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Cheng Y.,Jilin University | Cheng Y.,Tumor Hospital of Jilin Province | Xu J.,Jilin University | Guo J.,Jilin University | And 4 more authors.
Clinical and Translational Oncology | Year: 2013

Purpose There is an urgent need to identify biomarkers for early diagnosis and prognosis of esophageal cancer. The present study was undertaken to test whether circulating autoantibodies to ATP-binding cassette C3 (ABCC3) transporter could serve as a biomarker for the malignant tumor. Methods An enzyme-linked immunosorbent assay approach was developed in-house to test circulating autoantibodies to ABCC3 in 114 patients with esophageal squamous cell carcinoma (ESCC) and 226 healthy subjects well matched in age and smoking history. Results Mann-Whitney U test showed that the IgA antibody levels were significantly higher in patients with ESCC than control subjects (Z = -4.226, p < 0.001) while the IgG antibody levels were not significantly different between the two groups (Z = -1.072, P = 0.284). The sensitivity against >95 % specificity was 13.2 % for the IgA assay with an inter-assay deviation of 13.0 and 7.9 % for the IgG assay with an inter-assay deviation of 9.4 %. Conclusions This work suggests that circulating IgA autoantibody to ABCC3 may be a potential biomarker for ESCC, which could be used for early diagnosis and prognosis of the malignant tumor. © Federación de Sociedades Españolas de Oncología (FESEO) 2012.


Guan G.,Jilin University | Zhang D.,Jilin University | Zheng Y.,Tumor Hospital of Jilin Province | Wen L.,Jilin University | And 3 more authors.
International Journal of Clinical and Experimental Pathology | Year: 2014

Despite of the variety of combined modality treatments for laryngeal carcinoma have been introduced, the distance recurrence rate and 5-year overall survival rate over the past decades are still the major issues, underlining the importance to better understand the biological bases that contribute to disease progression. Here, we reported that miR-423-3p overexpressed in primary laryngeal carcinoma cell line where it plays a critical role in tumor progression. Suppression of miR-423-3p expression resulted in decreasing cell proliferation, clonogenicity, cell migration and invasion. By using in silico prediction algorithms for target identification, AdipoR2 (adiponectin receptor 2) and DUSP4 (MAP kinase phosphatase 2) were identified to be potential targets of miR-423-3p. Overexpression of miR-423-3p was associated with epigenetic silencing of AdipoR2 in human laryngeal carcinoma samples, which have been previously implicated in suppression of tumor proliferation and angiogenesis. Luciferase reporter assays and western blot further confirmed the direct interaction of miR-423-3p with AdipoR2. Our findings have demonstrated that miR-423-3p plays an important oncogenic role in laryngeal carcinoma progression, and further suggest that suppression of miR-423-3p expression might be useful for its clinical management.


Wang Y.,Jilin University | Xu X.,Jilin University | Wang H.-B.,Tongji University | Wu D.,U.S. Center for Disease Control and Prevention | And 4 more authors.
International Immunopharmacology | Year: 2015

Osteoclasts (OC) are bone-specific multinucleated giant cells (MNCs) derived from the monocyte/macrophage hematopoietic lineage cells. Inhibiting osteoclast formation is considered as an effective therapeutic approach for the treatment of the pathological bone loss. In this study, we investigated effects of 17-hydroxy-jolkinolide A (HJA), an ent-abietane diterpenoid isolated from the dried root of Euphorbia fischeriana, on osteoclastogenesis induced by RANKL. The results showed that HJA significantly inhibited RANKL-induced osteoclast formation from primary bone marrow macrophages (BMMs). HJA also prevented bone resorption by mature osteoclasts in a dose-dependent manner. In addition, the expression of osteoclastic marker genes, such as tartrate-resistant acid phosphatase (TRAP), cathepsin K (Cts K) and MMP-9, was significantly inhibited by HJA. Furthermore, HJA also significantly inhibited RANKL-induced activation of NF-κB and phosphorylation of MAPK. Our results indicate that HJA has an inhibitory role in the bone loss by preventing osteoclast formation as well as its bone resorptive activity. Therefore, HJA may be useful as a therapeutic reagent for bone loss-associated diseases. © 2015 Elsevier B.V.


PubMed | Jilin University, Pei Ling Guan Si Hospital and Tumor Hospital of Jilin Province
Type: Journal Article | Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine | Year: 2016

The study was designed to test whether circulating autoantibodies against associated antigens (TAAs) were altered in early cervical cancer and benign cervical tumors. A total of 111 cervical cancer patients, 137 cervical benign tumor patients, and 160 healthy volunteers matched in age were recruited in this study. The expression of autoantibodies was tested using in-house developed enzyme-linked immunosorbent assay (ELISA) with linear peptide envelope antigens derived from TAAs. One-way ANOVA test showed that there was no difference in the CD25 autoantibody expression among the cervical cancer group, benign tumor group, and healthy control group (P=0.063; P=0.191). The expression of autoantibodies against survivin and TP53 in the cervical cancer group was significantly higher than that in the benign tumor group (P<0.001; P<0.001). The levels of autoantibodies against cyclinB-1 and ANXA-1 were higher in the cervical cancer group than in the healthy control group (P=0.010; P=0.001), while autoantibodies in the cervical cancer group showed no difference in expression compared with that in the benign tumor group. The panel of five TAAs showed a sensitivity of 37.8% and a specificity of 90%, which was much higher than the sensitivity of the single-TAA testing group. The data from this study further support our previous hypothesis that the detection of autoantibodies for the diagnosis of a specific cancer type can be enhanced using a panel of several selected TAAs as target antigens.


PubMed | Jilin University and Tumor Hospital of Jilin Province
Type: | Journal: Oxidative medicine and cellular longevity | Year: 2016

The aim of this study was to explore the protective effects of ulinastatin (urinary trypsin inhibitor, UTI) on liver ischemia-reperfusion injury (IRI) and graft survival. We employed mouse liver cold IRI and orthotopic liver transplantation (OLTx) models. UTI was added to lactated Ringers (LR) solution for liver perfusion and preservation in vitro or combined with UTI injection intraperitoneally to the liver graft recipient. Our results indicated that UTI supplementation protected the liver from cold IRI in a dose-dependent manner and prolonged liver graft survival from extended cold preserved liver donors significantly. The underlying mechanism of UTI on liver IRI may be mediated by inhibition of proinflammatory cytokine release, increasing the expression of the antiapoptotic gene Bcl-2 and decreasing the expression of the proapoptosis genes of Caspase-3 and Bax, and further protects hepatocytes from apoptotic death and improves liver function.


Zhou Z.-R.,Fudan University | Liu S.-X.,Tumor Hospital of Jilin Province | Zhang T.-S.,JingAn District Central Hospital of Shanghai | Chen L.-X.,Tianjin Medical University | And 3 more authors.
Surgical Oncology | Year: 2014

Background: Long-course chemoradiotherapy (LCRT) with delayed surgery or short-course radiotherapy (SCRT) with immediate surgery is probably the most frequent regimen in the treatment of rectal cancer. Debate is still going on whether SCRT or LCRT is more effective. So we performed this meta-analysis to evaluate the safety and efficacy of SCRT with immediate surgery versus LCRT with delayed surgery for the management of rectal cancer. Methods: Literature were searched from PubMed, Embase, Web of science, Cochrane Library up to May, 2014. Quality of the randomized controlled trials (RCTs) was evaluated according to the Cochrane's risk of bias tool of RCT. RevMan 5.3 was used for statistical analysis. Pooled risk ratio (RR) and 95% confidence interval (CI) were calculated. Subgroup analysis and sensitivity analysis were employed to explore heterogeneity. . Results: 16 trials were included in the qualitative systematic review. 12 trials were included in metaanalyses. 4 of them were RCTs; other 8 were non-RCTs. Meta-analysis demonstrated that there were no significant differences in overall survival (OS), disease free survival (DFS), local recurrence rate (LRR), distant metastasis rate (DMR), sphincter preservation rate, R0 resection rate and late toxicity. Compared with SCRT, LCRT obviously increased pCR rate [RR = 0.15, 95%CI (0.08, 0.28), P = 0.003], while LCRT obviously increased the grade 3e4 acute toxicity [RR = 0.13, 95%CI (0.06, 0.28), P < 0.00001]. . Conclusions: SCRT with immediate surgery is as effective as LCRT with delayed surgery for treatment of rectal cancer in terms of OS, DFS, LRR, DMR, Sphincter preservation rate, R0 resection rate and late toxicity. Though LCRT increased pCR rate, LCRT also increased acute toxicity compared with SCRT. SCRT is a better choice in centers with a long waiting list or lack of medical resources. . © 2014 Elsevier Ltd. All rights reserved.


Hou P.,Northeast Normal University | Zhao Y.,Northeast Normal University | Li Z.,Key Laboratory of Molecular Epigenetics of Ministry of Education MOE | Yao R.,Northeast Normal University | And 6 more authors.
Cell Death and Disease | Year: 2014

LncRNAs have critical roles in various biological processes ranging from embryonic development to human diseases, including cancer progression, although their detailed mechanistic functions remain illusive. The lncRNA linc-ROR has been shown to contribute to the maintenance of induced pluripotent stem cells and embryonic stem cells. In this study, we discovered that linc-ROR was upregulated in breast tumor samples, and ectopic overexpression of linc-ROR in immortalized human mammary epithelial cells induced an epithelial-to-mesenchymal transition (EMT) program. Moreover, we showed that linc-ROR enhanced breast cancer cell migration and invasion, which was accompanied by generation of stem cell properties. Contrarily, silencing of linc-ROR repressed breast tumor growth and lung metastasis in vivo. Mechanistically, our data revealed that linc-ROR was associated with miRNPs and functioned as a competing endogenous RNA to mi-205. Specifically, linc-ROR prevented the degradation of mir-205 target genes, including the EMT inducer ZEB2. Thus our results indicate that linc-ROR functions as an important regulator of EMT and can promote breast cancer progression and metastasis through regulation of miRNAs. Potentially, the findings of this study implicate the relevance of linc-ROR as a possible therapeutic target for aggressive and metastatic breast cancers. © 2014 Macmillan Publishers Limited All rights reserved.


PubMed | Tumor Hospital of Jilin Province, Lanzhou University and Shenzhen Center for Chronic Disease Control
Type: | Journal: Heart, lung & circulation | Year: 2016

MicroRNA-145 (miR-145) has been implicated in vascular smooth muscle cell differentiation, but the underlying mechanisms have not been fully understood, especially their role in abdominal aortic aneurysm (AAA) expansion. Here, we sought to explore and define the mechanisms of miR-145 function in the experimental AAA models in AngII-infused ApoEmiR-145 was overexpressed in ApoEIn vivo overexpression of miR-145 by lentivirus infection greatly decreased the incidence of AAA, maximum abdominal aortic diameter, and elastin degradation, accompanied with downregulation of MMP2 activation in AngII-infused ApoEThese data suggest that regulation of expression of miR-145 may be a potential therapeutic option for vascular disease progression such as AAA expansion.


Zhou Z.-R.,Tumor Hospital of Jilin Province | Liu S.-X.,Tumor Hospital of Jilin Province | Zhang T.-S.,Jingan District Central Hospital of Shanghai | Xia J.,China Academy of Traditional Chinese Medicine | Li B.,University of Nottingham
Asian Pacific Journal of Cancer Prevention | Year: 2014

Introduction: Although most prostate cancers initially respond to castration with luteinizing hormone-releasing analogues or bilateral orchiectomy, progression eventually occurs. Based on the exciting results of several randomized controlled trials (RCTs), it seems that patients with metastatic castration-resistant prostate cancer (mCRPC) might benefit more from treatment withabiraterone. Therefore we conducted a systematic review to evaluate the efficacy and toxicity of abiraterone in the treatment of mCRPC. Methods: Literature was searched from Embase, PubMed, Web of Science, and Cochrane Library up to July, 2013. Quality of the study was evaluated according to the Cochrane's risk of bias of randomized controlled trial (RCT) tool, then the Grading of Recommendations Assessment, Development and Evaluation (GRADE) System was used to rate the level of evidence. Stata 12.0 was used for statistical analysis. Summary data from RCTs comparing abiraterone plus prednisone versus placebo plus prednisone for mCRPC were meta-analyzed. Pooled hazard ratios (HRs) for overall survival (OS), radiographic progression-free survival (RPFS) and time to PSA progression (TTPP); Pooled risk ratios (RR) for PSA response rate, objective response rate and adverse event were calculated. Results: Ten trials were included in the systematic review; Data of 2,283 patients (1,343 abiraterone; 940 placebo) from two phase 3 trials: COU-AA-301 and COU-AA-302 were meta-analyzed. Compared with placebo, abiraterone significantly prolonged OS (HR, 0.74; 95% confidence interval [CI], 0.66 to 0.84), RPFS (HR, 0.59; 95% CI, 0.48 to 0.74) and time to PSA progression (HR, 0.55; 95% CI, 0.43 to 0.70); it also significantly increased PSA response rate (RR, 3.63; 95% CI, 1.72 to 7.65) and objective response rate (RR, 3.05; 95% CI, 1.51 to 6.15). This meta-analysis suggested that the adverse events caused by abiraterone are acceptable and can be controlled. Conclutios: Abiraterone significantly prolonged OS, RPFS and time to progression patients with mCRPC, regardless of prior chemotherapy or whether chemotherapy-naïve, and no unexpected toxicity was evident. Abiraterone can serve as a new standard therapy for mCRPC.


Li C.,CAS Changchun Institute of Applied Chemistry | Yang D.,CAS Changchun Institute of Applied Chemistry | Ma P.,CAS Changchun Institute of Applied Chemistry | Chen Y.,CAS Changchun Institute of Applied Chemistry | And 6 more authors.
Small | Year: 2013

Incorporating the agents for magnetic resonance imaging (MRI), optical imaging, and therapy in one nanostructured matrix to construct multifunctional nanomedical platform has attracted great attention for simultaneous diagnostic and therapeutic applications. In this work, a facile methodology is developed to construct a multifunctional anticancer drug nanocarrier by combining the special advantages of upconversion nanoparticles and mesoporous silica. β-NaYF4:Yb3+, Er3+atβ-NaGdF 4:Yb3+ is chosen as it can provide the dual modality of upconversion luminescence and MRI. Then mesoporous silica is directly coated onto the upconversion nanoparticles to form discrete, monodisperse, highly uniform, and core-shell structured nanospheres (labeled as UCNPs@mSiO 2), which are subsequently functionalized with hydrophilic polymer poly(ethylene glycol) (PEG) to improve the colloidal stability and biocompatibility. The obtained multifunctional nanocomposites can be used as an anticancer drug delivery carrier and applied for imaging. The anticancer drug doxorubicin (DOX) is absorbed into UCNPs@mSiO2-PEG nanospheres and released in a pH-sensitive pattern. In vitro cell cytotoxicity tests on cancer cells verify that the DOX-loaded UCNPs@mSiO2-PEG has comparable cytotoxicity with free DOX at the same concentration of DOX. In addition, the T1-weighted MRI that measures in aqueous solutions reveals that the contrast brightening increases with the concentration of Gd3+ component. Upconversion luminescence images of UCNPs@mSiO2-PEG uptaken by cells show green emission under 980 nm infrared laser excitation. Finally, the nanocomposites show low systematic toxicity and high in vivo antitumor therapy efficacy. These findings highlight the fascinating features of upconversion-mesoporous nanocomposites as multimodality imaging contrast agents and nanocarrier for drug molecules. A facile methodology is developed to construct a multifunctional nanocarrier composed of individual luminescent/magnetic β-NaYF4:Yb3+, Er3+@ β-NaGdF4:Yb3+ directly coated with mesoporous silica, followed by functionalization with poly(ethylene glycol), which can act as an effective platform for upconversion luminescence and magnetic resonance dual-modal imaging and in vivo anticancer drug delivery. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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