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.
Pubmed ID: 26990064 RIS Download
Mesh terms: Alleles | Animals | Apoptosis | Cell Proliferation | Disease Models, Animal | Disease Progression | Female | Mice | Multiple Endocrine Neoplasia | Multiple Endocrine Neoplasia Type 1 | Neuroendocrine Tumors | Somatostatin
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MRIcro allows Windows and Linux computers view medical images. It is a standalone program, but includes tools to complement SPM (software that allows neuroimagers to analyze MRI, fMRI and PET images). MRIcro allows efficient viewing and exporting of brain images. In addition, it allows neuropsychologists to identify regions of interest (ROIs, e.g. lesions). MRIcro can create Analyze format headers for exporting brain images to other platforms. Some features of MRIcro are: - Converts medical images to SPM friendly Analyze format. - View Analyze format images (big or little endian). - Create Analyze format headers (big or little endian). - Create 3D regions of interest (with computed volume & intensity). - Overlap multiple regions of interest. - Rotate images to match SPM template images. - Export images to BMP, JPEG, PNG or TIF format. - Yoked images: linked viewing of multiple images (e.g. view same coordinates of PET and MRI scans). Users familiar with other Windows programs will find that this software is fairly straightforward to use. Resting the mouse cursor over a button will cause a text hint to appear over the button. However, a tutorial with a step by step guide of how to use MRIcro with SPM is available.
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