-subunit of human chorionic gonadotrophin (hCGbeta) is well established as an ectopic product of epithelial tumors. Originally explained as an epi-phenomenon, hCGbeta production by many types of carcinoma is increasingly regarded as a significant tumor event. Studies in bladder cancer have shown that hCGbeta production, while not diagnostic, is a very good indicator for poor prognosis through correlations with resistance to radiotherapy and rapid metastasis. These clinical findings led to in vitro studies that have shown a direct response to hCGbeta by bladder carcinoma cell lines. This response is linked by inhibition of apoptosis to an increase in cell population. More recently, studies on hCGbeta as a marker for poor prognosis in other epithelial cancers now suggest that this phenomenon may not be restricted to bladder carcinoma. Thus, ectopic hCGbeta represents an ideal target for immunodepletive therapy. Antisera were generated from mice vaccinated with full-length hCGbeta carboxy terminal peptide (CTP37) and a truncated region comprising 24 of the amino acids of the CTP (CTP24), expressed on the surface of cowpea mosaic virus (CPMV). The effect of the resultant murine antiseras on bladder carcinoma cell growth in vitro was investigated. When CTP37 antisera, at dilutions of 1:50 and 1:100, were incubated with two hCGbeta-producing cell lines, SCaBER and RT112, significant reductions in cell number, up to 43%, were observed. In the bladder cancer cell line T24, which does not produce hCGbeta, CTP37 antisera had no growth effects. CTP24 antiserum, like control sera from mice immunized with wild-type CPMV, had no effects on the in vitro growth of any cell lines. This implies that full-length CTP37, but not CTP24, is involved in the oncogenic inhibition of apoptosis by hCGbeta. hCGbeta CTP37 vaccines are available as well-tested antifertility vaccines in the Third World. They have now been tested on cancer patients. This study is the only in vitro evidence that such a vaccine would have beneficial antitumor effects via immunodepletion mechanisms. We propose that vaccines such as this could be used as an adjuvant therapy in the treatment of hCGbeta-producing bladder cancers.

Human chorionic gonadotropin isoforms in the diagnosis of ectopic pregnancy.

BACKGROUND: Early diagnosis of ectopic pregnancy uses ultrasound with serial measurements of total human chorionic gonadotropin (hCG). The objective of this study was to explore the possibility that an isolated measurement of hCG isoforms/subunits rather than total hCG could be used as a single test for ectopic pregnancy. METHODS: Total and intact hCG, free hCG beta- and alpha-subunits (hCGbeta and -alpha), and hCG beta-core fragment were measured by RIA and IRMA in the serum and urine of 76 women presenting at outpatient emergency departments with a positive pregnancy test, lower abdominal pain, and/or vaginal bleeding. Final diagnoses were based on outcomes of pregnancies and tissue histology. RESULTS: Twenty-seven of the 76 women were subsequently diagnosed with viable pregnancies, 37 with spontaneous miscarriage, and 12 with ectopic pregnancy. Concentrations of all forms of hCG were lower in cases of ectopic pregnancy and spontaneous miscarriage than in viable pregnancies. Serum samples gave better results than urine samples. The free hCGbeta isoform (P <0.0001) had 100% sensitivity at a specificity of 79% at a 281 pmol/L (6.5 micro g/L) cutoff. Total hCG (P = 0.005) had comparable ROC characteristics with a 100% sensitivity and 68% specificity at a cutoff value of 1053 pmol/L (375 IU/L). Neither hCGbeta (P = 0.7) nor total hCG (P = 0.4) could distinguish ectopic pregnancies from spontaneous miscarriage. CONCLUSION: Measurement of serum free hCGbeta at the time of presentation can identify women with a high probability of ectopic pregnancy who may benefit from closer surveillance, reducing the risk of tubal rupture.