Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of a 7-day treatment with the maturational agents DMF and sodium butyrate on enzymes of pyrimidine metabolism, growth rate and cell maturation were assessed in 5 human tumor cell lines, ARH-77 (myeloma), K-562 (chronic myeloid leukemia), KG-1 (myeloid leukemia), HL-60 (promyelocytic leukemia) and RWLy-1 (non-Hodgkin's lymphoma). DMF lengthened the doubling times of all five cell lines while sodium butyrate lengthened only those of K-562, HL-60 and RWLy-1. Full maturation was induced only in HL-60 by either agent and in K-562 by butyrate. Exposure resulted in a decreased activity of the anabolic enzyme orotate phosphoribosyltransferase (EC 2.4.2.10) and increased activities of the catabolic enzymes thymidine phosphorylase (EC 2.4.2.4) and dihydrouracil dehydrogenase (EC 1.3.1.2). Changes in the amphibolic enzyme, uridine phosphorylase (EC 2.4.2.3) did not follow any apparent pattern. This study indicates that the pattern of pyrimidine metabolism differs between the differentiated and slowly growing, and undifferentiated rapidly growing counterpart of several human tumors, suggesting that enzymes of pyrimidine metabolism can be used as markers for cellular growth and/or maturity.
 ...
PMID:Effects of N,N-dimethylformamide and sodium butyrate on enzymes of pyrimidine metabolism in cultured human tumor cells. 368 65

OVERVIEW: Clinical indications for the use of interferons (IFNs) for cancer continue to expand and will likely continue to do so. IFNs have been approved for clinical use by the United States Food and Drug Administration for chronic myelogenous leukemia (CML), hairy cell leukemia, follicular lymphomas, Kaposi's sarcoma in the setting of AIDS, and melanoma for patients at high risk for recurrence after surgery. In addition, as a result of their antiviral activity, IFNs result in control of chronic active hepatitis and recurring papillomas that may reduce cancer development resulting from these processes and their underlying viruses. For almost all of these indications, therapeutic activity has been established from well-conducted, international phase III clinical trials. IFNs were the first successful biological therapy for human malignancy; they can synergize to produce tumor regression with surgery and chemotherapy and can potentiate other cytokines and monoclonal antibodies. IFNs and cytokines can modulate gene expression, resulting in enhanced immune effector-cell number, cytotoxicity, antigen expression, and production of other cytokines. IFNs have pleiotropic effects on cellular function, including influences on growth, differentiation, and immunologic function. For greatest effects, IFNs are used in combination with other modalities of therapy. This increases the effect of IFNs or allows IFNs to increase the effects of other therapies. Cytosine arabinoside improves the therapeutic effectiveness of IFNs in CML, and IFN-&agr;2b improves the prognosis, survival, and quality of life after surgery for high-risk patients with melanoma. Gene modulation by IFN-&agr; or IFN-&bgr; of thymidine phosphorylase, an enzyme important in DNA synthesis, has been suggested to be the basis for enhancing 5-fluorouracil (5-FU) effectiveness in preclinical models and may augment effectiveness in adenocarcinomas. IFNs increase the expression of some tumor-associated antigens that could be of benefit for combination use with monoclonal antibodies for imaging or therapy.
 ...
PMID:Gene Regulation and Clinical Roles for Interferons in Neoplastic Diseases. 1038 4