@article{GebauerMuellerFehmetal.2004, author = {Gebauer, Gerhard and Mueller, Natalia and Fehm, Tanja and Berkholz, Alexander and Beck, Eberhard and Jaeger, Wolfram and Licht, Peter}, title = {Expression and regulation of luteinizing hormone/human chorionic gonadotropin receptors in ovarian cancer and its correlation to human chorionic gonadotropin-doxorubicin sensitivity}, series = {In: American Journal of Obstetrics \& Gynecology 190 (2004), Iss. 6, pp. 1621-1628}, journal = {In: American Journal of Obstetrics \& Gynecology 190 (2004), Iss. 6, pp. 1621-1628}, pages = {1621 -- 1624}, year = {2004}, abstract = {Objective Ovarian cancer cell lines and tissues express gonadotropin receptors. Conjugation of cytostatics to ligands of these receptors may increase the specificity of cytotoxic drugs. Study design Toxicity of doxorubicin-human chorionic gonadotropin conjugates was determined in 4 ovarian cancer cell lines. Expression and regulation of luteinizing hormone/human chorionic gonadotropin receptors were analyzed before and after treatment with human chorionic gonadotropin, epidermal growth factor, and 8-bromo-cyclic adenosine monophosphate with a nested reverse transcriptase-polymerase chain reaction approach. Results Toxicity of human chorionic gonadotropin-doxorubicin conjugates was increased compared with unconjugated doxorubicin in OVCAR-3 cells. However, drug conjugates failed to demonstrate increased toxicity in other cell lines, especially after preincubation with human chorionic gonadotropin. All cell lines expressed luteinizing hormone/human chorionic gonadotropin receptors. Receptor expression in OVCAR-3 cells was not effected by human chorionic gonadotropin, endothelial growth factor, or 8-bromo-cyclic adenosine monophosphate treatment. In other cell lines, receptor expression was down-regulated by these agents. Conclusion Cytotoxic activity of doxorubicin was increased specifically by conjugation to human chorionic gonadotropin. However, the regulation of luteinizing hormone/human chorionic gonadotropin receptor expression and other compounds may reduce the drug-uptake of the conjugates.}, language = {en} } @article{GebauerFehmBecketal.2003, author = {Gebauer, Gerhard and Fehm, Tanja and Beck, Eberhard and Berkholz, Alexander and Licht, Peter and J{\"a}ger, Wolfram}, title = {Cytotoxic effect of conjugates of doxorubicin and human chorionic gonadotropin (hCG) in breast cancer cells}, series = {In: Breast Cancer Research and Treatment 77(2003)2, pp. 125-131}, journal = {In: Breast Cancer Research and Treatment 77(2003)2, pp. 125-131}, pages = {125 -- 131}, year = {2003}, abstract = {Cytotoxic activity of drug conjugates of human chorionic gonadotropin (hCG) and doxorubicin alone was investigated compared to doxorubicin in breast cancer cells with and without expression of hCG receptors. Expression of hCG receptor was determined in MCF-7 and MB231 breast cancer cell line using a multiplex nested rt-PCR approach. The entire sequence of mRNA encoding for hCG receptor was detected in MCF-7 but not in MB231 breast cancer cell line. Cytostatic effect of doxorubicin-hCG conjugates was investigated in these cell lines in comparison to unconjugated doxorubicin. The number of viable cells was determined after 24, 48, 72, 96, and 120 h. To exclude non-specific uptake of the carrier hCG from the culture media, a similar experiment was performed with albumin-doxorubicin conjugates. The number of viable cells decreased in a concentration depending manner after doxorubicin and hCG-doxorubicin conjugate treatment. However, the cytotoxic effect of hCG-doxorubicin conjugate was 10-fold increased compared to unconjugated doxorubin in hCG-receptor positive MCF-7 but not in hCG-receptor negative MB231 cells. Albumin-doxorubicin conjugates showed no increased toxicity compared to doxorubicin. We conclude that the cytotoxic effect of hCG-doxorubicin conjugates is mediated specifically via the hCG receptor. By using hCG conjugates, the development of more selective cytostatics can be achieved.}, language = {en} }