Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.
Molecular and biochemical effects of novel drugs derived from photoactivated compounds for chemotherapy of leukemia (Meeting abstract).
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 Gulliya KS; Sharma RK; Wiggs RB; Baylor Univ. Medical Center, Baylor Res. Inst., 3812 Elm, Dallas,; TX 75226
Abstract:
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.
Keywords: 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 ABSTRACT
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Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.
