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Wan J.,Key Laboratory of Carcinogenesis and Translational Research Ministry of Education | Wan J.,Peking University | Xu W.,Key Laboratory of Carcinogenesis and Translational Research Ministry of Education | Xu W.,Peking University | And 12 more authors.
Nucleic Acids Research | Year: 2016

HOXB9 is a homeobox domain-containing transcription factor, playing an important role in embryonic development and cancer progression. However, the precise post-Translational modifications (PTMs) of HOXB9 and the corresponding roles are unclear. Here, we report that acetyltransferase p300/CBPassociated factor (PCAF) interacts with and acetylates HOXB9 both in vivo and in vitro. Conversely, the acetylation of HOXB9 can be reversed by deacetylase SIRT1. Furthermore, we found that HOXB9 is acetylated at lysine 27 (AcK27). Functionally, in contrast to the wild type HOXB9, AcK27-HOXB9 decreased its capacity in promoting lung cancer cell migration and tumor growth in mice. Mechanistically, AcK27-HOXB9 suppresses the transcription of its target gene Jumonji domain-containing protein 6 (JMJD6) by direct occupying the promoter of JMJD6 gene. For clinical relevance, elevated HOXB9 acetylation at K27 predicts a better prognosis in lung adenocarcinoma patients. Taken together,we identified the first PTM of HOXB9 by demonstrating that HOXB9 can be acetylated and AcK27-HOXB9 counteracts the role of the wild-Type HOXB9 in regulating lung adenocarcinoma progression. © The Author(s) 2016.


Tu H.-K.,Peking University | Tu H.-K.,Key Laboratory of Carcinogenesis and Translational Research Ministry of Education | Pan K.-F.,Key Laboratory of Carcinogenesis and Translational Research Ministry of Education | Zhang Y.,Key Laboratory of Carcinogenesis and Translational Research Ministry of Education | And 5 more authors.
Cancer Epidemiology Biomarkers and Prevention | Year: 2010

Background: Manganese superoxide dismutase is the primary antioxidant enzyme in the mitochondria and is involved in carcinogenesis. To investigate the association between MnSOD Val16Ala polymorphism and risk of advanced gastric lesions, and its effects on chemoprevention, a population-based study was conducted in Linqu, a high-risk area of gastric cancer in China. Methods: Genotypes were determined by PCR-RFLP analysis in 3,355 subjects with the baseline histopathologic diagnosis in 1994, and 2,758 of these subjects received subsequent three interventions including vitamin supplementation for 7.3 years. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by unconditional logistic regression model. Results: We found an increased risk of dysplasia in subjects with the Val/Ala+Ala/Ala genotype (OR, 1.31; 95% CI, 1.02-1.68) compared with the Val/Val genotype. Stratified analysis indicated that a significantly elevated risk of intestinal metaplasia (OR, 3.40; 95% CI, 2.64-4.38) or dysplasia (OR, 4.01; 95% CI, 2.79-5.74) was found in subjects carrying the Val/Ala+Ala/Ala genotype and Helicobacter pylori infection, and an interaction between this genotype and a high serum H. pylori IgG titer (>2.94) on the risk of dysplasia was observed (Pinteraction= 0.01). Furthermore, an elevated chance for regression of gastric lesions was observed in subjects with the Val/Ala+Ala/Ala genotype and high IgG titer in an intervention trial with vitamin supplementation (OR, 2.45; 95% CI, 1.37-4.38). Conclusions: These findings suggest that Val16Ala polymorphism may play an important role in development of advanced gastric lesions and modify the effect of vitamin supplementation on the evolution of gastric lesions. Impact: Val16 Ala polymorphism is related to gastric cancer development. © 2010 AACR.


Li Z.,Key Laboratory of Carcinogenesis and Translational Research Ministry of Education | Li Z.,Peking University | Zhu W.-G.,Key Laboratory of Carcinogenesis and Translational Research Ministry of Education | Zhu W.-G.,Peking University | Zhu W.-G.,Tsinghua University
International Journal of Biological Sciences | Year: 2014

Genetic abnormalities have been conventionally considered as hallmarks of cancer. However, studies over the past decades have demonstrated that epigenetic regulation also participates in the development of cancer. The fundamental patterns of epigenetic components, such as DNA methylation and histone modifications, are frequently altered in tumor cells. Acetylation is one of the best characterized modifications of histones, which is controlled by histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDACs are a group of enzymes which catalyze the removal of the acetyl groups of both histones and non-histone proteins. HDACs are involved in modulating most key cellular processes, including transcriptional regulation, apoptosis, DNA damage repair, cell cycle control, autophagy, metabolism, senescence and chaperone function. Because HDACs have been found to function incorrectly in cancer, various HDAC inhibitors are being investigated to act as cancer chemotherapeutics. The primary purpose of this paper is to summarize recent studies of the links between HDACs and cancer, and further discuss the underlying mechanisms of anti-tumor activities of HDAC inhibitors and clinical implications. © Ivyspring International Publisher.


Yu R.,Key Laboratory of Carcinogenesis and Translational Research Ministry of Education | Sun Y.,Peking University | Cai Q.,The General Hospital of Air Force PLA | Li Y.,Key Laboratory of Carcinogenesis and Translational Research Ministry of Education | Zhu G.,Key Laboratory of Carcinogenesis and Translational Research Ministry of Education
Chinese Journal of Lung Cancer | Year: 2011

Background and objective Radiation-induced lung injure is one of the major factors of limitation in radiotherapy for lung cancer. Whether the use of thymosin and radiotherapy simultaneously would increase the radiation-induced lung injure is unclear. The aim of this study is to evaluate the effects of thymosin alpha-1 on radiation induced pneumonitis in mice. Methods Three groups of mice, control (C), radiation alone (RT), thymosin alpha-1 plus radiation (T+RT), were entered into the study. The weight and mortality of mice, pleural effusion, quantity of protein and cell count in the bronchoalvealar lavage (BAL) and pulmonary fibrosis score were evaluated as the outcome measures. Results The mortality ratio of the T+RT and RT groups were 3/14, 2/10, respectively. The time of death were all in the 23-24 weeks after radiotherapy. There was no pleural effusion in the T+RT group other than 2/2 occured in RT group. The quantity of protein, cell number and neutrophil number in the BAL and lung coefficient in mice of T+RT group were remarkably lower than that of RT group, but the BALF macrophages number was remarkably higher than that in RT group in the 8 weeks. The quantity of protein, cell number, neutrophil number and macrophages number in the BAL, lung coefficient, the scores of lung fibrosis in mice of T+RT group were significantly lower than that of RT group in the 24 weeks. All test data were lowest in mice of C group. And there was no obvious pulmonary fibrosis in the mice of C group. Conclusion Thymosin alpha-1 could relieve radiation-induced acute and late pulmonary injuries.


Bu Z.,Key laboratory of Carcinogenesis and Translational Research Ministry of Education | Bu Z.,Peking University | Ji J.,Key laboratory of Carcinogenesis and Translational Research Ministry of Education | Ji J.,Peking University
Current Cancer Drug Targets | Year: 2013

Gastric cancer remains one of the most common types of cancer worldwide, and most patients present with advanced disease. Sixty percent of these patients eventually relapse after curative surgical resection, and combination chemotherapy regimens only provide limited survival benefits. Mammalian target of rapamycin (mTOR) is a new target of cancer therapies. Preclinical data suggest that the suppression of the mTOR pathway inhibits the progression of gastric cancer in vitro and in animal models. In clinical trials, the mTOR inhibitor, everolimus, was well tolerated in phase I/II studies on patients with metastatic gastric cancer. The efficacy of everolimus was promising in a phase II clinical trial, but in a recently published phase III clinical trial everolimus monotherapy do not significantly improve the overall survival of patients with advanced gastric cancer who had been previously treated with one or two lines of systemic chemotherapy. Phosphoinositide 3-kinase/mTOR dual inhibitors have not yet entered early-stage clinical trials in patients with advanced gastric cancer. Further studies are needed to establish the role of mTOR inhibitors for the treatment of gastric cancer. © 2013 Bentham Science Publishers.


Dai N.,Key Laboratory of Carcinogenesis and Translational Research Ministry of Education | Xu D.,Key Laboratory of Carcinogenesis and Translational Research Ministry of Education | Zhong X.,Key Laboratory of Carcinogenesis and Translational Research Ministry of Education | Li L.,Key Laboratory of Carcinogenesis and Translational Research Ministry of Education | And 3 more authors.
Journal of Thoracic Disease | Year: 2014

We have entered an open access publishing era. The impact and significance of open access is still under debate after two decades of evolution. Open access journals benefit researchers and the general public by promoting visibility, sharing and communicating. Non-mainstream journals should turn the challenge of open access into opportunity of presenting best research articles to the global readership. Open access journals need to optimize their business models to promote the healthy and continuous development.


PubMed | Chinese Institute of Materia Medica and Key Laboratory of Carcinogenesis and Translational Research Ministry of Education
Type: Journal Article | Journal: Biomedical chromatography : BMC | Year: 2016

Marsdenia tenacissima, which is widely used as an anticancer herb in traditional Chinese medicine, has been shown to possess anticancer activity. However, its metabolic profile is poorly investigated. Tenacigenin B is the major steroidal skeleton of C-21 steroids in M. tenacissima. Tenacissoside H and Tenacissoside I are detected at relatively high levels in M. tenacissima. Therefore, we studied their metabolic characteristics in human liver microsomes by ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry. Fourteen metabolites were tentatively identified by accurate mass measurement and MS/MS fragmentation behavior. It was found that hydroxylation reactions were the major metabolic pathway of Tenacissoside H and Tenacissoside I in human liver microsomes, whereas the metabolic pathway of Tenacigenin B involved dehydrogenation reactions. This is the first time that the metabolic profile of C-21 steroids from M. tenacissima has been explored in human liver microsomes, which is of great significance for subsequent pharmacokinetic and interaction research. Biotransformation in vivo or in vitro may influence the structure of a compound and change its activity. Identification of their fragmentation behaviors and metabolites provides valuable and new information for further understanding the anti-tumor activity of M. tenacissima. Copyright 2016 John Wiley & Sons, Ltd.


PubMed | Key Laboratory of Carcinogenesis and Translational Research Ministry of Education
Type: Journal Article | Journal: Hepato-gastroenterology | Year: 2013

We aimed to evaluate whether elevated serum synuclein-gamma levels were of clinical significance as a serological marker in cancer diagnosis and monitoring.Pre-treatment serum synuclein-gamma levels of patients with gastrointestinal and esophageal squamous cell carcinomas, benign disease and healthy controls were analyzed by a specific sandwich ELISA for synuclein-gamma.Statistically significant differences in serum synuclein-gamma levels between patients with colo rectal cancer, gastric adenocarcinomas, esophageal cancer and healthy individuals were observed (p<0.001). When a cut-off value for synuclein-gamma was determined at 4 ng/mL by receiver operating characteristic curves, sensitivity and specificity were 16.4% and 97.7% in colorectal cancer, 23.0% and 99.3% in gastric adenocarcinomas, and 19.5% and 98.7% in esophageal cancer, respectively. Compared with carcinoembryonic antigen and carbohydrate antigen 19-9, synuclein-gamma was more sensitive in early detection of colorectal cancer (17.3% vs. 9.6% and 7.5%), gastric adenocarcinomas (20.6% vs. 0% and 3.2%) and esophageal cancer (22.2% vs. 3.4% and 0%), respectively. A combined analysis of the above markers yielded incremental positive rates compared with anyone alone.These results indicated that serum synuclein-gamma provided a promising diagnostic biomarker for early detection and was a complementary biomarker of carcinoembryonic antigen and/or CA19-9 in gastrointestinal and esophageal cancer.


PubMed | Key Laboratory of Carcinogenesis and Translational Research Ministry of Education
Type: Journal Article | Journal: Chinese journal of cancer research = Chung-kuo yen cheng yen chiu | Year: 2013

Most recurrent intrahepatic cholangiocarcinoma (RICC) lost the opportunity of radical resection while most nonsurgical management failed to prolong patients survival. The efficacy and safety of radiofrequency ablation (RFA) as a local treatment for recurrent hepatocellular carcinoma have been confirmed by many clinical studies. The purpose of this study was to evaluate the efficacy, long-term survival and complications of RFA for RICC.A total of 12 patients with 19 RICCs after radical resection were included in this study. The tumors were 1.9-6.8 cm at the maximum diameter (median, 3.21.6 cm). All patients were treated with ultrasound guided RFA. There were two RFA approaches including percutaneous and open.A total of 18 RFA treatment sessions were performed. Ablation was successful (evaluated by 1-month CT after the initial RFA procedure) in 18 (94.7%) of 19 tumors. By a median follow-up period of 29.9 months after RFA, 5 patients received repeated RFA because of intrahepatic lesion recurrence. The median local recurrence-free survival period and median event-free survival period after RFA were 21.0 months and 13.0 months, respectively. The median overall survival was 30 months, and the 1- and 3-year survival rates were 87.5% and 37.5%, respectively. The complication rate was 5.6% (1/18 sessions). The only one major complication was pleural effusion requiring thoracentesis.This study showed RFA may effectively and safely manage RICC with 3-year survival of 37.5%. It provides a treatment option for these RICC patients who lost chance for surgery.


PubMed | Key Laboratory of Carcinogenesis and Translational Research Ministry of Education
Type: Journal Article | Journal: Chinese journal of cancer research = Chung-kuo yen cheng yen chiu | Year: 2013

To investigate the value of c-Met in predicting progression of precancerous gastric lesions.A population-based study was conducted to detect the overexpression of c-Met by immunohisto- chemical analysis in 124 subjects with precancerous gastric lesions. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated for the association of c-Met overexpression with the risk of advanced gastric lesions.The positive rates of c-Met were 55.7% in intestinal metaplasia (IM) and 64.8% in dysplasia (DYS), respectively. Stratified analysis indicated that the proportion of c-Met overexpression was 71.4% for IM progressive group, significantly higher than that for IM persistent group (40.0%, P<0.05). Compared to the IM persistent group, unconditional logistic regression showed that OR of c-Met overexpression for the IM progressive group was 7.416 (95% CI: 2.084-26.398).c-Met plays an important role in gastric carcinogenesis. Detection of c-Met is of value in predicting progression of precancerous gastric lesions from IM to DYS.

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