BackgroundPatients with symptoms of both asthma and chronic obstructive pulmonary disease (COPD) may be classified with the term asthma-COPD overlap (ACO). ACO is of considerable interest as it is currently poorly characterised and has been associated with worse health outcomes and higher healthcare costs compared with COPD or asthma alone. Patients with ACO in Asia remain poorly described, and there is limited information regarding their resource utilisation compared with patients with asthma or COPD only. This study investigated the characteristics, disease burden and medical resource utilisation of patients with ACO in Taiwan.MethodsThis was a retrospective cohort study of patients identified from National Health Insurance (NHI) claims data in Taiwan in 2009–2011. Patients were classified into incident ACO, COPD or asthma cohorts according to International Classification of Disease, ninth revision, clinical modification codes in claims. Eligible patients were ≥40 years of age with 12 months’ continuous enrolment in the NHI programme pre- and post-index date (date of the first relevant medical claim).ResultsPatients with ACO (N = 22,328) and COPD (N = 69,648) were older and more likely to be male than those with asthma (N = 50,293). Patients with ACO had more comorbidities and exacerbations, with higher medication use: short-acting β2-agonist prescriptions ranged from 30.4% of patients (asthma cohort) to 43.6% (ACO cohort), and inhaled corticosteroid/long-acting β2-agonist combination prescriptions ranged from 11.1% (COPD cohort) to 35.0% (ACO cohort) in the 12 months following index. Patients with ACO generally had the highest medication costs of any cohort (long-acting muscarinic antagonist costs ranged from $227/patient [asthma cohort] to $349/patient [ACO cohort]); they also experienced more respiratory-related hospital visits than patients with asthma or COPD (mean outpatient/inpatient visits per patient post-index: 9.1/1.9 [ACO cohort] vs 5.7/1.4 [asthma cohort] and 6.4/1.7 [COPD cohort]).ConclusionsPatients with ACO in Taiwan experience a greater disease burden with greater healthcare resource utilisation, and higher costs, than patients with asthma or COPD alone.Electronic supplementary materialThe online version of this article (10.1186/s12890-017-0571-7) contains supplementary material, which is available to authorized users.
The current investigation attempted to confirm the beneficial actions of a chemically characterized Radix Astragali decoction (AM-W) against type 2 diabetic (T2D) Sprague-Dawley (SD) rats. Using a case/control design, after 2 months of treatment with AM-W (500 mg/kg, daily i.p.) in T2D rats therapeutic outcomes were compared. Sucrose and Astragalus polysaccharides (ASPs) were shown to exist in nearly equal proportions in AM-W. Body weight loss, an improvement in insulin sensitivity, and an attenuation of fatty liver after AM-W administration in T2D rats were evident. Surprisingly, blood sugar, beta-cell function, and glucose tolerance in T2D rats did not improve with AM-W treatment. Further investigation indicated the deleterious effects of the addition of sucrose (100 and 500 μg/mL) and APSs (500 μg/mL) on glucose-stimulated insulin secretion and viability, respectively. In conclusion, a proper administration dosage and a reduction in the sucrose content are keys to maximizing the merits of this herb.
Objectives
This hospital‐based cohort study evaluated whether ZNF582 and PAX1 methylation levels at baseline can be used as biomarkers to identify lesions with a high potential for malignant transformation in patients with normal mucosa and oral potentially malignant disorders.
Patients and methods
We recruited 171 adult patients with normal mucosa and oral potentially malignant disorders in 2012–2014. They were followed until 2017. Outcomes, including advanced histopathological findings and oral cancer occurrence, were obtained from medical charts, the Taiwan Cancer Registry, and cause‐of‐death data. Kaplan–Meier analysis and Cox proportional hazards regression models were used to examine the association of ZNF582 and PAX1 methylation levels at baseline with subsequent outcome occurrences.
Results
After 260,192 days of follow‐up, 11 cases of oral cancer and 4 cases of advanced histopathological progression occurred. Patients with higher ZNF582 and PAX1 methylation levels at baseline had a higher incidence of disease progression. After adjustment for all studied factors using Cox proportional hazards regression models, ZNF582m level (adjusted hazard ratio, 11.41; 95% CI, 2.05–63.36; p = 0.005) was the only significant and independent predictor of disease progression.
Conclusions
ZNF582 hypermethylation can be an effective and noninvasive biomarker for identifying oral lesions with a high potential for malignant transformation.
Background
DNA methylation of paired box gene 1 (PAX1) and zinc finger 582 (ZNF582) is promising cancer biomarkers for oral squamous cell carcinoma detection. This study aims to investigate the correlation between PAX1 or ZNF582 methylation and the progression of oral squamous cell carcinoma (OSCC).
Materials and Methods
A total of 135 OSCC cases from Peking University School and Hospital of Stomatology were enrolled in this study. Tissue specimens were collected from the lesion site and corresponding adjacent normal site. The methylation level of these two genes was evaluated in primary and recurrent OSCC group.
Results
Hypermethylation of PAX1 or ZNF582 was observed in lesion sites among primary and recurrent OSCC cases. In the lesion site of primary cases, promoter methylation was observed in T3/T4 (PAX1: P = .02; ZNF582: P = .01), stage III/IV (PAX1: P = .03; ZNF582: P = .01), and bone invasion cases (PAX1: P = .02; ZNF582: P = .047). In the subgroup analysis, the correlation between hypermethylation and OSCC severity remains significant with exposure to smoking/alcohol consumption.
Conclusions
Hypermethylated PAX1 and ZNF582 can sufficiently act as biomarkers to reflect the severity or progression of OSCC.
The tumorous niche may drive the plasticity of heterogeneity and cancer stemness, leading to drug resistance and metastasis, which is the main reason of treatment failure in most cancer patients. The aim of this study was to establish a tumor microenvironment (TME)-based screening to identify drugs that can specifically target cancer stem cells (CSCs) and cancer-associated fibroblasts (CAFs) in the TME.
Methods:
Lung cancer patient-derived cancer cell and CAFs were utilized to mimic the TME and reproduce the stemness properties of CSCs
in vitro
and develop a high-throughput drug screening platform with phenotypical parameters. Limiting dilution assay, sphere-forming and ALDH activity assay were utilized to measure the cancer stemness characteristics.
In vivo
patient-derived xenograft (PDX) models and single-cell RNA sequencing were used to evaluate the mechanisms of the compounds in CSCs and CAFs.
Results:
The TME-based drug screening platform could comprehensively evaluate the response of cancer cells, CSCs and CAFs to different treatments. Among the 1,524 compounds tested, several drugs were identified to have anti-CAFs, anticancer and anti-CSCs activities. Aloe-emodin and digoxin both show anticancer and anti-CSCs activity
in vitro
and
in vivo
, which was further confirmed in the lung cancer PDX model. The combination of digoxin and chemotherapy improved therapeutic efficacy. The single-cell transcriptomics analysis revealed that digoxin could suppress the CSCs subpopulation in CAFs-cocultured cancer cells and cytokine production in CAFs.
Conclusions:
The TME-based drug screening platform provides a tool to identify and repurpose compounds targeting cancer cells, CSCs and CAFs, which may accelerate drug development and therapeutic application for lung cancer patients.
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