Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.2 (topoisomerase)
 9,166 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was designed to investigate the biologic and molecular basis of the aggressive behavior of high-grade post-thymic T-cell malignancies. Freshly frozen tumor tissues from (1) human T-cell leukemia/lymphoma virus type I (HTLV-I)-positive adult T-cell lymphoma (ATL) (7 cases), (2) HTLV-I-negative aggressive T-cell lymphoma (12 cases), and (3) HTLV-I-negative nonaggressive T-cell lymphoma (11 cases) were studied for the expression of several growth-related genes or proliferation antigens including interleukin-2 receptor (IL-2R), Ki-67, transforming growth factor-beta (TGF-beta), topoisomerase, and the multidrug resistance (MDR) gene by immunohistochemistry and Northern blot hybridization. Our results showed that tumor cells associated with HTLV-I and anaplastic morphology had an enhanced expression of Ki-67, TGF-beta, and topoisomerase, as compared to nonaggressive T-cell lymphoma. The expression of IL-2R was limited to ATL and one Ki-1 lymphoma. The MDR gene was frequently expressed in ATL, but only infrequently in other, HTLV-I-negative, malignancies. Clinical progression or relapse was associated with the expression of MDR, in addition to an increased expression of Ki-67. We therefore conclude that the aggressive clinical behavior of high-grade T-cell lymphoma may result mainly from the high proliferative activity of tumor cells, but the association with HTLV-I and clinical relapse is further complicated by the development of drug resistance.
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PMID:Expression of growth-related genes and drug-resistance genes in HTLV-I-positive and HTLV-I-negative post-thymic T-cell malignancies. 167 81

Aryl-fluoroquinolone derivatives A-56619 (difloxacin) and A-56620 were found to inhibit human peripheral blood mononuclear cell (MNC) proliferation (measured by [3H]thymidine uptake) that was induced by concanavalin A or monoclonal antibody OKT3. These antimicrobial agents exert their maximum suppressive effect when added within the first 24 h after the onset of culture with concanavalin A. No increase in the concentration of mitogen or the duration of incubation of MNC cultures reversed this inhibitory effect, but the removal of the drug from cultures reversed the suppression of DNA synthesis. A-56619 appeared not to interfere with the triggering of MNC activation by mitogen because it did not inhibit mitogen-induced increase in protein synthesis (measured by [3H]leucine incorporation), interleukin-2 receptor expression (measured by the binding of fluorescein-conjugated monoclonal antibody against interleukin-2 receptor), and cell volume. These findings are considered in terms of possible interference of aryl-fluoroquinolones with mammalian topoisomerase and DNA polymerases.
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PMID:Aryl-fluoroquinolone derivatives A-56619 (difloxacin) and A-56620 inhibit mitogen-induced human mononuclear cell proliferation. 309 95