A novel gene delivery system targeting cells expressing VEGF receptors

Two ligand oligopeptides GV1 and GV2 were designed according to the putative binding region of VEGF to its receptors. GV1, GV2 and endosome releasing oligopeptide HA20 were conjugated with poly-L-lysine or protamine and the resulting conjugates could interact with DNA in a noncovalent bond to form a complex. Using pSV2-β-galactosidase as a reporter gene, it has been demonstrated that exogenous gene was transferred into bovine aortic arch-derived endothelial cells (ABAE) andhuman malignant melanoma cell lines (A375) in vitro. In vivo experiments, exogenous gene was transferred into tumor vascular endothelial cells and tumor cells of subcutaneously transplanted human colon cancer LOVO, human malignant melanoma A375 and human hepatoma graft in nude mice. This system could also target gene to intrahepatically transplanted human hepatoma injected via portal vein in nude mice. These results are correlated with theGene delivery system targeting VEGF receptors relevant receptors (flt-1, flk-1/KDR) expression on the targeted cells and tissues.

Relationship of VEGF/VEGFR with immune and cancer cells:staggering or forward?

Vascular endothelial growth factor(VEGF) is primarily known as a proangiogenic factor and is one of the most important growth and survival factors affecting the vascular endothelium. However, recent studies have shown that VEGF also plays a vital role in the immune environment. In addition to the traditional growth factor role of VEGF and VEGF receptors(VEGFRs), they have a complicated relationship with various immune cells. VEGF also reportedly inhibits the differentiation and function of immune cells during hematopoiesis. Dendritic cells(DCs), macrophages, and lymphocytes further express certain types of VEGF receptors.VEGF can be secreted as well by tumor cells through the autocrine pathway and can stimulate the function of cancer stemness.This review will provide a paradigm shift in our understanding of the role of VEGF/VEGFR signaling in the immune and cancer environment.

EXPRESSION OF VEGF RECEPTOR KDR IN DIFFERENT ORIGINATED CARCINOMAS

Objective: To detect the expression of KDR in different originated carcinomas and to explore its expressed ways and the relationship with tumor progression. Methods : KDR cDNA (V VII domains) fragment was cloned from human umbilical vein with RT PCR and was expressed in Ecoli.Jm109. The fusion protein of GST KDR was used for immunizing Balb/c mice to prepare monoclonal antibodies against KDR. The different tumor tissues and related normal tissues were examined with KDR McAb by S P immuno histochemistry. Results: the rate and intensification of KDR expression among different originated cancers are very different, bladder cancers from transmigrated epidermis are 100% positive and highest intensification. The expression of KDR in breast cancer and intestinal cancer lie in the second rate, the weakest expression of KDR is in lung squamous carcinoma. Moreover, expression of KDR in tumor tissues lie both in endothelial cells (EC) of tumor blood vessels and tumor cells. Conclusion: VEGF may be not only the para secretory factor making EC proliferation but also auto secretory factor stimulating the proliferation of tumor cells to benefit the growth and metastasis of malignant tumors. The different expression of KDR in different originated carcinomas may relate with malignant degree of tumor.

New approaches in angiogenic targeting for colorectal cancer

Colorectal carcinoma （CRC） is one of the leading causes of cancer death worldwide. In the last decade, the addition of irinotecan and oxaliplatin to standard fluorouracil-based chemotherapy regimens have set the new benchmark of survival for patients with metastatic CRC at approximately 20 too. Despite these advances in the management of CRC, there is a strong medical need for more effective and well-tolerated therapies. The dependence of tumor growth and metastasis on blood vessels makes angiogenesis a rational target for therapy. One of the major pathways involved in this process is the vascular endothelial growth factor （VEGF） and its receptors （VEGFR）. In 2004, the first agent targeting angiogenesis, bevacizumab （BV）, was approved as an adjunct to first-line cytotoxic treatment of metastatic CRC. The role of BV as part of adjuvant treatment and in combination with other targeted therapies is the subject of ongoing trials. However, BV is associated with an increase in the risk of arterial thromboembolic events, hypertension and gastrointestinal perforations and its use must be cautious. Novel VEGFR TK inhibitors with different ranges of nanomolar potencies, selectivities, and pharmacokinetic properties are entering phase 111 trials for the treatment of cancer. Conversely, one of these novel agents, vatalanib, has been shown not to confer survival benefit in first and second-line treatment of advanced CRC. The basis of these findings is being extensively evaluated. Ongoing and new well-designed trials will define the optimal clinical application of the actual antiangiogenic agents, and, on the other hand, intensive efforts in basic research will identify new agents with different antiangiogenic approaches for the treatment of CRC. In this review we discuss and highlight current and future approaches in angiogenic targeting for CRC.

Therapeutic potential of traditional Chinese medicine for vascular endothelial growth factor

Vascular endothelial growth factor(VEGF)is the main regulator of physiological angiogenesis during embryonic development,bone growth,and reproductive function,and it also participates in a series of pathological changes.Traditional Chinese medicine(TCM),with a history of more than 2000 years,has been widely used in clinical practice,while the exploration of its mechanisms has only begun.This review summarizes the research of recent years on the influence of TCM on VEGF.It is found that many Chinese medicines and recipes have a regulatory effect on VEGF,indicating that Chinese medicine has broad prospects as a complementary and alternative therapy,providing new treatment ideas for clinical applications and the theoretical basis for research on the mechanisms of TCM.