Background: In order to prevent tumor metastasis, we investigated more effective inhibition by combination therapy. The competition with native adhesion molecules by cell-binding domain, inhibition of neovascularization with angiogenesis inhibitor TNP-470, and intracellular regulation of store-operated Ca2+ entry by Ca2+ channel blocker. Methods: The cell-binding domain obtained from fibronectin included the Arg-Gly-Asp (RGD) sequence. Tumor metastasis model was created by injecting colon 26/TC-1 cells to CDF1 mice. A fibronectin- binding domain (FND)-treated group, an FND plus TNP-470 group, an FND plus Ca2+ channel blocker (nilvadipine) group, and a control group were established.The mice were sacrificed 4 weeks later and their livers were excised to count the metastatic tumor nodules. And the other study, the mice were not sacrificed and their survival was observed. Results: The mean number of nodules in the FND plus TNP-470 group was significantly smaller than in the control group (P=0.019337), and FND and nilvadipine was significantly smaller than the control group (P< 0.05). The inhibition rate was 51% in the FND group, 64% in the FND (10g) and TNP-470 (100 mg/kg) group, 56% in the inhibition rate in the FND (10g) and nilvadipine (100g) group. The combined effect of FND (10g) and TNP-470 (100 mg/kg) was greater than other treatment. In the survival, all mice died after 4-6 weeks in the control group, the FND plus nilvadipine group mice died after 8-2 weeks. Conclusions: Combination therapy blocks different steps in the process of metastasis may be effective treatment with the non-cytotoxic agents.
There are no strategies to predict a patient's response to therapy. In a previous report, we classified Japanese patients into four groups according to the incidence of HLA antigens, by using the quantification method III. We examined the HLA antigens of patients before surgery and evaluated their outcome according to the HLA classification by this quantification method. We also reported that HLA-oriented therapy was better than old fashioned therapy. The aim of the present study was to evaluate whether HLA classification is useful in the treatment of individual cancer patients, by using a consecutive retrospective study series of 1932 patients from Jan 1977 to May 1996 and a consecutive prospective study series of 582 patients from Jun 1996 to Aug 2005, all of whom received gastrectomies. There were significant differences between male patients who agreed to get the recommended therapy (the patients in agreement) and those who did not (the patients in disagreement), those with lymph node metastasis, those with undifferentiated adenocarcinoma, and those in stage 3A. Moreover, stage 2 and 3A patients benefitted from HLA-oriented therapy in a prospective study. In conclusion, our results showed that it is beneficial to examine HLA antigens preoperatively, that HLA-oriented therapy is promising, and that we must determine predictive factors for response to therapy in the future. We concluded that HLA antigens are promising predictive markers for cancer treatment.