Expression of the signal transducer and activator of transcription factor 3 in colorectal carcinomas, colonic adenomas and ulcerative colitis

Despite the growing understanding of the involvement of protooncogenes and tumour suppressor genes in the oncogenesis of CRC, the exact biological and molecular mechanisms underpinning this process remain poorly understood. The signal transducer and activator of transcription [STAT3] has been implicated in the regulation of growth and malignant transformation. Accumulating evidences have come to indicate that abnormalities in the Janus kinase [JAK]/STAT pathway are involved in oncogenesis of several cancers. The aim of this study was to investigate the expression of JAK3 and STAT3 in both normal and activated forms by immunohistochemistry in adenomas of the colon, ulcerative colitis and CRC compared to normal colonic mucosa. Tissues from 30 cases with primary CRC and seven cases with ulcerative colitis [UC], removed by colectomy, were included. In addition, tissues from 10 colonic adenomas, 15 CRC and eight cases with UC, obtained by endoscopic biopsies, were examined histopathologically. Immuno-histochemical evaluation of STAT3, p-STAT3, JAK3 and p-JAK3 expression in tissue sections was completed. Statistical analysis and correlation of data were then performed. Normal colonic mucosa showed expression of STAT3 only. Immunoreactivity of p-JAK3 increased significantly [p < 0.05] and correlated with the degree of dysplasia in colonic adenomas. Immunoreactivity of p-STAT3 increased significantly [p < 0.05] and correlated with the degree of dysplasia in cases with UC. In CRC a significant positive correlation was found between p-STAT3 expression and grading, STAT3, JAK3 and p-JAI<3 and TNM or Dukes' staging, and p-STAT3 and nodal status excluding distant metastasis [p<0.05]. JAK3 and STAT3, and particularly their activated forms, were found to correlate significantly with the degree of dysplasia in adenomas and UC, indicating their potential role in colorectal carcinogenesis. They also correlate with anaplasia and invasion, suggesting a definitive role in progression of CRC

Experimental schistosomal hepatitis: protective effect of coenzyme-Q10 against the state of oxidative stress

Schistosoma mansoni [S. mansoni] eggs trapped in the host liver elicit a chain of oxidative processes, where they not only trigger the production of reactive oxygen species, but also lead to alteration of the host antioxidant defense mechanisms. Such events may be, at least in part, responsible for the pathology and progression of fibrosis associated with schistosomal hepatitis. This study was designed to fulfill two aims; assessment of protective effect of the antioxidant Coenzyme-Q10 [Co-Q10] against the state of S. mansoni-induced oxidative stress in the liver, and evaluation of the potential role of Co-Q10 as an adjuvant to praziquantel [PZQ]. S. mansoni infected mice were divided into four main groups; group I: control non-treated group. Group II: received Co-Q10 after infection and was sacrificed 8 and 12 weeks post infection. Croup III: treated by single oral dose of PZQ 8 weeks post infection. Group IV: treated by single oral dose of PZQ 8 weeks post infection then was given Co-Q10 for four weeks. The oxidative stress and overall liver function were improved under Co-Q10 therapy as evidenced by significant reduction in oxidative stress markers, and preservation of antioxidant factors. Liver fibrosis was also reduced with a positive impact on liver function. Moreover, addition of Co-Q10 to PZQ therapy caused; significant reduction of liver egg load, significant improvement of the redox status, and lastly decreased liver fibrosis. From this study we concluded that Co-Q10: 1] ameliorated the oxidative stress status, 2] reduced the degree of liver fibrosis, and 3] enhanced the efficacy of classical therapy in experimental S. mansoni-induced hepatitis

Histopathological and immune-pathological changes in the prostates of golden hamsters experimentally infected with schistosoma mansoni

This work has been planned to study the histopathological and immune-pathological changes in the prostates of experimentally infected golden hamsters with Schistosoma mansoni. Fifty male golden hamsters, 10 weeks old, 200-250 gm in weight each and free from parasitic infections were used. They were classified into two groups. Group [1] 40 male golden hamsters infected with 350 S. mansoni cercariae S.C. each. Group [2] 10 male golden hamsters [control]. Viable S. mansoni eggs were collected, washed and egg hatching was performed. Biomphalaria alexandrina snails were infected by 6 - 8 miracidia each. The released cercariae were collected, counted and concentrated so as to contain 350 cercariae / 0.5 ml. [the infective dose / hamster S. C.]. Five infected hamsters were killed 6, 8, 10, 12, 14, 16, 18 and 20 weeks p. i. Control animals were sacrificed at once. The prostate- glands of the infected and control male hamsters were dissected; fixed in 10% phosphate buffered formalin. Microscopic examination was conducted on 4 microm thick H. and E. stained sections from paraffin embedded specimens. Immunohistochemical detection of hamster's schistosomal antigen in prostatic sections was performed by DAKO Avidin-biotin peroxidase technique. Other portions of the prostates were digested in 5% KOH for detection of S. mansoni eggs. The results of this work showed that there were diffuse, non granulomatous inflammatory reaction starting at 12[th] week p.i. and reaching maximum intensity at 16[th] week p.i. The epithelial linings of the prostatic acini showed hyperplasia, enfolding and lymphocytic cell infiltration. Stromal fibrosis started at 18[th] week p.i. in 10 [25%] infected hamsters. Immunohistochemical examination showed mild deposits at 12[th] week p.i., moderate deposits at 14[th] week p.i. and intense deposits at 16[th] week p.i. KOH digestion of prostatic pieces showed no S. mansoni ova at any period p. i. S. mansoni infection could involve the prostate gland by variable degrees of inflammation and fibrosis. These inflammatory reactions may be due to antigen deposition in such organ. The inflammation and fibrosis may interfere with the normal function of the prostatic gland leading to alteration of the chemical composition of the seminal fluid which may decrease the fertility capacity of the sperms. Also, prostatic hypertrophy may lead to problems in the erection and urinary tract obstruction

Study of angiogenesis, P53 and NM23 expression in colorectal carcinoma

Colorectal carcinoma [CRC] is not uncommon in Egypt. Sustained angiogenesis is characteristic of several pathological conditions including tumor growth. Many researches were conducted to investigate the role of P53 in colorectal carcinogenesis; also the role of NM23 in tumor progression and for metastasic potential is not so clear in CRC. In this research we are aiming to study the pattern and density of angiogenesis in colorectal carcinomas, in addition to other histopathological prognostic factors. Besides we are also aiming to study the expression of P53 and NM23 and the relation between these three factors [Angiogenesis, P53 and NM23] in different grades and stages of colorectal carcinomas. The study comprised 44 resection specimens of colorectal carcinomas collected from specimens of department of pathology, Faculty of Medicine, Tanta University Hospital and from same of the private laboratories. Each block was stained by hematoxylin and eosin [H and E], immunohistochemical stain for CD34, VEGF, P53 and NM23. Histopathological assessment of grading was done according to WHO classification and staged according to TNM classification. The present study includes 44 cases of colorectal adenocarcinoma 35 were male patients and 9 cases were females. The age range was 20 to 80 years. The patients were grouped into three groups as follows: Group [1]: CRC without nodal or distant metastasis, group [II]: CRC with nodal but no distant metastasis and group [III]: CRC with distant metastasis. Most of the tumors were conventional invasive adenocarcinomas, on studying angiogenesis we found that the relation of microvascular density [MVD] detected by CD34 was not significant with the tumor size. Besides there were a significant results between the microvascular density and metastatic history of the disease. There were significant results between VEGF expression and the studied variables. The study ol apoptosis using P53 reveals significant relation between it and the studied variables but not with the nodal or blood metastasis, there was an inverse relation between NM23 and both VEGF and P53, but the results was not significant with the tumor grade and size, so in the present study the relation between VEGF, P53 and NM23 was significant but each marker have its own variable result with the grade .size and the stage of the tumor. In the present study it can be concluded that MVD at vascular hot spots is a very important predictive factor in CRC in addition to VEGF .P53 over expression has an impact on the biological behavior of CRC being more expressed in biological aggressive tumors and it has a role in angiogenicStudy of Angiogenesis, P53 and NM23 Expression in Colorectal Carcinoma activity of the tumor. We also concluded that NM23 is an important metastatic suppressor gene in CRC. So NM23, P53, VEGF and MVD by CD34 all are important to predict the outcome of the disease and they can be used as a guide for treatment. MVD, microvascular density; VEGF, vascular endothelial growth factor; CRC, colorectal carcinoma