ABSTRACT
BACKGROUND: Is the complementary supplementation of selenium useful in the therapy of colorectal cancer? PATIENTS AND METHODS: Fifty-three patients with primary colorectal cancer received a selenium treatment for 19 days in addition to a complete in-patient rehabilitation cure based on a behavioural approach. A comparative control group consisted of 41 patients. Measured factors were the selenium content in serum and whole blood, GSH-Px activity and TBARS in serum. Both the intake of selenium by nutrition and the patients' life quality were determined additionally on day 1 and 19. The tumor marker CA 19-9 was measured only on day 1. RESULTS: A latent selenium deficiency was observed while gsh-px activity or concentration of TBARS were normal. The selenium status corresponds to the concentration of the tumor marker CA 19-9. The selenium status improves through supplementation, accompanied by a further increase of GSH-Px activity. During supplementation the patients' life quality improves; subjective physical complaints decrease. CONCLUSION: Further research will be necessary on both the dependency of the selenium status on the tumor marker concentration and on the development of the cancer. Optimum GSH-Px activity and individually different responses also need additional investigation. The influence of selenium on the patients' life quality should be investigated in the context of immunomodulation.
Subject(s)
Colorectal Neoplasms/rehabilitation , Selenium/administration & dosage , Adult , Aged , CA-19-9 Antigen/blood , Combined Modality Therapy , Female , Humans , Male , Middle Aged , Patient Admission , Quality of Life , Selenium/bloodABSTRACT
OBJECTIVE: E-selectin is an endothelial cell-specific membrane glycoprotein that participates in leukocyte adhesion and has also been suggested to function in angiogenesis. To gain further insights into E-selectin, we analyzed E-selectin polypeptide in proliferating versus quiescent bovine capillary endothelial cells and its expression as a function of the cell cycle. METHODS: E-selectin polypeptide was analyzed by immunoadsorption from 35Scysteine-labeled endothelial cells, by enzyme-linked immunosorbent assay, and by fluorescence-activated cell sorting. The distribution of endothelial cells in Gzero/G1, S, and G2/M phases of the cell cycle was determined using propidium iodide staining of DNA. RESULTS: E-selectin was upregulated in subconfluent proliferating bovine capillary endothelial cells compared to confluent quiescent cultures. The upregulation was independent of activation in that E-selectin was further increased by treatment with tumor necrosis factor alpha or lipopolysaccharide. In contrast to E-selectin, P-selectin and platelet-endothelial cell adhesion molecule-1 did not appear to be regulated by the growth state of the endothelial cells. The distribution of E-selectin-positive cells in GzeroG1, S, and G2/M phases of the cell cycle differed from E-selectin-negative cells in that more of the E-selectin-positive cells were in G2 and M. CONCLUSIONS: Increased E-selectin expression under noninflammatory conditions is correlated with cellular proliferation and G2/M phases of the cell cycle. The expression of E-selectin in proliferating endothelial cells in vitro is consistent with the presence of E-selectin in proliferating endothelial cells in vivo (Kräling et al. [18]).
Subject(s)
E-Selectin/chemistry , E-Selectin/metabolism , Endothelium, Vascular/metabolism , Up-Regulation , Animals , Antibody Specificity , Cattle , Cell Adhesion , Cell Division , Cells, Cultured , E-Selectin/immunology , Endothelium, Vascular/chemistry , Endothelium, Vascular/cytologyABSTRACT
The levels of E-selectin mRNA and protein were analyzed in bovine capillary cells treated with or without the angiogenesis inhibitor AGM-1470 (also known as TNP-470). Cells treated with AGM-1470 had a two- to sevenfold (median fivefold) increase in E-selectin mRNA compared with little or no increase in P-selectin, PECAM-1 and VCAM-1 mRNA. E-selectin protein was also significantly increased after exposure to AGM-1470. In contrast, there was no detectable effect on PECAM-1 protein. The increase in E-selectin mRNA and protein was always greater with subconfluent growing cells than with confluent cells. This apparent resistance of confluent endothelial cells to AGM-1470 may be relevant to its specificity in vivo. The fact that the effect of AGM-1470 on E-selectin is relatively selective for subconfluent growing cells may provide a clue as to how AGM-1470 is able to both reversibly inhibit endothelial cell proliferation in vitro and inhibit tumor growth in vivo without apparent effects to quiescent endothelium.
Subject(s)
Antibiotics, Antineoplastic/pharmacology , E-Selectin/biosynthesis , Endothelium, Vascular/physiology , Gene Expression/drug effects , Neovascularization, Physiologic/drug effects , Sesquiterpenes/pharmacology , Adrenal Cortex/blood supply , Animals , Antigens, Differentiation, Myelomonocytic/biosynthesis , Capillaries , Cattle , Cell Adhesion Molecules/biosynthesis , Cyclohexanes , Endothelium, Vascular/cytology , Endothelium, Vascular/drug effects , O-(Chloroacetylcarbamoyl)fumagillol , P-Selectin/biosynthesis , Platelet Endothelial Cell Adhesion Molecule-1 , Protein Biosynthesis , RNA, Messenger/biosynthesis , Transcription, Genetic , Vascular Cell Adhesion Molecule-1/biosynthesisABSTRACT
The levels of P-selectin mRNA and polypeptide were analyzed in bovine capillary cells treated with or without the cytokine tumor necrosis factor-alpha. The 3 kb P-selectin mRNA was upregulated three- to five-fold in cytokine-stimulated cells. The increase in mRNA correlated with a dramatic but short-lived increase in P-selectin polypeptide as determined by metabolic-labeling and immunoadsorption. These data confirm earlier studies on mouse P-selectin expressed in a mouse endothelioma cell line and further indicate that P-selectin function can be regulated not only by rapid translocation to the cell surface but also by cytokine-stimulation of P-selectin biosynthesis.
