Subject(s)
Cell Fractionation/methods , Cell Membrane , Trophoblasts/cytology , Adult , Alkaline Phosphatase/metabolism , Basement Membrane , Blotting, Western , Cell Membrane/metabolism , Dihydroalprenolol/metabolism , Female , Humans , Pregnancy , Sonication , Temperature , Trophoblasts/metabolismABSTRACT
Single and fractionated doses of radioimmunotherapy (RAIT) and standard chemotherapy (0.6 mg 5-FU/day and 0.36 leucovorin/day on days 1-5) result in decreases in vascular permeability (VP) in the GW-39 human colonic xenograft. The effect of a single dose of RAIT (MN-14 anticarcinoembryonic antigen, Mu-9 anticolon-specific antigen, PAM-4 anti-MUC-1, RS-7 and RS-11 antiepithelial glycoprotein labeled with 131I) has also been evaluated in 10 other tumors. Fourteen days after a fixed 1,500-cGy dose of RAIT, 3 colonic tumors (LS174T, HT-29 and MOSER) all exhibited decreases in VP (58, 75 and 70%, respectively). Two colonic (LoVo and GS-7) and 1 breast tumor (MDA-468) did not exhibit any change in VP, and 1 lung (CALU-3), 1 cervical (ME-180), 1 pancreatic (CaPan-1) and 1 breast cancer line (ZR-75) exhibited increases in tumor VP (214, 289, 170 and 139%, respectively). The differences in VP response to RAIT do not appear to be related to the type of tumor, the size of tumor or the antigen being targeted by RAIT. The differences in tumor VP response to RAIT are discussed in terms of the ability to achieve significant tumor accretion of a second dose of radioantibody on a multiple-dosing regimen. We have begun to investigate the mechanism(s) which regulate the varying responses of tumor VP to RAIT by assessing the role that nitric oxide plays. Administration of arginine, a substrate for nitric oxide synthase, results in increases in both baseline and RAIT-modified VP in GW-39 and ME-180 tumors.
Subject(s)
Capillary Permeability/radiation effects , Neoplasms, Experimental/blood supply , Neoplasms, Experimental/radiotherapy , Neovascularization, Pathologic/radiotherapy , Radioimmunotherapy , Animals , Antibodies, Bispecific/pharmacokinetics , Antibodies, Bispecific/therapeutic use , Antidotes/pharmacology , Antimetabolites, Antineoplastic/pharmacology , Capillary Permeability/drug effects , Colonic Neoplasms/blood supply , Colonic Neoplasms/radiotherapy , Cytotoxicity, Immunologic , Female , Fluorouracil/pharmacology , Humans , Leucovorin/pharmacology , Mice , Mice, Nude , Neovascularization, Pathologic/pathology , Transplantation, Heterologous , Tumor Cells, CulturedABSTRACT
A transcriptional enhancer which has a consensus binding sequence for transcription enhancer factor-1 (TEF-1) has been found 3' of the hPL(3) gene. We examined whether TEF-1 is expressed by the human placenta and whether such expression is co-ordinated with that of human placental lactogen (hPL). Probing Northern blots of total RNA from first trimester and term placenta, the choriocarcinoma-derived cell line JAr and primary cultured cytotrophoblast cells with a cDNA for TEF-1 revealed transcripts of 12-13 kb and 3-4 kb. The level of TEF-1 expression was the same in first trimester as compared with term placenta and in undifferentiated JAr as compared with differentiated cytotrophoblast cells. hPL expression was tenfold higher in term compared with first trimester placenta and, whilst detectable in cytotrophoblast cells, was undetectable in JAr cells. These data show that TEF-1 is expressed by the placenta but is not co-ordinated with hPL expression.
