In human patients, drugs that block tumor vessel growth are widely used to treat a variety of cancer types. Many rigorous phase 3 clinical trials have demonstrated signiifcant survival beneifts; however, the addition of an anti-angio-genic component to conventional therapeutic modalities has generally produced modest survival beneifts for cancer patients. Currently, it is unclear why these clinically available drugs targeting the same angiogenic pathways produce dissimilar effects in preclinical models and human patients. In this article, we discuss possible mechanisms of various anti-angiogenic drugs and the future development of optimized treatment regimens.

In a fusion of BABL/C murine spleen cells immunizated with human fetal thymocytes and P_3X_(3)Ag_(,3), myeloma cells, six monoclonal antibodies(McAb) were produced. They were termed HIT_1. HIT_2. HIT_3. HIT_4.HIT_(6-1) and HIT_(6-2), respectively. The specificity of these McAbs were analysed by indirect immunofluorescence technique and FACS.Results showed that they reacted with 80～90%thymocytes,but hardly with peripheral blood mononuclear cells and spleen cells in adults,and nonreactive with red blood cells, granulocytes and platelets, According to their reaction with the tonsil cells, we can divide these six McAbs into three groups: Groupl including HIT_1, HIT_2, and HIT_(?) McAbs reacted approximately with 1/3 tonsil cells; basically GroupⅡ including HIT_(6-1) and HIT_(6-2) McAbs gave negative reaction with tonsil cells; GroupⅢ McAb HIT_4 reacted with 15% tonsil cells, which suggested these were a heterogeneous group McAbs with different specificities. In comparision with OKT series of McAbs in thymus, peripheral blood and tonsil, HIT_(1-3) are similar to OKT_(10) and,HTT6-l and HIT_(6-2) are just like OKT_6,but HIT_4 seems to be a new McAb different frOm HIT_(1-3) and HIT_(6-1) HII_(6-2). The competitive binding assay showed that HIT_(6-1) and HIT_(6-2) labeled with FITC can be inhibited by unlabeled HIT_(6-1) and HIT_(6-2) each other and can also be blocked by OKT_6, suggesting further these antibodies recognized a same epitope on thymocytes. Cross reaction were also demonstrated on HIT_1, and HIT_2 but not on HIT_3, suggesting HIT_1 and HIT_2 recognized the same determinant and HIT_3 recognized another. So six antibodies are McAbs against T cell differentiation antigens.They are useful for research the differentiation of T cells and the classification of malignant lymphadenosis diseases.

Anti-angiogenic drugs (AADs), which mainly target the vascular endothelial growth factor-A signaling pathway, have become a therapeutic option for cancer patients for two decades. During this period, tremendous clinical experience of anti-angiogenic therapy has been acquired, new AADs have been developed, and the clinical indications for AAD treatment of various cancers have been expanded using monotherapy and combination therapy. However, improvements in the therapeutic outcomes of clinically available AADs and the development of more effective next-generation AADs are still urgently required. This review aims to provide historical and perspective views on tumor angiogenesis to allow readers to gain mechanistic insights and learn new therapeutic development. We revisit the history of concept initiation and AAD discovery, and summarize the up-to-date clinical translation of anti-angiogenic cancer therapy in this field.