TY - JOUR
T1 - Growth inhibition of experimental pancreatic cancers and sustained reduction in epidermal growth factor receptors during therapy with hormonal peptide analogs
AU - Szepesházi, Karoly
AU - Halmos, Gabor
AU - Schally, Andrew V.
AU - Arencibia, José M.
AU - Groot, Kate
AU - Vadillo-Buenfil, Manuel
AU - Rodriguez-Martin, Eulalia
N1 - Funding Information:
Acknowledgements The authors thank Amy Giroir, Dora Rigo, Veronica Lea, and Elena Glotser for their excellent technical assistance. This work was supported by a grant from ASTA Medica (Frankfurt/Main, Germany) to Tulane University School of Medicine and by the Research Service of the Department of Veterans Affairs (to A.V.S.). The work of M.V.-B. was supported by a fellowship from CONACYT (Consejo Nacional de Ciencia y Tecnologia, Mexico), and E.R.-M. was supported by the University of Alcala de Henares, Madrid, Spain. Part of this work was presented at the 10th International Congress of Endocrinology, San Francisco, Calif., in June 1996.
PY - 1999
Y1 - 1999
N2 - Reduction in receptors for epidermal growth factor (EGF) in cancers appears to be one of the principal mechanisms through which peptide hormone analogs can inhibit tumor growth. In this study, hamsters with nitrosamine-induced pancreatic cancers were treated for 8 weeks with bombesin/gastrin-releasing peptide (GRP) antagonist RC-3095, somatostatin analog RC-160 or the luteinizing hormone-releasing hormone antagonist Cetrorelix, using sustained delivery systems releasing 20, 35 and 20 μg analog/ day respectively. To establish the pattern of changes in the number and affinity of EGF receptors on tumors, groups of animals were sacrificed at regular intervals during therapy. Chronic treatment with RC-3095 or Cetrorelix resulted in an early (day 10) and sustained reduction (71% or 69% respectively) in EGF receptors on pancreatic tumors. In contrast, RC-160 decreased receptor concentration by 60% only after 20 days. Among the histological characteristics of proliferation, the decrease in argyrophilic nucleolar organizer regions, but not apoptotic and mitotic indices, showed a correlation with the fall in EGF receptors. The concentration of the receptors returned to the control level 4 days after cessation of chronic treatment with RC-3095. The effect of single injections of RC-3095, RC-160 and Cetrorelix on EGF receptors was also investigated. RC-160 decreased the number of EGF receptors on pancreatic cancers by 31% 3 h after administration, but the receptors had returned to normal level at 6 h. RC-3095 and Cetrorelix caused a 67% and 59% decline, respectively, in EGF receptors only 6 h after injection and the concentration of receptors remained low for 24 h. Thus, the pattern of down-regulation of EGF receptors in pancreatic cancers appears to depend on the peptide used for therapy. Since the antitumor effect may be the result of the fall in EGF receptors in cancers, information on the time course of changes in these receptors during treatment with these analogs may lead to an improvement in therapeutic regimens.
AB - Reduction in receptors for epidermal growth factor (EGF) in cancers appears to be one of the principal mechanisms through which peptide hormone analogs can inhibit tumor growth. In this study, hamsters with nitrosamine-induced pancreatic cancers were treated for 8 weeks with bombesin/gastrin-releasing peptide (GRP) antagonist RC-3095, somatostatin analog RC-160 or the luteinizing hormone-releasing hormone antagonist Cetrorelix, using sustained delivery systems releasing 20, 35 and 20 μg analog/ day respectively. To establish the pattern of changes in the number and affinity of EGF receptors on tumors, groups of animals were sacrificed at regular intervals during therapy. Chronic treatment with RC-3095 or Cetrorelix resulted in an early (day 10) and sustained reduction (71% or 69% respectively) in EGF receptors on pancreatic tumors. In contrast, RC-160 decreased receptor concentration by 60% only after 20 days. Among the histological characteristics of proliferation, the decrease in argyrophilic nucleolar organizer regions, but not apoptotic and mitotic indices, showed a correlation with the fall in EGF receptors. The concentration of the receptors returned to the control level 4 days after cessation of chronic treatment with RC-3095. The effect of single injections of RC-3095, RC-160 and Cetrorelix on EGF receptors was also investigated. RC-160 decreased the number of EGF receptors on pancreatic cancers by 31% 3 h after administration, but the receptors had returned to normal level at 6 h. RC-3095 and Cetrorelix caused a 67% and 59% decline, respectively, in EGF receptors only 6 h after injection and the concentration of receptors remained low for 24 h. Thus, the pattern of down-regulation of EGF receptors in pancreatic cancers appears to depend on the peptide used for therapy. Since the antitumor effect may be the result of the fall in EGF receptors in cancers, information on the time course of changes in these receptors during treatment with these analogs may lead to an improvement in therapeutic regimens.
KW - AgNOR
KW - Apoptosis
KW - Bombesin antagonist
KW - EGF receptor
KW - Experimental pancreatic cancer
KW - Hormonal therapy
KW - LH-RH antagonist
KW - Somatostatin analog
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U2 - 10.1007/s004320050301
DO - 10.1007/s004320050301
M3 - Article
C2 - 10480336
AN - SCOPUS:0032821184
VL - 125
SP - 444
EP - 452
JO - Journal of Cancer Research and Clinical Oncology
JF - Journal of Cancer Research and Clinical Oncology
SN - 0171-5216
IS - 8-9
ER -
