Zhu G.-H.,Fengxian Central Hospital |
Huang C.,Shanghai JiaoTong University |
Huang C.,Shanghai Key Laboratory of Pancreatic Diseases |
Feng Z.-Z.,Shanghai JiaoTong University |
And 3 more authors.
Digestive Diseases and Sciences | Year: 2013
Background: Intratumoral hypoxia and epithelial-mesenchymal transition are involved in tumor invasion and metastasis. Aims: This study investigated the molecular mechanisms that relay the hypoxia signal into the epithelial- mesenchymal transition and metastasis. Methods: Morphology analysis and tumor cell migration and invasion assays were performed to detect phenotypic changes of pancreatic cancer cells under normoxic and hypoxic conditions after lentiviral HIF-1α shRNA transfection. Quantitative reverse transcription polymerase chain reaction, western blot, and immunohistochemistry were used to detect gene expression in pancreatic cancer cell lines and tissues or normal pancreatic tissues. Luciferase, gel shift, and ChIP assays were used to assess gene regulation. Results: Under hypoxic conditions, these tumor cells underwent typical morphological and molecular changes to epithelial-mesenchymal transition. Moreover, Snail expression was induced by hypoxic conditions and was regulated by HIF-1α expression at the transcriptional level through HIF-1α-binding to the second site of hypoxia-responsive elements of the Snail gene promoter. In addition, Snail expression was associated with HIF-1α expression in pancreatic cancer tissues, and expression of both was associated with tumor metastasis and poor patient survival. Conclusions: Our study provides key evidence that HIF-1α and Snail are responsible for hypoxia-induced metastasis phenotypes in pancreatic cancer and that HIF-1α and Snail expression can be used as biomarkers to predict tumor metastasis and patient survival. © 2013 Springer Science+Business Media New York.
Wang R.,Fengxian Central Hospital
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2012
To compare the expression patterns of cytokeratin 7 (CK7) and CK20 in the Barrett's esophagus and gastric cardia intestinal metaplasia. Endoscopic biopsy specimens from 19 patients with long segment Barrett's esophagus, 36 with short segment Barrett's esophagus, and 20 with histological evidence of gastric cardia intestinal metaplasia were immunostained for CK7 and CK20. The immunohistochemical data were analyzed in relation with the clinicopathological data of the patients including age, hiatal hernia, and Helicobacter pylori status. The Barrett's pattern of CK7/20 expressions was found in all the 19 patients with long segment Barrett's esophagus, in 31 of the 36 (82%) patients with short segment Barrett's esophagus, and in 2 of the 20 (10%) patients with gastric cardia intestinal metaplasia. Patients with short segment Barrett's esophagus who had a Barrett's CK7/20 pattern showed similar clinicopathological findings to those with long segment Barrett's esophagus, while in cases of short segment Barrett's esophagus where no Barrett's CK7/20 pattern was found, the clinicopathological features were similar to those of gastric cardia intestinal metaplasia cases. A Barrett's CK7/20 expression pattern is an objective marker of Barrett's mucosa. CK7 and CK20 reactivity patterns in routine endoscopic biopsy samples can reliably identify the location of intestinal metaplasia in the esophagus and stomach.
Duan J.J.,Fengxian Central Hospital |
Zhou T.,Fengxian Central Hospital |
Chen X.,Zhujiang Hospital |
Wang Y.,Fengxian Central Hospital |
And 2 more authors.
European Review for Medical and Pharmacological Sciences | Year: 2012
Objectives: Efficacy and toxicity of the drug are mainly determined by physicochemical properties and pharmacological effects of its own. In addition, they are also affected by other factors, such as gender, age, genetic character, pathophysiological status, mood states and so on. The paper aims to study whether mood disorder alters drug metabolism process through the pharmacokinetic research on some clinically important anticancer drugs in depression model rats. Materials and Methods: The depression model rats were built by exposing to chronic unpredicted mild stresses (CUMS) for 8 weeks. 36 female Sprague-Dawley (SD) rats were randomized into model group and control group. In each group, 18 rats were randomized into 2 subgroups: 5-fluorouracil (5-FU) subgroup and cyclophosphamide (CP) subgroup which were given a certain doses of 5-FU and CP. The blood samples were collected at different time points and plasma drug concentration were respectively assayed by high performance liquid chromatography (HPLC) for 5-FU and high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) for CP. Pharmacokinetic parameters were processed with DAS software. Results: There were significant differences in the pharmacokinetic parameters of 5-FU and CP between in depression model rats group and in the normal control group (p < 0.05), except t 1/2α (p > 0.05) for CP pharmacokinetics in depression model rats group and in the normal control rats group, with the value of those was 0.07 and 0.09 h. Conclusions: Depression mood disorder might alter drug metabolism process.
Hou L.,Shanghai University |
Han X.,Fudan University |
Sheng P.,Shanghai University |
Tong W.,Pudong New Area Peoples Hospital |
And 7 more authors.
PLoS ONE | Year: 2013
Background:Sleep disturbance is very common following traumatic brain injury (TBI), which may initiate or exacerbate a variety of co-morbidities and negatively impact rehabilitative treatments. To date, there are paradoxical reports regarding the associations between inherent characteristics of TBI and sleep disturbance in TBI population. The current study was designed to explore the relationship between the presence of sleep disturbance and characteristics of TBI and identify the factors which are closely related to the presence of sleep disturbance in TBI population.Methods:98 TBI patients (72 males, mean age ± SD, 47 ± 13 years, range 18-70) were recruited. Severity of TBI was evaluated based on Glasgow Coma Scale (GCS). All participants performed cranial computed tomography and were examined on self-reported sleep quality, anxiety, and depression.Results:TBI was mild in 69 (70%), moderate in 15 (15%) and severe in 14 (15%) patients. 37 of 98 patients (38%) reported sleep disturbance following TBI. Insomnia was diagnosed in 28 patients (29%) and post-traumatic hypersomnia in 9 patients (9%). In TBI with insomnia group, 5 patients (18%) complained of difficulty falling asleep only, 8 patients (29%) had difficulty maintaining sleep without difficulty in initial sleep and 15 patients (53%) presented both difficulty falling asleep and difficulty maintaining sleep. Risk factors associated with insomnia were headache and/or dizziness and more symptoms of anxiety and depression rather than GCS. In contrast, GCS was independently associated with the presence of hypersomnia following TBI. Furthermore, there was no evidence of an association between locations of brain injury and the presence of sleep disturbance after TBI.Conclusion:Our data support and contribute to a growing body of evidence which indicates that TBI patients with insomnia are prone to suffer from concomitant headache and/or dizziness, report more symptoms of anxiety and depression and severe TBI patients are likely to experience hypersomnia. © 2013 Hou et al.
Xue F.,Fengxian Central Hospital |
Zhang C.,Shanghai JiaoTong University |
He Z.,Fengxian Central Hospital |
Ding L.,Fengxian Central Hospital |
Xiao H.,Fengxian Central Hospital
Molecular Medicine Reports | Year: 2013
Osteoarthritis (OA) and rheumatoid arthritis (RA) are the most prevalent forms of arthritis in the elderly. This study aimed to explore the molecular mechanisms of these diseases and identify underlying therapeutic targets. Using GSE1919 microarray data sets downloaded from the Gene Expression Omnibus database, we screened differentially expressed genes (DEGs) in OA and RA cells. The underlying molecular mechanisms of these crucial genes were investigated by Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Small molecule expression and SNP analysis were also conducted by searching CMap and dbSNP databases. More than 320 genes changed in the arthritic cells and there were only 196 DEGs between OA and RA. OA and RA activated the classic mitogen-activated protein kinase signaling pathway, insulin signaling pathway, antigen processing and presentation and intestinal immune network for IgA production. Graft-versus-host disease and autoimmune thyroid disease-related pathways were also activated in OA and RA. Parthenolide and alsterpaullone may be treatments for OA and RA and insulin-like growth factor 1, collagen α2(I) chain and special AT-rich sequence-binding protein 2 may be critical SNP molecules in arthritis. Our findings shed new light on the common molecular mechanisms of OA and RA and may provide theoretical support for further clinical therapeutic studies. Copyright © 2013 Spandidos Publications Ltd.