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Chemoprevention with Somatuline© Delays the Progression of Pancreatic Neuroendocrine Neoplasms in a Mouse Model of Multiple Endocrine Neoplasia Type 1 (MEN1)

  • Caroline L. Lopez
  • Barbara Joos
  • Detlef K. Bartsch
  • Jerena Manoharan
  • Max Albers
  • Emily P. Slater
  • Carmen Bollmann
  • Sylvia Roth
  • Aninja Bayer
  • Volker FendrichEmail author
Original Scientific Report (including Papers Presented at Surgical Conferences)

Abstract

Objective

Long-acting synthetic somatostatin analogues (SSA) are an essential part of the treatment of neuroendocrine neoplasms. We evaluated the chemopreventive effects of a long-acting somatostatin analogue on the development of pancreatic neuroendocrine neoplasms (pNENs) in a genetically engineered MEN1 knockout mouse model.

Materials and methods

Heterozygote MEN1 knockout mice were injected every 28 days subcutaneously with the somatostatin analogue lanreotide (Somatuline Autogel©; Ipsen Pharma) or a placebo starting at day 35 after birth. Mice were euthanized after 6, 9, 12, 15 and 18 months, and the size and number of pNENs were measured due histological analysis and compared to the placebo group.

Results

The median tumor size of pNENs was statistically significantly smaller after 9 (control group vs. SSA group; 706.476 µm2 vs. 195.271 µm2; p = 0.0012), 12 (placebo group vs. SSA group 822.022 vs. 255.482; p ≤ 0.001), 15 (placebo group vs. SSA group 1192.568 vs. 273.533; p ≤ 0.001) and after 18 months (placebo group vs. SSA group 1328.299 vs. 864.587; p ≤ 0.001) in the SSA group. Comparing the amount of tumors in both groups, a significant reduction was achieved in treated Men1(+/) mice (41%, p = 0.002). Immunostaining showed, however, no significant difference in the expression of the apoptosis marker caspase-3, but a significant difference in Ki67 index as a marker for tumor cell proliferation (p ≤ 0.005).

Conclusion

Long-acting somatostatin analogues may be an effective chemopreventive approach to delay the progression of MEN1-associated pNENs. After our preclinical results, we would recommend to evaluate the effects of long-acting SSA in a prospective clinical trial.

Notes

Funding

This research was financed by an independent fund to support women in medicine (Anneliese Pohl Stiftung für Habilitationsförderung).

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research/data reported. The somatostatin analogue Somatuline Autogel© used in this trail was, however, provided gratis from Ipsen Pharma, Paris, France.

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Copyright information

© Société Internationale de Chirurgie 2019

Authors and Affiliations

  • Caroline L. Lopez
    • 1
  • Barbara Joos
    • 1
  • Detlef K. Bartsch
    • 1
  • Jerena Manoharan
    • 1
  • Max Albers
    • 1
  • Emily P. Slater
    • 1
  • Carmen Bollmann
    • 1
  • Sylvia Roth
    • 1
  • Aninja Bayer
    • 1
  • Volker Fendrich
    • 2
  1. 1.Department of Visceral, Thoracic and Vascular SurgeryPhilipps University MarburgMarburgGermany
  2. 2.Department of Endocrine SurgerySchön Klinik Hamburg EilbekHamburgGermany

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