TY - JOUR
T1 - Effective treatment of experimental human endometrial cancers with targeted cytotoxic luteinizing hormone-releasing hormone analogues AN-152 and AN-207
AU - Engel, Jörg B.
AU - Keller, Gunhild
AU - Schally, Andrew V.
AU - Nagy, Attila
AU - Chism, David D.
AU - Halmos, Gabor
PY - 2005/4
Y1 - 2005/4
N2 - Objective: To treat experimental human endometrial cancers based on targeted chemotherapy with the cytotoxic luteinizing hormone-releasing hormone (LHRH) analogues AN-152 and AN-207. Design: Experimental study using athymic nude mice bearing xenografts of HEC-1A and RL-95-2 human endometrial cancers to assess the efficacy and toxicity of AN-152 and AN-207. The expression of LHRH receptors in HEC-1A and RL-95-2 cancers was determined by reverse transcription-polymerase chain reaction, Western blot analysis, and radioligand binding assays. Setting: Experimental laboratory research. Animal(s): Female athymic nude mice (Ncr, nu/nu). Intervention(s): Animals were treated with IV injections of the cytotoxic LHRH analogues AN-152 and AN-207 and their respective cytotoxic radicals doxorubicin (DOX) and AN-201 (2- pyrrolinodoxorubicin) on a control vehicle solution. Main Outcome Measure(s): Tumor volume, final tumor weight, tumor doubling time, body weight, white blood cell count, and LHRH receptor expression. Result(s): AN-152 significantly inhibited the growth of HEC-1A tumors. AN-207 also significantly suppressed the proliferation in vivo of HEC-1A and RL-95-2 cancers. The cytotoxic radicals DOX and AN-201 had no effect. Furthermore, mRNA for LHRH receptors, LHRH receptor protein, and high-affinity binding sites for LHRH were demonstrated on tumors. Conclusion(s): Targeted chemotherapy with AN-152 and AN-207 strongly inhibits the growth of human endometrial cancers, which express LHRH receptors, and could provide a new treatment modality for women with advanced endometrial carcinoma.
AB - Objective: To treat experimental human endometrial cancers based on targeted chemotherapy with the cytotoxic luteinizing hormone-releasing hormone (LHRH) analogues AN-152 and AN-207. Design: Experimental study using athymic nude mice bearing xenografts of HEC-1A and RL-95-2 human endometrial cancers to assess the efficacy and toxicity of AN-152 and AN-207. The expression of LHRH receptors in HEC-1A and RL-95-2 cancers was determined by reverse transcription-polymerase chain reaction, Western blot analysis, and radioligand binding assays. Setting: Experimental laboratory research. Animal(s): Female athymic nude mice (Ncr, nu/nu). Intervention(s): Animals were treated with IV injections of the cytotoxic LHRH analogues AN-152 and AN-207 and their respective cytotoxic radicals doxorubicin (DOX) and AN-201 (2- pyrrolinodoxorubicin) on a control vehicle solution. Main Outcome Measure(s): Tumor volume, final tumor weight, tumor doubling time, body weight, white blood cell count, and LHRH receptor expression. Result(s): AN-152 significantly inhibited the growth of HEC-1A tumors. AN-207 also significantly suppressed the proliferation in vivo of HEC-1A and RL-95-2 cancers. The cytotoxic radicals DOX and AN-201 had no effect. Furthermore, mRNA for LHRH receptors, LHRH receptor protein, and high-affinity binding sites for LHRH were demonstrated on tumors. Conclusion(s): Targeted chemotherapy with AN-152 and AN-207 strongly inhibits the growth of human endometrial cancers, which express LHRH receptors, and could provide a new treatment modality for women with advanced endometrial carcinoma.
KW - Cytotoxic conjugates AN-152 and AN-207
KW - Endometrial cancer
KW - LHRH receptor
KW - Targeted chemotherapy
UR - http://www.scopus.com/inward/record.url?scp=17444391204&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=17444391204&partnerID=8YFLogxK
U2 - 10.1016/j.fertnstert.2004.10.042
DO - 10.1016/j.fertnstert.2004.10.042
M3 - Article
C2 - 15831285
AN - SCOPUS:17444391204
VL - 83
SP - 1125
EP - 1133
JO - Fertility and Sterility
JF - Fertility and Sterility
SN - 0015-0282
IS - 4 SUPPL.
ER -