Feng-Ying Huang

Hainan Medical College, Haikou, Yunnan, China

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Publications (23)45.81 Total impact

  • Molecules 04/2015; 20(4):5714-5728. DOI:10.3390/molecules20045714 · 2.42 Impact Factor
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    ABSTRACT: Keywords: Tumor vaccine Macrophage inflammatory protein 3a Tumor suppressive microenvironment DC vaccine a b s t r a c t The combination of several potential strategies so as to develop new tumor vaccines is an attractive field of translational medicine. Pulsing tumor lysates with dendritic cells (DCs), in-vivo attraction of DCs by macrophage inflammatory protein 3a (MIP-3a), and reversion of the tumor suppressive microenviron-ment have been tested as strategies to develop tumor vaccines. In this study, we generated an alginate microsphere (named PaLtTcAdMIP3a) that encapsulated tumor lysates, live tumor cells engineering with a recombinant MIP-3a adenovirus and BCG. We used PaLtTcAdMIP3a as a model vaccine to test its antitumor activities. Our results showed that PaLtTcAdMIP3a expressed and excreted MIP-3a, which effectively attracted DCs ex vivo and in vivo. Injection of PaLtTcAdMIP3a into tumor-bearing mice effectively induced both therapeutic and prophylactic antitumor immunities in CT26, Meth A, B16-F10 and H22 models, but without any ensuing increase in adverse effects. Both tumor-specific cellular and humoral immune responses, especially the CD8 þ T cell-dependent cytotoxic T immunity, were found in the mice injected with PaLtTcAdMIP3a. The anti-tumor activity was abrogated completely by depletion of CD8 þ and partially by CD4 þ T lymphocytes. In addition, the number of IFN-g-producing CD8 þ T cells in spleen and tumor tissues was significantly increased; but the number of CD4 þ CD25 þ FOXP3 þ regulatory T cells (Treg) in tumor tissues was decreased. These data strongly suggest that a combination of multi-current-using strategies such as the novel approach of using our PaLtTcAdMIP3a microspheres could be an effective tumor model vaccine.
    Biomaterials 03/2015; 53. DOI:10.1016/j.biomaterials.2015.02.123 · 8.31 Impact Factor
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    ABSTRACT: Various angiogenesis-related self-molecules have been considered to be therapeutic targets. However, the direct use of self-molecules as vaccines is not recommended because of the inherent ability of the host to develop immune tolerance. Antigen 43 (Ag43) is a surface protein found in E. coli and contains an α and a β subunits, which contains multiple T epitopes in α subunit. Here we construct a novel Ag43 surface display system (Ag43 system) to express Ag43 chimeric proteins to disrupt immune tolerance against self-molecules. The Ag43 system was constructed from an Escherichia coli strain Tan109, derived from JM109, in which the Ag43 gene was deleted and a recombinant plasmid (pETAg43') expressing a partial Ag43 gene was introduced. The extracellular domain of angiogenesis-related endoglin gene was then subcloned into plasmid pETAg43', resulting in a recombinant plasmid pETAg43'/END(e) which was then used to transform Tan109 for protein expression. We found that Ag43 and endoglin chimeric protein (Ag43'/END(e) ) was expressed on the bacterial surface. The chimeric protein could be separated from the bacterial surface by heating to 60°C and yet retain activity. We used Ag43'/END(e) as a protein vaccine and found that it could disrupt immune tolerance against endoglin by inducing significant antitumor activities and inhibit angiogenesis in several tumor models without significant side effects. These data suggest that Ag43'/END(e) chimeric protein is a potential model vaccine for active tumor immunotherapy, and that Ag43 system could be an effective tool for novel vaccine preparation to break immune tolerance to other angiogenesis-related self-molecules for cancer therapy.
    International Journal of Cancer 04/2014; 134(8). DOI:10.1002/ijc.28511 · 5.01 Impact Factor
  • Huan-Ge Zhao · Feng-Ying Huang · Jun-Li Guo · Guang-Hong Tan
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    ABSTRACT: To examine the immunoprotection effect induced by MIC8 DNA vaccine co-immunized with a plasmid encoding murine IL-12 (pcIL-12) as an adjuvant in mice against the challenge of Toxoplasma gondii. The gene sequence encoding MIC8 of T. gondii RH strain was inserted into eukaryotic expression vector pcDNA3.1 to construct the pcMIC8 expression plasmid. The recombinant plasmid was transfected into HeLa cells to test its expression and the recombinant protein was then characterized by Western blotting. Eighty Kunming mice were randomly divided into 5 groups (16 per group): 3 control groups (PBS, pcDNA3.1, and pcIL-12), pcMIC8 group, and pcMIC8 plus pcIL-12 group. Mice in the pcMIC8 plus pcIL-12 group were co-injected intramuscularly at a dosage of 100 microl each of pcMIC8 and pcIL-12 suspended in 100 microg sterile PBS. Mice in other groups were inoculated with PBS, pcDNA3.1, pcIL-12, and pcMIC8 respectively following the same protocol. All the mice received three immunizations at 2-week intervals. Serum samples were collected on day 0, 13, 27, 41, and 55 before each inoculation for determining antibody IgG, IgG subclass IgG2a. Four weeks after the final immunization, IFN-gamma and IL-4 levels in splenocytes cultures from immunized mice were detected by ELISA. The mice were challenged with 10(3) tachyzoites of the virulent T. gondii RH strain three weeks after the last immunization to observe the survival time. Western blotting showed that the protein extracts in HeLa cells upon transfection with pcMIC8 were effectively expressed in cells. The levels of IgG (0.51 +/- 0.028) and IgG2a (0.261 +/- 0.04)(on day 55) in mice immunized with pcMIC8 plus pcIL-12 were higher than pcMIC8 group (497.65 +/- 98.15) and control groups (PBS 47.18 +/- 2.73, pcDNA3.1 50.08 +/- 4.62, pcIL-12 118.15 +/- 12.73) (P < 0.05). There was no significant difference in the level of IgG 1 and IL-4 among the five groups (P > 0.05). After a lethal challenge of T. gondii RH strain, the survival time in mice immunized with pcMIC8 plus pcIL-12 (15d) was prolonged in comparison to that of pcMIC8 (10d) and control groups (PBS 5 d, pcDNA3.1 6d, pcIL-12 8 d) (P < 0.05). The immune responses induced by the combined use of the recombinant plasmid encoding MIC8 of T. gondii with murine IL-2 gene adjuvant can be enhanced.
    Zhongguo ji sheng chong xue yu ji sheng chong bing za zhi = Chinese journal of parasitology & parasitic diseases 08/2013; 31(4):284-9.
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    ABSTRACT: Cytochalasin D (CytD) targets actin, a ubiquitous protein in eukaryotic cells. Previous studies have focused mainly on the antitumor effects of CytD. We previously found CytD to promote lung metastasis in B16 melanoma cells, which we had not anticipated, and, therefore, in the present study we investigated the possible underlying mechanisms. B16 melanoma cells were co-cultured with CytD and other agents and used to establish a lung metastatic model. In this B16 melanoma metastatic model, significantly increased lung metastasis and lung weight were found in CytD-treated mice, which was almost completely suppressed by tissue factor (TF) RNA interference expressed via lentivirus. The results of northern and western blot, and real-time RT-PCR analysis showed that the expression of TF was significantly upregulated in B16 cells treated with CytD but was significantly inhibited by TF RNA interference. In addition, upregulation and phosphorylation of mitogen-activated protein kinase p38 were also found in the metastatic lung tissues treated with CytD and in the B16 cells co-cultured with CytD and factor VIIa (FVIIa), but not in cells cultured with CytD, dimethyl sulfoxide or FVIIa alone. These results indicate that CytD stimulates the expression of TF in B16 melanoma cells, activating both coagulation-dependent and -independent pathways via binding to FVIIa, eventually promoting lung metastasis. TF interference is a potential approach to the prevention of B16 melanoma metastasis.
    Oncology Reports 04/2013; 30(1). DOI:10.3892/or.2013.2423 · 2.19 Impact Factor
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    ABSTRACT: To observe the immune response induced by complex gene vaccine pcSAG1-ROP5 of Toxoplasma gondii in mice. The recombinant eukaryotic expression plasmids pcSAG1, pcROP5 and pcSAG1-ROP5 were constructed and identified by PCR, restriction enzyme digestion, and sequencing. The three recombinant plasmids were transfected into HeLa cells to express in vitro and identified by Western blotting analysis. Seventy Kunming mice were randomly divided into 5 groups with 14 each, i.e. pcSAG1 group, pcROP5 group, pcSAG1-ROP5 group, blank plasmid group and PBS control group. The mice were immunized intramuscularly with pcSAG1, pcROP5, pcSAG1-ROP5, pcDNA3.1, and PBS, respectively, every two weeks for three times. Sera were collected before each injection and 2 weeks after the last immunization. The titer of mice serum in pcSAG1-ROP5 group combined with recombinant protein SAG1, ROP5 and SAG1-ROP5 and the level of IgG against T. gondii in 5 groups were determined by ELISA. Three weeks after the last immunization, ten mice of each group were challenged with 10(3) tachyzoites of the virulent T. gondii RH strain to observe the survival time. One week later, the rest four mice in each group were sacrificed and the supernant of cultured splenocytes was collected for the detection of IFN-gamma and IL-4. Western blotting showed that the recombinant plasmids pcSAG1, pcROP5 and pcSAG1-ROP5 were expressed in HeLa cells with M(r) 31 000, 57 000, and 88 000, respectively. The serum titer in pcSAG1-ROP5 group combined with SAG1, ROP5 and SAG1-ROP5 was 1:320, 1:160, and 1:2560, respectively. The IgG level kept rising in pcSAG1, pcROP5 and pcSAG1-ROP5 groups. Two weeks after the last immunization, the IgG level in pcSAG1-ROP5 group was higher than those in other groups (P<0.05). After a lethal challenge of T. gondii RH strain, the survival time of the mice in pcSAG1-ROP5 group was (288 +/- 7) h, which was 48 h and 96h longer than the groups of pcSAG1 and pcROP5, respectively (P< 0.05). Four weeks after the last immunization, IFN-gamma in splenocyte culture of pcSAG1-ROP5 group [(908.52 +/- 6.31) pg/ml] was higher than other groups (P<0.05), with no significant difference in IL-4 (P>0.05). Compared with the single gene vaccines pcSAG1 and pcROP5, higher levels of IgG and IFN-gamma and longer survival time are observed in mice immunized with pcSAG1-ROP5.
    Zhongguo ji sheng chong xue yu ji sheng chong bing za zhi = Chinese journal of parasitology & parasitic diseases 02/2013; 31(1):1-5.
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    ABSTRACT: Novel antibacterial agents against Mycobacterium tuberculosis (MTB) are crucial due to the high infection and mortality rates associated with the disease. Our previous study confirmed that aptamers from a whole bacterium obtained by the Systematic Evolution of Ligands by Exponential Enrichment method specifically bound to the MTB virulent strain (H37Rv). In the present study, the function of aptamers against MTB in a mouse model was further determined. It was demonstrated that the NK2 aptamer has marked inhibitory effects on the adhesion/invasion of H37Rv to macrophages in vitro and stimulates intracellular IFN-γ production in CD4+ T-cells. The aptamer pool exhibited the strongest inhibitory effect on H37Rv adhesion/invasion to CD8+ T-cells in vitro compared with all aptamers-treated and control groups. Histopathological examination of lung biopsy specimens revealed a correlation between aptamer presence and lower pulmonary alveoli fusion, swelling and more prominent air spaces. Acid-fast staining of biopsy specimens from the lungs of the mice demonstrated parallel treatment effects. Results of the present study indicate that the 10th pool aptamers and NK2 may play an active role against H37Rv, however, the effect was different in vivo and in vitro. The treatment effect of 10th pool aptamers was found to be better in comparison to NK2 in vivo. Additional target sites involved in pathogenicity of H37Rv were also revealed and the NK2 binding site and aptamers, including the 10th pool aptamers, may antagonize these sites. Further studies are required to screen for other valuable aptamers which may be used as therapeutic drugs in combination with NK2.
    Molecular Medicine Reports 12/2012; 7(2). DOI:10.3892/mmr.2012.1229 · 1.48 Impact Factor
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    ABSTRACT: Toxicarioside A is a cardenolide isolated mainly from plants and animals. Emerging evidence demonstrate that cardenolides not only have cardiac effects but also anticancer effects. In this study, we used in vivo models to investigate the antitumor activities of toxicarioside A and the potential mechanisms behind them. Murine colorectal carcinoma (CT26) and Lewis lung carcinoma (LL/2) models were established in syngeneic BALB/c and C57BL/6 mice, respectively. We found that the optimum effective dose of toxicarioside A treatment significantly suppressed tumor growth and angiogenesis in CT and LL/2 tumor models in vivo. Northern and Western blot analysis showed significant inhibition of endoglin expression in toxicarioside A-treated human umbilical vein endothelial cells (HUVECs) in vitro and tumor tissues in vivo. Toxicarioside A treatment significantly inhibited cell proliferation, migration and invasion, but did not cause significant cell apoptosis and affected other membrane protein (such as CD31 and MHC I) expression. In addition, TGF-β expression was also significantly inhibited in CT26 and LL/2 tumor cells treated with toxicarioside A. Western blot analysis indicated that Smad1 and phosphorylated Smad1 but not Smad2/3 and phosphorylated Smad2/3 were attenuated in HUVECs treated with toxicarioside A. Smad1 and Smad2/3 signaling remained unchanged in CT26 and LL/2 tumor cells treated with toxicarioside A. Endoglin knockout by small interfering RNA against endoglin induced alternations in Smad1 and Smad2/3 signaling in HUVECs. Our results indicate that toxicarioside A suppresses tumor growth through inhibition of endoglin-related tumor angiogenesis, which involves in the endoglin/TGF-β signal pathway.
    PLoS ONE 11/2012; 7(11):e50351. DOI:10.1371/journal.pone.0050351 · 3.23 Impact Factor
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    ABSTRACT: To study the antitumor efficacy of an immunoconjugate composed of adriamycin (ADM) and downsized Fab fragment of mouse anti-Endoglin monoclonal antibody. The Fab fragment of mouse anti-Endoglin monoclonal antibody was downsized and conjugated with ADM by m-Maleimidobenzoyl-N-hydroxysuccinimide ester (MBS). The antitumor effect of the conjugate was tested in mice bearing subcutaneous injection of H22 tumor in vivo. The molecular ratio of Fab:ADM in conjugate was approximately 1:2. The Fab-ADM conjugate inhibited the growth of H22 by 91.94% on day 14 after injection at the dose of 0.4 mg/ kg, much higher the inhibition rate of 25.00% by the equivalent dose of free ADM. The median survival time of the mice treated with the conjugate was longer than those treated with free ADM. The Fab-ADM conjugate was significantly more effective than free ADM in tumor suppression and life span prolongation. Fab -ADM displayed more significant antitumor efficacy than free ADM in vivo and might be a novel candidate for cancer treatment.
    Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition 05/2012; 43(3):340-3.
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    ABSTRACT: To investigate the inhibitory role of toxicarioside A on the gastric cancer cell line human gastric cancer cell line (SGC-7901) and determine the underlying molecular mechanism. After SGC-7901 cells were treated with toxicarioside A at various concentrations (0.5, 1.5, 4.5, 9.0 μg/mL) for 24 h or 48 h, cell viability was determined by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay, and the motility and invasion of tumor cells were assessed by the Transwell chamber assay. Immunofluorescence staining, reverse transcription polymerase chain reaction and Western blotting were performed to detect the expression of basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor-1 (FGFR1), and nuclear factor-kappa B (NF-κB) activation was examined by electrophoretic mobility shift assay. The results showed that toxicarioside A was capable of reducing cell viability, inhibiting cell growth, and suppressing cell migration and invasion activities in a time- and dose-dependent manner in SGC-7901 cells. Further analysis revealed that not only the expression of bFGF and its high-affinity receptor FGFR1 but also the NF-κB-DNA binding activity were effectively blocked by toxicarioside A in a dose-dependent manner compared with the control group (P < 0.05 or P < 0.01). Interestingly, application of the NF-κB specific inhibitor, pyrrolidinedithiocarbamate (PDTC), to SGC-7901 cells significantly potentized the toxicarioside A-induced down-regulation of bFGF compared with the control group (P < 0.05). These findings suggest that toxicarioside A has an anti-gastric cancer activity and this effect may be achieved partly through down-regulation of NF-κB and bFGF/FGFR1 signaling.
    World Journal of Gastroenterology 04/2012; 18(14):1602-9. DOI:10.3748/wjg.v18.i14.1602 · 2.43 Impact Factor
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    Feng-Ying Huang · Yue-Nan Li · Wen-Li Mei · Hao-Fu Dai · Peng Zhou · Guang-Hong Tan
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    ABSTRACT: To investigate whether cytochalasin D can induce antitumor activities in a tumor model. Murine CT26 colorectal carcinoma cells were cultured in vitro and cytochalasin D was used as a cytotoxic agent to detect its capabilities of inhibiting CT26 cell proliferation and inducing cell apoptosis by MTT and a TUNEL-based apoptosis assay. Murine CT26 tumor model was established to observe the tumor growth and survival time. Tumor tissues were used to detect the microvessel density by immunohistochemistry. In addition, alginate encapsulated tumor cell assay was used to quantify the tumor angiogenesis in vivo. Cytochalasin D inhibited CT26 tumor cell proliferation in time and dose dependent manner and induced significant CT26 cell apoptosis, which almost reached the level induced by the positive control nuclease. The optimum effective dose of cytochalasin D for in vivo therapy was about 50 mg/kg. Cytochalasin D in vivo treatment significantly inhibited tumor growth and prolonged the survival times in CT26 tumor-bearing mice. The results of immunohistochemistry analysis and alginate encapsulation assay indicated that the cytochalasin D could effectively inhibited tumor angiogenesis. Cytochalasin D inhibits CT26 tumor growth potentially through inhibition of cell proliferation, induction of cell apoptosis and suppression of tumor angiogenesis.
    Asian Pacific Journal of Tropical Medicine 03/2012; 5(3):169-74. DOI:10.1016/S1995-7645(12)60019-4 · 0.93 Impact Factor
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    ABSTRACT: To investigate possible mechanism of toxicarioside A in HS-5 bone stromal cells. HS-5 bone stromal cells were cultured in media supplemented with various concentrations of toxicarioside A or control DMSO (not treatment). Endoglin and TGF-β were detected by Northern and Western blot analysis and quantified in a standard method. Downstream molecules of endoglin and TGF-β (Smad1, Smad2 and their active phosphorylated counterparts, pSmad1 and pSmad2) were also detected and quantified by Western blot analysis. In addition, cell proliferation assay and small interfering RNA (siRNA) against endoglin were used to certificate the function of endolgin in the HS-5 cells. Compared with the not treated (0 μg/mL) or DMSO treated control HS-5 cells, HS-5 cells treated with toxicarioside A were found significant attenuation of endolgin and TGF-β expression. Significant inhibition of cell proliferation was also found in the HS-5 cells treated with toxicarioside A. ALK1-related Smad1 and ALK5-related Smad2 were decreased in HS-5 cells treated with toxicarioside A. In addition, phosphorylated Smad1 (pSmad1) and Smad2 (pSmad2) were also found attenuation in toxicarioside A-treated HS-5 cells. RNA interference showed that blockage of endoglin by siRNA also decreased Smad1 and Smad2 expression in HS-5 cells. Our results indicate that toxicarioside A can influence bone marrow stromal HS-5's function and inhibit HS-5 cell proliferation by alteration of endoglin-related ALK1 (Smad1) and ALK5 (Smad2) signaling.
    Asian Pacific Journal of Tropical Medicine 02/2012; 5(2):91-7. DOI:10.1016/S1995-7645(12)60002-9 · 0.93 Impact Factor
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    ABSTRACT: Cytochalasin D targets actin and is ubiquitous in eukaryotic cells. When cytochalasin D is used as a cytotoxic agent in cancer therapy, it causes significant side effects. To prevent this, cytochalasin D can be encapsulated in polyethylene liposomes. In this study, high-performance liquid chromatography observation of the biodistribution of pegylated liposomal cytochalasin D in tumour-bearing mice showed that liposomal cytochalasin D could be conveniently dissolved in water for i.v. injection and that it specifically accumulated in tumour tissues, more than natural cytochalasin D did. The half-time of liposomal cytochalasin D in the plasma was also significantly longer than that of natural cytochalasin D (4h versus 10 min). MTT 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that liposomal cytochalasin D treatment could cause significant inhibition of cell proliferation in vitro in a manner similar to that of natural cytochalasin D. The antitumour activities of liposomal cytochalasin D were investigated in B16 melanoma, CT26 colorectal carcinoma and H22 hepatoma models, and the results indicated that liposomal cytochalasin D could significantly inhibit tumour growth and prolong survival in a manner similar to that of cisplatin. TUNEL-based apoptosis assays showed that liposomal cytochalasin D induced significant tumour cell apoptosis. Significant inhibition of tumour angiogenesis was observed in mice treated with liposomal cytochalasin D. In addition, no significant side effects were observed in mice treated with liposomal cytochalasin D. Our results show that liposomal cytochalasin D increases solubility and bioavailability, a lower incidence of side effects and improves antitumour effects, indicating its potential as a chemical agent for cancer therapy.
    European journal of cancer (Oxford, England: 1990) 01/2012; 48(14):2260-9. DOI:10.1016/j.ejca.2011.12.018 · 4.82 Impact Factor
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    ABSTRACT: Interleukin-5 (IL-5) involves in the development of airway inflammation and hyperresponsiveness through activation of eosinophils. Thus, inhibition of IL-5 expression seems to be an attractive approach for asthma therapy. In this study, an antisense IL-5 gene transferred by recombinant adeno-associated virus (asIL-5) was constructed to transfect murine allergic asthma model. Our results showed that asIL-5 efficiently inhibited the IL-5 mRNA expression and significantly attenuated the inflammation in lung tissues. Significant decreasing of eosinophils and inflammatory cells were found in peripheral blood and bronchoalveolar lavage fluid (BALF). In addition, significant inhibition of airway hyperresponsiveness (AHR) was also found in the mice treated with asIL-5. These observations demonstrate that antisense oligonucleotid against IL-5 delivered by adeno-associated virus system is possibly an efficacious therapeutic strategy for allergic asthma and other eosinophil-related disorders.
    Asian Pacific journal of allergy and immunology / launched by the Allergy and Immunology Society of Thailand 04/2009; 27(1):35-41. · 1.26 Impact Factor
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    ABSTRACT: Interleukin-5 (IL-5) accompanies the development of airway inflammation and hyperresponsiveness through the activation of eosinophils. Therefore, interference of IL-5 expression in lung tissue seems to be an accepted approach in asthma therapy. In this study, we designed a small interfering RNA (siRNA) to inhibit the expression of IL-5. The siRNAs against IL-5 were constructed in a lentivirus expressing system, and 1.5x10(6) IFU (inclusion-forming unit) lentiviruses were administered intratracheally to ovalbumin (OVA)-sensitized murine asthmatic models. Our results show that lentivirus-delivered siRNA against IL-5 efficiently inhibited the IL-5 messenger ribonucleic acid (mRNA) expression and significantly attenuated the inflammation in lung tissue. Significant decrease of eosinophils and inflammatory cells were found in peripheral blood, bronchoalveolar lavage fluid (BALF), and lung tissue. In addition, significant inhibition of airway hyperresponsiveness (AHR) was found in the mice treated with siRNA against IL-5. These observations demonstrate that siRNA delivered by means of the lentivirus system is possibly an efficacious therapeutic approach for asthma.
    Journal of Zhejiang University SCIENCE B 01/2009; 10(1):22-8. DOI:10.1631/jzus.B0820226 · 1.29 Impact Factor
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    ABSTRACT: Induction of tumor vasculature occlusion by targeting a thrombogen to newly formed blood vessels in tumor tissues represents an intriguing approach to the eradication of primary solid tumors. In the current study, we construct and express a fusion protein containing vascular endothelial growth factor (VEGF) and tissue factor (TF) to explore whether this fusion protein has the capability of inhibiting tumor growth in a colon carcinoma model. The murine cDNA of VEGF A and TF were amplified by reverse transcriptase polymerase chain reaction (RT-PCR), and then cloned into prokaryotic expression plasmid pQE30 with a linker. The expression product recombinant VEGF-TF (rVEGF-TF) was purified and proved to have comparable enzyme activity to a commercial TF and the capability of specific binding to tumor vessels. Significant decrease of tumor growth was found in the mice administered with rVEGF-TF on Day 6 after initiated rVEGF-TF treatment (P<0.05), and the tumor masses in 2 of 10 mice were almost disappeared on Day 14 after the first treatment. In addition, valid thrombogenesis and tumor necrosis were observed in the tumor tissues injected with rVEGF-TF. Our results demonstrate that occlusion of tumor vasculature with rVEGF-TF is potentially an effective approach for cancer therapy.
    Journal of Zhejiang University SCIENCE B 08/2008; 9(8):602-9. DOI:10.1631/jzus.B0820120 · 1.29 Impact Factor
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    ABSTRACT: Eosinophils play a pivotal role in the generation of asthma inflammation. Interleukin (IL)-5 is the major activator of eosinophils. We hypothesize that modulating IL-5 activity could be an effective strategy for asthma therapy. In this study, we tested whether the plasmid encoding human IL-5 as a xenogeneic DNA vaccine could induce the production of autoantibodies, and be used for asthma treatment. A eukaryotic plasmid encoding the human IL-5 was constructed, and used as a DNA vaccine. A mouse model of asthma was established to observe its antiasthma activities. Eosinophils in tissue, blood and the bronchoalveolar lavage were stained and counted. Airway hyperresponsiveness (AHR) was determined by whole body plethysmography. Antibody characters and cytokines were detected with immunological methods. Immunization with a plasmid encoding the human IL-5 as DNA vaccine reduced airway inflammation, reversed Th2 cytokines, and decreased AHR in mice. In addition, this immunization induced the production of polyclonal antibodies that were cross-reactive with native murine IL-5, and IgG1 and IgG2a were the major subclasses. Adoptive transfer of the purified antibodies from the sera of mice immunized with the plasmid encoding the human IL-5 resulted in similar antiasthma effects. Our results suggest that active vaccination against IL-5 may be a rational therapeutic approach for the treatment of asthma and potentially other eosinophilic disorders.
    International Archives of Allergy and Immunology 02/2008; 145(4):313-23. DOI:10.1159/000110890 · 2.43 Impact Factor
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    ABSTRACT: Eosinophils are highly related to allergic asthma inflammation. Interleukin (IL)-5 is the major chemokine of eosinophils, inhibition of the activity of IL-5 thus seems to be a potential approach to asthma therapy. The current study was performed to determine whether a recombinant human IL-5 protein as a xenogeneic vaccine has the capability of inducing anti-asthma activities. Recombinant human IL-5 was used as a protein vaccine. Mouse asthma model was established to observe the anti-asthma activities. Lung histology was observed; eosinophils in blood and bronchoalveolar lavage were stained and counted. Airway hyperresponsiveness was determined by whole body plethysmograph. Antibody characters and cytokines were detected with enzyme linked immunosorbent assay (ELISA) and Western blot assay. Vaccination with recombinant human IL-5 protein as vaccine significantly reduced airway inflammation and airway hyperresponsiveness, and shifted the cytokine production from Th2 (IL-4) to Th1 (INF-gamma) in mice allergic-asthma model. Immunization with recombinant human IL-5 protein vaccine bypassed the immunological tolerance and induced production of polyclonal antibodies that were cross-reactive with murine IL-5. Active immunization with xenogeneic homologous IL-5 may be a possible therapeutic approach to the treatment of asthma and potentially of other eosinophilic disorders.
    Chinese medical journal 10/2007; 120(17):1517-22. · 1.02 Impact Factor
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    ABSTRACT: To explore the capability of a monoclonal antibody (mAb) against murine endoglin to inhibit tumor angiogenesis and suppression of hepatoma growth in murine models. A monoclonal antibody against murine endoglin was purified by affinity chromatography and passively transfused through tail veins in two murine hepatoma models. Tumor volume and survival time were observed at three-day intervals for 48 d. Microvessels in tumor tissues were detected by immunohistochemistry against CD31, and angiogenesis in vivo was determined by alginate encapsulated assay. In addition, tumor cell apoptosis was detected by TUNEL assay. Passive immunotherapy with anti-endoglin mAb could effectively suppress tumor growth, and prolonged the survival time of hepatoma-bearing mice. Angiogenesis was apparently inhibited within the tumor tissues, and the vascularization of alginate beads was also reduced in the mice passively transfused with anti-endoglin mAb. In addition, increased apoptotic cells were observed within the tumor tissues from the mice passively transfused with anti-endoglin mAb. Passive immunotherapy with anti-endoglin mAb effectively inhibits tumor growth via inhibiting tumor angiogenesis and increasing tumor cell apoptosis, which may be highly correlated with the blockage of endoglin-related signal pathway induced by anti-endoglin mAb.
    World Journal of Gastroenterology 06/2007; 13(17):2479-83. · 2.43 Impact Factor