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

Transforming growth factor beta, collagenase-1 and TIMP-1: Possible role as key mediators in scieroderma pathogenesis

Systemic sclerosis is a multisystem disease affecting the skin, dermal blood vessels and internal organs. It is characterized pathologically by the overproduction of connective tissue notably collagen. Scleroderma fibroblasts exhibit numerous phenotypic differences when compared with healthy skin fibroblasts; some of these differences in particular are over-expression of collagen and extracellular matrix [ECM] proteins. The fibroblasts produce enzymes as collagenase and other matrix metalloproteinases which can collectively digest all matrix components. Although the pathogenesis of scieroderma is still poorly understood, there is an increasing evidence that transforming growth factor beta is a key mediator of tissue fibrosis as a result of ECM accumulation in pathological states as systemic sclerosis. Also there is evidence of disturbed balance between collagenase-l and its inhibitor TIMP-1 in SSc patients leading to ECM accumulation. The aim of this study was to investigate the serum levels of TGF-beta1, TGF-beta2, collagenase-l and TIMP-l in patients with scleroderma in an attempt to throw lights on different factors which may represent an important clue for understanding the pathogenesis of sclerodernia and thus will probably help in the development of targeted drug therapy aiming at interrupting the abnormal fibrogenic process in this disease. The serum levels of TGF-beta1, TGF-beta2, collagenase-l and TIMP-l were measured in 20 patients with scleroderma [13 females and 7 males], and 15 healthy controls [9 females and 6 males]. The serum levels of TGF-beta1, TGF-beta2 and TIMP-l were found to be significantly higher in scieroderma patients compared with the control group [p<0.01] Meanwhile, the collagenase-l serum levels in SSc patients did not differ significantly from those of normal controls [p<0.05]. No significant correlation was found between either TGF-beta1 or TGF-beta2 serum levels in SSc patients and TIMP-l serum levels, disease duration, scl-70 or ESR [as an indicator of disease activity]. In TGF-beta1 TGF-beta2 andi-IMP-l are probably key mediators underlying the process of fibrosis in patients with SSc as a consequence of ECM accumulation. TGF-beta play a crucial role in the pathogenesis of SSc as it is the most potent inducer of collagen and connective tissue accumulation. The study of TGF-beta and TIMP-l and their biologic effects provides important clues to understanding the pathogenesis of SSc and to the development of new therapies acting directly on the causative factors underlying the pathogenesis of SSc as gene therapy or monoclonal antibodies to TGF-beta or the use of other cytokines as TNF-alpha aiming at interrupting the abnormal fibrogenic process in this disease

Study of the presence of Hcv-rna in semen of patients with hepatitis C

Hepatitis C virus is a worldwide problem. in Egypt, HCV infection is hyper-endemic, with sero-prevalence rates of 15-20% among volunteer blood donors, and even higher rates reported among segments of the general population. Although the parentral mode of HCV transmission is well established, there remains a high proportion of patients without an identifiable source of infection. The importance of sexual transmission in the epidemiology of HCV infection is still controversial. Better understanding ofroutes of transmission will help to combat the spread of disease. Thus there is a need for studies to define the routes of HCV transmission other than the parentral exposure. The aim of the present study is to investigate the role of sexual transmission in the transmission of HCV infection, and to investigate whether or not the detection of actively replicating HCV in serum coincides with the presence of HCV-RNA in seminal fluid, in an attempt to define one of the main possible routes of HCV infection transmission other than the parentral route. A group of 40 male married patients infected with hepatitis C virus were included in this study and HCV-RNA detection in their semen by nested RT-PCR test was done. We tested for the presence of inhibitors in the seminal plasma by the repetition of negative HCV-RNA seminal plasma samples with an internal control. Fractionation of the semen of five virospermic patients was done on percol gradient into seminal plasma, round cell and motile spermatozoa fractions, and HCV-RNA detection was repeated on each fraction in an attempt to understand which fraction could serve as a reservoir for the virus. The wives of the patients with detectable HCV-RNA in their semen were subjected to serum HCV-RNA detection. Of the forty male patients with HCV-RNA positive sera, ten patients [25%] had detectable HCV-RNA in semen. The test for PCR inhibitors revealed the presence of Taq inhibitors in seminal plasma of 16/30 patients [53.33%] who were considered to be false negative. HCV-blood viral load was significantly higher in virospermic patients, which supports the hypothesis that HCV is "leaked out" from the peripheral circulation. We identified HCV-RNA in serum of four out often wives of virospermic patients. The duration of marriage among HCV infected wives in this study was significantly higher than among the non-infected wives which suggests that a cumulative effect may be required for the sexual transmission of HCV. In the semen could be infectious and the role of sexual transmission in the spread of HCV infection should not be underestimated. Laboratory capability to accurately detect HCV positive semen is an important step in establishing the risk of sexual transmission and in identifing strategies for protecting uninfected partners