Overcoming immune tolerance of the growth factors associated with tumor growth should be a useful approach to cancer therapy by active immunity. We used vascular endothelial growth factor (VEGF) as a model antigen to explore the feasibility of the immunogene tumor therapy with a vaccine based on a single xenogeneic homologous gene, targeting the growth factors associated with angiogenesis. To test this concept, we constructed a plasmid DNA encoding Xenopus homologous VEGF (XVEGF-p) and control vectors. We found that immunogene tumor therapy with a vaccine based on XVEGF was effective at both protective and therapeutic antitumor immunity in several tumor models in mice. VEGF-specific autoantibodies in sera of mice immunized with XVEGF-p could be found in Western blotting analysis and ELISA assay. The purified immunoglobulins were effective at the inhibition of VEGFmediated endothelial cell proliferation in vitro, and at antitumor activity and the inhibition of angiogenesis by adoptive transfer in vivo. The elevation of VEGF in the sera of the tumor-bearing mice could be abrogated with XVEGF-p immunization. The antitumor activity and production of VEGF-specific autoantibodies, significantly elevated IgG1 and IgG2b, could be abrogated by the depletion of CD4 ؉ T lymphocytes. The observations may provide a vaccine strategy for cancer therapy through the induction of autoimmunity against the growth factors associated with tumor growth in a cross reaction with single xenogeneic homologous gene and may be of importance in the further exploration of the applications of other xenogeneic homologous genes identified in human and other animal genome sequence projects in cancer therapy.

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A biodegradable sponge, composed of chitosan (CS) and sodium alginate (SA), was successfully obtained in this work. The sponge was ethereal and pliable. The chemical structure and morphology of the sponges was characterized by FTIR and SEM. The swelling ability, in vitro drug release and degradation behaviors, and an in vivo animal test were employed to confirm the applicability of this sponge as a wound dressing material. As the chitosan content in the sponge decreased, the swelling ability decreased. All types of the sponges exhibited biodegradable properties. The release of curcumin from the sponges could be controlled by the crosslinking degree. Curcumin could be released from the sponges in an extended period for up to 20 days. An in vivo animal test using SD rat showed that sponge had better effect than cotton gauze, and adding curcumin into the sponge enhanced the therapeutic healing effect.

A series of biodegradable PCL-PEG-PCL block copolymers were successfully synthesized by ring-opening polymerization of epsilon-caprolactone initiated by poly(ethylene glycol) (PEG), which were characterized by (1)H NMR, (13)C NMR, and FTIR. Their aqueous solution displayed special gel-sol transition behavior with temperature increasing from 4 to 100 degrees C, when the polymer concentration was above corresponding critical gel concentration (CGC). The gel-sol phase diagram was recorded using test tube inverting method and DSC method, which depended not only on chemical composition of copolymers, but also on heating history of copolymer's aqueous solution. As a result, the gel-sol transition temperature could be adjusted, which might be very useful for its application in biomedical fields such as injectable drug delivery system. And the typical shell-core structure of PCL-PEG-PCL micelles was introduced. The micelle-packing and partial crystallization might be the key gelation machanism for this gel-sol transition behavior of PCL-PEG-PCL aqueous solution.

A series of low molecular weight poly(ethylene glycol)-polycaprolactone-poly(ethylene glycol) (PEG-PCL-PEG) biodegradable block copolymers were successfully synthesized using isophorone diisocyanate (IPDI) as the coupling agent, and were characterized using 1 H NMR and Fourier transform infrared spectroscopy. The aqueous solutions of the PEG-PCL-PEG copolymers displayed a special thermosensitive gel-sol transition when the concentration was above the corresponding critical gel concentration. Gel-sol phase diagrams were recorded using the test-tube-inversion method; they depended on the hydrophilic/hydrophobic balance in the macromolecular structure, as well as some other factors, including the heating history, volume, and the ageing time of the copolymer aqueous solutions and dissolution temperature of the copolymers. As a result, the gel-sol transition temperature range could be altered, which might be very useful for application in injectable drug delivery systems.

Fab fragments of rabbit anti-human IgG were immobilized in oriented form on derivatized silica surfaces containing pyridyl disulfide groups. The fragments were also covalently coupled in random form to glutaraldehyde-bound silanized silica surfaces. The surfaces were characterized by X-ray photoelectron spectroscopy and ellipsometry. Antigen binding activities of the immobilized Fab fragments were determined by solid-phase enzyme i"unoassay. The results showed that the changes in orientation of the immobilized fragments drastically influence the antigen binding activity of the fragments, and the antigen binding activity of the fragments in oriented form is 2.7 times higher than that in random form. Such immobilized fragments could find extensive applicability in the design of immunosensors for monitoring of soluble antigens.

Smart hydrogels that undergo structural changes in response to stimuli (for example, pH, heat, light) have promising biomedical applications as delivery systems, especially for the locally controlled release of drugs. Early prevention of locoregional recurrence (LRR) is critical for patients who have undergone breast-conserving therapy. This work reports the preparation of a hybrid hydrogel system in which gold nanorods (GNRs) were doped into a thermally responsive hydrogel. A near-infrared (NIR) laser was used to trigger the release of loaded Doxorubicin (DOX) by utilizing the photothermal effect of GNRs to induce the contraction of the thermo-responsive hydrogels. In a 4T1 breast cancer model of the in vivo locoregional prevention of post-operative recurrence, we found that after NIR irradiation, DOX/GNR-embedded Methoxylpoly(ethylene glycol)-poly(ε-caprolactone)-acryloyl chloride (PECA)/glycidylmethacrylated chitooligosaccharide (COS-GMA)/N-isopropylacrylamide (NIPAm)/acrylamide (AAm) (PCNA) hydrogels (DOX-PCNA-GNR hydrogels) significantly reduced tumor recurrence to 16.7%, compared with 50% for DOX-PCNAGNRs without NIR irradiation, 83.3% for PCNA-GNRs with NIR irradiation, 100% for PCNA-GNRs without NIR irradiation, 83.3% for single systemic or local administration of Dox, 100% for intravenous DOX administration once or three times, and 100% for the blank control. This study demonstrates that these DOX-PCNA-GNR hybrid hydrogels with NIR-triggered thermo-responsive drug release exhibit great potential in preventing post-operation cancer relapse.

To identify the possible microRNAs (miRNAs) which target the polycystic kidney disease-2 gene (PKD2), and clarify effects of the miRNAs on PKD2. We preliminarily used bioinformatics to analyze 3'UTR (3'untranslated regions) of PKD1 and PKD2 in order to predict the potential microRNAs targeted on them. Subsequently, the stable cell lines with overexpression of microRNA-17 (miR-17) were screened, and luciferase assay combined with the mutation 3'UTR of PKD2 were performed to verify PKD2 is the target of miR-17. Moreover, RT-PCR and Western Blotting were used to determine the post-transcriptionally regulation of PKD2 by miR-17. Finally, MTT cell assays allied with PKD2 rescued strategy were employed to evaluate cell proliferation effects. Our study firstly found that the 3'UTR of PKD2 was more conservation than that of PKD1, and microRNA-17 directly targets the 3'UTR of PKD2 and post-transcriptionally repress the expression of PKD2. Moreover, our findings also demonstrated that overexpression of miR-17 may promote cell proliferation via post-transcriptionally repression of PKD2 in HEK 293T. This suggested that microRNA might be a novel mechanism for cystogenesis as well as a potential therapeutic target for the cell proliferation of autosomal dominant polycystic kidney disease (ADPKD).