Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previously we showed that motility-related protein (MRP-1) is an antigen recognized by monoclonal antibody (mAb) M31-15 inhibiting cell motility and that the sequence of MRP-1 coincides with that of CD9. In the present study, plasmid was constructed in which human MRP-1/CD9 cDNA is expressed under the control of the Abelson murine leukemia virus promoter sequence. The expression plasmid for MRP-1/CD9 was introduced into Chinese hamster ovary cells, human lung adenocarcinoma cell line MAC10 (MRP-1 positive), and human myeloma cell line ARH77 (MRP-1 negative). All of the MRP-1/CD9 (over)expressing clones obtained from these transfected cells showed suppressed cell motility (penetration and phagokinetic track assays) depending on the degree of expression of MRP-1/CD9. Overexpression of MRP-1/CD9 by MAC10 cells resulted in the suppression of cell motility (maximally 73%) associated with considerable inhibition of the cell growth (maximally 48%). However, the inhibition of the growth of MAC10 cells by mAb M31-15 was < 17% at an antibody concentration of 1-5 micrograms/ml, which inhibits cell motility by > 90%. These results suggest that MRP-1/CD9 directly regulates cell motility and may also affect cell growth. Effects on metastasis by the expression of MRP-1 CD9 were investigated with mouse melanoma BL6 cells-BALB/c nu/nu mouse system. Metastatic potential of all transformants expressing MRP-1/CD9 was lower than that of parent BL6 cells.
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PMID:Suppression of cell motility and metastasis by transfection with human motility-related protein (MRP-1/CD9) DNA. 847 5

Sulphoraphane (SF), a naturally occurring isothiocyanate, is a potent anticarcinogen in animal experiments. The mechanism of action of sulphoraphane includes induction of Phase 2 detoxification enzymes, inhibition of carcinogen-activating Phase 1 enzymes, induction of apoptosis and cell cycle arrest, and anti-inflammation. We have recently found that it was accumulated in mammalian cells by up to several hundred-fold over the extracellular concentration, primarily by conjugation with intracellular GSH. The intracellular accumulation levels of SF can reach millimolar concentrations. The anticarcinogenic activity of SF is at least partly dependent on its accumulation levels in cells. Here we show, however, that the accumulated SF was rapidly exported mainly in the form of GSH conjugate (GS-SF) in cultured human cells. It appeared that to sustain the intracellular accumulation levels required a continuous uptake of SF to offset the rapid export of SF/GS-SF. These findings may have important implications for the development of an effective dosing regimen for SF. Moreover, the export was temperature-sensitive and was inhibited by known inhibitors of membrane pumps, suggesting the involvement of such a pump in exporting accumulated SF/GS-SF. Indeed, studies with human leukemia cells (HL60) with or without overexpression of multidrug resistance associated protein-1(MRP-1) and human myeloma cells (8226) with or without overexpression of P-glycoprotein-1 (Pgp-1) indicated that both MRP-1 and Pgp-1 are involved in the export of intracellular SF/GS-SF.
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PMID:High cellular accumulation of sulphoraphane, a dietary anticarcinogen, is followed by rapid transporter-mediated export as a glutathione conjugate. 1198 4

Multidrug resistance is one of the mechanisms how to explain failure of chemotherapy in patients with different hematological malignancies. In this study we aimed to evaluate and compare the drug resistance in B-cell acute lymphoid leukemia (B-ALL) and multiple myeloma (MM) in association with their immunophenotypes and genotypes. Eleven patients with B-ALL and 14 patients with MM were classified according to prognostic factors. Standard MoAb panel for ALL and triple labeled antibodies (CD38/CD56/CD19) and detection of intracellular light chains for MM were used. Flow cytometric calcein assay was performed for measure of P- glycoprotein (MDR-1) and multidrug resistance associated protein (MRP-1) activity. Markers CD19, CD20 and HLA-DR proved to be useful in identifying cells of B-lymphoid lineage. CD34 progenitor cell antigen was present in high proportion of ALL blasts. Both the abnormal plasmacell populations and their monoclonality in MM were confirmed by immunophenotyping, too. The mean MDR activity factor (MAF) values were not different in patients with MM and B- ALL. However, the mean MRP-1 values in MM were significantly lower than MAF-MDR-1 (1.85+/-3.8 versus 5.92+/-7.45, p=0.05), but we have found lower values in refractory conditions as expected from previous studies of acute myeloid leukemia. The immunophenotyping was helpful in detection of abnormal populations showing no correlation with the MDR. However, in this study we could not confirm high MDR activity despite of the failure of chemotherapy. The calcein assay seems to be useful for quantitative and sensitive measurement of the MDR proteins. The low activity of MDR- 1 and MRP-1 in MM need further clarification, indicating the involvement of different transport in the resistance mechanism.
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PMID:Application of flow cytometry immunophenotyping and multidrug resistance assay in B-cell acute lymphoid leukemia and multiple myeloma. 1573 24