Purpose: Repairing damaged DNA has been shown to be involved in an increased susceptibility to cancer development and prevention. Therefore, the genetic polymorphisms of the hOGG1 gene associated with the gene repair mechanism were investigated. In this study, the possible association of genetic polymorphisms in hOGG1 with bladder tumor risk was examined. MATERIALS AND METHODS: The hospital based, case-control investigation was carried out in 168 primary bladder tumor patients and 672 controls. The DNA extracted from the blood and tissue samples was analyzed by SSCP, PCR-based restriction fragment length polymorphism (RFLP) and direct DNA sequencing in order to characterize the genetic polymorphism of hOGG1. RESULTS: Two polymorphic sites in hOGG1 were found. A polymorphism at codon 326 (1a type) in exon 7 was associated with an amino acid exchange. Another polymorphic site at codon 324 (1b type) in exon 6 was silent. The association between the polymorphism at codon 326 and the risk of the bladder tumor was examined by age-sex adjusted analysis. The distribution of the hOGG1 codon 326 genotypes in the controls (Ser/Ser, 18.9%; Ser/Cys, 54.0%; Cys/Cys, 27.1%) was significantly different from that in the bladder tumor patients (26.2%, 51.8% and 22.0%, respectively) (p=0.034, adjusted OR=0.652, 95% CI=0.44-0.97). In particular, bladder tumor risk in Korean males under 40 years old was approximately 6 times higher than in males over 40 years old (p=0.015, adjusted OR=0.165, 95% CI=0.04-0.75). Furthermore, frequent mutations of codon 326 in the hOGG1 gene in tumor tissues (23.6%) might occur during tumorigenesis. CONCLUSIONS: The data suggests that polymorphism at codon 326 of hOGG1 gene might affect tumorigenesis of a bladder tumor.
Adult ; Carcinogenesis ; Case-Control Studies ; Codon ; DNA ; Exons ; Genotype ; Humans* ; Male ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single-Stranded Conformational ; Sequence Analysis, DNA ; Urinary Bladder Neoplasms* ; Urinary Bladder*

Purpose: Several polymorphic sites have been reported in the tumor necrosis factor alpha (TNF-alpha) promoter. Comparative studies on TNF-alpha production with promoter genotype have reported variable results, particularly in the 308 promoter region. Therefore, genetic polymorphism of TNF-alpha promoter region ( 308) was investigated to determine if it was associated with bladder tumor. MATERIALS AND METHODS: The DNA from 113 and 109 respective blood samples of bladder tumor patients and controls was analyzed by a PCR-based restriction fragment length polymorphism (RFLP) method to characterize the genetic polymorphism of the 308 region of the TNF-alpha promoter. TNF-alpha expression was also checked by measuring the mRNA and protein content using a quantitative-competitive PCR and ELISA method, respectively. RESULTS: The difference in the genetic variations of TNF-alpha promoter did not exist between the bladder tumor patients and the control group (p=0.259). The tumor grade was significantly related to the GA genotype (p=0.04). The mRNA levels of TNF-alpha in the GA genotype were significantly higher than those in the GG genotype in bladder tumors (p=0.022). The TNF-alpha serum levels in the GA genotype were significantly higher than those in the GG genotype regardless of whether there was a bladder tumor. In addition, the TNF-alpha serum levels in bladder tumor patients were significantly higher than the controls in either the GG or GA type (GG type, p=0.001; GA type, p=0.009). CONCLUSIONS: The GA genotype of the TNF-alpha promoter region ( 308) had a significant impact on TNF-alpha production and is related to a higher-grade tumor compared to the GG genotype. The TNF-alpha serum levels in the bladder tumor patients were significantly higher than in the controls. This suggests that TNF-alpha might be involved in the tumorigenesis of the bladder.
Carcinogenesis ; DNA ; Enzyme-Linked Immunosorbent Assay ; Genetic Variation ; Genotype* ; Humans ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; Promoter Regions, Genetic ; RNA, Messenger ; Tumor Necrosis Factor-alpha* ; Urinary Bladder Neoplasms* ; Urinary Bladder*

PURPOSE: Magnolia officinalis has been used in traditional Chinese medicine to treat a variety of diseases. The main constituents of Magnolia officinalis are honokiol and magnolol, which have a variety of pharmacological effects, such as antitumor, antioxidant, antimicrobial, anti-inflammatory etc. This study examined the anticancer effect of a Magnolia officinalis' extract on urinary bladder cancer in vivo. MATERIALS AND METHODS: Male mice C3H/He were used as the experimental animals. The mice were divided into ten groups. Normal drinking water was provided to group 1(5 mice) for 20 weeks and 0.05% N-butyl- N-(4-hydroxybutyl) nitrosamine(BBN) was added to in the drinking water of group 2(5 mice). 0.1, 0.3, 1.0 and 3.0% Magnolia officinalis' extract was added to groups 3, 4, 5 and 6, respectively(5 mice each), and 0.1, 0.3, 1.0 and 3.0% Magnolia officinalis' extract plus 0.05% BBN was added to groups 7, 8, 9 and 10, respectively(10 mice each) for the same period. All surviving mice were sacrificed at week 20 to investigate the occurrence of bladder cancer, stage and grade. RESULTS: Bladder cancer was not observed in groups 1, 3, 4, 5 and 6 mice. The rates of bladder cancer occurrence were 57.1, 66.7, 44.4 and 20.0% in groups 7, 8, 9 and 10, respectively. The incidence decreased with increasing concentration of Magnolia officinalis (p=0.005). However, the stage and grade were not associated with the concentration of Magnolia officinalis(each p>0.05). CONCLUSIONS: This study showed that Magnolia officinalis has some protective effect against bladder cancer. In the future, Magnolia officinalis may be expected to play an important role as a chemo-preventive and therapeutic agent or as a complementary agent in bladder cancer.
Animals ; Biphenyl Compounds ; Drinking Water ; Humans ; Incidence ; Lignans ; Magnolia ; Male ; Medicine, Chinese Traditional ; Mice ; Urinary Bladder ; Urinary Bladder Neoplasms

PURPOSE: The SAPK/JNK group of MAP (mitogen-activated protein) kinases is known to regulate cellular proliferation, apoptosis and tissue morphogenesis. This study was performed to assess the clinical usefulness of the SAPK/JNK for a bladder tumor. MATERIALS AND METHODS: Ninety-five bladder tumors and 23 normal bladder mucosa were included in this study. Expression of the phosphorylated and unphosphorylated forms of JNK1 and 2 were examined using western blot analysis. The relationship between JNK expression and the bladder tumor stage, grade, recurrence, survival and P53 expression level were analyzed. RESULTS: The unphosphorylated JNK1 level was higher in bladder tumors than in normal bladder mucosa. With respect to the stage, the absolute and relative values of the phosphorylated JNK1 were higher in superficial tumors than in invasive tumors, while those of unphosphorylated JNK1 were higher in invasive tumors. The phosphorylated JNK1 level also had a negative correlation with the tumor grade and recurrence. A positive correlation existed between the p53 expression level and the absolute values of unphosphorylated JNK1 and 2. CONCLUSIONS: Among the 3 isoforms, JNK1 plays a role in the development of a bladder tumor. Higher expressions of the inactive forms in a bladder tumor than in a normal control and the active forms in a low stage and grade tumor might support the hypothesis that the loss of JNK1 activation may contribute to tumorigenesis.
Apoptosis ; Blotting, Western ; Carcinogenesis ; Carcinoma, Transitional Cell* ; Cell Proliferation ; Morphogenesis ; Mucous Membrane ; Phosphotransferases* ; Protein Isoforms ; Protein Kinases ; Recurrence ; Urinary Bladder Neoplasms ; Urinary Bladder*

PURPOSE: A multi-subunit transcription factor NF-kappaB mediates the antiapoptotic signals in several cancer cell lines and it is activated in a broad range of human tumors. In this study, we investigated whether the expression levels of the NF-kappaB and the apoptosis inducing genes were related to the pathogenesis and clinical properties of human bladder tumor. MATERIALS AND METHODS: The expressions of NF-kappaB, BCL2-associated X protein (BAX), BCL2-associated death protein (BAD) and BH3-interacting domain death agonist protein (BID) were investigated by performing immunohistochemical staining on 133 archival bladder tissue paraffin blocks; these blocks included 122 transitional cell carcinomas of the urinary bladder and 11 normal bladder mucosae. RESULTS: The expression levels of NF-kappaB were significantly higher in the bladder tumors than those of the normal bladder mucosae (p=0.001). The expression levels of BAX in the superficial and low-grade (grade 1 and 2) bladder tumors were significantly enhanced more than those of the high-grade and invasive cases (p=0.042 and p=0.045, respectively), while the expression levels of BAD in the tumor tissues and low-grade tumors were significantly elevated compared with those of the normal mucosae and high grade tumor (p=0.007 and p=0.048, respectively). But the expressions of BID were not correlated with any pathologic and clinical properties. CONCLUSIONS: The expressions of the NF-kappaB and apoptosis inducing genes such as BAX and BAD are strongly associated with the pathogenesis and clinical properties of bladder tumor. (Korean J Urol 2007;48:483-488)
Apoptosis* ; bcl-2-Associated X Protein ; BH3 Interacting Domain Death Agonist Protein ; Carcinoma, Transitional Cell ; Cell Line ; Humans ; Mucous Membrane ; NF-kappa B* ; Paraffin ; Transcription Factors ; Urinary Bladder Neoplasms* ; Urinary Bladder*

The potential use of urinary nucleic acids as diagnostic markers in prostate cancer (PCa) was evaluated. Ninety-five urine samples and 234 prostate tissue samples from patients with PCa and benign prostatic hyperplasia (BPH) were analyzed. Micro-array analysis was used to identify candidate genes, which were verified by the two-gene expression ratio and validated in tissue mRNA and urinary nucleic acid cohorts. Real-time quantitative polymerase chain reaction (qPCR) was used to measure urinary nucleic acid levels and tissue mRNA expression. The TSPAN13-to-S100A9 ratio was selected to determine the diagnostic value of urinary nucleic acids in PCa (P = 0.037) and shown to be significantly higher in PCa than in BPH in the mRNA and nucleic acid cohort analyses (P < 0.001 and P = 0.013, respectively). Receiver operating characteristic (ROC) analysis showed that the area under the ROC curve was 0.898 and 0.676 in tissue mRNA cohort and urinary nucleic acid cohort, respectively. The TSPAN13-to-S100A9 ratio showed a strong potential as a diagnostic marker for PCa. The present results suggest that the analysis of urine supernatant can be used as a simple diagnostic method for PCa that can be adapted to the clinical setting in the future.
Aged ; Aged, 80 and over ; Biomarkers, Tumor/*genetics/*urine ; Calgranulin B/*genetics ; Cohort Studies ; Humans ; Male ; Middle Aged ; Nucleic Acids/*genetics/*urine ; Oligonucleotide Array Sequence Analysis ; Prostate/metabolism ; Prostatic Hyperplasia/diagnosis/genetics/urine ; Prostatic Neoplasms/diagnosis/*genetics/*urine ; RNA, Messenger/genetics/metabolism ; RNA, Neoplasm/genetics/metabolism ; ROC Curve ; Real-Time Polymerase Chain Reaction ; Tetraspanins/*genetics

PURPOSE: MicroRNAs (miRNAs) in biological fluids are potential biomarkers for the diagnosis and assessment of urological diseases such as benign prostatic hyperplasia (BPH) and prostate cancer (PCa). The aim of the study was to identify and validate urinary cell-free miRNAs that can segregate patients with PCa from those with BPH. METHODS: In total, 1,052 urine, 150 serum, and 150 prostate tissue samples from patients with PCa or BPH were used in the study. A urine-based miRNA microarray analysis suggested the presence of differentially expressed urinary miRNAs in patients with PCa, and these were further validated in three independent PCa cohorts, using a quantitative reverse transcriptionpolymerase chain reaction analysis. RESULTS: The expression levels of hsa-miR-615-3p, hsv1-miR-H18, hsv2-miR-H9-5p, and hsa-miR-4316 were significantly higher in urine samples of patients with PCa than in those of BPH controls. In particular, herpes simplex virus (hsv)-derived hsv1-miR-H18 and hsv2-miR-H9-5p showed better diagnostic performance than did the serum prostate-specific antigen (PSA) test for patients in the PSA gray zone. Furthermore, a combination of urinary hsv2-miR-H9-5p with serum PSA showed high sensitivity and specificity, providing a potential clinical benefit by reducing unnecessary biopsies. CONCLUSIONS: Our findings showed that hsv-encoded hsv1-miR-H18 and hsv2-miR-H9-5p are significantly associated with PCa and can facilitate early diagnosis of PCa for patients within the serum PSA gray zone.
Biomarkers ; Biopsy ; Cohort Studies ; Diagnosis ; Early Diagnosis ; Herpes Simplex ; Humans ; Microarray Analysis ; MicroRNAs* ; Passive Cutaneous Anaphylaxis ; Prostate ; Prostate-Specific Antigen ; Prostatic Hyperplasia ; Prostatic Neoplasms* ; Sensitivity and Specificity ; Simplexvirus ; Urologic Diseases

In this article, a part of fund and grant supports was omitted unintentionally.

PURPOSE: Previously, we reported the presence of virus-encoded microRNAs (miRNAs) in the urine of prostate cancer (CaP) patients. In this study, we investigated the expression of two herpes virus-encoded miRNAs in prostate tissue. METHODS: A total of 175 tissue samples from noncancerous benign prostatic hyperplasia (BPH), 248 tissue samples from patients with CaP and BPH, and 50 samples from noncancerous surrounding tissues from these same patients were analyzed for the expression of two herpes virus-encoded miRNAs by real-time polymerase chain reaction (PCR) and immunocytochemistry using nanoparticles as molecular beacons. RESULTS: Real-time reverse transcription-PCR results revealed significantly higher expression of hsv1-miR-H18 and hsv2-miRH9- 5p in surrounding noncancerous and CaP tissues than that in BPH tissue (each comparison, P<0.001). Of note, these miRNA were expressed equivalently in the CaP tissues and surrounding noncancerous tissues. Moreover, immunocytochemistry clearly demonstrated a significant enrichment of both hsv1-miR-H18 and hsv2-miR-H9 beacon-labeled cells in CaP and surrounding noncancerous tissue compared to that in BPH tissue (each comparison, P<0.05 for hsv1-miR-H18 and hsv2- miR-H9). CONCLUSIONS: These results suggest that increased expression of hsv1-miR-H18 and hsv2-miR-H95p might be associated with tumorigenesis in the prostate. Further studies will be required to elucidate the role of these miRNAs with respect to CaP and herpes viral infections.
Carcinogenesis ; Herpesviridae ; Humans ; Hyperplasia* ; Immunohistochemistry ; MicroRNAs ; Nanoparticles ; Prostate* ; Prostatic Hyperplasia ; Prostatic Neoplasms ; Real-Time Polymerase Chain Reaction