| 11. |
- Lotfi, Kourosh, 1966-, et al.
(författare)
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Pharmacological basis for cladribine resistance in a human acute T lymphoblastic leukaemia cell line selected for resistance to etoposide
- 2001
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 113:2, s. 339-346
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Tidskriftsartikel (refereegranskat)abstract
- Cross-resistance between different classes of anti-neoplastic agents can jeopardize successful combination cancer chemotherapy. In this study, we observed an unexpected cross-resistance between the podophyllotoxine derivative etoposide (VP) and the nucleoside analogue cladribine (CdA) in CCRF-CEM cells developed for resistance to VP. The resistant cells also displayed 14- and twofold resistance to cytarabine (ara-C) and gemcitabine respectively. Closer analysis of these cells showed that they contained lower amounts of topoisomerase (topo) IIα (P < 0·001) and β protein (P < 0·026), formed substantially lower amounts of the topo II–DNA complex, and had a markedly decreased level of Fas (CD95/APO-1)-ligand mRNA expression. Interestingly, Fas expression in the resistant cells did not differ from that in the parental cell line. No differences were observed in the accumulation/efflux of daunorubicin or in the gene expressions of P-glycoprotein, multidrug resistance-associated protein and the lung resistance-related protein. The activity of deoxycytidine kinase (dCK), responsible for activation of CdA and ara-C, was the same for resistant and wild-type cells. However, there was an increase in the activity of the cytosolic 5′-nucleotidases (5′-NT), responsible for deactivation of nucleotides, amounting to 206% (P < 0·001) for the high Km and 134% (P < 0·331) for the low Km 5′-NT in resistant cells. The high Km 5′-NT is probably responsible for the decreased amount of the active metabolite CdA 5′-triphosphate [40% decreased (P < 0·045)], as well as for other purine ribonucleosides and deoxyribonucleosides triphosphates in the resistant cells. In contrast, a significantly higher deoxycytidine triphosphate (dCTP) level (167%, P < 0·001) was observed in the resistant cells. Thus, this study suggests that the major cause of resistance to the nucleoside analogues CdA and ara-C in cells selected for resistance to VP is a result of metabolic alterations producing increased activity of 5′-NT and higher dCTP levels. Furthermore, these results indicate that there is a common factor in the regulation of nucleotide-degrading enzymes and DNA topoisomerases, which may be altered in cross-resistant cells.
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| 12. |
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| 13. |
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| 14. |
- Wang, XB, et al.
(författare)
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Expression of CTLA-4 by human monocytes
- 2002
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Ingår i: Scandinavian journal of immunology. - : Wiley. - 0300-9475. ; 55:1, s. 53-60
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Tidskriftsartikel (refereegranskat)
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| 15. |
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| 16. |
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| 17. |
- Xu, DW, et al.
(författare)
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Downregulation of telomerase reverse transcriptase mRNA expression by wild type p53 in human tumor cells
- 2000
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Ingår i: Oncogene. - 0950-9232 .- 1476-5594. ; 19:45, s. 5123-5133
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Tidskriftsartikel (refereegranskat)abstract
- The p53 tumor suppressor protein inhibits the formation of tumors through induction of cell cycle arrest and/or apoptosis, In the present study we demonstrated that p53 is also a powerful inhibitor of human telomerase reverse transcriptase (hTERT), a key component for telomerase, Activation of either exogenous temperature-sensitive (ts) p53 in BL41 Burkitt lymphoma cells or endogenous wild type (wt) p53 at a physiological level in MCF-7 breast carcinoma cells triggered a rapid downregulation of hTERT mRNA expression, independently of the induction of the p53 target gene p21, Co-transfection of an hTERT promoter construct with wt p53 but not mutant p53 in HeLa cells inhibited the hTERT promoter activity. Furthermore, the activation of the hTERT promoter in Drosophila Schneider SL2 cells was completely dependent on the ectopic expression of Sp1 and was abrogated by wt p53, Finally, wt p53 inhibited Sp1 binding to the hTERT proximal promoter by forming a p53-Sp1 complex. Since activation of telomerase, widely observed in human tumor cell lines and primary tumors, is a critical step in tumorigenesis, wt p53-triggered inhibition of hTERT/telomerase expression may reflect yet another mechanism of p53-mediated tumor suppression. Our findings provide new insights into both the biological function of p53 and the regulation of hTERT/telomerase expression.
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| 18. |
- Xu, Hong-Tao, et al.
(författare)
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Effects of fucosylated milk of goat and mouse on Helicobacter pylori binding to Lewis b antigen
- 2004
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Ingår i: World Journal of Gastroenterology. - Beijing : WJG Press. - 1007-9327 .- 2219-2840. ; 10:14, s. 2063-2066
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Tidskriftsartikel (refereegranskat)abstract
- Aim:To evaluate the effects of animal milk containing fucosylated antigens on Helicobacter pylori (H pylon) binding to Lewis b antigen. Methods:A mammary gland expression vector containing human α1-3/4-fucosyltransferase cDNA sequences was constructed. Transient expression of human(α1-3/4-fucosyltransferase cDNA in goat mammary cell and establishment of transgenic mice were performed. The adhesion inhibitory properties of milk samples were analyzed by using Hpylori. Results: Goat milk samples were found to inhibit bacterial binding to Lewis b antigen. The highest inhibition was observed 42 h after injection of the plasmid. The binding activity of Hpylori to Lewis b antigen reduced mostly, by 83%, however milk samples from transgenic mice did not inhibit Hpylori binding to Lewis b antigen. Conclusion: The use of “humanized“ animal milk produced by the transgenic introduction of fucosylated antigen can perhaps provide an alternative therapy and preventive measure for Hpylori infection.
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| 19. |
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| 20. |
- Xu, Y., et al.
(författare)
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A Security Framework for Collaborative Distributed System Control at the Device-Level
- 2003
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Ingår i: INDIN 2003. - : Institute of Electrical and Electronics Engineers (IEEE). - 0780382005 ; , s. 192-198
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Konferensbidrag (refereegranskat)abstract
- In today's globalized business world, outsourcing, joint ventures, and cross-border collaborations have led to work environments that are geographically distributed across organizational and national boundaries. There are critical research needs to develop highly secured collaborative work environments and security solutions for deployment, configuration, monitoring, and device control of interoperating services. We present a well-shaped security framework for distributed system control with a focus on device-level system control, monitoring and services reconfiguration in open and dynamic environments. The characteristics of portability, reconfigurability, interoperability, and interchangeability of these new environments are considered as key factors to produce new security risks and challenges. By adopting public key cryptography, software agent and XML binding technologies, the major security problems of authenticity, integrity, confidentiality, and safe execution are addressed in this framework. The core modules for secure task delivery and execution are presented in detail.
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