Qinghui Wu

Publications (5)22.58 Total impact

• Article: Noninvasive urinary metabonomic diagnosis of human bladder cancer.

  Kishore Kumar Pasikanti, Kesavan Esuvaranathan, Paul C Ho, Ratha Mahendran, Revathi Kamaraj, Qing Hui Wu, Edmund Chiong, Eric Chun Yong Chan
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  ABSTRACT: Cystoscopy is considered the gold standard for the clinical diagnosis of human bladder cancer (BC). As cystoscopy is expensive and invasive, it may compromise patients' compliance and account for the failure in detecting recurrent BC in some patients. In this paper, we investigated the role of urinary metabonomics in the diagnosis of human BC. Gas chromatography/time-of-flight mass spectrometry was applied for the urinary metabolic profiling of 24 BC patients and 51 non-BC controls. The acquired data were analyzed using multivariate principal component analysis followed by orthogonal partial least-squares discriminant analysis (OPLS-DA). Model validity was verified using permutation tests and receiver operating characteristic (ROC) analysis. BC patients were clearly distinguished from non-BC subjects based on their global urinary metabolic profiles (OPLS-DA, 4 latent variables, R(2)X = 0.420, R(2)Y = 0.912 and Q(2) (cumulative) = 0.245; ROC AUC of 0.90; 15 marker metabolites). One-hundred percent sensitivity in detecting BC was observed using urinary metabonomics versus 33% sensitivity achieved by urinary cytology. Additionally, urinary metabonomics exhibited potential in the staging and grading of bladder tumors. In summary, urinary metabonomics is amenable for the noninvasive diagnosis of human BC.
  Journal of Proteome Research 03/2010; 9(6):2988-95. · 5.11 Impact Factor
• Article: Monitoring the response of orthotopic bladder tumors to granulocyte macrophage colony-stimulating factor therapy using the prostate-specific antigen gene as a reporter.

  Qinghui Wu, Kesavan Esuvaranathan, Ratha Mahendran
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  ABSTRACT: Although orthotopic animal models of cancer best reflect the disease in humans, a major drawback of these models is the inability to monitor tumor growth accurately. Our aims were to produce a bladder tumor cell line (MB49) that secreted human prostate-specific antigen (PSA), analyze the feasibility and accuracy of PSA as a biomarker for monitoring orthotopic bladder tumor growth, and evaluate the effectiveness of granulocyte macrophage colony-stimulating factor (GM-CSF) gene therapy using this model. PSA secretion was assessed after both s.c. and orthotopic implantation of MB49-PSA cells in C57BL/6 mice. PSA levels in mouse serum and urine samples were monitored at 2- to 3-day intervals by ELISA. Using the orthotopic model, mice with confirmed tumors were given liposome-mediated GM-CSF gene therapy twice a week for 3 weeks intravesically and PSA levels monitored. The MB49-PSA cells behaved similarly as the parental cell line and produced high levels of PSA both in vitro and in vivo. In the s.c. model, the level of PSA produced correlated with tumor volume (r = 0.96). In the orthotopic model, PSA could be detected in serum and urine on the fourth day after implantation. PSA levels over the treatment period indicated that tumor growth was inhibited by GM-CSF gene therapy. Up to 50% of the treated mice were cured. Cytokine array analysis revealed that GM-CSF gene therapy induced the production of other cytokines and chemokines. MB49 cells modified to secrete PSA are a reliable method to evaluate therapeutic modalities for bladder cancer.
  Clinical Cancer Research 11/2004; 10(20):6977-84. · 7.74 Impact Factor
• Article: Non-viral tumor necrosis factor-alpha gene transfer decreases the incidence of orthotopic bladder tumors.

  Zhijiang Zang, Ratha Mahendran, Qinghui Wu, Thomas Yong, Kesavan Esuvaranathan
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  ABSTRACT: Our aim was to evaluate the feasibility and efficacy of tumor necrosis factor-alpha gene therapy in preventing bladder tumor recurrence using an orthotopic model of bladder cancer. We transiently transfected a murine bladder cancer cell line MB49 with pBud-TNF-alpha using a transfection system consisting of the cationic liposome N-(1-(2,3-dioleoyloxyl)propyl)-N,N,N-trimethylammoniummethyl sulfate (DOTAP) plus methyl-beta-cyclodextrin solubilized cholesterol (MBC). MB49 cells produced 893.7+/-24.0 pg/ml of TNF-alpha 2 days after transfection. Cell growth was inhibited, apoptosis was induced and MHC class I, B7.1 and Fas expression on the MB49 cells were increased. In vivo, an orthotopic murine bladder cancer model was established by intravesical instillation of bladder cancer cells after transurethral cauterization of the mouse bladder mucosa. TNF-alpha gene transfer was initiated 2 days after the tumor inoculation, when the tumor burden was small, and given twice per week for 3 weeks. RT-PCR showed TNF-alpha mRNA was observed to increase after the first instillation and then return to basal level 1 month after the sixth instillation. Histology revealed that TNF-alpha gene transfer decreases the bladder tumor incidence from 75% for the control group to 25% for the treated group. Increased level of T lymphocytes and NK cells was found in the TNF-alpha transfected bladders. In situ cytokine gene transfer provides significant protection against tumor growth. This approach may be useful to reduce the incidence of a subsequent tumor after endoscopic resection when used for prophylaxis.
  International Journal of Molecular Medicine 11/2004; 14(4):713-7. · 1.98 Impact Factor
• Article: Nonviral cytokine gene therapy on an orthotopic bladder cancer model.

  Qinghui Wu, Ratha Mahendran, Kesavan Esuvaranathan
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  ABSTRACT: The purpose is to assess cytokine gene transfection in tumor cells and its therapeutic efficacy in an orthotopic mouse bladder cancer model after liposome-mediated gene transfer. A total of 1 x 10(5) MB49 cells was instilled into the bladder of C57BL/6 mice after electrocautery to establish the tumor model. The plasmids were constructed by inserting the coding sequences for murine IFN-alpha1 and granulocyte macrophage colony-stimulating factor into a plasmid vector pBudCE4.1. Transient transfection was performed using a cationic lipid N-[1-(2,3-dioleoyloxyl)propyl]-N,N,N-trimethylammoniummethyl sulfate and methyl-beta-cyclodextrin-solubilized cholesterol. The in vitro expression of cytokines was checked by ELISA. The expression of the transgene in situ was confirmed by immunohistochemistry and 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside staining. Mice bearing orthotopic tumors were treated with plasmid DNA/liposome complex by intravesical instillation twice a week for 3 weeks. Superficial bladder tumors were established by intravesical instillation of MB49 into cauterized bladders. The expression level of cytokines in transfected cell lines was increased significantly. In situ gene transfer to bladder tumors was accomplished via intravesical instillation of plasmid DNA/N-[1-(2,3-dioleoyloxyl)propyl]-N,N,N-trimethylammoniummethyl sulfate/methyl-beta-cyclodextrin-solubilized cholesterol after a single 2 h in situ transfection. The tumor incidence in the treatment groups was dramatically decreased from 76.9% in the control group to 15.4-30.8% in the treatment groups. We demonstrated in the orthotopic mouse bladder cancer model that successful inhibition of tumor cell growth could be obtained with cytokine gene therapy. The results suggest that our liposome transfection system appears to be a promising method for gene therapy of bladder cancer in vivo.
  Clinical Cancer Research 11/2003; 9(12):4522-8. · 7.74 Impact Factor
• Article: 264. Non-Invasive Monitoring of the Response of Orthotopic Bladder Tumors to GM-CSF Gene Therapy Using the Prostate Specific Antigen Gene as a Reporter

  Qinghui Wu, Ratha Mahendran, Kesavan Esuvaranathan