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)

Genistein (4'5, 7-trihydroxyisoflavone) occurs as a glycoside (genistin) in the plant family Leguminosae, which includes the soybean (Glycine max). A significant correlation between the serum/plasma level of genistein and the incidence of gender-based cancers in Asian, European and American populations suggests that genistein may reduce the risk of tumor formation. Other evidence includes the mechanism of action of genistein in normal and cancer cells. Genistein inhibits protein tyrosine kinase (PTK), which is involved in phosphorylation of tyrosyl residues of membrane-bound receptors leading to signal transduction, and it inhibits topoisomerase II, which participates in DNA replication, transcription and repair. By blocking the activities of PTK, topoisomerase II and matrix metalloprotein (MMP9) and by down-regulating the expression of about 11 genes, including that of vascular endothelial growth factor (VEGF), genistein can arrest cell growth and proliferation, cell cycle at G2/M, invasion and angiogenesis. Furthermore, genistein can alter the expression of gangliosides and other carbohydrate antigens to facilitate their immune recognition. Genistein acts synergistically with drugs such as tamoxifen, cisplatin, 1,3-bis 2-chloroethyl-1-nitrosourea (BCNU), dexamethasone, daunorubicin and tiazofurin, and with bioflavonoid food supplements such as quercetin, green-tea catechins and black-tea thearubigins. Genistein can augment the efficacy of radiation for breast and prostate carcinomas. Because it increases melanin production and tyrosinase activity, genistein can protect melanocytes of the skin of Caucasians from UV-B radiation-induced melanoma. Genistein-induced antigenic alteration has the potential for improving active specific immunotherapy of melanoma and carcinomas. When conjugated to B43 monoclonal antibody, genistein becomes a tool for passive immunotherapy to target B-lineage leukemias that overexpress the target antigen CD19. Genistein is also conjugated to recombinant EGF to target cancers overexpressing the EGF receptor. Although genistein has many potentially therapeutic actions against cancer, its biphasic bioactivity (inhibitory at high concentrations and activating at low concentrations) requires caution in determining therapeutic doses of genistein alone or in combination with chemotherapy, radiation therapy, and/or immunotherapies. Of the more than 4500 genistein studies in peer-reviewed primary publications, almost one fifth pertain to its antitumor capabilities and more than 400 describe its mechanism of action in normal and malignant human and animal cells, animal models, in vitro experiments, or phase I/II clinical trials. Several biotechnological firms in Japan, Australia and in the United States (e.g., Nutrilite) manufacture genistein as a natural supplement under quality controlled and assured conditions.
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PMID:Anticancer therapeutic potential of soy isoflavone, genistein. 1558 72

We describe here a new case of therapy-related acute leukemia with t(1;21)(p36;q22). A 25-year-old man was admitted because of anemia and thrombocytopenia. Four years before, he had received combination chemotherapy including etoposide for seminoma. Bone marrow was hypercellular, with 49% myeloperoxidase (MPO) staining-negative blasts. Chromosome analysis showed 46,XY,t(1;21)(p36.3;q22)[11]/49,sl,+8,+16,+20[9]. Fluorescence in situ hybridization demonstrated that RUNX1 signals at 21q22 were split onto the der(1)t(1;21) and der(21)t(1;21). Immunophenotypic analyses revealed that blasts were positive for CD19, CD79a, and cytCD22, as well as MPO, CD13, and CD33, fulfilling the diagnostic criteria of mixed phenotype acute leukemia, B/myeloid. The patient died of disease progression after 10 months. Thus, acute leukemia with t(1;21) and RUNX1 rearrangement could be associated with B/myeloid mixed phenotype as well as previous topoisomerase II inhibitor therapy and poor prognoses.
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PMID:Therapy-related, mixed phenotype acute leukemia with t(1;21)(p36;q22) and RUNX1 rearrangement. 2068 97