Effective treatment of experimental human endometrial cancers with targeted cytotoxic luteinizing hormone–releasing hormone analogues AN-152 and AN-207

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Effective treatment of experimental human endometrial cancers with targeted cytotoxic luteinizing hormone–releasing hormone analogues AN-152 and AN-207 Jörg B. Engel, M.D., Gunhild Keller, M.D., Andrew V. Schally, Ph.D., M.D.h.c., Attila Nagy, Ph.D., David D. Chism, M.S., Gabor Halmos, Ph.D. Fertility and Sterility Volume 83, Issue 4, Pages 1125-1133 (April 2005) DOI: 10.1016/j.fertnstert.2004.10.042 Copyright © 2005 American Society for Reproductive Medicine Terms and Conditions

FIGURE 1 Experiment 1: effects of the targeted cytotoxic luteinizing hormone-releasing hormone (LHRH) analogue AN-152 at doses equivalent to 10 mg/kg doxorubicin (DOX) and the radical DOX at equimolar doses on the growth of HEC-1A human endometrial carcinoma xenografts (mean ± SE; *P<.05, two-sided Student's t-test). Fertility and Sterility 2005 83, 1125-1133DOI: (10.1016/j.fertnstert.2004.10.042) Copyright © 2005 American Society for Reproductive Medicine Terms and Conditions

FIGURE 2 Experiment 2: effects of the targeted cytotoxic luteinizing hormone-releasing hormone (LHRH) analogue AN-207 and the radical AN-201 administered at doses of 250 nmol/kg on day 1 on the growth of HEC-1A human endometrial carcinoma xenografts (mean ± SE; *P<.05, two-sided Student's t-test). Fertility and Sterility 2005 83, 1125-1133DOI: (10.1016/j.fertnstert.2004.10.042) Copyright © 2005 American Society for Reproductive Medicine Terms and Conditions

FIGURE 3 Experiment 3: effects of the targeted cytotoxic luteinizing hormone-releasing hormone (LHRH) analogue AN-207, the radical AN-201, a mixture of AN-201 and the carrier [D-Lys6]LHRH, and [D-Lys6]LHRH alone administered at doses of 200 nmol/kg on day 1 and 150 nmol/kg on day 22 on the growth of RL-95-2 human endometrial carcinoma xenografts (mean ± SE). Effects of AN-207 after blockade of the LHRH receptors with the LHRH agonist decapeptyl are also shown (*P<.05, two-sided Student's t-test). Fertility and Sterility 2005 83, 1125-1133DOI: (10.1016/j.fertnstert.2004.10.042) Copyright © 2005 American Society for Reproductive Medicine Terms and Conditions

FIGURE 4 Experiment 3: effect of cytotoxic luteinizing hormone-releasing hormone (LHRH) analogue AN-207 and cytotoxic radical AN-201 at a dose of 200 nmol/kg followed by 150 nmol/kg on the WBC of nude mice bearing RL-95-2 human ovarian cancer xenografts (mean ± SE; *P<.05, two-sided Student's t-test). Fertility and Sterility 2005 83, 1125-1133DOI: (10.1016/j.fertnstert.2004.10.042) Copyright © 2005 American Society for Reproductive Medicine Terms and Conditions

FIGURE 5 (A), Expression of mRNA3 for luteinizing hormone-releasing hormone (LHRH) receptors in HEC-1A and RL-95-2 human endometrial carcinoma xenografts as revealed by reverse transcriptase-polymerase chain reaction (RT-PCR). PCR products were separated on a 1.8% agarose gel and stained with ethidium bromide. Lane M: 100-bp DNA ladder. Lanes 1–3: control tumor samples. Lane −: Total RNA. Lane +: mRNA from DU-145 human prostate cancer cell line as positive control for LHRH receptor. (B), Expression of LHRH receptor protein in HEC-1A and RL-95-2 human endometrial carcinoma xenografts as revealed by Western blot analysis. Lanes 1–3: RL-95-2; lanes 4–6: HEC-1A. Fertility and Sterility 2005 83, 1125-1133DOI: (10.1016/j.fertnstert.2004.10.042) Copyright © 2005 American Society for Reproductive Medicine Terms and Conditions