PMID- 30600364
OWN - NLM
STAT- MEDLINE
DCOM- 20190624
LR  - 20200225
IS  - 1432-2323 (Electronic)
IS  - 0364-2313 (Linking)
VI  - 43
IP  - 3
DP  - 2019 Mar
TI  - Chemoprevention with Somatuline(c) Delays the Progression of Pancreatic 
      Neuroendocrine Neoplasms in a Mouse Model of Multiple Endocrine Neoplasia Type 1 
      (MEN1).
PG  - 831-838
LID - 10.1007/s00268-018-4839-8 [doi]
AB  - 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(c); 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 microm(2) vs. 195.271 microm(2); 
      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.
FAU - Lopez, Caroline L
AU  - Lopez CL
AD  - Department of Visceral, Thoracic and Vascular Surgery, Philipps University 
      Marburg, Baldingerstrasse, 35041, Marburg, Germany.
FAU - Joos, Barbara
AU  - Joos B
AD  - Department of Visceral, Thoracic and Vascular Surgery, Philipps University 
      Marburg, Baldingerstrasse, 35041, Marburg, Germany.
FAU - Bartsch, Detlef K
AU  - Bartsch DK
AD  - Department of Visceral, Thoracic and Vascular Surgery, Philipps University 
      Marburg, Baldingerstrasse, 35041, Marburg, Germany.
FAU - Manoharan, Jerena
AU  - Manoharan J
AD  - Department of Visceral, Thoracic and Vascular Surgery, Philipps University 
      Marburg, Baldingerstrasse, 35041, Marburg, Germany.
FAU - Albers, Max
AU  - Albers M
AD  - Department of Visceral, Thoracic and Vascular Surgery, Philipps University 
      Marburg, Baldingerstrasse, 35041, Marburg, Germany.
FAU - Slater, Emily P
AU  - Slater EP
AD  - Department of Visceral, Thoracic and Vascular Surgery, Philipps University 
      Marburg, Baldingerstrasse, 35041, Marburg, Germany.
FAU - Bollmann, Carmen
AU  - Bollmann C
AD  - Department of Visceral, Thoracic and Vascular Surgery, Philipps University 
      Marburg, Baldingerstrasse, 35041, Marburg, Germany.
FAU - Roth, Sylvia
AU  - Roth S
AD  - Department of Visceral, Thoracic and Vascular Surgery, Philipps University 
      Marburg, Baldingerstrasse, 35041, Marburg, Germany.
FAU - Bayer, Aninja
AU  - Bayer A
AD  - Department of Visceral, Thoracic and Vascular Surgery, Philipps University 
      Marburg, Baldingerstrasse, 35041, Marburg, Germany.
FAU - Fendrich, Volker
AU  - Fendrich V
AD  - Department of Endocrine Surgery, Schon Klinik Hamburg Eilbek, Dehnhaide 120, 
      22081, Hamburg, Germany. fendrich@schoen-kliniken.de.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - World J Surg
JT  - World journal of surgery
JID - 7704052
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Ki-67 Antigen)
RN  - 0 (Men1 protein, mouse)
RN  - 0 (Mki67 protein, mouse)
RN  - 0 (Peptides, Cyclic)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0G3DE8943Y (lanreotide)
RN  - 51110-01-1 (Somatostatin)
RN  - EC 3.4.22.- (Casp3 protein, mouse)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*therapeutic use
MH  - Caspase 3/metabolism
MH  - Cell Proliferation
MH  - Chemoprevention
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Ki-67 Antigen/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Multiple Endocrine Neoplasia Type 1/metabolism/pathology/*prevention & control
MH  - Neuroendocrine Tumors/metabolism/pathology/*prevention & control
MH  - Pancreatic Neoplasms/metabolism/pathology/*prevention & control
MH  - Peptides, Cyclic/*therapeutic use
MH  - Proto-Oncogene Proteins/genetics
MH  - Somatostatin/*analogs & derivatives/therapeutic use
MH  - Tumor Burden
EDAT- 2019/01/03 06:00
MHDA- 2019/06/25 06:00
CRDT- 2019/01/03 06:00
PHST- 2019/01/03 06:00 [pubmed]
PHST- 2019/06/25 06:00 [medline]
PHST- 2019/01/03 06:00 [entrez]
AID - 10.1007/s00268-018-4839-8 [pii]
AID - 10.1007/s00268-018-4839-8 [doi]
PST - ppublish
SO  - World J Surg. 2019 Mar;43(3):831-838. doi: 10.1007/s00268-018-4839-8.