• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1723-1726
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• 2012

Objective: To summarize and evaluate various urinary markers for early detection, diagnosis and follow-up of human bladder cancer. Methods: A MEDLINE and PUBMED search of the latest literature on urinary markers for bladder cancer was performed. We reviewed these published reports and made a critical analysis. Results: Most urinary markers tend to be less specific than cytology, yielding more false-positive results, but demonstrating an advantage in terms of sensitivity, especially for detecting low grade, superficial tumors. Some tumor markers appear to be good candidates for early detection, diagnosis, and follow-up of human bladder cancer. Conclusion: A number of urinary markers are currently available that appear to be a applicable for clinical detection, diagnosis, and follow-up of bladder cancer. However, further studies are required to determine their accuracy and widespread applicability.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.1
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• pp.135-138
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• 2012

Objective: To investigate whether apoptin is a apoptosis-inducing protein with a potential for bladder cancer therapy. Methods: We constructed a PCDNA3/Apoptin eukaryotic expression vector, and transfected this vector into bladder cancer cell lines BIU-87 and EJ, then observed the results by RT-PCR, transmission electron microscopy, MTT assay and the flow cytometry (TUNEL method). Results: PCDNA3/Apoptin successfully induced a high level apoptosis in both bladder cancer cell lines, compared with the controls (p<0.05). Conclusions: Apoptin can induce high level apoptosis in human bladder cancer EJ and BIU-87 cells, which suggests a potential for human bladder cancer therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6375-6378
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• 2013

Background: The glutathione S transferase (GST) family of enzymes plays a vital role in the phase II biotransformation of environmental carcinogens, pollutants, drugs and other xenobiotics. GSTs are polymorphic and polymorphisms in GST genes have been associated with cancer susceptibility and prognosis. GSTP1 is associated with risk of various cancers including bladder cancer. A case control study was conducted to determine the genotype distribution of GSTP1 A>G SNP, to elucidate the possible role of this SNP as a risk factor in urinary bladder cancer (UBC) development and to examine its correlation with clinico-pathologic variables inUBC cases. Materials and Methods: Using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach, we tested the genotype distribution of 180 bladder cancer patients in comparison with 210 cancer-free controls from the same geographical region with matched frequency in age and gender. Results: We did not observe significant genotype differences between the control and bladder cancer patients overall with an odds ratio (OR)=1.23 (p>0.05). The rare allele (AG+GG) was found to be present more in cases (28.3%) than in controls (24%), though the association was not significant (p<0.05). However, a significant risk of more than 2-fold was found for the variant allele (AG+GG) with smokers in cases as compared to controls (p>0.05). Conclusions: Thus, it is evident from our study that GSTP1 SNP is not implicated overall in bladder cancer, but that the rare, valine-related allele is connected with higher susceptibility to bladder cancer in smokers and also males.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.2
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• pp.119-129
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• 2021

Bladder cancer is one of the most common types of cancer. Most gene mutations related to bladder cancer are dominantly acquired gene mutations and are not inherited. Previous comparative transcriptome analysis of urinary bladder cancer and control samples has revealed a set of genes that may play a role in tumor progression. Here we set out to investigate further the expression of two candidate genes, centromere protein U (CENPU) and mitochondrial ribosomal protein s28 (MRPS28) to better understand their role in bladder cancer pathogenesis. Our results confirmed that CENPU is up-regulated in human bladder cancer tissues at mRNA and protein levels. Gain-of-function and loss-of-function studies in T24 human urinary bladder cancer cell line revealed a hierarchical relationship between CENPU and MRPS28 in the regulation of cell viability, migration and invasion activity. CENPU expression was also up-regulated in in vivo nude mice xenograft model of bladder cancer and mice overexpressing CENPU had significantly higher tumor volume. In summary, our findings identify CENPU and MRPS28 in the molecular pathogenesis of bladder cancer and suggest that CENPU enhances the progression of bladder cancer by promoting MRPS28 expression.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.895-901
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• 2013

Resistance to induction of apoptosis is a major obstacle for bladder cancer treatment. Bcl-2 is thought to be involved in anti-apoptotic signaling. In this study, we investigated the effect of Bcl-2 overexpression on apoptotic resistance and intracellular reactive oxygen species (ROS) generation in bladder cancer cells. A stable Bcl-2 overexpression cell line, BIU87-Bcl-2, was constructed from human bladder cancer cell line BIU87 by transfecting recombinant Bcl-2 [pcDNA3.1(+)-Bcl-2]. The sensitivity of transfected cells to adriamycin (ADR) was assessed by MTT assay. Apoptosis was examined by flow cytometry and acridine orange fluorescence staining. Intracellular ROS was determined using flow cytometry, and the activities of superoxide dismutase (SOD) and catalase (CAT) were also investigated by the xanthinoxidase and visible radiation methods using SOD and CAT detection kits. The susceptibility of BIU87-Bcl-2 cells to ADR treatment was significantly decreased as compared with control BIU87 cells. Enhanced expression of Bcl-2 inhibited intracellular ROS generation following ADR treatment. Moreover, the suppression of SOD and CAT activity induced by ADR treatment was blocked in the BIU87-Bcl-2 case but not in their parental cells. The overexpression of Bcl-2 renders human bladder cancer cells resistant to ADR-induced apoptosis and ROS might act as an important secondary messenger in this process.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5653-5657
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• 2012

Objectives: To investigate the effect of glycopeptide-preferring polypeptide GalNAc transferase 1 (ppGalNAc T1 ) targeted RNA interference (RNAi) on the growth and migration of human bladder carcinoma EJ cells in vitro and in vivo. Methods: DNA microarray assays were performed to determine ppGalNAc Ts(ppGalNAc T1-9) expression in human bladder cancer and normal bladder tissues. We transfected the EJ bladder cancer cell line with well-designed ppGalNAc T1 siRNA. Boyden chamber and Wound healing assays were used to investigate changes of shppGalNAc T1-EJ cell migration. Proliferation of shppGalNAc T1-EJ cells in vitro was assessed using [3H]-thymidine incorporation assay and soft agar colony formation assays. Subcutaneous bladder tumors in BALB/c nude mice were induced by inoculation of shppGalNAc T1-EJ cells and after inoculation diameters of tumors were measured every 5 days to determine gross tumor volumes. Results: ppGalNAc T1 mRNA in bladder cancer tissues was 11.2-fold higher than in normal bladder tissues. When ppGalNAc T1 expression in EJ cells was knocked down through transfection by pSUPER-shppGalNAc T1 vector, markedly reduced incorporation of [3H]-thymidine into DNA of EJ cells was observed at all time points compared with the empty vector transfected control cells. However, ppGalNAc T1 knockdown did not significantly inhibited cell migration (only 12.3%). Silenced ppGalNAc T1 expression significantly inhibited subcutaneous tumor growth compared with the control groups injected with empty vector transfected control cells. At the end of observation course (40 days), the inhibitory rate of cancerous growth for ppGalNAc T1 knockdown was 52.5%. Conclusion: ppGalNAc T1 might be a potential novel marker for human bladder cancer. Although ppGalNAc T1 knockdown caused no remarkable change in cell migration, silenced expression significantly inhibited proliferation and tumor growth of the bladder cancer EJ cell line.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3543-3549
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• 2015

Background: Bladder cancer is one of the most common cancers worldwide. Gene expression profiling using microarray technologies improves the understanding of cancer biology. The aim of this study was to determine the gene expression profile in Egyptian bladder cancer patients. Materials and Methods: Samples from 29 human bladder cancers and adjacent non-neoplastic tissues were analyzed by cDNA microarray, with hierarchical clustering and multidimensional analysis. Results: Five hundred and sixteen genes were differentially expressed of which SOS1, HDAC2, PLXNC1, GTSE1, ULK2, IRS2, ABCA12, TOP3A, HES1, and SRP68 genes were involved in 33 different pathways. The most frequently detected genes were: SOS1 in 20 different pathways; HDAC2 in 5 different pathways; IRS2 in 3 different pathways. There were 388 down-regulated genes. PLCB2 was involved in 11 different pathways, MDM2 in 9 pathways, FZD4 in 5 pathways, p15 and FGF12 in 4 pathways, POLE2 in 3 pathways, and MCM4 and POLR2E in 2 pathways. Thirty genes showed significant differences between transitional cell cancer (TCC) and squamous cell cancer (SCC) samples. Unsupervised cluster analysis of DNA microarray data revealed a clear distinction between low and high grade tumors. In addition 26 genes showed significant differences between low and high tumor stages, including fragile histidine triad, Ras and sialyltransferase 8 (alpha) and 16 showed significant differences between low and high tumor grades, like methionine adenosyl transferase II, beta. Conclusions: The present study identified some genes, that can be used as molecular biomarkers or target genes in Egyptian bladder cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8901-8904
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• 2014

Background: Genetic factors play important roles in the pathogenesis of human cancer. A recent genome wide association study (GWAS) identified an association between the rs2294008 polymorphism of the prostate stem cell antigen (PSCA) gene and bladder cancer risk in Caucasians. The aim of this study was to determine whether the rs2294008 polymorphism is similarly associated with bladder cancer susceptibility in a Korean population. Materials and Methods: We conducted a case-control study of 411 bladder cancer patients and 1,700 controls. Results: The frequencies of the CC, CT, and TT genotypes of the rs2294008 polymorphism were 16.9, 54.0, and 28.8% in bladder cancer patients and 24.4, 48.1, and 27.5% in controls, respectively. We found that the combined CT/TT genotypes were associated with a significantly increased risk of bladder cancer (OR CT/TT =1.58, 95% CI= 1.15-2.17), compared with the CC genotype. Smoking habits, tumor grade and tumor stage did not modify the association between rs2294008 and the risk of bladder cancer. Conclusions: Our study showed that the rs2294008 polymorphism in the PSCA gene is associated with the risk of bladder cancer in a Korean population, providing evidence that it may contribute to bladder carcinogenesis regardless of ethnicity.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3847-3850
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• 2013

The three homologous members of the p160 SRC family (SRC-1, SRC-2 and SRC-3) mediate the transcriptional functions of nuclear receptors and other transcription factors, and are the most studied of all the transcriptional co-activators. Recent work has indicated that the SRC-3 gene is subject to amplification and overexpression in various human cancers. Some of the molecular mechanisms responsible for SRC overexpression, along with the mechanisms by which SRC-3 promotes breast and prostate cancer cell proliferation and survival, have been identified. However, the function of SRC-3 in bladder cancer remains poorly understood. In the present study, our results indicate that overexpression of SRC-3 promotes bladder cancer cell proliferation whereas knockdown of SRC-3 results in inhibition. At the molecular level, we further established that CXCR4 is a transcriptional target of SRC-3. Therefore, our study first identified that SRC-3 plays a critical role in the bladder cancer, which may be a target beneficial for its prevention and treatment.

• Herbal Formula Science
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• v.25 no.2
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• pp.145-154
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• 2017

Objectives : Bufalin is one of the bioactive component of 'Sum Su (蟾酥)', which is obtained from the skin and parotid venom gland of toad. Bufalin has been known to possess the inhibitory effects on cell proliferation and inducing apoptosis in various cancer cells. The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has concerned, because it can selectively induce apoptotic cell death in many types of malignant cells, while it is relatively non-toxic to normal cells. Here, we investigated whether bufalin can trigger TRAIL-induced apoptotic cell death in EJ human bladder cancer cells. Methods : Effects on the cell viability and apoptotic activity were quantified using MTT assay and flow cytometry analysis, respectively. To investigate the morphological change of nucleus, DAPI staining was performed. Protein expressions were measured by immunoblotting. Results : A combined treatment with bufalin (10 nM) and TRAIL (50 ng/ml) significantly promoted TRAIL-mediated growth inhibition and apoptosis in EJ cells. The apoptotic effects were associated with the up-regulation of death receptor proteins, and the down-regulation of cFLIP and XIAP. Moreover, our data showed that bufalin and TRAIL combination activated caspases and subsequently increased degradation of poly(ADP-ribose) polymerase. Conclusions : Taken altogether, the nontoxic doses of bufalin sensitized TRAIL-mediated apoptosis in EJ cells. Therefore, bufalin might be an effective therapeutic strategy for the safe treatment of TRAIL-resistant bladder cancers.