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Studies confirm that gefitinib treatment of epidermal growth factor receptor(EGFR)muta-tions for patients with non-small cell lung cancer(NSCLC)has a clear effect,and with radiotherapy sensitiza-tion effect. Many studies both at home and abroad show that gefitinib combined with radiotherapy can signifi-cantly improve the survival times of patients,especially for the elderly patients or the patients with brain metas-tases,which has fewer adverse reactions and with higher life qualities. Therefore,gefitinib combined with radiotherapy will be an effective treatment for the patients with advanced NSCLC.
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<p><b>OBJECTIVE</b>To explore the efficacy of PSC 833 on multidrug resistance (MDR) reversal and its mechanism.</p><p><b>METHODS</b>Human erythroleukemic cell line K562 and its doxorubicin-resistant counterpart K562/A02 were used in the study. Cytotoxicity was assessed by MTT assay, P-gp expression by direct immunofluorescence and mdr1 mRNA expression by reverse transcriptase polymerase chain reaction (RT-PCR) with beta-actin as internal control. Intracellular DNR retention was measured with flow cytometry.</p><p><b>RESULTS</b>K562/A02 cells displayed high levels of mdr1 mRNA and P-glycoprotein and reduced DNR retention compared to their parental K562 cells. 1 micromol/L of PSC 833 had no effect on the levels of mdr1 mRNA and P-gp expression in K562/A02 cells (P > 0.05). PSC 833 conferred a dose-dependent increase on chemosensitivity of K562/A02 to DNR, and its effect was at least 3-fold more potent than that of CsA or Ver. PSC 833 could increase DNR retention in K562/A02 cells. A 100.9% restoration of intracellular DNR retention of the level of K562 cells was gained by PSC 833 at 1.0 micromol/L in K562/A02 cells, whereas only a 86.9% restoration of DNR retention was obtained by CsA at 10 micromol/L in the K562/A02 cells. No effect on DNR sensitivity and retention was found in K562 cells (P > 0.05).</p><p><b>CONCLUSION</b>PSC 833 is at least 3 approximately 10 fold more potent than CsA or Ver with respect to MDR reversing activity, and it may function by inhibiting the function of P-gp and not reducing the levels of mdr1 mRNA and P-gp directly.</p>
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Humanos , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP , Genética , Metabolismo , Bloqueadores de los Canales de Calcio , Farmacología , Ciclosporina , Farmacología , Ciclosporinas , Farmacología , Relación Dosis-Respuesta a Droga , Resistencia a Antineoplásicos , Células K562 , Biología Celular , Metabolismo , ARN Mensajero , Genética , Metabolismo , Verapamilo , FarmacologíaRESUMEN
AIM and METHODS: To investigate the expression of adhesion molecule ? 2 integrins (CD11a、CD11b) and L-selectin(CD62L )on Acute Lymophocyte Leukemia(ALL) cells and its Clinical Implications. Adhesion molecules CD11a、CD11b、 CD62L of 45 ALL patients and 25 health people were measured by flow-cytometric analysis. RESULTS:①CD11a and CD11b expression were lower on ALL cells than the normal hematopoietic cells. The rate of low expression was 100% for CD11b, 50% for CD11a,respectively. CD62L expression were higher on ALL cells than the normal hematopoietic cells.②The CD11a was lower expressed on B-ALL than T-ALL. CD62L was higher on T-ALL than B-ALL. ③ The expression of CD11a in the invasion group was much higher than that in the non-invasive group(P
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AIM and METHODS: To investigate the expression of adhesion molecule β2 integrins (CD11a、 CD11b) and L-selectin(CD62L )on Acute Lymophocyte Leukemia(ALL) cells and its Clinical Implications. Adhesion molecules CD11a、CD11b、 CD62L of 45 ALL patients and 25 health people were measured by flow - cytometric analysis. RESULTS :①CD11a and CD11b expression were lower on ALL cells than the normal hematopoietic cells. The rate of low expression was 100% for CD11b, 50% for CD11a,respectively. CD62L expression were higher on ALL cells than the normal hematopoietic cells.②The CD11a was lower expressed on B - ALL than T- ALL. CD62L was higher on T- ALL than B- ALL. ③The expression of CD11a in the invasion group was much higher than that in the non - invasive group( P < 0.05).④The levels of CD11a,CD11b were returned to normal levels at remission. CONCLUSION: These results suggest that there are abnormalities in the expression of cell adhesion molecules in ALL which may help identify ALL subtypes and the treatment effect.