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Hai-Yan Zhang,Zhen-Xian Du,Bao-Qin Liu,Yan-Yan Gao,Xin Meng,Yifu Guan,Wei-Wei Deng,Hua-Qin Wang 생화학분자생물학회 2009 Experimental and molecular medicine Vol.41 No.5
TNF-related apoptosis-inducing ligand (TRAIL) has been proposed as a promising cancer therapy that preferentially induces apoptosis in cancer cells, but not most normal tissues. However, many cancers are resistant to TRAIL by mechanisms that are poorly understood. In this study, we showed that tunicamycin, a naturally occurring antibiotic, was a potent enhancer of TRAIL-induced apoptosis through downregulation of survivin. The tunicamycin-mediated sensitization to TRAIL was efficiently reduced by forced expression of survivin, suggesting that the sensitization was mediated at least in part through inhibition of survivin expression. Tunicamycin also repressed expression of cyclin D1, a cell cycle regulator commonly overexpressed in thyroid carcinoma. Furthermore, silencing cyclin D1 by RNA interference reduced survivin expression and sensitized thyroid cancer cells to TRAIL; in contrast, forced expression of cyclin D1 attenuated tunicamycin-potentiated TRAIL-induced apoptosis via over-riding downregulation of survivin. Collectively, our results demonstrated that tunicamycin promoted TRAIL-induced apoptosis, at least in part, by inhibiting the expression of cyclin D1 and subsequent survivin. Of note, tunicamycin did not sensitize the differentiated thyroid epithelial cells to TRAIL-induced apoptosis. Thus, combined treatment with tunicamycin and TRAIL may offer an attractive strategy for safely treating resistant thyroid cancers. TNF-related apoptosis-inducing ligand (TRAIL) has been proposed as a promising cancer therapy that preferentially induces apoptosis in cancer cells, but not most normal tissues. However, many cancers are resistant to TRAIL by mechanisms that are poorly understood. In this study, we showed that tunicamycin, a naturally occurring antibiotic, was a potent enhancer of TRAIL-induced apoptosis through downregulation of survivin. The tunicamycin-mediated sensitization to TRAIL was efficiently reduced by forced expression of survivin, suggesting that the sensitization was mediated at least in part through inhibition of survivin expression. Tunicamycin also repressed expression of cyclin D1, a cell cycle regulator commonly overexpressed in thyroid carcinoma. Furthermore, silencing cyclin D1 by RNA interference reduced survivin expression and sensitized thyroid cancer cells to TRAIL; in contrast, forced expression of cyclin D1 attenuated tunicamycin-potentiated TRAIL-induced apoptosis via over-riding downregulation of survivin. Collectively, our results demonstrated that tunicamycin promoted TRAIL-induced apoptosis, at least in part, by inhibiting the expression of cyclin D1 and subsequent survivin. Of note, tunicamycin did not sensitize the differentiated thyroid epithelial cells to TRAIL-induced apoptosis. Thus, combined treatment with tunicamycin and TRAIL may offer an attractive strategy for safely treating resistant thyroid cancers.
Slide Session : OS-END-38 ; Endocrinology : Awareness of Vitamin D Defi ciency Among Medical Doctors
( Yan Qin ),( Kok Seng Wong ),( Haresh Tulsidas ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1
Background: Vitamin D deficiency is a well-known under-diagnosed condition that is seeing a growing prevalence globally. It can lead to osteomalacia with diffuse bone and joint pain, muscle weakness, and difficulty walking. It is also associated with osteoporosis, increased risk of falls and fractures with little or no trauma especially among elderly. However it is not cost effective to screen everyone without adequate sun exposure for vitamin D deficiency. We conducted a study to determine the awareness of vitamin D deficiency among medical doctors. Methods: A cross-sectional survey using a piloted questionnaire was conducted among medical doctors in Internal Medicine department in our institution. It consisted of 5 questions: laboratory definition and symptoms of vitamin D deficiency, prevalence of vitamin D deficiency among adult Singaporeans, recommended daily vitamin D doses for adults who do not have adequate sun exposure and advice to patients on the sources of vitamin D acquisition. Results: A total of 59 (52.2% of 113 doctors of the department) doctors comprising 9 consultants, 5 registrars and 45 residents/medical officers/house officers responded. 47% (28) of doctors were aware of the laboratory definition of vitamin D deficiency, 63% (37) and 68% (40) were familiar with symptoms and prevalence respectively, majority 92% (54) would advise patients to acquire adequate vitamin D through sunlight, diet and dietary supplements. However, only 25% (15) were aware of the recommended daily dose. Conclusions: The awareness of vitamin D deficiency among Internal Medicine doctors who are the major medical care providers to Geriatric patients in our institution remained suboptimal. Periodic education through case studies or literature review of such topic especially to junior doctors is necessary. We believe that recognizing and treating vitamin D deficiency especially among elderly will have a great impact on healthcare policy decision and resource utilization.
Association Between the XRCC3 Thr241Met Polymorphism and Cervical Cancer Risk: a Meta-analysis
Qin, Ling-Yan,Chen, Xu,Li, Ping,Yang, Zheng,Mo, Wu-Ning Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.11
Background: Numerous epidemiological studies have been conducted to evaluate the association between variants of the DNA repair gene XRCC3 and cancer risk. Here we focused on one XRCC3 polymorphism and development of cervical cancer, performing a meta-analysis. Methods: The pooled association between the XRCC3 Thr241Met polymorphism and cervical cancer risk was assessed by odds ratios (ORs) and their 95% confidence intervals (95%CIs). Results: A total of 5 case-control studies met the inclusion criteria. The pooled ORs for the total included studies showed no association among homozygotes TT vs. CC: OR=1.93, 95%CI=0.68-5.49, P=0.22; dominant model TT+TC vs. CC: OR=1.37, 95%CI=0.90-2.06, P=0.14; and recessive model TT vs. TC+CC: OR=1.76, 95%CI=0.68-4.55, P=0.25, but might be a slight risk factor for cervical cancer in heterozygote contrast TT vs. CT: OR= 1.33, 95%CI=1.04-1.71, P=0.02. In subgroup analysis, significant associations were found for Asians under all genetic models. Conclusions: Our meta-analysis suggested the XRCC3 Thr241Met polymorphism might not act as a cervical cancer risk factor overall. However, in subgroup analysis, a significant association was found in Asians under all genetic models. The association should be studied with a larger, stratified population, especially for Asians.
The CCND1 G870A Gene Polymorphism and Brain Tumor Risk: a Meta-analysis
Qin, Ling-Yan,Zhao, Li-Gang,Chen, Xu,Li, Ping,Yang, Zheng,Mo, Wu-Ning Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.8
Background: In recent years, numerous studies have been performed to investigate the CCND1 G870A gene polymorphism impact on brain tumors susceptibility. Unfortunately, the results of previous studies were inconsistent. Therefore, we performed a meta-analysis to derive a more precise estimation of any association. Materials and Methods: We conducted a search in PubMed, Embase and CNKI covering all published papers up to November, 2013. Odds ratios (ORs) and their 95% confidence intervals (95%CIs) were applied to assess associations. Results: A total of 6 publications including 9 case-control studies met the inclusion criteria. The pooled ORs for the total included studies showed significant association among comparison A vs G (OR= 1.246, 95%CI= 1.092-1.423, p= 0.001), homozygote comparison AA vs GG (OR= 1.566, 95%CI= 1.194-2.054, p= 0.001), heterozygote comparison AG vs GG (OR= 1.290, 95%CI= 0.934-1.782, p= 0.122), dominant model AA/GA vs GG (OR= 1.381, 95%CI= 1.048-1.821, p= 0.022) and recessive model AA vs GA/GG (OR= 1.323, 95%CI= 1.057-1.657, p= 0.015) especially in glioma. Conclusions: CCND1 G870A polymorphism may increase brain tumor risk, especially for gliomas. However, more primary large scale and well-designed studies are still required to evaluate the interaction of CCND1 G870A polymorphism with brain tumor risk.
( Yan-jun Wang ),( Xiu-qiong Lang ),( Dan Wu ),( Yu-qin He ),( Chun-hui Lan ),( Xiao-xiao ),( Bin Wang ),( Duo-wu Zou ),( Ji-min Wu ),( Yong-bin Zhao ),( Peter W Dettmar ),( Dong-feng Chen ),( Min Yan 대한소화기 기능성질환·운동학회 2020 Journal of Neurogastroenterology and Motility (JNM Vol.26 No.1
Background/Aims To determine the value of salivary pepsin in discriminating sub-types of gastroesophageal reflux disease (GERD) and GERD-related disorders. Methods Overall, 322 patients with different sub-types of GERD and 45 healthy controls (HC) were studied. All patients took Gastroesophageal Reflux Disease Questionnaire (GerdQ) and underwent endoscopy and 24-hour esophageal pH monitoring and manometry. Salivary pepsin concentration (SPC) was detected by using colloidal gold double-antibody immunological sandwich assay. Oral esomeprazole treatment was administrated in the patients with non-erosive reflux disease (NERD) and extra-esophageal symptoms (EES). Results Compared to HC, patients with erosive esophagitis, NERD, EES, EES plus typical GERD symptoms, or Barrett’s esophagus had a higher prevalence of saliva and SPC (all P < 0.001). There was no significant difference in the positive rate for pepsin in patients with functional heartburn or GERD with anxiety and depression, compared to HC. After esomeprazole treatment, the positive rate and SPC were significantly reduced in NERD (both P < 0.001) and in EES (P = 0.001 and P = 0.002, respectively). Of the 64 NERD patients, 71.9% (n = 46) were positive for salivary pepsin, which was significantly higher than the rate (43.8%, n = 28) of pathological acid reflux as detected by 24-hour esophageal pH monitoring (P = 0.002). Conclusions Salivary pepsin has an important significance for the diagnosis of GERD and GERD-related disorders. Salivary pepsin and 24-hour esophageal pH monitoring may complement with each other to improve the diagnostic efficiency.
The CCND1 G870A Gene Polymorphism and Leukemia or Non-Hodgkin Lymphoma Risk: a Meta-analysis
Qin, Ling-Yan,Zhao, Li-Gang,Chen, Xu,Yang, Zheng,Mo, Wu-Ning Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.16
In recent years, mounting evidence has indicated that the CCND1 G870A gene polymorphism, which impacts the mitotic cell cycle, may influence leukemia or non-Hodgkin lymphoma risk. Unfortunately, the previous results were inconsistent. Therefore, a meta-analysis was performed to obtain a more precise estimation of any association. We conducted a search in PubMed, Embase and CNKI covering all published papers up to March, 2014. A total of 9 publications including 10 case-control studies met the inclusion criteria. Odds ratios (ORs) and their 95% confidence intervals (95%CIs) were applied to assess association. The pooled ORs showed significant association in non-Hodgkin lymphoma (comparison A vs G: OR= 1.114, 95%CI=1.053-1.179, p=0.000; homozygote comparison AA vs GG: OR=1.245, 95%CI=1.110-1.396, p=0.000; heterozygote comparison AG vs GG: OR=1.095, 95%CI=1.000-1.199, p=0.05; dominant model AA/GA vs GG: OR=1.137, 95%CI=1.043-1.239, p=0.003; and recessive model AA vs GA/GG: OR=1.177, 95%CI=1.066-1.301, p=0.001). However, there was no association between the CCND1 G870A polymorphism and leukemia risk. In conclusion, the CCND1 G870A polymorphism may increase risk of non-Hodgkin lymphoma, but not leukemia. However, more primary large scale and well-designed studies are still required to evaluate the interaction of CCND1 G870A polymorphism with leukemia and non-Hodgkin lymphoma risk.