Protein expression of metastasis-related genes in human bladder carcinoma

The discovery of genetic alterations in oncogenes and tumor suppressor genes that accompany tumor formation has encouraged the search for genes that may promote or suppress tumor metastasis. This study aimed to investigate, by immunohistochemical analysis, protein expression of the metastasis-related genes metalloproteinase-2 [MMP-2] and nm-23 in human bladder carcinoma. Their role as prognostic factors against established clinicopathological variables in bladder carcinoma was evaluated. A total of 60 specimens of bladder carcinoma were obtained by radical cystectomy with pelvic lymphadenectomy. In addition, 10 tissue samples from normal mucosa adjacent to tumors were examined and served as controls. Immunohistochemical expression of MMP-2 and nm-23 was correlated with histological grade, tumor stage, lymph node metastases, and the presence or absence of bilharziasis. MMP-2 was expressed in 63% of patients with human bladder carcinoma and was shown to be positively correlated with histological grade, lymph node metastasis, and tumor stage. In contrast, nm-23 was expressed in 61% of patients with carcinoma but with insignificant correlation between its expression and the previous variables. Both proteins showed insignificant correlation with the presence or absence of bilharziasis. The study revealed that nm-23 expression was nonsignificantly correlated with MMP-2 expression and that nm-23 does not behave as a metastasis suppressor gene in bladder carcinoma. MMP-2 overexpression seems to be related to more aggressive tumors with advanced stages and grades; therefore, it may be used not only as a promoting prognostic marker for bladder carcinoma but also as a novel target for clinical therapy

Comparative in vivo and in vitro hepato-toxicity studies for oral anabolic steroids abused in sports

Studies on hepatotoxicity of anabolic- androgenic steroids in experimental animals and in controlled clinical studies were based on the use of doses at substantially lower level than those practiced by the abusers. the aim of this study was to investigate acute hepatotoxic effects after administration of suprapharmacological doses to experimental animals as well as to isolated hepatocytes suspension to reflect any hepatic dysfunction caused by anabolic steroid abuse. Male adult albino rats were administered daily oral doses of methyltestosterone [175mg/Kg], testosterone-undecanoate [420 mg/Kg], and their combination for 7 days. In vivo results showed significant increase in serum aspartate aminotransferase [AST] and lactate dehydrognease [LDU]. While both steroids did not affect serum levels of alanine aminotransferase [ALT], thiobarbituric acid reactive substances [TBARS], reduced glutathione levels and total protein, when administered either individually or in combination. Leakage of ALT, AST and LDH was observed in any vitro studies in addition to increase in TBARS content. All treatments did not result in any significant difference in reduced glutathione content compared to the respective control. Histopathological examination of the liver revealed inflammatory and degenerative lesions in addition to focal necrosis. The histopathological findings confirm the biochemical studies [both in vivo and in vitro] and show clear toxic manifestations of suprapharmacological doses of theses anabolies on the liver

Ductal breast tumours: mean nuclear area and metallothionein expression in correlation with estrogen receptor status

Estrogen is an important growth Ilictor for breast tumour playing an important role in regulating the proliferation and differentiation of normal and malignant mammary epithelial cells. Nuclear morphometry and Metallothioneins [MTs] are indicators of proliferation that have been used as predictors of prognosis in many tumours. The present study aimed to study mean nuclear area and MT; ER expression in fibroadenoma, ductal carcinoma in situ and infiltrating ductal carcinoma of the breast. Also MNA and MT expression will be correlated with histologic grade and ER status in breast carcinoma. Breast tissues from 12 patients with fibroadenoma [FA], 6 patients with ductal carcinoma in situ [DCIS] and 20 patients with infiltrating durtal carcinoma [IDC] were used in this study. Mean nuclear area [MNA] and metallothionein [MT] expression; as proliferation markers; were investigated and correlated with estrogen receptor [ER] status. All cases of fibroadenoma, 4 out of 6 cases [66.7%] of DCIS and 12 out of 20 cases [60%] of IDC were positive for ER. MNA of cancer cells was significantly larger than that of normal and benign breast tissue. A significant direct correlation was found between MNA and histologic grades. MNA of ER negative carcinomas was significantly larger than that of ER positive tumours. In normal and benign breast tissue, myoepithelial cells consistently expressed the MT protein. Two out of 6 DCIS cases [33.3%] and 13 out of 20 cases of IDC cases [65%] were positively stained for MT. MT positivity was directly correlated with histologic grade of JDC. There was a highly significant inverse correlation between MT and ER over-expression. From this study, it is concluded that in invasive ductal carcinoma of the breast, the large MNA and MT over-expression are correlated with histologic grades and ER negativity. Therefore, MNA and MT overe-expression may be possible important indicators for more aggressive and less differentiated breast carcinoma

protective role of ginseng against liver damage caused by potassium dichromate Cr [IV]: light and electron microscopic studies

Human exposure to carcinogenic Hexavalent Chromium Cr [VI] compounds is found among workers in a large number of professional groups, and it can also occur through environmental pollution. A significant number of toxic waste sites contain Cr as a major contaminant. Chromium is a heavy metal which is widely used in the painting, pigments, dyes, and leather tanning industries. Ginseng is one of the most popular herbal remedies. In a series of experiments we have studied the possible role of the water ginseng extract, in modulating the histological and histochemical damage induced by potassium dichromate Cr [VI] in liver tissue of albino rats. Fourty male albino rats were used in this study. Potassuim dichromate was given orally in a dose of 50mg/kg body weight. Rats were treated orally with ginseng extract in a dose of 20 mg/kg body weight. Specimens of the liver were taken and prepared for light and electron microscopic investigations. Other specimens were stained with, periodic-shiff reagent and Feulgen stain for histochemical investigations. The morphometric analysis of hepatocytes nuclear diameters, the optical density of mucopolysaccharide and DNA reactions were evaluated by the computer image analysis. Light microscopic investigation of liver of rats treated with Cr [VI] showed massive vacuolar degeneration and circumscribed nodule formed of a homogenous acidophilic material infiltrated by mononuclear cells. Apoptic cells with deep eosinophilic cytoplasm and small deeply stained [pyknotic] or fragmented nuclei were clearly demonstrated together with fatty degeneration manifested by round empty well-circumscribed spaces. Necrosis of hepatocytes was observed, they showed irregular nuclei densly packed with chromatin. At the ultrastructural level the hepatocytes revealed that endoplasmic reticulum was slightly swollen and vesiculated. In addition, different degrees of mitochondrial damage were present in the form of differences in shape and size and distortion of their ridges. The results have manifested a possible protective role of ginseng extract on the general cellular morphology, as well as significant improvement in glycogen and DNA contents in ginseng treated rats against chromium toxicity

Protective effect of melatonin, methionine and zink on cadmium nephrotoxicity: histopathologically, histochemically and AgNORs quantitation

Cadmium [Cd] is a highly toxic heavy metal that is naturally present in the environment. Chronic exposure to Cd causes hepatotoxicity and nephrotoxicity. The present study aimed to study the protective effect of melatonin, methionine and zinc against histopathological, histochemical and proliferative effects of cadmium on the kidney of rats. A total of 80 female albino rats were included in this study and divided into 8 groups. They were injected intraperitonealy with cadmium chloride [CdCl2] [2 mg / kg b.w.], melatonin [10 mg / kg b.w.], methionine [42.8 mg / b.w.] or zinc [20 mg / kg b.w.] with or without CdCl2 daily for 10 days. Treatment with CdCl2 induced marked tubular cell degeneration with large areas of interstitial hemorrhage.There were marked destruction of the brush borders with decrease in glycogen and protein contents of the degenerated tubules. AgNORs count significantly increased. Injection of melatonin or methionine to CdCl2 treated rats resulted in improvement of Cd-induced histopathological and histochemical changes. AgNORs count significantly decreased. Zinc injection partially protected the kidney from Cd-induced effects. In conclusion, melatonin and methionine have a more protective effect than zink against Cd nephrotoxicity