lthough gastric carcinoma has recently shown a gradual decrease in prevalence, it still accounts for a significant proportion of cancer-related deaths in Japan. To improve the cure rate, more attention should be directed to early detection and prevention of metastasis of this cancer. Scirrhous carcinoma of the stomach, known as diffusely infiltrative carcinoma or Borrmann's type-IV carcinoma, or linitis plastica-type carcinoma, is characterized clinically as having the worst prognosis among the various types of gastric cancer, because it is frequently associated with metastases to lymph nodes and peritoneal dissemination. However, the mechanisms underlying this propensity for metastasis are not yet clearly understood. Therefore, establishment of relevant animal models of metastasis is considered to be extremely important for the elucidation of these mechanisms and establishment of appropriate therapeutic approaches. Transplants of human tumors into nude mice have been used increasingly as experimental systems for this purpose.1) Many human tumors can proliferate when injected s.c. into nude mice, but metastasis from the site of injection is rare.2) It has been found that in most models of human cancers, including gastric carcinoma, i.v. or intrasplenic injection, or orthotopic implantation of the tumor cells is necessary to generate metastasis. [3][4][5][6] There are few reports of spontaneous metastasis from human gastric tumor xenografts in nude mice. 7,8) To date, only one experimental model of signet-ring cell or scirrhous carcinoma of the stomach has been reported. 9) In order to address this problem, we previously established and characterized four cell lines from a primary gastric carcinoma and disseminated metastatic lesions of gastric scirrhous carcinoma.10-12) These cell lines did not exhibit the potential to form experimental or spontaneous metastases when injected s.c. or i.v., or implanted orthotopically into nude mice.We now report the establishment and the biological characterization of new human signet-ring cell gastric carcinoma cell lines that exhibit the ability to metastasize spontaneously in nude mice. Materials and MethodsOrigin and establishment of the cell lines. The HSC-44PE cell line was established from the pleural fluid, obtained by thoracocentesis, of a 28-year-old female Japanese patient with scirrhous gastric carcinoma (linitis plastica-type). The previously reported 12) and the HSC-44PE cells reported in this paper, were derived from the same patient. The former was derived from the ascitic fluid in the early stage of scirrhous gastric carcinoma, while the latter was established by culture of tumor cells collected from the pleural fluid in the terminal stage of the cancer. The HSC-58 cell line was established from the ascitic fluid, obtained by peritoneocentesis, of a 57-year-old male Japanese patient with scirrhous gastric carcinoma. The HSC-60 cell line was established from the ascitic fluid, obtained by peritoneocentesis, of a 40-year-old male patient with scirrhous gastric car...

Our results indicate that the T allele in the MMP-9 promoter is associated with the invasive phenotype of gastric cancer.

Background The FOXP3 mRNA expression and the other regulatory T cell-related molecules were investigated and compared with clinicopathological parameters in human primary breast cancer. Method This study included 136 breast cancer patients operated in our department from 2003 to 2006. Total RNA was extracted from frozen normal breast and breast cancer tissues, and the expression of FOXP3, IL-10, TGF 1 and CCL22 mRNA was evaluated using quantitative real-time RT-PCR. Result FOXP3, IL-10, TGF 1 and CCL22 mRNA expressions were signiWcantly higher in cancer tissue than in normal tissue, not only at pT1, 2, and 3 stages but also at the DCIS stage. There were positive correlations between FOXP3 and IL-10, FOXP3 and TGF 1, as well as FOXP3 and CCL22 mRNA expressions, respectively. FOXP3 and IL-10 mRNA expressions were signiWcantly upregulated in PgR-negative or HER2-positive tumors. ConclusionThese results suggest that regulatory T cells are involved in tumor onset and progression in human primary breast cancer, possibly contributing to poor prognosis of patients with breast cancer.

In patients with breast carcinoma, cellular immune responses, from DC maturation to Th-1 responses, appeared to be less active in SNs compared with non-SNs before metastasis developed. Once metastasis was established in SNs, DC maturation was triggered and was followed by the up-regulation of Th-1 responses, which may reflect antigen-specific immune responses in SNs. Unlike DC maturation and Th-1 responses after metastasis in SNs, up-regulation of Th-2 and regulatory T-cell responses developed in parallel.