Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Graft-versus-host disease (GVHD) in leukemia patients following allogeneic bone marrow transplantation (BMT) has a lot of demerits but it also has a merit, namely graft-versus-leukemia effect. We reported the results of our recent trials on prevention, treatment and induction of GVHD, and prevention of viral infection after BMT. The results were as follows: 1) Twenty-four percent of patients who received prophylactic administration of cyclosporine and short term methotrexate still developed II degree-IV degree acute GVHD. 2) Patients with I degree or II degree acute GVHD showed good clinical courses. But, most patients with III degree GVHD gradually developed chronic GVHD. All patients with IV degree GVHD died of GVHD or infection. 3) Mizoribine and deoxyspergualin were effective for steroid-resistant GVHD. 4) Bestatin was administered to recipients who did not develop GVHD until day 30 after BMT. An interim report suggests that bestatin may induce chronic GVHD and suppress the relapse of leukemia. 5) Oral administration of gamma-globulin may prevent viral enteritis. Intravenous administration of anti-cytomegalovirus monoclonal antibody may prevent cytomegalovirus pneumonia.
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PMID:[Control of graft-versus-host disease and infection associated with immunosuppression]. 190 15

Considering the merit and demerit of GVHD in leukemia patients following allogeneic BMT, our strategies for GVHD are as follows; (1) a mild prevention, (2) a treatment to control the severity, if occurred, and (3) an induction of GVHD in recipients who did not develop GVHD. We reported the results of recent trials in prevention, treatment and induction of GVHD. For the prevention, T cells were depleted from bone marrow cells in 11 recipients with the results of graft failure in 5 and death in 9. The data from IBMTR were similar to our data. For the treatment, new drugs, 15-Deoxyspergualin. Mizoribine and anti-human lymphocyte globulin were introduced with compromising outcomes and mild adverse effects. For the induction, Ubenimex, an immunostimulator, was administered to recipients who did not develop GVHD until 30 days after BMT. The interim data suggests that Ubenimex may induce chronic GVHD and suppress the relapse of leukemia. We experienced the sudden onset of GVHD during the tapering of immunosuppressants in two recipients, who were found to have arbitrarily discontinued them. The interruption of drugs for the prevention of GVHD may cause the induction of GVHD.
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PMID:[Control of graft-vs-host disease]. 239 9

Inhibitors of IMP dehydrogenase (EC 1.2.1.14), including mizoribine (Bredinin) and mycophenolic acid, have significant antitumor and immunosuppressive activities. Studies were aimed at determining the mechanism by which intracellular GTP depletion induced by these agents results in inhibition of DNA synthesis. Incubation of human CEM leukemia cells for 2 hr with IC50 concentrations of either mizoribine (4 microM) or mycophenolic acid (0.5 microM) reduced cellular GTP levels an average of 68% or 58%, respectively, compared with the levels in control cells. Under similar conditions, mizoribine and mycophenolic acid decreased the amount of [3H]adenosine incorporated into primer RNA by 75% and 70%, respectively, relative to the untreated controls, but had no significant effect on total RNA synthesis. Repletion of the guanine nucleotide pools by coincubation of CEM cells with guanosine plus 8-aminoguanosine prevented both the inhibition of primer RNA synthesis and the inhibition of tumor cell growth induced by these agents. Additional studies demonstrated that GTP depletion alone was capable of directly inducing inhibition of primer RNA synthesis. Primer RNA synthesis was inhibited an average of 84% in whole-cell lysates that lacked GTP but contained all remaining ribo- and deoxyribonucleoside triphosphates. On an M13 DNA template, RNA-primed DNA synthesis catalyzed by the purified complex of DNA primase (EC 2.7.7.6) and DNA polymerase alpha (EC 2.7.7.7) was decreased an average of 70% in the absence of GTP, compared with synthesis in the presence of 0.5 mM GTP. These results provide evidence that mizoribine and mycophenolic acid inhibit DNA replication by inducing GTP depletion, which suppresses the synthesis of RNA-primed DNA intermediates.
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PMID:GTP depletion induced by IMP dehydrogenase inhibitors blocks RNA-primed DNA synthesis. 774 81