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  • 1
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 27, No. 1 ( 2021-01-01), p. 107-119
    Abstract: Cancer-associated fibroblasts have emerged to be highly heterogenous and can play multifaceted roles in dictating pancreatic ductal adenocarcinoma (PDAC) progression, immunosuppression, and therapeutic response, highlighting the need for a deeper understanding of stromal heterogeneity between patients and even within a single tumor. We hypothesized that image analysis of fibroblast subpopulations and collagen in PDAC tissues might guide stroma-based patient stratification to predict clinical outcomes and tumor characteristics. Experimental Design: A novel multiplex IHC-based image analysis system was established to digitally differentiate fibroblast subpopulations. Using whole-tissue slides from 215 treatment-naïve PDACs, we performed concurrent quantification of principal fibroblast subpopulations and collagen and defined three stroma types: collagen-rich stroma, fibroblast activation protein α (FAP)-dominant fibroblast-rich stroma, and α smooth muscle actin (ACTA2)-dominant fibroblast-rich stroma. These stroma types were assessed for the associations with cancer-specific survival by multivariable Cox regression analyses and with clinicopathologic factors, including CD8+ cell density. Results: FAP-dominant fibroblasts and ACTA2-dominant fibroblasts represented the principal distinct fibroblast subpopulations in tumor stroma. Stroma types were associated with patient survival, SMAD4 status, and transcriptome signatures. Compared with FAP-dominant fibroblast-rich stroma, collagen-rich stroma correlated with prolonged survival [HR, 0.57; 95% confidence interval (CI), 0.33–0.99], while ACTA2-dominant fibroblast-rich stroma exhibited poorer prognosis (HR, 1.65; 95% CI, 1.06–2.58). FAP-dominant fibroblast-rich stroma was additionally characterized by restricted CD8+ cell infiltrates and intense neutrophil infiltration. Conclusions: This study identified three distinct stroma types differentially associated with survival, immunity, and molecular features, thereby underscoring the importance of stromal heterogeneity in subtyping pancreatic cancers and supporting the development of antistromal therapies.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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  • 2
    In: BMC Oral Health, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2021-12-15)
    Abstract: This cross-sectional study performed to clarify the relationship between periodontal disease and non-communicable diseases (NCDs), such as obesity, diabetes mellitus, impaired glucose tolerance (IGT), chronic obstructive pulmonary disease (COPD), and atherosclerotic cardiovascular disease (ASCVD) by introducing dental examinations into the annual health examinations conducted by Japanese companies, and to highlights the importance of a medical system that connects dental and medical professionals. Methods A total of 1.022 Hitachi Ltd. employees were enrolled in this cross-sectional study. We examined correlations and odds ratios (ORs) between the dental and overall health of employees using stratification and multiple logistic regression analyses based on the periodontal health indicators, general health indicators, and occlusal force. Results The adjusted OR of PPD for obesity (OR, 1.42; 95% confidence interval [CI], 1.09–1.84; p  = 0.009), IGT (OR, 1.48; 95% CI, 1.00–2.20; p  = 0.049), and COPD (OR, 1.38; 95% CI, 1.02–1.88; p  = 0.038) significantly differed. The adjusted OR of body mass index (OR, 1.28; 95% CI 1.15–1.42; p   〈  0.001), haemoglobin A1C (HbA1c) (OR, 4.34; 95% CI, 1.89–9.98; p   〈  0.001), fasting blood glucose (FBG) levels (OR, 1.08; 95% CI 1.04–1.11; p   〈  0.001), postbronchodilator forced expiratory volume in one second/forced vital capacity ratio (%FEV 1 ) (OR, 0.95; 95% CI 0.91–1.00; p  = 0.031) and smoking (OR, 2.32; 95% CI 1.62–3.33; p   〈  0.001) for severe periodontal disease also significantly differed. Occlusal force was significantly reduced in employees aged 50–59 years compared to those aged 40–49 years. Both PPD, HbA1c, FBG levels were significantly associated with occlusal force among employees with moderate/severe periodontitis. PPD was significantly associated with occlusal force among employees with and moderate COPD, and ASCVD. %FEV 1 was significantly associated with occlusal force among employees with IGT. Conclusions This cross-sectional study revealed mutual relationships among periodontal disease, NCDs, and occlusal force on Japanese corporate workers. We demonstrated that a comprehensive, regional healthcare system centred on annual integrated dental and physical health examinations in the workplace will benefit employees and positively impact corporate health insurance.
    Type of Medium: Online Resource
    ISSN: 1472-6831
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2091511-1
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  • 3
    In: Cell Reports, Elsevier BV, Vol. 38, No. 9 ( 2022-03), p. 110444-
    Type of Medium: Online Resource
    ISSN: 2211-1247
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 2649101-1
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