Dongming Liu

Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, Shanghai Shi, China

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Publications (14)36.4 Total impact

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    ABSTRACT: Astrocyte elevated gene-1 (AEG-1), a novel oncoprotein, has been implicated in oncogenesis and cancer progression in various types of human cancers. Here, immunohistochemistry was used to detect AEG-1 expression in nonmuscle-invasive bladder cancer (NMIBC), and these data were examined for correlation with clinicopathological parameters, and prognosis. Immunohistochemical analysis revealed that AEG-1 expression was significantly higher in bladder cancer tissues than that in normal tissues. High expression of AEG-1 was found in 45 % of bladder cancers and significantly associated with tumor grade (P = 0.002) and progression (P = 0.028). The Kaplan-Meier survival analysis demonstrated that AEG-1 expression was significantly associated with shorter progression-free survival (P = 0.0011). Multivariate analysis further demonstrated that AEG-1 was an independent prognostic factor for patients with BC. AEG-1 protein may contribute to the malignant progression of bladder cancer, and present as a novel marker to predict the progression of NMIBC.
    Medical Oncology 06/2014; 31(6):986. · 2.14 Impact Factor
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    ABSTRACT: MicroRNAs (miRNAs) are a class of small non-coding RNAs that bind protein-coding mRNAs and negatively regulate protein expression by translation repression or mRNA cleavage. Accumulating evidence suggests that miRNAs are involved in cancer development and progression, acting as either tumor suppressors or oncogenes. It has been shown that miR-199a-3p was significantly down-regulated in several types of cancers. However, its role and relevance in renal cell carcinoma (RCC) are still largely unknown. Here, we show that miR-199a-3p is significantly down-regulated in human RCC primary tumors and cell lines compared to their non-tumor counterparts. Moreover, the down-regulation of miR-199a-3p is correlated with the histological grade and TNM (tumor-lymph node-metastasis) stage of RCC. Reintroducing miR-199a-3p in RCC cell lines 769-P and Caki-1 inhibited cell proliferation and caused G1 phase arrest. We found that c-Met was up-regulated in RCC cell lines and its expression could be repressed by miR-199a-3p. Moreover, c-Met was up-regulated in RCC primary tumors and reversely correlated with miR-199a-3p expression in the same paired RCC tissues. Reintroducing miR-199a-3p inhibited c-Met expression and led to attenuated activation of c-Met downstream signaling pathways including STAT3, mTOR and ERK1/2. We found that the concentrations of serum hepatocyte growth factor (HGF), the ligand of c-Met receptor, were significantly elevated in RCC patients compared to healthy persons. In addition, HGF treatment could promote proliferation of RCC cells, and the increased cell proliferation was abrogated by miR-199a-3p. Our findings indicated that miR-199a-3p target HGF/c-Met signaling pathway which is crucial for RCC development and suggest that miR-199a-3p may serve as a potential target miRNA for RCC therapy.
    Tumor Biology 03/2014; · 2.52 Impact Factor
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    ABSTRACT: MicroRNAs (miRNAs), which negatively regulate protein expression by binding protein-coding mRNAs, have been integrated into cancer development and progression as either oncogenes or tumor suppressor genes. miR-30c was reported to be down-regulated in several types of cancer. However, its role in human renal cell carcinoma (RCC) remains largely unknown. Here, we show that miR-30c is significantly down-regulated in human RCC tissues and cell lines. We found that miR-30c down-regulation could be induced by hypoxia in RCC cells in a hypoxia-inducible factors (HIFs) dependent manner. Repression of miR-30c through its inhibitor resulted in reduction of E-cadherin production and promotion of epithelial-mesenchymal transition (EMT), while overexpression of miR-30c inhibited EMT in RCC cells. We identified Slug as a direct target of miR-30c in RCC cells. Slug was up-regulated in RCC tissues and its expression could be induced by hypoxia, which is consistent with down-regulation of miR-30c by hypoxia. Forced overexpression of Slug in 786-O cells reduced E-cadherin production, and promoted EMT as well as cell migration. Moreover, Slug overexpression abrogated the inhibitory role of miR-30c in regulating EMT and cell migration, indicating miR-30c regulates EMT through Slug in RCC cells. Our findings propose a model that hypoxia induces EMT in RCC cells through down-regulation of miR-30c which leads to subsequent increase of Slug expression and repression of E-cadherin production, and suggest a potential application of miR-30c in RCC treatment. This article is protected by copyright. All rights reserved.
    Cancer Science 09/2013; · 3.48 Impact Factor
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    Molecular Biology Reports 03/2013; · 2.51 Impact Factor
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    ABSTRACT: OBJECTIVE: To evaluate whether remote ischaemic preconditioning (RIPC) reduces renal injury in patients undergoing laparoscopic partial nephrectomy (LPN). PATIENTS AND METHODS: In all, 82 patients undergoing LPN were randomly assigned to either the RIPC or control group, with 40 and 38 patients, respectively completing 6-months follow-up. RIPC was conducted after induction of anaesthesia, which consisted of three 5-min cycles of right lower limb ischaemia and 5 min of reperfusion during each cycle. The primary outcome was the absolute change in glomerular filtration rate (GFR) of the affected kidney by renal scintigraphy from baseline to 6 months. The secondary outcomes included urinary retinol-binding protein (RBP) levels measured at 24 and 48 h, serum creatinine, and estimated GFR (eGFR) at 1 and 6 months, and changes in GFR by renal scintigraphy. RESULTS: There were no differences in the change of GFR of the affected kidney at 6 months, while it was significantly decreased by 15.0% in the control group vs 8.8% in the RIPC group at 1 month (P = 0.034). The urinary RBP levels increased 8.4-fold at 24 h in the control group compared with a lower increase of 3.9-fold in the RIPC group (P < 0.001). There were no differences in the serum creatinine level or eGFR at 1 and 6 months between the two groups. CONCLUSIONS: In patients undergoing LPN, RIPC using transient lower limb ischaemia may reduce renal impairment in the short term, but failed in the longer term despite a non-significant trend in favour of RIPC. These novel data support the need for a larger study of RIPC during LPN surgery.
    BJU International 03/2013; · 3.05 Impact Factor
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    ABSTRACT: Background and Purpose: Radiofrequency ablation (RFA) has been considered as an important therapy of small renal lesions. However, the main limitation of RFA is the lacking of pathological confirmation of complete tumor eradication. A single centre, open label, randomized pilot study was designed to evaluate whether contrast-enhanced ultrasonography (CEUS) with Sonovue, performed in real time could allow us to determine the endpoint during laparoscopic radiofrequency ablation (LRFA) and the clinical outcome of this method. Patients and Methods: Ninety-six patients undergoing LRFA were randomly assigned to CEUS or control group and finally 38 and 40 patients with pathological diagnosis of renal cell carcinoma completed 3-month follow-up. CEUS was conducted in real time during procedure to determine the endpoint in CEUS group. The primary outcome was the incomplete ablation rate according to radiographic image at 3-month after procedure. The secondary outcome included the local tumor control rate and disease-free survival rate. Results: There were no differences in the incomplete ablation rate and disease-free survival rate between two groups. Within median 16-month follow-up period, 3 incomplete ablation and 2 local recurrence according to radiographic image were found in control group. Meanwhile, there was no incomplete ablation or recurrence but one lung metastasis in CEUS group. The local tumor control rate was 87.5%(35/40) in control group vs 100%(38/38)(P=0.073) in the CEUS group. Conclusion: In patients undergoing LRFA, there were no differences in the incomplete ablation rate and local tumor control rate between the CEUS group and the control group in our study despite of a non-significant trend in favor of CEUS. CEUS may have the potential to provide more effective renal tumor ablation. These novel data support the need for a larger study of CEUS during LRFA surgery.
    Journal of endourology / Endourological Society 02/2013; · 1.75 Impact Factor
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    ABSTRACT: To explore the mechanism and synergistic effect of vitamin A and vitamin D in inducing apoptosis of prostate cancer cells. The cell proliferation activity was determined by MTT assay. The proportion of apoptotic cells was analyzed by FACS and fluorescence intensity. TUNEL was used to evaluate vitamin A and vitamin D's induction of apoptosis in prostate cancer cells. The protein and mRNA expression level of Cyclin D1 and Bax were determined by real time-PCR and western blot. The results of MTT showed vitamin A and vitamin D's inhibition on proliferation ratio in prostate cancer cells is time and concentration dependent. FACS and fluorescence intensity analysis proved that the proportion of apoptotic cells increased after vitamin A and vitamin D treatment. TUNEL showed vitamin A and vitamin D induced prostate cancer cells apoptosis. The combination of vitamin A and vitamin D markedly enhanced the expression of Bax and reduced the expression of Cyclin D1 by real time-PCR and western blot assay. In conclusion, vitamin A and vitamin D could synergistically induce apoptosis in prostate cancer cells.
    Molecular Biology Reports 02/2013; · 2.51 Impact Factor
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    ABSTRACT: To investigate the clinical features, diagnosis, treatment, and prognosis of ductal adenocarcinoma of the prostate. The clinicopathological and immunohistochemical data of seven patients with ductal adenocarcinoma of the prostate were retrospectively analyzed. All patients underwent physical examination, magnetic resonance imaging (MRI), bone scan, cystoscopy, and computed tomography (CT) scan. The level of prostate-specific antigen (PSA) before and after surgery was assessed. Different prostate cancer markers were used for immunohistochemical staining. The mean age of the seven patients diagnosed with prostatic ductal adenocarcinoma in this study was 76.2 years (range 57-88). Five patients presented with intermittent and painless gross hematuria, one patient with progressive dysuria, and one patient with elevated serum PSA on routine health examination. The level of PSA before surgery ranged from 1.3 to 45.0 ng/mL. Immunohistochemical staining results of the prostatic ductal adenocarcinoma confirmed positivity for PSA, prostatic acid phosphatase, androgen receptor, and alpha-methyacyl co-enzyme A (CoA)-reductase markers. Two of the patients underwent bilateral orchiectomy combined with anti-androgen therapy, three underwent transurethral resection of prostate, one received radical prostatectomy, and one received medical castration therapy. The clinical outcomes of all patients were satisfactory, based on follow-up data. The symptoms of hematuria and dysuria were ameliorated well, and the postoperative PSA level decreased below 4.0 ng/mL. Recurrence or metastasis of disease was not detected on MRI and bone scan. Ductal adenocarcinoma of the prostate is a rare subtype of prostate carcinoma, the diagnosis of which could be based on pathological and immunohistochemical examination. Earlier management promises better prognosis.
    OncoTargets and Therapy 01/2013; 6:1501-6. · 2.07 Impact Factor
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    ABSTRACT: Objective: Renal primitive neuroectodermal tumor (PNET) is a rare and highly malignant neoplasm. Our study aims to present the clinical findings and prognosis of 6 patients with renal PNET from China. Material and Methods: From January 2003 to February 2012, 6 patients with renal PNET confirmed by immunohistochemical staining and fluorescence in situ hybridization (FISH) treated in our institution were reviewed retrospectively and our data compared with the literature. Results: There were 4 male and 2 female patients with a mean age of 35.0 years. The mean diameter was 13.3 cm. Five of the masses had renal vein thrombosis, and 3 extended into the inferior vena cava. A lymph node metastasis was detected in 1 patient and a liver metastasis in another patient. Radical nephrectomy was performed in all cases, with 5 patients following chemotherapy and 1 receiving Sutent treatment. Within a median follow-up of 7.5 months (range 1-71), median overall survival was 22.1 months. Conclusions: The diagnosis of renal PNET should be considered in young patients presenting with renal mass and venous thrombosis. It seems that Asian renal PNET patients had a higher rate of venous thrombosis than Caucasian populations. CD99 positivity on immunohistochemistry and EWS-FL1 chimera gene detected by FISH support the diagnosis. The prognosis is poor despite multimodal treatment.
    Urologia Internationalis 10/2012; · 1.07 Impact Factor
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    ABSTRACT: The purpose of this study was to comparatively evaluate the efficacy of pyrosequencing (PS) and Sanger sequencing (SS) methods for detecting K-Ras codon 12 and 13 mutations in formalin-fixed paraffin-embedded (FFPE) prostate cancer (PCa) samples from Chinese patients. The cancer cell lines, including the LS174T G12D mutant (GGT to GAT) and the COLO320 wild-type, were tested to determine the limitation of detection and reproducibility of the PS method. In addition, 101 PCa patient samples, 13 benign prostatic hyperplasia (BPH) and 12 normal adjacent tissue samples, were assayed by PS and SS to evaluate their detection abilities for K-Ras mutations in codons 12 and 13. The PS assay was able to reproducibly detect 5% mutant alleles and had an intra-assay variability of 4.21% and inter-assay variability of 11.37%. The PS assay detected a higher number of K-Ras mutations in PCa samples than the SS assay (8.91% vs. 3.96%). Correlation and stratification analyses of the PCa samples and K-Ras mutation status revealed no associations between age, serum prostate specific antigen (PSA), depth of invasion (pT category), or Gleason score. We demonstrated that the PS method detected more K-Ras mutations in codons 12 and 13 of FFPE prostate cancer samples from Chinese patients than the traditional SS method. In addition, the K-Ras mutation was more frequent in Chinese population than in Western populations but was similar to that of other Eastern populations, suggesting that these K-Ras mutations may contribute to the pathogenesis of prostate carcinoma in Asian patients.
    Clinica chimica acta; international journal of clinical chemistry 06/2012; 413(19-20):1532-5. · 2.54 Impact Factor
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    ABSTRACT: Preoperative aspects and dimensions used for an anatomical classification is a standardized system to assess the anatomical complexity of renal tumors and its impact on perioperative outcomes of partial nephrectomy. The objective is to apply the preoperative aspects and dimensions used for an anatomical classification in a series of Chinese patients undergoing open or laparoscopic partial nephrectomy. A total of 195 consecutive renal tumors treated with open partial nephrectomy or laparoscopic partial nephrectomy between June 2008 and May 2011 were included in this analysis. All the preoperative images and clinical records were retrospectively evaluated. Complication rate, warm ischemia time, operation time and degree of blood loss were compared among different risk groups (low risk: preoperative aspects and dimensions used for an anatomical score 6-7; intermediate risk: preoperative aspects and dimensions used for an anatomical score 8-9; high risk: preoperative aspects and dimensions used for an anatomical score ≥10). The original preoperative aspects and dimensions used for an anatomical score system was modified by replacing rim location with hilar vasculature involvement and tested for prediction of overall complications. The median preoperative aspects and dimensions used for an anatomical score was 8. Overall complication rate was 17.9%. Preoperative aspects and dimensions used for an anatomical score was an independent predictor for perioperative complications. Intermediate and high-risk patients had a four- and 37-fold higher risk of complications respectively (P = 0.012, P < 0.001). Higher preoperative aspects and dimensions used for an anatomical score predicted longer operation time (P = 0.007), warm ischemia time (P < 0.001) and higher degree of blood loss (P = 0.003) in open partial nephrectomy patients. In laparoscopic partial nephrectomy patients, preoperative aspects and dimensions used for an anatomical score was also a predictor for warm ischemia time (P = 0.033); however, it was not significant for operation time and degree of blood loss (P = 0.325, P = 0.302). The modified preoperative aspects and dimensions used for an anatomical score was an independent predictor for overall complications (P < 0.001); however, its superiority could not be verified (P = 0.847). The preoperative aspects and dimensions used for an anatomical classification predicts the risk of overall complications in Chinese patients undergoing nephron-sparing surgery. Replacing the rim location with hilar vasculature involvement might be a promising modification of this scoring system.
    International Journal of Urology 03/2012; 19(6):551-8. · 1.73 Impact Factor
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    ABSTRACT: Objective. Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by overexpression of monocyte chemoattractant protein-1 (MCP-1) in bladder tissues and induction of mast cell (MC) degranulation. This study was undertaken to explore the mechanism of action of MCP-1 in the development of IC/BPS. Methods. A rat model of IC/BPS was developed by perfusing bladders of nine SPF- grade female Sprague-Dawley rats with protamine sulfate and lipopolysaccharide (PS+LPS). MCP-1 and histamine levels in bladder tissue and urine were detected by immunohistochemistry and ELISA. MC degranulation was measured by immunofluorescence techniques and chemokine (C-C motif) receptor 2 (CCR2) was assayed by flow cytometry. Results. Increased MCP-1 expression in bladder tissue and elevated MCP-1 and histamine levels were observed in the urine of LS+LPS-treated rats. This was accompanied by the expression of CCR2 on MC surfaces, suggesting MCP-1 may induce MC degranulation through CCR2. Exposure to LPS stimulated MCP-1 expression in bladder epithelial cells, and exposure to MCP-1 induced histamine release from MCs. Conclusions. MCP-1 upregulation in IC/BPS is one of possible contributing factors inducing histamine release from MCs. CCR2 is involved in the process of mast cell degranulation in bladder tissues. These changes may contribute to the development of symptoms of IC/BPS.
    Mediators of Inflammation 01/2012; 2012:358184. · 3.88 Impact Factor
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    ABSTRACT: It is increasingly clear that microRNAs (miRNAs) play an important role in many diseases, including tumorigenesis. However, the mechanisms by which miRNAs regulate bladder cancer development remain poorly understood. Here, we evaluated the expression of microRNA-203 (miR-203) in bladder cancer tissues using real-time PCR, and defined the target genes and biologically functional effect using luciferase reporter assay, flow cytometry and western blot analysis. We first verified that the expression of miR-203 was decreased in bladder cancer tissues. Moreover, ectopic expression of miR-203 promoted the apoptosis of human bladder cancer cell lines and inhibited cell proliferation, whereas its depletion increased cell growth. We further verified that miR-203 directly targeted 3'-untranslated region of the bcl-w gene, and decreased its expression in vitro and in vivo. Western blot analysis also showed that the expression level of miR-203 was negatively correlated with bcl-w level in tumor tissues. These data suggest an important role for miR-203 in the molecular etiology of bladder cancer and implicate the potential application of miR-203 in bladder cancer therapy.
    FEBS Journal 03/2011; 278(5):786-92. · 4.25 Impact Factor
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    ABSTRACT: von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome caused by germline mutations in the VHL gene. To date, more than 500 VHL families have been reported worldwide. However, few information is available about VHL germline mutations in mainland Chinese families. To provide some preliminary information about the germline VHL mutations in mainland Chinese population. A total of 27 index patients suspected of having VHL disease from unrelated Chinese families were studied by using direct DNA sequencing analysis and universal primer quantitative fluorescent multiplex polymerase chain reaction. The VHL germline mutations were detected in 26 (96%) probands. A total of 20 intragenic mutations (77%) were identified consisting of 12 missenses, 5 nonsenses, 2 micro-deletions and 1 novel intron mutation (IVS1-38C>T). Six large deletions (23%) were detected including four partial deletions and two complete deletions. Furthermore, a C>T substitution at nucleotide 470 (Pro86Leu) was observed in two unrelated Chinese families. Of note, two mutations (Asn78Ser and Ser80Ile) previously characterized as VHL type I mutations in Western VHL were associated with the type II Chinese family. In addition, a VHL germline mutation was also identified in a proband who did not fulfill the clinical diagnostic criteria for VHL disease. The spectrum of VHL germline mutations in mainland Chinese population is similar to that observed in Western population, and Genetic testing can be powerful in diagnosis and clinical management of VHL disease.
    Journal of Cancer Research and Clinical Oncology 05/2008; 134(11):1211-8. · 2.91 Impact Factor

Publication Stats

43 Citations
36.40 Total Impact Points

Institutions

  • 2012–2013
    • Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
      Shanghai, Shanghai Shi, China
    • Shanghai Jiao Tong University
      • School of Medicine
      Shanghai, Shanghai Shi, China
  • 2011–2013
    • Renji Hospital
      Shanghai, Shanghai Shi, China