In D2-resected GC, both adjuvant chemotherapy and chemoradiotherapy are tolerated and equally beneficial in preventing relapse. Because results suggest a significant DFS effect of chemoradiotherapy in subsets of patients, the ARTIST 2 trial evaluating adjuvant chemotherapy and chemoradiotherapy in patients with node-positive, D2-resected GC is under way.

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Primary cutaneous, extranodal natural killer/T-cell lymphoma, nasal type (PC-ENKTL), is a rare Epstein-Barr virus (EBV)-associated neoplasm with poorly defined clinicopathologic features. We performed a multinational retrospective study of PC-ENKTL and CD56-positive EBV-negative peripheral T-cell lymphoma (PC-CD56+PTCL) in Asia in an attempt to elucidate their clinicopathologic features. Using immunohistochemistry for T-cell receptors (TCRs), in situ hybridization for EBV, and TCR gene rearrangement, we classified 60 tumors into 51 with PC-ENKTL (20 of NK-cell, 17 T-cell, and 14 indeterminate lineages) and 9 with PC-CD56+PTCL. Tumors of T-cell origin accounted for 46% of PC-ENKTLs with half of these cases being TCR-silent. As compared with T-lineage tumors, PC-ENKTLs of NK-cell lineage had more frequent involvement of regional lymph nodes and more frequently CD8-negative and CD56-positive. Cases of PC-ENKTL showed more frequent tumor necrosis, younger age, and a higher frequency of CD16 and CD30 expression than cases of PC-CD56+PTCL. CD56-positive T-lineage PC-ENKTL tumors (n=8) had more localized disease in the TNM (tumor-node-metastasis) staging and were more often of γδ T-cell origin compared with cases of PC-CD56+PTCL (n=9). PC-ENKTLs and PC-CD56+PTCLs were equally aggressive, with a 5-year overall survival rate of 25%. Tumor necrosis and CD16 expression may serve as useful surrogates for differentiating PC-ENKTL from PC-CD56+PTCL. A single lesion, an elevated lactate dehydrogenase level, and the presence of B symptoms were independent poor prognostic factors for PC-ENKTL in multivariate analysis. Further studies with more cases are warranted to delineate the clinicopathologic features and significance of EBV in these rare lymphomas.

Although Saccharomyces cerevisiae is capable of fermenting galactose into ethanol, ethanol yield and productivity from galactose are significantly lower than those from glucose. An inverse metabolic engineering approach was undertaken to improve ethanol yield and productivity from galactose in S. cerevisiae. A genome-wide perturbation library was introduced into S. cerevisiae, and then fast galactose-fermenting transformants were screened using three different enrichment methods. The characterization of genetic perturbations in the isolated transformants revealed three target genes whose overexpression elicited enhanced galactose utilization. One confirmatory (SEC53 coding for phosphomannomutase) and two novel targets (SNR84 coding for a small nuclear RNA and a truncated form of TUP1 coding for a general repressor of transcription) were identified as overexpression targets that potentially improve galactose fermentation. Beneficial effects of overexpression of SEC53 may be similar to the mechanisms exerted by overexpression of PGM2 coding for phosphoglucomutase. While the mechanism is largely unknown, overexpression of SNR84, improved both growth and ethanol production from galactose. The most remarkable improvement of galactose fermentation was achieved by overexpression of the truncated TUP1 (tTUP1) gene, resulting in unrivalled galactose fermentation capability, that is 250% higher in both galactose consumption rate and ethanol productivity compared to the control strain. Moreover, the overexpression of tTUP1 significantly shortened lag periods that occurs when substrate is changed from glucose to galactose. Based on these results we proposed a hypothesis that the mutant Tup1 without C-terminal repression domain might bring in earlier and higher expression of GAL genes through partial alleviation of glucose repression. mRNA levels of GAL genes (GAL1, GAL4, and GAL80) indeed increased upon overexpression of tTUP. The results presented in this study illustrate that alteration of global regulatory networks through overexpression of the identified targets (SNR84 and tTUP1) is as effective as overexpression of a rate limiting metabolic gene (PGM2) in the galactose assimilation pathway for efficient galactose fermentation in S. cerevisiae. In addition, these results will be industrially useful in the biofuels area as galactose is one of the abundant sugars in marine plant biomass such as red seaweed as well as cheese whey and molasses.