EGFRチロシンキナーゼ阻害剤とTEAD阻害剤の併用療法はEGFR遺伝子変異陽性肺がんの腫瘍抑制効果を増強する

京都大学新制・課程博士博士(医学)甲第25190号医博第5076号京都大学大学院医学研究科医学専攻(主査)教授 伊藤 貴浩, 教授 藤田 恭之, 教授 武藤 学学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Pneumonia Caused by Severe Acute Respiratory Syndrome Coronavirus 2 and Influenza Virus: A Multicenter Comparative Study

Background: Detailed differences in clinical information between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia (CP), which is the main phenotype of SARS-CoV-2 disease, and influenza pneumonia (IP) are still unclear. Methods: A prospective, multicenter cohort study was conducted by including patients with CP who were hospitalized between January and June 2020 and a retrospective cohort of patients with IP hospitalized from 2009 to 2020. We compared the clinical presentations and studied the prognostic factors of CP and IP. Results: Compared with the IP group (n = 66), in the multivariate analysis, the CP group (n = 362) had a lower percentage of patients with underlying asthma or chronic obstructive pulmonary disease (P < .01), lower neutrophil-to-lymphocyte ratio (P < .01), lower systolic blood pressure (P < .01), higher diastolic blood pressure (P < .01), lower aspartate aminotransferase level (P < .05), higher serum sodium level (P < .05), and more frequent multilobar infiltrates (P < .05). The diagnostic scoring system based on these findings showed excellent differentiation between CP and IP (area under the receiver operating characteristic curve, 0.889). Moreover, the prognostic predictors were different between CP and IP. Conclusions: Comprehensive differences between CP and IP were revealed, highlighting the need for early differentiation between these 2 pneumonias in clinical settings

Supplementary Table S5 from Combination Therapy with EGFR Tyrosine Kinase Inhibitors and TEAD Inhibitor Increases Tumor Suppression Effects in <i>EGFR</i> Mutation–positive Lung Cancer

Supplementary Table S5 shows antibodies used for immunohistochemical staining.</p

Supplementary Table S2 from Combination Therapy with EGFR Tyrosine Kinase Inhibitors and TEAD Inhibitor Increases Tumor Suppression Effects in <i>EGFR</i> Mutation–positive Lung Cancer

Supplementary Table S2 shows antibodies used for immunofluorescence staining.</p

Supplementary Figure S5 from Combination Therapy with EGFR Tyrosine Kinase Inhibitors and TEAD Inhibitor Increases Tumor Suppression Effects in <i>EGFR</i> Mutation–positive Lung Cancer

Supplementary Figure S5 shows the relative expression of CYR61 in KTOR27 cells treated with afatinib with or without VT104.</p

Supplementary Figure S11 from Combination Therapy with EGFR Tyrosine Kinase Inhibitors and TEAD Inhibitor Increases Tumor Suppression Effects in <i>EGFR</i> Mutation–positive Lung Cancer

Supplementary Figure S11 shows immunofluorescent staining of H1975 cells treated with osimertinib.</p

Supplementary Table S4 from Combination Therapy with EGFR Tyrosine Kinase Inhibitors and TEAD Inhibitor Increases Tumor Suppression Effects in <i>EGFR</i> Mutation–positive Lung Cancer

Supplementary Table S4 shows siRNA oligonucleotides.</p

Supplementary Data S1 from Combination Therapy with EGFR Tyrosine Kinase Inhibitors and TEAD Inhibitor Increases Tumor Suppression Effects in <i>EGFR</i> Mutation–positive Lung Cancer

Supplementary Data S1 shows the list of compound names and relative cell viability rates.</p

Supplementary Figure S7 from Combination Therapy with EGFR Tyrosine Kinase Inhibitors and TEAD Inhibitor Increases Tumor Suppression Effects in <i>EGFR</i> Mutation–positive Lung Cancer

Supplementary Figure S7 shows the relative expression of TEAD1 and CTGF in KTOR27 cells treated with afatinib with TEAD1 knockdown.</p