Summary It is known that angiogenesis plays an important role in the growth and metastasis of solid tumours. Several angiogenic factors have been identified and platelet-derived endothelial cell growth factor (PD-ECGF) is thought to be one such factor. Recently, it was reported that thymidine phosphorylase (dThdPase) is identical to PD-ECGF. Using immunohistochemical staining with an anti-dThdPase antibody, we investigated the correlation between dThdPase expression and the microvessel density in 120 gastric carcinomas. The microvessel density, determined by immunostaining for factor VIII-related antigen, was significantly higher in dThdPase-positive tumours than in dThdPase-negative tumours. There was a significant correlation between dThdPase expression and the increment of microvessel density. Moreover, regarding distant organ metastasis, the frequency of hepatic metastasis was significantly higher (P<0.01) in patients with dThdPase-positive tumours than in those with dThdPase-negative tumours. In summary, it was suggested that dThdPase expression is closely associated with the promotion of angiogenesis and hepatic metastasis in gastric carcinoma.

Thymidine Phosphorylase (dThdPase) is the rate-tissues expressed high levels of DPD (median >70 U/mg limiting enzyme that metabolizes 5'-deoxy-5-fluorouridine protein), while high concentrations of the dThdPase were (5'-dFUrd, doxifluridine), an intermediate metabolite of expressed in esophageal, cervical, breast, and pancreatic capecitabine, to the active drug 5-fluorouracil (5-FUra), while cancers and hepatoma (median >150 U/mg protein). The dihydropyrimidine dehydrogenase (DPD) catabolizes 5-FUra dThdPase/DPD ratio, which was reported to correlate with to an inactive molecule. The susceptibility of tumors to the susceptibility of human cancer xenografts to capecitabine, fluoropyrimidines is reported to correlate with tumor levels was high in esophageal, renal, breast, colorectal, and gastric of these enzymes. To obtain some insight into the tumor cancers (median ratio of > 1.5). In any of these three parameters, types susceptible to fluoropyrimidine therapy, we measured the inter-patient DPD variability for each cancer type was expression levels of these two enzymes in various types of much larger than the DPD variability among cancer types; human cancer tissues (241 tissue samples) by the ELISA highest/lowest ratios for dThdPase, DPD, and dThdPase/DPD methods. DPD exists in all the cancer types studied, such were 10-321, 7-513, and 2-293, respectively. These results as bladder, breast, cervical, colorectal, esophageal, gastric, indicate that measurements of the three parameters, DPD, hepatic, pancreatic, prostate, and renal cancers. Among them, dThdPase and dThdPase/DPD, would be useful criteria for the cervical, hepatic, pancreatic, esophageal, and breast cancer selecting cancer patients suitable for fluoropyrimidine therapy rather than for selecting cancer types.

Human metastatic colorectal carcinomas (CRCAs) express carcinoembryonic antigen (CEA) and/or MUC1 tumor-associated antigens as potential targets for the induction of active specific immunity. In the present study, freshly isolated metastatic CRCA cells were successfully fused with immature autologous human monocyte-derived dendritic cells (DCs). The created heterokaryons (DC/CRCA) coexpress the CRCA-derived CEA and MUC1 antigens and DC-derived MHC class II and costimulatory molecules. The fusion cells were functional in stimulating the proliferation of autologous T cells. In addition, both CD4 1 and CD81 T cells were activated by fusion cells, as demonstrated by the production of high levels of IFN-c. More importantly, coculture of fusion cells with patient-derived peripheral blood mononuclear cells (PBMCs) resulted in the induction of antigen-specific cytotoxic T lymphocytes (CTLs). CTLs were effective at lysis of not only autologous CRCA cells but also the CEA and/or MUC1-positive and HLA partially matched target cells. Antigen-specific CTL responses were confirmed by tetrameric analysis. Coculture of PBMCs with fusion cells resulted in increased frequency of CEAand MUC1-specific CTLs simultaneously. Taken together, these results indicate that freshly isolated human metastatic CRCA cells expressing the CEA and/or MUC1 may represent a potential partner for the creation of DC/tumor fusion cells targeting induction of antigen-specific CTL responses. Our report demonstrates the simultaneous induction of CRCA-specific CTL responses restricted by HLA-A2 and -A24. ' 2005 Wiley-Liss, Inc.Key words: dendritic cell; cytotoxic T lymphocyte; cytokine; MHC; tumor immunity CRCA is one of the most common malignancies and often metastasizes to the liver, lymph nodes and lung. At diagnosis, 15-20% of patients with CRCA have presented with metastatic liver disease. 1 Surgical resection is the treatment of choice for colorectal liver metastasis. However, tumor recurrence in the liver occurs in up to 60% of patients who undergo surgical resection.2 Therefore, therapy to prevent the recurrence of liver metastasis is needed. In this context, immunotherapy represents a potential approach for the prevention of recurrence of colorectal metastases. In support of the immunotherapy approach is the finding that CRCA cells overexpress the CEA, MUC1, Ep-CAM and Her-2/ neu antigens.3-8 CRCA cells also express mutated forms of the p53 and adenomatous polyposis coli 5,9 tumor-suppressor genes. In fact, there is increasing evidence that tumor-reactive and antigenspecific CTLs exist in patients with CRCA and have been expanded from tumor-infiltrating lymphocytes and PBMCs in CRCA patients. 7,8,10 These results indicate that active specific immunotherapy can be developed in patients with metastatic CRCA.DCs are potent professional APCs capable of priming naive T cells and inducing antigen-specific CTLs.11,12 DCs derive their potency from the expression of MHC class I and II, and costimulatory molecules that provide secondary signals for the acti...

Perioperative change in peripheral blood monocyte count is an independent risk factor for overall survival after hepatic resection for CRLM, and may reflect immunosuppressive state.

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