17 research outputs found

    A novel method for screening peptides that bind to proteins by using multiple fluorescent amino acids as fluorescent tags

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    We describe a new screening method for simultaneously detecting peptides that bind to a target protein by fluorescence obtained from fluorescent amino acid-modified peptides

    Quantitative screening of EGF receptor-binding peptides by using a peptide library with multiple fluorescent amino acids as fluorescent tags

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    EGF receptor-binding peptides could be found by a peptide screening method using fifteen fluorescent amino acids as fluorescent tags. Of 225 peptides, we found an 8-mer peptide containing a dipeptide unit, Y-F, which was the strongest binding peptide to the EGF receptor

    Serum Antibody Against NY-ESO-1 and XAGE1 Antigens Potentially Predicts Clinical Responses to Anti–Programmed Cell Death-1 Therapy in NSCLC

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    Introduction: Programmed cell death-1 (PD-1) inhibitors effectively treat NSCLC and prolong survival. Robust biomarkers for predicting clinical benefits of good response and long survival with anti-PD-1 therapy have yet to be identified; therefore, predictive biomarkers are needed to select patients with benefits. Methods: We conducted a prospective study to explore whether serum antibody against NY-ESO-1 and/or XAGE1 cancer-testis antigens predicted primarily good clinical response and secondarily long survival with anti-PD-1 therapy for NSCLC. The serum antibody was detected by enzyme-linked immunosorbent assay, and tumor immune microenvironment and mutation burden were analyzed by immunohistochemistry and next-generation sequencing. Results: In the discovery cohort (n = 13), six antibody-positive NSCLC cases responded to anti-PD-1 therapy (two complete and four partial responses), whereas seven antibody-negative NSCLC cases did not. Antibody positivity was associated with good response and survival, regardless of tumor programmed death ligand 1 (PD-L1) expression, mutation burden, and CD8+ T-cell infiltration. In the validation cohort (n = 75), 17 antibody-positive NSCLC cases responded well to anti-PD-1 therapy as compared with 58 negative NSCLC cases (objective response rate 65% versus 19%, p = 0.0006) and showed significantly prolonged progression-free survival and overall survival. Antibody titers highly correlated with tumor reduction rates. In the multivariate analysis, response biomarkers were tumor programmed death ligand 1 expression and antibody positivity, and only antibody positivity was a significantly better predictive biomarker of progression-free survival (hazard ratio = 0.4, p = 0.01) and overall survival (hazard ratio = 0.2, p = 0.004). Conclusions: Our results suggest that NY-ESO-1 and/or XAGE1 serum antibodies are useful biomarkers for predicting clinical benefits in anti-PD-1 therapy for NSCLC and probably for other cancers

    AMINO-ACID-SEQ from Mitochondrial determinants of mammalian longevity

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    Current ageing theories are far from satisfactory because of the many determinants involved in ageing. The well-known rate-of-living theory assumes that the product (lifetime energy expenditure (LEE)) of maximum lifespan (MLS) and mass-specific basal metabolic rate (msBMR) is approximately constant. Although this theory provides a significant inverse correlation between msBMR and MLS as a whole for mammals, it remains problematic for two reasons. First, several interspecies studies within respective orders (typically within rodents) have shown no inverse relationships between msBMR and MLS. Second, LEE values widely vary in mammals and birds. Here, to solve these two problems, we introduced a new quantity designated as mitochondrial (mt) lifetime energy output, mtLEO = MLS × mtMR in place of LEE, by using the mt metabolic rate (mtMR) per mitochondrion. Thereby, we found that mtLEO values were distributed more narrowly than LEE ones, and strongly correlated with the four amino-acid variables (AAVs) of Ser, Thr and Cys contents and hydrophobicity of mtDNA-encoded membrane proteins (these variables were related to the stability of these proteins). Consequently, only these 2 mt items, mtMR and the AAVs, solved the above-mentioned problems in the rate-of-living theory, and thus extensively improved the correlation with MLS compared with that given by LEE

    Figure S1. Rodent phylogeny. from Mitochondrial determinants of mammalian longevity

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    Rodents were separated into 2 groups of rats/mice, one with a small MLS and the other with a large MLS

    Figure S2. Phylogenetic analysis of the rodent lineage. from Mitochondrial determinants of mammalian longevity

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    MLS and mtBMR denote maximum life span and basal metabolic rate per mitochondrion in an arbitrary unit (a. u.), respectively. The optimization procedure given by adjusting α in equation 2 provided mtBMR≈constant at α=8.0. The variable values used in this analysis are listed in Table S2
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