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ABSTRACT: The secreted frizzled-related protein 1 (SFRP1) gene, as a Wnt signaling modulator, is frequently inactivated by promoter methylation in many tumors including gastric cancer, breast cancer, oral squamous cell carcinoma, and esophageal adenocarcinoma. However, the role of SFRP1 in esophageal squamous cell carcinoma (ESCC) is not clear. In this study, we investigated the epigenetic inactivation of the SFRP1 gene in ESCC.
Nine ESCC cell lines, two immortalized human esophageal epithelial cell lines, twenty ESCC tissues, and paired adjacent nontumor tissues were analyzed in the study. Methylation-specific polymerase chain reaction (PCR), bisulfite sequencing, reverse-transcription PCR, immunohistochemistry, and chromatin immunoprecipitation assay were used to detect SFRP1 promoter methylation, expression of the SFRP1 gene, and histone modification in the SFRP1 promoter region.
The SFRP1 promoter was found to be highly methylated in 95% (19/20) of the ESCC tissues and in nine ESCC cell lines, compared with 65% (13/20) of the paired nontumor tissues. Moreover, we confirmed that complete methylation of the SFRP1 gene promoter was correlated with its greatly reduced expression level. After individual treatment with 5-aza-2'-deoxycytidine (DAC) and trichostatin A (TSA), the messenger RNA (mRNA) level of the SFRP1 gene was not obviously rescued in the EC9706 cell line. Combined incubation with DAC and TSA can, however, substantially increase the SFRP1 mRNA expression level in the EC9706 cell line. Chromatin immunoprecipitation assay showed that acetylated histone H3 and H4 were found in the SFRP1 promoter region.
Promoter hypermethylation of SFRP1 is a frequent event in ESCC. Promoter methylation and histone acetylation may cooperatively regulate expression of the SFRP1 gene.
Digestive Diseases and Sciences 05/2011; 56(11):3195-203. · 2.12 Impact Factor
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ABSTRACT: Although benefits of pulsatile flow during cardiopulmonary bypass (CPB) in pediatric heart surgery remain controversial and nonpulsatile CPB is still widely used in clinical cardiac surgery, pulsatile CPB must be reconsidered due to its physiologic features. In this study, we aimed to evaluate the effects of pulsatile perfusion (PP) and nonpulsatile perfusion (NP) on cerebral regional oxygen saturation (rSO₂) and endothelin-1 (ET-1) in pediatric tetralogy of Fallot (TOF) patients undergoing open heart surgery with CPB. Forty pediatric patients were randomly divided into the PP group (n = 20) and the NP group (n = 20). Pulsatile patients used a modified roller pump during the cross-clamp period in CPB, while NP patients used a roller pump with continuous flat flow perfusion. The subjects were monitored for rSO₂ from the beginning of the operation until 6 h after returning to the intensive care unit (ICU). We also monitored the hemodynamic status and ET-1 concentration and plasma free hemoglobin (PFH) in blood samples of all patients over time. Effective PP was monitored in PP patients, and pulse pressure was significantly higher in the PP group than in the NP group (P < 0.01). rSO₂ of the PP group was higher than that of the NP group (P < 0.01) during the cross-clamp period, and this advantage of PP would be maintained until 2 h after patients returned to the ICU (P < 0.05). ET-1 level in blood samples was lower at clamping off and CPB weaning and early ICU period in the PP group than in the NP group (P < 0.01), and ET-1 concentration remained at a normal level after patients were transferred to the ICU 24 h in all patients. PFH levels in the PP group at pre-clamp off and CPB weaned off were higher than those of the NP group (P < 0.05) in these cyanotic patients. PP can increase rSO₂ and improve microcirculation during cross-clamping period in TOF pediatric patients, while PP resulted in more severe hemolysis in these cyanotic patients than NP.
Artificial Organs 03/2011; 35(3):E54-8. · 2.00 Impact Factor
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ABSTRACT: To study the clinicopathologic features of primary cardiac valve tumors.
Eleven cases of primary valve tumors collected from Fuwai Hospital during the period from 1983 to 2005 were enrolled into the study. The tumors were stained with hematoxylin and eosin and Weigert-Van Gieson stain. Immunohistochemistry was also carried out in selected examples.
Primary cardiac valve tumors were uncommon and accounted for only 3% (11/426) of all primary cardiac tumors. Most of them (10/11) were benign and malignancy was rarely encountered (1/11). The tumor subtypes included papillary fibroelastoma (4/11), cavernous hemangioma (4/11), glomus tumor (1/11), angiosarcoma (1/11) and hamartoma (1/11). Of the 11 tumors studied, 4 involved the tricuspid valve, 4 involved the mitral valve, 2 involved the pulmonary valve and 1 involved the aortic valve. The diagnosis was established by preoperative echocardiography in 7 patients. The remaining 4 cases were either misdiagnosed or undiagnosed.
Preoperative diagnosis of primary cardiac valve tumors can be difficult due to lack of detailed information related to this group of lesions. Although benign cardiac valve tumors carry a good prognosis, the clinical outcome may be disastrous as a result of hemodynamic disturbances. Intraoperative frozen section examination is advisable for guiding proper surgical management.
Zhonghua bing li xue za zhi Chinese journal of pathology 04/2006; 35(3):142-4.
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ABSTRACT: To examine the degree of intimal hyperplasia and the prevalence of atherosclerosis in radial arteries taken from the patients undergoing coronary artery bypass grafting (CABG), and to analyze the risk factors to obtain some helpful information for choosing arterial conduits.
Forty-one radial arteries and 11 internal mammary arteries samples were collected. The average age of patients was 48.5 years, and they all were male. Intimal hyperplasia, atherosclerosis, medial calcification were evaluated by routine histological methods, and the severity of diseases was measured on the percentage of luminal narrowing and the intima-to-media ratio (the intima area/media area). The risk factors for coronary heart disease were also analyzed.
Ninety-three percent (38 of 41) of radial arteries showed mild intimal hyperplasia, which was not regarded to influence blood flowing after CABG. As a part of them, 54% (22/41) of radial arteries had a lower than 25% of luminal narrowing, meanwhile 39% (16/41) of radial arteries had the percentage of luminal narrowing between 25% and 50%. Only 7% (3 of 41) of radial arteries were found to have occlusive lesions, which made arterial lumen decreased more than 75%. The 3 patients including 2 with severe atherosclerosis and another 1 aged 17 years was involved by fibromuscular dysplasia. The later vessel was discarded after harvesting. The percentage of luminal narrowing and the intima-to-media ratio were higher in radial artery than that in internal mammary artery (t = 3.00, 2.49, P < 0.05). The two parameters were positively correlated with age (r = 0.398, 0.310, P < 0.05), but this study failed to show any relationship between intimal hyperplasia of radial artery and coronary lesions and other risk factors. Medial calcification was not found by routine histological method in all cases.
Only mild intimal hyperplasia and no medial calcification are found in radial arteries used for CABG in the patients. Because the risk factors could not yet predict the severity of radial arterial lesions, this study strongly suggests that the Doppler ultrasonography and pre-operation clinical consideration should be emphasized to screen out some arteries with occlusive lesions.
Zhonghua wai ke za zhi [Chinese journal of surgery] 02/2006; 44(2):83-6.
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ABSTRACT: The radial artery differs from internal mammary artery in its vascular biology and long-term patency after coronary artery bypass grafting (CABG). This study was designed to investigate their ultrastructural differences that may have implications in arterial remodeling and graft failure.
Thirty-four radial artery and 11 internal mammary artery samples were obtained from patients underwent CABG, and subjected to routine electron microscopic examination. A semi-quantitative method was used to evaluate secretary endothelial cells, endothelial denudation, synthetic smooth muscle cells (SMCs), matrix accumulation, lipid deposition and medial submicroscopic calcification.
Compared with internal mammary arteries, the radial arteries had more secretory endothelial cells (47.1%, 16/34 vs 27.2%, 3/ 11) and synthetic type SMCs in a background (14.4% vs 0.9%) that had more intimal lipid deposition and matrix accumulation (14.7%, 5/34 vs 9.1%, 1/11). Matrix vesicles and calcifications were frequently present in the media of both types of arteries. The calcifications, however, could not be visualized by routine histological stains, and therefore, named as submicroscopic calcification in this study. Fewer endothelial denudations were observed in the radial arteries, but no differences in medial lipid deposition and submicroscopic calcification were observed between these two types of arteries. The ultrastructural features and the arrangement of medial SMCs in radial arteries were similar to those of internal mammary arteries.
Radial arteries have a higher SMC proliferative potential and more actively secretory status of endothelial cells, which may enhance the remodeling process and correlate with a decreased long-term patency. Better preservation of endothelial cells in radial arteries could be attributed to the "no touch" technique utilized in surgical harvesting. The significance of submicroscopic medial calcification during graft remodeling requires further investigations.
Zhonghua bing li xue za zhi Chinese journal of pathology 09/2005; 34(8):528-32.
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ABSTRACT: To investigate the protective and therapeutic effects of pulmonary surfactant in the pathogenesis of chronic obstructive pulmonary disease (COPD) in hamsters.
COPD animal model was established by smoke inhalations and intratracheal instillations of pancreatic elastase in hamsters. Ninty hamsters were divided into 9 groups as follows: normal group (N), two groups received smoke inhalations for 1 and 3 months (S1 and S3), one group received intratracheal instillation of surfactant (10 mg/100 g BW) for once after 1 month smoking (SP1), one group was treated with surfactant after 1.5, 2 and 2.5 months of smoking (SP3), and two groups received intratracheal administration of elastase (40 U/100 g BW) and were killed after 1 month and 3 months, respectively (E1 and E3). The surfactant was injected intratracheally after 1 week, 0.5, 1.0, 1.5, 2.0, and 2.5 months, followed by administration with elastase (EP1 and EP3). EP1 group were killed at the first month, and EP3 at the third month. Light microscopy and electromicroscopy observations were performed in each group. Pulmonary mean linear intercept (MLI), mean alveolar numbers (MAN), and pulmonary alveolar area (PAA) was measured by image analysis. The expression of surfactant protein A (SP-A) were observed by immunohistochemistry.
Smoking for 3 months and instillations of elastase resulted in chronic bronchitis and emphysema. MLI and PAA increased and MAN decreased in all the experimental groups compared with in the normal group (P < 0.05 or P < 0.01). Administration of surfactant for 3 months resulted in statistically significant inhibition of pulmonary injury. MLI and PAA decreased and MAN increased in SP3 compared with in S3. Only MLI decreased in EP3 compared with E3. The expressions of SP-A in the type II alveolar epithelia decreased in S3 and E3 (compared with the normal group P < 0.01). After pulmonary surfactant intervention, the expression of SP-A increased significantly.
Pulmonary surfactant may have a long-term protective effect on chronic smoking and elastase-induced COPD.
Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae 07/2004; 26(3):279-84.
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ABSTRACT: To study the effect of exogenous pulmonary surfactant (PS) on the acute lung injury to ischemia-reperfusion injury.
The model of ischemia-reperfusion was established. Thirty male Sprague-Dawley rats were randomly divided into control (n = 10), I/R (n = 10), and PS (n = 10) groups. Control group: the isolated rat lungs were reperfused for 4 hours. I/R group: the isolated rat lungs were reperfused for 2 hours after 2 hours ischemia. PS group: exogenous pulmonary surfactant (10 mg/100 g BW) were given to the ischemic lungs through bronchus 2 hours before reperfusion. Wet to dry lung weight ratio (W/D) and pulmonary artery pressure (PAP) were checked. Immunohistochemical technique was used to determine the immune reactivity of lung tissues to endothelia nitric oxide synthase (eNOS) and surfactant protein A (SP-A). The pulmonary changes were also observed by light and electronic microscopes.
W/D and PAP in I/R group were significantly higher than in PS group (P < 0.01). The expression of eNOS and SP-A in I/R group were significantly lower than those in PS group (P < 0.05).
PS can significantly protect lung injury induced by ischemia-reperfusion in the isolated rat lungs. This protective effect is associated with the mechanism that the exogenous PS may reduce SP-A loss in the ischemia-reperfusion and activate the up-regulation of eNOS.
Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae 07/2004; 26(3):302-5.
