The results of several experimental and epidemiological studies have shown an inverse correlation between Mg status and the risk of some cancers. However, relationship between magnesium and cancer is complex. The aim of our work was to examine the precise effect of Mg deficiency on transplantable mouse tumor growth and metastasis. The results obtained indicate a significant retardation of primary tumor growth (up to 70%) in mice receiving Mg-deficient diet. However, Mg repletion caused in these mice significant increase of primary tumor burden. Analysis of cell cycle distribution showed a reduced percentage of cells in the S phase and an increase of cells in the G(0)/G(1) phase of the cell cycle in LLC tumors caused by Mg deficiency. This is in agreement with the effect of low Mg level on cell growth observed in vitro. Interestingly, in mice inoculated with LLC cells and receiving low-magnesium diet, a higher metastatic potential was observed as compared to control mice. In conclusion, our results demonstrate a direct role of magnesium in tumor growth and also point at deleterious effect of low magnesium status on tumor metastasis.
The study aimed at immunohistochemical analysis of various markers of cell proliferation and comparison of the results with canine mast cell tumours grading systems according to the Patnaik and Kiupel. Tissue sections were stained using classical technique with haematoxylin and eosin, and immunohistochemical studies were performed with Ki-67, PCNA and MCM-3 antibodies. Additionally the mitotic index was assessed. Statistical analysis including rank correlation Spearman's and ANOVA Friedman analysis was performed. The significance was set at p<0.05. Expression of all examined antigens was detected. The results obtained allow concluding that there is a strong relationship between all the cell markers. However, due to the very strong response and positive reaction in the majority of tumours PCNA is not recommended as a prognostic indicator. Ki-67 and MCM-3 can be successfully used in the evaluation of canine mast cell tumours.
Several lines of evidence indicate that sialosyl Le(a), tumor-associated carbohydrate antigen present on human colon carcinoma cells, is involved in formation of metastases. To study the role of this carbohydrate structure in development of metastases, we have used the clone of human colon carcinoma CX-1 cells transfected with antisense expression vector containing fragment of cDNA for alpha1,3/4-fucosyltransferase (FT III), which is involved in synthesis of sialosyl Le(a) tetrasaccharide. It has been reported previously that, in contrast to the parental cells, the antisense-transfected CX-1.1AS5 cells do not express sialosyl Le(a) and do not adhere to E-selectin-expressing CHO cells. In the present work we have studied the formation of liver metastases by CX-1.1AS5 cells after their orthotopic or intrasplenic implantation into athymic nu/nu mice. After orthotopic implantation of sialosyl Le(a)-negative colon carcinoma CX-1.1AS5 cells, the number of mice with liver metastases was markedly lower (21% of mice) in comparison with their number after implantation of the parental CX-1.1 cells (86% of mice). However, no differences in ability to form colonies in liver were observed between parental CX-1.1 cells and antisense-transfected CX-1.1AS5 cells after intrasplenic inoculation. The liver metastases were formed in 89% and 84% of mice, respectively. Our data support the thesis on the importance of sialosyl Le(a) antigen expression in the development of liver metastases by colon cancer cells, and indicate the role of transplantation route and primary tumor localization in formation of metastases.
ABSTRACT:In this study, the immunohistochemical features of primary hepatocellular carcinomas and their metastases in visceral organs, including the lungs, spleen and kidneys were examined using antibodies against carcino-embryonic antigen (CEA) cytokeratin (CK) 7 and 20, CD4, CD8, minichromosome maintenance protein 3 (MCM3), vimentin, and alpha 1 foetoprotein (AFP). In addition, Mallory's connective tissue stain, van Gieson's stain and Gomori methenamine silver stain were used. The study was performed on liver samples collected post mortem from five mixed-breed dogs aged 9-12 years. The tumours were classified according to the World Health Organization Classification of Tumours. Strong expression of MCM3 and AFP was found in the hepatic cancer cells and in the metastases to the lungs, spleen and kidneys. The primary tumours and metastatic foci did not react positively with the anti-CD4, anti-CD8, CEA, CK7 and CK20 antibodies. The connective tissue in the primary tumour and the metastases showed a positive reaction to vimentin. Canine hepatocellular carcinomas that metastasise are highly-malignant well-differentiated tumours that produce AFP and trace amounts of both carcinoembryonic antigen and cytokeratin. Therefore, the metastasis resembles the primary tumour and has a common phenotype and genotype with the primary tumour.
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