• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3545-3549
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• 2016

Background: The incidence of bladder cancer is lower in Asian than in Western countries. However, the crude incidence and mortality of bladder cancer have recently increased in Japan because of the increased number of senior citizens. We have already reported risk factors for urothelial cancer in a large population-based cohort study in Japan (JACC study). However, we did not evaluate the cancer risk in the upper and lower urinary tract separately in our previous study. Materials and Methods: Here we evaluated the risk of cancer death in the upper and lower urinary tracts, separately, using the database of the JACC study. The analytic cohort included 46,395 males and 64,190 females aged 40 to 79 years old. The Cox proportional hazard model was used to determine hazard ratios and their 95% confidence intervals. Results: Current smoking increased the risk of both upper and lower urinary tract cancer deaths. A history of kidney disease was associated with an increased risk of bladder cancer death, even after controlling for age, sex and smoking status. Conclusions: The present study confirmed that current smoking increases the risk of both upper and lower urinary tract cancer deaths and indicated the possibility that a history of kidney disease may be a risk factor for bladder cancer death in the Japanese population.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2515-2518
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• 2012

Aim: To study the causes and significance of both microscopic and macroscopic haematuria in adult patients and assess possible relevance to early detection of urological cancers. Methods: 417 patients presenting with haematuria were assessed in our Urology Unit. Following confirmation of haematuria, these patients were subjected to imaging techniques and flexible cystoscopy. Parameters analysed included clinical characteristics, imaging results, flexible cystoscopy findings, time delay to diagnoses and eventual treatment and final diagnoses of all cases. Results: 390 haematuria cases were analysed from 417 consecutive patients with haematuria. After 27 cases were excluded as they had previous history, 245 microscopic and 145 macroscopic. Age range was 17 to 95 years old with predominance of 152 females to 239 males. The racial distribution included 180 Chinese, 100 Indians,95 Malays and 15 other races. The final diagnoses were benign prostatic hyperplasia (22.6%), no cause found (22.3%), other causes (18.7%), urolithiasis (11.5%), urinary tract infection UTI (10.8%), non specific cystitis (10.3%), bladder tumours (2.8%) and other genitourinary tumours (1%). 11 new cases (2.8%) of bladder cancers were diagnosed, with a mean age of 59 years. Only 3 of 245 (1.2%) patients with microscopic haematuria had newly diagnosed bladder tumour compared with 8 of 145 (5.5%) patients with frank haematuria (p=0.016). Mean time taken from onset of symptoms to diagnosis of bladder cancer was 53.3 days with definitive treatment (TURBT) in 20.1 days from diagnosis. Conclusion:- This study has highlighted the common causes of haematuria in our local setting. We recommend that full and appropriate investigations be carried out on patients with frank haematuria especially those above 50 years old in order to provide earlier detection and prompt management of bladder diseases especially tumours.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2477-2479
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• 2012

Objective: To study the histomorphological pattern of urothelial tumors of the urinary bladder in Manipur and to evaluate whether any correlation exists between tumor grade and muscle invasion. Methods: A 10 year retrospective study of all consecutive cases diagnosed in the Department of Pathology RIMS - Imphal, between $1^{st}$ January 2001 to $31^{st}$ December 2010. Results: The study included 26 cases of transitional cell tumors of urinary bladder. The male to female ratio was 1.5:1 and the ages ranged from 38 years to 73 years (medians of 60 and 64 years, respectively). Of the total, 14 (53.9%) cases were low grade, 9 (34.6%) were high grade, 2 (7.7%) were papillomas and 1 (3.9%) was a papillary urothelial neoplasm of low malignant potential (PUNLMP). Pathological staging showed that 14 (53.9%) of the cases were stage PTa, four (15.4%) PT1, and eight (30.9%) PT2. Some 18.2% of low grade tumors and 75% of high grade tumors were invasive to the detrusor muscle layer. Conclusion: Bladder cancer is an uncommon disease, transitional tumors being the only histological type observed. It was more common in males than females, with peak incidence in seventh decade. Most of the tumors were non-invasive (PTa) and invasion to the detrusor muscle layer was seen in more than half of the high grade tumors. There is a definite correlation between advancing tumor grade and muscle invasion.

• Radiation Oncology Journal
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• v.33 no.2
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• pp.134-141
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• 2015

Purpose: This study investigates morphologic change of the rectosigmoid colon using a belly board in prone position and distended bladder in patients with rectal cancer. We evaluate the possibility of excluding the proximal margin of anastomosis from the radiation field by straightening the rectosigmoid colon. Materials and Methods: Nineteen patients who received preoperative radiotherapy between 2006 and 2009 underwent simulation in a prone position (group A). These patients were compared to 19 patients treated using a belly board in prone position and a distended bladder protocol (group B). Rectosigmoid colon in the pelvic cavity was delineated on planning computed tomography (CT) images. A total dose of 45 Gy was planned for the whole pelvic field with superior margin of the sacral promontory. The volume and redundancy of rectosigmoid colon was assessed. Results: Patients in group B had straighter rectosigmoid colons than those in group A (no redundancy; group A vs. group B, 10% vs. 42%; p = 0.03). The volume of rectosigmoid colon in the radiation field was significantly larger in group A (56.7 vs. 49.1 mL; p = 0.009). In dose volume histogram analysis, the mean irradiated volume was lower in patients in group B (V45 27.2 vs. 18.2 mL; p = 0.004). In Pearson correlation coefficient analysis, the in-field volume of rectosigmoid colon was significantly correlated with the bladder volume (R = 0.86, p = 0.003). Conclusion: Use of a belly board and distended bladder protocol could contribute to exclusion of the proximal margin of anastomosis from the radiation field.

• Journal of radiological science and technology
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• v.36 no.1
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• pp.39-47
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• 2013

For radiotherapy in rectal cancer patients treated with small bowel displacement device (SBDD) and belly board, We will suggest new indication of using SBDD depending on obesity index by analyzing correlation between obesity and irradiated small bowel volume. In this study, We reviewed 29 rectal cancer patients who received pelvic radiation therapy with belly board and SBDD from January to April in 2012. We only analyzed those patients treated with three-field technique (PA and both LAT) on 45 Gy (1.8 Gy/fx). We measured patients' height, weight, body mass index (BMI), waist-hip ratio (WHR) and divided BMI into two groups.(${\geq}23$:BMI=group1, <23:BMI=group2) We performed a statistical analysis to evaluate correlation between total volume of bladder($TV_{bladder}$), obesity index and high dose volume of small bowel (small bowel volume irradiated at 90% of prescribed dose, $HDV_{sb}$), low dose volume of small bowel (small bowel volume irradiated at 33% of prescribed dose, $LDV_{sb}$). The result shows, gender, WHR and status of pre operative or post operative do not greatly affect $HDV_{sb}$ and $LDV_{sb}$. Statistical result shows, there are significant correlation between $HDV_{sb}$ and BMI (p<0.04), $HDV_{sb}$ and $TV_{bladder}$ (p<0.01), $LDV_{sb}$ and $TV_{bladder}$ (p<0.01). BMI seems to correlate with $HDV_{sb}$ but does not with $LDV_{sb}$ (p>0.05). There are negative correlation between $HDV_{sb}$ and BMI, $TV_{bladder}$ and $HDV_{sb}$, $TV_{bladder}$ and $LDV_{sb}$. Especially, BMI group1 has more effective and negative correlation with $HDV_{sb}$ (p=0.027) than in BMI group2. In the case of BMI group 1, $TV_{bladder}$ has significant negative correlation with $HDV_{sb}$ and $LDV_{sb}$ (p<0.04). In conclusions, we confirmed that Using SBDD with belly board in BMI group1 could more effectively reduce irradiated small bowel volume in radiation therapy for rectal cancer. Therefore, We suggest using belly board with SBDD in order to reduce the small bowel toxicity in rectal radiotherapy, if patients' BMI is above 23.

• The Korean Journal of Cytopathology
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• v.12 no.2
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• pp.121-125
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• 2001

Primary small cell carcinoma of the urinary bladder is a rare malignant tumor. A more rapidly fatal course may be seen in advanced stages of small cell carcinoma as compared to similar stages of urothelial carcinoma. It is very important to recognize this distinct form of bladder cancer by urinary cytology The differential diagnosis of small cell carcinoma of the urinary bladder includes metastatic small cell carcinoma, urothelial carcinoma, and primary or secondary malignant lymphoma. This article highlights the urinary cytologic diagnosis of a case of primary small cell carcinoma. A 59-year-old male presented with gross hematuria for five months. Urinary cytology showed high cellularity consisting of tiny monotonous tumor cells in the necrotic background. The tumor cells occurred predominantly singly, but a few in clusters. The cytoplasm was so scanty that only a very narrow rim of it was seen. The nuclei were oval or round and had finely stippled chromatin. Rarely, the nuclei contain visible nucleoli. Frequently cell molding was noted in clusters. Many single cells demonstrated nuclear pyknosis or karyorrhexis. The histologic findings of transurethral resection and partial cystectomy specimen were those of small cell carcinoma. Cytologic distinction may be very difficult but careful attention to clinical features and cellualr details can classify these neoplasms correctly.

• BMB Reports
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• v.48 no.9
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• pp.531-536
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• 2015

Gecko proteins have long been used as anti-tumor agents in oriental medicine, without any scientific background. Although anti-tumor effects of Gecko proteins on several cancers were recently reported, their effect on bladder cancer has not been investigated. Thus, we explored the anti-tumor effect of Gecko proteins and its cellular mechanisms in human bladder cancer 5637 cells. Gecko proteins significantly reduced the viability of 5637 cells without any cytotoxic effect on normal cells. These proteins increased the Annexin-V staining and the amount of condensed chromatin, demonstrating that the Gecko proteinsinduced cell death was caused by apoptosis. Gecko proteins suppressed Akt activation, and the overexpression of constitutively active form of myristoylated Akt prevented Gecko proteins-induced death of 5637 cells. Furthermore, Gecko proteins activated caspase 9 and caspase 3/7. Taken together, our data demonstrated that Gecko proteins suppressed the Akt pathway and activated the intrinsic caspase pathway, leading to the apoptosis of bladder cancer cells. [BMB Reports 2015; 48(9): 531-536]

• Biomedical Science Letters
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• v.15 no.1
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• pp.47-53
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• 2009

Urinary bladder cancer is diagnosed through urine cytology and cytoscopy with biopsy. An atypical urothelial cast is often found by voided urine cytology in a papillary urothelial cell carcinoma. The objective of this study is to demonstrate the significance of the evaluation of urinary nuclear matrix protein (NMP22) level and Sure Path Liquid-based cytology (SP-LBC) as compared to the examination of atypical urothelial cast in voided urine sediment for monitoring bladder cancer. From October 2007 to January 2008, we observed 3240 patients who visited the emergency laboratory of urology of Soonchunhyang University, Cheonan Hospital. Both NMP22 measurement and SP-LBC were performed in 31 patients who were positive in an atypical urothelial cast test. In particular, 26 men and 5 women were found to be atypical urothelial cast-positive persons. The average age for both men and women is 61.8. NMP22 test is positive in 23 of 31 cases (74.2%) from patients with atypical urothelial cast, while the test is negative in 8 of 31 cases (25.8%). The percentages of negativity, atypicality, suspicious malignancy, and malignancy in SP-LBC are 25.8% (8/31), 58.1% (18/31), 9.7% (3/31), and 6.5% (2/31), respectively. The relation of NMP22 positivity with the malignant degree in LBC is significant (P<0.01). Two malignant patients resulting from SP-LBC show the same results in histological examination. Overall, the study suggests the usefulness of NMP22 measurement and LBC as well as the examination of atypical urothelial cast for the diagnosis of early bladder cancer.

• IMMUNE NETWORK
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• v.14 no.3
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• pp.156-163
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• 2014

Interleukin (IL) 17 is produced by T-helper (Th) 17 with a vigorous effect on cells of the immune system playing important roles in pathogenesis of immune-mediated diseases, including autoimmune disorders and cancers. Therefore, the aim of current study was to determine the serum levels of IL-6, IL-17, and transforming growth factor beta (TGF-${\beta}$) in Iranian bladder cancer patients, and to correlate them with disease status. Blood samples were collected from 40 bladder cancer patients and 38 healthy individuals with no history of malignancies or autoimmune disorders. The serum levels of IL-6, IL-17, and TGF-${\beta}$ were measured by the enzyme-linked immunosorbent assay (ELISA). The results showed that the levels of IL-17 (p<0.0001) and TGF-${\beta}$ (p<0.0001) were significantly lower in the patients compared to the controls. No significant differences in the level of serum IL-6 (p=0.16) was observed between the patients and controls. In addition, demographic characteristics between control and patients groups were not significantly different. As most of the cases studied in this investigation were in stage I and II, it is concluded that reduced Th17-related cytokines can be used as indicators for following the course and clinical stages of bladder carcinoma progress and immune response to cancer.