PMID- 26990064
OWN - NLM
STAT- MEDLINE
DCOM- 20170605
LR  - 20220129
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 157
IP  - 5
DP  - 2016 May
TI  - 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.
PG  - 1789-98
LID - 10.1210/en.2015-1965 [doi]
AB  - 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.
FAU - Walls, Gerard V
AU  - Walls GV
AD  - Academic Endocrine Unit (G.V.W., M.S., B.S.S., K.E.L., R.V.T.), Radcliffe 
      Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism 
      (OCDEM), University of Oxford, Churchill Hospital, Oxford, OX3 7LJ, United 
      Kingdom; Nuffield Department of Surgical Sciences (G.V.W., B.S.S.), University of 
      Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, United Kingdom; Department of 
      Endocrinology (A.B.G.), OCDEM, Churchill Hospital, Oxford, OX3 7LJ, United 
      Kingdom; and Novartis Pharma AG (H.A.S.), Novartis Institutes for Biomedical 
      Research, Oncology, CH-4057 Basel, Switzerland.
FAU - Stevenson, Mark
AU  - Stevenson M
AD  - Academic Endocrine Unit (G.V.W., M.S., B.S.S., K.E.L., R.V.T.), Radcliffe 
      Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism 
      (OCDEM), University of Oxford, Churchill Hospital, Oxford, OX3 7LJ, United 
      Kingdom; Nuffield Department of Surgical Sciences (G.V.W., B.S.S.), University of 
      Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, United Kingdom; Department of 
      Endocrinology (A.B.G.), OCDEM, Churchill Hospital, Oxford, OX3 7LJ, United 
      Kingdom; and Novartis Pharma AG (H.A.S.), Novartis Institutes for Biomedical 
      Research, Oncology, CH-4057 Basel, Switzerland.
FAU - Soukup, Benjamin S
AU  - Soukup BS
AD  - Academic Endocrine Unit (G.V.W., M.S., B.S.S., K.E.L., R.V.T.), Radcliffe 
      Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism 
      (OCDEM), University of Oxford, Churchill Hospital, Oxford, OX3 7LJ, United 
      Kingdom; Nuffield Department of Surgical Sciences (G.V.W., B.S.S.), University of 
      Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, United Kingdom; Department of 
      Endocrinology (A.B.G.), OCDEM, Churchill Hospital, Oxford, OX3 7LJ, United 
      Kingdom; and Novartis Pharma AG (H.A.S.), Novartis Institutes for Biomedical 
      Research, Oncology, CH-4057 Basel, Switzerland.
FAU - Lines, Kate E
AU  - Lines KE
AD  - Academic Endocrine Unit (G.V.W., M.S., B.S.S., K.E.L., R.V.T.), Radcliffe 
      Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism 
      (OCDEM), University of Oxford, Churchill Hospital, Oxford, OX3 7LJ, United 
      Kingdom; Nuffield Department of Surgical Sciences (G.V.W., B.S.S.), University of 
      Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, United Kingdom; Department of 
      Endocrinology (A.B.G.), OCDEM, Churchill Hospital, Oxford, OX3 7LJ, United 
      Kingdom; and Novartis Pharma AG (H.A.S.), Novartis Institutes for Biomedical 
      Research, Oncology, CH-4057 Basel, Switzerland.
FAU - Grossman, Ashley B
AU  - Grossman AB
AD  - Academic Endocrine Unit (G.V.W., M.S., B.S.S., K.E.L., R.V.T.), Radcliffe 
      Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism 
      (OCDEM), University of Oxford, Churchill Hospital, Oxford, OX3 7LJ, United 
      Kingdom; Nuffield Department of Surgical Sciences (G.V.W., B.S.S.), University of 
      Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, United Kingdom; Department of 
      Endocrinology (A.B.G.), OCDEM, Churchill Hospital, Oxford, OX3 7LJ, United 
      Kingdom; and Novartis Pharma AG (H.A.S.), Novartis Institutes for Biomedical 
      Research, Oncology, CH-4057 Basel, Switzerland.
FAU - Schmid, Herbert A
AU  - Schmid HA
AD  - Academic Endocrine Unit (G.V.W., M.S., B.S.S., K.E.L., R.V.T.), Radcliffe 
      Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism 
      (OCDEM), University of Oxford, Churchill Hospital, Oxford, OX3 7LJ, United 
      Kingdom; Nuffield Department of Surgical Sciences (G.V.W., B.S.S.), University of 
      Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, United Kingdom; Department of 
      Endocrinology (A.B.G.), OCDEM, Churchill Hospital, Oxford, OX3 7LJ, United 
      Kingdom; and Novartis Pharma AG (H.A.S.), Novartis Institutes for Biomedical 
      Research, Oncology, CH-4057 Basel, Switzerland.
FAU - Thakker, Rajesh V
AU  - Thakker RV
AD  - Academic Endocrine Unit (G.V.W., M.S., B.S.S., K.E.L., R.V.T.), Radcliffe 
      Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism 
      (OCDEM), University of Oxford, Churchill Hospital, Oxford, OX3 7LJ, United 
      Kingdom; Nuffield Department of Surgical Sciences (G.V.W., B.S.S.), University of 
      Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, United Kingdom; Department of 
      Endocrinology (A.B.G.), OCDEM, Churchill Hospital, Oxford, OX3 7LJ, United 
      Kingdom; and Novartis Pharma AG (H.A.S.), Novartis Institutes for Biomedical 
      Research, Oncology, CH-4057 Basel, Switzerland.
LA  - eng
GR  - 913/DH_/Department of Health/United Kingdom
GR  - G0501780/MRC_/Medical Research Council/United Kingdom
GR  - G1000467/MRC_/Medical Research Council/United Kingdom
GR  - G9825289/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160318
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 51110-01-1 (Somatostatin)
RN  - 98H1T17066 (pasireotide)
SB  - IM
MH  - Alleles
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Cell Proliferation/drug effects
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Female
MH  - Mice
MH  - Multiple Endocrine Neoplasia/*drug therapy/genetics/pathology
MH  - Multiple Endocrine Neoplasia Type 1/*genetics
MH  - Neuroendocrine Tumors/*drug therapy/genetics/pathology
MH  - Somatostatin/*analogs & derivatives/pharmacology/therapeutic use
PMC - PMC4870877
EDAT- 2016/03/19 06:00
MHDA- 2017/06/06 06:00
PMCR- 2016/03/18
CRDT- 2016/03/19 06:00
PHST- 2016/03/19 06:00 [entrez]
PHST- 2016/03/19 06:00 [pubmed]
PHST- 2017/06/06 06:00 [medline]
PHST- 2016/03/18 00:00 [pmc-release]
AID - EN-15-1965 [pii]
AID - 10.1210/en.2015-1965 [doi]
PST - ppublish
SO  - Endocrinology. 2016 May;157(5):1789-98. doi: 10.1210/en.2015-1965. Epub 2016 Mar 
      18.