[Treatment of superior sulcus tumor].

We reported on 34 patients with superior sulcus non-small-cell lung cancer and clinical outcome. It is necessary to select the most appropriate approach from preoperative examination and the degree of infiltration at the chest wall. Recently, various approach and preoperative chemoradiotherapy followed by surgical resection is effective for the treatment of superior sulcus tumor (SST), we should keep challenging for radical resection in mind.

The possible use of HLA-G1 and G3 in the inhibition of NK cell-mediated swine endothelial cell lysis.

The splicing isoform of HLA-G that is expressed in xenogeneic cells, and its effect on NK-mediated direct cytotoxicity was examined, using stable Chinese hamster ovary (CHO) cell or swine endothelial cell (SEC) transfectants. cDNAs of HLA-G (G1 and G3) and human beta2-microglobulin were prepared and subcloned into the expression vector, pCXN. The transfected HLA-G1 was easily expressed on SEC, and co-transfection with human beta2-microglobulin led to an enhanced level of HLA-G1 expression, as evidenced by flow cytometry. The expressed HLA-G1 significantly suppressed NK-mediated SEC cell lysis, which is an in vitro delayed-type rejection model of a xenograft. On the other hand, the swine leucocyte antigen (SLA) class I molecules could be up-regulated as the result of the transfection of human beta2-microglobulin, but did not down-regulate human NK-mediated SEC lysis. The HLA-G3 was not expressed on CHO and SEC in contrast to HLA-G1, as the result of the transfection. The gene introduction of HLA-G3 in SEC showed no protective effect from human NK cells. However, indirect evidence demonstrated that HLA-G3 transfection resulted in HLA-E expression, but not itself, when transfected to the human cell line, 721.221, thus providing some insight into its natural function in human cells. The present findings suggest that the expression of HLA-G1 on the cell surface could serve as a new approach to overcoming NK-mediated immunity to xenografts.

Remodeling of the major pig xenoantigen by N-acetylglucosaminyltransferase III in transgenic pig.

We have been successful in generating several lines of transgenic mice and pigs that contain the human beta-d-mannoside beta-1,4-N-acetylglucosaminyltransferase III (GnT-III) gene. The overexpression of the GnT-III gene in mice and pigs reduced their antigenicity to human natural antibodies, especially the Galalpha1-3Galbeta1-4GlcNAc-R, as evidenced by immunohistochemical analysis. Endothelial cell studies from the GnT-III transgenic pigs also revealed a significant down-regulation in antigenicity, including Hanganutziu-Deicher antigen, and dramatic reductions in both the complement- and natural killer cell-mediated pig cell lyses. Changes in the enzymatic activities of other glycosyltransferases, such as alpha1,3-galactosyltransferase, GnT-IV, and GnT-V, did not support cross-talk between GnT-III and these enzymes in the transgenic animals. In addition, we demonstrated the effect of GnT-III in down-regulating the xenoantigen of pig heart grafts, using a pig to cynomolgus monkey transplantation model, suggesting that this approach may be useful in clinical xenotransplantation in the future.

Competitive amino acid transport between L-tryptophan and other amino acids in Schizophyllum commune.

In our study on nutritional requirement for the hyphal growth of Schizophyllum commune, we found that a Trp- mutant could not grow in the L-Trp-supplied medium in the presence of L-Ser. Further growth studies showed that not only L-Ser but also as many as 11 kinds of amino acid including L-Ala, L-Arg, L-Asn, L-His, L-Leu, L-Met, L-Phe, L-Ser, L-Thr, L-Tyr and L-Val inhibited the growth of the Trp- mutant in the L-Trp-supplied medium. However, these amino acids did not inhibit the growth of a Trp+ strain. The inhibition of growth of Trp+ strain induced by a Trp analogue of 5-fluoro-DL-tryptophan (5FT), which was usually recovered by L-Trp, was rescued by the same amino acids mentioned above. The exceptions were Gly and L-Ile, which also recovered the growth inhibition induced by 5FT. These results indicate that the permease responsible for the Trp transport in S. commune might also be active to other amino acids. However, it is considered that the permease shows high affinity to L-Trp and low affinity to other amino acids. As a result, the transport of L-Trp and 5FT may be counteracted by other amino acids.