Chen Y.-T.,Genomic Health |
Chang J.W.-C.,Chang Gung Memorial Hospital |
Liu H.-P.,Chang Gung Memorial Hospital |
Liu H.-P.,Bendical Center |
And 9 more authors.
Journal of Thoracic Oncology | Year: 2011
Introduction: Recently, two studies revealed that MET amplification was associated with secondary epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance in non-small cell lung cancer (NSCLC) patients. But it remains uncertain whether MET amplification could be related to primary TKI resistance in NSCLC because of limited data. MATERIALS AND Methods: MET gene dosage of the tumor tissues from 208 NSCLC patients was investigated by real time quantitative polymerase chain reaction and compared with molecular and clinical features, including EGFR mutations, KRAS mutations, EGFR gene copy numbers, and patient survivals. Three copies were used as the cutoff. Among them, 25 patients were also evaluable for EGFR TKI responsiveness. Results: The proportion of high MET gene dosage was 10.58% (22/208) with higher incidence in squamous cell carcinoma (11.86%) and smokers (16.18%), although the differences with adenocarcinoma and nonsmokers were nonsignificant. Coexisting EGFR mutations were identified, and the incidence (8.54%) was similar to wild type (12.0%). High MET gene dosage was significantly associated with higher tumor stage (stage I + II versus stage III + IV; p = 0.0254) and prior chemotherapy for stage III + IV adenocarcinoma patients (35.71% versus 7.41%; p = 0.0145) but not correlated with primary TKI resistance. Among the 155 surgically resectable patients (stage I to IIIA), high MET gene dosage was significantly associated with shorter median survival (21.0 months versus 47.1 months; p = 0.042) by univariate analysis. Conclusions: High MET gene dosage was not related to primary TKI resistance and the incidence was increased after chemotherapy, suggesting high MET gene dosage may also be related to chemotherapy resistance. Copyright © 2011 by the International Association for the Study of Lung Cancer.
Prognostic implications of epidermal growth factor receptor and KRAS gene mutations and epidermal growth factor receptor gene copy numbers in patients with surgically resectable non-small cell lung cancer in Taiwan
Liu H.-P.,Chang Gung University |
Liu H.-P.,Bendical Center |
Isaac Wu H.-D.,National Chung Hsing University |
Chang J.W.-C.,Chang Gung University |
And 8 more authors.
Journal of Thoracic Oncology | Year: 2010
Introdution: The prognostic role of epidermal growth factor receptor (EGFR) mutations in patients with surgically resectable non-small cell lung cancer (NSCLC) without EGFR tyrosine kinase inhibitor treatment has not been well established, because the reports are still few. MATERIALS AND Methods:We analyzed the survival data of 164 patients with surgically resectable (stages I to IIIA) NSCLC of two year groups (1996-1998 and 2002-2004), and compared with EGFR mutations, KRAS mutations, and EGFR gene copy numbers. Results: Comparing the survival of wild-type patients and patients having L858R mutations or exon 19 deletion, the median survival was much longer for patient with EGFR mutations (54.7 months) than wild type (34.9 months). The difference was not statistically significant by univariate analysis (p = 0.1981) but had borderline significance by multivariate analyses (p = 0.0506). In addition, the 3-year survival rates of patients with EGFR mutations were also significantly higher than wild type (p = 0.0232). After exclusion of 18 patients treated by EGFR-tyrosine kinase inhibitor for tumor recurrence, the trends were still the same. Patients with KRAS mutations had shorter median survival (21 months) than wild type (44.4 months). Patients with EGFR polysomy (≥copies) also had longer median survival (56.2 months) than wild type (53.4 months). But the survival differences of these two genetic markers were all not significant statistically. Conclusion: It is intriguing that patients with NSCLC with EGFR mutations had better survival than wild type. Such a tumor biology may confound the survival data in a study without the stratification by EGFR mutation. © 2010 by the International Association for the Study of Lung Cancer.
PubMed | Southern Medical University, Nanjing University and Bendical Center
Type: | Journal: BMC infectious diseases | Year: 2016
Invasive aspergillosis is a life-threatening disease, and its incidence has increased in the recent past. Dectin-1 recognizes -glucans and mediates innate immune responses to Aspergillus fumigatus. Transcription factor PU.1 has been the focus of recent research due to its role in inflammation and infection. However, its role in Dectin-1 regulation during A. fumigatus infection remains to be elucidated.THP-1 cells were stimulated with A. fumigatus conidia. We then used real-time RT-PCR, Western blot, and immunofluorescence assays to analyze the mRNA and protein levels and cellular distribution, respectively, of Dectin-1 and PU.1 in stimulated THP-1 cells. Additionally, we used the luciferase reporter assays, chromatin immunoprecipitation (ChIP) assays, electrophoretic mobility shift assays (EMSA), and RNA interference experiments to investigate the role of PU.1 in Dectin-1 regulation.Our results revealed that Dectin-1 mRNA and protein levels as well as the PU.1 protein level were increased in THP-1 cells stimulated with A. fumigatus conidia, while the mRNA expression level did not significantly change between the stimulated and control groups. We also observed that PU.1 translocated into the nucleus in stimulated THP-1 cells. The results of the luciferase reporter assay showed that PU.1 promoted human Dectin-1 (hDectin-1) gene activity. ChIP and EMSA indicated that PU.1 could bind with hDectin-1 gene promoter at three potential transcription factor-binding sites (TFBSs). In addition, knockdown of PU.1 significantly decreased Dectin-1 expression.This study demonstrated the novel role of PU.1 in the immune response to A. fumigatus through upregulation of Dectin-1 expression and its translocation to the nucleus in A. fumigatus-stimulated THP-1 cells.
Han Y.,Fudan University |
Han Y.,Bendical Center |
Zou S.-E.,Fudan University |
Long Q.-Q.,Fudan University |
Zhang S.-F.,Fudan University
International Journal of Clinical and Experimental Medicine | Year: 2013
To evaluate the incidence and characteristics of uterine bleeding during postoperative gonadotropinreleasing hormone agonist (GnRHa) treatment combined with the lowest effective dose of estrogen-progestogen add-back therapy in Chinese women of reproductive age with endometriosis. Seventy Chinese women aged 18 to 50 years with stage III or IV endometriosis and treated with postoperative GnRHa after conservative surgery for endometriosis were eligible for this study. Patients were randomly divided into two equal groups, G and A. Group G (n = 35) received three 28-day cycles of postoperative GnRHa treatment by subcutaneous injection (goserelin, 3.6 mg). Group A (n = 35) received the same GnRHa treatment in addition to daily estradiol valerate (0.5 mg) and dydrogesterone (5 mg) add-back therapy. Serum E2 and FSH levels were assessed at the end of each treatment cycle, as well as incidence and patterns of uterine bleeding. After the last GnRHa treatment cycle, endometrial thickness was evaluated by ultrasonography and the recovery of menstruation was recorded. Uterine bleeding incidence was above 90% in both groups during the first treatment cycle (group G: 90.6%; group A: 93.8%), but decreased markedly in the second treatment cycle (group G: 15.6%; group A: 21.9%), and continued to decline until the end of the third treatment cycle (group G: 6.3%; group A: 12.5%). For each cycle, the incidence of uterine bleeding in group A was slightly but not statistically higher. Irregular spotting was the most common uterine bleeding pattern observed in each of the three treatment cycle. The addition of estrogen and progestogen therapy to a postoperative GnRHa regimen does not lead to an increase in the duration or amount of treatment-induced uterine bleeding.
PubMed | Fudan University and Bendical Center
Type: Journal Article | Journal: Journal of clinical pharmacology | Year: 2015
Seventy patients with stage III or IV endometriosis were randomly assigned to 2 groups after conservative surgery. Group O (n=35) received 3 cycles of a 28-day gonadotropin-releasing hormone agonist (GnRH-a) treatment (goserelin, 3.6mg) starting 3-5 days postoperatively. Group M (n=35) received the same treatment starting on days 1-5 of menstruation. Groups were further subdivided according to add-back treatment. Pre- and posttreated levels of estradiol (E2 ), follicle stimulating hormone (FSH), and luteinizing hormone (LH) and visual analog scale (VAS), Kupperman menopausal index (KMI), and bone mineral density (BMD) scores were recorded. The incidence of uterine bleeding was assessed. In both groups, serum levels of E2 , FSH, and LH and VAS scores decreased significantly after treatment. Spotting was the most frequent bleeding pattern. During cycle 1, the bleeding time in group M was much longer that than that in group O (P=.001), and the bleeding rate in group M was significantly higher than that in group O (P=.024, RR=1.185). In patients with stage III or IV endometriosis, the efficacy of GnRH-a initiated 3-5 days postoperatively was equivalent to that of GnRH-a initiated on days 1-5 of menstruation. Female patients who initiated GnRH-a treatment 3-5 days postoperatively experienced less uterine bleeding during the first cycle of treatment.
Zhang R.,Nanjing Medical University |
Zhu W.,Nanjing University |
Du X.,Nanjing Medical University |
Xin J.,Nanjing Medical University |
And 4 more authors.
Metabolism: Clinical and Experimental | Year: 2012
Dietary calcium influences the regulation of energy metabolism, and weight gain is attenuated by a high-calcium diet. S100A16 is a novel calcium-binding signaling protein of the EF-hand superfamily that promotes adipogenesis. This study aimed to investigate the effect of S100A16 on weight gain attenuation with a calcium-rich diet. An obese rat model was produced after feeding with a high-fat diet. Animals were randomly divided into 4 groups according to the diet provided over 8 weeks: normal diet group; high-fat, normal-calcium diet group; high-fat, high-calcium diet (HH) group; and high-fat, low-calcium diet group. Serum biochemistry was analyzed, and body weight and visceral fat pads were measured. Expression of S100A16 was assayed by Western blotting. Adipogenesis was detected by oil red O staining. Increases in body weight and visceral fat weight were attenuated in the HH group. High-calcium diets decreased the concentrations of serum total cholesterol and triglyceride. Expression of S100A16 decreased in the HH group. Using the 3T3-L1 preadipocyte model, it was observed that elevation of intracellular Ca 2+ via calcium ionophores led to the exclusion of S100A16 from the nucleus. Overexpression of S100A16 in 3T3-L1 preadipocytes enhanced adipogenesis, although a significant reduction in Akt phosphorylation was also detected. High-calcium diets were associated with a significant reduction in body weight gain. High-calcium diets may lead to nuclear exclusion of S100A16, which results in the inhibition of adipogenesis and enhanced insulin sensitivity. © 2012 Elsevier Inc. All rights reserved.
Wang J.,Nanjing Medical University |
Tang B.,Vazyme Biotechnology Company |
Liu X.,Nanjing Medical University |
Wu X.,Bendical Center |
And 3 more authors.
Atherosclerosis | Year: 2015
Background: Monomeric CRP (mCRP) plays an important role in the process of atherosclerotic plaque rupture. Recently, it has been reported that mCRP was associated with acute myocardial infarction (AMI). Objectives: The aim of this study was to examine whether mCRP is increased in AMI patients and to investigate the possibility of using circulating mCRP as a biomarker for AMI diagnosis and severity assessment of disease. Methods: A mCRP monoclonal antibody was generated and verified for its specificity. Immunofluorescence was used to assess the localization of mCRP in the infarcted myocardium. Furthermore, 101 AMI, 38 unstable angina pectoris (UAP) and 41 stable angina pectoris (SAP) patients were enrolled, and 43 healthy volunteer were recruited as controls in the study. Venous blood samples were collected to measure the circulating mCRP, cardiac Troponin T and hs-CRP levels. Results: Significantly increased mCRP levels were observed in the infarcted myocardium of model mice. In addition, significantly increased plasma mCRP levels were also detected in AMI patients (20.96±1.64ng/ml) compared to those with UAP, SAP or in control patients (all 0ng/ml, p<0.001). ROC analysis revealed that circulating mCRP had considerable diagnostic accuracy for AMI with an AUC of 0.928 (95% confidence interval 0.887-0.969). Furthermore, nine patients (9/101, 8.91%) in AMI group died before the 30-day follow-up, and their plasma mCRP concentration was significantly higher than those in surviving patients (36.70±10.26 vs. 19.41±1.43ng/ml, P=0.002). Conclusions: These results indicate that mCRP is increased in AMI and that circulating mCRP might be a potential biomarker for diagnosis and severity assessment of disease in AMI. © 2015.
PubMed | Nanjing Medical University, Bendical Center and Vazyme Biotechnology Company
Type: Journal Article | Journal: Atherosclerosis | Year: 2015
Monomeric CRP (mCRP) plays an important role in the process of atherosclerotic plaque rupture. Recently, it has been reported that mCRP was associated with acute myocardial infarction (AMI).The aim of this study was to examine whether mCRP is increased in AMI patients and to investigate the possibility of using circulating mCRP as a biomarker for AMI diagnosis and severity assessment of disease.A mCRP monoclonal antibody was generated and verified for its specificity. Immunofluorescence was used to assess the localization of mCRP in the infarcted myocardium. Furthermore, 101 AMI, 38 unstable angina pectoris (UAP) and 41 stable angina pectoris (SAP) patients were enrolled, and 43 healthy volunteer were recruited as controls in the study. Venous blood samples were collected to measure the circulating mCRP, cardiac Troponin T and hs-CRP levels.Significantly increased mCRP levels were observed in the infarcted myocardium of model mice. In addition, significantly increased plasma mCRP levels were also detected in AMI patients (20.961.64ng/ml) compared to those with UAP, SAP or in control patients (all 0ng/ml, p<0.001). ROC analysis revealed that circulating mCRP had considerable diagnostic accuracy for AMI with an AUC of 0.928 (95% confidence interval 0.887-0.969). Furthermore, nine patients (9/101, 8.91%) in AMI group died before the 30-day follow-up, and their plasma mCRP concentration was significantly higher than those in surviving patients (36.7010.26 vs. 19.411.43ng/ml, P=0.002).These results indicate that mCRP is increased in AMI and that circulating mCRP might be a potential biomarker for diagnosis and severity assessment of disease in AMI.
Chung W.-M.,China Medical University at Taichung |
Chang W.-C.,China Medical University at Taichung |
Chen L.,China Medical University at Taichung |
Chen L.,Bendical Center |
And 4 more authors.
Stem Cell Research and Therapy | Year: 2013
Introduction. Resistance of cancer stem/progenitor cells (CSPCs) to chemotherapy can lead to cancer relapse. Ovarian teratocarcinoma (OVTC) arises from germ cells and comprises pluripotent cells that can be used to study cancer cell stemness. In this study, we evaluated whether microRNA-21 (miR-21) promotes ovarian teratocarcinoma by maintaining cancer stem/progenitor populations. Methods. The lentiviral delivery system was used to upregulate or to suppress the expression of miR-21 in the human ovarian teratocarcinoma cell line PA1 and cell growth assays were used to monitor the expression of miR-21 at different time points. Antibodies directed toward CD133, a stem cell marker, were used to identify CSPCs in the PA1 cell population, and the level of miR-21 expression was determined in enriched CSPCs. Stem cell functional assays (sphere assay and assays for CD133 expression) were used to assess the effects of miR-21 on progression of the CD133+ population. Results: Knockdown of miR-21 in PA1 cells attenuated growth of PA1 cells whereas overexpression of miR-21 promoted cell growth. Moreover, knockdown of miR-21 resulted in a marked reduction in the CD133+ population and sphere formation of CSPCs. In contrast, overexpression of miR-21 resulted in a marked increase in the population of CD133+ cells as well as sphere formation of CSPCs. Conclusions: MicroRNA-21 plays a significant role in cancer growth by regulating stemness in cancer cells. © 2013 Chung et al.; licensee BioMed Central Ltd.
Huang C.-Y.,I - Shou University |
Hsu M.-C.,I - Shou University |
Pan K.-C.,Bendical Center |
Huang C.-K.,E Da Hospital |
Chi S.-C.,E Da Hospital
Bariatric Nursing and Surgical Patient Care | Year: 2011
Background: Patients undergoing surgical treatment for obesity are likely to experience changes in their health-related quality of life (HRQOL). The purposes of this study were to investigate HRQOL before and after laparoscopic gastric bypass (LGB) surgery, and to describe the influence of weight loss surgery on HRQOL in morbidly obese patients. Methods: Patients with morbid obesity who underwent weight loss surgery at a hospital in Taiwan were recruited. The standard survey was administered before surgery and again 3 months after LGB to patients with a body mass index (BMI) of >40 kg/m 2 or a BMI ≥35 kg/ m 2 when combined with diabetes/hypertension. Results: The sample included 40 patients; 62.5% were women and the average age of participants was 30.1 years. Scores on the subscales of the Medical Outcomes Study SF-36 demonstrated significant improvements between baseline and follow-up. The physical health domain was most affected. There were also significant improvements related to physical functioning, physical-role limitations, bodily pain, general health perceptions, emotional-role limitations, and general mental health at 3 months after LGB. BMI explained 26.5% of the variance in HRQOL change after LGB. The higher the BMI level, the poorer the HRQOL after LGB. Marital status and body weight explained 26.8% of variances of mental component summary after LGB. Conclusions: Significant weight loss was achieved as early as 3 months after LGB and was associated with substantial improvement in HRQOL in patients. The results of the study foster knowledge of and support research about improving the HRQOL and lives and nursing care of those suffering from obesity. © Copyright 2011, Mary Ann Liebert, Inc.