Shen L.,Qiqihar Medical School |
Wang P.,Harbin Medical University |
Yang J.,Jilin Province Tumor Hospital |
Li X.,Jiamusi University
PLoS ONE | Year: 2014
Osteosarcoma is the most common type of primary tumor of bone which mainly affects adolescents and young adults. Osteosarcoma causes large number of deaths because of its complex pathogenesis and resistance to conventional treatment. MicroRNAs are a class of small noncoding RNAs that function as critical gene regulators through targeting mRNAs, causing translational repression or degradation. In this study, we showed that miR-217 was down-regulated in osteosarcoma cell lines and tissues in comparison to that in normal bone cells or tissues. Meanwhile, the lower level of miR-217 was associated with metastasis in clinical osteosarcoma patients. Furthermore, we found that overexpession of miR-217 markedly suppressed cell proliferation, migration, and invasion of osteosarcoma cells. Conversely, the inhibition of miR-217 expression significantly accelerated the cell proliferation, migration, and invasion. Moreover, we identified WASF3 as a novel functional downstream target of miR-217. The ectopic expression of WASF3 can partially reverse the inhibition of cell proliferation and invasion caused by miR-217. Take together, our results demonstrate that miR-217 functions as a tumor-suppressive miRNA and inhibits the osteosarcoma tumorigenesis through targeting WASF3. Copyright: © 2014 Bischoff et al.
Wang Q.-Z.,Northeast Dianli University |
Sun N.,Northeast Dianli University |
Wang B.,Jilin Province Tumor Hospital
Moshi Shibie yu Rengong Zhineng/Pattern Recognition and Artificial Intelligence | Year: 2015
In the existing 3D active appearance model (AAM), a 3D appearance matrix must be transformed into a 1D vector. Thus, the segmentation accuracy is affected by the transformation and the segmentation efficiency is affected by the generated oversize vector. For the above problems, a 3D tensor based AAM is proposed aiming at direct operating on 3D appearances of lungs by higher order singular value decomposition, rather than transforming it from 3D to 1D. Firstly, the tensor-based model is built and the parameters are deduced. Then, a block-based Kronecker is designed to determine the optimal scheme for low rank representation of appearance tensors. This optimization avoids repeated computation. Finally, the whole segmentation system is constructed and used in the segmentation of lung images. Experimental results of clinical CT images are compared to other 3D landmark-based methods. The proposed model performs a better result in both precision and efficiency. ©, 2015, Journal of Pattern Recognition and Artificial Intelligence. All right reserved.
Wang Q.,Northeast Dianli University |
Wang B.,Jilin Province Tumor Hospital
ICIC Express Letters | Year: 2013
To improve the poor performance of current computer-aided diagnosis (CAD) in lung CT images caused by irregular nodules, new detection scheme based on manifold learning with latent variable is proposed. Testing dataset used in this study consisted of CT scans from 100 different patients in our Hospital. Characteristics of most nodules in these scans were irregular. These nodules have caused seriously false recognition by both current CAD and radiologists. Relative position from the suspected nodule to the centre of the whole lung area is added as a new feature to traditional shape and texture features to optimize Support Vector Machine (SVM). Four CAD schemes were investigated for the same 100 irregular samples. Our scheme achieved a 93.7% overall sensitivity with 1.83% False Positives (FPs) per section, which was in general superior compared with the other three CAD schemes for our application. © 2013 ICIC International.
Li Y.,Changchun Institute of Technology |
Miao Z.,Jilin University |
Wang B.,Jilin Province Tumor Hospital
Proceedings of 2013 3rd International Conference on Computer Science and Network Technology, ICCSNT 2013 | Year: 2014
An adapt Active Appearance Model (AAM) which can initialize the contour automatically is proposed to segment lung CT images with pathologies. Current segmentation methods have failed because the traditional PCA is not suitable to handle outliers caused by update points of pathology area. A fast robust PCA is cited to design the active AAM which can effectively segment the pathology lungs. For the same 30-cases from Jilin Province Tumor Hospital, two other schemes and algorithm in the paper are compared. The experiment results confirm feasibility of the active AAM which achieved a 93.9% overall sensitivity per section. © 2013 IEEE.
Jin F.,Jilin University |
Jin F.,Jilin Province Tumor Hospital |
Jin F.,University of Duisburg - Essen |
Ji H.,Jilin University |
And 6 more authors.
PLoS ONE | Year: 2012
Combination treatment with endostar, a novel modified endostatin, and cytotoxic chemotherapies showed a survival benefit in Chinese clinical trials. However, the exact mechanism for this synergism remains unclear. In this study, we report for the first time that the chemokine receptor CXCR4 and the hypoxia-inducible transcription factors (HIF)-1α and HIF-2α are involved in these synergistic antitumor effects in human colorectal cancer SW1116 cells in vitro when endostar treatment is combined with the cytotoxic drug oxaliplatin. Under normoxia, we demonstrate that endostar and oxaliplatin treatments synergize to inhibit SW1116 cell proliferation, Matrigel adhesion and invasion by reduction of CXCR4 expression. Consistently, these antitumor abilities of endostar and oxaliplatin were markedly reduced by silencing of CXCR4 in SW1116 cells. Under low oxygen conditions (hypoxia, 1% oxygen), enhanced proliferation of SW1116 cells exposed to oxaliplatin was observed due to the emergence of drug resistance. Strikingly, endostar overcame oxaliplatin-resistance, most likely as a consequence of reduced HIF-2α and CXCR4 levels. CXCR4, is only dependent on HIF-2α, which promotes more aggressive phenotype and more significant for oxaliplatin resistance in SW1116 cells. Our data not only provide clues to aid understanding of the mechanism of the synergism of endostar and chemotherapy under either normoxia or hypoxia, but also suggests a new strategy of combination endostar and chemotherapy treatments which might potentiate therapeutic efficacies and/or counteract chemotherapy resistance. © 2012 Jin et al.
Zhou Q.,Guangdong General Hospital and Guangdong Academy of Medical science |
Zhou C.-C.,Shanghai Pulmonary Hospital |
Chen G.-Y.,Haerbin Medical University Affiliated Tumor Hospital |
Cheng Y.,Jilin Province Tumor Hospital |
And 9 more authors.
Lung Cancer | Year: 2014
Objectives: Aim of the study was to investigate efficacy and safety of sorafenib in patients with advanced lung adenocarcinoma after failure of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) therapy. Patients and methods: Patients who were diagnosed with stage IIIB or stage IV lung adenocarcinoma, and benefited from one prior EGFR-TKI therapy and then failed, were eligible. No more than one previous chemotherapy regimen was permitted. Patients received oral sorafenib 400. mg twice daily continuously until disease progression or intolerable toxicity. Primary endpoint was disease control rate (DCR). Secondary endpoints included safety, progression-free survival (PFS) and overall survival (OS). For patients who agreed to provide peripheral blood or tumor tissue, we analyzed the genotype of Bcl-2-interacting mediator of cell death (BIM) deletion polymorphism and EGFR mutation status. Results: Of 65 enrolled patients, 64 were evaluable. The DCR was 32.8%, which did not meet the predefined statistical hypothesis of 38.4%. The median PFS and OS were 3.7 months [95% (confidence interval), 3.5-3.9 months] and 7.4 months (95% CI, 5.7-9.2 months), respectively. Logistic regression analysis showed no correlation between DCR and age, gender, smoking status and performance status. Hand-foot syndrome (HFS) was the predominant toxicity occurring in 71.9% of patients. Fourteen patients (21.9%) had ≥grade 2 dermatologic reactions that resulted sorafenib dose reduction in three patients (4.7%). Of 36 patients, the BIM deletion polymorphism was found in 3, and no response to sorafenib was observed. In 30 tumor tissues, 22 EGFR active mutations were found. The DCR had no significant difference between mutation-positive and wild-type patients (31.8% vs. 42.9%, respectively; HR, 0.622; p= 0.665). Conclusion: Sorafenib monotherapy did not achieve positive result in patients defined in our trial and we need better biomarker to determine the population who can benefit from sorafenib treatment (ClinicalTrials.gov number: NCT00922584). © 2014 Elsevier Ireland Ltd.
PubMed | Jilin Province Tumor Hospital
Type: | Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie | Year: 2016
Gastric cancer (GC) is one of the most common malignancies and ranks the second leading cause of cancer death worldwide. Some studies had reported the tumor-promoting effects of long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) as a competing endogenous RNA (ceRNA) by sponging to microRNAs. However, the molecular mechanism of ceRNA regulatory pathway involving MALAT1 in GC remains unclear.MALAT1 and miR -202 expression was detected by quantitative real time PCR (qRT-PCR) in 60 gastric cancer tissues and adjacent normal tissues, CCK8 cell proliferation assays, cell cycle analysis and cell apoptosis assays were performed to detect the GC cell proliferation and apoptosis. The mRNA and protein levels of Gli2 were analyzed by quantitative real-time PCR and Western blotting assays. Furthermore, using online software, luciferase reporter assays, RNA immunoprecipitation (RIP) and RNA pulldown assays demonstrated miR-202 was a target of MALAT1.We found that MALAT1 was upregulated in GC tissues and higher MALAT1 expression was correlated with larger tumor size, lymph node metastasis, and TNM stage. Moreover, we revealed that MALAT1 was a direct target of miR-202 and knockdown of MALAT1 significantly decreased the expression of Gli2 through negatively regulating miR-202. In addition, knockdown of Malat1 inhibited GC cells proliferation, S-phase cell number, and induced cell apoptosis via negatively regulating miR-202 in vitro.Our results elucidated MALAT1/miR-202/Gli2 regulatory pathway, which maybe contribute to a novel therapeutic strategy for GC patients.
PubMed | Jilin University, Jilin Province Tumor Hospital, Jilin Province Tumor Institute and Northeast Normal University
Type: Evaluation Studies | Journal: Zhongguo fei ai za zhi = Chinese journal of lung cancer | Year: 2015
The mechanisms of small molecule targeting drug resistance and ways to overcome resistance are now both urgent need to improve the clinical efficacy. This study aimed to investigate the feasibility of using different methods to establish the crizotinib-resistant non-small cell lung cancer NCI-H2228/Crizotinib cell lines and to clarify the mechanisms of resistance to small molecule targeting drug, thus providing experimental and theoretical bases for further studies to overcome the mechanisms of Crizotinib resistance.The study utilized stepwise increase of drug concentrations and chemical mutagen to induce Crizotinib-resistant NCI-H2228 cells. The drug 50% inhibitory concentration (IC50) values of parental and resistant cells and the population doubling time were determined by MTT assay. The echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) expression was evaluated by RT-PCR and Western blot. Full-length sequencing method was used to compare the EML4-ALK genes in the parent and drug-resistant cells and analyze the mechanisms of drug resistance.The method of gradually increasing drug concentration to induce Crizotinib-resistant NCI-H2228 cells was time-consuming because the cell growth recovery was extremely slow. Thus, this method was considered invalid. However, chemical mutagen ENU can effectively induce NCI-H2228 cells resistant to crizotinib in a short time [IC50]= (3.8101.100) mol/L, P=0.002,9 vs parental cells]. Furthermore, the gene mutation frequency of EML4-ALK in the resistant cells was significantly higher than that in the parent cells.Chemical mutagen-induced cell resistance was easily operated and had effectively shortened the experimental process. Preliminary technical methods and experimental evidence for in-depth study of drug resistance mechanisms and approaches to overcome the targeted drug resistance were also provided..
PubMed | Jilin University, Beijing Institute of Pharmacology and Toxicology, Jilin Province Tumor Hospital and Jilin Province Tumor Institute
Type: | Journal: Archives of biochemistry and biophysics | Year: 2016
CPT-11 (irinotecan) is a derivative of camptothecin which is a natural product derived from the Chinese tree Camptotheca acuminta and widely used in antitumor therapy. Here, the invitro anti-tumor activity and associated mechanisms of a novel derivative of camptothecin, ZBH-1205, were investigated in a panel of 9 human tumor cell lines, as well as in HEK 293 and SK-OV-3/DPP, a multi-drug resistant (MDR) cell line, and compared to CPT-11 and 7-ethyl-10-hydroxy-camptothecin (SN38). Comparisons between the different compounds were made on the basis of IC50 values as determined by the MTT assay, and flow cytometry was used to evaluate cell cycle progression, apoptosis, and the levels of pro- and active caspase-3 among different treatment groups. Interaction between the molecules and topoisomerase-1 (Topo-1)-DNA complexes was detected by a DNA relaxation assay. Our results demonstrated that IC50 values for ZBH-1205 ranged from 0.0009mol/L to 2.5671mol/L, which were consistently lower than IC50 values of CPT-11 or SN38 in the panel of cell lines, including SK-OV-3/DPP. Furthermore, ZBH-1205 was more effective than CPT-11 or SN38 at stabilizing Topo-1-DNA complexes and inducing tumor cell apoptosis. Therefore, ZBH-1205 is a promising chemotherapeutic agent to be further assessed in large-scale clinical trials.
PubMed | Jilin University and Jilin Province Tumor Hospital
Type: Journal Article | Journal: Oncology letters | Year: 2016
The objective of the present study was to investigate the incidence of and possible risk factors associated with sarcopenia among cancer patients. Patients with cancer were examined through the use of lumbar magnetic resonance imaging, and clinical data was collected between September and December, 2012, at Jilin Province Tumor Hospital (Changchun, China). The data was subsequently compared between patients with and without sarcopenia. Of the 113 treated cancer patients, 96 patients [39 males (L3 index, <52.4 cm