Fei Z.-H.,Wenzhou University |
Yu X.-J.,Huaian First Peoples Hospital |
Zhou M.,Yangzhou University |
Su H.-F.,Wenzhou University |
And 2 more authors.
Tumor Biology | Year: 2015
Emerging evidences indicate that dysregulated long non-coding RNAs (lncRNAs) are implicated in cancer tumorigenesis and progression and might be used as diagnosis and prognosis biomarker or potential therapeutic targets. Therefore, identification of cancer-associated lncRNAs and investigation of their biological functions and molecular mechanisms are important for understanding the development and progression of cancer. In this study, we identified a novel lncRNA LINC00982, whose expression was downregulated in tumor tissues in 106 patients with gastric cancer (GC) compared with those in the adjacent normal tissues (P < 0.001). Furthermore, decreased LINC00982 expression was negatively correlated with invasion depth (P < 0.001), advanced TNM stage (P = 0.004), and regional lymph node metastasis (P = 0.005). LINC00982 levels were robust in differentiating gastric cancer tissues from controls [area under the curve (AUC) = 0.742; 95 % confidence interval (CI) = 0.678–0.800, P < 0.01]. Kaplan–Meier analysis demonstrated that decreased LINC00982 expression contributed to poor overall survival (P < 0.01) and disease-free survival (P < 0.01) of patients. A multivariate survival analysis also indicated that LINC00982 could be an independent prognostic marker. The levels of LINC00982 in gastric juice from gastric patients were significantly lower than those from normal subjects (P = 0.026). Furthermore, knockdown of LINC00982 expression by small interfering RNA (siRNA) could promote cell proliferation and cell cycle progression, while ectopic expression of LINC00982 inhibited cell proliferation and rendered cell cycle arrest in GC cells partly via regulating P15 and P16 protein expressions. Our findings present that decreased lncRNA LINC00982 could be identified as a poor prognostic biomarker in GC and regulate cell proliferation. © 2015 International Society of Oncology and BioMarkers (ISOBM)
Zhang H.,Hangzhou Cancer Hospital |
Luo H.,Huaian First Peoples Hospital |
Hu Z.,Hangzhou Cancer Hospital |
Peng J.,Huaian First Peoples Hospital |
And 8 more authors.
Oncotarget | Year: 2015
Radiotherapy is a primary treatment modality for esophageal squamous cell carcinoma (ESCC). However, most of patients benefited little from radiotherapy due to refractory radioresistance. We found that WISP1, a downstream target gene of Wnt/ß-catenin pathway, was re-expressed in 67.3 % of ESCC patients as an oncofetal gene. Expression of WISP1 predicted prognosis of ESCC patients treated with radiotherapy. Overall survival in WISP1-positive patients was significantly poorer than in WISP1-negative patients. Serum concentration of WISP1 after radiotherapy reversely correlated with relapse-free survival. Gain and loss of function studies confirmed that WISP1 mediated radioresistance both in esophageal squamous cancer cells and in xenograft tumor models. Further studies revealed that WISP1 contributed to radioresistance primarily by repressing irradiation-induced DNA damage and activating PI3K kinase. LncRNA BOKAS was up-regulated following radiation and promoted WISP1 expression and resultant radioresistance. Furthermore, WISP1 facilitated its own expression in response to radiation, creating a positive feedback loop and increased radioresistance. Our study revealed WISP1 as a potential target to overcome radioresistance in ESCC.
Wu J.,Huaian First Peoples hospital |
Zhang C.,Huaian First Peoples hospital |
Qiao H.,Lianshui County Hospital
Scientific Reports | Year: 2014
To explore the histogenesis of cuboidal and polygonal tumor cells in the sclerosing hemangioma of lung (SHL), eighteen cases of SHL were retrospectively studied. SPB, p40, TTF-1, EMA, CKpan, vimentin, SMA, CgA, Syn and CD34 were immunohistochemically labeled by the En Visionmethod. It was found that the four main types of structure in SHL were solid, papillary, hemorrhagic and sclerotic patterns. The tumor cells were composed mainly of two types of cells: cuboidal tumor cells and polygonal tumor cells. The immunohistochemistry showed that p40 was expressed only in cuboidal tumor cells. TTF-1 and EMA were expressed in both polygonal cells and cuboidal cells. SPB was also expressed in cuboidal tumor cells; vimentin was expressed in all polygonal tumor cells and some cuboidal cells. The findings suggest that the p40-positive cuboidal tumor cells may be pluripotent original respiratory epithelial cells, with multi-directional differentiation capacity.
Liu X.,Huaian First Peoples Hospital |
Feng W.,Huaian Women And Childrens Hospital
International Journal of Clinical and Experimental Medicine | Year: 2016
Orbital rhabdomyosarcoma (RMS) is a malignant tumor most frequently seen in children and teens, with a poor 5-year survival rate. To improve our understanding of anti-tumor immunity to orbital RMS and aid T cell-based immunotherapy research, we analyzed the phenotype and functions of preexisting RMS-specific T cells in orbital RMS patients. We first identified RMS-specific CD4+ and CD8+ T cells as proliferating cells in response to RMS antigen. Compared to hemaglutinin- and tetanus toxin-specific T cells, RMS-specific CD4+ T cells had fewer rounds of proliferation and lower Th1-to-Treg ratio, while RMS-specific CD8+ T cells were lower in frequency, had fewer rounds of proliferation, and presented less CD107a and IFN-gamma production. Together, we discovered a novel and tumor-specific suppression of RMS-specific T cells. © 2016, E-Century Publishing Corporation. All rights reserved.
Kuai W.,Huaian First Peoples Hospital |
Bai J.,Xuzhou Medical College |
Guo A.,Chuzhou Hospital |
Hong Z.,Huaian First Peoples Hospital
OncoTargets and Therapy | Year: 2012
Objective: MicroRNA-100 (miR-100), a small noncoding RNA molecule, acts as a tumor suppressor or an oncogene in different cancers. The aberrant expression of this microRNA has been demonstrated as a frequent event in adult patients with acute myeloid leukemia (AML), but little is known for pediatric AML. The aim of this study was to investigate the expression and clinical significance of miR-100 in pediatric AML. Methods: The expression levels of miR-100 in bone marrow mononuclear cells were detected by real-time quantitative polymerase chain reaction in a cohort of 106 patients with de novo pediatric AML. The prognostic values of miR-100 in pediatric AML were also analyzed. Results: Compared with normal controls, upregulation of miR-100 in the bone marrow of pediatric AML patients with statistically significant differences (P, 0.001) was found. The expression levels of miR-100 were found to be significantly higher in pediatric AML patients with extramedullary disease, with the French-American-British classification subtype M7, and with unfavorable day 7 response to induction chemotherapy (P = 0.008, 0.001 and 0.01, respectively). Moreover, both univariate and multivariate analyses revealed that miR-100 upregulation was associated with poorer relapse-free and overall survival in pediatric AML patients. Conclusion: This is the first report demonstrating the upregulation of miR-100 in pediatric AML, and its association with poor relapse-free and overall survival. These results suggest that miR-100 upregulation may be used as an unfavorable prognostic marker in pediatric AML. © 2012 Bai et al, publisher and licensee Dove Medical Press Ltd.
Ren Y.,Nanjing Medical University |
Ren Y.,Huaian First Peoples Hospital |
Han X.,Huaian First Peoples Hospital |
Yu K.,Huaian First Peoples Hospital |
And 4 more authors.
Molecular Medicine Reports | Year: 2014
Despite advances in the understanding of breast cancer, patients most commonly have a poor prognosis, particularly those with triple negative breast cancer (TNBC). microRNAs (miRNAs) are endogenous non-coding small RNAs, and their aberrant expression is linked to numerous malignancies. In the present study, the expression levels of miR-200c in patients with TNBC were analyzed and it was identified that miR-200c was downregulated in TNBC samples, compared with that in normal adjacent tissues. miR-200c was overexpressed in the TNBC cell line MDA-MB-231 and its functions were studied in vitro and in vivo. An in vitro study revealed that the overexpression of miR-200c inhibited MDA-MB-231 cell proliferation and resulted in the induction of apoptosis. The in vivo data indicated that the overexpression of miR-200c significantly inhibited tumor growth and increased the rate of apoptosis. Target prediction revealed that the X-linked inhibitor of apoptosis (XIAP) had putative complementary sequences to miR-200c, which was confirmed by a dual luciferase reporter assay. Western blot analysis further demonstrated that the expression of XIAP was markedly reduced and that caspase-3 was highly activated by the overexpression of miR-200c. These findings suggested that miR-200c may function as a tumor suppressor gene in TNBC, at least partly via directly targeting XIAP, and may therefore act as a potential therapeutic target in the development of novel treatment strategies for TNBC.
Wang Q.,Louisville Veterans Administration Medical Center |
Wang Q.,University of Louisville |
Ren Y.,Huaian First Peoples Hospital |
Mu J.,University of Louisville |
And 8 more authors.
Cancer Research | Year: 2015
Inflammation is a hallmark of cancer. Activated immune cells are intrinsically capable of homing to inflammatory sites. Using three inflammatory-driven disease mouse models, we show that grapefruit-derived nanovectors (GNV) coated with inflammatory-related receptor enriched membranes of activated leukocytes (IGNVs) are enhanced for homing to inflammatory tumor tissues. Blocking LFA-1 or CXCR1 and CXCR2 on the IGNVs significantly inhibits IGNV homing to the inflammatory tissue. The therapeutic potential of IGNVs was further demonstrated by enhancing the chemotherapeutic effect as shown by inhibition of tumor growth in two tumor models and inhibiting the inflammatory effects of dextran sulfate sodium-induced mouse colitis. The fact that IGNVs are capable of homing to inflammatory tissue and that chemokines are overexpressed in diseased human tissue provides the rationale for using IGNVs to more directly deliver therapeutic agents to inflammatory tumor sites and the rationale for the use of IGNVs as treatment for certain cancers in personalized medicine. © 2015 American Association for Cancer Research.
Pu D.,Nanjing Medical University |
Xing Y.,Nanjing Medical University |
Gao Y.,HuaiAn First Peoples Hospital |
Gu L.,Nanjing Medical University |
Wu J.,Nanjing Medical University
European Journal of Obstetrics Gynecology and Reproductive Biology | Year: 2014
Objective Premature ovarian failure (POF) is a complex, heterogeneous disorder that is influenced by multiple genetic components. This meta-analysis aimed to investigate the association between gene variants and susceptibility to POF. Study design MEDLINE and CNKI were searched for studies published from inception (1950) to June 2014. Meta-analysis was performed when three or more studies reported genetic data on the same polymorphism or mutation. Additive and dominant models were analyzed using RevMan Version 5.1. Results The literature search yielded 575 articles, of which 59 studies on the association between POF and gene variants were identified for meta-analysis. Five genes were selected for analysis, including 10 common gene polymorphisms [BMP15 (-9C>G, 788insTCT and 852C>T), ESR1 (-351A>G and -397C>T), FMR1 CGG repeat, FSHR (919A>G and 2039A>G), INHA (-16C>T and -124A>G)] and two mutations (BMP15 538G>A and INHA 769G>A). BMP15 538G>A was found to be significantly more common in patients with POF compared with controls. No significant associations were found between the other variants of BMP15 and POF. With respect to ESR1, the accumulative results were not significant, although the findings of the individual studies were controversial. The incidence of FMR1 premutation was significantly higher in patients with POF compared with controls [odds ratio (OR) 9.2, 95% confidence interval (CI) 5.42-15.61; p < 0.001] in the overall population, as well as in both Caucasian and Asian subgroups. Stratified analysis was applied for INHA 769G>A by ethnicity; a significant association with POF was only found in the Asian subgroup (allelic frequency: OR 8.89, 95% CI 2.1-5.52; p = 0.004). No significant associations were found between the other variants of INHA and POF. Conclusions BMP15 538A, FMR1 premutation and INHA 769A (in Asians alone) may indicate susceptibility to POF. Further well-designed studies and larger samples are required to confirm the association between gene variants and POF. © 2014 Elsevier Ltd. All rights reserved.
Zhu Y.,Nanjing Medical University |
Zhu Y.,Huaian First Peoples Hospital |
Ye X.,Nanjing Medical University |
Zhu B.,Nanjing Medical University |
And 4 more authors.
PLoS ONE | Year: 2014
Objective: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) reported two equations in 2012: one based on cystatin C concentration (CKD-EPI2012cys) and the other using both serum creatinine and cystatin C concentrations (CKD-EPI2012Scr-cys). We compared the adaptability of new formulae with other four equations. Methods: Participants (n = 788; median age, 54 [range, 19-94] years) were recruited from the First Affiliated Hospital of Nanjing Medical University. The reference glomerular filtration rate (rGFR) was measured by a 99mTc-DTPA renal dynamic imaging method, and the estimated glomerular filtration rate (eGFR) was calculated separately by the Chinese adapted Modification of Diet in Renal Disease equation (C-MDRD), MacIsaac, Ma, serum creatinine-based CKD-EPI equation (CKD-EPI2009Scr), CKD-EPI2012cys and CKD-EPI 2012Scr-cys equations. We compared the performance of six equations with rGFR. Results: Median rGFR was 76.35 (interquartile range, 59.03-92.50) mL/min/1.73 m2. Compared with CKD-EPI2009Scr, CKD-EPI 2012Scr-cys formula had better diagnostic value with larger area under the receiver operating characteristic curve (ROCAUC, 0.879, p = 0.006), especially in young participants (ROCAUC, 0.883, p = 0.005). CKD-EPI2012cys equation did not perform better than other available equations. Accuracy (the proportion of eGFR within 30% of rGFR [P30]) of the CKD-EPI2012Scr-cys equation (77.03%) was inferior only to MacIsaac equation (80.2%) in the entire participants, but performed best in young participants with normal or mildly-injured GFR. Neither of the two new CKD-EPI equations achieved any ideal P30 in the elderly participants with moderately-severely injured GFR. Linear regression analysis demonstrated a consistent result. In this study, CKD-EPI2012Scr-cys had a relatively better diagnosis consistency of GFR stage between the eGFR and rGFR in the whole cohort. Conclusion: CKD-EPI2012Scr-cys appeared less biased and more accurate in overall participants. Neither of the new CKD-EPI equations achieved ideal accuracy in senior participants with moderately-severely injured GFR. A large-scale study with more subjects and cooperating centers to develop new formulae for the elderly is assumed to be necessary. © 2014 Zhu et al.
Chang Z.,Huaian First Peoples Hospital |
Jian W.,Huaian First Peoples Hospital
Acta Endocrinologica | Year: 2013
Objective. To investigate clinicopathologic feature, diagnosis and differential diagnosis of gangliocytic paraganglioma (GP). Methods. Clinical data, histologic findings of one GP case in our hospital were reported and we reviewed the published literature on GP. Results. GP is composed of three types of cells: spindle cells, ganglion-like cells, and epithelioid cells. Several kinds of antibodies were used to evaluate and identify tumor cells immunohistochemically. Epithelioid cells showed positive results with antibodies for NSE, CgA, Syn, Ck and negative results with antibodies for S-100 protein, CD117.Spindle cells showed positive results with antibodies for S-100 protein, CD34 and negative results with antibodies for CD117, NSE, CgA, Syn, CK. Ganglion-like cells showed positive results with antibodies for NSE, CgA, Syn, CD117 and negative results with antibodies for S-100 protein and CK. In some cases, metastatic spread to regional lymph nodes or recurrence has been reported. Conclusions. GP is a rare true neuroendocrine tumor of potential metastatic capacity.