Showing papers by "Li Yang published in 2009"

Anti-tumor effect of adenovirus-mediated gene transfer of pigment epithelium-derived factor on mouse B16-F10 melanoma

Abstract: Angiogenesis plays an important role in tumor growth, invasion, and eventually metastasis. Antiangiogenic strategies have been proven to be a promising approach for clinical therapy for a variety of tumors. As a potent inhibitor of tumor angiogenesis, pigment epithelium-derived factor (PEDF) has recently been studied and used as an anticancer agent in several tumor models. A recombined adenovirus carrying PEDF gene (Ad-PEDF) was prepared, and its expression by infected cells and in treated animals was confirmed with Western blotting and ELISA, respectively. Its activity for inhibiting human umbilical vein endothelial cell (HUVEC) proliferation was tested using the MTT assay. C57BL/6 mice bearing B16-F10 melanoma were treated with i.v. administration of 5 × 108 IU/mouse Ad-PEDF, or 5 × 108 IU/mouse Ad-Null, or normal saline (NS), every 3 days for a total of 4 times. Tumor volume and survival time were recorded. TUNEL, CD31 and H&E stainings of tumor tissue were conducted to examine apoptosis, microvessel density and histological morphology changes. Antiangiogenesis was determined by the alginate-encapsulated tumor cell assay. The recombinant PEDF adenovirus is able to transfer the PEDF gene to infected cells and successfully produce secretory PEDF protein, which exhibits potent inhibitory effects on HUVEC proliferation. Through inhibiting angiogenesis, reducing MVD and increasing apoptosis, Ad-PEDF treatment reduced tumor volume and prolonged survival times of mouse bearing B16-F10 melanoma. Our data indicate that Ad-PEDF may provide an effective approach to inhibit mouse B16-F10 melanoma growth.

Biodegradable thermosensitive injectable PEG-PCL-PEG hydrogel for bFGF antigen delivery to improve humoral immunity

Abstract: In this contribution, a biodegradable and injectable thermosensitive poly(ethylene glycol)-poly(e-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) hydrogel system was successfully prepared for basic fibroblastic growth factor (bFGF) antigen delivery. bFGF encapsulated PECE hydrogel system (bFGF-hydrogel) is an injectable free-flowing sol at ambient temperature, and forms a non-flowing gel at physiological temperature acting as antigen depot. Furthermore, the cytotoxicity results showed that the PECE hydrogel could be regarded as a safe carrier, and bFGF could be released from the hydrogel system in an extended period in vitro. Otherwise, the immunogenicity of bFGF was improved significantly after encapsulated into the hydrogel. Strong humoral immunity created by bFGF-hydrogel was maintained for more than 14 weeks. Therefore, the prepared bFGF loaded PECE hydrogel might have great potential as a novel vaccine adjuvant for protein antigen.

Gene therapy with the angiogenesis inhibitor endostatin in an orthotopic lung cancer murine model.

Abstract: Angiogenesis plays an important role in the growth of solid tumors. To date, no information has been acquired on the effectiveness of gene therapy in the orthotopic lung cancer model of syngeneic immunocompetent mice treated with an angiogenesis inhibitor. Here, we report the establishment of such a model in which Lewis lung carcinoma (LL/2) cell suspensions were orthotopically inoculated into the lung parenchyma of C57BL/6 mice, which were also injected with a recombinant adenoviral vector delivering the human endostatin gene (Ad-hE). We found that orthotopic implantation of LL/2 cells into the lung parenchyma produced a solitary tumor nodule in the lung followed by remote mediastinal lymph node metastasis. Conditioned medium from Ad-hE-transfected LL/2 cells apparently inhibited proliferation of human umbilical vein endothelial cells (HUVECs). The level of endostatin protein in serum could be identified by enzyme-linked immunosorbent assay. Treatment with Ad-hE resulted in inhibition of tumor growth and prolongation of survival time of tumor-bearing mice. Immunohistochemical analysis revealed that intratumoral angiogenesis was significantly suppressed. Furthermore, the finding of angiogenesis inhibition was also supported by measuring the number of circulating endothelial cells (CECs). Apoptotic cells were found to be increased within tumor tissues from mice treated with Ad-hE. In addition, treatment with Ad-hE combined with cis-diamminedichloroplatinum(II) (cisplatin) enhanced antitumor activity. These observations provide further evidence of the antitumor effect of endostatin gene therapy, and may be of importance for further exploration of potential application of this combined approach in the treatment of human lung cancer as well as other solid tumors.

Ethyl 3-amino-4H-thieno[2,3-b]pyridine-2-carboxyl-ate.

Abstract: The mol­ecule of the title compound, C10H10N2O2S, is essentially planar, except for the ethyl group, which is twisted away from the carboxyl plane by −90.5 (3)°. In the crystal structure, mol­ecules are linked into a zigzag sheet propagating along the b axis by inter­molecular N—H⋯O and N—H⋯N hydrogen bonds.

Intravenous Delivery of Cationic Liposomes Conjugation to Recombinant Adenoviral Vectors Containing Human Endostatin Gene Inhibits Ovarian Cancer Growth in Nude Mice

Abstract: OBJECTIVE To evaluate the anticancer effect of liposome plus Ad-Endostatin complex on human ovarian serous cystocarcinoma. METHODS The recombinant endostatin was expressed in the SKOV3 cells transfected with constructed adenovirus. The nude mice models with human ovarian serous cystocarcinoma were divided into six groups randomly: (1) Ad-hEndo-H plus liposome group (abbreviation: lipo+Ad-hEndo-H), i.v. administration of 1 x 10(9) pfu (plaque-forming units) recombinant adenovirus plus 200 microg liposome (n=5); (2) Ad-hEndo-L plus liposome group (abbreviation: lipo+Ad-hEndo-L), i.v. administration of 1 x 10(8) pfu recombinant adenovirus plus 20 microg liposome (n=5); (3) Ad-hEndo group, i.v. administration of 1 x 10(9) pfu recombinant adenovirus (n=4) (4) Ad-null plus liposome group, i.v. administration of 1 x 10(9) pfu adenovirus plus 200 microg liposome (n=4); (5) liposome group, i.v. administration of liposome 200 microg (n=4) (6) NS group, i.v. administration of equal volume of normal saline as above (n=4). The tumor size was monitored every 7 days. All of the nude mice were sacrificed 49 days after the tumor establishment. The tumors were removed and weighted. The micro-vessel density (MVD) was counted and the apoptotic cells were measured in the tumors tissue by TUNEL. The effect of the antibody of adenovirus was investigated with the SKOV3 cells transfected with liposome-complexed adenovirus. RESULTS The tumors of the mice in the lipo+Ad-hEndo-H and lipo+Ad-hEndo-L groups weighted 54.74% and 70.65% lighter than the NS controls, respectively (P < 0.05). The tumors in the lipo+Ad-hEndo-L and lipo+Ad-hEndo-H groups had fewer MVD and more apoptotic cells than those in the other groups (P < 0.05). The antibody of adenovirus had less impact on the adenovirus capability of transfect when it was combined with liposome than without liposome. CONCLUSIONS The liposome plus Ad-Endostatin complex inhibits the growth of human ovarian serous cystocarcinoma effectively. Lower dose of repeated injection of adenovirus with liposome is preferable.

3-Amino-4,6-dimethyl-thieno[2,3-b]pyridine-2-carbonitrile.

Abstract: The mol­ecule of the title compound, C10H9N3S, is almost planar, with a dihedral angle of 1.38 (4)° between the thio­phene and pyridine rings. In the crystal packing, mol­ecules are linked into layers parallel to the ab plane by inter­molecular N—H⋯N hydrogen bonds and by π⋯π stacking inter­actions involving adjacent pyridine and thio­phene rings with a centroid–centroid distance of 3.537 (3) A.