Murine leukemia

Ricin [9009-86-3], a phytotoxin found in the seeds of the castor oil plant Acinus communis, conjugated to murine monoclonal antibody (Immunogen Corp.), has been approved by the U.S. Food and Dmg Administration (FDA) for the treatment of patients with B-ceU leukemia and lymphoma (59). 

Imidazole antimycotics, ketoconazole, clotrimazole, and miconazole are potent inhibitors of various cytochrome P450-isoenzymes that also affect the metabolism of retinoids. They were fust shown to inhibit the metabolism of RA in F9 embryonal carcinoma cells. When tested in vitm liarazole, a potent CYP-inhibitor, suppressed neoplastic transformation and upregulated gap junctional communication in murine and human fibroblasts, which appeared to be due to the presence of retinoids in the serum component of the cell culture medium. Furthermore, liarazole magnified the cancer chemopreventive activity of RA and (3-carotene in these experiments by inhibiting RA-catabolism as demonstrated by absence of a decrease in RA-levels in the culture medium in the presence of liarazole over 48 h, whereas without liarazole 99% of RA was catabolized. In vivo, treatment with liarazole and ketoconazole reduced the accelerated catabolism of retinoids and increased the mean plasma all-irans-RA-concentration in patients with acute promyelocytic leukemia and other cancels. 

PMEA and its congeners are more effective in vivo than could be predicted from their in vitro potency. While less potent as an antiretrovirus agent than AZT in vitro, PMEA proved clearly superior to AZT when the two drugs were compared for their effectiveness in vivo, in mice infected with murine Moloney sarcoma virus [51,52]. PMEA was also shown to be effective against various other retrovirus infections, including Friend leukemia virus (FLV), Rauscher leukemia virus (RLV), and LP-BM5 (murine AIDS) virus infection in mice, feline leukemia virus (FeLV) or feline immunodeficiency virus (FIV) infection in cats, and SIV infection in macaque (rhesus) monkeys (for review, see Ref. 53). In the latter model [54], again PMEA proved far superior to AZT in suppressing several parameters of the disease. 

Wang, J., and Baltimore, D. (1983). Cellular RNA homologous to the Abelson murine leukemia virus transforming gene expression and relationship to the viral sequence. Mol. Cell. Biol. 3 773-779. 

FIGURE 8.13 Nonreceptor PTKs. These protein kinases form a large family, and most of them contain SH2 and SH3 domains. Several were originally discovered as transforming genes of a viral genome, hence names such as src or abl, derived from Rous sarcoma virus or Abelson murine leukemia virus, respectively. (Adapted from Hunter, T., Biochem. Soc. Trans., 24(2), 307-327, 1996.)... 

Dunkel VC, Pienta RJ, Sivak A, et al. 1981. Comparative neoplastic transformation responses of Balb/3T-3 cells, Syrian hamster embryo cells, and Rauscher murine leukemia virus-infected Fischer 344 rat embryo cells to chemical carcinogens. J Nat Cancer Inst 67 1303-1315. 

Chen, JY, Cheung, NH, Fung, MC, Wen, JM, Leung, WN, and Mak, NK, 2000. Subcellular localization of merocyanine 540 (MC540) and induction of apoptosis in murine myeloid leukemia cells. Photochem Photobiol 72, 114-120. 

Abelson murine leukemia virus abi Tyrosine kinase... 

Wang S, Crute BE, Melnikova IN, Keller SR, Speck NA. Cloning and characterization of subunits of the T-cell receptor and murine leukemia virus enhancer core-binding factor. Mol Cell Biol 1993 13 3324-3339. 

As described in several monographs [4], bryostatin 1 exhibits significant in vitro and in vivo antineoplastic activity against a range of tumor cell lines including murine leukemia, B-cell lymphoma, reticulum cell sarcoma, ovarian carcinoma, and melanoma. It is also effective in the modulation of apoptotic function [5], the reversal of multidrug resistance [6], and stimulation of the immune system [7]. These unique features displayed by bryostatin 1 are attributed to its high affinity for protein kinase C (PKC) isozymes and its ability to selectively modulate their functions [8]. PKCs are a type of intracellular serine and threonine kinase that... 

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