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Wang L.,Peking University | Wang L.,Jilin University | Du Y.,Key Laboratory of Carcinogenesis and Translational Research | Lu M.,Peking University | Li T.,Peking University
Nucleic Acids Research | Year: 2012

Protein lysine acetylation plays an important role in the normal functioning of cells, including gene expression regulation, protein stability and metabolism regulation. Although large amounts of lysine acetylation sites have been identified via large-scale mass spectrometry or traditional experimental methods, the lysine (K)-acetyl-transferase (KAT) responsible for the acetylation of a given protein or lysine site remains largely unknown due to the experimental limitations of KAT substrate identification. Hence, the in silico prediction of KAT-specific acetylation sites may provide direction for further experiments. In our previous study, we developed the acetylation set enrichment based (ASEB) computer program to predict which KAT-families are responsible for the acetylation of a given protein or lysine site. In this article, we provide KAT-specific acetylation site prediction as a web service. This web server not only provides the online tool and R package for the method in our previous study, but several useful services are also included, such as the integration of protein-protein interaction information to enhance prediction accuracy. This web server can be freely accessed at http://cmbi.bjmu.edu.cn/ huac. © 2012 The Author(s).

Deng Q.J.,Key Laboratory of Carcinogenesis and Translational Research | Wang C.Y.,Hua County Bureau of Health | Li F.L.,Hua County Peoples Hospital
Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences | Year: 2013

To determine the epidemiological characteristics and associated risk factors of hepatitis B surface antigens (HBsAg) prevalence in rural areas of Hua County, Henan Province, and to provide scientific evidence for Hepatitis B prevention and control in local areas. On the basis of an ongoing esophageal cancer cohort study in rural Anyang, a total of 5 104 subjects aged 25-65 years were clustered and selected from 5 targeted villages for this study in rural areas of Hua County, Henan Province. HBsAg was detected in their blood samples and a questionnaire was completed by all the subjects in a manner of one-on-one interview. All statistical analyses were conducted using SPSS for Windows version 13.0. Of the 5 104 studied subjects (overall participation rate: 92.05%), 5.17% were positive for HBsAg. The detection rate was significantly higher in males than in females (6.54% vs. 3.87%, P<0.001) and the highest detection rates were observed in the 25-29 and 55-59 years groups in both males and females. Multiple Logistic analyses showed unmarried status (OR=1.80, 95% CI: 1.00-3.25) and high frequency of sexual intercourse (Ptrend=0.049) were associated with higher the risk for hepatitis B virus (HBV) infection. The prevalence of HBsAg in rural Hua County, Henan Province, was slightly lower than the national average of the same time period. More attention should be attached to high risk groups of HBV infection in this population, i.e. males aged 25-29 years and 55-59 years and sexually active population. Immunization and health education projects against hepatitis B should be carried out in this population to further reduce the overall prevalence of hepatitis B.

Yang W.,Key Laboratory of Carcinogenesis and Translational Research | Cui M.,Peking University | Lee J.,Key Laboratory of Carcinogenesis and Translational Research | Gong W.,Beijing Institute of Pharmacology and Toxicology | And 5 more authors.
Chinese Journal of Cancer Research | Year: 2016

Background: We investigated the effect of a small molecular inhibitor of heat shock protein (HSP), quercetin, on tumor radiofrequency (RF) ablation, and explored the underlying molecular mechanisms. Methods: In in vivo study, rats with R3230 breast adenocarcinoma were sacrificed 24 h post-treatment and gross coagulation areas were compared, and next, randomized into four treatment arms (control, quercetin alone, RF alone, and combination) for Kaplan-Meier analysis of defined endpoint survival. Then the distribution and expression levels of heat shock protein 70 (HSP70), cleaved caspase-3 and heat shock factor 1 (HSF1) were analyzed after different treatments. In in vitro study, we used quercetin to promote SK-HEP-1 (hepatic) and MCF-7 (breast) cancer cell apoptosis in heat shock cell model, and siRNA was used to block c-Jun and to explore the role of activating protein-1 (AP-1) signaling pathways. Results: We found the effects of quercetin plus RFA resulted in increase on the tumor destruction/endpoint survival (26.5±3.4 d) in vivo, compared with RF alone (17.6±2.5 d) and quercetin alone (15.7±3.1 d). Most importantly, quercetin-induced cancer cell death required the presence of HSF1 in animal model. Furthermore, quercetin directly down-regulated expression of HSF1 in vitro, which our findings have revealed, required the activation of AP-1 signaling pathways by loss-of-function analysis using siRNA mediated targeting of c-Jun. Conclusions: These results indicated a protective role of quercetin in tumor ablation and highlighted a novel mechanism involving HSP70 with HSF1 pathway in thermal ablation of solid tumors. © Chinese Journal of Cancer Research. All rights reserved.

Cao J.,Peking University | Jin J.,Beijing Hospital | Deng D.,Key Laboratory of Carcinogenesis and Translational Research | Liu H.,Peking University
Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences | Year: 2016

METHODS: The hybrid capture (HC-II) was used to detect infection of HPV in 255 samples taken from 12 cases of healthy oral mucosa, 211 cases of patients with pathological diagnosis and 32 cases of patients with clinical diagnosis. The diagnosed cases included 8 cases of benign lesions of the oral mucosa, precancerous lesions [74 cases of oral leukoplakia (OLK) with hyperplasia and 42 cases of OLK with oral epithelial dysplasia (OED)], 91 cases of precancerous condition [oral lichen planus (OLP)] and 28 cases of oral squamous cell carcinoma (OSCC). And in situ hybridization (ISH) was used to detect infection of HPV in 33 cases of OSCC and 76 cases of OLK, including 30 cases of hyperplasia, 15 cases of mild OED, 15 cases of moderate OED and 16 cases of severe OED.RESULTS: The prevalence of HPV in OLP samples was higher (12.12%, 8/66) than that of OLK (2.59%, 3/116) (χ(2)=4.666, P=0.031) and OSCC(7.14%, 2/28, χ(2)=0.513, P=0.474). The prevalence of HPV in OSCC (7.14%, 2/28) was higher than that of OLK (2.59%, 3/116), and no significant difference was found. There was only one case of smoke spot and statistical analysis was not carried out. ISH was used to detect type 16/18 and type 31/33 HPV DNA in 109 cases of oral mucosal lesions in paraffin sections and only one case of OSCC was HPV positive. Thirty-seven cases were detected by HC-II and ISH methods at the same time. The same negative results by the two methods were found in 94.6% samples (35/37). In the other two samples, one was OSCC with early infiltration and the other was OLK with hyperplasia, The HC-II results were positive while the ISH results were negative. The patients with OLP and HPV testing results were followed up and the average follow-up period was (36.2 ± 10.5) months. It was found that three of them had a malignant transformation, and the malignant transformation rate of HPV positive patients was 12.50% (1/8), which was higher than that of HPV negative patients (3.45%, 2/58), and the difference was not statistically significant, P=0.249.CONCLUSION: HC-II assay was more sensitive in detecting HPV infection of oral mucosal lesions than ISH. The results of this study showed that there was insufficient evidence for taking HPV infection as a predictor of OLK carcinogenesis. Patients suffering from OLP were in a precancerous condition. The prevalence of HPV in OLP patients of this study was higher than that in OLK and OSCC patients, suggesting that for some reason, OLP patients were susceptible to HPV. HPV testing can be considered as routine in patients with OLP, and HC-II assay was recommended. And patients with OLP and HPV positive should be followed up regularly.OBJECTIVE: To investigate the possibility for human papillomavirus (HPV) infection to be a predictable signal for the carcinogenesis of oral mucosa by comparing the prevalences of HPV in each stage of oral mucosal carcinogenesis and to compare the sensitivity differences of the two methods in detecting HPV infection in oral cavity.

Liu Z.,Peking University | Liu H.,Peking University | Ma T.,Peking University | Sun X.,Peking University | And 10 more authors.
Journal of Nuclear Medicine | Year: 2014

Integrin αvβ6, a member of the integrin family, is specifically expressed in many malignancies but not in normal organs. Overexpression of integrin αvβ6 is usually correlated with malignant potential and poor prognosis. In this study, we describe the synthesis and evaluation of a 99mTc-labeled integrin αvβ6-targeting peptide as a SPECT radio-tracer for the in vivo imaging of integrin αvβ6 expression. Methods: An integrin αvβ6-targeting peptide (denoted as the HK peptide) was conjugated with 6-hydrazinonicotinyl (HYNIC) and radiolabeled with 99mTc using tricine and TPPTS (trisodium triphenylphosphine-3,3′,3″- trisulfonate) as coligands. The in vitro and in vivo characteristics of 99mTc-HYNIC(tricine) (TPPTS)-HK (99mTc-HHK) were investigated in BxPC-3 (integrin αvβ6-positive) and HEK293 (integrin αvβ6-negative) models. The ability of 99mTc-HHK to detect liver metastasis of pancreatic cancer was evaluated using small-animal SPECT/CT. Results: 99mTc-HHK showed high integrin αvβ6 -binding specificity both in vitro and in vivo. 99mTc-HHK was cleared rapidly from the blood and normal organs except for the kidneys. The highest uptake (0.88 ± 0.12 percentage injected dose per gram) of 99mTc-HHK in BxPC-3 tumors was observed at 0.5 h after injection. High-contrast images of integrin αvβ6-positive tumors were obtained using 99mTc- HHK. The minimum nonspecific activity accumulation in normal liver tissues rendered high-quality SPECT/CT images of metastatic lesions. Conclusion: 99mTc-HHK is a promising SPECT radiotracer for the noninvasive imaging of integrin αvβ6 expression in vivo. SPECT/ CT with 99mTc-HHK could provide an effective approach for the noninvasive detection of primary and metastatic lesions of integrin αvβ6-positive tumors. Copyright © 2014 by the Society of Nuclear Medicine and Molecular Imaging Inc.

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