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Wu C.,Peking Union Medical College | Miao X.,Huazhong University of Science and Technology | Huang L.,Peking Union Medical College | Che X.,Chinese Academy of Sciences | And 34 more authors.
Nature Genetics | Year: 2012

Pancreatic cancer has the lowest survival rate among human cancers, and there are no effective markers for its screening and early diagnosis. To identify genetic susceptibility markers for this cancer, we carried out a genome-wide association study on 981 individuals with pancreatic cancer (cases) and 1,991 cancer-free controls of Chinese descent using 666,141 autosomal SNPs. Promising associations were replicated in an additional 2,603 pancreatic cancer cases and 2,877 controls recruited from 25 hospitals in 16 provinces or cities in China. We identified five new susceptibility loci at chromosomes 21q21.3, 5p13.1, 21q22.3, 22q13.32 and 10q26.11 (P = 2.24 × 10 -13 to P = 4.18 × 10 -10) in addition to 13q22.1 previously reported in populations of European ancestry. These results advance our understanding of the development of pancreatic cancer and highlight potential targets for the prevention or treatment of this cancer.


Gu H.,Shanghai JiaoTong University | Guo F.,Shanghai JiaoTong University | Zhou X.,Hunan Province Tumor Hospital | Gong L.,Shanghai JiaoTong University | And 7 more authors.
Biomaterials | Year: 2011

Our previous study indicates that akermanite, a type of Ca-, Mg-, Si-containing bioceramic, can promote the osteogenic differentiation of hASCs. To elucidate the underlying mechanism, we investigated the effect of the extract from akermanite, on proliferation and osteogenic differentiation of hASCs. The original extract was obtained at 200 mg akermanite/ml LG-DMEM and further diluted with LG-DMEM. The final extracts were denoted as 1/2, 1/4, 1/8, 1/16, and 1/32 extracts based on the concentrations of the original extract. The LDH assay and live/dead stain were used to reveal the cytotoxicity of the different extracts on hASCs, while the DNA assay was carried out to quantitatively evaluate the proliferation of cells after being cultured with the extracts for 1, 3 and 7 days. Flow cytometry for cell cycle analysis was carried out on cells cultured in two media (GM and 1/2 extract) in order to further analyze the effect of the extract on cell proliferation behaviors. Osteogenic differentiation of hASCs cultured in the extracts was detected by ALP expression and calcium deposition, and further confirmed by real-time PCR analysis. It was shown that Ca, Mg and Si ions in the extract could suppress the LDH release and proliferation of hASCs, whereas promote their osteogenic differentiation. Such effects were concentration-dependent with the 1/4 extract (Ca 2.36 mM, Mg 1.11 mM, Si 1.03 mM) being the optimum in promoting the osteogenic differentiation of hASCs. An immediate increase in ERK was observed in cells cultured in the 1/4 extract and such osteogenic differentiation of hASCs promoted by released ions could be blocked by MEK1-specific inhibitor, PD98059. Briefly, Ca, Mg and Si ions extracted from akermanite in the concentrations of 2.36, 1.11, 1.03 mM, respectively, could facilitate the osteogenic differentiation of hASCs via an ERK pathway, and suppress the proliferation of hASCs without significant cytotoxicity. © 2011 Elsevier Ltd.


Shen T.,Zhejiang Provincial Peoples Hospital | Pan Z.-G.,Fudan University | Zhou X.,Hunan Province Tumor Hospital | Hong C.-Y.,Zhejiang Provincial Peoples Hospital
Chinese Medical Journal | Year: 2013

Background Diabetic wound is one of the most serious complications of diabetes mellitus. There are no significantly effective therapies for chronic non-healing diabetes ulcer so far. This study aimed to explore the feasibility of healing impaired wound using artificial dermis constructed with human adipose derived stem cells (ASCs) and poly(L-glutamic acid)/chitosan (PLGA/CS) scaffold in streptozotocin-induced diabetic mice. Methods ASCs were isolated from fresh human lipoaspirates and expanded ex vivo for three passages, and then cells were seeded onto PLGA/CS scaffold to form artificial dermis. Expression of VEGF and TGF β1 by ASCs presented in artificial dermis was determined. The artificial dermis was transplanted to treat the 20 mm × 20 mm full-thickness cutaneous wound created on the back of diabetic mice. Wound treated with scaffold alone and without treatment, and wound in normal non-diabetic mice served as control. Results Cells growing within scaffold showed great proliferation potential, depositing abundant collagen matrix. Meanwhile, expression of VEGF and TGF-β1 by seeded ASCs maintained at a consistent high level. After treated with ASC based artificial dermis, diabetic wounds exhibited significantly higher healing rate compared with wounds treated with scaffold alone or without treatment. Histological examination also demonstrated an improvement in cutaneous restoration with matrix deposition and organization. Further quantitative analysis showed that there was a significant increase in dermis thickness and collagen content on artificial dermis treated wounds. Conclusion ASC/PLGA artificial dermis can effectively accelerate diabetic wound healing by promoting angiogenic growth factors and dermal collagen synthesis.


PubMed | Chinese Academy of Sciences, Shandong University, Peking Union Medical College, Harbin Medical University and 2 more.
Type: | Journal: Lancet (London, England) | Year: 2016

Comprehensive health economic evaluation, a key component of the Cancer Screening Program in Urban China (CanSPUC), was expected to support government policy-making on screening initiatives for common cancers (lung, breast, colorectal, oesophageal, liver, and stomach cancer) in urban China. Estimation of expenditure for cancer diagnosis and treatment from a societal perspective was an essential component. The aim of this study was to estimate direct medical and non-medical expenditure and to discern the resultant financial burden.A multicentre cross-sectional survey of patients with target cancers or precancerous lesions was conducted in 37 tertiary hospitals in 13 provinces across China, from 2012 to 2014. Each patient was interviewed with a structured questionnaire for sociodemographic, clinical, and expenditure information. Expenditure data was converted to 2014 values and presented as US$. Expenditure and financial burden were quantified as a whole and by subgroups.Of the included 14594 patients with cancer (mean age 567 years, 58% male), annual household income was $8607. Mean expenditure per patient was $9739 (95% CI 9612-9866), and non-medical expenditure accounted for 93%. Expenditure per patient with colorectal, oesophageal, lung, stomach, liver or breast cancer was $10978 (10636-11321), $10506 (10199-10813), $9970 (9664-10 276), $9891 (9606-10176), $8668 (8358-8977) and $8532 (8234-8831), respectively. Expenditure increased from stage I to stage IV for colorectal, stomach, and breast cancer (p<00001). Out-of-pocket expenditure of newly diagnosed cancer (2 months before and 10 months after diagnosis) per cancer patient was $4947 (4875-5020), accounting for 575% of annual household income, presenting 776% of families with an unmanageable financial burden. Apart from cancer site and stage, hospital type, education, occupation, insurance type, and previous years household income were also significant predictors of expenditure (F=2479, 563, 297, 128, and 287, respectively; all p<00001) as well as self-reported financial burden (Expenditure for diagnosis and treatment seemed catastrophic for patients with cancer in China, and non-medical expenditure was substantial. Expenditure and financial burden varied within subgroups, especially between patients with different degrees of lesions, suggesting that cancer screening might be cost-effective in China.National Health and Family Plan Committee of China.


PubMed | Chinese Academy of Sciences, Harbin Medical University, Lanzhou University, Hunan Province Tumor Hospital and Peking Union Medical College
Type: | Journal: Lancet (London, England) | Year: 2016

The measurement of quality-adjusted life-years (QALYs) forms a key component of cost-utility evaluation in cancer intervention; however, detailed data for utility weights by cancer type and health status are still scarce both in China and other regions. The aim of this study was to systematically evaluate utility scores in relation to the most common six cancers in China in 2012 (lung, breast, colorectal, oesophageal, liver, and stomach cancer).As a part of a Screening Program in Urban China (CanSPUC) supported by the central government of China, we undertook a cross-sectional survey in 13 provinces across China from 2013 to 2014. Two generic instruments, EQ-5D (EuroQol 5-dimensions) and SF-12 (12-item Short Form Health Survey), and a cancer-specific instrument, FACTs (Function Assessment of Cancer Therapy) were applied. 46394 participants were interviewed in five groups: general population (n=11699, group A), individuals who had attended single cancer screening (n=11805, group B), individuals who had attended multiple screenings (n=6838, group C), patients with precancerous lesions (n=1942, group D), and patients with cancer (n=14 110, group E). All participants had no psychosis and provided written consent to participate in the study. The survey was approved by the Institutional Review Board of the Cancer Hospital of Chinese Academy of Medical Sciences.The EQ-5D utility scores were 096 (95% CI 096-096) for group A, 094 (094-094) for group B, 094 (094-094) for group C, 085 (084-086) for group D, and 077 (077-077) for group E. Cancer-specific analysis showed that EQ-5D utility scores were 077 (076-078) for lung cancer, 078 (077-079) for breast cancer, 075 (074-076) for colorectal cancer, 075 (074-076) for oesophageal cancer, 080 (079-081) for liver cancer, and 076 (075-077) for stomach cancer. The utility scores for cancer at different clinical stages also differed; for example, the scores for patients with breast cancer were estimated as 079 (077-080) at stage I, 079 (078-080) at stage II, 077 (076-079) at stage III, and 069 (065-072) at stage IV. Compared with data from EQ-5D, results from SF-12 on differences among subgroups seemed narrower; for example, the utility score among the six cancers ranged from 060 to 062.These data will be applied to future cost-utility evaluation on various cancer screening strategies in China, and could contribute more precise evaluation of burden of disease related to disability-adjusted life-years globally.The National Health and Family Plan Committee of China.


PubMed | Hunan Normal University and Hunan Province Tumor Hospital
Type: Journal Article | Journal: Oncology letters | Year: 2014

Casticin is an active ingredient derived from Fructus Viticis, a traditional Chinese medicine. This study aimed to investigate the role of forkhead box O3 (FOXO3a) in breast cancer cells and examine the regulatory mechanisms of FOXO3a in response to casticin treatment of the cells by ELISA, flow cytometry, small interfering RNA (siRNA) transfection and western blot analysis. Casticin treatment induced apoptosis and reduced the expression of the transcription factor forkhead box protein M1 (FOXM1). In addition, FOXM1 repression induced by casticin treatment was associated with the activation of FOXO3a via increased dephosphorylation. Notably, silencing FOXO3a expression by siRNA-mediated gene knockdown attenuated casticin-mediated apoptosis. Collectively, these findings suggest that FOXO3a is a critical mediator of the inhibitory effects of casticin on apoptosis in breast cancer cells.


Liu W.,Central South University | Yin T.,Central South University | Ren J.,Central South University | Li L.,Nanchang University | And 3 more authors.
European Archives of Oto-Rhino-Laryngology | Year: 2014

Cholesteatoma is a benign keratinizing squamous epithelial lesion characterized by the hyper-proliferation of keratinocytes with abundant production of keratin debris in the middle ear. The epidermal growth factor receptor (EGFR)/Akt/nuclear factor-kappa B (NF-κB)/cyclinD1 signaling pathway is one of the most important pathways in regulating cell survival and proliferation. We hypothesized that the EGFR/Akt/NF-κB/cyclinD1 signaling pathway may be activated and involved in the cellular hyperplasia mechanism in acquired cholesteatoma epithelium. Immunohistochemical staining of phosphorylated EGFR (p-EGFR), phosphorylated Akt (p-Akt), activated NF-κB and cyclinD1 protein was performed in 40 cholesteatoma samples and 20 samples of normal external auditory canal (EAC) epithelium. Protein expression of p-EGFR, p-Akt, activated NF-κB and cyclinD1 in cholesteatoma epithelium was significantly increased when compared with normal EAC epithelium (p < 0.01). In cholesteatoma epithelium, a significant positive association was observed between p-EGFR and p-Akt expression and between the expressions of p-Akt and NF-κB, NF-κB and cyclinD1, respectively (p < 0.01). No significant relationships were observed between the levels of investigated proteins and the degree of bone destruction (p > 0.05). The increased protein expression of p-EGFR, p-Akt, NF-κB and cyclinD1 and their associations in cholesteatoma epithelium suggest that the EGFR/Akt/NF-κB/cyclinD1 survival signaling pathway is active and may be involved in the regulatory mechanisms of cellular hyperplasia in cholesteatoma epithelium. © Springer-Verlag 2013.


Chen J.,Hunan Province Tumor Hospital
Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery | Year: 2011

To investigate the diagnosis and treatments of thyroid goiters invading mediastinum and thoracic cavity. Seventy-eight cases of thyroid goiters invading mediastinum and thoracic cavity and undergoing surgery from 1995 to 2005 were reviewed. There were 22 males and 56 females and their age ranged from 45 years to 78 years with a median age of 59 years. According to the classification of intrathoracic thyroid goiters, there were 50 cases in Class I, 20 cases in Class II and 8 cases in Class III. In these patients, 38 cases suffered from dyspnea at degree I and 20 cases at degree II. Of the patients, 71 underwent thyroidectomy through neck approach and 7 underwent thyroidectomy by a combined approach of neck incision plus sternotomy or lateral thoracotomy. Tracheal defects in 4 cases and esophageal defects in 3 cases were repaired. Postoperative residual diseases were found in tracheoesophageal wall (5 cases) and mediastinum (6 cases). Eleven patients received postoperative radiotherapy and 18 underwent (131)I treatment. No case died of operation and no case with wound infection. The time of follow-up was 60 - 180 months with a median of 110 months. Three patients lost follow-up. Dyspnea in 58 cases were improved after operation. Three of 49 patients with nodular goiters died from cardiocerebrovascular diseases. Of 29 patients with thyroid papillary carcinoma, 2 died from lung metastasis and 3 died from neck relapse. Five-year survival rate was 75.0% in the patients with thyroid cancer. Most of thyroid goiters invading mediastinum and thoracic cavity can be completely resected via neck approach, but a combined approach of neck incision plus sternotomy or lateral thoracotomy may be used in some cases with malignant goiters to dissect the diseases completely. Postoperative external beam radiotherapy are required for the residual diseases. (131)I may be considered in high-risk differentiated thyroid carcinoma cases.


Chen J.,Hunan Province Tumor Hospital
Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery | Year: 2012

To investigate the surgical managements for residual or recurrent diseases in the neck after radiotherapy in nasopharyngeal carcinoma. Seventy-eight cases of neck masses (39 cases for unilateral residual diseases, 9 for bilateral residual diseases and 30 for recurrent diseases) after radiotherapy in nasopharyngeal carcinoma who were treated surgically between January 1990 and December 2005 were retrospectively analyzed. There were 56 males and 22 females. Their ages ranged from 28 to 65 years (median 41 years). There were 27 patients with skin involvement. After preoperative imaging assessment, 17 patients whose common carotid arteries or internal carotid arteries were difficult to separate routinely attained the carotid balloon occlusion test which confirmed that 15 cases of cerebral arterial circle open to compensation, however, two cases of poor compensation. Surgical procedures included expanded neck mass resection (21 cases), unilateral radical neck dissection (49 cases) and bilateral radical neck dissection (8 cases). Of them 5 patients were with unilateral internal carotid artery resection. Neck defects were repaired with pectoralis major muscle flaps (15 cases), free anterolateral femoral skin flaps (9 cases) and trapezius muscle flaps (3 cases). Of the 78 patients, 13 with microscopic positive diseases and 2 with residual diseases in internal carotid artery walls underwent postoperative radiotherapy, with the doses of 45 to 50 Gy. All patients were closely followed-up more than 5 years. Three- and five-year survival rates were 46.2% and 28.3% respectively. Neck defects were successfully repaired with skin flaps immediately after resecting diseases in 27 cases, only one patient with delayed healing. Of 51 patients without skin flap repair, neck wounds healed successfully in 45 patients and with delayed healing in 6 patients. Pathological positive rates of lymph nodes located in the level I, II, III, IV and V were 10.5%, 61.4%, 10.5%, 1.8% and 28.1% respectively. Preoperative balloon occlusion test is required to assess the function of Willis' ring before determining ligation or resection of internal carotid artery. Residual or recurrent diseases commonly exist in level II, VA and III, which should be included in neck dissection. Pectoralis major muscle flap and free anterolateral femoral skin flap are recommended for the repair of neck defect.


PubMed | Womens Reproductive Health Laboratory of Zhejiang Province, Hunan Province Tumor Hospital and Huazhong University of Science and Technology
Type: | Journal: Scientific reports | Year: 2017

To identify genomic markers associated with the response to neoadjuvant chemotherapy (NACT) in patients with cervical cancer, we performed a three-stage genome-wide association study (GWAS) in the Han Chinese population. A total of 596 patients with stage IA2-IIIB cervical cancer were enrolled in this study. One single nucleotide polymorphism (SNP) (rs6812281, per allele OR=2.37, P=9.010

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