Limin Zhang

Fudan University, Shanghai, Shanghai Shi, China

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Publications (7)21.53 Total impact

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    ABSTRACT: To retrospectively evaluate intravesical recurrence and oncological outcomes after open or laparoscopic radical nephroureterectomy (RNU) for the upper urinary tract urothelial carcinoma (UUT-UC). This study comprised 122 patients diagnosed UUT-UC and subsequently nephroureterectomy was performed on. Several clinical and pathological parameters were emphasized for comparison of clinical outcomes. Among 122 patients with UUT-UC, 101 (82.8 %) and 21 (17.2 %) underwent open or laparoscopic radical nephroureterectomy (ONU or LNU), respectively. In univariable and multivariable Cox regression models, the surgical procedure exerted an impact neither on post-operative intravesical recurrence rate (p = 0.179 and 0.213, respectively) nor on cancer-specific mortality rate (p = 0.561 and 0.159, respectively). The 1-, 2- and 5-year cancer-specific survival (CSS) rates of patients undergoing ONU or LNU were 92.1 versus 95.2 %, 87.1 versus 90.5 %, 79.2 versus 85.7 %, respectively, and the Kaplan-Meier plot illustrated that patients from two groups enjoyed an equivalent survival rate (p = 0.559). Moreover, we added that previous history of bladder tumor and pre-operative hydronephrosis was associated with intravesical recurrence, whereas three prognostic factors, including pathological tumor stage, grade, and lymphovascular invasion, showed possibility to be predictors of cancer-specific mortality. There existed no significant difference of intravesical recurrence and CSS between patients after ONU and LNU. Conclusively, laparoscopic radical nephroureterectomy did not present superiority to open management for patients with UUT-UC.
    World Journal of Urology 09/2013; · 2.89 Impact Factor
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    ABSTRACT: Additional prostate cancer (PCa) risk-associated single nucleotide polymorphisms (SNPs) continue to be identified. It is unclear whether addition of newly identified SNPs improves the discriminative performance of biopsy outcomes over previously established SNPs. A total of 667 consecutive patients that underwent prostate biopsy for detection of PCa at Huashan Hospital and Changhai Hospital, Shanghai, China were recruited. Genetic scores were calculated for each patient using various combinations of 29 PCa risk-associated SNPs. Performance of these genetic scores for discriminating prostate biopsy outcomes were compared using the area under a receiver operating characteristic curve (AUC). The discriminative performance of genetic score derived from a panel of all 29 SNPs (24 previous and 5 new) was similar to that derived from the 24 previously established SNPs, the AUC of which were 0.60 and 0.61, respectively (P = 0.72). When SNPs with the strongest effect on PCa risk (ranked based on contribution to the total genetic variance from an external study) were sequentially added to the models for calculating genetic score, the AUC gradually increased and peaked at 0.62 with the top 13 strongest SNPs. Under the 13-SNP model, the PCa detection rate was 21.52%, 36.74%, and 51.98%, respectively for men with low (<0.5), intermediate (0.5-1.5), and high (>1.5) genetic score, P-trend = 9.91 × 10(-6) . Genetic score based on PCa risk-associated SNPs implicated to date is a significant predictor of biopsy outcome. Additional small-effect PCa risk-associated SNPs to be discovered in the future are unlikely to further improve predictive performance. Prostate 9999: 1-12, 2013. © 2013 Wiley Periodicals, Inc.
    The Prostate 08/2013; · 3.84 Impact Factor
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    ABSTRACT: Twenty-four prostate cancer (PCa) risk-associated single nucleotide polymorphisms (SNPs) in Chinese men have been cataloged. We evaluated whether these SNPs can independently predict outcomes of prostate biopsy, and improve the predictive performance of existing clinical variables. Three hundred eight consecutive patients that underwent prostate biopsy for detection of PCa at Huashan Hospital, Shanghai, China between April 2011 and August 2012 were recruited. Clinical variables such as serum prostate-specific antigen (PSA) levels and peripheral blood samples were collected prior to a 10-core biopsy. A genetic score based on these 24 PCa associated SNPs was calculated for each individual. Among 308 patients underwent prostate biopsy, 141 (45.8%) were diagnosed with PCa. Genetic score was significantly higher in patients with PCa (median = 1.30) than without (median = 0.89), P = 3.81 × 10(-6) . The difference remained significant after adjusting for age and total PSA, P = 0.007. The PCa detection rate increased with increasing genetic score; 26.3%, 43.2%, and 60.0% for men with lower (<0.5), average (0.5-1.5), and higher (>1.5) genetic score, respectively, P-trend = 0.0003. For patients with moderately elevated PSA levels (1.6-20 ng/ml), the PCa detection rate was 31.2% overall and was 16.7%, 31.2%, and 40.9% for men with lower (<0.5), average (0.5-1.5), and higher (>1.5) genetic score, respectively, P-trend = 0.03. For patients with PSA ≥ 20 ng/ml, however, the PCa detection rates were high (>69%) regardless of genetic score. A genetic score based on PCa risk-associated SNPs is an independent predictor of prostate biopsy outcomes in Chinese men and may be helpful to determine the need for prostate biopsy among patients within a "gray zone" of PCa risk. Prostate © 2013 Wiley Periodicals, Inc.
    The Prostate 07/2013; · 3.84 Impact Factor
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    ABSTRACT: High mobility group box 1 (HMGB1) and HMGB2 overexpression has been observed in several human tumor types, and is involved in cancer progression and prognosis. However, the clinicopathological significance of HMGB1 and HMGB2 expression in bladder carcinoma (BCa), particularly the involvement of these proteins in angiogenesis, remains unclear. In the present study, immunohistochemistry and real-time polymerase chain reaction (PCR) of HMGB1 and HMGB2 in 64 BCa patients revealed that HMGB1 and HMGB2 were overexpressed in BCa tissues compared with normal tissues, and were correlated with tumor clinical stage and pathological grade. In addition, correlation analysis of vascular endothelial growth factor (VEGF) and microvessel density (MVD) counts indicated that the overexpression of HMGB1 and HMGB2 was also correlated with angiogenesis. We conclude that HMGB proteins act as key regulators in the progression and angiogenesis of bladder carcinoma, and serve as potential diagnostic and therapeutic targets.
    Oncology letters 03/2013; 5(3):884-888. · 0.24 Impact Factor
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    ABSTRACT: Though prostate cancer (PCa) has slow progression, the hormone refractory (HRCP) and metastatic entities are substantially lethal and lack effective treatments. Transcription factor Slug is critical in regulating metastases of various tumors including PCa. Here we studied targeted therapy against Slug using combination of 3 drugs targeting 3 pathways respectively converging via Slug and further regulating PCa metastasis. Using in vitro assays we confirmed that Slug up-regulation incurred inhibition of E-cadherin that was anti-metastatic, and inhibited Bim-regulated cell apoptosis in PCa. Upstream PTEN/Akt, mTOR, Erk, and AR/Hsp90 pathways were responsible for Slug up-regulation and each of these could be targeted by rapamycin, CI-1040, and 17-AAG respectively. In 4 PCa cell lines with different traits in terms of PTEN loss and androgen sensitivity we tested the efficacy of mono- and combined therapy with the drugs. We found that metastatic capacity of the cells was maximally inhibited only when all 3 drugs were combined, due to the crosstalk between the pathways. 17-AAG decreases Slug expression via blockade of HSP90-dependent AR stability. Combination of rapamycin and CI-1040 diminishes invasiveness more potently in PCa cells that are androgen insensitive and with PTEN loss. Slug inhibited Bim-mediated apoptosis that could be rescued by mTOR/Erk/HSP90 inhibitors. Using mouse models for circulating PCa DNA quantification, we found that combination of mTOR/Erk/HSP90 inhibitors reduced circulating PCa cells in vivo significantly more potently than combination of 2 or monotherapy. Conclusively, combination of mTOR/Erk/Hsp90 inhibits metastatic capacity of prostate cancer via Slug inhibition.
    PLoS ONE 01/2013; 8(10):e77400. · 3.53 Impact Factor
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    ABSTRACT: Prostate-specific antigen (PSA) screening is growing in popularity in China, but its impact on biopsy characteristics and outcomes are poorly understood. Our objective was to characterize prostate biopsy outcomes and trends in Chinese men over a 10-year period, since the increasing use of PSA tests. All men (n = 1,650) who underwent prostate biopsy for PCa at Huashan Hospital, Shanghai, China from 2003-2011 were evaluated. Demographic and clinical information was collected for each patient, including age, digital rectal examination (DRE), transrectal ultrasound (prostate volume and nodule), total prostate-specific antigen (tPSA) levels and free PSA ratio (fPSA/tPSA) prior to biopsy. Prostate biopsy was performed using six cores before October 2007 or ten cores thereafter. Logistic regression and multivariate analysis were used to evaluate our data. The overall positive rate of prostate biopsy for PCa was 47% and the rate decreased significantly over the years from 74% in 2003 to 33% in 2011 (P-trend = 0.004) . Age at diagnosis was slightly increased (P-trend = 0.04) while fPSA/tPSA was significantly decreased (P-trend = 1.11×10-5). A statistically significant trend was not observed for tPSA levels, prostate volume, or proportion of positive nodule. The model including multiple demographic and clinical variables (i.e., age, DRE, tPSA, fPSA/tPSA and transrectal ultrasound results) (AUC = 0.93) statistically outperformed models that included only PSA (AUC = 0.85) or fPSA/tPSA (AUC = 0.66) to predict PCa risks (P<0.05). Similar results were observed in a subgroup of men whose tPSA levels were lower than 20 ng/mL (AUC = 0.87, vs. AUC of tPSA  = 0.62, P<0.05). Detection rates of PCa and high-grade PCa among men that underwent prostate biopsy at the institution has decreased significantly in the past 10 years, likely due to increasing use of PSA tests. Predictive performance of demographic and clinical variables of PCa was excellent. These variables should be used in clinics to determine the need for prostate biopsy.
    PLoS ONE 01/2012; 7(11):e49914. · 3.53 Impact Factor
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    ABSTRACT: OBJECTIVES:: The human Med19 gene encodes a critical subunit that stabilizes the whole mediator complex. To understand the role of Med19 in bladder cancer, we studied the effects of lentivirus-mediated suppression of Med19 expression on bladder cancer cells in vitro and in vivo. METHODS AND: materials: In this study, immunohistochemical analysis was used to demonstrate the expression of Med19 in human bladder cancer. The lentivirus vectors containing a small hairpin RNA (shRNA) to target Med19 were constructed. After bladder cancer cells (5637 and T24) were infected, RT-PCR and Western blotting were used to measure Med19 expression. The influence of Med19 on the proliferation of bladder cancer cells were assessed using MTT, BrdU, colony formation and tumorigenicity experiments. Cell cycle was analyzed with flow cytometric assay. RESULTS:: Med19 was up-regulated in human bladder cancers compared with adjacent benign tissues by immunohistochemical analysis, but was strongly inhibited in 5637 and T24 bladder cancer cells infected with lentiviruses delivering shRNA against Med19. The down-regulation of Med19 increased the proportion of cells in G0/G1 phases and attenuated the growth of 5637 and T24 cells in vitro. The tumorigenicity of Med19-suppressed T24 cells was decreased after inoculation into nude mice. CONCLUSIONS:: Our results suggested that lentiviruses delivering shRNA against Med19 may be a promising tool for bladder cancer therapy.
    Urologic Oncology 04/2011; · 3.65 Impact Factor

Publication Stats

33 Citations
21.53 Total Impact Points

Institutions

  • 2011–2013
    • Fudan University
      • Fudan-VARI Center for Genetic Epidemiology
      Shanghai, Shanghai Shi, China