The breaking of immune tolerance against autologous angiogenic endothelial cells should be a useful approach for cancer therapy. Here we show that immunotherapy of tumors using fixed xenogeneic whole endothelial cells as a vaccine was effective in affording protection from tumor growth, inducing regression of established tumors and prolonging survival of tumor-bearing mice. Furthermore, autoreactive immunity targeting to microvessels in solid tumors was induced and was probably responsible for the anti-tumor activity. These observations may provide a new vaccine strategy for cancer therapy through the induction of an autoimmune response against the tumor endothelium in a cross-reaction.

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.

In the present study, we examined the relationship between Beclin-1 expression and HIF-1α expression in esophageal squamous cell carcinoma(ESCC). There was a loss of Beclin-1 protein expression in 33% of ESCCs. Beclin-1 expression significantly correlated with depth of invasion, lymph node metastasis and clinical stage. Among the 54 patients, The survival rate of the Beclin-1-positive group was better than that of the Beclin-1-negative group. Twenty-five of the 54 (46%) tumor specimens showed high levels of HIF-1α immunoreactivity. Beclin-1 expression was associated with HIF-1α expression. The survival rate of patients with Beclin-1-positive and HIF-1α-low tumors was significantly higher than that of the other groups. These results suggest that Beclin-1 and HIF-1α expression are important determinants of survival in ESCCs.

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Use of stiffness values measured in the liver parenchyma at more than 2 cm from the lesion allowed better diagnostic performance than did values measured in a region closer to the tumor. Stiffness value was more accurate than stiffness ratio for differentiation of malignant from benign focal liver lesions, but the stiffness ratio might be useful for subclassification of benign and malignant lesions. Online supplemental material is available for this article.