Pasireotide (SOM230) is effective for the treatment of pancreatic neuroendocrine tumors (PNETs) in a multiple endocrine neoplasia type 1 (MEN1) conditional knockout mouse model

Thomas J. Quinn, Ziqiang Yuan, Asha Adem, Rula Geha, Chakravarthy Vrikshajanani, Wade R. Koba, Eugene Fine, David T. Hughes, Herbert A. Schmid, Steven K. Libutti

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Abstract

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 μg/L to 0.37 ± 0.17 μg/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 μm2) compared with the control group (7,067 ± 955 μm2; 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.

Original languageEnglish (US)
Pages (from-to)1068-1077
Number of pages10
JournalSurgery (United States)
Volume152
Issue number6
DOIs
StatePublished - Dec 2012

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Multiple Endocrine Neoplasia Type 1
Neuroendocrine Tumors
Knockout Mice
Control Groups
Insulinoma
Insulin
Serum
Glucose
Therapeutics
Apoptosis
Neoplasms
Somatostatin Receptors
Enzyme Assays
Subcutaneous Injections
Growth
Somatostatin
Transgenic Mice
pasireotide
Enzyme-Linked Immunosorbent Assay
Mutation

ASJC Scopus subject areas

  • Surgery

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Pasireotide (SOM230) is effective for the treatment of pancreatic neuroendocrine tumors (PNETs) in a multiple endocrine neoplasia type 1 (MEN1) conditional knockout mouse model. / Quinn, Thomas J.; Yuan, Ziqiang; Adem, Asha; Geha, Rula; Vrikshajanani, Chakravarthy; Koba, Wade R.; Fine, Eugene; Hughes, David T.; Schmid, Herbert A.; Libutti, Steven K.

In: Surgery (United States), Vol. 152, No. 6, 12.2012, p. 1068-1077.

Research output: Contribution to journalArticle

Quinn, Thomas J. ; Yuan, Ziqiang ; Adem, Asha ; Geha, Rula ; Vrikshajanani, Chakravarthy ; Koba, Wade R. ; Fine, Eugene ; Hughes, David T. ; Schmid, Herbert A. ; Libutti, Steven K. / Pasireotide (SOM230) is effective for the treatment of pancreatic neuroendocrine tumors (PNETs) in a multiple endocrine neoplasia type 1 (MEN1) conditional knockout mouse model. In: Surgery (United States). 2012 ; Vol. 152, No. 6. pp. 1068-1077.
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abstract = "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 μg/L to 0.37 ± 0.17 μg/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 μm2) compared with the control group (7,067 ± 955 μm2; 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.",
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T1 - Pasireotide (SOM230) is effective for the treatment of pancreatic neuroendocrine tumors (PNETs) in a multiple endocrine neoplasia type 1 (MEN1) conditional knockout mouse model

AU - Quinn, Thomas J.

AU - Yuan, Ziqiang

AU - Adem, Asha

AU - Geha, Rula

AU - Vrikshajanani, Chakravarthy

AU - Koba, Wade R.

AU - Fine, Eugene

AU - Hughes, David T.

AU - Schmid, Herbert A.

AU - Libutti, Steven K.

PY - 2012/12

Y1 - 2012/12

N2 - 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 μg/L to 0.37 ± 0.17 μg/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 μm2) compared with the control group (7,067 ± 955 μm2; 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.

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 μg/L to 0.37 ± 0.17 μg/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 μm2) compared with the control group (7,067 ± 955 μm2; 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.

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