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  • American Society of Hematology  (37)
  • 2005-2009  (37)
  • Medicine  (37)
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  • American Society of Hematology  (37)
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  • 2005-2009  (37)
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  • Medicine  (37)
RVK
  • 1
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 4171-4171
    Abstract: Objective: This paper was to study the reversal effect of magnetic Nano-Fe3O4 or Nano-Au with DNR, on multidrug resistance cell line K562/A02 and to investigate the reversal mechanism of this combination, and to provide theoretic evidence for the clinical application of them as resistance modifying agents. Method: The IC50 (the concentration causing 50% inhibition of cell growth) of DNR, Nano-Fe3O4 and Nano-Au respectively were assayed by MTT method.The drug-loaded nanoparticles were prepared by solvent diffusion method.Some nanoparticales, volume ratio from 1.5% to 50%, were combined with some DNR to find the best combination to prepare best drug-loaded nanopartilces.At last, the K562/A02 cells was treated with the composite of 25% nanoparticales and 10mg/L DNR, which MDR1 mRNA was assayed by RT-PCR;intracellular drug concentration and the apoptosis was determined by fluorometry and confocal fluorescence microscope. Results: The IC50 of DNR for K562/A02 and K562 cells were 23.23mg/L and0.307mg/L respectively.Two nanoparticles themselves have not evident cytotoxic effect to K562/A02 and K562 cells.Pretreating K562/A02 cells with the composite of 25% nanoparticales and 10mg/L DNR for 48 hours partially restored the sensitivity of K562/A02 cells to DNR;K562/A02 showed apoptotic characteristics after treated with this composite;drug-loaded nanopartilces elevated the intracellular DNR accumulation in K562/A02 and its MDR1 mRNA were down regulated.Data was analyzed by SPSS 11.5 software and expressed as mean ± SD. Conclusions: Nano- Fe3O4 or Nano-Au can increases the intracellular free DNR concentration of the K562/A02 cells, which lead to more K562/A02 cells apoptosis. Two nanoparticles themselves could not lower the MDR1 gene expression of the K562/A02 cells, but they degraded the MDR1 gene level with combine DNR. These results suggested that Nano- Fe3O4 or Nano-Au with DNR can reverse the resistance of K562/A02 cells significantly.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 2
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 3901-3901
    Abstract: Objective: An attempt was made to investigate the effect of platelet-derived microparticles (PMPs) on the angiogenesis. Methods: Thrombin was adopted to activate the platelets to release PMPs. Flow cytometry(FCM)was adopted to evaluate the efficiencies of different concentrations of thrombin to produce PMPs and BCA was adopted to evaluate the content of PMPs. By the carrier of human umbilical vein cell line ECV-304 cultivated in vitro, investigate the effect of PMPs on the proliferation and apoptosis of human umbilical vein endothelial cells using MTT and FCM. PMPs were put into CAM and observe the effects of PMPs on angiogenesis in Chick embryo chorioallantoic membrane (CAM). Results: The efficiencies of PMPs activated by 1.0U/ml thrombin were 50.1%; PMPs induced proliferation of human umbilical vein cell line ECV-304 in a dose dependent manner. At the concentration of 40ug/ml PMPs, the proliferation rate of human umbilical vein cell line ECV-304 was as 1.8±0.3 times as control and there was no difference with the group of vascular endothelial growth factor (VEGF),which the proliferation rate was 1.9±0.5 times vs. control, p & gt; 0.05;PMPs inhibited human umbilical vein cell line ECV-304 apoptosis. Compared with control group (apoptosis rate 9.4%±0.5%), apoptosis rate of PMPs (40μg/ml) is 3.9%±0.4%, which was significantly reduced, p & lt;0.05. The addition of VEGF (10μl/ml) did not successfully prevented apoptosis of human umbilical vein cell line ECV-304 (apoptosis rate 8.0%±0.8%);After 72 h of incubation, showing an implant of PMPs by allantoic vessels developing radially towards it (implant) in a ’spoked-wheel’ pattern, at the concentration of 80μg/ml PMPs, number of vessel ramification is 112.5±11.31 and vessel area/CAM area is (6.19±1.29)%, compared with the VEGF(p & gt;0.05). But there are not localized allantoic vessels developing in the NS control group(P & lt;0.05). Conclusion: 1.0U/ml thrombin activated platelet could get the best efficiency of PMPs, which could stimulate proliferation of human umbilical vein cell line ECV-304 and inhibit its apoptosis and PMPs have certain promotive effect on the formation of capillary in chick chorioallantoic membranes.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 3
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 4175-4175
    Abstract: Objective: The present study aimed to evaluate the MDR reversal activity of bromotetrandrine (BrTet), a bromized derivative of tetrandrine (Tet), in vitro. Methods: Drug sensitivity was determined using the MTT assay. Adriamycin (ADM) accumulation, the protein levels of P-glycoprotein (P-gp) and the apoptotic changes were analyzed by fluorospectrophotometry, respectively. The mRNA levels of P-gp was determined by RT-PCR. Results: BrTet at 0.25, 0.5 and reversed ADM resistance in MDR K562/A02 cells dose-dependently and its potency was greater than that of Tet at the same concentrations. The IC50 of ADM for K562 and K562/A02 cells were 55.122 mg/l and 1.1373 mg/l, respectively. Treating K562/A02 cells with BrTet(1uM)and TTD(1uM)both for 48 hours partially restored the sensitivity of K562/A02 cells to ADM (IC50 were 4.7729 mg/l and 13.584 mg/l respectively) but had not effect on K562 cells. The fold reversal (FR) were 11.55 and 4.06 respectively. K562/A02 cells showed apoptotic characteristics after treated with Brtet and Tet both for 48 hours compared with control group(apoptosis rate was 61.1%, 11.1% and 9.9%,respectively); Fluorospectrophotometric assay showed that BrTet significantly increased the intracellular accumulation of ADM in K562/A02 cells in a dose-dependent manner. The fluorescence intensity of intracellelar ADM in K562/A02 cells treated with ADM(1mg/L)was 33% of that in K562 cells. BrTet and Tet elevated the intracellular ADM concentration in K562/A02 cells up to 52% and 69%,respectively. BrTet also inhibited the overexpression of P-gp in K562/A02 cells. The fluorescence intensity of P-gp in K562 and K562/A02 cells was 0.5 and 97.97.The P-gp expression was down after treated with BrTet and TTD (65.05 and 54.86). The mdr1 mRNA was also down regulated. Conclusions: BrTet showed significant MDR reversal activity in vitro. Its activity may be related to the inhibition of P-gp overexpression and the increase in intracellular accumulation of anticancer drugs. BrTet may be a promising MDR modulator for eventual assessment in the clinic.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 4
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 5061-5061
    Abstract: Objective: To investigate the effect of 6-phenylhexyl isothiocyanate (PHI) on drug resistance and sensitivity on K562/A02 cell line to ADM and elucidate the probable mechanisms. Methods: We measured growth inhibition of ADM on K562/A02 cell line by MTT assay. Apoptosis rate of K562/A02 cell line, the change of intracellular ADM and MRP1 protein level were detected by Flow Cytometry. Intracellular deoxidized GSH by spectrometric enzyme assay and MRP1 mRNA by RT-PCR semiquantitative assay were observed anteroposterior using PHI. Results: PHI can enhance the sensitivity of K562/A02 cell line to ADM, survival rate of K562/A02 cell line decreased with the increasing concentration of PHI and ADM. Apoptosis rate increased with treating by combination of two above drugs, and multiple of drug resistance had statistical significance (P & lt;0.05) when the concentration of PHI was more than 20μmol/l. Intracellular GSH of K562/A02 cell line reduced 5% when 1μg/ml ADM was single used, and when more than 10μmol/l PHI was used it increased slightly at first then decreased. When more than 20μmol/l PHI and 1μg/ml ADM were used combination, intracellular GSH of K562/A02 cell line decreased progressively with increasing the concentration of PHI. Protein and gene level of MRP1 have no statistical significance (P & gt;0.05) no matter after or before PHI was used on different concentration. Conlusion: The depletion effect of PHI on the intracellular GSH can not only partly enhance the reverse effect of ADM, but also enhance the sensitivity of K562/A02 cell line to ADM. Such depletion may diminish side effect and treatment dosage of ADM. It provides a new view to the therapy of leukaemia.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 5
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 5058-5058
    Abstract: Objective: To establish the xenograft leukemia model with stable multiple drug resistance in nude mice; to investigate the reversal effect of 5-Bromotetrandrine and Magnetic nanoparticle of Fe3O4 combined with DNR in vivo and to search for the possible reversal mechanisms. Methods: K562 and K562/A02 cells were respectively inoculated subcutaneously into back of athymic nude mice (1×107 cells/each) to establish the xenograft models. The tumor formation was evaluated by animal ultrasonic inspection. Tumors-bearing nude mice were assigned randomly to five groups which were treated with NS (A group); DNR 1mg/kg (B group); nanoparticle of Fe3O4 combined with DNR 0.63mg/kg(C group): 5-BrTet 2.5mg/kg combined with DNR(D group); 5-Bromotetrandrine 2.5mg/kg and Magnetic nanoparticle of Fe3O4 combined with DNR 0.63mg/kg(E group) respectively. The incidence of tumor formation, growth characteristics, weight and volume of tumor were observed. The histopathologic examination of tumors and organs were detected. For resistant tumors, the protein levels of P-glycoprotein (P-gp) were detected by Western blot. Results: The tumor incidence was 100% in the nude mice inoculated with either K562 or K562/A02 cells. In 6 to 9 days,the tumors reached a volume of more than 1 00 mm3. In vivo, MTT assay showed K562/A02 tumor maintained the drug resistance. For K562 cells xenograft tumors, there were no apparent differences in tumor suppression effect between the B AC AD AE group. For K562/A02 cells xenograft tumors, 5-BrTet and Magnetic nanoparticle of Fe3O4 combined with DNR significantly suppressed growth of tumor: the inhibition rate was 62.76% while DNR alone be used, the inhibition rate was 3.68%. Pathologic examination of resistant tumors showed the tumors necrosis obviously in E group. Application of 5-BrTet and Magnetic nanoparticle of Fe3O4 inhibited the overexpression of P-gp. Conclusion: The xenograft leukemia nude mice model was maintain the multiple drug resistance. 5-Bromotetrandrine and Magnetic nanoparticle of Fe3O4 combined with DNR had a significant tumor-suppressing effect on MDR leukemia cells xenograft model.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 6
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 5038-5038
    Abstract: Object: To the effect of Fe3O4-magnetic nanoparticle loaded with DNR on multidrugresistant K562 cells in vivo. Methods: K562-n and its MDR counterpart K562-n/VCR cell were inoculated subcutaneously into both sides of the back of nude mice (5×106 cells/each) to establish a human leukemia xenograft model. The mice were randomly divided into group A receiving normal saline every other day for 20days, group B receiving DNR every other day for 20days, group C receiving Fe3O4-magnetic nanoparticle every other day for 20days, group D receiving Fe3O4-magnetic nanoparticle loaded with DNR every other day for 20days, and group E receiving Fe3O4-magnetic nanoparticle containing DNR every other day for 20days with a magnetic field built on the surface of the tumor tissue. The tumor volume was measured on the day 1, 5, 9, 13, 17 and 21d after the first treatment. Tumor tissues were isolated for examination of the expression of mdr-1, bcl-2, bax and caspase-3 by reverse transcription polymerase chain reaction and Western blotting. Results: For K562-n/VCR tumor, the tumor volume was markedly lower in groups D and E than in groups A, B and C (group D or E vs group A, B or C, P & lt; 0.05). The transcription of mdr-1 and Bcl-2 gene was significantly lower in groups D and E than in groups A, B and C (group D or E vs group A, B or C, P & lt; 0.05). So did the protein expression of Bcl-2. However, there were no differences among these groups about the protein expression of P-gp. The protein and mRNA expressions of Bax and Caspase-3 in groups D and E were increased significantly compared with groups A, B and C (group D or E vs group A, B or C, P & lt; 0.05). The tumor volume of K562-n was markedly lower in groups C, D and E than in groups A and B (group C, D or E vs group A or B, P & lt; 0.05). Conclusion: In conclusion, DNR loaded Fe3O4-magnetic nanoparticles can suppress the growth and induce apoptosis further on the MDR K562-n/VCR tumor in vivo compared to DNR alone but not on the K562-n tumor. The external magnetic field failed to improve the antitumor effect.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 7
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 4358-4358
    Abstract: Objective: This paper was to study the reverse effect of cyclosporine A and the estrogen-receptor inhibitor, raloxifene, on multidrug resistance cell line K562/A02 and to investigate the reversal mechanism of this combination, and to provide theoretic evidence for the clinical application of them as resistance modifying agents. Method: The IC50 (the concentration causing 50% inhibition of cell growth) of DNR were assayed by MTT method; mdr-1 mRNA was assayed by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR).; intracellular DNR concentrations and the apoptosis and p-glycoprotein (p-gp) expression in K562 and K562/A02 were detected by fluorometry . Results: The IC50 of DNR for K562/A02 and K562 cells were 23.51mg/L and 0.29mg/L respectively. Pretreating K562/A02 cells with CsA(1mg/L) or raloxifene(2.5mg/L) for 48 hours partially restored the sensitivity of K562/A02 cells to DNR (IC50 were5.98mg/L and 8.15mg/L respectively) ,but had no effect on K562 cells;IC50 of combined cyclosporine A and raloxifene was 3.68mg/L The intracellular DNR concentrations( [DNR]i) in K562 cells were higher than that in K562/A02 cells,[DNR] i in K562/A02 cells was 12% of K562. Pretreating K562/A02 cells with cyclosporine A and raloxifene alone or combination for 48 hours induced the enhancement of [DNR]i in K562/A02 cells([DNR] i:CsA alone 33% of K562; raloxifene alone 12.78%of K562;CsA+raloxifene 45.29% of K562 Cyclosporine A and raloxifene alone or combination could decrease the expression of P-gp in K562/A02,the effect for 48 hours as follows: control(K562) 3.58,control(K562/A02) 104.96; CsA alone 78.29; raloxifene alone 85.02;CsA+raloxifene 59.89 K562/A02 showed apoptotic characteristics after treated with cyclosporine A for 48 hours and no apoptotic characteristics after treated with raloxifene for 48 hours Cyclosporine A and raloxifene alone could down regulate the expression of mdr-1 gene mRNA in K562/A02, cyclosporine A and raloxifene combination could markedly down regulate the expression of mdr-1 gene mRNA in K562/A02, the effect for 48 hours as follows(mdr1/β-action):control 1.313;CsA alone 1.232;raloxifene alone 1.052;CsA+raloxifene 0.449. Data was analyzed by SPSS 11.0 software and expressed as mean ± SD. Conclusions: Activation of P-gp may be involved in the mechanism of MDR of K562/A02 cell line; Multidrug resistance (MDR) can be partially reversed by CsA or raloxifene, of which the combination shows a great synergistic reversal effect.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 8
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 5059-5059
    Abstract: Objective This study was to compare the reversal effect of 5-bromotetrandrine (BrTet) with Tetrandrine (Tet) when combined with ADM on multidrug resistance cell line K562/A02 and to investigate the reversal mechanism of this new derivative. Methods The protein levels of P-glycoprotein (P-gp) were detected by fluorospectrophotometry and Western blot. The mRNA levels of P-gp were determined by RT-PCR. The in vivo effect of Tet was investigated using nude mice grafted with sensitive human leukemia cell line K562 and MDR cell line K562/A02. Results Flow cytometry assay showed that 1.0 μMol/L BrTet significantly increased the apoptosis percentage. BrTet also enhanced the intracellular accumulation of ADM in K562/A02 cells and its potency was greater than that of Tet at the same concentrations. BrTet inhibited the overexpression of P-gp and down regulated MDR1 mRNA expression in K562/A02 cells in a dose-dependent manner. In nude mice bearing K562 xenografts on the left flank and K562/A02 xenografts on the right flank, i.p. injection of 10 mg/kg BrTet significantly enhanced the antitumor activity of ADM against K562/A02 xenografts with inhibitory rates of 26.1%, while ADM alone inhibited the growth of KBv200 xenografts by only 5.8%. Conclusion BrTet showed significant MDR reversal activity in vitro and in vivo. Its activity may be related to the inhibition of P-gp overexpression and the increase in intracellular accumulation of anticancer drugs, which lead to more K562/A02 cells apoptosis.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 9
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 5062-5062
    Abstract: Object: To the effect of Fe3O4-magnetic nanoparticle loaded with DNR on In order to study the multidrug-resistant reversal effect of Fe3O4-magnetic nanoparticle loaded with DNR in vivo. Methods: K562-n,a leukemia cell line with high tumorigenicity in nude mice and its multidrug-resistant counterpart K562-n/VCR cells were inoculated subcutaneously into each groins of nude mice (5×106 cells/each) to establish a human leukemia xenograft model. The mice were randomly divided into group A receiving normal saline, group B receiving anti-tumor drugs daunorubicin (DNR), group C receiving Fe3O4-magnetic nanoparticle, group D receiving Fe3O4-magnetic nanoparticle loaded with DNR, and group E receiving Fe3O4-magnetic nanoparticle containing DNR with a magnetic field built on the surface of tumor tissues. After 20 days treatments, mice were killed and tumor tissues were isolated for pathological observation. The volume and weight of tumors were measured, then tumor suppression rate was calculated. The side effects of DNR loaded Fe3O4-magnetic nanoparticle were also evaluated. Results: The results showed that DNR loaded Fe3O4-magnetic nanoparticle can significantly suppress the growth of K562-n/VCR tumor in vivo, DNR alone can greatly suppress the growth of K562-n, Fe3O4-magnetic nanoparticle loaded with DNR can not further inhibit the K562-n tumor. Conclusion: In conclusion, Fe3O4-magnetic nanoparticle loaded with DNR can reverse the leukemia multidrug resistance in vivo.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 10
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 5063-5063
    Abstract: Objective: To study the reversal effect of Tetrandrine(Tet) and the estrogen-receptor inhibitor,toremifene(Tor),on multidrug resistance cell line K562/A02 and to investigate the reversal mechanism of this combination. Methods: ADM accumulation and the apoptosis percentage of K562 and K562/A02 cells were analyzed by fluorospectrophotometry, respectively. The protein levels of P-glycoprotein (P-gp) were detected by fluorospectrophotometry. The mRNA levels of mdr1 and Survivin were determined by RT-PCR. Results: The IC50 of ADM for K562/A02 and K562 cells were 57.43±4.55mg/L and 1.16±0.05mg/L respectively. Pretreating K562/A02 cells with toremifene(2.5μmol/L) or Tet(1μmol/L) for 72 hours partially restored the sensitivity of K562/A02 cells to ADM (IC50 were 20.74±1.62mg/L and 14.12±1.20mg/L respectively) but had no effect on K562 cells; IC50 of combined tetrandrine and toremifene was 9.14±1.03mg/L;K562/A02 showed apoptotic characteristics after treated with tetrandrine, toremifene (alone or combination);tetrandrine and toremifene (alone or combination) elevated the intracellular ADM accumulation in K562/A02; P-gp, mdr1 and Survivin mRNA were down regulated. Conclusion: Tetrandrine, toremifene (alone or combination) showed significant MDR reversal activity in vitro The reversal activity may be related to the inhibition of P-gp overexpression and down regulation the expression of mdr1 and Survivin mRNA to increase the intracellular accumulation of anticancer drugs, which lead to more K562/A02 cells apoptosis; Multidrug resistance (MDR) can be partially reversed by Tet or Tor of which the combination shows a great synergistic reversal effect.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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