P53 alterations in a group of Egyptian colorectal cancer patients

The p53 gene is located on human chromosome 17p13.1 and consists of 11 exons. Deficiencies in the p.53 gene can cause the cancerous cells to spread to distant organs. The most common p53 abnormalities that can lead to metastasis of colorectal tumours are mutation and deregulation of the gene. Aim of the study in the present study, we assessed the presence of P53 gene mutations and p53 protein expression and their prognostic significance in 43 patients with colorectal cancer. Histopathological examination of colonoscopic biopsies specimens, chest and abdomen CT were done for all patients. Genomic DNA was extracted, and exons 4-8 of the p53 gene were amplified, and analyzed for mutations by single strand conformation polymorphism [SSCP] and direct sequencing. The production of p53 proteins was studied by immunohistochemistry [IHC]. Results P53 mutations were found in 27/43 [63%] cases. A total of 11 types of p53 gene mutations were found by direct sequencing. More than half of these mutations appear in three hot spot codons: 175, 248 and 273. The SSCP analysis demonstrate that most common p53 gene alterations were found in exon 5 [35%]. IHC detected 34 tumors [79%] with protein overexpressior [when a cut point of 20% positive cells] and 25 tumours [58%] [When a cut point of >/= 50% positive cells were used]. it was found that p53 mutation analysis corresponds well with p53 immunohistochemistry [p < 0.001]. The majority of gene mutations were found in tumours from the rectum and distal colon. No statistical signitficant relation was found between P53 gene mutations and Duke's staging [P > 0.05]. However, a significant statistical relation was found between P53 gene mutations and prognosis in the studied colorectal cancer patients [p < 0.05]. Molecular and cellular evaluation. of p53 is clinically important, and there are strong indications, especially in colorectal cancer, that mutational status and mutational position in the P53 gene have a prognostic value. However the study of other genes involved in colorectal cancer is necessary

Subclinical pancreatic exocrine insufficiency in type 2 diabetes

Background/ Aim: Anatomical and functional studies suggest a close interrelationship between endocrine and exocrine pancreas. It is recognized that a significant proportion of diabetic patients may have a deficit of the exocrine function. The availability of faecal elastase 1[E1] as a non-invasive test has aided the detection of impaired exocrine function in population studies. Aim of the present study is to investigate subclinical pancreatic exocrine insufficiency in patients with type 2 diabetes

Methods: 51 Type 2 diabetic patients [ age range 43 -71 years ] and 39 age matched non diabetic control subjects were enrolled in the study . All patients underwent the same study protocol ,which included clinical evaluation , laboratory determination of fasting blood glucose [FBG], post prandial blood glucose [PPBG],hemoglobin A1c [HbA1c], screening of low faecal E1 using an enzyme linked immunosorbent assay [ELISA]. Plain x - rays of the abdomen and abdominal ultrasound were done

Results : Faecal elastase 1 concentrations were significantly lower in diabetic patients than controls [ median : cases 298 microg/g ., controls 406 microg/g stool; p <0.01] . Low levels of faecal elastase 1[<100 microg/g] were found in 13.7% of cases and 5.1% of controls . Among patients with dia- betes , poor glycaemic control [HbA1c > 7%] was associated with higher risk of low elastase 1 level . There was a significant inverse association of body mass index with low elastase1 concentrations . No significant as- sociation was found with diabetes duration and type of treatment

Conclusions: Pancreatic exocrine insufficiency occurs more frequently in diabetic patients than in controls. The risk of having low elastase1 levels was associated with glycaemic control .Diabetic patients with less weight [BMI<25] may be at increased risk for underlying exocrine pan- creatic insufficiency