The nm23-H1 gene is known as a potential metastasis suppressor gene in various types of carcinomas. However, the role of nm23-H1 in colorectal carcinoma still remains controversial and the cellular mechanisms by which its protein may modulate the metastatic phenotype are not yet known. We transfected nm23-H1 cDNA into the human colon cancer cell line, HT-29, to test the effects and cellular biological mechanism of nm23 protein in colon cancer. We found that nm23-H1 strongly inhibited the liver metastasis of HT-29 cells in nude mice and inhibited the epidermal growth factor (EGF)-induced cell migration in vitro. The nm23 gene was first identified as a gene whose expression was reduced in highly metastatic rodent tumors relative to poorly metastatic tumor cells. 1 The transfection of nm23 cDNA into various cancer cell lines resulted in the suppression of metastatic potential of motility, invasion or colonization. [2][3][4][5][6][7] This implies that nm23 is a potential metastasis suppressor gene and could function on the invasion and migration steps of the metastatic pathway. The nm23 protein has a kinase activity and is recognized as a nucleoside diphosphate (NDP) kinase. Eight human nm23 genes have been characterized so far. The initial 4 human genes of this family, nm23- H1,) and nm23-H4, encode proteins products that process NDP kinase activity and are named NDP kinase A-D, respectively. Of the 8 human nm23 genes, the H1 gene is most closely correlated with the metastatic phenotype in human breast, colorectal and ovarian carcinoma. 8 -12 However, the role of nm23-H1 in colorectal carcinoma is still controversial. Conflicting observations have been reported. Allelic deletion or mutation of the nm23-H1 gene appears to be associated with distant metastasis in some studies; 13-16 on the other hand, there are several studies that denied the correlation between the progression of colorectal carcinogenesis or distant metastasis and nm23-H1 expression. [17][18][19] The cellular mechanisms by which the nm23-H1 protein may directly or indirectly modulate the metastatic phenotype are not yet known; however, several studies reported that nm23-H1 inhibited the cell motility toward polypeptide growth factors such as platelet derived growth factor (PDGF) and insulin-like growth factor (IGF). 20,21 Among those growth factor receptors, the epidermal growth factor receptor (EGFR) is one of the receptors most commonly associated with human tumors and has been shown to correlate with the progression of many types of tumors, 22,23 and it is associated with the aspects of tumor growth (i.e., proliferation, apoptosis and cell survival). However, it has been reported that EGF stimulated the migration of both normal and tumor cells. 24 -27 Furthermore, it has been reported that mitogen-activated protein kinase (MAPK) (ERK1 and ERK2) influenced the cellular motility mechanism by phosphorylating and thereby enhanced myosin light chain kinase (MLCK) activity leading to the phosphorylation of myosin light chains (MLC). 28 In our study...

GCDFP-15 is useful for confirming the primary site of breast carcinoma. Ultrasonography, computed tomography, and magnetic resonance imaging are thought to be good for detecting occult primary tumors. The incidence of OBC is still unclear, but it is possible that these patients need to be treated as typical stage II patients.

The present work demonstrates the utility of packed bed reactors for the production of monoclonal antibody. We present data from a continuous process run for the production of over 100 grams of antibody, using serum-free medium. An additional pilot run also demonstrates the potential for continued antibody production under protein-free conditions, using a standard basal medium.

No abstract

No abstract