Purpose: Small cell lung cancer (SCLC) possesses high tendency to disseminate. However, SCLC patients with paraneoplastic syndrome mediated by immunity against onconeural antigens remain in limited-stage disease (LD) without distant metastases. Cumulative evidence regulates that a balance between immune and regulatory T (Treg) cells determines the magnitude of immune responses to not only self-antigens but also tumor-associated antigens. The purpose of this study was to elucidate the immunologic balance induced in SCLC patients. + T-cell balance may be a biomarker that distinguishes ED-SCLC from LD-SCLC and predicts recurrence. This study also suggests the importance of inducingTeff cells, particularlyTh17 cells, while eliminatingTreg cells to control systemic dissemination of SCLC.

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The beta-cell promoter variant in homozygous state was associated with impaired glucose tolerance, but not with diabetes, and low HDL cholesterol levels in Japanese men. It is unlikely that the glucose intolerance associated with the promoter variant is progressive with age.

It was reported recently that monomeric O6-benzylguanine (1) acts as an alternative substrate for a DNA repair enzyme, O6-alkylguanine-DNA alkyltransferase (AGT), and that therefore pretreatment of cells with 1 induces depletion of AGT resulting in an enhanced cytotoxic response to alkylating antitumor agents. In order to study the interaction of O6-benzylguanine derivatives with AGT and to obtain greater AGT depletion, we synthesized the following O6-arylmethylguanine derivatives and related compounds: O6-(4-, 3- and 2-fluorobenzyl)guanines (2, 3, 4), O6-(4-, 3- and 2-trifluoromethylbenzyl)guanines (5, 6, 7), O6-(4-, 3- and 2-pyridylmethyl)guanines (8, 9, 10), O6-(2- and 1-naphthylmethyl)guanines (11, 12), O6-biphenylmethylguanine (13), S and Se analogues of O6-benzylguanine (14, 15) and O6-phenylguanine (16). Ten of these are new compounds. All these compounds were tested for their potentiation of N'-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-N-(2-chloroethyl)-N-nitrosou rea (ACNU) cytotoxicity using HeLa S3 and C6-1 cells. Compounds 2, 3, 5, 8, 9, 11 and 13 were active, as was 1. Compounds 7 and 12, with a substituent at the alpha position of the benzyl group, and compound 10, the alpha-nitrogen analogue of 1, were almost completely devoid of potentiating activity. These results suggest that the alpha-position of the O6-benzyl group plays an important role in the interaction of O6-benzylguanines with AGT. Of the other compounds, 4 and 6 exhibited very weak activity and 14, 15 and 16 were inactive. Possible reasons for these differences in activity are discussed in relation to the biomimetic dealkylation rates of O6-benzylguanine derivatives and the chemical characteristics of their substituents.