No abstract available.

No abstract available.
Extremities*

No abstract available.
Observer Variation*

Development of antibody-based cancer therapies will be greatly facilitated if antibodies are better standardized in two fundamental issues that are specificity analysis of antibody reactivity and the detailed biodistribution and pharmacokinetic profile of antibodies. In the current endeavor we attempted to use an antibody binding specificity to target the tumor in a syngeneic carcinoembryonic antigen (CEA) tumor model. CEA, a 180 kDa glycoprotein, expressed at high levels on the surface of nearly all tumors of the gastrointestinal tract was used a potential target for antibody immunotherapy of gastrointestinal carcinomas. Using the CEA model antibody-based cancer therapy directed against CEA has been evaluated in a syngeneic animal model of disseminated disease. We constructed mouse/human chimeric anti-CEA IgG3, which has been evaluated for the specificity for CEA and the detailed biodistribution and pharmacokinetic profiles. Anti-CEA IgG3 heavy chain was expressed with the expected 180kDa molecular weight, assembled as H2L2 forms with a co-expressed mouse/human chimeric anti-CEA light chain, and were secreted. On FACS the purified anti-CEA IgG3 specifically recognized the mouse colon adenocarcinoma cell line MC-38 transduced with CEA (MCA32a), but not MC 38 without expressing CEA. After subcutaneous injection in C57BL/6 mice the half- lives of anti-CEA IgG3 and an irrelevant anti-dansyl IgG3 showed the bi-phasic kinetic patterns, and their pharmacokinetics of the distribution and the elimination were similar in mice. However, the biodistribution patterns of anti-CEA IgG3 were very different from those of anti-dansyl IgG3. Anti-dansyl IgG3 was mainly distributed into kidney until 72 hours, but anti-CEA IgG3 was slowly rernoved from blood and distributed into liver, kidney, spleen, and tumor. It is note worthy that anti- CEA IgG3 increased in targeting MCA32a tumor expressing human CEA by time, but the targeting to MC38 tumor was negligible. Thus, the increased targeting of anti- CEA IgG3 made MCA32a tumor grow slowly
Adenocarcinoma ; Animals ; Antibodies ; Carcinoembryonic Antigen ; Cell Line ; Colon ; Gastrointestinal Tract ; Glycoproteins ; Humans ; Immunoglobulin G* ; Immunotherapy ; Injections, Subcutaneous ; Kidney ; Liver ; Mice ; Models, Animal ; Molecular Weight ; Pharmacokinetics ; Sensitivity and Specificity ; Spleen

To generate drug delivery vector to locales in the body, genetic engineering and expression techniques have been used to produce antibody avidin fusion proteins. Chicken avidin has been fused to mouse-human chimeric IgG3 immediately after the hinge with a flexible linker (H-Flex-Av) and at the end of CH2 (CH2-Av). Fusion heavy chains were expressed with the expected molecular weight, assembled as H2L2 forms with a co-expressed light chain, and were secreted. The expression level of H- Flex-Av was 1~10 ug/ml/10(8)/24 hrs, but that of C2-Av was a very little (0.08~0.9 ug/ ml/10(8)/24 hrs). The resulting H-Flex-Av and CH2-Av fusion proteins continued to bind antigen dansyl and also bound biotinylated bovine serum albumin; both H-Flex-Av and CH2-Av had shown to retain 3-4 times higher relative affinity than that of CH3-Av in ELISA. Importantly the fact that both avidin fusion proteins had a higher relative affinity suggests that these avidin fusion proteins can be effectively used to deliver biotinylated ligands such as drugs and peptides to a certain locale, such as the brain.
Avidin ; Biotin* ; Brain ; Chickens ; Enzyme-Linked Immunosorbent Assay ; Genetic Engineering ; Immunoglobulin G ; Ligands ; Molecular Weight ; Peptides ; Serum Albumin, Bovine

No abstract available.
Pregnancy* ; Ultrasonography*

No abstract available.
Epidemiologic Studies* ; Humans ; Infant, Newborn*

No abstract available.
Postpartum Period* ; Pregnancy*

Intrathecal administration of methotrexate(IT-MTX) has constituted the standard approach to prophylaxis and treatment of central nevous system(CNS) leukemia. We experienced a quadriplegia and motor aphasia in a 14-year-old boy following repeated IT-MTX for the prophylaxis of meningeal leukemia. He was diagnosed as ALL without CNS involvement and treated by CCG- 1882 protocol. IT-MTX was administered for CNS prophylaxis. The patient began complaining of urinary incontinence, motor aphasia and weakness in his right leg from 12 days after the 5th dose of the IT-MTX therapy. Even though the IT-MTX was discontinued, loss of muscle power progressed upward resulting in quadriplegia. The patient showed slow and partial recovery on right extremities over 3 months. We report this case with brief review of literature.
Adolescent ; Aphasia, Broca* ; Extremities ; Humans ; Leg ; Leukemia ; Male ; Methotrexate* ; Quadriplegia* ; Urinary Incontinence

No abstract available.
Carcinoma, Squamous Cell* ; Cervix Uteri* ; Female ; Biomarkers, Tumor*