Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.69 (BMT)
 2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several new cytostatic drugs have entered clinical Phase I-II studies for treatment of leukemia: most promising are pyrimidine analogues such as 5-Azacytosine arabinoside, 5-Aza-2-deoxycytidine, 5-Azacytidine, cyclocytidine, and 2'-2'-difluorodeoxycytidine. They act on different biochemical levels towards DNA-synthesis. Fludarabine is a purin analogue and seems very active in treating CLL. Tiazofurin is an antimetabolite counter-acting nicotinic acid with most promising activity in CML blast crisis. Other substances include deoxycoformycin, an adenosine analogue for treatment of T-cell neoplasias, 1, 25-dihydroxy vitamin D 3 as differentiation inducer, and homoharringtonine, an alkylating agent widely used for treating de novo AML in China. New anthracyclines are THP-adriamycin, fluoroadriamycin, and 4-demethoxydaunorubicin. Amsacrine (mAMSA) finally, is a synthetic aminoacridine with DNA-intercalating properties. The intact acridine ring appears essential for antitumor activity. The plasma clearance of both total amsacrine and unchanged parent species is biphasic. There is a considerable influence of hepatic and renal impairment on plasma clearance. Clinical toxicities include marked myelosuppression, gastrointestinal symptomes, phlebitis, mucocutaneous lesions, occasionally alopecia and neurotoxities. It is a very active drug, particularly in treating AML. Studies using mAMSA alone or in combination revealed comparable results to the anthracyclines. The E.O.R.T.C. Leukemia Cooperative Group has used successfully mAMSA in several trials: relapsed and refractory AML, intensive maintenance treatment during first remission in AML, and, still on-going, during intensive consolidation randomized against BMT in AML-patients under the age of 45 years, and randomized against standard consolidation between the age of 45 and 60 years.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:New drugs in the treatment of acute and chronic leukaemia: current role of mAMSA. 269 2

BRCA1 (breast cancer-associated gene 1) is a tumor suppressor gene that plays a role in DNA repair when phosphorylated. Many DNA-damaging agents including UVC and hydrogen peroxide have been shown to induce phosphorylation of BRCA1. Results of this study now show that both UVB and a bicyclic monoterpene diol (BMT diol) result in phosphorylation of BRCA1. This phosphorylation was maximal 2 h after treatment with either agent and declined to basal levels by 24 h. Inhibitor studies revealed that both UVB and the BMT diol phosphorylate BRCA1 through the FK506-binding protein-FKBP rapamycin-associated binding protein pathway, but the BMT diol also led to phosphorylation of BRCA1 through casein kinase II. This suggests that the signaling pathways for UVB and the BMT diol may diverge. Results of this study also show that the BMT diol stimulates the repair of UVB-induced cyclobutane pyrimidine dimers (CPD). Inhibitors of BMT diol-induced BRCA1 phosphorylation blocked the BMT diol-stimulated repair of CPD. This indicates that the BMT diol induces the phosphorylation of BRCA1, which, in turn, leads to an increase in repair of UVB-induced CPD. Therefore, this BMT diol may be useful for ameliorating the damaging effects of UVB.
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PMID:A bicyclic monoterpene diol and UVB stimulate BRCA1 phosphorylation in human keratinocytes. 1285 82