ABSTRACT
Intrahepatic cholangiocarcinoma (ICC), a malignant tumor derived from the intrahepatic bile duct epithelium, has a poor prognosis and is refractory to conventional chemotherapy and radiation therapy. Thus, there is an urgent need to develop new effective therapeutic strategies for this disease. We previously found that L1 cell adhesion molecule (L1CAM) plays an important role in tumor progression of ICC, and we generated a murine mAb, A10-A3 (IgG1), that binds to the Ig1 domain of L1CAM. In the present study, we further characterized A10-A3, constructed a chimeric A10-A3 antibody (cA10-A3) containing the constant regions of human IgG1, and evaluated the therapeutic potential in a human ICC xenograft nude mice model. The affinities (K D) of A10-A3 and cA10-A3 for soluble L1CAM were 1.8 nM and 1.9 nM, respectively, as determined by competition ELISA. A10-A3 inhibited L1CAM homophilic binding and was slowly internalized into the tumor cells, but it did not significantly inhibit proliferation of ICC cells in vitro. cA10-A3 mediated antibody-dependent cell-mediated cytotoxicity in vitro and displayed anti-tumor activity in the ICC animal model. These results suggest that the humanized A10-A3 antibody may have potential as an anticancer agent for the treatment of ICC.
Subject(s)
Animals , Cricetinae , Humans , Mice , Antibodies, Monoclonal/genetics , Antibody-Dependent Cell Cytotoxicity , Bile Ducts, Intrahepatic/drug effects , CHO Cells , Cell Adhesion/drug effects , Cell Proliferation/drug effects , Cholangiocarcinoma/drug therapy , Disease Models, Animal , Endocytosis/drug effects , Immunoglobulin G/genetics , Liver Neoplasms/drug therapy , Mice, Nude , Neoplasm Transplantation , Neural Cell Adhesion Molecule L1/genetics , Protein Binding , Protein Structure, Tertiary , Recombinant Fusion Proteins/immunologyABSTRACT
OBJECTIVE: It is widely known that the menopausal complication in the surgical menopause is to proceed rather than that of natural menopause. But, it has not obviously been proven so far. In this study, we surveyed whether BMD between surgical and natural menopausal group, in terms of decrease of the BMD of the menopausal complication would have a difference. METHOD: By using dual energy X-ray absorptiometry, we compared 2nd-4th Lumbar spine BMD in 28 of surgical menopause with that of 187 of natural menopause. RESULT: There is no obvious distinction in FSH and estradiol concentration between two groups. Surgical and natural menopausal groups showed the BMD -1.046+/-0.175 g/cm2, -0.942+/-0.124 g/cm2, respectively. Also, there is no statistical significance. CONCLUSION: Although there is no statistical significance in the BMD of the surgical menopausal group was lower than that of the natural menopausal group. Prevention of the menopausal complication as well as decrease of the BMD in the surgical menopausal group needs to be required more active attitude.