Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The dihydrofolate reductase activity has been studied cytochemically in various haematological diseases. The variation between normal controls, Hodgkin's disease, myeloma, polycythaemia vera, chronic lymphocytic leukaemia and chronic myeloid leukamia was not significant, comparing the same type of cells. In acute myeloid leukaemia and acute lymphoblastic leukaemia the blast cells were weakly positive or negative. This finding is very interesting as the blast cells are capable of division. Probably the dihydrofolate reductase appears in the blast cells in some stage of mitosis. Lymphocytes stimulated by phytohaemagglutinin showed increased enzyme activity compared with normal non-stimulated lymphocytes. The "blast like" cells were more strongly positive than the blast cells of leukaemic patients. The patients with acute lymphoblastic leukaemia or acute myeloid leukaemia treated with methotrexate showed increased dihydrofolate reductase activity cytochemically.
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PMID:Cytochemical demonstration of dihydrofolate reductase in leukaemia and other haematological diseases. 26 23

Methotrexate is a dihydrofolate reductase inhibitor with application both as a chemotherapeutic agent and as a disease-modifying antirheumatic drug. Although its ability to inhibit cellular proliferation is a desired effect in its role as an antineoplastic agent, this property may also hinder normal physiologic regeneration of the nasal epithelium. This effect may predispose patients to septal cartilage ischemia, necrosis and, eventually, perforation. We report 2 cases of septal perforations in the setting of prolonged methotrexate use and present a literature review. Patient 1 is an 8-year-old boy with juvenile rheumatoid arthritis managed with weekly methotrexate who developed a 4-mm septal perforation with an unremarkable biopsy. This was closed with a mucosal advancement flap without incident. Patient 2 is an 11-year-old boy with non-Hodgkin lymphoma treated with methotrexate. His examination was significant for a large perforation of the dorsocaudal septum. A biopsy was negative for malignancy in this patient. Repair has been deferred-initially for chemotherapy and currently for treatment relapse. We hypothesize that prolonged use of methotrexate alters the balance between physiologic desquamation and epithelial regeneration. This imbalance may promote septal ischemia and predispose patients to the development of septal perforations.
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PMID:Potential predisposition for nasal septal perforation with methotrexate use: report of 2 cases and literature review. 1968 2

T-cell lymphoma is a rare hematologic malignancy with an incidence rate between 10% and 20% of that of non-Hodgkin lymphomas. Patients with peripheral T-cell lymphoma (PTCL) generally have a poor prognosis when treated with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)/CHOP-like chemotherapy; once relapse occurs, it is mostly regarded as an incurable disease. To overcome the chemorefractoriness of PTCL, several novel agents have been developed. Since the first approval of pralatrexate, a dihydrofolate reductase inhibitor, for relapsed/refractory PTCL by the US Food and Drug Administration, several new agents, such as romidepsin (histone deacetylase inhibitor), brentuximab vedotin (antibody-drug conjugate targeting CD30), chidamide (histone deacetylase inhibitor), and mogamulizumab (anti-CC chemokine receptor 4 monoclonal antibody), have been approved as a therapeutic option for relapsed/refractory PTCL in several countries, including the US, Europe, China, and Japan. Forodesine is a novel, potent purine nucleoside phosphorylase inhibitor that is effective against T-cell malignancies. Although the clinical development of forodesine was discontinued in the US and Europe, a multicenter Phase I/II study of oral forodesine for relapsed PTCL was recently completed in Japan. The overall response rate was 24% (10 of 41 patients), which included four patients with complete response. In general, the toxicity of forodesine is manageable. As the study met the primary end point, forodesine was approved for the treatment of relapsed/refractory PTCL in Japan in March 2017, which was the first approval of forodesine in the world. As forodesine is an oral formulation, it is more convenient than other novel intravenous agents approved for PTCL. However, it is necessary to appropriately manage opportunistic infections and secondary lymphomas possibly associated with long-lasting lymphocytopenia caused by forodesine. In this manuscript, we have summarized the currently available evidence for forodesine and discussed the clinical implications for PTCL treatment.
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PMID:Forodesine in the treatment of relapsed/refractory peripheral T-cell lymphoma: an evidence-based review. 2971 11