PMID- 30025403
OWN - NLM
STAT- MEDLINE
DCOM- 20190110
LR  - 20190110
IS  - 1423-0194 (Electronic)
IS  - 0028-3835 (Linking)
VI  - 107
IP  - 3
DP  - 2018
TI  - Chemoprevention with Enalapril and Aspirin in Men1(+/T) Knockout Mouse Model.
PG  - 257-266
LID - 10.1159/000492224 [doi]
AB  - Pancreatic neuroendocrine neoplasias (pNEN) are the most common cause of death in 
      adult patients with multiple endocrine neoplasia type 1 (MEN1). So far, only few 
      chemopreventive strategies (e.g., with somatostatin analogues) have been 
      evaluated for MEN1 associated pNENs. In this experimental study on 75 Men1(+/T) 
      knockout mice, the effect of aspirin (n = 25) and an inhibitor of angiotensin-I 
      converting enzyme (enalapril, n = 25) compared to controls (n = 25) were 
      evaluated as single chemopreventive strategies for pNENs after 6, 9, 12, 15, and 
      18 months. After each study period, mice were sacrificed and the resected 
      pancreata were evaluated by histopathological analysis, immunostaining, and 
      real-time PCR. PNEN size and number was measured. Aspirin and enalapril lead to a 
      pNEN size reduction of 80% (167,518 vs. 838,876 microm2, p < 0.001) and 79% (174,758 
      vs. 838,876 microm2, p < 0.001) compared to controls. Furthermore, aspirin and 
      enalapril treatment resulted in a significant reduction of the number of pNENs by 
      33%, (p = 0.04) and 41% (p = 0.002) respectively. The apoptosis marker caspase 3 
      revealed a higher positive expression in pNEN of treated Men1(+/T) mice. 
      Immunostaining of VEGF in pNEN detected a downregulation of its expression in 
      treated Men1(+/T) mice compared to the control group. REL A transcript was 
      significantly downregulated in 18-months treated enalapril Men1(+/T) mice, but 
      not in aspirin-treated Men1(+/T) mice. There was no significant difference in the 
      Ki-67 index. Using a transgenic mouse model that imitates human MEN1, this study 
      provides first evidence that aspirin and enalapril are effective chemopreventive 
      agents that aid in the progression of pNENs.
CI  - (c) 2018 S. Karger AG, Basel.
FAU - Manoharan, Jerena
AU  - Manoharan J
AD  - Department of Visceral, Thoracic and Vascular Surgery, Philipps University 
      Marburg, Marburg, Germanyjerena_manoharan@outlook.com.
FAU - Fendrich, Volker
AU  - Fendrich V
AD  - Department of Visceral, Thoracic and Vascular Surgery, Philipps University 
      Marburg, Marburg, Germany.
FAU - Di Fazio, Pietro
AU  - Di Fazio P
AD  - Department of Visceral, Thoracic and Vascular Surgery, Philipps University 
      Marburg, Marburg, Germany.
FAU - Bollmann, Carmen
AU  - Bollmann C
AD  - Department of Visceral, Thoracic and Vascular Surgery, Philipps University 
      Marburg, Marburg, Germany.
FAU - Roth, Silvia
AU  - Roth S
AD  - Department of Visceral, Thoracic and Vascular Surgery, Philipps University 
      Marburg, Marburg, Germany.
FAU - Joos, Barbara
AU  - Joos B
AD  - Department of Visceral, Thoracic and Vascular Surgery, Philipps University 
      Marburg, Marburg, Germany.
FAU - Mintziras, Ioannis
AU  - Mintziras I
AD  - Department of Visceral, Thoracic and Vascular Surgery, Philipps University 
      Marburg, Marburg, Germany.
FAU - Albers, Max B
AU  - Albers MB
AD  - Department of Visceral, Thoracic and Vascular Surgery, Philipps University 
      Marburg, Marburg, Germany.
FAU - Ramaswamy, Annette
AU  - Ramaswamy A
AD  - Department of Pathology, Philipps University Marburg, Marburg, Germany.
FAU - Bertolino, Philippe
AU  - Bertolino P
AD  - Centre de Recherche en Cancerologie de Lyon, Inserm U1052, CNRS UMR5286, 
      Universite Lyon 1, Lyon, France.
FAU - Zhang, Chang X
AU  - Zhang CX
AD  - Centre de Recherche en Cancerologie de Lyon, Inserm U1052, CNRS UMR5286, 
      Universite Lyon 1, Lyon, France.
FAU - Slater, Emily P
AU  - Slater EP
AD  - Department of Visceral, Thoracic and Vascular Surgery, Philipps University 
      Marburg, Marburg, Germany.
FAU - Bartsch, Detlef K
AU  - Bartsch DK
AD  - Department of Visceral, Thoracic and Vascular Surgery, Philipps University 
      Marburg, Marburg, Germany.
FAU - Lopez-Lopez, Caroline L
AU  - Lopez-Lopez CL
AD  - Department of Visceral, Thoracic and Vascular Surgery, Philipps University 
      Marburg, Marburg, Germany.
LA  - eng
PT  - Journal Article
DEP - 20180719
PL  - Switzerland
TA  - Neuroendocrinology
JT  - Neuroendocrinology
JID - 0035665
RN  - 0 (Men1 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 69PN84IO1A (Enalapril)
RN  - R16CO5Y76E (Aspirin)
SB  - IM
MH  - Animals
MH  - Aspirin/*therapeutic use
MH  - Chemoprevention/*methods
MH  - Enalapril/*therapeutic use
MH  - Mice
MH  - Mice, Knockout
MH  - Multiple Endocrine Neoplasia Type 1/genetics/*pathology
MH  - Neuroendocrine Tumors/genetics/pathology/*prevention & control
MH  - Pancreatic Neoplasms/genetics/pathology/*prevention & control
MH  - Proto-Oncogene Proteins/*genetics
OTO - NOTNLM
OT  - Aspirin
OT  - Chemoprevention
OT  - Enalapril
OT  - Multiple endocrine neoplasia type 1
EDAT- 2018/07/20 06:00
MHDA- 2019/01/11 06:00
CRDT- 2018/07/20 06:00
PHST- 2018/03/26 00:00 [received]
PHST- 2018/07/18 00:00 [accepted]
PHST- 2018/07/20 06:00 [pubmed]
PHST- 2019/01/11 06:00 [medline]
PHST- 2018/07/20 06:00 [entrez]
AID - 000492224 [pii]
AID - 10.1159/000492224 [doi]
PST - ppublish
SO  - Neuroendocrinology. 2018;107(3):257-266. doi: 10.1159/000492224. Epub 2018 Jul 
      19.