Yang J.,Zhongshan Hospital |
Yang J.,Anhui Medical University |
Liu K.-X.,Huadong Hospital |
Qu J.-M.,Huadong Hospital |
Wang X.-D.,Zhongshan Hospital
European Journal of Pharmacology | Year: 2013
Infection is one of the most commonly encountered complication during chemotherapy treatment, and recent studies showed that such infections are aroused primarily from the intestinal microflora through bacterial translocation. We aimed to investigate the alterations of mucosal barrier and colonization resistance in mouse treated with cyclophosphamide (CTX) to further understand the translocation mechanism. Male Balb/c mice were administered intraperitoneally with CTX at 25 mg/kg, 50 mg/kg and 100 mg/kg for 5 days. We found that pretreatment with CTX, especially at high dose, increased the potentially pathogenic bacteria counts (Escherichia coli, enterobacteraceae, Pseudomonas and enterococci) and the intestinal permeability, which was associated with the reduction of tight junctions and adherens junctions. Our results suggested that disruption of mucosal barrier and colonization resistance may be partly responsible for the bacterial translocation during chemotherapy. Thus, modulation of mechanical mucosal barrier and colonization resistance might represent a new opportunity for applications in cancer patients to reduce infectious complications. © 2013 Elsevier B.V. All rights reserved.
Zhu Y.,CAS Shanghai Institute of Technical Physics |
Tan Y.,CAS Shanghai Institute of Technical Physics |
Hua Y.,Huadong Hospital |
Wang M.,Huadong Hospital |
And 2 more authors.
Journal of Digital Imaging | Year: 2010
There are lots of work being done to develop computer-assisted diagnosis and detection (CAD) technologies and systems to improve the diagnostic quality for pulmonary nodules. Another way to improve accuracy of diagnosis on new images is to recall or find images with similar features from archived historical images which already have confirmed diagnostic results, and the content-based image retrieval (CBIR) technology has been proposed for this purpose. In this paper, we present a method to find and select texture features of solitary pulmonary nodules (SPNs) detected by computed tomography (CT) and evaluate the performance of support vector machine (SVM)-based classifiers in differentiating benign from malignant SPNs. Seventy-seven biopsy-confirmed CT cases of SPNs were included in this study. A total of 67 features were extracted by a feature extraction procedure, and around 25 features were finally selected after 300 genetic generations. We constructed the SVM-based classifier with the selected features and evaluated the performance of the classifier by comparing the classification results of the SVM-based classifier with six senior radiologists' observations. The evaluation results not only showed that most of the selected features are characteristics frequently considered by radiologists and used in CAD analyses previously reported in classifying SPNs, but also indicated that some newly found features have important contribution in differentiating benign from malignant SPNs in SVM-based feature space. The results of this research can be used to build the highly efficient feature index of a CBIR system for CT images with pulmonary nodules. © 2008 Society for Imaging Informatics in Medicine.
Wang J.,Huadong Hospital |
Zhang G.,Fudan University |
Hu X.,Fudan University |
Liu Y.,Fudan University |
And 2 more authors.
Saudi Journal of Gastroenterology | Year: 2015
Background and Aim: To evaluate a high effective and practical regimen for the eradication of Helicobacter pylori infection. Patients and Methods: The 298 patients with H. pylori infection, diagnosed by biopsies performed during the endoscopy, were randomized into two groups. Group 1: Treated for one week with a combination of omeprazole, amoxicillin, and clarithromycin (OAC), named by OAC-1 group (n = 143); Group 2: OAC-2 group (n = 155) treated for two weeks with OAC. The OAC-1 group was treated with triple therapy of omeprazole 20 mg, amoxicillin 1000 mg, and clarithromycin 500 mg bid for 1 week. OAC-2 group was treated likewise, but for two weeks. A 13C-urea breath test was used to monitorH. pylori after four to eight weeks following therapy. Results: The eradication of infection was 55% and 68% in the OAC-1 and OAC-2 groups, respectively. Moreover, the eradication rates in the two groups were 63% and 75%, respectively. Compared with the OAC-1 group, the efficacy of treatment in the OAC-2 group is significantly higher (P < 0.05). Conclusion: Two-week OAC regimen yields a higher eradication rate of H. pylori, which might be a practical regimen for the eradication of H. pylori. © 2015 Saudi Journal of Gastroenterology (Official journal of The Saudi Gastroenterology Association).
Zhang J.,Zhongshan Hospital |
Zhang Y.-L.,Huadong Hospital |
Ma K.-X.,Fuyuan Peoples Hospital |
Qu J.-M.,Huadong Hospital
Thorax | Year: 2013
Background: Patients with lung cancer are at high risk of venous thromboembolism (VTE), and VTE predicts a poor prognosis. Anticoagulation therefore might be beneficial for these patients. It is not clear whether anticoagulants could improve survival and other outcomes in patients with lung cancer with no indication for anticoagulation. Methods: We searched the Web of Science, Medline, EMBASE and Cochrane databases for relevant studies. Two reviewers evaluated the studies and extracted data independently. The primary outcomes were 1-year survival and incidence of VTE. Pooled risk ratios (RR) were calculated using control as a reference group and significance was determined by the Z test. Results: Nine eligible studies with 2185 participants were included. Anticoagulation showed significant improvement in survival at 1 year (RR 1.18, 95% CI 1.06 to 1.32; p=0.004) and at 2 years (RR 1.27, 95% CI 1.04 to 1.56; p=0.02), but not at 6 months. Subgroup analysis showed a survival benefit for patients with small cell lung cancer (SCLC) and those with non-advanced/limited cancer. The incidence of VTE (RR=0.55, 95% CI 0.31 to 0.97; p=0.04) and thromboembolic events (RR=0.48, 95% CI 0.28 to 0.82; p=0.008) was reduced with anticoagulation. Both vitamin K antagonist (VKA) and subcutaneous heparin increased the risk of haemorrhage, but heparin did not increase the incidence of major bleeding. Conclusions: Anticoagulation showed a survival benefit, especially for those with SCLC and prolonged life expectancy, and reduced the risk of VTE in lung cancer patients with no indication for anticoagulants. Subcutaneous heparin is superior to VKA because of a potentially smaller risk of major bleeding.
Zhu Y.,CAS Shanghai Institute of Technical Physics |
Tan Y.,CAS Shanghai Institute of Technical Physics |
Hua Y.,Huadong Hospital |
Zhang G.,Huadong Hospital |
Zhang J.,CAS Shanghai Institute of Technical Physics
Journal of Digital Imaging | Year: 2012
Chest radiologists rely on the segmentation and quantificational analysis of ground-glass opacities (GGO) to perform imaging diagnoses that evaluate the disease severity or recovery stages of diffuse parenchymal lung diseases. However, it is computationally difficult to segment and analyze patterns of GGO while compared with other lung diseases, since GGO usually do not have clear boundaries. In this paper, we present a new approach which automatically segments GGO in lung computed tomography (CT) images using algorithms derived from Markov random field theor y. Further, we systematically evaluate the performance of the algorithms in segmenting GGO in lung CT images under different situations. CT image studies from 41 patients with diffuse lung diseases were enrolled in this research. The local distributions were modeled with both simple and adaptive (AMAP) models of maximum a posteriori (MAP). For best segmentation, we used the simulated annealing algorithm with a Gibbs sampler to solve the combinatorial optimization problem of MAP estimators, and we applied a knowledge-guided strategy to reduce false positive regions. We achieved AMAP-based GGO segmentation results of 86.94%, 94.33%, and 94.06% in average sensitivity, specificity, and accuracy, respectively, and we evaluated the performance using radiologists' subjective evaluation and quantificational analysis and diagnosis. We also compared the results of AMAP-based GGO segmentation with those of support vector machine-based methods, and we discuss the reliability and other issues of AMAP-based GGO segmentation. Our resear chresults demonstrate the accept ability and usefulness of AMAP-based GGO segmentation for assisting radio logists in detect ing GGO in high-resolution CT diagnostic procedures. © 2011 Society for Imaging Informatics in Medicine.
Yao Y.,Huadong Hospital |
Kong Z.,Fudan University
National Medical Journal of China | Year: 2015
Objective To evaluate the effect of Ixabepilone on quiescent or hypoxic cells response to ionizing radiation. Methods NCI-H460 and A549, two human NSCLC cell lines, were employed in this experiment. Quiescent cells (QC) or hypoxic cells (HC) were induced as mentioned previously and untreated cells as control. A colony forming assay was applied to compare cellular radio-sensitivity with or without Ixabepilone. Flow cytometry and Western blot analysis were used to detect cell cycle distribution and apoptosis. Results Along with an increased population of G1 cell (NCI-H46 P = 0. 001 3; A549 P = 0. 006) , both HC and QC were exhibited radio-resistance compared to untreated cells (survival fraction; NCI-H460 P = 0.003; A549 P = 0. 000 1). Moreover, it was found that Ixabepilone, which induced apoptosis in both IR-treated or untreated NSCLC cells, significantly enhanced cells death under hypoxia (decrease of survival fraction; NCI-H460 P = 0. 000 2; A549 P < 0. 01). Conclusion The existence of quiescent or hypoxic cells in solid tumors poses a critical therapeutic problem since they were resistant to IR. Ixabepilone, which induces apoptosis in NSCLC, showed great radio-sensitization effect on hypoxic cells. Following work will focus on whether Ixabepilone could increase hypoxic tumor cells radio-sensitivity in vivo, which could provide useful data for the application of Ixabepilone in clinical practice.
Gu B.,Fudan University |
Xie C.,Fudan University |
Zhu J.,Fudan University |
He W.,Huadong Hospital |
Lu W.,Fudan University
Pharmaceutical Research | Year: 2010
Purpose A novel conjugate, Folate-PEG-CKK2-DTPA, was designed and prepared as a carrier for lymphatic metastasized tumor imaging diagnosis and targeting therapy. Methods Folate-PEG-CKK2-DTPA was synthesized and characterized by analysis High Performance Liquid Chromatography, Size Exclusive Chromatography and 1H-NMR. 99mTc-labeled conjugation was prepared, and in vivo quantitative biodistribution and SPECT imaging were studied after subcutaneously injected into the rats and rabbits, respectively. Cell uptake study was carried in a KB cell line using fluorescent methods. In vivo and ex vivo fluorescent imaging study was carried in tumor-bearing nude mouse to evaluate its targeting ability. Results Folate-PEG-CKK2-DTPA was synthesized with high purity. Both in vivo biodistribution study and SPECT imaging study show the rapid direction and high distribution of the conjugation to the lymph nodes. The uptake of fluorescencelabeled Folate-PEG-CKK 2-DTPA in human oral epidermis carcinoma cells was observed. In vivo and ex vivo fluorescent imaging study indicated it could accumulate in tumor region after vein tail injection in nude mouse. Conclusions All these findings suggested Folate-PEG-CKK2DTPA as a novel and dependable carrier for tumor diagnosis and therapy, especially for lymph-metastasized tumors. © 2010 Springer Science+Business Media, LLC.
Mao Y.-X.,Huadong Hospital |
Xu J.-F.,Tongji University |
Seeley E.J.,University of California at San Francisco |
Tang X.-D.,Huadong Hospital |
And 5 more authors.
Stem Cells | Year: 2015
Rationale: New strategies for treating Pseudomonas aeruginosa pulmonary infection are urgently needed. Adipose tissue-derived mesenchymal stem cells (ASCs) may have a potential therapeutic role in P. aeruginosa-induced pulmonary infection. Methods: The therapeutic and mechanistic effects of ASCs on P. aeruginosa pulmonary infection were evaluated in a murine model of P. aeruginosa pneumonia. Results: ASCs exhibited protective effects against P. aeruginosa pulmonary infection, evidenced by reduced bacterial burdens, inhibition of alveolar neutrophil accumulation, decreased levels of myeloperoxidase, macrophage inflammatory protein-2 and total proteins in broncho-alveolar lavage fluid (BALF), and attenuated severity of lung injury. ASCs had no effects on BALF and serum levels of keratinocyte growth factor or Ang-1. ASCs had no effects on the levels of insulin growth factor 1 (IGF-1) in BALF, but increased IGF-1 levels in serum. ASCs inhibited the overproduction of prostaglandin E2 (PGE2) by decreasing the expression of cyclooxygenase-2 (COX2) and enhancing the expression of 15-PGDH. In addition, the addition of exogenous PGE2 with ASCs abolished many of the protective effects of ASCs, and administrating PGE2 alone exacerbated lung infection. By inhibiting production of PGE2, ASCs improved phagocytosis and the bactericidal properties of macrophages. Furthermore suppressing PGE2 signaling by COX2 inhibition or EP2 inhibition exhibited protective effects against pulmonary infection as well. Conclusions: In a murine model of P. aeruginosa pneumonia, ASCs exhibited protective effects by inhibiting production of PGE2, which subsequently improved phagocytosis and the bactericidal properties of macrophages. ASCs may provide a new strategy for managing pulmonary infection caused by P. aeruginosa. Stem Cells 2015;33:2331-2342 © 2015 AlphaMed Press.
Yong D.,East China Normal University |
Luo Y.,East China Normal University |
Du F.,East China Normal University |
Huang J.,East China Normal University |
And 5 more authors.
Colloids and Surfaces B: Biointerfaces | Year: 2013
This research is aimed to develop a nano-sized supramolecular micelle delivery system of cis-dichlorodiammine platinum (II) (CDDP) in order to achieve the passive tumor targeting. Firstly, star-shaped poly (γ-benzyl-l-glutamate) was synthesized by the ring-opening polymerization of γ-benzyl-l-glutamate-N-carboxyanhydride initiated with per-6-amino-β-cyclodextrin. After removal of benzyl groups, β-cyclodextrin based seven-armed poly (l-glutamic acid) (β-CD-7PLGA) was obtained. β-CD-7PLGA/CDDP complexes were prepared by the complex reaction between the carboxylic groups of β-CD-7PLGA and CDDP. Further inclusion of β-CD-7PLGA/CDDP complexes with adamantine terminated mPEG (mPEG-Ad) gave CDDP supramolecular micelles (mPEG-Ad@β-CD-7PLGA/CDDP). The formation of mPEG-Ad@β-CD-7PLGA/CDDP supramolecular micelles was confirmed by fluorescence spectrophotoscopy and particle size measurements. All the micelles showed spherical shape, and their sizes increased from 100 to 135. nm with the increase of PLGA arm molecular weight. mPEG-Ad@CD-7PLGA/CDDP micelles showed sustained drug release profiles over 50. h in PBS. Compared with CDDP, mPEG-Ad@β-CD-7PLGA/CDDP supramolecular micelles showed essential decreased cytotoxicity to KB cells, suggesting their great potential as the delivery carriers of CDDP. © 2013 Elsevier B.V.
PubMed | Shanghai JiaoTong University and Huadong Hospital
Type: Journal Article | Journal: Oncotarget | Year: 2016
Growth arrest DNA damage-inducible gene 45 (GADD45), which influences cell growth, apoptosis and cellular response to DNA damage, is downregulated in hepatocellular carcinoma (HCC). S-adenosylmethionine (SAMe) serves as an essential methyl donor in multiple metabolic pathways and is a polyamine and glutathione (GSH) precursor. In this study, we assessed the roles of GADD45 and SAMe in cell survival during acute ischemia-hypoxia (I/H). SAMe treatment induced growth of HL-7702 normal hepatic cells, but decreased the viability of HepG2 (p53 wild-type) and Hep3B (p53 null) HCC cells. Cells were exposed to I/H with or without SAMe pre-treatment. I/H exposure alone triggered HCC cell proliferation promoted by autophagy. SAMe pre-treatment restored GADD45 expression and activated HCC cell apoptosis and eliminated I/H-induced HCC cell proliferation. p53 loss blunted the response to SAMe and I/H exposure in Hep3B cells; thus, the inhibitory effect of SAMe on cell proliferation may be reduced in p53-null cells as compared to wild-type cells. These results indicate that GADD45 induction by SAMe inhibits HCC cell proliferation during I/H as a result of increased apoptosis, and that SAMe also protects normal hepatocytes from apoptotic cell death and promotes normal cell regeneration. SAMe should be considered a potential therapeutic agent for the management of HCC.