PDF - 158KB, PAI-1 expression in subcutaneous tumors of LLC or B16 cells excised from PAI-1-/- mice

Supplementary Figure Legends 1-2 from Cancer-Testis Antigen Lymphocyte Antigen 6 Complex Locus K Is a Serologic Biomarker and a Therapeutic Target for Lung and Esophageal Carcinomas

PDF - 41KB, Supplementary Figure Legends for Supplementary Figures 1 through 3

Supplementary Table 1 from Wnt Inhibitor Dickkopf-1 as a Target for Passive Cancer Immunotherapy

Legends for Supplementary Figures S1-S8

PDF file - 113K, Supplementary Table S1. Lung cancer cell lines used in analysis. Supplementary Table S2. Background of lung cancer patients analyzed by tissue microarray (n=341).

Supplementary Tables 1-2 from Identification of Nectin-4 Oncoprotein as a Diagnostic and Therapeutic Target for Lung Cancer

Supplementary Figures 1-4 from Identification of Nectin-4 Oncoprotein as a Diagnostic and Therapeutic Target for Lung Cancer

Supplementary Methods and Materials from Cancer-Testis Antigen Lymphocyte Antigen 6 Complex Locus K Is a Serologic Biomarker and a Therapeutic Target for Lung and Esophageal Carcinomas

Supplementary Figures 1-9 from Wnt Inhibitor Dickkopf-1 as a Target for Passive Cancer Immunotherapy

Description of additional methods and procedures used in the study

Effects of PAI-1 silencing on the degrees of proliferation, migration, and tube formation of HUVECs

PDF file - 2714K, S1. Western blot analysis with anti-RASEF antibody after phosphatase treatment of NCI-H2170 cells. S2. Kaplan-Meier analysis of tumor-specific survival of surgically treated NSCLC patients (n = 341) according to expression levels of RASEF. Markers on survival curves mean censored cases. S3. Kaplan-Meier analysis of tumor-specific survival of another set of NSCLC patients (n = 243) who underwent resection of primary tumors (P= 0.0382 by log-rank test). Makers on survival curves mean censored cases. S4. Statistical analysis of colony formation assay in Figure 3C. S5. The correlation between RASEF expression and ERK1/2 phosphorylation in lung cancer cells. S6. Immunohistochemistry on the serial sections of clinical lung cancer tissues using anti-RASEF antibody and anti-phosphorylated ERK1/2 antibody.

PDF - 51KB, Immunohistochemical staining of PAI-1

BACKGROUND:Identifying early stages of hypersensitivity pneumonitis (HP) is hampered by variable presentation, heterogeneous or undetected causal antigens and lack of gold-standard biomarkers. Krebs von den Lungen (KL)-6 is pathophysiological biomarker of alveolar epithelial damage. Pigeon fanciers, susceptible to HP, provide a model to investigate early HP.OBJECTIVE:To test the hypothesis that plasma concentrations of KL-6 are increased in early-stage acute HP.METHODS:Clinical history, spirometry and blood samples were obtained from pigeon fanciers, 20 with intermittent acute symptoms indicative of developing HP, 27 with no symptoms and 10 healthy subjects with no avian exposure. Plasma KL-6 (units/mL) and pigeon antigen-specific IgG antibody were quantified by enzyme immunoassay. Blood lymphocytes were quantified by flow cytometry and antigen specificity by in vitro cytokine production.RESULTS:KL-6 was higher in fanciers than controls, median (IQR) 452 (244, 632) vs 274 (151, 377), P = .01. Although fanciers with symptoms had similar antigen exposure and lung function, they had higher KL-6 than those without, 632 (468, 1314) vs 320 (200, 480), P < .001. KL-6 correlated with IgG antibody titre in those with symptoms, r = .591, P = .006. High KL-6, irrespective of symptom category, was associated with higher antibody (P = .006) and lymphocyte proliferation (P = .041), and lower CD4+ T lymphocyte proportion (P = .032).CONCLUSION AND CLINICAL RELEVANCE:Raised KL-6 is associated with acute symptoms of early-stage HP, and its correlation with antibody may support therapeutic strategies when HP is suspected. KL-6 may act as a mechanistic biomarker of early pathogenesis by linking lung pathophysiological changes with an endotype of immune hypersensitivity.