scholarly journals O4: A NOVEL BOWEL DISEASE MODEL: PHENOTYPIC DIVERSITY OF CONTROL VS FAP ORGANOIDS

2021 ◽  
Vol 108 (Supplement_1) ◽  
Author(s):  
I Martin ◽  
Y Wu ◽  
R Patel ◽  
P Kalra ◽  
S Clark K ◽  
...  
Keyword(s):  
Familial Adenomatous Polyposis ◽  
Phenotypic Diversity ◽  
Disease Model ◽  
Duodenal Mucosa ◽  
In Vitro Models ◽  
Upper Gastrointestinal Endoscopy ◽  
Adenomatous Polyposis ◽  
Ki 67 ◽  
Ring Structures

Abstract Introduction The lifetime risk of colorectal cancer in familial adenomatous polyposis (FAP) approaches 100%. In patients who have undergone prophylactic colectomy, duodenal cancer is 100-300 times more common than in the general population, and an important cause of death. We aimed to develop in vitro models of mucosal crypt-derived organoids from patients with FAP. Method Biopsies from apparent healthy duodenal mucosa of FAP patients undergoing upper gastrointestinal endoscopy or surgery yielded crypts that were immobilised in Matrigel Basement Membrane Matrix (Corning) and cultured in IntestiCult Organoid Growth Medium (StemCell Technologies) to generate organoids for further morphologic and immunocytochemistry analyses (Dako and Abcam antibodies). Result Duodenal crypt-derived organoids from one healthy volunteer formed ring structures (days 1 -2) that progressed to expected branched structures (days 4-7). FAP-derived organoids from 9 patients all generated organoids with aberrant morphologies. These organoids expressed markers of Paneth cells (lysozyme), proliferation (Ki-67), goblet cells (Muc-2) and the single cell layer of mucosal epithelium (CK18). Conclusion This is the first report of duodenal crypt-derived organoids generated from FAP patients. Aberrant organoid morphologies were observed in all 9 patients. Immunocytochemistry confirmed markers of duodenal epithelium, suggesting a promising in vitro model to study disease aetiology in FAP. Take-home message This is a step towards a personalised model of disease for patients with familial adenomatous polyposis.

scholarly journals Expression Profiling of Proliferation and Apoptotic Markers along the Adenoma-Carcinoma Sequence in Familial Adenomatous Polyposis Patients

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Jayson Wang ◽  
Nabil El-Masry ◽  
Ian Talbot ◽  
Ian Tomlinson ◽  
Malcolm R. Alison ◽  
...  
Keyword(s):  
Familial Adenomatous Polyposis ◽  
Cyclin D1 ◽  
Caspase 3 ◽  
Normal Mucosa ◽  
Beta Catenin ◽  
Adenomatous Polyposis ◽  
Ki 67 ◽  
Cd10 Expression ◽  
Apc Protein ◽  
Apoptotic Factors

Introduction. Familial adenomatous polyposis (FAP) patients have a germline mutation in the adenomatous polyposis coli (APC) gene. The APC protein interacts with beta-catenin, resulting in the activation of the Wnt signalling pathway. This results in alterations in cell proliferation and apoptosis. We investigated the expression of beta-catenin and related proliferation and apoptotic factors in FAP patients, exploring the expression along the adenoma-carcinoma sequence.Methods. The expression of beta-catenin, p53, bcl-2, cyclin-D1, caspase-3, CD10, and Ki-67 proteins was studied by immunohistochemistry in samples of colonic nonneoplastic mucosa (n=71), adenomas (n=152), and adenocarcinomas (n=19) from each of the16 FAP patients.Results. The expression of beta-catenin, caspase-3, cyclin-D1, and Ki-67 was increased in both adenomas and carcinomas in FAP patients, compared with normal mucosa. p53 and CD10 expression was only slightly increased in adenomas, but more frequently expressed in carcinomas. Bcl-2 expression was increased in adenomas, but decreased in carcinomas.Conclusion. This is the first study investigating collectively the expression of these molecules together in nonneoplastic mucosa, adenomas, and carcinomas from FAP patients. We find that beta-catenin and related proliferative and apoptotic factors (cyclin-D1, bcl-2, caspase-3, and Ki-67) are expressed early in the sequence, in adenomas. However, p53 and CD10 are often expressed later in the sequence, in carcinomas.

Cell proliferation of the duodenal mucosa in patients affected by familial adenomatous polyposis

1997 ◽  
Vol 113 (4) ◽  
pp. 1159-1162 ◽  
Author(s):  
R Santucci ◽  
L Volpe ◽  
U Zannoni ◽  
GM Paganelli ◽  
B Poggi ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Familial Adenomatous Polyposis ◽  
Duodenal Mucosa ◽  
Adenomatous Polyposis

scholarly journals Biologically Active Echinulin-Related Indolediketopiperazines from the Marine Sediment-Derived Fungus Aspergillus niveoglaucus

Molecules ◽  
2019 ◽  
Vol 25 (1) ◽  
pp. 61 ◽  
Author(s):  
Olga F. Smetanina ◽  
Anton N. Yurchenko ◽  
Elena V. Girich (Ivanets) ◽  
Phan Thi Hoai Trinh ◽  
Alexander S. Antonov ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Model ◽  
In Vitro Models ◽  
Biologically Active ◽  
Neuroprotective Activity ◽  
Chiral Hplc ◽  
Cytoprotective Activity ◽  
First Time

Seven known echinulin-related indolediketopiperazine alkaloids (1–7) were isolated from the Vietnamese sediment-derived fungus Aspergillus niveoglaucus. Using chiral HPLC, the enantiomers of cryptoechinuline B (1) were isolated as individual compounds for the first time. (+)-Cryptoechinuline B (1a) exhibited neuroprotective activity in 6-OHDA-, paraquat-, and rotenone-induced in vitro models of Parkinson’s disease. (−)-Cryptoechinuline B (1b) and neoechinulin C (5) protected the neuronal cells against paraquat-induced damage in a Parkinson’s disease model. Neoechinulin B (4) exhibited cytoprotective activity in a rotenone-induced model, and neoechinulin (7) showed activity in the 6-OHDA-induced model.

scholarly journals FORMULATION AND DEVELOPMENT OF MICROSPHERES FOR THE TREATMENT OF FAMILIAL ADENOMATOUS POLYPOSIS

2017 ◽  
Vol 9 (5) ◽  
pp. 66 ◽  
Author(s):  
Md. Gulshan ◽  
M. Lakshmi Swapna Sai ◽  
T. Hemalatha ◽  
U. Jhansi Sri ◽  
N. Ramarao
Keyword(s):  
Familial Adenomatous Polyposis ◽  
Drug Release ◽  
Polymer Concentration ◽  
Methyl Cellulose ◽  
Angle Of Repose ◽  
In Vitro Dissolution ◽  
Size Analysis ◽  
Adenomatous Polyposis ◽  
Polymer Interactions

Objective: Familial adenomatous polyposis (FAP) also known as familial polyposis coli, is a hereditary disease characterized by progressive appearance of numerous polyps mainly in the large intestine. Polyps are initially benign but can easily become cancerous and as such it is a life threatening condition. Celecoxib, a cyclooxygenase-2 (COX-2) inhibitor is thought to induce cell death, and thus prevent or delay the growth of polyps. So in the present study celecoxib loaded microspheres were prepared using control release Hydroxy propyl methyl cellulose (HPMC K4M) and pH dependent polymer eudragit L 100-55 in different ratios (1:1 to 1:4) respectively. The main objective of the study is to identify the polymer concentration required to prevent the drug release in stomach region and promotes in intestinal region.Methods: Emulsification solvent evaporation method was selected for the preparation and all the optimized formulations were evaluated for drug-polymer interactions, percentage yield, micrometric properties, entrapment efficiency, particle size analysis, differential scanning calorimetry and in vitro dissolution study.Results: Drug and polymer interactions were evaluated by using FTIR and DSC. The FTIR spectrum and DSC thermograms stated that drug and polymer are compatible to each other. The micrometric properties of drug loaded microspheres were carried out and they were found to be as the angle of repose (18.26 °-40.69 °), bulk density (0.2846-0.3875), tapped density (0.4111-0.5428), Carr’s index (9.66-14.77), Hausner’s ratio (1.112-1.2642) which were within the limits. In vitro dissolution, drug release was found to be from 4.5 to 6.5 h for the prepared four formulations (F1–F4). From the kinetic data modeling the order of drug release was found to be zero order and korsmeyer-peppas with n value above 0.5 for all the formulations indicating non-fickian diffusion.Conclusion: All the result demonstrated that celecoxib microspheres can be effectively used in the treatment of familial adenomatous polyposis

Detoxification enzymes in the duodenal mucosa of patients with familial adenomatous polyposis

2005 ◽  
Vol 92 (6) ◽  
pp. 754-755 ◽  
Author(s):  
M. Berkhout ◽  
H. M. J. Roelofs ◽  
P. Friederich ◽  
J. H. J. M. van Krieken ◽  
F. M. Nagengast ◽  
...  
Keyword(s):  
Familial Adenomatous Polyposis ◽  
Duodenal Mucosa ◽  
Detoxification Enzymes ◽  
Adenomatous Polyposis

scholarly journals In Vitro Disease Models of the Endocrine Pancreas

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1415
Author(s):  
Marko Milojević ◽  
Jan Rožanc ◽  
Jernej Vajda ◽  
Laura Činč Ćurić ◽  
Eva Paradiž ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Endocrine Pancreas ◽  
Disease Model ◽  
In Vitro Models ◽  
Disease Models ◽  
Human Pancreas ◽  
Cell Dysfunction ◽  
Experimental Systems ◽  
Models Of Disease

The ethical constraints and shortcomings of animal models, combined with the demand to study disease pathogenesis under controlled conditions, are giving rise to a new field at the interface of tissue engineering and pathophysiology, which focuses on the development of in vitro models of disease. In vitro models are defined as synthetic experimental systems that contain living human cells and mimic tissue- and organ-level physiology in vitro by taking advantage of recent advances in tissue engineering and microfabrication. This review provides an overview of in vitro models and focuses specifically on in vitro disease models of the endocrine pancreas and diabetes. First, we briefly review the anatomy, physiology, and pathophysiology of the human pancreas, with an emphasis on islets of Langerhans and beta cell dysfunction. We then discuss different types of in vitro models and fundamental elements that should be considered when developing an in vitro disease model. Finally, we review the current state and breakthroughs in the field of pancreatic in vitro models and conclude with some challenges that need to be addressed in the future development of in vitro models.

scholarly journals Tu1563 KI-67 EXPRESSION CAN BE A MARKER OF AGRESSIVENESS OF DUODENAL DISEASE IN FAMILIAL ADENOMATOUS POLYPOSIS

2020 ◽  
Vol 91 (6) ◽  
pp. AB620-AB621
Author(s):  
Marianny Sulbaran ◽  
Fabio G. Campos ◽  
Vitor R. Paes ◽  
Venancio A. Alves ◽  
Humberto Kishi ◽  
...  
Keyword(s):  
Familial Adenomatous Polyposis ◽  
Adenomatous Polyposis ◽  
Ki 67 ◽  
Duodenal Disease

P53 overexpression and the Ki-67 labeling index in duodenal tumors from familial adenomatous polyposis patients

1998 ◽  
Vol 114 ◽  
pp. A652
Author(s):  
S. Nakamura ◽  
M. Iida ◽  
T. Matsumoto ◽  
T. Yao ◽  
K. Aoyagi ◽  
...  
Keyword(s):  
Familial Adenomatous Polyposis ◽  
Labeling Index ◽  
Adenomatous Polyposis ◽  
Ki 67 ◽  
P53 Overexpression
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