Document 0792
 DOCN  M94B0792
 TI    Proliferation of leiomyosarcoma cell lines is inhibited in vitro by
       antisense oligonucleotides directed against the insulin growth factor
       Type I receptor (Meeting abstract).
 DT    9412
 AU    Hirschfeld S; Helman LJ; Pediatric Branch, NCI, Bethesda, MD
 SO    Proc Annu Meet Am Assoc Cancer Res; 35:A1543 1994. Unique Identifier :
       AIDSLINE ICDB/94603229
 AB    Smooth muscle proliferation can lead to a variety of pathologic
       conditions, including benign (leiomyoma) and malignant (leiomyosarcoma;
       LMS). Published studies have shown that smooth muscle cell proliferation
       can be enhanced by insulin growth factor I (IGF-I), and that surgical
       specimens of LMS contain RNA transcripts for IGF-II. In addition, in
       children with HIV infection, there is an unusually high incidence of
       smooth muscle tumors compared to uninfected children. The present study
       was performed to see if the IGF signaling pathway could regulate
       proliferation of LMS cell lines. Cell lines were tested for the presence
       of IGF RNA transcripts by northern blotting using cloned fragments of
       IGF-I and IGF-II as probes. In contrast to the reports on surgical
       specimens, none of the lines showed detectable levels of IGF-II RNA, and
       only minimally detectable levels of IGF-I RNA. Monoclonal antibody
       directed against the Type I receptor showed a 15% decrease in growth
       rate for one line, and had no effect on the others. Using
       oligonucleotide sequences from two different regions of the IGF type I
       receptor, we were able to show a 30-50% decrease in the rate of
       proliferation, with a peak effect between 48 and 72 hours after the
       addition of the oligonucleotides to the medium. A combination of
       sequences was more effective on a molar basis than either sequence
       alone. Alterations in growth rate were not observed using sequences
       directed against the epidermal growth factor receptor. These results
       suggest a role for the IGF Type I receptor in the regulation of LMS
       proliferation, which may have therapeutic implications.
 DE    Human  Leiomyosarcoma/*PATHOLOGY/*THERAPY  Oligonucleotides,
       Antisense/PHARMACOLOGY  Receptors, Insulin-Like-Growth Factor I/*DRUG
       EFFECTS/*METABOLISM  Receptors, Insulin-Like-Growth-Factor II/METABOLISM
       Tumor Cells, Cultured  MEETING ABSTRACT

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).