Record number :
641997
Title of article :
Antitumor effects of the cytotoxic luteinizing hormone–releasing hormone analog AN-152 on human endometrial and ovarian cancers xenografted into nude mice
Author/Authors :
Carsten Gründker، نويسنده , , Peter V?lker، نويسنده , , Frank Griesinger، نويسنده , , Annette Ramaswamy، نويسنده , , Attila Nagy، نويسنده , , Andrew V. Schally، نويسنده , , Günter Emons، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2002
Pages :
10
From page :
528
To page :
537
Abstract :
Objective: Most human endometrial and ovarian cancers express receptors for luteinizing hormone– releasing hormone. These receptors can be used for targeted chemotherapy with cytotoxic luteinizing hormone–releasing hormone analogs such as AN-152, in which doxorubicin is linked to [D-Lys6]luteinizing hormone–releasing hormone. Study Design: The antitumor effects of doxorubicin and AN-152 were assessed in vivo in human luteinizing hormone–releasing hormone receptor–positive HEC-1B endometrial cancers and NIH:OVCAR-3 ovarian cancers and in the luteinizing hormone–releasing hormone receptor–negative SK-OV-3 ovarian line. Nude mice bearing these tumors subcutaneously were injected intravenously with saline solution (control), AN-152, or doxorubicin at equimolar doses. Luteinizing hormone–releasing hormone receptor expression in tumors and specimens of human reproductive (n = 5) and nonreproductive (n = 15) normal tissues and in hematopoietic stem cells were analyzed with reverse transcriptase–polymerase chain reaction and radioligand binding assay. Results: The tumor volumes of luteinizing hormone–releasing hormone receptor–positive HEC-1B and NIH:OVCAR-3 cancers were reduced significantly (P< .001) 1 week after treatment with AN-152 at 700 nmol/20 g or at 300 nmol/20 g. No toxic side effects were observed. Treatment with doxorubicin arrested tumor growth but did not reduce tumor volume. Doxorubicin at 700 nmol/20 g caused a high mortality rate and at 300 nmol/20 g (8.7 mg/kg) caused a loss of body weight, but no deaths occurred. The growth of luteinizing hormone–releasing hormone receptor–negative SK-OV-3 cancers was not affected by AN-152. Normal human nonreproductive tissues, hematopoietic stem cells, and vaginal tissue did not express luteinizing hormone–releasing hormone receptors, but luteinizing hormone–releasing hormone receptors were found in the ovary, fallopian tube, cervix, endometrium, and myometrium. Conclusion: Targeted chemotherapeutic luteinizing hormone–releasing hormone analog AN-152 is more effective and less toxic than cytotoxic radical doxorubicin on luteinizing hormone–releasing hormone receptor–positive tumors. AN-152 could be considered for targeted chemotherapy in patients with ovarian or endometrial cancers. (Am J Obstet Gynecol 2002;187:528-37.)
Keywords :
LHRH receptor , cytotoxic LHRH analog , endometrial cancer , AN-152 , ovarian cancer
Journal title :
American Journal of Obstetrics and Gynecology
Serial Year :
2002
Link To Document :
بازگشت