Clinical Significance of the Expression of Gli2 and Gli3 in Bladder Cancer / 대한비뇨기과학회지

PURPOSE: The HedgehogGli(HHGli) signaling pathway controls many aspects of tissue patterning, cell proliferation, differentiation and regeneration, and regulates the number of cells in various organs. Inappropriate and uncontrolled activation of the HHGli signaling pathway has been demonstrated in a variety of human cancers. The Gli1, Gli2, and Gli3 genes encoding the Gli family transcription factors play a role as HH effectors. This study examined the significance in Gli2 and Gli3 expression in human bladder cancer. MATERIALS AND METHODS: The tumor tissues were obtained from 144 patients with a primary bladder cancer. The mRNA levels of Gli2, and Gli3 were examined using a real-time polymerase chain reaction(PCR) assay in 144 tumor specimens, and immunohistochemical staining was performed on 127 tumor paraffin blocks. The relationships between their expression and the pathological or clinical characteristics, such as tumor stage, grade, recurrence and progression were also analyzed. RESULTS: Gli2 mRNA expression was higher in the invasive bladder tumors than in the superficial bladder tumors(p<0.001) but, there was no difference in Gli3 mRNA expression according to the tumor stage and grade. The multivariate Cox regression model revealed that Gli2 mRNA expression(hazards ratio(HR): 2.329, 95% confidence interval(CI): 1.043- 5.202, p=0.039) was the only strong predictor of superficial bladder tumor recurrence. Kaplan-Meier analysis also showed identical results (log-rank test, p=0.043). CONCLUSIONS: The enhanced expression of Gli2 mRNA was strongly correlated with the recurrence of superficial bladder cancer. These results suggest that Gli2 may be a useful marker for assessing the recurrence of superficial bladder cancer in human bladder cancers.

Analysis of the NF-kappaB and Apoptosis Inducing Genes in Bladder Tumor / 대한비뇨기과학회지

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)

Local Effects of Antimuscarinics on Muscarinic Receptors in Bladder Sensory Nerves

PURPOSE: To investigate the role of muscarinic receptors in bladder sensory mechanism. MATERIALS AND METHODS: Normal adult volunteers collected voided urine after taking five days of trospium(20 mg bid), tolterodine LA(4 mg qd) and oxybutynin XL(10 mg qd). The effect of intravesical administration of human urine on carbachol-induced bladder overactivity was studied in female Sprague-Dawley rats. Cystometric parameters during continuous infusion for over one hour each of saline, human urine, then mixture of carbachol and human urine were compared(n=6 in each group). Then 0.1 and 0.5microgram/ml of oxybutynin, trospium, tolerodine, and dimethindene were studied with the same methods. RESULTS: Human urine with or without intake of antimuscarinic agents had no effect on normal bladder function. Bladder capacity and intercontraction intervals were significantly decreased after an addition of carbachol to human urine containing vehicle, tolterodine or oxybutynin. Human urine after ingestion of trospium, however, prevented the carbachol-induced reduction in bladder capacity and intercontraction intervals. Maximum voiding pressure and pressure threshold were not changed in any case. 0.1 and 0.5microgram/ml of oxybutynin, trospium, tolerodine, and dimethindene prevented the decrease of intercontraction interval with intravesical carbachol(65+/-0.1% compared with baseline). CONCLUSION: The excreted urine after oral ingestion of 20 mg bid of trospium has a significant inhibitory effect in a rat model of detrusor overactivity. Intravesical instillation of antimuscarinic agents at clinically meaningful concentrations also suppressed carbachol-induced bladder overactivity. Antimuscarinic agents may be effective in treating bladder overactivity, not only by suppression of muscarinic receptor-mediated detrusor muscle contraction, but also by blocking muscarinic receptors in bladder-afferent pathways.

The thickness of palatal masticatory mucosa / 대한치주과학회지

The Palatal masticatory mucosa was widely used as a donor site in periodontal and implant surgery. but there were relatively few studies investigating the thickness of the palatal mucosa in dentate subjects. The purpose of this study was to study the thickness of palatal masticatory mucosa in korean subjects by direct clinical technique. Forty systemically and periodontally healthy subjects(20 males:20 females) participated in this study. A bone sounding method using a periodontal probe with minimal anesthesia and a prepared clear acrylic stent was utilized to assess the thickness of palatal mucosa at 24 measurement points defined according to the gingival margin and mid palatal suture. The results are as follows; 1. Mean thickness of palatal masticatory mucosa was 3.5+/-0.4mm. and no gender differences were identified in the thickness of palatal masticatory mucosa. 2. The thickness of palatal masticatory mucosa increased from canine to second molar area(with the exception of the first molar area). canine and first molar areas were significantly thinner than other areas(P<0.05). 3. The thickness of palatal masticatory mucosa significantly increased in the sites farther from the gingival margin towarding the mid-palate(P<0.05). The results suggest that within the limits of the present study, premolar area appears to be the most appropriate donor site for soft tissue grafting procedures.

Effect of Panax Ginseng Water Extract for Treatment of Male Infertility / 대한남성과학회지

PURPOSE: We previously reported that Panax ginseng water extract (PG-WE) played both preventive and therapeutic roles on testicular toxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in animal study, one of the most potent environmental pollutants. Thus we investigated whether PG-WE might be useful in the treatment of male infertility, because men in modern society are exposed by numerous environmental hormones. MATERIALS AND METHODS: Eighteen patients with abnormal semen analysis and 8 volunteers whose semen analysis were normal as control group were enrolled in this study. Before PG-WE administration, semen analysis, hormonal study, liver and renal function test, CBC, and urinalysis were checked in all subjects. PG-WE (2.4 gm) was administered everyday for 8 weeks in both groups. Follow-up semen analysis and laboratory studies were checked at 13th week. RESULTS: In patient group semen volume was increased (2.4 1.3 ml vs 2.6 1.6 ml, p=0.051). Semen volume as well as sperm concentration in oligospermia patient were increased but not significantly. Serum estradiol level decreased by PG-WE treatment in patient group (p=0.005). All subjects showed no toxic effect. CONCLUSIONS: Our data suggest that Panax ginseng is a potential agent that can improve abnormal sperm parameters in infertile male patients and also improve the sperm quality in healthy men.

Value of Urinary 8-hydroxydeoxyguanosine (oh(8)dG) Measurement in Patients with Bladder Cancer / 대한비뇨기과학회지

PURPOSE: Oxidative DNA damage may play a role in the aging process, carcinogenesis and other degenerative diseases and can be assessed in humans in vivo from the urinary excretion of the DNA repair product, 8-hydroxydeoxyguanosine (oh(8)dG). In order to estimate the urinary oh(8)dG concentration in bladder cancer patients and the effect of smoking on the urinary oh(8)dG excretion, the urinary oh(8)dG levels in bladder cancer patients and control subjects were measured. MATERIALS AND METHODS: Urine samples were collected from 110 bladder cancer patients and 64 controls. The subjects' smoking history was gathered from a standardized self-completed questionnaire. The urinary oh(8)dG concentration was measured using an oh(8)dG ELISA Kit. The relationship between the urinary oh(8)dG concentration and the bladder cancer stage, grade and smoking history were analyzed. RESULTS: The urinary oh(8)dG concentration was significantly higher in the control group than in both preoperative and postoperative bladder cancer patients (p=0.049 and p=0.013, respectively). In the bladder cancer patients, the urinary oh(8)dG concentration did not correlate with either the stage or the grade. Regarding the smoking status, the urinary oh(8)dG concentrations of smokers in bladder cancer patients were lower than those of smokers in the control group (p=0.018). In the control group, the urinary oh(8)dG concentrations in smokers were higher than those in nonsmokers (p=0.013). There was no difference of urinary oh(8)dG concentration in bladder cancer patients irrespective of the smoking status. CONCLUSIONS: The decreased urinary excretion of oh(8)dG in bladder tumor patients suggests that the repair mechanism of oxidative DNA damage, oh(8)dG, might be impaired in bladder cancer patients. Further studies aimed at measuring the DNA concentration of oh(8)dG or its repair activity in bladder tumor tissues are needed to test this possibility.

Value of Urinary 8-hydroxydeoxyguanosine (oh(8)dG) Measurement in Patients with Bladder Cancer / 대한비뇨기과학회지

PURPOSE: Oxidative DNA damage may play a role in the aging process, carcinogenesis and other degenerative diseases and can be assessed in humans in vivo from the urinary excretion of the DNA repair product, 8-hydroxydeoxyguanosine (oh(8)dG). In order to estimate the urinary oh(8)dG concentration in bladder cancer patients and the effect of smoking on the urinary oh(8)dG excretion, the urinary oh(8)dG levels in bladder cancer patients and control subjects were measured. MATERIALS AND METHODS: Urine samples were collected from 110 bladder cancer patients and 64 controls. The subjects' smoking history was gathered from a standardized self-completed questionnaire. The urinary oh(8)dG concentration was measured using an oh(8)dG ELISA Kit. The relationship between the urinary oh(8)dG concentration and the bladder cancer stage, grade and smoking history were analyzed. RESULTS: The urinary oh(8)dG concentration was significantly higher in the control group than in both preoperative and postoperative bladder cancer patients (p=0.049 and p=0.013, respectively). In the bladder cancer patients, the urinary oh(8)dG concentration did not correlate with either the stage or the grade. Regarding the smoking status, the urinary oh(8)dG concentrations of smokers in bladder cancer patients were lower than those of smokers in the control group (p=0.018). In the control group, the urinary oh(8)dG concentrations in smokers were higher than those in nonsmokers (p=0.013). There was no difference of urinary oh(8)dG concentration in bladder cancer patients irrespective of the smoking status. CONCLUSIONS: The decreased urinary excretion of oh(8)dG in bladder tumor patients suggests that the repair mechanism of oxidative DNA damage, oh(8)dG, might be impaired in bladder cancer patients. Further studies aimed at measuring the DNA concentration of oh(8)dG or its repair activity in bladder tumor tissues are needed to test this possibility.

The Neutralizing Effect of Panax Ginseng for Toxicities in the Survival, Sperm Quality, Pregnancy and F1 Generation of Guinea Pigs Exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin / 대한비뇨기과학회지

PURPOSE: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), one of the most potent environmental pollutants, is known to disrupt the endocrine, immune, and reproductive system. This study was carried out to investigate the effect of a panax ginseng water extract (PG-WE) on the survival rate, sperm quality, and fertility impaired by TCDD. MATERIALS AND METHODS: Eighty male guinea pigs were divided into 8 groups. The normal control group received the vehicle and saline. TCDD was intraperitoneally injected at a single dose of 1microgram/kg. A PG-WE was administered at 100 or 200mg/kg/ day 1wk prior to (P groups) or subsequent to (C groups) TCDD-exposure for 12 and 10 weeks, respectively. The G groups received the vehicle and the PG-WE of 100 or 200mg/kg/day, respectively. The parameters for the male guinea pigs were assessed for 40 weeks. The effects on the F1 generation were assessed at a growth period of F1. RESULTS: All single TCDD-treated group animals died within 18 days and the survival rate of the PG-WE-treated groups increased in a dose dependant manner. Forty to 70% of the P and C groups survived until the 40th week and reached sexual maturation. The death rate of the progeny born from the PG-WE-treated groups was significantly lower than that in the NC group (14.3%). The M/F ratio of the F1 generation in the P and C groups had higher female birth ratio. The sperm number and morphology showed no significant differences among the groups. The PG-WE increased the sperm motility in the guinea pigs exposed to TCDD. CONCLUSIONS: Panax ginseng is a useful agent that can neutralize endocrine disrupters and environmental pollutants, and help maintain a high sperm quality after a growth period.

Xanthogranulomatous Cystitis / 대한비뇨기과학회지

Xanthogranulomatous cystitis is a rare benign chronic inflammatory disease. To the best of our knowledge, only 16 cases have been reported in the literature. The etiology of xanthogranulomatous cystitis may include immunological disorders, abnormal lipid metabolism, a reduction of chemotactic activities, and metaplasia of the urothelium due to a chronic infection. Only one case has been reported in the Korean literature. Here we describe two cases of xanthogranulomatous cystitis with a review of the previous reports.

Altered Expression of p33(ING1) in Human Bladder Cancer / 대한비뇨기과학회지

PURPOSE: p33(ING1) seems to be a candidate of novel growth inhibitor as a tumor suppressor gene and plays a critical role in regulation of cell cycle progression and susceptibility to apoptosis. In this study, we investigated p33(ING1) expression pattern in human bladder cancer and normal tissue. MATERIALS AND METHODS: RNA was extracted from 42 bladder cancer specimens and 24 normal bladder mucosa. Expression of p33(ING1) was examined by quantitative RT- PCR in which the ratio to GAPDH, an internal control, was used as a standardized expression value of the p33(ING1). Alterations of p33(ING1) expression between cancer and normal mucosa were compared and interrelationship with stage and grade was analyzed. To detect the mutations in the p33(ING1), PCR-SSCP analysis was also performed. RESULTS: Out of 42 bladder cancer (25 superficial and 17 invasive), 9 were grade I, 23 were grade II, and 10 were grade III. p33(ING1) expression in bladder cancer significantly decreased compared to that in normal bladder mucosa. The ratio of p33(ING1)/ GAPDH was 0.45 +/- 0.13 in bladder cancer, whereas for normal bladder mucosa this ratio was 0.66 +/- 0.17 (p <0.001). However, expression of p33(ING1) was neither correlated with tumor stage nor grade (p=0.489 and p=0.375, respectively). Changes in electrophoretic mobility of PCR-SSCP products were not detected in any of bladder cancers. CONCLUSIONS: These data suggest that decreased expression of p33(ING1) may contribute to the development of bladder cancer in part, even though the gene is mostly preserved. However, considering a discrepancy between the rate of mutation and the decreased expression, further study is warranted to determine the mechanism.

Development of 166Ho-Stent for the Treatment of Esophageal Cancer / 대한핵의학회잡지

PURPOSE: Esophageal cancer patients have a difficulty in the intake of meals through the blocked esophageal lumen, which is caused by an ingrowth of cancer cells and largely influences on the prognosis. It is reported that esophageal cancer has a very low survival rate due to the lack of nourishment and immunity as the result of this. In this study a new radioactive stent, which prevents tumor ingrowth and restenosis by additional radiation treatment, has been developed. MATERIALS AND METHODS: Using HANARO research reactor, the radioactive stent assembly (166Ho-SA) was prepared by covering the metallic stent with a radioactive sleeve by means of a post-irradiation and pre-irradiation methods. RESULTS: Scanning electron microscopy and autoradiography exhibited that the distribution of 165/166Ho (NO3) compounds in polyurethane matrix was homogeneous. A geometrical model of the esophagus considering its structural properties, was developed for the computer simulation of energy deposition to the esophageal wall. The dose distributions of 166Ho-stent were calculated by means of the EGS4 code system. The sources are considered to be distributed uniformly on the surface in the form of a cylinder with a diameter of 20 mm and length of 40 mm. As an animal experiment, when radioactive stent developed in this study was inserted into the esophagus of a Mongrel dog, tissue destruction and widening of the esophageal lumen were observed. CONCLUSION: We have developed a new radioactive stent comprising of a radioactive tubular sleeve covering the metallic stent, which emits homogeneous radiation. If it is inserted into the blocked or narrowed lumen, it can lead to local destruction of the tumor due to irradiation effect with dilatation resulting from self-expansion of the metallic property. Accordingly, it is expected that restenosis esophageal lumen by the continuous ingrowth and infiltration of cancer after insertion of our radioactive stent will be decreased remarkably.

The Effect of Anoxia and Reoxygenation on the Production of Prostaglandin I2 from the Endothelial Cells of Umbilical Vein

The successful revascularization and reperfusion of ischemia are still associated with high systemic complication rates and severe local tissue injuries. The morality rates after revascularization have been reported to range from 10% to 20% and the amputation rates from 12% to 22%. It is well recognized that the microvasculature is highly sensitive to ischemia-reperfusion (I/R) and that the initial damage of endothelial cells contributes to I/R-induced tissue injury. In an effort to define the mechanisms responsible for reperfusion-induced vascular injury number of in vitro models have been developed to stimulate the responses of endothelial cells to I/R. Because of its simplicity, many investigators have used monolayers of cultured endothelial cells exposed to anoxia and reoxygenation as a model system to minic I/R-induced vascular changes in vivo. The endothelium serves as an important modulator of vascular homeostases by secreting various levels of both thrombotic and antithrombotic agents. One of the important product of endothelial cells, prostaglandin I2 or prostacyclin (PGI2) helps to maintain hemostasis through its involvement in coagulation, platelet activation, leukocyte migration and adhesion, vascular tone regulation and growth control. PGI2 synthesis is a readily quantifiable index of endothelial cell perturbation and thus serves as a marker for the identification of injurious stimuli. Endothelial cells were isolated from human umbilical vein and cultured in M-199 medium plus 20% fetal calf serum. Purity of culture was determined by immunological fluorescent staining of factor VIII related antigen, phase-contrast microscopy. TRK 790 radio-immunoassay kit was used for the measuring of 6-keto-PGF1 alpha released by endothelial cells. The results were as follows: 1) The concentration of PGI(2) released from the cultured endothelial cells was 33.44 +/- 2.26 pg/1 105 cells/mL 2) Incubation of endothelial cells with anoxia and reoxygenation resulted in PGI(2) release of 42.98 +/- 2.29 pg/1x10(5) cells/ml and 62.44 2.11 pg/1 105 cells/ml, respectively. 3) Incubation of endothelial cells with allopurinol (20 mumol/L) decreased the PGI(2) release to 40.68 +/- 2.99 pg/1x10(5) cells/ml. In conclusion, our data showed that the damage of endothelial cells in reoxygenotion group was significantly increased comparing anoxia group (p<0.005) and that allopurinol can inhibit reoxygenation-induced injury of endotheial cells.