       Document 1090
 DOCN  M9591090
 TI    Role of scatter factor and the c-met protooncogene in the pathogenesis
       of AIDS-associated Kaposi's sarcoma.
 DT    9509
 AU    Polverini PJ; Nickoloff BJ; Department of Oral Medicine, University of
       Michigan School of; Dentistry, Ann Arbor 48109-1078, USA.
 SO    Adv Cancer Res. 1995;66:235-53. Unique Identifier : AIDSLINE
       MED/95313611
 AB    Kaposi's sarcoma is a highly lethal tumor in patients with sexually
       acquired AIDS. A number of etiologic agents have been implicated in the
       development of this disease in this patient population and there is
       ample evidence that aberrant production of and responsiveness to KS
       tumor and host cell-derived cytokines plays a central role in the
       pathogenesis of AIDS-KS. In this review we propose that aberrant
       expression SF and c-met is central to the pathogenesis of KS. KS is a
       serious and life-threatening consequence for many patients with AIDS.
       Unfortunately, current therapeutic strategies for the treatment of this
       complex neoplasm have met with only limited success. In view of the poor
       survival rates for AIDS-KS patients which continue to decline at an
       alarming rate, it is eminently clear that a better understanding of the
       etiology and pathogenesis of this form of KS is needed if novel
       therapeutic strategies designed to successfully combat this disease are
       to be developed. If our hypothesis is validated, one could envision
       several approaches whereby the modulation of SF/c-met function or
       production might lead to a reduction in the incidence and severity of KS
       lesions. Antibody therapy directed against either SF-producing tumor
       cells or against the c-met receptor might decrease the incidence of new
       tumors by limiting their clonal expansion and lead to regression of
       established tumors by blocking SF-mediated tumor cell proliferation and
       neovascularization. It might also be possible to suppress production of
       SF or accessory cytokines involved in the induction SF production and
       thus short circuit SF/c-met growth-promoting effects. We have outlined a
       novel hypothesis for understanding the mechanism underlying the
       development of AIDS-associated KS. This is most certainly not the whole
       story, however. Clearly, other cytokines and alterations in natural host
       defenses and the immune system contribute significantly to the
       development of AIDS-associated KS. We believe, however, that recognition
       of SF/c-met as a participant in this disease is necessary if we are to
       more fully understand the pathogenesis of AIDS-associated KS.
 DE    Acquired Immunodeficiency Syndrome/*COMPLICATIONS  Hepatocyte Growth
       Factor/*PHYSIOLOGY  Human  *Proto-Oncogenes  Receptor Protein-Tyrosine
       Kinase/*GENETICS  Sarcoma, Kaposi's/*ETIOLOGY  Support, U.S. Gov't,
       P.H.S.  JOURNAL ARTICLE  REVIEW  REVIEW, ACADEMIC

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

