Objective:To enhance the role targeting,design to link NGR sequence with tumstatin active peptides -T7's C-terminal,the derivant called ***:The cloning vector pMD-T7 and pMD-T7N were constructed by PCR and gene sy...
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Objective:To enhance the role targeting,design to link NGR sequence with tumstatin active peptides -T7's C-terminal,the derivant called ***:The cloning vector pMD-T7 and pMD-T7N were constructed by PCR and gene synthesis methods respectively,identificated by digestion and DNA sequencing. After the digested plasmids were isolated by the low melting point agarose electrophoresis,the target-fragment was cut off and mixed with the recovery of the digested vector *** vector pET-T7 and pET-T7N were constructed in low melting point agarose,identificated by digestion and DNA sequencing,transformed into competent *** BL21(DE3),induced by ***:Identification result shows that pET-T7 and pET-T7N were ***-SDS-PAGE results showed that IPTG concentration of 1 mM,after the induction of 25℃,8h,T7 peptides and T7-NGR peptides have achieved the optimum conditions of ***: Has been successfully constructed the expression vectors of the two peptides,and got product,no coverage at home and abroad,laid the foundation for further activity experiments.
TS-1 is an orally administered antitumor drug composed of tegafur,5-chloro-2,4-dihydroxypyridine (CDHP),and oteracil potassium in a molar ratio of 1:0.4:*** is hydroxylated and converted to a cytotoxic drug,5-FU,by he...
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TS-1 is an orally administered antitumor drug composed of tegafur,5-chloro-2,4-dihydroxypyridine (CDHP),and oteracil potassium in a molar ratio of 1:0.4:*** is hydroxylated and converted to a cytotoxic drug,5-FU,by hepatic microsomal *** is a reversible competitive inhibitor of dihydropyrimidine dehydrogenase,which is involved in the degradation of *** therapeutic effect of concurrent chemoradiotherapy with TS-1 has been confirmed in various solid tumors;however,the detailed mechanism of action has not yet been fully elucidated. Here,we identified hypoxia-inducible factor-1(HIF-1)as one of the targets of TS-1 in ehemoradiotherapy. In growth delay assays using a tumor xenograft of non-small-cell lung carcinoma,H441,TS-1 treatment enhanced the therapeutic effect of single?-ray radiotherapy(14 Gy) and significantly delayed tumor growth tripling time by 1.94-fold compared to radiotherapy alone(P < 0.01).An optical in vivo imaging experiment using a HIF-1-dependent 5 HREp-luc reporter gene revealed that TS-1 treatment suppressed radiation-induced activation of HIF-1 in the tumor *** suppression led to apoptosis of endothelial cells resulting in both a significant decrease in microvessel density(P < 0.05;*** alone) and a significant increase in apoptosis of tumor cells(P < 0.01;*** alone) in tumor *** of these results indicate that TS -1 enhances radiation-induced apoptosis of endothelial cells by suppressing HIF-1 activity resulting in an increase in radiosensitivity of the tumor *** findings strengthen the importance of HIF-1 as a therapeutic target to enhance the effect of radiotherapy.
Purpose:The present study was undertaken to examine the expression level of p16 mRNA in mouse hematopoietic stem cell after irradiation and to explore its molecular *** and Materials: Bone marrow mononuclear cells was...
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Purpose:The present study was undertaken to examine the expression level of p16 mRNA in mouse hematopoietic stem cell after irradiation and to explore its molecular *** and Materials: Bone marrow mononuclear cells was isolation from 30 C57 male mice and then lineage negative hematopoietic(Lin -) cells was sorted using magnetic *** hematopoietic stem cell was divided into 5 groups,including control group,radiation group,p38 inhibition group(SB203580(5 umol) was added into culture medium 30 minutes before radiation) and transcription inhibition *** the control group,the other four groups were exposed toγray at a dose of 4 *** expression status of p16 mRNA was examined using Real-time PCR after 5 *** the transcription inhibition group,actinomycin D(5ug/ml) was added into culture medium 3 hours before RNA extraction. Results:Comparing with the control group,the expression of p16 in radiation group was significant increased, showing radiation can induce the expression of p16 in hematopoietic stem *** contrast,the p16 expression level in SB203580 group was not increased after *** data suggested that the increased p16 expression in hematopoietic stem cell after irradiation was mediated by p38 signal *** with control group,the p16 expression level in transcription inhibition group was still increased,suggesting the stability of p16 mRNA was increased. Conclusion:These data showed that the increased expression of p16 in mouse hematopoietic stem cell was mediated by p38 signal ***,this kind of increasing was partly due to the increased stability of p16 mRNA.
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