Hai-Feng Song

Guangxi Medical University, Yung-ning, Guangxi Zhuangzu Zizhiqu, China

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Publications (18)32.59 Total impact

  • Xiao-Lin Wang, Qing-Qing Wang, Hai-Feng Song
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    ABSTRACT: RNA interference (RNAi), as a new technology of gene therapy, has been used in the studies of many diseases in vitro, however, targeting delivery of small interference RNA (siRNA) is still a bottleneck for clinical therapy of siRNA agents. Aptamer is a group of oligonucleotides with high affinity and targeting, and is becoming another important means of delivery for siRNA. In this review, we summarized siRNA delivery obstacles in vivo and recent attractive developments increatively using cell-internalizing aptamers to deliver siRNAs to target cells.
    Yao xue xue bao = Acta pharmaceutica Sinica 07/2012; 47(7):850-5.
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    ABSTRACT: DNAs containing unmethylated CpG motifs can stimulate innate and adaptive immunity. The aim of this study was to investigate the immunostimulatory and anti-neoplasm effects of a novel CpG oligodeoxynucleotide, ODN10, in tumor-bearing mice. B16 melanoma-bearing C57BL/6 mice were administered ip or sc with ODN10 or conventional CpG ODN1826 on the indicated days post inoculation. The animal survival rate and the inhibitory effect on tumor growth were observed in vivo. B and T lymphocyte proliferation, natural killing cell cytotoxicity and the phagocytic ability of peritoneal macrophages from the animals were determined using [(3)H]-thymidine incorporation assay, 4-h (51)Cr release assay and neutral red chromometry method, respectively. The serum levels of IL-12, IL-4 and IgE were quantified using ELISA assays. Histological examination of tumor tissues was performed after HE staining, and the expression of PCNA, CD63, and CD80 in tumor tissues was analyzed with immunohistochemistry. ODN10 (1, 5 and 25 mg/kg) significantly inhibited the growth and metastasis of the tumor, and significantly prolonged the survival of tumor-bearing mice, as compared with ODN1826. The immune status was suppressed in tumor-bearing mice. Both ODN10 and ODN1826 significantly reversed the suppressed immunoactivities in tumor-bearing mice, which included promoting B and T lymphocyte proliferation, enhancing NK cell and peritoneal macrophage activities, inducing IL-12 secretion and inhibiting IL-4 and IgE secretion. Further, CpG ODNs decreased PCNA and CD63 expression while induced expression of CD80. ODN10 presented more potent activity, and displayed the most prominent immunostimulatory potential. ODN10 produces prominent immunomodulatory effects on cellular immunity in tumor-bearing mice, which might help reverse the established Th2-type responses to the Th1-type responses, thus may be used as a potent anti-tumor immunotherapy agent or adjuvant.
    Acta Pharmacologica Sinica 06/2012; 33(8):1047-54. · 2.35 Impact Factor
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    ABSTRACT: To study the pharmacokinetics of cantide, an antisense oligonucleotide, and its metabolites after iv gtt administration in rhesus monkeys, a dual solid phase extraction pretreatment method coupling with non-gel sieving capillary electrophoresis analysis method was used for determination of cantide and its metabolites in plasma and their pharmacokinetic parameters were calculated. The pharmacokinetic behavior of cantide and its metabolites (M1 and M2) after iv gtt administration (8, 16 and 24 mg kg(-1)) in rhesus monkeys were investigated. After iv gtt administration of cantide to rhesus monkeys, cantide in plasma was eliminated rapidly and the terminal elimination half-life (t1/2) was 57.91-77.97 min, the correlation coefficients (r) to the dose of Cmax AUC(o-inf) and AUC(0-t) of the prototype was 0.9918, 0.9568 and 0.9773, respectively. The metabolites of cantide reached the Cmax following cantide immediately and the Cmax of metabolites were lower than that of the prototype. The CL(S) of cantide and its metabolites (M1 and M2) were 1.60-2.19, 5.92-8.58 and 6.07-8.78 mL min(-1) kg(-1), respectively. So, it is concluded that the Cmax of cantide and its metabolites increased with the dose, which is the same as their AUC(0-inf) and AUC(0-t). The CL(S) of metabolites were higher than that of the prototype. The MRT and t1/2 of metabolites in the high dose group increased obviously.
    Yao xue xue bao = Acta pharmaceutica Sinica 11/2011; 46(11):1370-3.
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    ABSTRACT: To investigate the population pharmacokinetics of recombinant human tumor necrosis factor receptor-Fc fusion protein (rhTNFR-Fc) administered via subcutaneous (SC) injection in healthy Chinese volunteers and in Chinese patients with ankylosing spondylitis (AS). Thirty-two healthy volunteers were randomly assigned to receive a single SC injection of 12.5, 25, 37.5, or 50 mg of rhTNFR-Fc. Twenty male patients with moderate AS were randomly assigned to receive seven consecutive SC injections of rhTNFR-Fc at either 25 mg twice a week (BIW) or 50 mg once a week (QW). Population pharmacokinetic (PK) analysis was applied to obtain PK parameters of rhTNFR-Fc by the NONMEM method. The data were best described by a one-compartment model with lag time. We found that gender had a significant effect on the apparent clearance (CL/F), with the male CL/F ratio being only 0.665 times the female ratio; the absorption coefficient (F) of multiple dosages of rhTNFR-Fc was only 0.674 times that of a single dosage. The outcome parameters were CL/F (female: 0.168 L/h, male: 0.110 L/h), the apparent volume of distribution (Vd/F: 15.5 L), the absorption rate constant (Ka) (single dosage: 0.0605 h⁻¹, multiple dosage: 0.0408 h⁻¹), and the lag time (T(lag): 1.03 h). The inter-individual variability in the CL/F, Vd/F, Ka, and T(lag) were 33.3%, 42.7%, 55.6%, and 81.8%, respectively. Chinese females have a higher CL/F than Chinese males, and multiple dosings can significantly decrease the absorption of rhTNFR-Fc (SC). The population PK parameters of rhTNFR-Fc in healthy Chinese volunteers and patients with AS were similar to those reported for subjects in published American studies.
    Acta Pharmacologica Sinica 11/2010; 31(11):1500-7. · 2.35 Impact Factor
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    ABSTRACT: An improved liquid chromatographic method with on-line solid phase extraction (SPE) and tandem mass spectrometric detection was optimised for quantification of the anti-HIV peptide Sifuvirtide in human plasma. The SPE sorbents, loading buffer composition and other aspects of the on-line SPE column were investigated in detail for efficiently extracting the interesting peptides and simultaneously discarding the large amount of proteins. The gradient elution program was optimised on the analysis column to decrease the matrix effect and obtain excellent selectivity. The multiple charge ion at m/z 946.4 of Sifuvirtide was quantified by a linear ion trap mass spectrometer, operating in the positive mode, and selective reaction monitoring (SRM) acquisition. Method validation results demonstrated that the linear calibration curve covered a range of 6.1-6250 ng/mL, and the correlation coefficients (r(2)) were above 0.992. The lower limit of detection (LLOD) with a signal-to-noise (S/N) ratio higher than 10 was 6.1 ng/mL. The accuracy ranged from -7.6 to 10.6%, and the intra- and inter-batch precisions were less than 8.7% and 5.5%, respectively. Finally, more than nine hundred of samples from a clinical trial was completely analyzed using this on-line SPE coupled HPLC-MS/MS system in one single week, due to the rapid run-time of individual sample (6.5 min).
    Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 07/2010; 878(21):1893-8. · 2.78 Impact Factor
  • Ying JI, Qing-Qing WANG, Jie FU, Xin GAO, Hai-Feng SONG
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    ABSTRACT: Polymerase chain reaction (PCR) amplification is one of the vital steps for selecting aptamers from random DNA libraries via systematic evolution of ligands exponential enrichment (SELEX) technology. The influencing factors on PCR amplification were investigated and optimized based on the changes of dsDNA product, ss-dsDNA by-products and primers, which were monitored by capillary electrophoresis with laser-induced fluorescence (CE-LIF) detector. Results show that PCR amplification profiles are remarkably different when a homogeneous DNA or a random DNA library was used as template, while random DNA library was used as template, the yield of products reached its maximum at the eighteenth cycle in this study. Other influencing factors including the number of initial templates, annealing temperature of PCR, concentration of DNA polymerase were also studied. It is suggested that the optimization of PCR amplification conditions might be necessary for guaranteeing the efficiency of SELEX with random DNA libraries as template. For the N39 DNA libraries in the present study, the optimum conditions were as follows: the number of initial templates was 105 molecules, the concentration of DNA polymerase was 0.05 U μL−1, the annealing temperature in PCR was 70°C, and the cycle number was 18. The results from the present study might be helpful for screening aptamers with high efficacy from DNA libraries by SELEX.
    Chinese Journal of Analytical Chemistry 05/2010; 38(5):622-626. · 0.79 Impact Factor
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    ABSTRACT: Optimal design of antiviral short-interfering RNA (siRNA) targeting highly divergent hepatitis B virus (HBV) was validated by quantitative structure activity relationship (QSAR) analysis. The potency of 23 synthetic siRNAs targeting 23 sites throughout HBV pregenomic RNA were evaluated at 10 nmol/L by determining the inhibition on the expression of S/P/pregenomic mRNA and hepatitis B surface antigen (HBsAg) quantitatively in HepG2.2.15 cells. Genotype homology within HBV genomes was identified through plentiful computational analysis and the multiple linear regression analysis was made to validate the relationship between the functional siRNAs and primary characteristics. Based on the preliminary results, relationships between different determined endpoints [S/P mRNA, HBsAg, C/P mRNA, hepatitis B e antigen (HBeAg) and viral DNA load] and siRNA efficacy evaluation were investigated. Genotype homology, open reading frame (ORF) S/P, X and C had tight correlation with the ability of siRNAs on inhibiting the expression of S/P/Pregenomic mRNA and HBsAg (P<0.01), of which, ORF C was negatively correlated with the siRNA potency (P<0.05). Further study showed that siRNA potency evaluation was influenced by different determined endpoints. P-target siRNAs showed significant inhibition on the S mRNA and HBsAg expression. S-target siRNAs inhibited the expression of S mRNA and HBsAg strongly. X-target siRNAs played active roles in inhibiting all 5 determined endpoints. C-target siRNAs blocked the expression of C mRNA, HBeAg and viral DNA load significantly. The antiviral potency of siRNA was relevant to its primary characteristics and determined endpoints were important for siRNA efficacy evaluation for complex genome with overlapping ORF, which was helpful for siRNA optimal design.
    Acta Pharmacologica Sinica 01/2009; 29(12):1522-8. · 2.35 Impact Factor
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    ABSTRACT: To study the relationship between primary structures of oligodeoxynucleotides (ODN) containing unmethylated deoxycytidyldeoxyguanosine (CpG) dinucleotide motifs and their immunostimulatory activities in mouse spleen cells. A series of CpG ODN with different primary structures were synthesized. Their capabilities to stimulate mouse spleen cell proliferation were determined by [3H]thymidine incorporation assay. Cytokine (interleukin [IL]-6, IL-12, and IFN-alpha) secretion spectra induced by CpG ODN were assessed by ELISA. The ability of CpG ODN to activate natural killer cells was evaluated by standard 4 h (51)Cr-release assay. Flow cytometry was utilized to examine the expressions of various lymphocyte surface molecules on diverse immunocytes. An effective CpG ODN for murine, ODN1826, was set as the template of modification and the positive control. The immunostimulatory activities of CpG ODN with different sequences and compositions varied markedly, both in character and in extent. It was useless for improving the immunostimulatory activity of ODN1826 by simply increasing the functional hexameric CpG motif number, modifying the site of CpG motifs, or changing the distance between multi-CpG motifs. However, an addition of a self-complementary palindrome structure at the 3'-end, but not the 5'-end of CpG ODN, aroused marked improvement in its activity. Several designed ODN had superior comprehensive immunostimulatory properties compared to ODN1826. The immunostimulatory activity of a CpG ODN was relevant to its primary structure. It was useless for promoting immunostimulatory activity to simply change CpG motif number, space, or distance. The 3'-end palindrome structure of CpG ODN is associated with enhanced immunostimulatory activity.
    Acta Pharmacologica Sinica 11/2007; 28(10):1637-44. · 2.35 Impact Factor
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    ABSTRACT: To study the relationship between the structure of dermatan sulfate (DS) derivatives and their anti-thrombotic activities, DS-derived oligosaccharides (with different structures and relative molecular weight (M(r))) were prepared, and the effects of the DS-derived oligosaccharides on the activities of heparin cofactor II (HCII), activated protein C (APC), blood platelet, and vascular endothelial cells were studied. The major disaccharides of DS and polysulfated dermatan sulfate (PSDS) were IdoA-1-->3-GalNAc-4-OSO(3) and IdoA-2OSO(3)-1-->3-GalNAc4, 6-diOSO(3), respectively. The results showed that the consequence of the thrombotic inhibitory effects of DS and its derivatives were as follows: PSDS>low molecular weight polysulfated dermatan sulfate (LPSDS)>DS. Both DS and PSDS inhibited platelet aggregation in the concentration-dependent manner, and the IC(50) value of DS and PSDS is 12.7+/-1.3 and 28.6+/-0.9 mg/mL, respectively. DS oligosaccharides (DSOSs) and PSDS oligosaccharides (PSDSOSs) both significantly inhibited P-selectin expression on platelet surface (P<0.01), while DSOSs have no different effect compared with PSDSOSs. DSOSs and PSDSOSs significantly enhanced the activity of HCII in inhibiting thrombin in the plasma. The most active PSDSOS was PSDSOS(1) with M(r) of 4959, which enhanced the HCII activity by 91% (P<0.01). The experiments on APC activity showed that DS and its derivatives enhanced APC activity. The most active PSDSOS was PSDSOS(3) with M(r) of 2749, which enhanced the APC activity to 331+/-27% (P<0.01). DSOSs and PSDSOSs enhanced tissue plasminogen activator (t-PA) activity and reduced the plasminogen activator inhibitor (PAI) activity from cultured human umbilical vein endothelial cells (HUVEC), resulting in the ratio of t-PA/PAI going up. PSDSOSs which have the same M(r) as DSOSs produced more active effects in above assays, except for platelet aggregation.
    Thrombosis Research 02/2007; 119(3):377-84. · 3.13 Impact Factor
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    ABSTRACT: To investigate the inhibitory effect of antisense oligodeoxynucleotides targeting HER-2 mRNA on growth of breast cancer. Human breast cancer cells of the line SK-BR-3 that overexpresses HER-2 were injected subcutaneously into BALB/c nude mice. Seven to ten days after tumors were collected and made into homogenate. Antisense oligodeoxynucleotide HA6722 targeting HER-2 mRNA and its control sequence Scramble were synthesized. Forty-nine BALB/c nude mice were injected with homogenate of SK-BR-3 cells and then randomly divided into 7 equal groups: Group 1, injected intravenously with docetaxel (TXT) 7.5 mg.kg(-1).d(-1) once a week twice; Group 2, injected intravenously with TXT 15 mg.kg(-1).d(-1) once a week twice; Group 3, injected intravenously with TXT 7.5 mg.kg(-1).d(-1) once a week twice + HA6722 5 mg.kg(-1).d(-1) for 12 days; Group 4, injected intravenously with HA6722 5 mg.kg(-1).d(-1) for 12 days; Group 5, injected intravenously with TXT 7.5 mg.kg(-1).d(-1) once a week twice + Scramble6722 5 mg.kg(-1).d(-1) for 12 days; and Group 7, injected with normal saline. After the drug administration the mice were observed for additional 3-4 weeks to measure the size of tumor every other day. Then the mice were killed and the tumors were taken out to be examined. The inhibition rate was calculated. The inhibition rate of tumor in Group 3 was 88.3%, not significantly different from that in Group 2 (88.7%, P > 0.05). The inhibition rate in Group 4 was 76.3%. The inhibition rates of tumor of Groups 2, 3, and 4 were all significantly higher than that in Group 7. However, the inhibition rate of tumor of Group 6 was not significantly different from that in Group 7. Antisense oligodeoxynucleotides targeting HER-2 mRNA inhibits the growth of breast cancer in a sequence specific and dose-dependent manner.
    Zhonghua yi xue za zhi 03/2006; 86(8):540-3.
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    ABSTRACT: To study the pharmacokinetics of sifuvirtide, a novel anti-human immunodeficiency virus (HIV) peptide, in monkeys and to compare the inhibitory concentrations of sifuvirtide and enfuvirtide on HIV-1-infected-cell fusion. Monkeys received 1.2 mg/kg iv or sc of sifuvirtide. An on-line solid-phase extraction procedure combined with liquid chromatography tandem mass spectrometry (SPE-LC/MS/MS) was established and applied to determine the concentration of sifuvirtide in monkey plasma. A four-(127)I iodinated peptide was used as an internal standard. Fifty percent inhibitory concentration (IC(50)) of sifuvirtide on cell fusion was determined by co-cultivation assay. The assay was validated with good precision and accuracy. The calibration curve for sifuvirtide in plasma was linear over a range of 4.88-5000 microg/L, with correlation coefficients above 0.9923. After iv or sc administration, the observed peak concentrations of sifuvirtide were 10 626+/-2886 microg/L and 528+/-191 microg/L, and the terminal elimination half-lives (T(1/2)) were 6.3+/-0.9 h and 5.5+/-1.0 h, respectively. After sc, T(max) was 0.25-2 h, and the absolute bioavailability was 49%+/-13%. Sifuvirtide inhibited the syncytium formation between HIV-1 chronically infected cells and uninfected cells with an IC(50) of 0.33 microg/L. An on-line SPE-LC/MS/MS approach was established for peptide pharmacokinetic studies. Sifuvirtide was rapidly absorbed subcutaneously into the blood circulation. The T(1/2) of sifuvirtide was remarkably longer than that of its analog, enfuvirtide, reported in healthy monkeys and it conferred a long-term plasma concentration level which was higher than its IC(50) in vitro.
    Acta Pharmacologica Sinica 11/2005; 26(10):1274-80. · 2.35 Impact Factor
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    ABSTRACT: To study the pharmacokinetics and accumulation of an Escherichia coli expressed His-tag fused recombinant human endostatin (rh-endostatin) in Rhesus monkeys. Rh-endostatin was iv or sc injected in Rhesus monkeys, and the rh-endostatin concentration in serum samples was determined by an enzyme immunoassay (EIA) method. The serum drug concentration-time data were analyzed by compartmental analysis using the practical pharmacokinetic program 3p97. Following iv administration at a dose rate of 1.5, 4.5, and 13.5 mg/kg in rhesus monkeys, the concentration-time curves of rh-endostatin were best fitted to a three-compartment open model. AUC(0-infinity) linearly increased with dose, while Cls exhibited no significant difference among different dose groups. The terminal half-lives (lambda3) were 8+/-8, 3.1+/-1.4, and 20+/-14 h, respectively. After sc administration at a dose rate of 1.5 mg/kg, the concentration-time curve was best fitted to a two-compartment open model, with a terminal half-life (T(1/2beta)) of 8+/-3 h. Bioavailability following sc injection was approximately 70%+/-3%. After consecutive iv injection of rh-endostatin at a dose rate of 1.5 mg.kg(-1).d(-1) for 7 d, the AUC(0-24 h) substantially increased from 22+/-13 mg.h.L(-1) (d 1) to 50+/-29 mg.h.L(-1) (d 7), with an accumulation factor of 2.3+/-0.6 (P < 0.05). The pharmacokinetic behavior of rh-endostatin in Rhesus monkeys complies with linear kinetics within the examined dose range. It tends to be accumulated in bodies after repeated administration at a dose level of 1.5 mg.kg(-1).d(-1) for more than 7 consecutive days.
    Acta Pharmacologica Sinica 02/2005; 26(1):124-8. · 2.35 Impact Factor
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    ABSTRACT: To establish the method for quantitation of the phosphorothioate oligodeoxynucleotides (S-ODNs) in plasma. Two solid-phase extraction columns combined with a strong anion-exchange column were utilized to remove proteins and lipids in plasma, and the salts were removed by a reverse-phase column followed by dialysis with a 2500 Da-cutoff membrane. The concentration of the tested S-ODNs, PS20, and its metabolites extracted from the plasma were determined by the method of non-gel sieving capillary electrophoresis (NGCE) with diode array detection in the presence of internal standard (IS). The method was with good base number specificity. Relative standard deviation % of both intra and inter assay were all less than 10 %, and the total mean recovery was about 91 %. The methodology was successfully used to determine the PK behavior of an anti-tumor antisense S-ODNs in monkeys and identify the metabolites with single base difference. The combined method of solid-phase extraction and NGCE could be used to study the pharmacokinetics of S-ODNs, and the main parameters of the methodology met the requirement of PK study.
    Acta Pharmacologica Sinica 07/2004; 25(6):801-6. · 2.35 Impact Factor
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    ABSTRACT: To study the role of mRNA secondary structure stability in antisense drug design and obtain better antisense candidates against neu/HER-2/erbB-2 mRNA than previous report. Program RNAstructure was utilized to simulate the secondary structures of HER-2 mRNA. Then 21 antisense phosphorothioate oligodeoxynucleotides (S-ODN) targeting different parts of secondary structural motif were designed. HA4 was set as positive control. Mean 50 % inhibitory effects (IC(50)) of S-ODN on proliferations of SK-BR-3 breast cancer cells were evaluated. The expression of target mRNA was detected by RT-PCR. The multiple regression and quantitative structure-activity relationship (QSAR) analysis was preformed by SPSS software. One optimal and two suboptimal secondary structures of target mRNA were obtained. Nine out of 11 S-ODN against completely conservative local motif (LM) (conservative among all simulant secondary structures) got lower or similar IC(50) values compared with HA4. On the other hand, 2 out of 3 S-ODN against relatively conservative LM (conservative between any two simulant secondary structures) got lower or similar IC(50) values compared with HA4. Only 2 out of 5 S-ODN targeting variable LM (variable among different predicted secondary structures) had acceptable activities. Average IC(50) of S-ODN against completely conservative LM was significantly lower than that of S-ODN against diverse LM. QSAR analysis suggested that stability, base number of bulge loops, and target free energies Delta GoT were statistically significant. In the multiple regression, R was 0.967, P=0.005. Antisense drug design against conservative LM was helpful for improving the positive rate. Several S-ODN candidates better than positive control were screened.
    Acta Pharmacologica Sinica 10/2003; 24(9):897-902. · 2.35 Impact Factor
  • Shuan-Ping Yang, San-Tai Song, Hai-Feng Song
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    ABSTRACT: Breast cancer is one kind of multi-gene related malignancy. Overexpression of some oncogenes such as HER-2 (c-erbB-2, Neu), bcl-2/bcl-xL, protein kinase A (PKA), and transferrin receptor gene (TfR gene), etc significantly affect the prognosis of breast cancer. It was shown that specific suppression of the overexpressed genes above resulted in the improvement of the therapy of breast cancer. Antisense interference, one of useful tools for inhibiting the overexpression of specific oncogenes, was involved in the therapy of breast cancer in recent years. Data indicated that antisense oligonucleotides (ON) could inhibit specially the expression of the target genes on mRNA or protein levels in most of cases; some ON candidates showed encouraging therapeutic effects in vitro and in vivo on breast cancer cell lines or xenografts. Furthermore, the combination use of the antisense ON and normal chemotherapeutic agents indicated synergistic antitumor effects, which was probably the best utilization of antisense ON in the treatment of breast cancer.
    Acta Pharmacologica Sinica 05/2003; 24(4):289-95. · 2.35 Impact Factor
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    ABSTRACT: To optimize the antisense drug design by the combined method of phylogenetic analysis and secondary structure prediction and to get ideal candidates. The phylogenetic analysis and the secondary structure simulation were performed by computer. Oligodeoxynucleotides (ODN) were designed against the full-conserved blocks with low local reaction free energy of protein kinase C (PKC)-alpha mRNA. The in vitro effects of ODN were evaluated by human A549 lung carcinoma cells and mouse B16-BL6 melanoma cells, the expression of target mRNA was detected by in situ hybridization and RT-PCR. The in vivo effects of ODN were also evaluated by models of A549 xenografts in nude mice and B16 melanoma in mice. Three ODN had significantly lower IC50 values than that of ISIS3521, the positive control, on A549 cells in vitro. Five ODN inhibited the growth of B16-BL6 cells with IC50 <100 nmol/L, while IC50 of ISIS3521 was >200 nmol/L. In situ hybridization and RT-PCR showed that the best candidate AP1261 inhibited the expression of PKC-alpha at mRNA level in a dose-dependent manner. AP1261 inhibited the growth of A549 and B16 tumors in vivo at 0.005-0.5 mg.kg(-1).d(-1). The inhibitory rate of AP1261 on A549 tumors was greater than that of ISIS3521 at the same dose. ISIS3521 did not affect the growth of B16 tumors. AP1261 may be of value as an antitumor agent or adjuvant and the combined method of phylogenetic analysis and secondary structure prediction is a potential helpful tool for antisense drug design.
    Acta Pharmacologica Sinica 03/2003; 24(3):269-76. · 2.35 Impact Factor
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    ABSTRACT: To study the pharmacokinetics (PK) and changes of kaolin partial thromboplastin time (KPTT) following single or multiple (7 d) dosing of a novel recombinant hirudin variant-2 (rHV-2) via the route of iv bolus injection (50 % of the total dose) plus infusion (the remained 50 % of the dose) in rhesus monkeys. A crossover design was applied to research the PK and KPTT profiles of rHV-2 after single (with total dose at 1, 3, and 6 mg/kg, respectively) and multiple dosing (3 mg/kg). An enzyme-linked immunosorbent assay (ELISA) method was utilized to determine the level of rHV-2 in plasma. The concentration profiles of rHV-2 during or after administration were dependent both on the loading dose and the infusion rate. Mean Cmax after bolus in three single dose groups were 2.90, 9.78, and 15.68 mg/L, respectively. Infusions at rate of 8.35, 25, and 50 g/kg/h in 1 h resulted in steady-state levels of 0.73-0.86, 1.94-2.04, and 5.41-5.59 mg/L, respectively. The plasma rHV-2 levels during or after administration among doses were significantly different at most of the time points. Area under concentration-time curve (AUC) increased linearly with dose but systemic clearances were similar among different groups. KPTT was significantly prolonged (compared with baseline) at all dose levels, and trended to increase with dose. Both the loading dose and the infusion rate are very important for controlling the rHV-2 level, and the data may be helpful for optimizing dosage-regimen in clinical trials.
    Acta Pharmacologica Sinica 10/2002; 23(9):842-6. · 2.35 Impact Factor
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    ABSTRACT: The metabolism, distribution and excretion profiles of recombinant human thrombopoietin (rhTPO) in mice were studied by means of (125)I-labeled rhTPO ((125)I-rhTPO) combined with size exclusive high performance liquid chromatography (SHPLC) or trichloroacetic acid (TCA) precipitation analysis. (125)I-rhTPO was prepared by iodogen method. Purification was performed on Sephacryl S-200 HR gel. Radioactive-purity of (125)I-rhTPO identified by SHPLC was (96.9 +/- 1.5)% (n = 3). The proliferation effect of TPO dependent cell line (TD-3) and the increase of peripheral platelet counts in mouse by (125)I-rhTPO demonstrated that (125)I-labeled protein maintained the biological activities of TPO both in vitro and in vivo. SHPLC analysis of serum and urine samples taken after sc 1 micro g/mouse (345 kBq/mouse) of (125)I-rhTPO revealed that there were two lower molecular weight (125)I-degradation metabolites ((125)I-MI and (125)I-MII) other than parent molecule. (125)I-MI was mainly found in urine, and (125)I-MII was detected both in serum and in urine. The maximal concentration of (125)I-rhTPO was reached at 2 hours after injection. The terminal half-life was 10.8 hours, which was much longer than those of other peptides. TCA precipitable radioactivity in tissue showed that the radioactivity in bone marrow was rather high. The highest level was found in urinary system. Levels in adrenals, lymph nodes, and fat were near to that in serum. Lowest was found in brain. The main excretion route was urinary system and (98 +/- 5.6)% of (125)I-rhTPO was excreted within 72 hours after dosing.
    Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 01/2002; 9(4):318-322.

Publication Stats

64 Citations
32.59 Total Impact Points

Institutions

  • 2012
    • Guangxi Medical University
      Yung-ning, Guangxi Zhuangzu Zizhiqu, China
  • 2003–2010
    • Academy of Military Medical Sciences
      T’ien-ching-shih, Tianjin Shi, China
  • 2005–2007
    • Beijing Institute of Microbiology and Epidemiology
      Peping, Beijing, China