DNA adducts, detected by 32P-postlabelling, in DNA treated in vitro with bile from patients with familial adenomatous polyposis and from unaffected controls

1993 ◽  
Vol 14 (6) ◽  
pp. 1107-1110 ◽  
Author(s):  
D.K. Scates ◽  
A.D. Spigelman ◽  
K.P. Nugent ◽  
R.K.S. Phillips ◽  
S. Venitt
2021 ◽  
Vol 108 (Supplement_1) ◽  
Author(s):  
I Martin ◽  
Y Wu ◽  
R Patel ◽  
P Kalra ◽  
S Clark K ◽  
...  

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.


2017 ◽  
Vol 9 (5) ◽  
pp. 66 ◽  
Author(s):  
Md. Gulshan ◽  
M. Lakshmi Swapna Sai ◽  
T. Hemalatha ◽  
U. Jhansi Sri ◽  
N. Ramarao

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


1991 ◽  
Vol 12 (9) ◽  
pp. 1727-1732 ◽  
Author(s):  
Allan D. Spigelman ◽  
Debra K. Scates ◽  
Stanley Venitt ◽  
Robin K.S. Phillips

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