PMID- 23102680
OWN - NLM
STAT- MEDLINE
DCOM- 20130122
LR  - 20211021
IS  - 1532-7361 (Electronic)
IS  - 0039-6060 (Print)
IS  - 0039-6060 (Linking)
VI  - 152
IP  - 6
DP  - 2012 Dec
TI  - Pasireotide (SOM230) is effective for the treatment of pancreatic neuroendocrine 
      tumors (PNETs) in a multiple endocrine neoplasia type 1 (MEN1) conditional 
      knockout mouse model.
PG  - 1068-77
LID - S0039-6060(12)00474-6 [pii]
LID - 10.1016/j.surg.2012.08.021 [doi]
AB  - BACKGROUND: Pasireotide (SOM230), a long-acting somatostatin analogue (LAR), has 
      improved agonist activity at somatostatin receptors. We tested the effect of 
      SOM230 on insulin secretion, serum glucose concentrations, tumor growth, and 
      survival using an MEN1 transgenic mouse model. METHODS: Eight 12-month-old 
      conditional Men1 knockout mice with insulinoma were assessed. The treatment (n = 
      4) and control groups (n = 4) received monthly subcutaneous injections of SOM230 
      or PBS. Serum insulin and glucose levels were determined by enzyme-linked 
      immunosorbent assay and enzymatic colorimetric assay, respectively. Tumor 
      activity, growth, and apoptosis were determined by microPET/CT scan and 
      histologic analysis. RESULTS: On day 7, there was a decrease in serum insulin 
      levels from 1.06 +/- 0.28 mug/L to 0.37 +/- 0.17 mug/L (P = .0128) and a significant 
      increase in serum glucose from 4.2 +/- 0.45 mmol/L to 7.12 +/- 1.06 mmol/L (P = 
      .0075) in the treatment group but no change in the control group. Tumor size was 
      less in the treatment group (2,098 +/- 388 mum(2)) compared with the control group 
      (7,067 +/- 955 mum(2); P = .0024). Furthermore, apoptosis was increased in the 
      treatment group (6.9 +/- 1.23%) compared with the control group (0.29 +/- 0.103%; P = 
      .002). CONCLUSION: SOM230 demonstrates antisecretory, antiproliferative, and 
      proapoptotic activity in our MEN1 model of insulinoma. Further studies of the 
      effects of SOM230 in PNET patients with MEN1 mutations are warranted.
CI  - Copyright (c) 2012 Mosby, Inc. All rights reserved.
FAU - Quinn, Thomas J
AU  - Quinn TJ
AD  - Department of Surgery, Albert Einstein College of Medicine, New York, NY 10467, 
      USA.
FAU - Yuan, Ziqiang
AU  - Yuan Z
FAU - Adem, Asha
AU  - Adem A
FAU - Geha, Rula
AU  - Geha R
FAU - Vrikshajanani, Chakravarthy
AU  - Vrikshajanani C
FAU - Koba, Wade
AU  - Koba W
FAU - Fine, Eugene
AU  - Fine E
FAU - Hughes, David T
AU  - Hughes DT
FAU - Schmid, Herbert A
AU  - Schmid HA
FAU - Libutti, Steven K
AU  - Libutti SK
LA  - eng
GR  - R01 CA103830/CA/NCI NIH HHS/United States
GR  - U54 CA151668/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121024
PL  - United States
TA  - Surgery
JT  - Surgery
JID - 0417347
RN  - 0 (Blood Glucose)
RN  - 0 (Insulin)
RN  - 51110-01-1 (Somatostatin)
RN  - 98H1T17066 (pasireotide)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Blood Glucose/analysis
MH  - Insulin/blood
MH  - Mice
MH  - Mice, Knockout
MH  - Multimodal Imaging
MH  - Multiple Endocrine Neoplasia Type 1/*drug therapy/genetics
MH  - Neuroendocrine Tumors/blood/diagnostic imaging/*drug therapy/pathology
MH  - Pancreatic Neoplasms/blood/diagnostic imaging/*drug therapy/pathology
MH  - Positron-Emission Tomography
MH  - Somatostatin/*analogs & derivatives/therapeutic use
MH  - Tomography, X-Ray Computed
PMC - PMC3732168
MID - NIHMS484957
EDAT- 2012/10/30 06:00
MHDA- 2013/01/23 06:00
PMCR- 2013/08/02
CRDT- 2012/10/30 06:00
PHST- 2012/03/01 00:00 [received]
PHST- 2012/08/16 00:00 [accepted]
PHST- 2012/10/30 06:00 [entrez]
PHST- 2012/10/30 06:00 [pubmed]
PHST- 2013/01/23 06:00 [medline]
PHST- 2013/08/02 00:00 [pmc-release]
AID - S0039-6060(12)00474-6 [pii]
AID - 10.1016/j.surg.2012.08.021 [doi]
PST - ppublish
SO  - Surgery. 2012 Dec;152(6):1068-77. doi: 10.1016/j.surg.2012.08.021. Epub 2012 Oct 
      24.