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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% (167518 µm2 vs 838876 µm2, p<0.001) and 79% (174758 µm2 vs 838876 µm2, 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 down-regulation of its expression in treated Men1(+/T) mice compared to the control group. REL A transcript was significantly down-regulated in 18-months treated enalapril Men1(+/T) mice, but not in aspirin treated Men1(+/T) mice. There was no significant difference in 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 for the progression of pNENs.
This article was published in the following journal.
Pituitary adenomas (PAs) may rarely occur in well-defined hereditary conditions, like multiple endocrine neoplasia type 1 (MEN1) syndrome and familial isolated pituitary adenoma (FIPA) associated with...
Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant disease caused by mutations in the tumor suppressor gene MEN1 and can be diagnosed based on clinical, familial and/or genetic criter...
Prostate cancer is recognized as a heterogeneous disease demanding appropriate preclinical models that reflect tumor complexity. Previously, we established the PSA-Cre;PtenLoxP/LoxP genetic engineered...
Objectives: The aim of the present study is to assess the significance of metabolomics and genetics in diagnosing and survival evaluation for pNET in the periodic follow-up of MEN1 patien...
The study is to assess the safety and efficacy of the anti-MUC1 CAR T cells and /or PD-1 knockout engineered T cells for patients with advanced non-small cell lung cancer.
The poupose of this study is to evaluate the efficacy and safety of various dosage combinations of lercanidipine (10 and 20 mg)and enalapril (10 and 20 mg) in comparison with their respect...
The target of rapamycin complex 2 (TORC2) is an evolutionarily conserved serine/threonine protein kinase that controls growth and metabolism. In mammals (including humans), mammalian TOR c...
To demonstrate the acceptability and feasibility of recruitment to a randomised chemoprevention study of standard (300mg) or low dose (100mg) aspirin vs. placebo and/or Vitamin D3 vs. plac...
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
A non-steroidal anti-inflammatory agent that is less effective than equal doses of ASPIRIN in relieving pain and reducing fever. However, individuals who are hypersensitive to ASPIRIN may tolerate sodium salicylate. In general, this salicylate produces the same adverse reactions as ASPIRIN, but there is less occult gastrointestinal bleeding. (From AMA Drug Evaluations Annual, 1992, p120)
Asthmatic adverse reaction (e.g., BRONCHOCONSTRICTION) to conventional NSAIDS including aspirin use.
One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases.
A mouse substrain that is genetically predisposed to the development of systemic lupus erythematosus-like syndrome, which has been found to be clinically similar to the human disease. It has been determined that this mouse strain carries a mutation in the fas gene. Also, the MRL/lpr is a useful model to study behavioral and cognitive deficits found in autoimmune diseases and the efficacy of immunosuppressive agents.
The pancreas secretes a number of important hormones into the digestive tract and the blood stream. Cancers are most commonly exocrine than endocrine (neuroendocrine) tumors. Functional tumors secrete hormones; Insulinoma, Gastrinoma, Somatostatinoma, VI...
Pancreatitis Acute pancreatitis is inflammation of the pancreas caused by the release of activated pancreatic enzymes. Common triggers are biliary tract disease and chronic heavy alcohol intake. Diagnosis is based on clinical presentation...