Document 1062
 DOCN  M9471062
 TI    Molecular and biochemical effects of novel drugs derived from
       photoactivated compounds for chemotherapy of leukemia (Meeting
       abstract).
 DT    9409
 AU    Gulliya KS; Sharma RK; Wiggs RB; Baylor Univ. Medical Center, Baylor
       Res. Inst., 3812 Elm, Dallas,; TX 75226
 SO    International Association for Comparative Research on Leukemia and
       Related Diseases, 16th Symposium. July 11-16, 1993, Montreal, Quebec,
       Canada, A60, 1993.. Unique Identifier : AIDSLINE ICDB/94698657
 AB    The novel technology termed 'preactivation' in which optical radiation
       is used to produce heretofore unknown therapeutic compounds has been
       reported (Gulliya et al, 1991). Because of this invention, photoactive
       compound-derived photoproducts can now be used, for the first time, for
       systemic therapy (independent of light energy) of malignancies and viral
       diseases. Previously, we have demonstrated that preactivated merocyanine
       540 (dubbed optimix 280) is effective against enveloped viruses and
       certain types of tumor cells (Gulliya et al, 1992). Leukemia and
       lymphoma cells were found to be particularly susceptible to the in vitro
       action of this drug. Now we report that treatment of L1210-bearing BDF1
       mice with optimix 280 (250 mg/kg/day; 7 im injections) resulted in a 40%
       increase in the median life-span of the treated animals. Similarly,
       treatment of feline leukemia and feline immunodeficiency virus
       (FIV)-positive cats with lymphocytic plasmocytic stomatitis resulted in
       dramatic improvement of the oral stomatitis, associated foul mouth odor,
       wt, hair coat, and general well-being. The rate of change of the Cite
       FeLV and FIV was significantly slower but did not change to negative
       during the short course of the treatment. There were no observable side
       effects as judged by CBC and SMA profiles. However, gradual relapse
       occurred a few weeks after cessation of the iv therapy. At the molecular
       level, c-myc and c-myb oncogenes, which are known to be involved in the
       regulation of cell proliferation and the process of neoplastic
       transformation, were downregulated by as little as a 2-hr treatment of
       cells with optimix 280. Mice transplanted with drug-treated L1210 cells
       (120 ug/ml for 2 hr) continue to survive (greater than 90 days) compared
       to the median survival of 10 days for the control group. These results
       suggest that optimix 280 may be exerting its in vitro and in vivo
       cytotoxic effects at least in part via downregulation of c-myc and c-myb
       oncogenes.
 DE    Animal  Cats  Cell Transformation, Neoplastic/PATHOLOGY  Feline Acquired
       Immunodeficiency Syndrome/COMPLICATIONS/DRUG  THERAPY  Leukemia
       L1210/*DRUG THERAPY/PATHOLOGY  Leukemia, Feline/DRUG THERAPY  Mice
       Proto-Oncogene Proteins/METABOLISM  Proto-Oncogene Proteins
       c-myc/METABOLISM  Pyrimidinones/*THERAPEUTIC USE
       Stomatitis/COMPLICATIONS  MEETING ABSTRACT

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