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Objective: To investigate the pharmacokinetics and the distribution in tumor tissues of docetaxel nanomicelles. Method: The docetaxel nanomicelles was prepared by filming-rehydration method.HPLC was employed to determine the content of docetaxel in biological samples and the corresponding methodological evaluation was carried out.The mouse Lewis lung carcinoma model was established,when dosage of administration in tail vein was 20 mg·kg-1,and then the effect of free drug(DTX),non-pH-sensitive drug-loaded micelles(PELA-DTX) and pH-sensitive drug-loaded micelles(PBAE-DTX) on the pharmacokinetics and tissue distribution of tumor-bearing mice were investigated. Result: The docetaxel nanomicelles(PELA-DTX and PBAE-DTX) were successfully prepared.The method for the determination of docetaxel in mice was established by HPLC,the linearity,precision of the method and the recovery rate of samples all met the requirements.In the pharmacokinetic study,the plasma concentration of PBAE-DTX was always at a high level within 24 h.Compared with PELA-DTX and DTX,the areas under the curve(AUC0-∞) of PBAE-DTX were increased by 3.63% and 8.96%,the mean residence times(MRT) were extended by 2.86% and 6.43%,the half-life and the drug blood circulation time were prolonged.In the tissue distribution study,it was found that three docetaxel preparations were distributed in the heart,liver,spleen,lung,kidney and tumor tissue within 1 h after administration,but the distribution of these drugs in the tissues was reduced along with the extension of time,the accumulation of PBAE-DTX in tumor tissue was significantly higher than that in DTX and PELA-DTX at 24 h. Conclusion: PBAE-DTX can prolong the circulation time of docetaxel in the blood,increase its bioavailability,and significantly increase its distribution in tumor tissue.
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Aim To investigate the effects of mmLDL on the up-regulation ofα1 receptors in moues mesenter- ic arteries. Methods Mice tail intravenous injection of mmLDL was used . Vitro sensitive myograph was empl- oyed to examine Noradrenaline ( NA) induced vascular contraction on mice mesenteric artery, and the mRNA and protein expressions ofα1 andα2 receptors were an-alyzed by real-time PCR and Western blot, respective-ly. Results mmLDL significantly increased NA in-duced concentration-contractile curve, and the data of Emax and pEC50 were from ( 122. 61 ± 9. 40 )% and (5. 65 ± 0. 05 ) in normal saline ( NS ) group to (161. 01 ± 6. 90 )% and ( 6. 20 ± 0. 08 ) in mmLDL group (P tion-contractile curve induced by NA towards right. Af-ter using mmLDL, the mRNA and protein levels of α1 adrenoceptor were significantly increased, but the mR-NA and protein levels of α2 adrenoceptor were not changed. Conclusion Tail intravenous injection of mmLDL enhances the vascular expressions of α1 adre-noceptors and the contractile effects mediated byα1 ad-renoceptors.
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Objective To investigate the functional role of 25 microRNAs in breast cancer ,and to find new tumor suppressor microRNAs that may serve as specific targets of new gene therapies . Methods Twenty-five microRNAs expression vectors were constructed and stably transfected into mouse mammary tumor cells 4To7 by Lipofectamine2000. Cells were selected with G418 and sorted by Flow cytometry.The cells in logarithmic phase were collected and 2 ×105 cells/mouse was inoculated into BALB/c mice via tail vein .Lungs were harvested 14 days after tumor cell inoculation , and the number of metastasis foci was counted .Results Mice inoculated with mir-449a-expressing 4To7 cells via tail vein developed reduced lung metastases compared with mice inoculated with negative control cells .Mice inoculated with mir-1935-expressing 4To7 cells via tail vein developed increased lung metastases compared with mice inoculated with negative control cells .Other twenty-three microRNAs neither promoted nor inhibited lung metastases of breast cancer .Conclusions Two of twenty-five microRNA were identified to be associated with breast cancer metastasis .MiR-449a may play a tumour suppressor role in the regulation of migration and metastasis in breast cancer .miR-1935 transgenic over-expression promoted tumor growth and metastasis .
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Objective To investigate the effects of allogenic intra-bone marrow bone marrow transplantation (IBM-BMT) on re-establishing hematopoiesis in mice. Methods Bone marrow mononuclear cells (BMNCs) from BALB/ c mice were transplanted into the C57BL/6 mice treated with a lethal dose of ~(60)Coγ-ray radiation through intra-bone marrow injection or intravenous injection. Sixty of the C57BL/6 mice were randomly divided into three groups as higher dose intra-bone marrow injection group (IBM1 group), lower dose intra-bone marrow injection group (IBM2 group) and intravenous injection group (IV group). The nucleated cell numbers of whole bone marrow from the tibia of each recipient mouse were counted respectively at the day 1, day 3, day 6 and day 9 after the transplantation. The donor-derived total nucleated cells and myeloid cells were quantified by flow cytometry. Results At 6th day after transplantation, more total bone marrow nucleated cells, total donor-derived nucleated cells and donor-derived myeloid cells in the tibia of injected side in both IBM1 group and IBM2 group were found than that in IV group (P<0.05 or P<0.01). Conclusion Compared with traditional bone marrow transplantation (IV-BMT),IBM-BMT improves the bone marrow hematopoiesis in the early hematopoietic re-establishing stage in allogenic bone marrow transplantation.