Back to Search
Start Over
Pasireotide Therapy of Multiple Endocrine Neoplasia Type 1-Associated Neuroendocrine Tumors in Female Mice Deleted for an Men1 Allele Improves Survival and Reduces Tumor Progression.
- Source :
-
Endocrinology [Endocrinology] 2016 May; Vol. 157 (5), pp. 1789-98. Date of Electronic Publication: 2016 Mar 18. - Publication Year :
- 2016
-
Abstract
- Pasireotide, a somatostatin analog, is reported to have anti-proliferative effects in neuroendocrine tumors (NETs). We therefore assessed the efficacy of pasireotide for treating pancreatic and pituitary NETs that develop in a mouse model of multiple endocrine neoplasia type 1 (MEN1). Men1(+/-) mice were treated from age 12 mo with 40 mg/kg pasireotide long-acting release formulation, or PBS, intramuscularly monthly for 9 mo. The Men1(+/-) mice had magnetic resonance imaging at 12 and 21 mo, and from 20 mo oral 5-bromo-2-deoxyuridine for 1 mo, to assess tumor development and proliferation, respectively. NETs were collected at age 21 mo, and proliferation and apoptosis assessed by immunohistochemistry and TUNEL assays, respectively. Pasireotide-treated Men1(+/-) mice had increased survival (pasireotide, 80.9% vs PBS, 65.2%; P < .05), with fewer mice developing pancreatic NETs (pasireotide, 86.9% vs PBS, 96.9%; P < .05) and smaller increases in pituitary NET volumes (pre-treated vs post-treated, 0.803 ± 0.058 mm(3) vs 2.872 ± 0.728 mm(3) [pasireotide] compared with 0.844 ± 0.066 mm(3) vs 8.847 ±1.948 mm(3) [PBS]; P < .01). In addition, pasireotide-treated mice had fewer pancreatic NETs compared with PBS-treated mice (2.36 ± 0.25 vs 3.72 ± 0.32, respectively; P < .001), with decreased proliferation in pancreatic NETs (pasireotide, 0.35 ± 0.03% vs PBS, 0.78 ± 0.08%; P < .0001) and pituitary NETs (pasireotide, 0.73 ±0.07% vs PBS, 1.81 ± 0.15%; P < .0001), but increased apoptosis in pancreatic NETs (pasireotide, 0.42 ± 0.05% vs PBS, 0.19 ± 0.03%; P < .001) and pituitary NETs (pasireotide, 14.75 ± 1.58% vs PBS, 2.35 ± 0.44%; P < .001). Thus, pasireotide increased survival and inhibited pancreatic and pituitary NET growth, thereby indicating its potential as an anti-proliferative and pro-apoptotic therapy.
- Subjects :
- Alleles
Animals
Apoptosis drug effects
Cell Proliferation drug effects
Disease Models, Animal
Disease Progression
Female
Mice
Multiple Endocrine Neoplasia genetics
Multiple Endocrine Neoplasia pathology
Neuroendocrine Tumors genetics
Neuroendocrine Tumors pathology
Somatostatin pharmacology
Somatostatin therapeutic use
Multiple Endocrine Neoplasia drug therapy
Multiple Endocrine Neoplasia Type 1 genetics
Neuroendocrine Tumors drug therapy
Somatostatin analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 1945-7170
- Volume :
- 157
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 26990064
- Full Text :
- https://doi.org/10.1210/en.2015-1965