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)

The inhibition by IFN-beta of acquired resistance to the epipodophillotoxin etoposide was studied using a human glioblastoma cell line, T98G. T98G cells were exposed to either etoposide alone or both etoposide and IFN-beta, and after subculture, the same two series of drug exposure were repeated. Degree of level of resistance was tested by the response of the cells to etoposide and changes in their DNA histograms. Furthermore, topoisomerase II in each set of cells was subjected to fluorescence staining with monoclonal anti-topoisomerase II antibody, and the amount of fluorescence was measured by flow cytometry. Secondary etoposide exposure showed less cytotoxicity when the first exposure was to etoposide alone. In contrast, the cytotoxicity was almost the same as that after the first exposure when IFN-beta was added. Resistance to etoposide may result from qualitative or quantitative alterations in the target enzyme, topoisomerase II. The present results show that resistant cells have less topoisomerase II than sensitive cells, suggesting that IFN-beta inhibits the acquisition of resistance to etoposide by suppressing the alteration in topoisomerase II. The inhibition of acquired resistance to etoposide by IFN-beta suggests that continuous and repeated chemotherapy for glioblastoma and other malignant tumors may be clinically advantageous.
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PMID:IFN-beta inhibition of etoposide resistance acquisition in vitro: studies using a human glioblastoma cell line. 776 95

Multiple sclerosis is a chronic, autoimmunological disease of central nervous system in which axonal damage in brain and spinal cord is observed. It is second most common cause of disability in young adults in West Europe and North America after injuries. There is 2.5 million people suffered from multiple sclerosis worldwide. The worse prognosis is connected with primary progressive MS in which recovery after first symptoms of central nervous system damage isn't observed. That subtype of disease is seen in case of 10-20% people with MS. MTX is a synthetic antracycline with antineoplastic, immunomodulatory and anti-inflammatory effects. Drug was allowed to treatment of leukemia. It is also used in treatment of breast, prostate, ovarian, stomach and liver cancer. Additionally MTX is used in treatment of secondary progressive SM and relapsing - remitting subtype of disease with no respond to treatment with interferon beta and glatiramer acetate. MTX inhibits topoisomerase II activity, matches to DNA molecule and damage her structure. Drug inhibits limphocyte T, B and macrophages activity and antibodies synthesis. The most dangerous side effects of MTX treatment are cardiotoxicity and induction of leukemia. There is lack of studies describing MTX effectiveness and safety in treatment of primary progressive SM.
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PMID:[Mitoxantrone role in treatment of primary progressive multiple sclerosis]. 2689 41