ABSTRACT
BACKGROUND: Asthma has been proven to be a respiratory disorder that is characterized by the airway remodeling, airway inflammation and reversible airway obstruction. The 1,25-hydroxyvitamin D3 (1,25-(OH)2D3) plays critical roles in delaying remodeling. OBJECTIVES: To investigate the effects of 1,25-(OH)2D3 on the airway remodeling in tumor necrosis factor α (TNF-α)-induced airway smooth muscle cells (ASMCs). MATERIAL AND METHODS: The human ASMCs were divided into a blank control group (without treatment), a TNF-α group (treated with 10 ng/mL TNF-α) and a 1,25-(OH)2D3+TNF-α group (pre-treated with 10-7 M 1,25-(OH)2D3, then with 10 ng/mL TNF-α). The MTT assay was used to evaluate cell proliferation. Matrix Gla protein (MGP) and transforming growth factor ß1 (TGF-ß1) were examined using western blot assay. RESULTS: The TNF-α treatment significantly increased ASMCs proliferation and enhanced MGP and TGF-ß1 expression compared to a blank control group (p < 0.05). The 1,25-(OH)2D3 treatment (1,25-(OH)2D3+TNF-α group) significantly inhibited cell viability (0.83 ±0.01), compared to that in the TNF-α group (0.92 ±0.01) (p < 0.05). The 1,25-(OH)2D3 treatment significantly downregulated MGP expression (0.61 ±0.02), compared to that of the TNF-α group (1.51 ±0.35) (p < 0.05). The 1,25-(OH)2D3 treatment significantly reduced TGF-ß1 expression (0.69 ±0.17), compared to that of the TNF-α group (1.6 ±0.18) (p < 0.05). CONCLUSIONS: The 1,25-(OH)2D3 could participate and modulate airway remodeling by reducing MGP and TGF-ß1 expression in TNF-α-induced ASMCs. This study provided therapeutic insight and theoretical basis for clinical research.
Subject(s)
Airway Remodeling , Transforming Growth Factor beta1 , Calcium-Binding Proteins , Extracellular Matrix Proteins , Humans , Myocytes, Smooth Muscle/metabolism , Transforming Growth Factor beta1/metabolism , Transforming Growth Factor beta1/pharmacology , Tumor Necrosis Factor-alpha/metabolism , Tumor Necrosis Factor-alpha/pharmacology , Matrix Gla ProteinABSTRACT
OBJECTIVE: To analyze the clinical features, diagnosis, treatment, and prognosis of epithelioid sarcoma (ES). METHODS: The clinical data of 13 cases with epithelioid sarcoma in the Tianjin Medical University Cancer Institute and Hospital from March 1995 to December 2009 were collected and analyzed. There were 10 males and 3 females in the group, with an average age of 41.5 years (range: 13 to 68 years). Nine patients had classic ES and 4 had proximal-type ES. Surgery was the mainstay of treatment. After the operation, four patients received radiotherapy, five received chemotherapy, and one received chemoradiotherapy. RESULTS: Of the 13 cases, only 1 had multi-locus lesion. The average tumor size was (6.07 ± 1.34) cm. The lymph node involvement was found in 46.2% of the patients. Local and distant failure occurred in 50% and 30% patients, respectively. The most common site for dissemination was the lung. Four cases died within 3 years after initial operation. The 1-, 2-, 5-, 10-year overall survival rates of the 11 cases were 72.7%, 54.5%, 27.3% and 9.1%, respectively, with a median survival time of 27 months. CONCLUSIONS: Epithelioid sarcoma is a rare disease. The prognosis for patients with epithelioid sarcoma is poor because of a high propensity for local recurrence, lymph node metastases, and/or distant metastases. The definite diagnosis depends mainly on the pathologic examination. Wide surgical excision is the mainstay treatment, and radiation and chemotherapy have been used occasionally as adjuvant therapy but have had limited success.
