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M9471062.TXT
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1994-08-09
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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
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).