Buchholz, Stefan and Schally, Andrew V. and Engel, Joerg B. and Hohla, Florian and Heinrich, Elmar and Koester, Frank and Varga, Jozsef L. and Halmos, Gabor (2007) Potentiation of mammary cancer inhibition by combination of antagonists of growth hormone-releasing hormone with docetaxel. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 104 (6). pp. 1943-1946. ISSN 0027-8424,
Full text not available from this repository. (Request a copy)Abstract
Antagonists of growth hormone-releasing hormone (GHRIH) are being developed for the treatment of various cancers. In this study, we investigated the effectiveness of treatment with GHRH antagonist JMR-132 alone and in combination with docetaxel chemotherapy in nude mice bearing MX-1 human breast cancers. Specific high-affinity binding sites for GHRH were found on MX-1 tumor membranes using ligand competition assays with I-125-labeled GHRH antagonist JV-1-42. JMR-132 displaced radiolabeled JV-1-42 with an IC50 of 0.14 nM, indicating a high affinity of JMR-132 to GHRH receptors. Treatment of nude mice bearing xenografts of MX-1 with JMR-132 at 10 mu g per day s.c. for 22 days significantly (P < 0.05) inhibited tumor volume by 62.9% and tumor weight by 47.8%. Docetaxel given twice at a dose of 20 mg/kg i.p. significantly reduced tumor volume and weight by 74.1% and 58.6%, respectively. Combination treatment with JMR-132 (10 tLg/day) and docetaxel (20 mg/kg i.p.) led to growth arrest of most tumors as shown by an inhibition of tumor volume and weight by 97.7% and 95.6%, respectively (P < 0.001). Because no vital cancer cells were detected in some of the excised tumors, a total regression of the tumors was achieved in some cases. Treatment with JMR-132 also strongly reduced the concentration of EGF receptors in MX-1 tumors. Our results demonstrate that GHRIH antagonists might provide a therapy for breast cancer and could be combined with clocetaxel chemotherapy to enhance the efficacy of treatment.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | METASTATIC BREAST-CANCER; IN-VIVO PROLIFERATION; HUMAN PROSTATE-CANCER; CELL LUNG-CARCINOMA; PHASE-II TRIAL; SPLICE VARIANTS; NUDE-MICE; IGF-II; GH-RH; ADJUVANT BREAST; breast cancer; cancer therapy; chemotherapeutic agents; growth hormone-releasing hormone receptors |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Frauenheilkunde und Geburtshilfe (Schwerpunkt Frauenheilkunde) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Dec 2020 10:29 |
| Last Modified: | 22 Dec 2020 10:29 |
| URI: | https://pred.uni-regensburg.de/id/eprint/33189 |
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