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Similarly, neutralization of TGF-b in a metastatic orthotopic mouse model of breast cancer again showed that 4T1 inoculated animals that were treated with a control antibody had a twofold number of metastases, as compared with animals that received a TGF-b-neutralizing antibody (13). Given these promising results, investigators have turned their attention to developing a system to delivery the anti-TGF-b fusion molecule to human patients. Investigators believe that a feasible gene therapy approach can be developed by using the fusion protein to transfect an oncolytic adenovirus capable of replicating in all cancer cells, regardless of specific genetic defect (14).
Its clinical significance in esophageal cancer warrants further study. A subgroup of patients considered N0 at standard single-section pathological examination may have occult micrometastases associated with a poor prognosis. Bonavina et al. (27) tested the hypothesis that 59 patients with esophageal adenocarcinoma undergoing resection were studied by standard histological examinations, serial sections, and immunohistochemistry. Their long-term prognoses were then compared. Eight (26%) out of 31 patients previously staged as pN0 at standard histological examination were staged as pN1 or pN2 by serial sections and/or immunohistochemistry and had a prognosis which was significantly worse than that of true pN0 patients (five-year survival: 38 vs.
Sipa1 is a candidate for underlying the metastasis efficiency modifier locus Mtes1. Nat Genet 2005; 37: 1055–1062. 11. Crawford NP, Ziogas A, Peel DJ, et al. Germline polymorphisms in SIPA1 are associated with metastasis and other indicators of poor prognosis in breast cancer. Breast Cancer Res 2006; 8(2): R16. 12. Yang Y, Dukhanina O, Tang B, et al. Lifetime exposure to a soluble TGF-b antagonist protects mice against metastasis without adverse side effects. J Clin Invest 2002; 109(12): 1607–1615.