The immuno-pharmacological profile of a novel immunosuppressive agent, produced by a streptomycete, is presented here. Weproceeded to test the effect of the agent on various in vitro immunesystems. It showed that mixed lymphocyte reaction, cytotoxic T cell generation, the production of T cell-derived soluble mediators such as interleukin 2 (IL-2), interleukin 3 and gamma-interferon and the expression of the IL-2 receptor were suppressed by this agent. The IC50 values of FK-506 and ciclosporin (CS) in all tests were approximately 0.1 nM and 10 nM, respectively. Therefore, the novel agent, FK-506 suppressed in vitro immunesystems at about hundred times lower concentration than CS.

The findings show that LADG with extraperigastric lymph node dissection is a safe and less invasive alternative to the open procedure.

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Purpose: Although numerous proteome studies have been performed recently to identify cancer-related changes in protein expression, only a limited display of relatively abundant proteins has been identified. The aim of this study is to identify novel proteins as potential tumor markers in primary colorectal cancer tissues using a high-resolution two-dimensional gel electrophoresis (2-DE).Experimental Design: 2-DE using an agarose gel for isoelectric focusing was used to compare protein profiling of 10 colorectal cancer tissues and adjacent normal mucosa. Altered expression and post-translational modification of several proteins were examined using Western blot analysis and immunohistochemistry.Results: Ninety-seven proteins of 107 spots (90.7%) that were differentially expressed between matched normal and tumor tissues were identified by mass spectrometry. Among them, 42 unique proteins (49 spots) significantly increased or decreased in the tumors. They include eukaryotic translation initiation factor 4H, inorganic pyrophosphatase, anterior gradient 2 homologue, aldolase A, and chloride intracellular channel 1, whose elevated expression in tumor tissues was confirmed by Western blot analysis and immunohistochemistry. Interestingly, only isoform 1 of two transcript variants of eukaryotic translation initiation factor 4H was greatly up-regulated in most of the tumor tissues.Moreover, post-translational modifications of the prolyl-4-hydroxylase ␤ subunit and annexin A2 also were identified.Conclusions: We identified several novel proteins with altered expression in primary colorectal cancer using agarose 2-DE. This method is a powerful technique with which to search for not only quantitative but also qualitative changes in a biological process of interest and may contribute to the deeper understanding of underlying mechanisms of human cancer.

Chromosomal instability (CIN) has been recognized as a hallmark of human cancer and is caused by continuous chromosome missegregation during mitosis. Proper chromosome segregation requires a physical connection between spindle microtubules and centromeric DNA and this attachment occurs at proteinaceous structures called kinetochore. Several centromere proteins such as CENP-A and CENP-H are the fundamental components of the human active kinetochore, and inappropriate expression of the centromere proteins could be a major cause of CIN. We have previously shown that CENP-A was overexpressed in primary human colorectal cancer. In this study, we show that CENP-H was also up-regulated in all of 15 primary human colorectal cancer tissues as well as in CIN tumor cell lines. Surprisingly, transient transfection of CENP-H expression plasmid into the diploid cell line HCT116 remarkably induced aneupoidy. Moreover, CENP-H stable transfectant of mouse embryonic fibroblast/3T3 cell lines showed aberrant interphase micronuclei, characteristic of chromosome missegregation. In these CENP-H overexpressed cells, CENP-H completely disappeared from the centromere of mitotic chromosomes, which might be the cause of the chromosome segregation defect. These results suggest that the aberrant expression and localization of a kinetochore protein CENP-H plays an important role in the aneuploidy frequently observed in colorectal cancers. (Cancer Res 2005; 65(11): 4683-9)

Determinants of prognosis after hepatic resection for metastasis from gastric cancer were studied in a retrospective series of 21 patients, including four who survived more than 5 years after surgery. All patients underwent apparently curative resection. Synchronous or metachronous resection, age, sex, histological type, depth of invasion, lymphatic and venous invasion, lymph node involvement and number of hepatic metastases were analysed as prognostic factors for survival. Serosal invasion was the only significant determinant at synchronous resection. Both lymphatic and venous invasion were significant prognostic factors available after histological examination. Combined analysis of these two histological variables revealed that patients positive for both were at a significantly higher risk for both overall and disease-free survival. It is suggested that hepatic resection should be attempted in patients with synchronous or metachronous metastases if there is no serosal invasion by the primary gastric tumour, and if the primary tumour has neither venous nor lymphatic invasion in the case of metachronous metastases.