Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The methods of mobilization and collection of stem cells in peripheral blood stem cells transplantation (PBSCT) and the association between the number of stem cells transplanted and hematopoietic recovery were studied. The investigation was carried in 22 patients (11 acute leukemia, 6 multiple myeloma, 4 non-Hodgkin's lymphoma, 1 breast cancer). Three regimens for mobilization were carried out as follows: 1) chemotherapy + tetrahydrofolic acid + dexamethasone, 2) chemotherapy + rhGM-CSF + dexamethasone, 3) chemotherapy + rhG-CSF + dexamethasone. Besides, CD34/CD33 dual-color direct immunofluorescence flow cytometry assay was performed in 7 cases in the rhG-CSF group. The results showed: 1) The mean number of collected cells (MNC) in the rhG-CSF group was MNC (8.29 +/- 6.14) x 10(8)/kg and CFU-GM (21.35 +/- 17.24) x 10(4)/kg, being highest among the 3 groups. 2) The number of CD34+ cells correlated with MNC and CFU-GM. CD34+ cells in the peripheral blood were 0 or < 0.5% before mobilization and increased markedly 6-8 days after rhG-CSF administration. Harvesting should be started at that time and carried out every day until CD34+ cells reached 5 x 10(6)/kg. 3) The number of PBSC transplanted was the key to hematopoietic recovery.
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PMID:[A study on the peripheral blood stem cells mobilization, collection and their effects on engraftment]. 873 24

Methotrexate (MTX) is a clinically important antifolate that has been used in combination with other chemotherapeutic agents in the treatment of malignancies including acute lymphocytic leukemia, osteosarcoma, carcinomas of the breast, head and neck, choriocarcinoma and non-Hodgkin's lymphoma. The primary target of MTX is the enzyme dihydrofolate reductase (DHFR) which catalyzes the reduction of folate and 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate. Understanding of MTX action has revealed how cells acquire resistance to this drug. The four known mechanisms of MTX resistance are a decrease in the uptake of the drug, a decrease in the retention of the drug due to defective polyglutamylation or an increase in polyglutamate breakdown, an increase in the enzyme activity and a decrease in the binding of MTX to DHFR. The molecular basis for some of these mechanisms has been elucidated in MTX resistant cell lines; in particular the occurrence of gene amplification resulting in increased DHFR and point mutations resulting in altered DHFR with reduced affinity for MTX. Cloning of the human folylpolyglutamate synthase gene and the reduced folate transport gene have been reported recently and should facilitate the identification of the molecular basis of these resistant phenotypes. DHFR protein has been shown to regulate its synthesis by exerting an inhibitory influence on its own translation. Addition of MTX relieves this inhibition thus providing a possible molecular explanation for the rapid rise in DHFR activity noted in some cells after MTX administration. Alterations in genes involved in regulating the cell cycle such as cyclin D1 and the retinoblastoma (Rb) gene have also been shown to influence cellular response to MTX. Overexpression of cyclin D1 in HT1080, a human fibrosarcoma cell line, results in decreased MTX sensitivity. The molecular basis of this observation is under investigation. Abnormalities in the Rb gene may also have profound effects on MTX sensitivity. Rb interacts with the family of transcription factors called E2F reducing transcription of genes that contain E2F binding sites in the promoter regions e.g. DHFR. When Rb is deleted or rendered nonfunctional levels of "free" or unbound E2F are high resulting in enhanced transcription of genes such as DHFR. This results in increased DHFR protein and may lead to MTX resistance. As the knowledge regarding mechanisms of resistance increases newer approaches to circumvent such resistance or to target resistant cells can be undertaken.
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PMID:Molecular mechanisms of resistance to antifolates, a review. 885 36