To characterize molecular mechanism involved in pancreatic carcinogenesis, we analysed gene-expression profiles of 18 pancreatic tumors using a cDNA microarray representing 23,040 genes. As pancreatic ductal adenocarcinomas usually contain a low proportion of cancer cells in the tumor mass, we prepared 95% pure populations of pancreatic cancer cells by means of laser microbeam microdissection, and compared their expression profiles to those of similarly purified, normal pancreatic ductal cells. We identified 260 genes that were commonly upregulated and 346 genes that were downregulated in pancreatic cancer cells. Because of the high degree of purity in the cell populations, a large proportion of genes that we detected as upregulated or downregulated in pancreatic cancers were different from those reported in previous studies. Comparison of clinicopathological parameters with the expression profiles indicated that altered expression of 76 genes was associated with lymph-node metastasis and that of 168 genes with liver metastasis. In addition, expression levels of 30 genes were related to the recurrence of disease. These genome-wide expression profiles should provide useful information for finding candidate genes whose products might serve as specific tumor markers and/or as molecular targets for treatment of patients with pancreatic cancer.

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Studies have been done to determine the optimal dosage of vitamin E. Vitamin E is generally considered to be relatively nontoxic at high dosage in spite of the fact that it is a fat-soluble vitamin. From our experiments using mice, when various dosages of all-rac-alpha-tocopherol were injected into the intraperitoneal cavity every day, 1) the body weight decreased when the dose was more than 100 IU/kg per day, and all the mice died within 3 days at 400 IU/kg per day; 2) immune responses investigated by lymphoproliferative assays with phytohemagglutinin, concanavalin A and lipopolysaccharide were enhanced significantly between 5 and 20 IU/kg per day, but were inhibited by 80 IU/kg per day. When the immunopotentiation effect of vitamin E was discernible, serum tocopherol levels were about twice the control values. From our results, the optimal dosage of vitamin E was between 5 and 20 IU/kg per day, and dosages over 80 IU/kg per day were toxic to mice. We then experimented similarly with vitamin K, which is fat soluble and possesses a quinone structure resembling vitamin E. When doses between 12.5 and 150 mg/kg per day of vitamin K were injected into the intraperitoneal cavity daily fore 14 days, increase of body weight was generally inhibited. This did not depend on the dose, and there was no definite relationship between mitogen responses and vitamin K.

We studied the therapeutic effect of OK-432 combined with adoptive immunotherapy in 19 cases of liver metastases from breast cancer. Of the 14 patients who received intraarterial OK-432 injection and transfer of cultured lymphocytes, 9 responded to this therapy, whereas no patients responded to intravenous administration. The minimum cell number for a therapeutic response was 8 x 10(8) cells. Metastatic lesions other than those in the liver regressed after therapy in 4 patients. The serum carcinoembryonic antigen level paralleled the therapeutic effect. There were no severe side-effects accompanying this therapy. These results indicate that intraarterial adoptive immunotherapy combined with OK-432 is effective as a new therapeutic approach against liver metastases from breast cancer.

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