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

Immunohistochemical and neurotransmitter changes in the brain of mice infected with hymenolepis nana

Hymenolepis nana is one of opportunistic parasites which is widely distributed specially amongst children and immunosuppressed patients. Some neurological manifestations can occur in immunosupressed hosts, however, their possible pathogenesis is not clearly yet idenified. The aim of the present work is to study the possible pathogenesis of the neurological manifestations in Hymenolepis nana infection. Swiss albino mice were used in this study which was divided into two groups. Group I: Mice were maintained immunocompetent [IC]. Group II: Mice were immunosupressed [IS] by subcutaneous injection of cortisone. Mice of both groups were orally infected with H.nana eggs. Mice were sacrificed at different durations post infecion [p.i.]. Small intestine, liver and brain of each sacrificed mouse were removed. Couning of cysticercoids and adult worms in small intestine was performed. Livers were examined histopathologically for the possible cysticercoid disseminalion. Brains were processed for histopathological examination and immunohistochemical examinalion for the possible antigenic deposition by PAP technique. In addition the brain tissue was processed for biochemical estimation of the levels of some neurotransmitters as: Gamma-aminobutyric acid [GABA], norepinephfine [NE] and serotonin [5-HT] as well as zinc as one of trace elements. The results of the present study showed a significant increase in the number of cysicercoids and adult worms with delayed expulsion in immunosupressed [IS] mice with manifest histopathological changes in small intestinal mucosa. Aberrant cysticercoids were detected in the liver of IS mice. Regarding the brain examination, there were marked histopathological changes with specific antigenic deposition in IS mice. There were statistical increase in the levels of GABA and NE and staistical decrease in the levels of 5-HT and zinc in brains of IS mice examined at 3 and 5 months p.i. On the basis of the results of the present study, it has been shown that in case of immunosuppression, Hymenolepis nana infection can affect the brain as evidenced by the marked histopathological changes, specific antigenic deposition and the significant changes in the levels of neurotransmitters and zinc in the brain tissue. Since H. nana is widespread and since increasing numbers of patients are given immunosuppressive treatment, it is possible that this peculiar neurological manifestation of H.nana infection is occurring but not being diagnosed. The pathogenesis of such manifestations seemed to be dependent on multifactors that acting together and affecting each other

P63 and cytokeratin 8/18 expression in breast, atypical ductal hyperplasia, ductal carcinoma in situ and invasive duct carcinoma

The pattern and distribution of p63 expression as a myoepithelial/basal stem cell marker can be different between atypical ductal hyperplasia [ADH], ductal carcinoma in situ [DCIS] and invasive ductal carcinoma [IDC] and may denote basal phenotype of breast ductal carcinoma. CK8/18 is a luminal marker and may indicate a luminal phenotype of IDC and its expression in ADH and DCIS may refer to a possible precursor lesion to IDC. This work was designed to study and compare the expression of p63 and cytokeratin 8/18 [CK8/18] in some cases of ADH, DCIS and IDC. Histopathological evaluation and immunohistochemical study of anti-p63 and anti- CK8/18 was performed on selected archival cases of 7 ADH, 12 DCIS, 30 IDC of known clinicopathological data and previous estrogen receptor status [ER] for IDC. Confirmatory anti-smooth muscle actin [ASMA] expression for positive p63 cases was performed. p63 was expressed in the peripheral rim of the myoepithelial cell layer in ADH and DCIS with occasional gabs in DCIS. It was positive and stained occasional malignant cells in 3/30 [10%] of IDC cases. Confirmatory ASMA staining decorated the same peripheral rim of cells in ADH and DCIS, but was negative in p63 positive IDC cases. CK8/18 was positive in 100% of ADH, 8/12 [66.7%] of DCIS and 22/30 [73%] of IDC cases. Combined p63 and CK8/18 expression was noticed in 3/30 [10%] of IDC. It is concluded from this study that p63 is specific and valuable in differentiating myoepithelial cells and is more specific and valuable than other myoepithelial markers, as ASMA and can differentiate between ADH, DCIS, IDC as it stains peripheral myoepithelial cells in ADH and DCIS with gabs in the latter and does not stain any neoplastic cells. In IDC, it is positive in malignant cells in a minority of cases which may indicate basal/stem cell/myoepithelial cell origin of breast carcinoma. Comparatively, CK8/18 cannot differentiate ADH, DCIS and IDC as there is no difference in its staining pattern among them, which may suggest that they are a continuum or that ADH and DCIS are precursors for the luminal phenotype of IDC

Role Of alpha- chymotrypsin and colchicine as adjuvant therapy in experimental muscular trichinellosis : parasitological, biochemical and immunohistochemical study

Muscular trichinellosis is a crippling disease, and it is not satisfactorily treated by the anti-parasitic drug albendazole. Trichinella spiralis larvae can survive for long time in muscle phase by formation of fibrous [collagenous] capsule around it, for their protection from host immune system. Colchicine, is a well known antifibrotic that is used long time ago in different fibrotic diseases, and proved recently to be safe for use even in long durations. Also, alpha-chymotrypsin is one member of proteinase enzymes that were proved to cause degradation of extracellular matrix components. So, this study aimed to investigate the effect of adding these antifibrotic agents to albendazole during treatment of muscular trichinellosis. The study was performed on 175 albino mice comprising 7 equal groups 25 mice each. Mice from groups I to VI were infected by T.spiralis larvae orally [200larvae / mouse], group VII served as the healthy non infected group for comparison of biochemical and immunohistochemical results. Group II was treated by albendazole alone orally for three successive days, groups III, IV were given alpha-chymotrypsin intramuscularly and colchicine orally respectively, for four weeks. Groups V,VI were given combined therapy of albendazole and alpha-chymotrypsin and albendazole and colchicine respectively for four weeks. Assessment of results was achieved through; parasitological, biochemical and immunohistochemical studies. Total larval count was done to all studied infected groups, measurement of tissue markers of fibrosis'' muscle hydroxyproline and [MMP-2]'', and also immunohistochemical staining of collagen type IV and fibronectin was done to both infected groups and the non infected one for comparison. Statistical analysis was performed to determine differences between studied groups in different measured parameters. In groups treated with combination therapy [albendazole and alpha-chymotrypsin, ''group V'' and albendazole and colchicine'' group VI''], there was a marked reduction in total larval count, reduction of muscular hydroxyproline levels, elevation of muscular MMP-2 when compared to the group treated with albendazole alone ''group II'', the differences were found to be statistically significant [p<0.05]. At the same time, the differences in the previously mentioned parameters were proved to be non significant statistically between group V and group VI. There was also a decrease in staining intensity of collagen type IV and fibronectin in groups received the antifibrotics[groups III to VI] in comparison to both groups I and II and the, there was a statistical positive correlation between hydroxyproline biochemical mean value and staining intensity [p<0.05]. Addition of antifibrotic drugs [alpha- chymotrypsin and colchicine] as adjuvant therapy to antiparasitic drugs in treatment of muscular trichinellosis could be a beneficial measure to improve treatment outcome by decreasing both numbers of larvae in the muscle, and fibrous tissue formation, which form together the backbone of pathology and crippling to the patient