Citations 2
Age-associated differences in the human lung extracellular matrix
Ngassie, Maunick Lefin Koloko , Vries, Maaike de , Borghuis, Theo, Timens, Wim , Nickle, David C. , Marko‐Varga, György , Teske, Jacob J. , Burgess, Janette K. , Brandsma, Corry‐Anke , Koloko Ngassie, Maunick Lefin , Sin, Don D , Horvatovich, Peter , Teske, Jacob J , Vonk, Judith M , Gosens, Reinoud , Prakash, Y S , Burgess, Janette K , Brandsma, Corry-Anke , Timens, Wim , Joubert, Philippe , Vonk, Judith M. , Gosens, Reinoud , Prakash, Y. S.
American Journal of Physiology-Lung Cellular and Molecular Physiology | April 11, 2023 | Volume: 324 | Issue: 6 | Pages: L799-L814
We identified seven age-associated extracellular matrix (ECM) proteins, i.e., COL1A1, COL6A1, COL6A2 COL14A1, FBLN2, LTBP4, and LUM with higher transcript and protein levels in human lung tissue with age. Extensive immunohistochemical analysis revealed significant age-associated differences for COL6A2 in whole tissue, parenchyma, airway wall, and vessel, for COL14A1 and LUM in bronchial epithelium, and COL1A1 in parenchyma. Our findings lay a new foundation for the investigation of ECM differences in age-associated chronic lung diseases.
A Randomized Phase IIb Trial of myo -Inositol in Smokers with Bronchial Dysplasia
Lam, Stephen , Mandrekar, Sumithra J. , Gesthalter, Yaron , Ziegler, Katie L. Allen, Seisler, Drew K., Midthun, David E. , Mao, Jenny T., Aubry, Marie Christine, McWilliams, Annette , Shaipanich, Tawimas , Liu, Gang , Johnson, Evan, Bild, Andrea H. , Lenburg, Marc E. , Mayo, John R. , Yi, Joanne, Tazelaar, Henry D. , Harmsen, William S. , Smith, Judith, Beane, Jennifer , Szabó, Éva , Johnson, W. Evan , Allen Ziegler, Katie L, Yi, Joanne Eunhee, Tazelaar, Henry, Limburg, Paul J. , Sin, Don D , Johnson, Evan, Ionescu, Diana N. , Tazelaar, Henry D. , Spira, Avrum , Szabo, Eva
Cancer Prevention Research | September 22, 2016 | Volume: 9 | Issue: 12 | Pages: 906-914
10.1158/1940-6207.capr-15-0254
Abstract Previous preclinical studies and a phase I clinical trial suggested that myo-inositol may be a safe and effective lung cancer chemopreventive agent. We conducted a randomized, double blind, placebo-controlled phase IIb study to determine the chemopreventive effects of myo-inositol in smokers with bronchial dysplasia. Smokers with ≥1 site of dysplasia identified by autofluorescence bronchoscopy-directed biopsy were randomly assigned to receive oral placebo or myo-inositol, 9 g once a day for 2 weeks, and then twice a day for 6 months. The primary endpoint was change in dysplasia rate after 6 months of intervention on a per-participant basis. Other trial endpoints reported herein include Ki-67 labeling index, blood and bronchoalveolar lavage fluid (BAL) levels of proinflammatory, oxidant/antioxidant biomarkers, and an airway epithelial gene expression signature for PI3K activity. Seventy-four (n = 38 myo-inositol and n = 36 placebo) participants with a baseline and 6-month bronchoscopy were included in all efficacy analyses. The complete response and the progressive disease rates were 26.3% versus 13.9% and 47.4% versus 33.3%, respectively, in the myo-inositol and placebo arms (P = 0.76). Compared with placebo, myo-inositol intervention significantly reduced IL6 levels in BAL over 6 months (P = 0.03). Among those with a complete response in the myo-inositol arm, there was a significant decrease in a gene expression signature reflective of PI3K activation within the cytologically normal bronchial airway epithelium (P = 0.002). The heterogeneous response to myo-inositol suggests a targeted therapy approach based on molecular alterations is needed in future clinical trials to determine the efficacy of myo-inositol as a chemopreventive agent. Cancer Prev Res; 9(12); 906–14. ©2016 AACR.