GDP-L-Fuc:N-acetyl-␤-D-glucosaminide ␣136fucosyl-transferase (␣1-6FucT; EC 2.4.1.68), which catalyzes the transfer of fucose from GDP-Fuc to N-linked type complex glycopeptides, was purified from a Triton X-100 extract of porcine brain microsomes. The purification procedures included sequential affinity chromatographies on GlcNAc␤1-2Man␣1-6(GlcNAc␤1-2Man␣1-2)-Man␤1-4GlcNAc␤1-4GlcNAc-Asn-Sepharose 4B and synthetic GDP-hexanolamine-Sepharose 4B columns. The enzyme was recovered in a 12% final yield with a 440,000-fold increase in specific activity. SDS-polyacrylamide gel electrophoresis of the purified enzyme gave a major band corresponding to an apparent molecular mass of 58 kDa. The ␣1-6FucT has 575 amino acids and no putative N-glycosylation sites. The cDNA was cloned in to pSVK3 and was then transiently transfected into COS-1 cells. ␣1-6FucT activity was found to be high in the transfected cells, as compared with non-or mocktransfected cells. Northern blotting analyses of rat adult tissues showed that ␣1-6FucT was highly expressed in brain. No sequence homology was found with other previously cloned fucosyltransferases, but the enzyme appears to be a type II transmembrane protein like the other glycosyltransferases.It has been reported that the structures of glycopeptides change during the development and differentiation of embryos (1-4). Detailed analysis of specific antigens on the surface of various carcinoma cells revealed that carcinoma-specific sugar chains are expressed on the cell surface. A well documented phenotypic alteration of these specific sugar chains is the increase in the molecular weight of cell surface complex type N-linked glycan in transformed cells. This change has been observed regardless of the nature of the transforming agent: oncogenic viruses (5-9), chemical mutagens (10 -11), or DNA from unrelated tumor cells (12)(13)(14). This phenomenon was thought to reflect the deviation of carcinoma cells from the ordinary differentiation processes. ␣-Fucose residue attached to asparagine-linked GlcNAc also have some relationship with carcinogenesis. A difference in the binding pattern of serum ␣-fetoprotein with lentil lectin between hepatocellular carcinomas and benign liver diseases has been reported (15-17). Analyses of the carbohydrate structure of ␣-fetoprotein from hepatocellular carcinoma cell lines have indicated that almost all of the carbohydrates of ␣-fetoprotein are ␣1-6-fucosylated (18). ␣-Fetoprotein produced by germ cell tumors, such as yolk sac tumors, is also highly fucosylated (19). The activity of ␣1-6FucT 1 was higher in hepatocellular carcinoma tissue than in non-tumor tissue (20) and was induced by the transfection of the ras protooncogene into 3T3 fibroblast cells (21). Schachter et al. (22,23) first characterized ␣1-6FucT in porcine liver using a partially purified enzyme extract. The special release of ␣1-6FucT from platelets during blood clotting has been reported (24, 25), alteration of fucosylation has been reported in cystic fibrosis glycoproteins from different s...

Superb biological effectiveness and dose conformity represent a rationale for heavy-ion therapy, which has thus far achieved good cancer controllability while sparing critical normal organs. Immediately after irradiation, heavy ions produce dense ionization along their trajectories, cause irreparable clustered DNA damage, and alter cellular ultrastructure. These ions, as a consequence, inactivate cells more effectively with less cell-cycle and oxygen dependence than conventional photons. The modes of heavy ion-induced cell death/inactivation include apoptosis, necrosis, autophagy, premature senescence, accelerated differentiation, delayed reproductive death of progeny cells, and bystander cell death. This paper briefly reviews the current knowledge of the biological aspects of heavy-ion therapy, with emphasis on the authors' recent findings. The topics include (i) repair mechanisms of heavy ion-induced DNA damage, (ii) superior effects of heavy ions on radioresistant tumor cells (intratumor quiescent cell population, TP53-mutated and BCL2-overexpressing tumors), (iii) novel capacity of heavy ions in suppressing cancer metastasis and neoangiogenesis, and (iv) potential of heavy ions to induce secondary (especially breast) cancer.

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