Brenner tumor of the ovary: a correlative histologic, histochemical, immunohistochemical, and ultrastructural investigation.

PubMed

Santini, D; Gelli, M C; Mazzoleni, G; Ricci, M; Severi, B; Pasquinelli, G; Pelusi, G; Martinelli, G

1989-08-01

The histologic, histochemical, immunohistochemical, and ultrastructural features of Brenner tumor (BT) were studied. BT was compared with transitional bladder cells, and close similarities between the two tissues were identified. Abundant glycogen in all cellular layers, an alcianophilic/sialomucinic surface mucous coat, and argyrophilic cells characterized both BT and bladder epithelium. Immunohistochemically, chromogranin and neuron-specific enolase reactivity was observed in all cases examined. An additional relevant finding was the presence of serotonin-storing cells in both BT and urothelium. Moreover, carcinoembryonic antigen, epithelial membrane antigen, and keratin reaction were found in BT and urothelium, indicating an additional antigenic similarity. Additionally, malignant Brenner tumor was ultrastructurally found to share many common features with the bladder tissue. The distinct histochemical, ultrastructural, and antigenic pattern of BT, primarily of the transitional type, is emphasized.

The Impact of Multiple Malignancies on Patients with Bladder Carcinoma: A Population-Based Study Using the SEER Database

PubMed Central

Ehrlich, Joshua R.; Schwartz, Michael J.; Ng, Casey K.; Kauffman, Eric C.; Scherr, Douglas S.

2009-01-01

Purpose. To date, no study has examined a population-based registry to determine the impact of multiple malignancies on survival of bladder cancer patients. Our experience suggests that bladder cancer patients with multiple malignancies may have relatively positive outcomes. Materials & Methods. We utilized data from the Surveillance Epidemiology and End Results (SEERs) database to examine survival between patients with only bladder cancer (BO) and with bladder cancer and additional cancer(s) antecedent (AB), subsequent (BS), or antecedent and subsequent to bladder cancer (ABS). Results. Analyses demonstrated diminished survival among AB and ABS cohorts. However, when cohorts were substratified by stage, patients in the high-stage BS cohort appeared to have a survival advantage over high-stage BO patients. Conclusions. Bladder cancer patients with multiple malignancies have diminished survival. The survival advantage of high-stage BS patients is likely a statistical phenomenon. Such findings are important to shape future research and to improve our understanding of patients with multiple malignancies. PMID:20069054

Noninvasive Electromagnetic Detection of Bladder Cancer

PubMed Central

Cormio, Luigi; Vedruccio, Clarbruno; Leucci, Giorgio; Massenio, Paolo; Di Fino, Giuseppe; Cavaliere, Vincenzo; Carrieri, Giuseppe

2014-01-01

Objectives. Normal and neoplastic human tissues have different electromagnetic properties. This study aimed to determine the diagnostic accuracy of noninvasive electromagnetic detection of bladder cancer (BC) by the tissue-resonance interaction method (TRIM-prob). Patients and Methods. Consecutive patients were referred for cystoscopy because of (i) microscopic or gross hematuria and/or irritative voiding symptoms and (ii) bladder ultrasounds and urinary cytology findings negative or just suspicious of malignancy. Patients were first submitted to TRIM-prob bladder scanning by a single investigator and then to cystoscopy by another investigator blind to TRIM-prob data. Results. In 125 evaluated patients cystoscopy was positive for BC in 47 and negative in the remaining 78; conversely, TRIM-prob bladder scanning was positive for BC in 53 and negative in 72. In particular, TRIM-prob scanning yielded 7 false positives and only one false negative; therefore, its overall sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 97.9%, 89.9%, 86.8%, 98.6%, and 93.6%, respectively. Conclusions. TRIM-prob bladder scanning was a simple and quite accurate method for non-invasive electromagnetic detection of BC. If the elevated positive and negative predictive values will be replicated in further well-designed studies, it could be used to screen asymptomatic patients at high risk of BC. PMID:24563795

Role of androgen receptor and associated lysine-demethylase coregulators, LSD1 and JMJD2A, in localized and advanced human bladder cancer.

PubMed

Kauffman, Eric C; Robinson, Brian D; Downes, Martin J; Powell, Leagh G; Lee, Ming Ming; Scherr, Douglas S; Gudas, Lorraine J; Mongan, Nigel P

2011-12-01

Bladder cancer is approximately three times more common in men as compared to women. We and others have previously investigated the contribution of androgens and the androgen receptor (AR) to bladder cancer. JMJD2A and LSD1 are recently discovered AR coregulator proteins that mediate AR-dependent transcription via recently described histone lysine-demethylation (KDM) mechanisms. We used immunohistochemistry to examine JMJD2A, LSD1, and AR expression in 72 radical cystectomy specimens, resulting in evaluation of 129 tissue samples (59 urothelial carcinoma, 70 benign). We tested levels of these proteins for statistical association with clinicopathologic variables and patient survival. Expression of these markers was also assessed in human bladder cancer cell lines. The effects of pharmacological inhibition of LSD1 on the proliferation of these bladder cancer cells was determined. JMJD2A and AR levels were significantly lower in malignant versus benign urothelium, while increased LSD1 levels were observed in malignant urothelium relative to benign. A significant reduction in all three proteins occurred with cancer stage progression, including muscle invasion (JMJD2A/LSD1/AR), extravesical extension (JMJD2A/LSD1), and lymph node metastasis (JMJD2A/AR). Lower JMJD2A intensity correlated with additional poor prognostic features, including lymphovascular invasion, concomitant carcinoma in situ and tobacco usage, and predicted significantly worse overall survival. Pharmacological inhibition of LSD1 suppressed bladder cancer cell proliferation and androgen-induced transcription. Our results support a novel role for the AR-KDM complex in bladder cancer initiation and progression, identify JMJD2A as a promising prognostic biomarker, and demonstrate targeting of the KDM activity as an effective potential approach for bladder cancer growth inhibition. Copyright © 2011 Wiley Periodicals, Inc.

The effect of 6 and 15 MV on intensity-modulated radiation therapy prostate cancer treatment: plan evaluation, tumour control probability and normal tissue complication probability analysis, and the theoretical risk of secondary induced malignancies

PubMed Central

Hussein, M; Aldridge, S; Guerrero Urbano, T; Nisbet, A

2012-01-01

Objective The aim of this study was to investigate the effect of 6 and 15-MV photon energies on intensity-modulated radiation therapy (IMRT) prostate cancer treatment plan outcome and to compare the theoretical risks of secondary induced malignancies. Methods Separate prostate cancer IMRT plans were prepared for 6 and 15-MV beams. Organ-equivalent doses were obtained through thermoluminescent dosemeter measurements in an anthropomorphic Aldersen radiation therapy human phantom. The neutron dose contribution at 15 MV was measured using polyallyl-diglycol-carbonate neutron track etch detectors. Risk coefficients from the International Commission on Radiological Protection Report 103 were used to compare the risk of fatal secondary induced malignancies in out-of-field organs and tissues for 6 and 15 MV. For the bladder and the rectum, a comparative evaluation of the risk using three separate models was carried out. Dose–volume parameters for the rectum, bladder and prostate planning target volume were evaluated, as well as normal tissue complication probability (NTCP) and tumour control probability calculations. Results There is a small increased theoretical risk of developing a fatal cancer from 6 MV compared with 15 MV, taking into account all the organs. Dose–volume parameters for the rectum and bladder show that 15 MV results in better volume sparing in the regions below 70 Gy, but the volume exposed increases slightly beyond this in comparison with 6 MV, resulting in a higher NTCP for the rectum of 3.6% vs 3.0% (p=0.166). Conclusion The choice to treat using IMRT at 15 MV should not be excluded, but should be based on risk vs benefit while considering the age and life expectancy of the patient together with the relative risk of radiation-induced cancer and NTCPs. PMID:22010028

Secondary signet-ring cell adenocarcinoma of urinary bladder from a gastric primary.

PubMed

Sharma, Pramod K; Vijay, Mukesh K; Das, Ranjit K; Chatterjee, Uttara

2011-05-01

Primary bladder tumor is a frequent urological malignancy, whereas the incidence of secondary bladder tumor from a distant organ is quite rare. Secondary bladder neoplasms represent 1% of all malignant bladder tumors, of which distant metastases from stomach account for about 4% of cases. We present the case of a 30-year-old male who underwent partial gastrectomy for Signet-ring cell carcinoma of the stomach and presented 2 years later with hematuria. On computerized tomography scan, a bladder tumor was found which was resected cystoscopically. The histopathological examination revealed secondary Signet-ring cell adenocarcinoma of the urinary bladder.

Positioning accuracy during VMAT of gynecologic malignancies and the resulting dosimetric impact by a 6-degree-of-freedom couch in combination with daily kilovoltage cone beam computed tomography.

PubMed

Yao, Lihong; Zhu, Lihong; Wang, Junjie; Liu, Lu; Zhou, Shun; Jiang, ShuKun; Cao, Qianqian; Qu, Ang; Tian, Suqing

2015-04-26

To improve the delivery of radiotherapy in gynecologic malignancies and to minimize the irradiation of unaffected tissues by using daily kilovoltage cone beam computed tomography (kV-CBCT) to reduce setup errors. Thirteen patients with gynecologic cancers were treated with postoperative volumetric-modulated arc therapy (VMAT). All patients had a planning CT scan and daily CBCT during treatment. Automatic bone anatomy matching was used to determine initial inter-fraction positioning error. Positional correction on a six-degrees-of-freedom (6DoF) couch was followed by a second scan to calculate the residual inter-fraction error, and a post-treatment scan assessed intra-fraction motion. The margins of the planning target volume (MPTV) were calculated from these setup variations and the effect of margin size on normal tissue sparing was evaluated. In total, 573 CBCT scans were acquired. Mean absolute pre-/post-correction errors were obtained in all six planes. With 6DoF couch correction, the MPTV accounting for intra-fraction errors was reduced by 3.8-5.6 mm. This permitted a reduction in the maximum dose to the small intestine, bladder and femoral head (P=0.001, 0.035 and 0.032, respectively), the average dose to the rectum, small intestine, bladder and pelvic marrow (P=0.003, 0.000, 0.001 and 0.000, respectively) and markedly reduced irradiated normal tissue volumes. A 6DoF couch in combination with daily kV-CBCT can considerably improve positioning accuracy during VMAT treatment in gynecologic malignancies, reducing the MPTV. The reduced margin size permits improved normal tissue sparing and a smaller total irradiated volume.

Secondary signet-ring cell adenocarcinoma of urinary bladder from a gastric primary

PubMed Central

Sharma, Pramod K.; Vijay, Mukesh K.; Das, Ranjit K.; Chatterjee, Uttara

2011-01-01

Primary bladder tumor is a frequent urological malignancy, whereas the incidence of secondary bladder tumor from a distant organ is quite rare. Secondary bladder neoplasms represent 1% of all malignant bladder tumors, of which distant metastases from stomach account for about 4% of cases. We present the case of a 30-year-old male who underwent partial gastrectomy for Signet-ring cell carcinoma of the stomach and presented 2 years later with hematuria. On computerized tomography scan, a bladder tumor was found which was resected cystoscopically. The histopathological examination revealed secondary Signet-ring cell adenocarcinoma of the urinary bladder. PMID:21747602

Bladder Mucosal Graft Vaginoplasty: A Case Report.

PubMed

Chiaramonte, Cinzia; Vestri, Elettra; Tripi, Flavia; Giannone, Antonino Giulio; Cimador, Marcello; Cataliotti, Ferdinando

2018-06-18

Female vaginoplasty reconstruction, by choice, is usually performed with adjacent tissue. However in some clinical conditions such as high urogenital confluence sinus, cloacal malformation with extreme vaginal hypoplasia, local tissue may not be available. When vaginal replacement is performed in pediatric patients intestinal segments is preferred to non-operative procedures that require continuative dilations. However mucus production, malignant transformation risk and diversion colitis are important side effects. We present a nouvel technique for vaginoplasty in a female child presenting with an isolated urogenital sinus malformation without virilization. The patient at 20 months underwent vaginoplasty using tubularized bladder mucosal graft. Surgical procedure was devoid of complications. Pubertal development occurred at age of 15. She underwent regular follow up until 18 years of age. At this age we performed clinical evaluation: absence of vaginal introitus stenosis and good cosmetic results were observed. Then she underwent vaginoscopy with multiple biopsies. Pathology examination of the bladder mucosal graft evidenced a normal structure of the mucosa, with a stratified squamous epithelium. Different techniques are taken into account for vaginal reconstruction according to the severity and to the type of malformation. We describe the use of bladder mucosal graft with favorable results after long term follow-up. Copyright © 2018. Published by Elsevier Inc.

Predictive value of Sox2 expression in transurethral resection specimens in patients with T1 bladder cancer.

PubMed

Ruan, Jun; Wei, Bingbing; Xu, Zhuoqun; Yang, Shudong; Zhou, You; Yu, Minhong; Liang, Jiabei; Jin, Ke; Huang, Xing; Lu, Peng; Cheng, Huan

2013-03-01

Sox2 is thought to be an important regulator of self-renewal in embryonic stem cell. According to the cancer stem cell (CSC) theory, the overexpression of Sox2 is potentially involved in carcinogenesis and could affect tumor recurrence and metastasis. Previous study proved Sox2 might be prognostic marker for multiple human malignancies. The purpose of this study was to investigate the clinicopathological significance of Sox2 expression in human non-muscle-invasive bladder cancer. We examined Sox2 expression in 32 paired non-muscle-invasive bladder cancer tissues and adjacent non-cancerous tissues by quantitative real-time RT-PCR (qrtRT-PCR). In addition, we analyzed Sox2 and Ki-67 expression in 126 non-muscle-invasive bladder cancer samples and bladder cancer cell line T24 by immunohistochemistry and immunofluorescence assays. The recurrence-free survival was determined by Kaplan-Meier method and log-rank test. Cox regression was adopted for univariate and multivariate analyses of prognostic factors. The expression of Sox2 was significantly increased in non-muscle-invasive bladder cancer tissues. Sox2 expression was significantly correlated with that of Ki-67 (P < 0.001). The expression of Sox2 was significantly associated with tumor size (P = 0.006), tumor number (P = 0.037), and tumor grade (P < 0.001). Patients with high Sox2 expression had significantly poorer recurrence-free survival (P = 0.0002) when compared with patients with the low expression of Sox2. On multivariate analysis, Sox2 expression and tumor grade were found to be independent prognostic factors for recurrence-free survival (P < 0.05). Our data suggested for the first time that the high expression of Sox2 may contribute to the development of non-muscle-invasive bladder cancer and serve as a novel prognostic marker in patients with T1 bladder cancer.

Associations of non-melanoma skin cancer and melanoma, extra-cutaneous cancers and smoking in adults: a US population-based study.

PubMed

Silverberg, J I; Ratner, D

2015-07-01

Non-melanoma skin cancer (NMSC) and melanoma are common malignancies in the US and may be associated with other types of cancer. We sought to determine whether NMSC and melanoma are associated with extra-cutaneous cancers and identify modifiable risk factors for such an association. We analysed data from 447,801 adult participants in the 1997-2011 National Health Interview Surveys. Survey logistic regression models were constructed that accounted for the complex sample weights. History of NMSC, melanoma and 27 primary extra-cutaneous cancers was assessed. NMSC was associated with increased odds of one (multinomial survey logistic regression, unadjusted odds ratio [95% CI]: 2.43 [2.20-2.68]) or multiple (2.94 [2.21-3.92]) extra-cutaneous malignancies. Melanoma was also associated with increased odds of one (3.25 [2.70-3.90]) or multiple (6.11 [4.34-8.61]) extra-cutaneous malignancies. Extra-cutaneous cancers were more common in younger patients (ages 18-39 and 40-49 years) and Caucasians with NMSC or melanoma (P < 0.0001). Smokers with a history of NMSC or melanoma had even higher odds of extra-cutaneous malignancy at ages 18-39 and 40-49 years compared to smokers without NMSC or melanoma (P < 0.0001). History of NMSC was associated with higher odds of malignancies of the bladder, brain, breast, colon, oesophagus, kidney, lung, lymphoma, melanoma, prostate, soft tissue, throat/pharynx, thyroid and uterus. Melanoma was associated with malignancies of the bladder, breast, colon, kidney, lung, pancreas, prostate, soft tissue, throat/pharynx, thyroid and uterus. The prevalence of extra-cutaneous cancers increased between 1997 and 2011 in all subjects (4.51% and 5.73%, P < 0.0001), with even higher rates of increase in those with history of NMSC or melanoma. Patients with history of NMSC and melanoma have increased odds of developing extra-cutaneous cancers, especially those with younger age and smoking history. © 2014 European Academy of Dermatology and Venereology.

The Long Non-Coding RNA XIST Interacted with MiR-124 to Modulate Bladder Cancer Growth, Invasion and Migration by Targeting Androgen Receptor (AR).

PubMed

Xiong, Yaoyao; Wang, Long; Li, Yuan; Chen, Minfeng; He, Wei; Qi, Lin

2017-01-01

Long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) is involved in the progression of several tumors. The interaction between lncRNA and miRNA or miRNA's target genes is reported to play crucial roles in malignancy. In addition, Androgen receptor (AR) is considered to be involved in bladder cancer progression. In this study, we investigated the role of XIST in human bladder cancer and its interaction with miR-124 and AR. XIST and AR expression was detected in bladder tumor samples and cell lines. Effects of XIST and AR on bladder cancer cells growth, invasion and migration were analyzed. Bioinformatic analysis and luciferase assays were used to identify the interaction among XIST, AR and miR-124. The correlations of miR-124 with XIST and AR in bladder cancer samples were statistically analyzed. XIST and AR were upregulated in bladder cancer tissues and positively correlated. Higher XIST and AR expression were related to poorer TNM stage of bladder cancer. XIST knockdown reduced bladder cancer cells' proliferation, invasion and migration. While this inhibitory effect could be partially restored by AR overexpression. XIST inhibited miR-124 expression by directly targeting. Moreover, miR-124 could bind to the 3'UTR of AR to regulate its expression. MiR-124 inhibition partially restored the XIST knockdown-induced reduction of AR, c-myc, p27, MMP13 and MMP9 expression. In bladder cancer tissues, miR-124 level was inversely correlated with the expression of XIST and AR, respectively. These findings indicated that XIST might be an oncogenic lncRNA that promoted the bladder cancer growth, invasion and migration via miR-124 dependent AR regulation. © 2017 The Author(s). Published by S. Karger AG, Basel.

Expression of pigment epithelium-derived factor and tumor necrosis factor-α is correlated in bladder tumor and is related to tumor angiogenesis.

PubMed

Feng, Chen-Chen; Wang, Pao-Hsun; Ding, Qiang; Guan, Ming; Zhang, Yuan-Fang; Jiang, Hao-Wen; Wen, Hui; Wu, Zhong

2013-02-01

Angiogenesis is a pivotal process on which solid tumor growth is substantially dependent. Pigment epithelium-derived factor (PEDF) is the most potent natural anti-angiogenic factor, which has seldom been studied in bladder tumor, and whose functioning pathway remains unclear. We have thus investigated PEDF expression in relation to tumor necrosis factor-α (TNF-α) and microvessel density (MVD) with immunohistochemistry. Antibodies of PEDF and TNF-α were examined by Western blotting before immunohistochemistry. Sixty-four urothelial tumor sections and 23 normal controls were stained and expression of PEDF, TNF-α, and MVD were studied. Decreased PEDF expression and increased TNF-α expression was noticed in tumorous tissue compared with healthy urothelium. Lower PEDF expression was related to higher tumor grade but stage. Increased TNF-α expression was noticed in recurrent, larger tumors as well as in tumors with progression in grade and stage. Expression of PEDF and TNF-α was correlated in bladder tumor. PEDF or TNF-α was correlated with MVD negatively or positively, respectively, in cancerous tissue and tumorous grouping without correlation in papillary urothelial neoplasm of low malignant potential. Expressional change of PEDF and TNF-α is in relation to angiogenesis of bladder tumor, especially in bladder cancer development. Copyright © 2013 Elsevier Inc. All rights reserved.

Mitomycin C Intravesical Chemotherapy in Conjunction With Synergo® Radiofrequency-Induced Hyperthermia for Treatment of Carcinoma in Situ Non-Muscle Invasive Bladder Cancer Patients Unresponsive to Bacillus Calmette-Guérin, With or Without Papillary Tumors.

ClinicalTrials.gov

2018-03-20

Bladder Cancer; Bladder Neoplasm; Bladder Tumors; Cancer of Bladder; Cancer of the Bladder; Malignant Tumor of Urinary Bladder; Neoplasms, Bladder; Urinary Bladder Cancer; Carcinoma in Situ of Bladder; Papillary Carcinoma of Bladder (Diagnosis); BCG-Unresponsive Bladder Cancer

Embryonal Rhabdomyosarcoma of the Adult Urinary Bladder: A Rare Case Report of Misclassification as Inflammatory Myofibroblastic Tumor

PubMed Central

Chen, Kelven Weijing; Wu, Fiona Mei Wen; Lee, Victor Kwan Min; Esuvaranathan, Kesavan

2015-01-01

Embryonal rhabdomyosarcoma (ERMS) of the adult urinary bladder is a rare malignant tumour. Inflammatory myofibroblastic tumour (IMT) of the bladder is a benign genitourinary tumour that may appear variable histologically but usually lacks unequivocal malignant traits. Techniques like flow cytometry and immunohistochemistry may be used to differentiate these two tumours. Our patient, a 46-year-old male, had rapidly recurring lower urinary tract symptoms after two transurethral resections of the prostate. He subsequently underwent a transvesical prostatectomy which showed IMT on histology. However, his symptoms did not resolve and an open resection done at our institution revealed a 6 cm tumour arising from the right bladder neck. This time, histology was ERMS with diffuse anaplasia of the bladder. Rapid recurrence of urinary symptoms with prostate regrowth after surgery is unusual. Differential diagnoses of uncommon bladder malignancies should be considered if there is an inconsistent clinical course as treatment approaches are different. PMID:25737794

Nanoparticle Albumin-Bound Rapamycin in Treating Patients With Advanced Cancer With mTOR Mutations

ClinicalTrials.gov

2018-06-01

Advanced Malignant Neoplasm; Cervical Squamous Cell Carcinoma; Endometrial Carcinoma; Malignant Uterine Neoplasm; Recurrent Bladder Carcinoma; Recurrent Breast Carcinoma; Recurrent Cervical Carcinoma; Recurrent Head and Neck Carcinoma; Recurrent Malignant Neoplasm; Recurrent Ovarian Carcinoma; Recurrent Prostate Carcinoma; Recurrent Renal Cell Carcinoma; Solid Neoplasm; Stage III Bladder Cancer; Stage III Prostate Cancer; Stage III Renal Cell Cancer; Stage IIIA Breast Cancer; Stage IIIA Cervical Cancer; Stage IIIA Ovarian Cancer; Stage IIIB Breast Cancer; Stage IIIB Cervical Cancer; Stage IIIB Ovarian Cancer; Stage IIIC Breast Cancer; Stage IIIC Ovarian Cancer; Stage IV Breast Cancer; Stage IV Ovarian Cancer; Stage IV Prostate Cancer; Stage IV Renal Cell Cancer; Stage IVA Bladder Cancer; Stage IVA Cervical Cancer; Stage IVB Bladder Cancer; Stage IVB Cervical Cancer

Trigriluzole With Nivolumab and Pembrolizumab in Treating Patients With Metastatic or Unresectable Solid Malignancies or Lymphoma

ClinicalTrials.gov

2018-05-23

Lymphoma; Metastatic Malignant Solid Neoplasm; Metastatic Melanoma; Metastatic Renal Cell Cancer; Recurrent Bladder Carcinoma; Recurrent Classical Hodgkin Lymphoma; Recurrent Head and Neck Squamous Cell Carcinoma; Recurrent Lymphoma; Recurrent Malignant Solid Neoplasm; Recurrent Renal Cell Carcinoma; Stage III Bladder Cancer; Stage III Lymphoma; Stage III Non-Small Cell Lung Cancer AJCC v7; Stage III Renal Cell Cancer; Stage III Skin Melanoma; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIA Skin Melanoma; Stage IIIB Non-Small Cell Lung Cancer AJCC v7; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Bladder Cancer; Stage IV Lymphoma; Stage IV Non-Small Cell Lung Cancer AJCC v7; Stage IV Renal Cell Cancer; Stage IV Skin Melanoma; Stage IVA Bladder Cancer; Stage IVB Bladder Cancer; Unresectable Head and Neck Squamous Cell Carcinoma; Unresectable Solid Neoplasm

Squamous cell carcinoma in exstrophy of the bladder.

PubMed

Sharma, Pramod Kumar; Pandey, Praveen Kumar; Vijay, Mukesh Kumar; Bera, Malay Kumar; Singh, Jitendra Pratap; Saha, Kaushik

2013-08-01

Exstrophy of the bladder is a rare congenital anomaly with an incidence of about 1 per 50,000 newborns. The malignant potential of the exstrophied bladder mucosa is well known; 95% are adenocarcinomas, and 3% to 5% are squamous cell carcinomas. Most of the malignant tumors (60%) associated with an exstrophy of the bladder occur during the fourth and fifth decades of life. Of the remaining, about 20% each occur after 60 years and before 40 years. Here we present a case in which squamous cell carcinoma developed in an unrepaired exstrophy of the bladder. We present the management of the case and a brief review of the literature.

Squamous Cell Carcinoma in Exstrophy of the Bladder

PubMed Central

Pandey, Praveen Kumar; Vijay, Mukesh Kumar; Bera, Malay Kumar; Singh, Jitendra Pratap; Saha, Kaushik

2013-01-01

Exstrophy of the bladder is a rare congenital anomaly with an incidence of about 1 per 50,000 newborns. The malignant potential of the exstrophied bladder mucosa is well known; 95% are adenocarcinomas, and 3% to 5% are squamous cell carcinomas. Most of the malignant tumors (60%) associated with an exstrophy of the bladder occur during the fourth and fifth decades of life. Of the remaining, about 20% each occur after 60 years and before 40 years. Here we present a case in which squamous cell carcinoma developed in an unrepaired exstrophy of the bladder. We present the management of the case and a brief review of the literature. PMID:23956833

Genetics of Bladder Malignant Tumors in Childhood

PubMed Central

Zangari, Andrea; Zaini, Johan; Gulìa, Caterina

2016-01-01

Bladder masses are represented by either benign or malignant entities. Malignant bladder tumors are frequent causes of disease and death in western countries. However, in children they are less common. Additionally, different features are found in childhood, in which non epithelial tumors are more common than epithelial ones. Rhabdomyosarcoma is the most common pediatric bladder tumor, but many other types of lesions may be found, such as malignant rhabdoid tumor (MRT), inflammatory myofibroblastic tumor and neuroblastoma. Other rarer tumors described in literature include urothelial carcinoma and other epithelial neoplasms. Rhabdomyosarcoma is associated to a variety of genetic syndromes and many genes are involved in tumor development. PAX3-FKHR and PAX7-FKHR (P-F) fusion state has important implications in the pathogenesis and biology of RMS, and different genes alterations are involved in the pathogenesis of P-F negative and embryonal RMS, which are the subsets of tumors most frequently affecting the bladder. These genes include p53, MEF2, MYOG, Ptch1, Gli1, Gli3, Myf5, MyoD1, NF1, NRAS, KRAS, HRAS, FGFR4, PIK3CA, CTNNB1, FBXW7, IGF1R, PDGFRA, ERBB2/4, MET, BCOR. Malignant rhabdoid tumor (MRT) usually shows SMARCB1/INI1 alterations. Anaplastic lymphoma kinase (ALK) gene translocations are the most frequently associated alterations in inflammatory myofibroblastic tumor (IMT). Few genes alterations in urothelial neoplasms have been reported in the paediatric population, which are mainly related to deletion of p16/lnk4, overexpression of CK20 and overexpression of p53. Here, we reviewed available literature to identify genes associated to bladder malignancies in children and discussed their possible relationships with these tumors. PMID:27013922

Tissue classification and diagnostics using a fiber probe for combined Raman and fluorescence spectroscopy

NASA Astrophysics Data System (ADS)

Cicchi, Riccardo; Anand, Suresh; Rossari, Susanna; Sturiale, Alessandro; Giordano, Flavio; De Giorgi, Vincenzo; Maio, Vincenza; Massi, Daniela; Nesi, Gabriella; Buccoliero, Anna Maria; Tonelli, Francesco; Guerrini, Renzo; Pimpinelli, Nicola; Pavone, Francesco S.

2015-03-01

Two different optical fiber probes for combined Raman and fluorescence spectroscopic measurements were designed, developed and used for tissue diagnostics. Two visible laser diodes were used for fluorescence spectroscopy, whereas a laser diode emitting in the NIR was used for Raman spectroscopy. The two probes were based on fiber bundles with a central multimode optical fiber, used for delivering light to the tissue, and 24 surrounding optical fibers for signal collection. Both fluorescence and Raman spectra were acquired using the same detection unit, based on a cooled CCD camera, connected to a spectrograph. The two probes were successfully employed for diagnostic purposes on various tissues in a good agreement with common routine histology. This study included skin, brain and bladder tissues and in particular the classification of: malignant melanoma against melanocytic lesions and healthy skin; urothelial carcinoma against healthy bladder mucosa; brain tumor against dysplastic brain tissue. The diagnostic capabilities were determined using a cross-validation method with a leave-one-out approach, finding very high sensitivity and specificity for all the examined tissues. The obtained results demonstrated that the multimodal approach is crucial for improving diagnostic capabilities. The system presented here can improve diagnostic capabilities on a broad range of tissues and has the potential of being used for endoscopic inspections in the near future.

Tissue classification and diagnostics using a fiber probe for combined Raman and fluorescence spectroscopy

NASA Astrophysics Data System (ADS)

Cicchi, Riccardo; Anand, Suresh; Crisci, Alfonso; Giordano, Flavio; Rossari, Susanna; De Giorgi, Vincenzo; Maio, Vincenza; Massi, Daniela; Nesi, Gabriella; Buccoliero, Anna Maria; Guerrini, Renzo; Pimpinelli, Nicola; Pavone, Francesco S.

2015-07-01

Two different optical fiber probes for combined Raman and fluorescence spectroscopic measurements were designed, developed and used for tissue diagnostics. Two visible laser diodes were used for fluorescence spectroscopy, whereas a laser diode emitting in the NIR was used for Raman spectroscopy. The two probes were based on fiber bundles with a central multimode optical fiber, used for delivering light to the tissue, and 24 surrounding optical fibers for signal collection. Both fluorescence and Raman spectra were acquired using the same detection unit, based on a cooled CCD camera, connected to a spectrograph. The two probes were successfully employed for diagnostic purposes on various tissues in a good agreement with common routine histology. This study included skin, brain and bladder tissues and in particular the classification of: malignant melanoma against melanocytic lesions and healthy skin; urothelial carcinoma against healthy bladder mucosa; brain tumor against dysplastic brain tissue. The diagnostic capabilities were determined using a cross-validation method with a leave-one-out approach, finding very high sensitivity and specificity for all the examined tissues. The obtained results demonstrated that the multimodal approach is crucial for improving diagnostic capabilities. The system presented here can improve diagnostic capabilities on a broad range of tissues and has the potential of being used for endoscopic inspections in the near future.

Innovation in Bladder Cancer Immunotherapy.

PubMed

Grossman, H Barton; Lamm, Donald L; Kamat, Ashish M; Keefe, Stephen; Taylor, John A; Ingersoll, Molly A

2016-10-01

Bladder cancer is understudied despite its high prevalence and its remarkable response to immunotherapy. Indeed, funding for studies to explore mechanisms of tumor immunity and novel new therapeutics is disproportionately lower for bladder cancer in comparison with malignancies of the breast, prostate, or lung. However, the recent successes of checkpoint blockade therapy suggest that new therapeutic strategies are on the horizon for bladder cancer. Here, we give a perspective into the evolution of bladder cancer therapy, focusing on strategies to treat high-risk nonmuscle invasive disease, followed by a discussion of recent advances in the treatment of muscle invasive bladder cancer and their potential applicability to lower stage disease. Finally, we explore immunotherapeutic strategies, which have been demonstrated to be successful in the treatment of other malignancies, for their potential to treat and cure patients with nonmuscle and muscle invasive bladder cancer.

Primary adenocarcinomas of the human urinary bladder: histochemical, immunological and ultrastructural studies.

PubMed

Alroy, J; Roganovic, D; Banner, B F; Jacobs, J B; Merk, F B; Ucci, A A; Kwan, P W; Coon, J S; Miller, A W

1981-01-01

Neoplastic and non-neoplastic tissue specimens from ten patients with primary adenocarcinoma of the urinary bladder were examined. Most of these tumors were associated with either foci of transitional cell carcinoma and/or with glandular metaplasia of the bladder epithelium. The mucin produced by the neoplastic cells was PAS, alcian blue, mucicarmine, PB/KOH/PAS, and RPB/KOH/PAS-positive. ABH isoantigens of these tumors were not always deleted. Ultrastructurally, the neoplastic cells resembled goblet cells. Their plasma membrane had numerous microvilli with prominent glycocalyx. Proliferation and attenuation of tight junctions were noted. The gap junctions were few and small. Two types of desmosomes were found. The ultrastructural features of the neoplastic cells were attributed in part to the malignant transformation and in part to the direction of their differentiation. We have not observed any distinctive morphologic, histochemical, immunologic or ultrastructural features that might be diagnostic for these adenocarcinomas.

MicroRNA-137 Upregulation Increases Bladder Cancer Cell Proliferation and Invasion by Targeting PAQR3

PubMed Central

Xia, Shunyao; Jin, Chengjun; Yin, Huaifu; Zhao, Weiming; Wu, Qiong

2014-01-01

There is increasing evidence suggesting that dysregulation of some microRNAs (miRNAs) may contribute to tumor progression and metastasis and have been proposed to be key regulators of diverse biological processes such as transcriptional regulation, cell growth and tumorigenesis. Previous studies have shown that miR-137 is dysregulated in some malignancies, but its role in bladder cancer is still unknown. In our study, we find that miR-137 is up-regulated in human bladder cancer tissues and cell lines. Moreover, the higher level of miR-137 was associated with pM or pTNM stage in clinical bladder cancer patients. Enforced expression of miR-137 in bladder cancer cells significantly enhanced their proliferation, migration and invasion. Bioinformatics analysis identified the tumor suppressor gene PAQR3 as a potential miR-137 target gene. Further studies indicated that miR-137 suppressed the expression of PAQR3 by binding to its 3′-untranslated region. Silencing of PAQR3 by small interfering RNAs phenocopied the effects of miR-137 overexpression, whereas restoration of PAQR3 in bladder cancer cells bladder cancer cells overexpressing miR-137, partially reversed the suppressive effects of miR-137. These findings indicate that miR-137 could be a potential oncogene in bladder cancer. PMID:25330156

Prompt diagnosis key in bladder cancer.

PubMed

DeSouza, Karen; Chowdhury, Simon; Hughes, Simon

2014-01-01

Bladder cancer is the most frequently diagnosed cancer involving the urinary tract and is the seventh most common cancer in the UK. Delayed diagnosis is associated with high-grade muscle invasive disease which has the potential to progress rapidly, metastasise and is often fatal. Urothelial cancer (transitional cell carcinoma) is the predominant histological subtype in Europe, where it accounts for 90% of all bladder cancers. Haematuria, which is typically intermittent, frank, painless and at times present throughout micturition, is the classical and most common presentation of bladder cancer. However, irritative symptoms such as dysuria, urgency, urge incontinence and frequency as well as obstructive symptoms can also be experienced. Fatigue; weight loss; anorexia; renal failure; respiratory symptoms and a suprapubic palpable mass are usually signs of advanced or metastatic malignancy. Cigarette smokers have up to four times the risk of bladder cancer compared with non-smokers. Other risk factors include: exposure to aniline dyes; use of cyclophosphamide; history of pelvic radiation; exposure to chemical carcinogens associated with certain industries; spinal cord injuries requiring long-term indwelling catheters; type 2 diabetes treated with pioglitazone and condylomata acuminata. Frank haematuria has a high diagnostic yield for malignancies involving the urinary tract and initial routine tests should be directed towards identifying a variety of potential non-malignant causes. A thorough physical examination should be undertaken to identify evidence of bleeding diathesis and metastatic malignancy. Suggested laboratory investigations include FBC, coagulation, creatinine and PSA. The diagnosis of bladder cancer is based on urine cytology, cystoscopy and pathological assessment of the bladder biopsy.

Tissue engineering as innovative chance for organ replacement in radical tumor surgery.

PubMed

Alberti, C

2013-03-01

Different pathological conditions such as congenital organ absence, severe organ injuries, end-stage organ failure and malignancy-related organ removal, have few effective therapeutic options a part from a whole organ transplant, that, however, often meets with a serious shortage of suitable donor organs. The purpose of this paper consists in highlighting what the novel tissue engineering approaches might help to solve such problems. EMERGING CONCEPTS: A recent approach in tissue/organ engineering, particularly to build bioartificial airways, is the procedure of decellularizing a whole donor organ to obtain a complex 3D-biomatrix-scaffold maintaining the intrinsic vascular network, that is subsequently recellularized with recipient's autologous organ-specific differentiated cells or/and stem cells, to build a potentially functional biological substitute. Such strategy has been clinically used to replace organ in trachea/broncus tumor patients. In another approach, mainly used to construct a bioartificial urinary bladder tissue, different types of either biodegradable synthetic polymers or naturally-derived matrices or even polymer/biomatrix-composite materials are used as scaffold for either cell-free or autologous cell-seeded tissue engineering procedures. So far, such technique has been mainly used to make an augmentation cystoplasty in patients with end-stage poorly compliant neuropathic bladder or in exstrophic bladder subjects. Intriguing developments in biomaterial science, nanotechnologies, stem cell biology, and further improvements in bioreactor manufacturing will allow to generate, in the near future, tissue engineered organs that, as for structure/function so the native one-like, might represent the optimum solution to replace organs in tumor surgery.

A Population-Based Study of Subsequent Primary Malignancies After Endometrial Cancer: Genetic, Environmental, and Treatment-Related Associations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, Aaron P.; Neeley, E. Shannon; Werner, Theresa

2010-09-01

Purpose: To examine the risk of subsequent primary malignancies (SPMs) in women diagnosed with endometrial cancer. Methods and Materials: The National Cancer Institute's Survival, Epidemiology, and End Results database was used to determine the risk of SPM after endometrial cancer in 69,739 women diagnosed between 1973 and 2005. Standardized incidence ratios were calculated (observed/expected [O/E]) for SPM sites. Results: Median follow-up was 11.2 years, representing 757,567 person-years of follow-up. The risk of SPM was significantly increased for small intestine (O/E = 1.48; 99% confidence interval [CI], 1.03-2.05), colon (O/E = 1.16; CI, 1.09-1.24), vagina (O/E = 2.71; CI, 1.86-3.8), andmore » urinary bladder (O/E = 1.41; CI, 1.25-1.59) SPMs and decreased for oral cavity and pharynx (O/E = 0.75; CI, 0.6-0.93), lung and bronchus (O/E = 0.78; CI, 0.72-0.84), and esophagus (O/E = 0.58; CI, 0.37-0.86) SPMs. Patients receiving external-beam radiotherapy for endometrial cancer had an increased risk of colon (p < 0.001), bladder (p < 0.001), vagina (p = 0.04), and soft-tissue (p = 0.014) SPMs. Patients treated with brachytherapy had an increased risk of bladder SPM (p = 0.006). A positive bidirectional association with endometrial cancer was observed for colorectal cancer, with a negative bidirectional association for oropharyngeal and lung cancers. Conclusions: Genetic, environmental, and treatment-related factors influence SPM risk. Genetic factors may contribute to the increased risk of colorectal cancer. Smoking's negative effect on endometrial cancer risk factors might explain the decreased risk of lung and oropharyngeal cancer. Patients treated with radiotherapy likely have a small but significantly increased risk of bladder, vagina, colon, and soft-tissue SPM.« less

A population-based study of subsequent primary malignancies after endometrial cancer: genetic, environmental, and treatment-related associations.

PubMed

Brown, Aaron P; Neeley, E Shannon; Werner, Theresa; Soisson, Andrew Patrick; Burt, Randall W; Gaffney, David K

2010-09-01

To examine the risk of subsequent primary malignancies (SPMs) in women diagnosed with endometrial cancer. The National Cancer Institute's Survival, Epidemiology, and End Results database was used to determine the risk of SPM after endometrial cancer in 69,739 women diagnosed between 1973 and 2005. Standardized incidence ratios were calculated (observed/expected [O/E]) for SPM sites. Median follow-up was 11.2 years, representing 757,567 person-years of follow-up. The risk of SPM was significantly increased for small intestine (O/E = 1.48; 99% confidence interval [CI], 1.03-2.05), colon (O/E = 1.16; CI, 1.09-1.24), vagina (O/E = 2.71; CI, 1.86-3.8), and urinary bladder (O/E = 1.41; CI, 1.25-1.59) SPMs and decreased for oral cavity and pharynx (O/E = 0.75; CI, 0.6-0.93), lung and bronchus (O/E = 0.78; CI, 0.72-0.84), and esophagus (O/E = 0.58; CI, 0.37-0.86) SPMs. Patients receiving external-beam radiotherapy for endometrial cancer had an increased risk of colon (p < 0.001), bladder (p < 0.001), vagina (p = 0.04), and soft-tissue (p = 0.014) SPMs. Patients treated with brachytherapy had an increased risk of bladder SPM (p = 0.006). A positive bidirectional association with endometrial cancer was observed for colorectal cancer, with a negative bidirectional association for oropharyngeal and lung cancers. Genetic, environmental, and treatment-related factors influence SPM risk. Genetic factors may contribute to the increased risk of colorectal cancer. Smoking's negative effect on endometrial cancer risk factors might explain the decreased risk of lung and oropharyngeal cancer. Patients treated with radiotherapy likely have a small but significantly increased risk of bladder, vagina, colon, and soft-tissue SPM. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Fibroblast growth factor receptor 1 and cytokeratin 20 expressions and their relation to prognostic variables in bladder cancer.

PubMed

Abdul-Maksoud, Rehab S; Shalaby, Sally M; Elsayed, Walid S H; Elkady, Saad

2016-10-15

Tumor grade and stage are currently the most important prognostic variables in bladder cancer but establishing additional criteria is still needed for effective treatment. The aim of the study was to assess the expression of fibroblast growth factor receptor 1 (FGFR1) and cytokeratin 20 (CK20) in cancer bladder (CB) and to evaluate their association with the clinicopathological features of the disease. The study included 80 patients diagnosed as bladder cancer of different stages and grades and 80 patients with nonmalignant urothelial diseases of matched age and sex to the malignant group. The expressions of FGFR1 and CK20 in tissue samples were determined by RT-PCR and immunohistochemistry. The expression levels of FGFR1 and CK20 were increased in the malignant group when compared to the control group (P<0.001 for each). Analysis of their expression showed that levels of FGFR1 and CK20 were significantly higher in invasive tumor stages (pT2-pT4) than in non-invasive stages (pTis, pTa, pT1) (P<0.001). Interestingly, the sensitivity and specificity of combined detection with CK20 and FGFR1 for the differentiation between invasive and non-invasive stages of bladder cancer reached 97.5% and 92.5%, respectively. Our results determined overexpression of both FGFR1 and CK20 in CB specimens. The alterations in the expression of FGFR1 and CK20 were associated with disease stage and grade. Lastly, combined detection of FGFR1 and CK20 had a high predictive prognostic value in differentiating invasive from non-invasive carcinoma. Copyright © 2016 Elsevier B.V. All rights reserved.

Acute radiation impacts contractility of guinea-pig bladder strips affecting mucosal-detrusor interactions.

PubMed

McDonnell, Bronagh M; Buchanan, Paul J; Prise, Kevin M; McCloskey, Karen D

2018-01-01

Radiation-induced bladder toxicity is associated with radiation therapy for pelvic malignancies, arising from unavoidable irradiation of neighbouring normal bladder tissue. This study aimed to investigate the acute impact of ionizing radiation on the contractility of bladder strips and identify the radiation-sensitivity of the mucosa vs the detrusor. Guinea-pig bladder strips (intact or mucosa-free) received ex vivo sham or 20Gy irradiation and were studied with in vitro myography, electrical field stimulation and Ca2+-fluorescence imaging. Frequency-dependent, neurogenic contractions in intact strips were reduced by irradiation across the force-frequency graph. The radiation-difference persisted in atropine (1μM); subsequent addition of PPADs (100μM) blocked the radiation effect at higher stimulation frequencies and decreased the force-frequency plot. Conversely, neurogenic contractions in mucosa-free strips were radiation-insensitive. Radiation did not affect agonist-evoked contractions (1μM carbachol, 5mM ATP) in intact or mucosa-free strips. Interestingly, agonist-evoked contractions were larger in irradiated mucosa-free strips vs irradiated intact strips suggesting that radiation may have unmasked an inhibitory mucosal element. Spontaneous activity was larger in control intact vs mucosa-free preparations; this difference was absent in irradiated strips. Spontaneous Ca2+-transients in smooth muscle cells within tissue preparations were reduced by radiation. Radiation affected neurogenic and agonist-evoked bladder contractions and also reduced Ca2+-signalling events in smooth muscle cells when the mucosal layer was present. Radiation eliminated a positive modulatory effect on spontaneous activity by the mucosa layer. Overall, the findings suggest that radiation impairs contractility via mucosal regulatory mechanisms independent of the development of radiation cystitis.

Growth factors in urologic tissues: detection, characterization, and clinical applications.

PubMed

Mydlo, J H; Macchia, R J

1992-12-01

During the last two decades, enormous strides have been made in understanding cellular and molecular biology. The direction of treatment of many neoplasms and other diseases are starting at the microscopic level. Growth factors are polypeptides that play a part in the development and maintenance of living tissues. We, as well as others, have investigated the role that growth factors play particularly in urologic tissues, both benign and malignant. We review several well-known growth factors and their function in prostate, kidney, and bladder tissues, as well as their functions in other regulating processes of the human body, and also the use of growth factors as tumor markers, and antibodies to growth factors as possible treatment of disease.

Novel Neoadjuvant Therapy Paradigms for Bladder Cancer: Results from the National Cancer Center Institute Forum

PubMed Central

Dinney, Colin P.N.; Hansel, Donna; McConkey, David; Shipley, William; Hagan, Michael; Dreicer, Robert; Lerner, Seth; Czerniak, Bogdan; Waldman, Fred; Groshen, Susan; True, Lawrence D.; Petricoin, Emanuel; Theodorescu, Dan; Hruszkewycz, Andrew; Bajorin, Dean

2014-01-01

Although bladder cancer (BC) is a significant health threat to the US population, integrated clinical and laboratory investigations of this disease lag behind those of other types of cancer. Advances in BC are especially challenged due in part to a general decreased level of funding over the past 5 years. It is ironic that despite the awareness that BC is the 5th most commonly diagnosed solid malignancy in the United States, and one of the most costly to treat, funding for this organ site lags far behind that of other less common malignancies. Moreover, BC offers several unique opportunities for translational research that make it an ideal candidate for investigation. One distinct advantage over other solid tumor sites is that urine and tissue are readily available for translational studies that can direct the development of novel therapy for this disease. The NCI sponsored “Novel Neoadjuvant Therapy for Bladder Cancer” forum held in brought leading clinical and laboratory-based scientists together with the advocacy community to lay the groundwork for collaborative discovery and translation. The goal of the meeting was to bridge the gaps in translational science and develop the concepts for two novel biomarker-driven clinical trials, one in the neoadjuvant presurgical setting and the other in the setting of bladder preservation with chemoradiation. The meeting provided a unique opportunity to launch a collective effort to establish molecular-based therapy for UC. Herein, we summarize the proceedings of this meeting, and the future plans resulting from this forum. PMID:25443274

An Unexpected Surge in Plasma BKPyV Viral Load Heralds the Development of BKPyV-Associated Metastatic Bladder Cancer in a Lung Transplant Recipient With BKPyV Nephropathy.

PubMed

Kuppachi, S; Holanda, D; Eberlein, M; Alexiev, B; Tyler, A J; Wissel, M C; Kleiboeker, S B; Thomas, C P

2017-03-01

We report a lung transplant recipient who developed BK polyoma virus (BKPyV) DNAemia and BKPyV nephropathy. With careful management of his immunosuppression he achieved significant reduction in BKPyV DNAemia and stabilization of his kidney function. He later developed a high-grade bladder cancer and shortly thereafter he experienced a major upsurge in the level of BKPyV DNAemia that coincided with the discovery of hepatic metastasis. Retrospectively, the bladder cancer and the hepatic secondary tumor stained uniformly for SV40 large T antigen, and the BKPyV DNA sequences identified in plasma corresponded to BKPyV DNA within hepatic tissue, indicating that the spike in BKPyV load was likely derived from the circulating tumor cells or cell-free tumor DNA following metastases of a BKV-associated cancer. To the best of our knowledge, this is the first description of a surge in BKPyV load in a patient with controlled BKPyVN that heralded the appearance of a metastatic urothelial malignancy. This report discusses the literature on BKPyV-associated malignancies and the possibility that unexplained increases in BKPyV DNAemia may be a biomarker for metastatic BKPyV-related urothelial cancer. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Adenoviral receptor expression of normal bladder and transitional cell carcinoma of the bladder.

PubMed

Buscarini, Maurizio; Quek, Marcus L; Gilliam-Hegarich, Susan; Kasahara, Nori; Bochner, Bernard

2007-01-01

The insertion of absent or underexpressed genes into cancer cells to alter their malignant phenotype is an important potential application of available gene therapy technology. One of the more common viral vector systems that has been extensively studied for this purpose are the replication-deficient adenoviruses (Ad). Adenoviral infection of cells is mediated through a complex pathway, initiated following viral-cell attachment. Adenoviral-cell attachment occurs following interactions with a 46-kDa transmembrane protein with high affinity for both the Coxsackie and adenovirus, designated the CAR (Coxsackie and adenoviral receptor). Additional important cell-viral interactions that occur involve the alpha(v)-based integrins, specifically alpha(v)beta3 and alpha(v)beta5. The purpose of the present study was to determine the extent of expression and localization of the known Ad receptor proteins (CAR, alpha(v)beta3, and alpha(v)beta5) in normal and cancerous human bladders. Frozen tissue samples of normal bladder and invasive transitional cell cancers of the bladder were evaluated. Tissue blocks containing muscle-invasive transitional cell carcinoma (TCC) were obtained following radical cystectomy, which were performed at our institution. Thirty-two invasive transitional cell bladder tumors were evaluated, each with a matched sample of histologically normal-appearing bladder used as a control. Four additional samples of normal bladder were obtained from patients with no evidence of disease of the bladder and served as further controls. Three additional cases of invasive bladder cancer with no matching normal tissue were also evaluated. Identification of the CAR receptor was performed using the anti-CAR mouse monoclonal antibody designated RmBC. The integrins alpha(v)beta3 and alpha(v)beta5 were identified using the mouse monoclonal antibodies designated LM609 and P1F6 respectively. All slides were evaluated by two of the authors (M.B., B.B.) without knowledge of the clinical and pathological data. Normal bladder: Normal bladder mucosa demonstrated a marked positivity for CAR in 29/35 (82.8%) cases. In contrast, normal transitional epithelial cells were uniformly negative when tested for the integrins alpha(v)beta3 and alpha(v)beta5. Subepithelial tissues, specifically the connective tissue components of the lamina propria and deep muscle wall of the bladder, were positive for alpha(v)beta3 and for alpha(v)beta5 in 61 and 75% of samples, respectively. Endothelial cells associated with the various layers throughout the bladder uniformly expressed both integrins and served as a consistent internal control for both antibodies. An almost identical staining pattern of the endothelium was observed using LM609 and P1F6 in all samples tested. Bladder transitional cell carcinoma: CAR immunoreactivity against TCC cells was uniformly decreased compared to normal transitional cells. Nine tumors exhibited a weak positivity for CAR while the remaining samples were negative. In some cases, the absence of CAR positivity was associated with histological evidence of carcinoma in situ. In 6 cases, it led to the identification of small regions of carcinoma in situ that were not noted on primary pathological evaluation. Peritumoral connective tissue expressed both integrins in the majority of cases, similar to the pattern described above for normal bladder. Transitional cell cancers demonstrated a similar pattern of expression of alpha(v)beta5, in which all tumor cells exhibited minimal or no staining. The success of all viral-mediated gene therapy strategies relies on the ability of the vector to efficiently deliver its genetic material to a target cell population. In the current study, we demonstrate that the bladder epithelial layer consistently expresses high levels of CAR. Deeper layers of the epithelium also express CAR, including the basal layer cells. A decrease in the expression of CAR appears as an early event in bladder carcinogenesis. We observed that both alpha(v)beta3 and alpha(v)beta5 are strongly expressed in muscle cells surrounding the neoplastic cells, as well as within the peritumoral connective tissue. In cases of invasive bladder cancer that have lost CAR expression, an adenoviral vector may still be utilized through the less efficient interactions with the integrins. Bladder tumor tissue may be less susceptible to an adenoviral-mediated gene therapy approach in which a significant percentage of tumor cells require transduction. Adenoviral uptake by tumor or peritumoral cells with subsequent gene transfer could be predicted by the level of CAR and alpha(v)-based integrin expression. This would enhance our ability to identify those patients whose tumors would be more susceptible to Ad-mediated gene delivery as part of an antitumor treatment. 2007 S. Karger AG, Basel

Concomitance of oncogenic HPV types, CHEK2 gene mutations, and CYP1B1 gene polymorphism as an increased risk factor for malignancy.

PubMed

Banaszkiewicz, Monika; Constantinou, Maria; Pietrusiński, Michał; Kępczyński, Lukasz; Jędrzejczyk, Adam; Rożniecki, Marek; Marks, Piotr; Kałużewski, Bogdan

2013-01-01

Urinary bladder carcinoma ranks the fourth position in malignancy incidence rates in men (6.1%) and the 17th position in women (1.6%). In general, neoplastic diseases should be approached from two perspectives: prevention with implementation of prophylactic measures and early diagnostics. Prophylactics is possible in the preclinical phase of neoplasm, being both justified and plausible in patients from high-risk groups. Thus, it is particularly important to select such groups, not only by referring to environmental carcinogenic factors (occupational and extra-occupational) but also from genetic predisposition, which may be conductive for neoplasm formation. The mutations / polymorphisms of CHEK2 and CYP1B1 genes predispose to neoplasm via multiorgan mechanisms, while the human papilloma virus (HPV) may participate in the neoplastic transformation as an environmental factor. 131 patients with diagnosed urinary bladder cancer were qualified to the study. Mutations/polymorphisms of CHEK2 (IVS2 + 1G > A gene, 1100delC, del5395, I157T) and CYP1B1- 355T/T were identified by the PCR in DNA isolated directly from the tumor and from peripheral blood. The ELISA test was used for the studies of 37 HPV genotypes in DNA, isolated tumour tissue. 11 mutations of CHEK2 gene were found, 355T/T polymorphism if CYP1B1 gene occurred in 18 patients (12.9%). Oncogenic HPV was found in 36 (29.3%), out of 123 examined patients. The concomitance of CHEK2 gene mutations or 355T/T polymorphism of CYP1B1 gene and the presence of oncogenic HPV types statistically significantly correlates with histological malignancy grades of urinary bladder carcinoma.

Incidental gall bladder carcinoma in laparoscopic cholecystectomy: a report of 6 cases and a review of the literature.

PubMed

Sujata, Jetley; S, Rana; Sabina, Khan; Mj, Hassan; Jairajpuri, Zeeba Shamim

2013-01-01

Gall bladder carcinoma accounts for 98% of all the gall bladder malignancies and it is the sixth most common malignancy of the gastrointestinal tract worldwide. The incidence of incidental gall bladder carcinoma which is diagnosed during or after a laparoscopic cholecystectomy is reported to be around 0.19-3.3% in the literature. This study was aimed at detecting the incidence of gall bladder carcinomas which were diagnosed incidentally during or after laparoscopic cholecystectomies which were done for gall stone disease and cholecystitis. We analyzed the medical records of patients with symptomatic gallstone disease and acute or chronic cholecystitis, who underwent laparoscopic cholecystectomies at the Hakeem Abdul Hameed Centenary Hospital during the period from January 2007 to June 2012. A total of 622 laparoscopic cholecystectomies were performed at our institute during the study period of five and a half years. In 6 (0.96%) cases, incidental carcinomas of the gallbladder were discovered. A laparoscopic cholecystectomy which is performed for benign gall bladder disease rarely results in a diagnosis of unexpected gallbladder cancer. The microscopic examination of the specimens, with special attention to the depth of invasion, range of the mucosal spread and the lymphovascular involvement, is critical in diagnosing the incidental malignancies as well as for the subsequent management of the cases.

Jarid2 is essential for the maintenance of tumor initiating cells in bladder cancer.

PubMed

Zhu, Xin-Xing; Yan, Ya-Wei; Ai, Chun-Zhi; Jiang, Shan; Xu, Shan-Shan; Niu, Min; Wang, Xiang-Zhen; Zhong, Gen-Shen; Lu, Xi-Feng; Xue, Yu; Tian, Shaoqi; Li, Guangyao; Tang, Shaojun; Jiang, Yi-Zhou

2017-04-11

Bladder cancer is the most common urologic malignancy in China, with an increase of the incidence and mortality rates over past decades. Recent studies suggest that bladder tumors are maintained by a rare fraction of cells with stem cell proprieties. Targeting these bladder tumor initiating cell (TICs) population can overcome the drug-resistance of bladder cancer. However, the molecular and genetic mechanisms regulating TICs in bladder cancer remain poorly defined. Jarid2 is implicated in signaling pathways regulating cancer cell epithelial-mesenchymal transition, and stem cell maintenance. The goal of our study was to examine whether Jarid2 plays a role in the regulation of TICs in bladder cancer. We found that knockdown of Jarid2 was able to inhibit the invasive ability and sphere-forming capacity in bladder cancer cells. Moreover, knockdown of Jarid2 reduced the proportion of TICs and impaired the tumorigenicity of bladder cancer TICs in vivo. Conversely, ectopic overexpression of Jarid2 promoted the invasive ability and sphere-forming capacity in bladder cancer cells. Mechanistically, reduced Jarid2 expression led to the upregulation of p16 and H3K27me3 level at p16 promoter region. Collectively, we provided evidence that Jarid2 via modulation of p16 is a putative novel therapeutic target for treating malignant bladder cancer.

Gemcitabine: Selective cytotoxicity, induction of inflammation and effects on urothelial function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farr, Stefanie E; Chess-Williams, Russ; McDermott,

Intravesical gemcitabine has recently been introduced for the treatment of superficial bladder cancer and has a favourable efficacy and toxicity profile in comparison to mitomycin c (MMC), the most commonly used chemotherapeutic agent. The aim of this study was to assess the cytotoxic potency of gemcitabine in comparison to MMC in urothelial cell lines derived from non-malignant (UROtsa) and malignant (RT4 and T24) tissues to assess selectivity. Cells were treated with gemcitabine or mitomycin C at concentrations up to the clinical doses for 1 or 2 h respectively (clinical duration). Treatment combined with hyperthermia was also examined. Cell viability, ROSmore » formation, urothelial function (ATP, acetylcholine and PGE2 release) and secretion of inflammatory cytokines were assessed. Gemcitabine displayed a high cytotoxic selectivity for the two malignant cell lines (RT4, T24) compared to the non-malignant urothelial cells (UROtsa, proliferative and non-proliferative). In contrast, the cytotoxic effects of MMC were non-selective with equivalent potency in each of the cell lines. The cytotoxic effect of gemcitabine in the malignant cell lines was associated with an elevation in free radical formation and was significantly decreased in the presence of an equilibrative nucleoside transporter inhibitor. Transient changes in urothelial ATP and PGE{sub 2} release were observed, with significant increase in release of interleukin-6, interleukin-8 and interleukin-1β from urothelial cells treated with gemcitabine. The selectivity of gemcitabine for malignant urothelial cells may account for the less frequent adverse urological effects with comparison to other commonly used chemotherapeutic agents. - Highlights: • Intravesical gemcitabine has recently been introduced to treat bladder cancer. • Gemcitabine is selectively toxic for malignant urothelial cells. • Urothelial ATP, PGE{sub 2} and inflammatory cytokines were altered by gemcitabine. • Selectivity of gemcitabine may account for less frequent urological side effects.« less

HPLC assisted Raman spectroscopic studies on bladder cancer

NASA Astrophysics Data System (ADS)

Zha, W. L.; Cheng, Y.; Yu, W.; Zhang, X. B.; Shen, A. G.; Hu, J. M.

2015-04-01

We applied confocal Raman spectroscopy to investigate 12 normal bladder tissues and 30 tumor tissues, and then depicted the spectral differences between the normal and the tumor tissues and the potential canceration mechanism with the aid of the high-performance liquid chromatographic (HPLC) technique. Normal tissues were demonstrated to contain higher tryptophan, cholesterol and lipid content, while bladder tumor tissues were rich in nucleic acids, collagen and carotenoids. In particular, β-carotene, one of the major types of carotenoids, was found through HPLC analysis of the extract of bladder tissues. The statistical software SPSS was applied to classify the spectra of the two types of tissues according to their differences. The sensitivity and specificity of 96.7 and 66.7% were obtained, respectively. In addition, different layers of the bladder wall including mucosa (lumps), muscle and adipose bladder tissue were analyzed by Raman mapping technique in response to previous Raman studies of bladder tissues. All of these will play an important role as a directive tool for the future diagnosis of bladder cancer in vivo.

Incidental Gall Bladder Carcinoma in Laparoscopic Cholecystectomy: A Report of 6 Cases and a Review of the Literature

PubMed Central

Sujata, Jetley; S, Rana; Sabina, Khan; MJ, Hassan; Jairajpuri, Zeeba Shamim

2013-01-01

Background: Gall bladder carcinoma accounts for 98% of all the gall bladder malignancies and it is the sixth most common malignancy of the gastrointestinal tract worldwide. The incidence of incidental gall bladder carcinoma which is diagnosed during or after a laparoscopic cholecystectomy is reported to be around 0.19-3.3% in the literature. Aim: This study was aimed at detecting the incidence of gall bladder carcinomas which were diagnosed incidentally during or after laparoscopic cholecystectomies which were done for gall stone disease and cholecystitis. Materials and Methods: We analyzed the medical records of patients with symptomatic gallstone disease and acute or chronic cholecystitis, who underwent laparoscopic cholecystectomies at the Hakeem Abdul Hameed Centenary Hospital during the period from January 2007 to June 2012. Results: A total of 622 laparoscopic cholecystectomies were performed at our institute during the study period of five and a half years. In 6 (0.96%) cases, incidental carcinomas of the gallbladder were discovered. Conclusion: A laparoscopic cholecystectomy which is performed for benign gall bladder disease rarely results in a diagnosis of unexpected gallbladder cancer. The microscopic examination of the specimens, with special attention to the depth of invasion, range of the mucosal spread and the lymphovascular involvement, is critical in diagnosing the incidental malignancies as well as for the subsequent management of the cases. PMID:23449518

Epithelioid variant of malignant peripheral nerve sheath tumor (malignant schwannoma) of the urinary bladder.

PubMed

Eltoum, I A; Moore, R J; Cook, W; Crowe, D R; Rodgers, W H; Siegal, G P

1999-10-01

Sarcoma represents less than 2% of all neoplasms diagnosed or recognized in effusions. Epithelioid peripheral nerve sheath tumor is a rare tumor that is difficult to differentiate from other epithelioid tumors without the use of ancillary studies. A 39-year-old paraplegic man presented with hematuria and a bladder mass that extended to involve the pelvic peritoneum. Light microscopy using hematoxylin-eosin, Papanicolaou, and immunohistochemical stains as well as transmission electron microscopy showed features of epithelioid malignant peripheral nerve sheath tumor with rhabdoid features and an accompanying eosinophilic infiltrate. Cytologic smears confirmed the similarities between the primary tumor in the bladder and the cells in the pelvic fluid and excluded the possibility of reactive changes related to postsurgical radiation. Ancillary studies were critical in narrowing the differential diagnoses and reaching the final conclusion.

Palliative management of malignant upper urinary tract obstruction

PubMed Central

Sountoulides, P; Mykoniatis, I; Dimasis, N

2014-01-01

Malignancies of the genitourinary tract are diagnosed with increased frequency compared to the past. Currently prostate and bladder cancer account for the majority of urological malignancies. While for prostate cancer recent developments in the management of local and metastatic disease are likely to lead the majority of patients to either cure from the disease or to longer survival time, for bladder cancer advanced disease will unfortunately lead to death within months. However, the common clinical scenario in both prostate and bladder cancer includes, in high incidence, upper urinary tract obstruction in the advanced stages of these malignancies. This coupled with the fact that average life expectancy in the western world is increasing, will result in a significant patient population with either advanced, non-curable disease or with problems related to the received therapeutic surgical or medical interventions. There is no doubt that in both circumstances the room and role of palliation therapy is increasing. The care of patients with advanced urologic malignancies requires a multi-disciplinary effort from physicians of many specialties under the guiding role of the treating urologist. This review focuses on currently available palliative therapeutic options for upper urinary tract obstruction in the setting of patients with advanced malignancies of the urinary tract, as recently significant advancements have been witnessed in this field. PMID:26052193

Palliative management of malignant upper urinary tract obstruction.

PubMed

Sountoulides, P; Mykoniatis, I; Dimasis, N

2014-01-01

Malignancies of the genitourinary tract are diagnosed with increased frequency compared to the past. Currently prostate and bladder cancer account for the majority of urological malignancies. While for prostate cancer recent developments in the management of local and metastatic disease are likely to lead the majority of patients to either cure from the disease or to longer survival time, for bladder cancer advanced disease will unfortunately lead to death within months. However, the common clinical scenario in both prostate and bladder cancer includes, in high incidence, upper urinary tract obstruction in the advanced stages of these malignancies. This coupled with the fact that average life expectancy in the western world is increasing, will result in a significant patient population with either advanced, non-curable disease or with problems related to the received therapeutic surgical or medical interventions. There is no doubt that in both circumstances the room and role of palliation therapy is increasing. The care of patients with advanced urologic malignancies requires a multi-disciplinary effort from physicians of many specialties under the guiding role of the treating urologist. This review focuses on currently available palliative therapeutic options for upper urinary tract obstruction in the setting of patients with advanced malignancies of the urinary tract, as recently significant advancements have been witnessed in this field.

Atezolizumab in urothelial bladder carcinoma.

PubMed

Hamilou, Zineb; Lavaud, Pernelle; Loriot, Yohann

2018-02-01

Metastatic bladder cancer is an aggressive malignancy with a poor prognosis when presenting with advanced stage. Cisplatin-based therapy has been the mainstay of first-line treatment but therapy in second-line setting has been an unmet medical need for decades. Moreover, many patients are unable to receive cisplatin-based therapy. Recently, immune-checkpoint inhibitors transformed the management and prognosis of many malignancies and will certainly redefine the standard of care for bladder cancer. Atezolizumab, an anti-PD-L1 antibody, was the first immune-checkpoint inhibitor to be approved by the US FDA in May 2016 for patients with urothelial carcinoma. In this review, we discuss the evidence behind this promising drug.

Urinary bladder: normal appearance and mimics of malignancy at CT urography

PubMed Central

Sadow, Cheryl A.; Anik Sahni, V.; Silverman, Stuart G.

2011-01-01

Abstract The objective of this review article is to learn how to recognize anatomic variants and benign entities that mimic bladder cancer at computed tomography (CT) urography. Building on recent data that suggest that CT urography can be used to diagnose bladder cancer, recognition of anatomic variants and benign entities will help improve radiologists’ ability to diagnose bladder cancer. PMID:21771710

Detection of bladder metabolic artifacts in (18)F-FDG PET imaging.

PubMed

Roman-Jimenez, Geoffrey; Crevoisier, Renaud De; Leseur, Julie; Devillers, Anne; Ospina, Juan David; Simon, Antoine; Terve, Pierre; Acosta, Oscar

2016-04-01

Positron emission tomography using (18)F-fluorodeoxyglucose ((18)F-FDG-PET) is a widely used imaging modality in oncology. It enables significant functional information to be included in analyses of anatomical data provided by other image modalities. Although PET offers high sensitivity in detecting suspected malignant metabolism, (18)F-FDG uptake is not tumor-specific and can also be fixed in surrounding healthy tissue, which may consequently be mistaken as cancerous. PET analyses may be particularly hampered in pelvic-located cancers by the bladder׳s physiological uptake potentially obliterating the tumor uptake. In this paper, we propose a novel method for detecting (18)F-FDG bladder artifacts based on a multi-feature double-step classification approach. Using two manually defined seeds (tumor and bladder), the method consists of a semi-automated double-step clustering strategy that simultaneously takes into consideration standard uptake values (SUV) on PET, Hounsfield values on computed tomography (CT), and the distance to the seeds. This method was performed on 52 PET/CT images from patients treated for locally advanced cervical cancer. Manual delineations of the bladder on CT images were used in order to evaluate bladder uptake detection capability. Tumor preservation was evaluated using a manual segmentation of the tumor, with a threshold of 42% of the maximal uptake within the tumor. Robustness was assessed by randomly selecting different initial seeds. The classification averages were 0.94±0.09 for sensitivity, 0.98±0.01 specificity, and 0.98±0.01 accuracy. These results suggest that this method is able to detect most (18)F-FDG bladder metabolism artifacts while preserving tumor uptake, and could thus be used as a pre-processing step for further non-parasitized PET analyses. Copyright © 2016. Published by Elsevier Ltd.

Carcinosarcoma of the Urinary Bladder: A Case Report

PubMed Central

Gupta, Limci; Elder, Jacqueline

2005-01-01

Carcinosarcomas are rare tumours containing both malignant mesenchymal and epithelial elements. This reports presents a 70-year-old man with carcinosarcoma of the urinary bladder, which is proven histologically. PMID:15962192

Use of donor bladder tissues for in vitro research.

PubMed

Garthwaite, Mary; Hinley, Jennifer; Cross, William; Warwick, Ruth M; Ambrose, Anita; Hardaker, Henry; Eardley, Ian; Southgate, Jennifer

2014-01-01

To evaluate deceased non-heart beating (DNHB) donors and deceased heart beating (DHB) brain-stem dead donors, as sources of viable urological tissue for use in biomedical research. To identify sources of viable human bladder tissue as an essential resource for cell biological research aimed at understanding human diseases of the bladder and for developing new tissue engineering and regenerative medicine strategies for bladder reconstruction. Typically, normal human urinary tract tissue is obtained from adult or paediatric surgical patients with benign urological conditions, but few surgical procedures yield useful quantities of healthy bladder tissue for research. Research ethics committee approval was obtained for collection of donor bladder tissue. Consent for DHB donors was undertaken by the Donor Transplant Coordinators. Tissue Donor Coordinators were responsible for consent for DNHB donors and the retrieval of bladders was coordinated through the National Blood Service Tissue Banking Service. All retrievals were performed by practicing urologists and care was taken to maintain sterility and to minimise bacterial contamination. Two bladders were retrieved from DNHB donors and four were retrieved from DHB donors. By histology, DNHB donor bladder tissue exhibited marked urothelial tissue damage and necrosis, with major loss or absence of urothelium. No cell cultures could be established from these specimens, as the urothelial cells were not viable in primary culture. Bladder urothelium from DHB donors was intact, but showed some damage, including loss of superficial cells and variable separation from the basement membrane. All four DHB bladder specimens yielded viable urothelial cells that attached in primary culture, but cell growth was slow to establish and cultures showed a limited capacity to form a functional barrier epithelium and a propensity to senesce early. We have shown that normal human bladder urothelial cell cultures can be established and serially propagated from DHB donor bladders. However, our study suggests that rapid post-mortem changes to the bladder affect the quality and viability of the urothelium, rendering tissue from DNHB donors an inadequate source for urothelial cell culture. Our experience is that whereas patients are willing to donate surgical tissue for research, there is a barrier to obtaining consent from next of kin for retrieved tissues to be used for research purposes. © 2013 The Authors. BJU International © 2013 BJU International.

Research progress on bladder cancer molecular genetics.

PubMed

Kang, Zhengjun; Li, Yuhui; Yu, Yang; Guo, Zhan

2014-11-01

Bladder cancer is a common malignant urinary tumor with a high rate of recurrence and quick progression, which threats human health. With the research on bladder cancer molecular genetics, the knowledge of gene modification and the development of molecular detection methods, more tumor markers have been discovered, which may have potential for early diagnosis, clinical examination and prognosis. This article reviews the research progress on bladder cancer molecular genetics.

Identification of "tumor-associated" nucleolar antigens in human urothelial cancer.

PubMed

Yu, D; Pietro, T; Jurco, S; Scardino, P T

1987-09-01

Nucleoli isolated from HeLa S3 cells were used to produce rabbit antisera capable of binding nucleoli of transitional cell carcinomas (TCCa) of the bladder. Cross-reactivity of the rabbit antiserum with normal nucleoli was reduced by absorption with fetal calf serum, normal human serum, and human placental nucleoli. This antinucleolar antiserum exhibited strong reactivity in immunoperoxidase assays performed on specimens of human bladder cancer. In frozen tissue sections of 24 patients with TCCa and eight individuals without tumor, nucleolar staining was observed in all malignant specimens, but was not observed in seven of the normal specimens. Cytologic examination of bladder washing specimens from 47 normal individuals showed absence of nucleolar staining in 43 (91%) of 47 normal specimens while 12 (86%) of 14 specimens from patients with TCCa were positive. These results suggest that there are antigens associated with the nucleoli of HeLa cells and transitional cell carcinomas which are generally absent (or in low concentration) in normal human urothelial cells, and that antisera to these antigens may be useful in the cytologic diagnosis of human transitional cell carcinoma.

Co-occurrence of acanthosis nigricans and bladder adenocarcinoma – case report

PubMed Central

Silny, Wojciech; Żaba, Ryszard; Osmola-Mańkowska, Agnieszka; Mackiewicz-Wysocka, Małgorzata; Dańczak-Pazdrowska, Aleksandra

2013-01-01

Acanthosis nigricans (AN) is characterized by the occurrence of symmetrical velvety hyperpigmented plaques that can be observed in each location on the skin. However, the lesions are most frequently located in the axillary, inguinal and nuchal areas. Primarily, the lesions appear as hyperpigmented focuses which later transform into papillary lesions. There are two forms of the disease – benign and malignant. Malignant AN is considered to represent paraneoplastic syndrome co-occurring with advanced cancer, but as such it is not malignant. This article presents a case of a patient diagnosed with AN and coexisting bladder cancer and discusses the case in the context of available literature. PMID:24596525

Bovine papillomavirus type 2 infection and a series of mesenchymal tumors of the urinary bladder in cattle.

PubMed

Martano, Manuela; Roperto, Franco; Stocco, Rita de Cassia; Russo, Valeria; Borzacchiello, Giuseppe; Paciello, Orlando; Iovane, Valentina; Leonardi, Leonardo; Maiolino, Paola; Restucci, Brunella; Papparella, Serenella; Roperto, Sante

2013-01-01

This report describes the histopathology of two hundred and fifty-three mesenchymal tumors of the urinary bladder in cattle grazing on lands rich in bracken fern. Approximately 80% were hemangiomas and angiosarcomas. Hemangioma (capillary, cavernous, and large vessels) was the most frequent mesenchymal tumor and was more common than angiosarcoma. Although the appearance of endothelial cells can vary remarkably, epithelioid angiosarcomas, often containing multinucleated cells, were the most frequent malignant vascular tumors. Hemangiopericytoma and tumors of muscle and soft connective tissue origin, alone and/or in association with tumor-like lesions, were less frequently seen. Furthermore, forty-five cases of intravascular papillary endothelial hyperplasia (IPEH), a lesion not previously reported in the urinary bladder of cattle, were also described. Bovine papillomavirus type-2 DNA was amplified in tumor samples. Forty vascular tumors were investigated by dual-labeling immunofluorescence, and, for the first time, a coexpression of E5 and platelet-derived growth factor β receptor (PDGF β R) was shown to occur. The results show that the BPV-2 E5 oncoprotein binds to the activated form of the PDGF β receptor thus playing an important role in mesenchymal as well as epithelial carcinogenesis of the urinary bladder. Furthermore, these findings demonstrate that BPV-2 infects both epithelial and mesenchymal cells.

Bovine Papillomavirus Type 2 Infection and a Series of Mesenchymal Tumors of the Urinary Bladder in Cattle

PubMed Central

Martano, Manuela; Roperto, Franco; Russo, Valeria; Borzacchiello, Giuseppe; Paciello, Orlando; Iovane, Valentina; Leonardi, Leonardo; Maiolino, Paola; Restucci, Brunella; Papparella, Serenella; Roperto, Sante

2013-01-01

This report describes the histopathology of two hundred and fifty-three mesenchymal tumors of the urinary bladder in cattle grazing on lands rich in bracken fern. Approximately 80% were hemangiomas and angiosarcomas. Hemangioma (capillary, cavernous, and large vessels) was the most frequent mesenchymal tumor and was more common than angiosarcoma. Although the appearance of endothelial cells can vary remarkably, epithelioid angiosarcomas, often containing multinucleated cells, were the most frequent malignant vascular tumors. Hemangiopericytoma and tumors of muscle and soft connective tissue origin, alone and/or in association with tumor-like lesions, were less frequently seen. Furthermore, forty-five cases of intravascular papillary endothelial hyperplasia (IPEH), a lesion not previously reported in the urinary bladder of cattle, were also described. Bovine papillomavirus type-2 DNA was amplified in tumor samples. Forty vascular tumors were investigated by dual-labeling immunofluorescence, and, for the first time, a coexpression of E5 and platelet-derived growth factor β receptor (PDGFβR) was shown to occur. The results show that the BPV-2 E5 oncoprotein binds to the activated form of the PDGFβ receptor thus playing an important role in mesenchymal as well as epithelial carcinogenesis of the urinary bladder. Furthermore, these findings demonstrate that BPV-2 infects both epithelial and mesenchymal cells. PMID:23862156

Complete treatment with partial cystectomy in giant xanthogranulomatous cystitis case imitating bladder tumor.

PubMed

Balasar, Mehmet; Sönmez, Mehmet Giray; Oltulu, Pembe; Kandemir, Abdülkadir; Kılıç, Mehmet; Gürbüz, Recai

2017-01-01

Xanthogranulomatous cystitis (XC) is a very rare chronic benign inflammatory disease of the bladder. It may cause local invasion although it is not a malign lesion and may occur together with malign lesions. It has a clinical importance as the distinction from malign lesions is difficult clinically and pathologically. Sharing a 37-year-old female case with giant XC imitating bladder tumor referring to the hospital with hematuria and stomach ache, together with current literature, we wanted to present that the disease can be treated with bladder-preserving approaches instead of radical approaches even though the mass is big in these cases. Application of basic excision and partial resection for small masses and radical cystectomy for large masses was reported in literature. We think that our case may provide a contribution to literature in treatment approach since we provided surgical cure with partial resection in a big mass with dimensions of 9 cm × 8 cm which is different from the present literature. Even though XC is a rare disease, it should be considered in prediagnosis for especially big dimensioned masses, and treatment should be planned according to the pathology result after together with cystoscopy in suitable patients.

Overexpression of HER-2 via immunohistochemistry in canine urinary bladder transitional cell carcinoma - A marker of malignancy and possible therapeutic target.

PubMed

Millanta, F; Impellizeri, J; McSherry, L; Rocchigiani, G; Aurisicchio, L; Lubas, G

2018-06-01

Transitional cell carcinoma (TCC) is the most commonly diagnosed neoplasm in the urinary bladder. Distant metastases to the regional lymph nodes, lungs, abdominal organs or bones are noted in up to 50% of dogs at time of death. Surgical excision is often not practical as TCC typically involve the trigone of the bladder and/or occurs multifocally throughout the bladder with field cancerization. Therapeutic approaches are very challenging and the requirement to evaluate alternative therapeutic protocols that may prolong survival times in dogs bearing these tumours is compelling. We assessed the immunohistochemical expression of HER-2 in 23 cases of canine TCCs of the urinary bladder and compare it with non-neoplastic urothelium in order to evaluate a rationale for targeted therapies and gene-based vaccines. HER-2 positivity was recorded in 13/23 (56%) neoplastic lesions. The receptor was significantly overexpressed in neoplastic than in non-neoplastic samples (P = .015). According to our preliminary results, it would be of interest to further evaluate the role of HER-2 in canine TCCs as a marker of malignancy and a therapeutic target for cancer vaccine and antibodies. Moreover, the significantly different overexpression of HER-2 in TCCs than in non-neoplastic urothelium further supports to investigate its role in the progression toward malignancy of non-neoplastic lesions. © 2017 John Wiley & Sons Ltd.

Xanthogranulomatous cystitis: a challenging imitator of bladder cancer.

PubMed

Ekici, Sinan; Dogan Ekici, Isin; Ruacan, Sevket; Midi, Ahmet

2010-06-29

Xanthogranulomatous cystitis is a rare, benign, chronic inflammatory disease of the bladder, mimicking malignancy with unknown etiology. Herein, we report a 57-year-old man who presented with pollakiuria, nocturia, dysuria, left flank pain, and a palpable mass on the right lower abdomen. Computerized tomography demonstrated an obstructing 10-mm stone in the lower third of the left ureter and a 6-cm solid mass on the right at the anterolateral wall of the bladder. The mass presented local perivesical invasion at the anterolateral side. Cystouretroscopy revealed a mass protruding into the bladder cavity with edematous smooth surface. Frozen section analysis of the partial cystectomy specimen could not rule out malignancy. Therefore, radical cystoprostatectomy and ureterolithotomy were performed. Histologically, fibrosis, numerous plasma cells, eosinophils, and, immunohistochemically, CD68-positive epithelioid and foamy macrophages were detected. Localized prostatic adenocarcinoma was also found. The present case of xanthogranulomatous cystitis is the 23rd to be reported in the world literature.

Factors associated with suicide in patients with genitourinary malignancies.

PubMed

Klaassen, Zachary; Jen, Rita P; DiBianco, John M; Reinstatler, Lael; Li, Qiang; Madi, Rabii; Lewis, Ronald W; Smith, Arthur M; Neal, Durwood E; Moses, Kelvin A; Terris, Martha K

2015-06-01

Approximately 70% of all suicides in patients aged >60 years are attributed to physical illness, with higher rates noted in patients with cancer. The purpose of the current study was to characterize suicide rates among patients with genitourinary cancers and identify factors associated with suicide in this specific cohort. Patients with prostate, bladder, kidney, testis, and penile cancer were identified in the Surveillance, Epidemiology, and End Results database (1988-2010). Standardized mortality ratios (SMRs) and 95% confidence intervals (95% CIs) were calculated for each anatomic site. Multivariable logistic regression models generated odds ratios (ORs) for the identification of factors associated with suicide for each malignancy. There were 2268 suicides identified among 1,239,522 individuals with genitourinary malignancies observed for 7,307,377 person-years. The SMRs for patients with cancer were 1.37 for prostate cancer (95% CI, 0.99-1.86), 2.71 for bladder cancer (95% CI, 2.02-3.62), 1.86 for kidney cancer (95% CI, 1.32-2.62), 1.23 for testis cancer (95% CI, 0.88-1.73), and 0.95 for penile cancer (95% CI, 0.65-1.35). On multivariable analysis, male sex was found to be associated with odds of suicide among patients with bladder cancer (OR, 6.63) and kidney cancer (OR, 4.98). Increasing age was associated with suicide for patients with prostate, bladder, and testis cancer (OR range, 1.03-1.06). Distant disease was associated with suicide in patients with prostate, bladder, and kidney cancer (OR range, 2.82-5.43). Among patients with prostate, bladder, and kidney cancer, African American patients were less likely to commit suicide compared with white individuals (OR range, 0.26-0.46). Suicide in patients with genitourinary malignancies poses a public health dilemma, especially among men, the elderly, and those with aggressive disease. Clinicians should be aware of risk factors for suicide in these patients. © 2015 American Cancer Society.

Optical assessment of tissue anisotropy in ex vivo distended rat bladders

NASA Astrophysics Data System (ADS)

Alali, Sanaz; Aitken, Karen J.; Shröder, Annette; Bagli, Darius J.; Alex Vitkin, I.

2012-08-01

Microstructural remodelling in epithelial layers of various hollow organs, including changes in tissue anisotropy, are known to occur under mechanical distension and during disease processes. In this paper, we analyze how bladder distension alters wall anisotropy using polarized light imaging (followed by Mueller matrix decomposition). Optical retardance values of different regions of normal rat bladders under different distension pressures are derived. Then optical coherence tomography is used to measure local bladder wall thicknesses, enabling the calculation of the tissue birefringence maps as a measure of the tissue anisotropy. Selected two-photon microscopy is also performed to better understand the compositional origins of the obtained anisotropy results. The dome region of the bladder shows maximum birefringence when the bladder is distended to high pressures, whereas the ventral remains roughly isotropic during distension. In addition, the average anisotropy direction is longitudinal, along the urethra to dome. The derived wall anisotropy trends are based on birefringence as an intrinsic property of the tissue organization independent of its thickness, to aid in understanding the structure-functions relation in healthy bladders. These new insights into the wall microstructure of ex vivo distending bladders may help improve the functionality of the artificially engineered bladder tissues.

Tissue engineering of the bladder--reality or myth? A systematic review.

PubMed

Sloff, Marije; Simaioforidis, Vasileios; de Vries, Rob; Oosterwijk, Egbert; Feitz, Wout

2014-10-01

We systematically reviewed preclinical studies in the literature to evaluate the potential of tissue engineering of the bladder. Study outcomes were compared to the available clinical evidence to assess the feasibility of tissue engineering for future clinical use. Preclinical studies of tissue engineering for bladder augmentation were identified through a systematic search of PubMed and Embase™ from January 1, 1980 to January 1, 2014. Primary studies in English were included if bladder reconstruction after partial cystectomy was performed using a tissue engineered biomaterial in any animal species, with cystometric bladder capacity as an outcome measure. Outcomes were compared to clinical studies available at http://www.clinicaltrials.gov and published clinical studies. A total of 28 preclinical studies are included, demonstrating remarkable heterogeneity in study characteristics and design. Studies in which preoperative bladder volumes were compared to postoperative volumes were considered the most clinically relevant (18 studies). Bladder augmentation through tissue engineering resulted in a normal bladder volume in healthy animals, with the influence of a cellular component being negligible. Furthermore, experiments in large animal models (pigs and dogs) approximated the desired bladder volume more accurately than in smaller species. The initial clinical experience was based on seemingly predictive healthy animal models with a promising outcome. Unfortunately these results were not substantiated in all clinical trials, revealing dissimilar outcomes in different clinical/disease backgrounds. Thus, the translational predictability of a model using healthy animals might be questioned. Through this systematic approach we present an unbiased overview of all published preclinical studies investigating the effect of bladder tissue engineering on cystometric bladder capacity. Preclinical research in healthy animals appears to show the feasibility of bladder augmentation by tissue engineering. However, in view of the disappointing clinical results based on healthy animal models new approaches should also be evaluated in preclinical models using dysfunctional/diseased bladders. This endeavor may aid in the development of clinically applicable tissue engineered bladder augmentation with satisfactory long-term outcome. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Endoscopic spray cryotherapy for genitourinary malignancies: safety and efficacy in a porcine model

PubMed Central

Power, Nicholas E.; Silberstein, Jonathan L.; Tarin, Tatum; Au, Joyce; Thorner, Daniel; Ezell, Paula; Monette, Sébastien; Fong, Yuman; Rusch, Valerie; Finley, David

2013-01-01

Objective: To examine the effects and safety of using endoscopic spray cryotherapy (ESC) on bladder, ureteral, and renal pelvis urothelium in a live porcine model. Subjects and methods: ESC treatments were systematically applied to urothelial sites in the bladder, ureter, and renal pelvis of eight female Yorkshire swine in a prospective trial. Freeze–thaw cycles ranged from 5 to 60 s/cycle for one to six cycles using a 7 French cryotherapy catheter. Tissue was evaluated histologically for treatment-related effects. Acute physiologic effects were evaluated with pulse oximetry, Doppler sonography, and postmortem findings. Results: In bladder, treatment depth was inconsistent regardless of dose, demonstrating urothelial necrosis in one, muscularis propria depth necrosis in two, and full thickness necrosis in all remaining samples. In ureter, full thickness necrosis was seen in all samples, even with the shortest spray duration (5 s/cycle for six cycles or 30 s/cycle for one cycle). Treatment to the renal pelvis was complicated by adiabatic gas expansion of liquid nitrogen to its gaseous state, resulting in high intraluminal pressures requiring venting to avoid organ perforation, even at the lowest treatment settings. At a planned dose of 5 s/cycle for six cycles of the first renal pelvis animal, treatment was interrupted by sudden and unrecoverable cardiopulmonary failure after three cycles. Repeated studies replicated this event. Ultrasound and immediate necropsy confirmed the creation of a large gaseous embolism and reproducible cardiopulmonary effects. Conclusion: ESC in a porcine urothelial treatment model results in full-thickness tissue necrosis in bladder, ureter, and renal pelvis at a minimal treatment settings of 5 s/cycle for six cycles. Adiabatic gas expansion may result in fatal pyelovenous gas embolism and collateral organ injury, as seen in both animals receiving treatment to the renal pelvis in this study. These results raise safety concerns for use of ESC as a treatment modality in urothelial tissues with current device settings. PMID:23730328

Predictive values of urinary bladder tumor markers survivin and soluble-Fas comparison with cystoscopy and bladder tumor antigen.

PubMed

Ganas, V; Kalaitzis, C; Sountoulides, P; Giannakopoulos, S; Touloupidis, S

2012-12-01

The aim of the study was to evaluate the predictive values of two novel urinary markers for bladder cancer: survivin and soluble-Fas (s-Fas). The study included 84 individuals divided in two groups. The first group contained 47 patients, who underwent transurethral bladder tumor resection and the second, control, group 20 patients with non-malignant conditions, who underwent cystoscopy and 17 health volunteers. Fresh, second morning voided urine was collected for measurement of s-Fas, survivin, BTA and for cytology. Sensitivity, specificity, positive and negative predictive values and accuracy were calculated. Bladder tumor patients had significantly higher survivin urine levels in comparison to the controls. Survivin correlated also with the tumor stage. Combination of survivin with BTA had a sensitivity of 86.4% but still lower than that of cystoscopy (97.8%). Only the specificity of the combination between survivin and BTA was higher than that of cystoscopy (86.4% and 75.6%, respectively). Survivin was a better marker for tumor detection than s-Fas and was better enough to discriminate cancer stage. Combination of survivin and BTA had a specificity of 86.4% to exclude bladder malignancy and the combination of s-Fas with survivin and BTA had a sensitivity of 93.6% to detect bladder cancer.

THE SIGNIFICANCE OF EPIDERMAL GROWTH FACTOR RECEPTOR AND SURVIVIN EXPRESSION IN BLADDER CANCER TISSUE AND URINE CYTOLOGY OF PATIENTS WITH TRANSITIONAL CELL CARCINOMA OF THE URINARY BLADDER.

PubMed

Kehinde, E O; Al-Maghrebi, M; Anim, J T; Kapila, K; George, S S; Al-Juwaiser, A; Memon, A

2013-01-01

To assess whether epidermal growth factor receptor (EGFR) and survivin immunostaining of tumour cells in urinary cytology and tissue of patients with bladder cancer has a prognostic significance. Prospective study Department of Surgery (Division of Urology), Mubarak Al-Kabeer Teaching Hospital and Faculty of Medicine, Kuwait University, Kuwait Urine cytology smears obtainedpriorto cystoscopy in patients with transitional cell carcinoma (TCC) of the bladder were immunostained for EGFR and survivin. Bladder cancer tissue resected at surgery was also immunostained for EGFR and survivin expression. Tissue expression of EGFR and survivin in TCC of the bladder was compared to their expression in urine cytology and relationship to tumour grade and stage. 178 patients were studied (43 newly diagnosed bladder cancer, 58 with recurrent TCC and 77 in disease remission). Twenty five patients with normal urothelium served as controls. The mean sensitivity of urine cytology, tissue survivin immunohistochemistry (IHC) and tissue EGFR IHC was 30.5%, 62% and 59% respectively. The corresponding mean specificity was 95%, 79% and 38% respectively. For grades 1, 2 and 3 bladder tumors, tissue expression positivity for EGFR was 47.8%, 92.9%, 100% and for tissue survivin it was 27.8%, 18.2% and 33.3% respectively. For grades 1, 2 and 3 bladder tumors, urine expression positivity for EGFR was 35.7%, 40% and 67.7% and for urine survivin it was 8.3%, 42.9% and 33.3% respectively. Positive EGFR immunostaining of urine cytology specimen or tumour tissue increases with histological grade of TCC of the bladder. Survivin expression is less consistent in both urine cytology specimen and tissue samples. EGFR immunostaining may provide a useful tool in the grading of bladder TCC and aid in the selection of patients that may benefit from administration of EGFR inhibitors.

Features of proteasome functioning in malignant tumors

NASA Astrophysics Data System (ADS)

Kondakova, I. V.; Spirina, L. V.; Shashova, E. E.; Kolegova, E. S.; Slonimskaya, E. M.; Kolomiets, L. A.; Afanas'ev, S. G.; Choinzonov, Y. L.

2017-09-01

Proteasome ubiquitin system is the important system of intracellular proteolysis. The activity of the proteasomes may undergo changes during cancer development. We studied the chymotrypsin-like activity of proteasomes, their subunit composition, and their association with tumor stage in breast cancer, head and neck squamous cell carcinoma, endometrial cancer, renal cancer, bladder cancer, stomach cancer, ovarian cancer, and colorectal cancer. The increase in chymotrypsin-like activity of proteasomes and decrease in total proteasome pool compared with adjacent tissues were shown in all malignant tumors excluding kidney cancer. The increase in chymotrypsin-like activity of proteasomes was found in primary tumors with all types of metastasis: lymphogenous of head and neck squamous cell carcinoma, intraperitoneal metastasis of ovarian cancer, hematogenous metastasis colorectal cancer. The exception was kidney cancer, in which there was a decrease in chymotrypsin-like activity with distant metastasis.

Bladder perivascular epithelioid cell tumor (PEComa): a case report and literature review.

PubMed

Sarti, Alessandra; Rubilotta, Emanuele; Balzarro, Matteo; Cerruto, Maria Angela; Brunelli, Matteo; Artibani, Walter

2015-01-01

Perivascular epithelioid cell tumors (PEComa) are a very uncommon mesenchymal cancer with uncertain malignant potential. A computerized research on Pub Med was performed regarding bladder PEComa. We evaluated the literature cases and described a case of bladder PEComa. PEComa of the bladder is a very rare neoplasm and only 15 cases have been reported so far. Bladder PEComa involves young subjects of both genders, mostly under 40 years of age. Surgical treatment (partial or radical cystectomy) is the most common management.A long-term follow-up and larger series are required to better understand the best clinical approach to bladder PEComa.

Photodynamic management of bladder cancer

NASA Astrophysics Data System (ADS)

Johansson, A.; Stepp, H.; Beyer, W.; Pongratz, T.; Sroka, R.; Bader, M.; Kriegmair, M.; Zaak, D.; Waidelich, R.; Karl, A.; Hofstetter, A.; Stief, C.; Baumgartner, R.

2009-06-01

Bladder cancer (BC) is among the most expensive oncological diseases. Any improvement in diagnosis or therapy carries a high potential for reducing costs. Fluorescence cystoscopy relies on a selective formation of Protoporphyrin IX (PpIX) or more general photoactive porphyrins (PAP) in malignant urothelium upon instillation of 5-aminolevulinic acid (5-ALA) or its hexyl-derivative h-ALA. Fluorescence cystoscopy equipment has been developed with the aim to compensate for the undesired distortion caused by the tissue optical properties by displaying the red fluorescence simultaneously with the backscattered blue light. Many clinical studies proved a high sensitivity in detecting flat carcinoma in situ and small papillary malignant tumours. As a result, recurrence rates were significantly decreased in most studies. The limitation lies in a low specificity, caused by false positive findings at inflamed bladder wall. Optical coherence tomography (OCT) is currently being investigated as a promising tool to overcome this limitation. H-ALA-PDT (8 or 16 mM h-ALA in 50 ml instillation for 1-2 h, white light source, catheter applicator) has recently been investigated in a phase I study. 17 patients were applied 100 J/cm2 (3 patients received incrementing doses of 25 - 50 - 100 J/cm2) during approx. 1 hour irradiation time in 3 sessions, 6 weeks apart. PDT was performed without any technical complications. Complete photobleaching of the PpIX-fluorescence, as intended, could be achieved in 43 of 45 PDT-sessions receiving 100 J/cm2. The most prominent side effects were postoperative urgency and bladder pain, all symptoms being more severe after 16 mM h-ALA. Preliminary evaluation shows complete response assessed at 3 months after the third PDT-session (i.e. 6 months after first treatment) in 9 of 12 patients. 2 of these patients were free of recurrence until final follow-up at 84 weeks.

Cytological Diagnosis of Small Cell Carcinoma of Urinary Bladder in a Patient with CLL

PubMed Central

Şimşek, Gülçin Güler; Güreşçi, Servet; Oğuz, Ural; Ünsal, Ali

2014-01-01

Small cell carcinoma of the urinary bladder (SCCUB) is an extremely rare bladder malignancy characterized by an aggressive clinical behavior. So, it is important to diagnose this high grade disease by urinary cytology. We report a case of SCCUB in an old man with chronic lymphocytic leukemia (CLL) in remission, while bladder tumor was diagnosed by cytology. With this article, we aimed to review and to update the literature concerning this tumor. PMID:24518979

SiRNA knockdown of the DEK nuclear protein mRNA enhances apoptosis and chemosensitivity of canine transitional cell carcinoma cells.

PubMed

Yamazaki, Hiroki; Iwano, Tomomi; Otsuka, Saori; Kagawa, Yumiko; Hoshino, Yuki; Hosoya, Kenji; Okumura, Masahiro; Takagi, Satoshi

2015-04-01

Transitional cell carcinoma (TCC) in dogs is an aggressive malignant neoplasm, originating in the epithelium of the urinary bladder. The DEK nuclear protein is overexpressed in several types of human bladder cancer, where it is involved in chromatin reconstruction, gene transcription and apoptosis. Since DEK represents a potential therapeutic target for canine TCC, this study was designed to investigate DEK expression in canine TCC and to determine the effects of DEK mRNA silencing on TCC cells in vitro. The gene expression profiles of seven selected cancer-associated genes was assessed in four canine TCC cell lines and expression of DEK protein was evaluated in bladder tissue biopsies from healthy dogs and those affected with cystitis or TCC. After transfection of four canine TCC cell lines with DEK-specific or scrambled siRNA, annexin V staining was performed to evaluate apoptosis, and methylthiazole tetrazolium assays were performed to assess both cell viability and sensitivity to carboplatin. DEK mRNA expression was relatively high in canine TCC cells and expression of the DEK protein was significantly greater in TCC tumours compared with the other tissue samples. After transfection with DEK-specific siRNA, apoptosis, cell growth inhibition, and enhanced sensitivity to carboplatin were observed in all TCC cells assessed. These research findings suggest that DEK could be a potential therapeutic target for canine TCC. Copyright © 2015 Elsevier Ltd. All rights reserved.

The emerging role of the androgen receptor in bladder cancer.

PubMed

Lombard, Alan P; Mudryj, Maria

2015-10-01

Men are three to four times more likely to get bladder cancer than women. The gender disparity characterizing bladder cancer diagnoses has been investigated. One hypothesis is that androgen receptor (AR) signaling is involved in the etiology and progression of this disease. Although bladder cancer is not typically described as an endocrine-related malignancy, it has become increasingly clear that AR signaling plays a role in bladder tumors. This review summarizes current findings regarding the role of the AR in bladder cancer. We discuss work demonstrating AR expression in bladder cancer and its role in promoting formation and progression of tumors. Additionally, we discuss the therapeutic potential of targeting the AR in this disease. © 2015 Society for Endocrinology.

Xanthogranulomatous Cystitis: A Challenging Imitator of Bladder Cancer

PubMed Central

Ekici, Sinan; Dogan Ekici, Isin; Ruacan, Sevket; Midi, Ahmet

2010-01-01

Xanthogranulomatous cystitis is a rare, benign, chronic inflammatory disease of the bladder, mimicking malignancy with unknown etiology. Herein, we report a 57-year-old man who presented with pollakiuria, nocturia, dysuria, left flank pain, and a palpable mass on the right lower abdomen. Computerized tomography demonstrated an obstructing 10-mm stone in the lower third of the left ureter and a 6-cm solid mass on the right at the anterolateral wall of the bladder. The mass presented local perivesical invasion at the anterolateral side. Cystouretroscopy revealed a mass protruding into the bladder cavity with edematous smooth surface. Frozen section analysis of the partial cystectomy specimen could not rule out malignancy. Therefore, radical cystoprostatectomy and ureterolithotomy were performed. Histologically, fibrosis, numerous plasma cells, eosinophils, and, immunohistochemically, CD68-positive epithelioid and foamy macrophages were detected. Localized prostatic adenocarcinoma was also found. The present case of xanthogranulomatous cystitis is the 23rd to be reported in the world literature. PMID:20602075

Bladder Cancer Treatment Response Assessment in CT using Radiomics with Deep-Learning.

PubMed

Cha, Kenny H; Hadjiiski, Lubomir; Chan, Heang-Ping; Weizer, Alon Z; Alva, Ajjai; Cohan, Richard H; Caoili, Elaine M; Paramagul, Chintana; Samala, Ravi K

2017-08-18

Cross-sectional X-ray imaging has become the standard for staging most solid organ malignancies. However, for some malignancies such as urinary bladder cancer, the ability to accurately assess local extent of the disease and understand response to systemic chemotherapy is limited with current imaging approaches. In this study, we explored the feasibility that radiomics-based predictive models using pre- and post-treatment computed tomography (CT) images might be able to distinguish between bladder cancers with and without complete chemotherapy responses. We assessed three unique radiomics-based predictive models, each of which employed different fundamental design principles ranging from a pattern recognition method via deep-learning convolution neural network (DL-CNN), to a more deterministic radiomics feature-based approach and then a bridging method between the two, utilizing a system which extracts radiomics features from the image patterns. Our study indicates that the computerized assessment using radiomics information from the pre- and post-treatment CT of bladder cancer patients has the potential to assist in assessment of treatment response.

Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)

ClinicalTrials.gov

2018-06-25

Advanced Malignant Solid Neoplasm; Bladder Carcinoma; Breast Carcinoma; Cervical Carcinoma; Colon Carcinoma; Colorectal Carcinoma; Endometrial Carcinoma; Esophageal Carcinoma; Gastric Carcinoma; Glioma; Head and Neck Carcinoma; Kidney Carcinoma; Liver and Intrahepatic Bile Duct Carcinoma; Lung Carcinoma; Lymphoma; Malignant Uterine Neoplasm; Melanoma; Ovarian Carcinoma; Pancreatic Carcinoma; Plasma Cell Myeloma; Prostate Carcinoma; Rectal Carcinoma; Recurrent Bladder Carcinoma; Recurrent Breast Carcinoma; Recurrent Cervical Carcinoma; Recurrent Colon Carcinoma; Recurrent Colorectal Carcinoma; Recurrent Esophageal Carcinoma; Recurrent Gastric Carcinoma; Recurrent Glioma; Recurrent Head and Neck Carcinoma; Recurrent Liver Carcinoma; Recurrent Lung Carcinoma; Recurrent Lymphoma; Recurrent Malignant Solid Neoplasm; Recurrent Melanoma; Recurrent Ovarian Carcinoma; Recurrent Pancreatic Carcinoma; Recurrent Plasma Cell Myeloma; Recurrent Prostate Carcinoma; Recurrent Rectal Carcinoma; Recurrent Skin Carcinoma; Recurrent Thyroid Gland Carcinoma; Recurrent Uterine Corpus Carcinoma; Refractory Lymphoma; Refractory Malignant Solid Neoplasm; Refractory Plasma Cell Myeloma; Skin Carcinoma; Thyroid Gland Carcinoma; Uterine Corpus Cancer

Understanding the Role of Non-Coding RNAs in Bladder Cancer: From Dark Matter to Valuable Therapeutic Targets

PubMed Central

Pop-Bica, Cecilia; Gulei, Diana; Cojocneanu-Petric, Roxana; Braicu, Cornelia; Petrut, Bogdan; Berindan-Neagoe, Ioana

2017-01-01

The mortality and morbidity that characterize bladder cancer compel this malignancy into the category of hot topics in terms of biomolecular research. Therefore, a better knowledge of the specific molecular mechanisms that underlie the development and progression of bladder cancer is demanded. Tumor heterogeneity among patients with similar diagnosis, as well as intratumor heterogeneity, generates difficulties in terms of targeted therapy. Furthermore, late diagnosis represents an ongoing issue, significantly reducing the response to therapy and, inevitably, the overall survival. The role of non-coding RNAs in bladder cancer emerged in the last decade, revealing that microRNAs (miRNAs) may act as tumor suppressor genes, respectively oncogenes, but also as biomarkers for early diagnosis. Regarding other types of non-coding RNAs, especially long non-coding RNAs (lncRNAs) which are extensively reviewed in this article, their exact roles in tumorigenesis are—for the time being—not as evident as in the case of miRNAs, but, still, clearly suggested. Therefore, this review covers the non-coding RNA expression profile of bladder cancer patients and their validated target genes in bladder cancer cell lines, with repercussions on processes such as proliferation, invasiveness, apoptosis, cell cycle arrest, and other molecular pathways which are specific for the malignant transformation of cells. PMID:28703782

Understanding the Role of Non-Coding RNAs in Bladder Cancer: From Dark Matter to Valuable Therapeutic Targets.

PubMed

Pop-Bica, Cecilia; Gulei, Diana; Cojocneanu-Petric, Roxana; Braicu, Cornelia; Petrut, Bogdan; Berindan-Neagoe, Ioana

2017-07-13

The mortality and morbidity that characterize bladder cancer compel this malignancy into the category of hot topics in terms of biomolecular research. Therefore, a better knowledge of the specific molecular mechanisms that underlie the development and progression of bladder cancer is demanded. Tumor heterogeneity among patients with similar diagnosis, as well as intratumor heterogeneity, generates difficulties in terms of targeted therapy. Furthermore, late diagnosis represents an ongoing issue, significantly reducing the response to therapy and, inevitably, the overall survival. The role of non-coding RNAs in bladder cancer emerged in the last decade, revealing that microRNAs (miRNAs) may act as tumor suppressor genes, respectively oncogenes, but also as biomarkers for early diagnosis. Regarding other types of non-coding RNAs, especially long non-coding RNAs (lncRNAs) which are extensively reviewed in this article, their exact roles in tumorigenesis are-for the time being-not as evident as in the case of miRNAs, but, still, clearly suggested. Therefore, this review covers the non-coding RNA expression profile of bladder cancer patients and their validated target genes in bladder cancer cell lines, with repercussions on processes such as proliferation, invasiveness, apoptosis, cell cycle arrest, and other molecular pathways which are specific for the malignant transformation of cells.

Risk of second primary malignancies among cancer survivors in the United States, 1992 through 2008.

PubMed

Donin, Nicholas; Filson, Christopher; Drakaki, Alexandra; Tan, Hung-Jui; Castillo, Alex; Kwan, Lorna; Litwin, Mark; Chamie, Karim

2016-10-01

In the current study, the authors attempted to describe the incidence, most common sites, and mortality of second primary malignancies among survivors of common cancers. The authors identified patients aged ≥18 years who were diagnosed with a primary malignancy from the 10 most common cancer sites (prostate, breast, lung, colon, rectum, bladder, uterus, kidney, melanoma, and non-Hodgkin lymphoma) between 1992 and 2008 from Surveillance, Epidemiology, and End Results data. Factors associated with the incidence of second primary malignancies were explored using bivariable and multivariable models, and mortality attributable to first and second primary malignancies was examined. A cohort of 2,116,163 patients was identified, 170,865 of whom (8.1%) developed a second primary malignancy. Survivors of bladder cancer had the highest risk of developing a second cancer. In a multivariable model controlling for age, race, tumor grade, stage of disease, marital status, educational level, and income, a history of non-Hodgkin lymphoma (hazard ratios of 2.70 and 2.88, respectively, for men and women) and bladder cancer (hazard ratios of 1.88 and 1.66, respectively, for men and women) predicted the highest risk of developing a second cancer. For patients with 2 incident cancers, 13% died of their initial cancer, but greater than one-half (55%) died of their second primary malignancy. Lung cancer was the cause of death in 12% of patients with 2 incident cancers. Nearly 1 in 12 patients diagnosed with a common cancer developed a second malignancy, the most common of which was lung cancer. Greater than one-half of patients with 2 incident cancers died of their secondary malignancy. The findings from the current study may inform care strategies among cancer survivors. Cancer 2016;122:3075-3086. © 2016 American Cancer Society. © 2016 American Cancer Society.

Metastatic signet-ring cell cancer of the bladder responding to chemotherapy with capecitabine: case report and review of literature

PubMed Central

Michels, Jorg; Barbour, Sean; Cavers, Douglas; Chi, Kim N.

2010-01-01

Signet-ring cell cancers deriving from the bladder are rare entities and usually present with advanced incurable disease and associated poor outlook. No standard effective chemotherapeutic option has been described largely due to the rarity of this malignancy. We report a case of a patient with metastatic bladder cancer, signet-ring cell variant. The patient progressed rapidly on standard first-line bladder cancer chemotherapy with gemcitabine and carboplatin. He responded well to second-line capecitabine with a clinically meaningful progression-free survival. PMID:20368884

Elevated expression of matrix metalloproteinase-9 is associated with bladder cancer pathogenesis.

PubMed

Wu, Gong-Jin; Bao, Jun-Sheng; Yue, Zhong-Jin; Zeng, Fan-Chang; Cen, Song; Tang, Zheng-Yan; Kang, Xin-Li

2018-01-01

This study investigated the association between abnormal matrix metalloproteinase-9 (MMP-9) expression and bladder cancer (BC) development. In a retrospective analysis, this study used tissue samples derived from 92 patients pathologically diagnosed with BC (experimental group), who were hospitalized between September 2012 and June 2014 at the Urinary Surgery of Department of Urology, Lanzhou University Second Hospital. As controls (control group), 63 normal pericancerous bladder mucosal tissues (3 cm distant form edge of BC foci) with confirmed pathology were selected from the same time period. Immunohistochemistry was employed to detect MMP-9 protein expression in the tissues and enzyme-linked immunosorbent assay was performed to measure MMP-9 protein levels in tissue samples of patients and control subjects. Finally, a meta-analysis was conducted to understand the overall impact of MMP-9 on BC pathogenesis. STATA 12.0 software (Stata Corp, College Station, TX, USA) was used for all statistical analyses. The MMP-9 positive expression rate in tissue samples and MMP-9 levels were significantly greater in the experimental group compared to the control group (both P < 0.001). The frequency of MMP-9 positive status showed statistically significant differences between G1 (low-grade) and G3 (high-grade) (P < 0.001), between G2 and G3 (P < 0.05), and between G1/G2 and G3 (P = 0.001). Our meta-analysis findings provided further evidence that MMP-9 positive expression status and MMP-9 levels in the experimental group were significantly higher than the control group (positive expressions: Odds ratio [OR] = 18.59, 95% confidence interval [95% CI] = 11.63-29.71, P < 0.001; expression levels: Standard mean difference = 1.51, 95%CI = 0.63-2.39, P = 0.001). The positive expression status of MMP-9 was notably lower in G1/G2 compared to G3 (OR = 0.24, 95%CI = 0.15-0.36, P < 0.001). Our study demonstrated that both positive expression status in tumor tissue and expression levels of MMP-9 are significantly elevated in BC patients and correlate with disease progression. Thus, MMP-9 can serve as a biomarker to determine the degree of BC malignancy.

Spectroscopic analysis of bladder cancer tissues using Fourier transform infrared spectroscopy

NASA Astrophysics Data System (ADS)

Al-Muslet, Nafie A.; Ali, Essam E.

2012-03-01

Bladder cancer is one of the most common cancers in Africa. It takes several days to reach a diagnosis using histological examinations of specimens obtained by endoscope, which increases the medical expense. Recently, spectroscopic analysis of bladder cancer tissues has received considerable attention as a diagnosis technique due to its sensitivity to biochemical variations in the samples. This study investigated the use of Fourier transform infrared (FTIR) spectroscopy to analyze a number of bladder cancer tissues. Twenty-two samples were collected from 11 patients diagnosed with bladder cancer from different hospitals without any pretreatment. From each patient two samples were collected, one normal and another cancerous. FTIR spectrometer was used to differentiate between normal and cancerous bladder tissues via changes in spectra of these samples. The investigations detected obvious changes in the bands of proteins (1650, 1550 cm-1), lipids (2925, 2850 cm-1), and nucleic acid (1080, 1236 cm-1). The results show that FTIR spectroscopy is promising as a rapid, accurate, nondestructive, and easy to use alternative method for identification and diagnosis of bladder cancer tissues.

In Vivo Demonstration of PSMA Expression in Adenocarcinoma Urinary Bladder Using 68Ga-PSMA 11 PET/CT.

PubMed

Roy, Shambo Guha; Parida, Girish Kumar; Tripathy, Sarthak; Singhal, Abhinav; Tripathi, Madhavi; Bal, Chandrasekhar

2017-07-01

In vitro and in vivo studies have demonstrated prostate-specific membrane antigen (PSMA) expression in various malignant and benign tumors. Based on the recent immunohistochemical study showing PSMA expression in adenocarcinoma of urinary bladder, we hypothesized that PSMA expression in adenocarcinoma of urinary bladder can be demonstrated in vivo using Ga-PSMA 11 PET/CT. We present a man with exstrophy bladder, presenting with adenocarcinoma urinary bladder referred for staging PET/CT. Both F-FDG and Ga-PSMA-11 PET/CT were done, which showed PSMA expression in the primary tumor as well as metastatic lymph nodes.

Metastasis of Non-Muscle-Invasive Bladder Cancer Into the Thyroid Gland: A Literature Review Accompanied by a Rare Case

PubMed Central

Tuncer, Murat; Faydaci, Gokhan; Altin, Gokhan; Kibar, Sermin; Sanli, Arif; Bilgici, Dilek

2014-01-01

Bladder cancer is the most prevalent malignancy of the urinary tract. About 90% of bladder cancers are urothelial carcinomas. Seventy percent of cases newly diagnosed are superficial diseases; roughly 30% of newly diagnosed cases are muscle-invasive metastatic diseases. Bladder urothelial carcinoma primarily metastasizes into regional lymph nodes and then into liver, lung, mediastinum, bone, and adrenal gland. In our case, non-muscle-invasive bladder cancer metastasized into the bone, mediastinum, iliac lymph node, and adrenal and thyroid glands. This is the first reported case in the current literature in which urothelial carcinoma metastasized into the thyroid gland. PMID:24648880

Chromium in urothelial carcinoma of the bladder.

PubMed

Golabek, Tomasz; Socha, Katarzyna; Kudelski, Jacek; Darewicz, Barbara; Markiewicz-Zukowska, Renata; Chlosta, Piotr; Borawska, Maria

2017-12-23

Many epidemiological and experimental studies report a strong role of chemical carcinogens in the etiology of bladder cancer. However, the involvement of heavy metals in tumourigenesis of urothelial carcinoma of the bladder has been poorly investigated. Therefore, the aim of this study was to examine the relationship between chromium (Cr) and bladder cancer. Chromium concentration in two 36-sample series of bladder cancer tissue and sera from patients with this neoplasm were matched with those of a control group. The amount of trace elements in every tissue sample was determined using atomic absorption spectrometry. This was correlated with tumour stage. While the median chromium concentration levels reached statistically higher values in the bladder cancer tissue, compared with the non-cancer tissue (99.632ng/g and 33.144ng/g, respectively; p<0.001), the median Cr levels in the sera of the patients with this carcinoma showed no statistical difference when compared to those of the control group (0.511μg/l and 0.710μg/l, respectively; p=0.408). The median levels of Cr in the bladder tissue, depending on the stage of the tumour, compared with the tissue without the neoplasm, observed the same relationship for both non-muscle invasive and muscle-invasive tumours (p<0.001 and p<0.01, respectively). This study shows that patients with urothelial carcinoma of the bladder had higher tissue Cr levels than people without tumour, while no difference was found in the Cr serum levels between the two groups of patients under investigation.

Spotlight on atezolizumab and its potential in the treatment of advanced urothelial bladder cancer.

PubMed

Aydin, Ahmet Murat; Woldu, Solomon L; Hutchinson, Ryan C; Boegemann, Martin; Bagrodia, Aditya; Lotan, Yair; Margulis, Vitaly; Krabbe, Laura-Maria

2017-01-01

Metastatic urothelial carcinoma of the bladder is an aggressive malignancy with poor prognosis, reflecting a lack of effective systemic therapies. The current standard of care includes multiagent platinum-based chemotherapy; however a majority of patients do not respond to treatment and most eventually succumb to disease. Recently, renewed interest in immunotherapy in the form of immune-checkpoint inhibition has gained widespread attention for a number of malignancies. Atezolizumab, an anti-PDL1 antibody, has been shown to be effective in a subset of patients previously treated with or unfit for platinum-based chemotherapy, and has shown durable responses with a good tolerability profile. We review the mechanism of action and clinical evidence of atezolizumab for metastatic urothelial bladder cancer, and discuss this drug within the context of ongoing developments in this dynamic field of immunooncology.

Spotlight on atezolizumab and its potential in the treatment of advanced urothelial bladder cancer

PubMed Central

Aydin, Ahmet Murat; Woldu, Solomon L; Hutchinson, Ryan C; Boegemann, Martin; Bagrodia, Aditya; Lotan, Yair; Margulis, Vitaly; Krabbe, Laura-Maria

2017-01-01

Metastatic urothelial carcinoma of the bladder is an aggressive malignancy with poor prognosis, reflecting a lack of effective systemic therapies. The current standard of care includes multiagent platinum-based chemotherapy; however a majority of patients do not respond to treatment and most eventually succumb to disease. Recently, renewed interest in immunotherapy in the form of immune-checkpoint inhibition has gained widespread attention for a number of malignancies. Atezolizumab, an anti-PDL1 antibody, has been shown to be effective in a subset of patients previously treated with or unfit for platinum-based chemotherapy, and has shown durable responses with a good tolerability profile. We review the mechanism of action and clinical evidence of atezolizumab for metastatic urothelial bladder cancer, and discuss this drug within the context of ongoing developments in this dynamic field of immunooncology. PMID:28331342

PDT for malignant tumors: a clinical analysis of 152 cases

NASA Astrophysics Data System (ADS)

Zhuang, Shi-Zhang; Wang, Yun-Zhen; Li, Xin; Zhang, Changjun; Wang, Jian-Zhao; Zhang, Da-Ren

1993-03-01

Hematoporphyrin derivative (HPD) laser photodynamic therapy (PDT) was applied for the patients of 152 cases of malignant tumors, including tumors of the lip, tongue, esophagus, urinary bladder, skin, larynx, vagina, etc. Since early 1981 good results have been obtained.

Bladder Cancer in HIV-infected Adults: An Emerging Issue? Case-Reports and Systematic Review.

PubMed

Chawki, Sylvain; Ploussard, Guillaume; Montlahuc, Claire; Verine, Jérome; Mongiat-Artus, Pierre; Desgrandchamps, François; Molina, Jean-Michel

2015-01-01

Non-AIDS-related malignancies now represent a frequent cause of death among HIV-infected patients. Albeit bladder cancer is one of the most common malignancies worldwide, it has been rarely reported among HIV-infected patients. We wished to assess the prevalence and characteristics of bladder cancer in HIV-infected patients. We conducted a single center retrospective study from 1998 to 2013 in a university hospital in Paris. Cases of bladder cancer among HIV-infected patients were identified using the electronic records of the hospital database and of the HIV-infected cohort. Patient characteristics and outcomes were retrieved from patients charts. A systematic review of published cases of bladder cancers in patients with HIV-infection was also performed. During the study period we identified 15 HIV-infected patients (0.2% of the cohort) with a bladder cancer. Patients were mostly men (73%) and smokers (67%), with a median age of 56 years at cancer diagnosis. Bladder cancer was diagnosed a median of 14 years after HIV-infection. Most patients were on ART (86%) with median current and nadir CD4 cell counts of 506 and 195 cells/mm3, respectively. Haematuria (73%) was the most frequent presenting symptom and HPV-associated lesions were seen in 6/10 (60%) patients. Histopathology showed transitional cell carcinoma in 80% and a high proportion of tumors with muscle invasion (47%) and high histologic grade (73%). One-year survival rate was 74.6%. The systematic review identified 13 additional cases of urothelial bladder cancers which shared similar features. Bladder cancers in HIV-infected patients remain rare but may occur in relatively young patients with a low nadir CD4 cell count, have aggressive pathological features and can be fatal.

[Primary upper urinary tract tumors and subsequent location in the bladder].

PubMed

Azémar, M-D; Audouin, M; Revaux, A; Misraï, V; Comperat, E; Bitker, M-O; Chartier-Kastler, E; Richard, F; Cussenot, O; Rouprêt, M

2009-10-01

The urothelium is the epithelium that lines the upper and lower urinary tract. Over 95% of urothelial carcinomas are derived from urothelium. They can be located in the lower tract (bladder, urethra) or upper tract (pyelocaliceal cavities, ureter). Urothelial carcinomas are the fourth most common tumours after prostate (or breast) cancer, lung cancer and colorectal cancer. On one hand, bladder tumours account for 90-95% of urothelial carcinomas. It is the most common malignancy of the urinary tract and the second most common malignancy of the urogenital tract after prostate cancer. It accounts for 5-10% of all cancers diagnosed each year in Europe. On the other hand, upper urinary tract urothelial cell carcinomas (UUT-UCC) are scarce and account for only 5-10% of urothelial carcinomas. Recurrence in the bladder after primary UUT-UCC occurs in 15-50% of UUT-UCC. Differences in treatment modalities of the primary UUT-UCC do not play a key role in the subsequent appearance of a bladder recurrence. However, others factors have been described such as stage and location in the upper tract of the primary tumour or upper tract tumour multifocality. Previous history of bladder tumour is also associated with the risk that another tumour arises in the bladder subsequently. However, it becomes difficult to distinguish between natural history of bladder tumour and evolution of UUT-UCC in these cases. In most cases, bladder cancer occurs in the first two years after UUT-UCC management. Surveillance protocol is based on cystoscopy and on urinary cytology during at least every three months for two years. Current surveillance regimen have a low level of evidence considering the paucity of UUT-UCC.

Inhibition of long non-coding RNA UCA1 by CRISPR/Cas9 attenuated malignant phenotypes of bladder cancer.

PubMed

Zhen, Shuai; Hua, Ling; Liu, Yun-Hui; Sun, Xiao-Min; Jiang, Meng-Meng; Chen, Wei; Zhao, Le; Li, Xu

2017-02-07

CRISPR/Cas9 is a novel and effective genome editing technique, but its application is not widely expanded to manipulate long non-coding RNA (lncRNA) expression. The lncRNA urothelial carcinoma-associated 1 (UCA1) is upregulated in bladder cancer and promotes the progression of bladder cancer. Here, we design gRNAs specific to UCA1 and construct CRISPR/Cas9 systems targeting UCA1. Single CRISPR/Cas9-UCA1 can effectively inhibit UCA1 expression when transfected into 5637 and T24 bladder cancer cells, while the combined transfection of the two most effective CRISPR/Cas9-UCA1s can generate more satisfied inhibitory effect. CRISPR/Cas9-UCA1s attenuate UCA1 expression via targeted genome-specific DNA cleavage, resulting in the significant inhibition of cell proliferation, migration and invasion in vitro and in vivo. The mechanisms associated with the inhibitory effect of CRISPR/Cas9-UCA1 on malignant phenotypes of bladder cancer are attributed to the induction of cell cycle arrest at G1 phase, a substantial increase of apoptosis, and an enhanced activity of MMPs. Additionally, urinary UCA1 can be used as a non-invasive diagnostic marker for bladder cancer as revealed by a meta-analysis. Collectively, our data suggest that CRISPR/Cas9 technique can be used to down-modulate lncRNA expression, and urinary UCA1 may be used as a non-invasive marker for diagnosis of bladder cancer.

Association of BDNF and BMPR1A with clinicopathologic parameters in benign and malignant gallbladder lesions

PubMed Central

2013-01-01

Background Neurotrophic factors such as brain derived neurotrophic factor (BDNF) are synthesized in a variety of neural and non-neuronal cell types and regulate survival, proliferation and apoptosis. In addition, bone morphogenetic proteins (BMPs) inhibit the proliferation of pulmonary large carcinoma cells bone morphogenetic protein receptor, type IA (BMPR1A). Little is known about the expression of BDNF or BMPR1A in malignant gall bladder lesions. This study was to evaluate BDNF and BMPR1A expression and evaluate the clinicopathological significance in benign and malignant lesions of the gallbladder. Methods The BDNF and BMPR1A expression of gallbladder adenocarcinoma, peritumoral tissues, adenoma, polyp and chronic cholecystitis were Immunohistochemically determined. Results BDNF expression was significantly higher in gallbladder adenocarcinoma than in peritumoral tissues, adenoma, polyps and chronic cholecystitis samples. However, BMPR1A expression was significantly lower in gallbladder adenocarcinoma than in peritumoral tissues, adenomas, polyps and chronic cholecystitis tissues. The specimens with increased expression of BDNF in the benign lesions exhibited moderate- or severe-dysplasia of gallbladder epithelium. BDNF expression was significantly lower in well-differentiated adenocarcinomas with maximum tumor diameter <2 cm, no metastasis to lymph nodes, and no invasion of regional tissues compared to poorly-differentiated adenocarcinomas with maximal tumor diameter >2 cm, metastasis of lymph node, and invasiveness of regional tissues in gallbladder adenocarcinoma. BMPR1A expression were significantly higher in the well-differentiated adenocarcinoma with maximal tumor diameter <2 cm, no metastasis of lymph node, and no invasion of regional tissues compared to poorly-differentiated adenocarcinomas with maximal tumor diameter >2 cm, metastasis of lymph node, and invasiveness of regional tissues in gallbladder. Univariate Kaplan-Meier analysis indicated increased expression of BDNF or decreased expression of BMPR1A was associated with decreased disease specific survival (DSS) rates. Similarly, multivariate Cox regression analysis showed increased expression of BDNF or decreased expression of BMPR1A are independent predictors of poor DSS rates in gallbladder adenocarcinoma. Conclusions In gallbladder malignancies, the increased expression of BDNF and decreased expression of BMPR1A were associated with increased risk of metastasis, regional invasion and mortality. They might serve as novel indicators of gallbladder adenocarcinoma outcomes, which may prove valuable for the development of personalized therapeutic paradigms. PMID:23531103

Transcriptome Profiling of a Multiple Recurrent Muscle-Invasive Urothelial Carcinoma of the Bladder by Deep Sequencing

PubMed Central

Zhang, Shufang; Liu, Yanxuan; Liu, Zhenxiang; Zhang, Chong; Cao, Hui; Ye, Yongqing; Wang, Shunlan; Zhang, Ying'ai; Xiao, Sifang; Yang, Peng; Li, Jindong; Bai, Zhiming

2014-01-01

Urothelial carcinoma of the bladder (UCB) is one of the commonly diagnosed cancers in the world. The UCB has the highest rate of recurrence of any malignancy. A genome-wide screening of transcriptome dysregulation between cancer and normal tissue would provide insight into the molecular basis of UCB recurrence and is a key step to discovering biomarkers for diagnosis and therapeutic targets. Compared with microarray technology, which is commonly used to identify expression level changes, the recently developed RNA-seq technique has the ability to detect other abnormal regulations in the cancer transcriptome, such as alternative splicing. In this study, we performed high-throughput transcriptome sequencing at ∼50× coverage on a recurrent muscle-invasive cisplatin-resistance UCB tissue and the adjacent non-tumor tissue. The results revealed cancer-specific differentially expressed genes between the tumor and non-tumor tissue enriched in the cell adhesion molecules, focal adhesion and ECM-receptor interaction pathway. Five dysregulated genes, including CDH1, VEGFA, PTPRF, CLDN7, and MMP2 were confirmed by Real time qPCR in the sequencing samples and the additional eleven samples. Our data revealed that more than three hundred genes showed differential splicing patterns between tumor tissue and non-tumor tissue. Among these genes, we filtered 24 cancer-associated alternative splicing genes with differential exon usage. The findings from RNA-Seq were validated by Real time qPCR for CD44, PDGFA, NUMB, and LPHN2. This study provides a comprehensive survey of the UCB transcriptome, which provides better insight into the complexity of regulatory changes during recurrence and metastasis. PMID:24622401

Noninvasive identification of bladder cancer with sub-surface backscattered light

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bigio, I.J.; Mourant, J.R.; Boyer, J.

1994-02-01

A non-invasive diagnostic tool that could identify malignancy in situ and in real time would have a major impact on the detection and treatment of cancer. We have developed and are testing early prototypes of an optical biopsy system (OBS) for detection of cancer and other tissue pathologies. The OBS invokes a unique approach to optical diagnosis of tissue pathologies based on the elastic scattering properties, over a wide range of wavelengths, of the microscopic structure of the tissue. Absorption bands in the tissue also add useful complexity to the spectral data collected. The use of elastic scattering as themore » key to optical tissue diagnostics in the OBS is based on the fact that many tissue pathologies, including a majority of cancer forms, manifest significant architectural changes at the cellular and sub-cellular level. Since the cellular components that cause elastic scattering have dimensions typically on the order of visible to near-IR wavelengths, the elastic (Mie) scattering properties will be strongly wavelength dependent. Thus, morphology and size changes can be expected to cause significant changes in an optical signature that is derived from the wavelength-dependence of elastic scattering as well as absorption. The data acquisition and storage/display time with the OBS instrument is {approximately}1 second. Thus, in addition to the reduced invasiveness of this technique compared with current state-of-the-art methods (surgical biopsy and pathology analysis), the OBS offers the possibility of impressively faster diagnostic assessment. The OBS employs a small fiber-optic probe that is amenable to use with any endoscope, catheter or hypodermic, or to direct surface examination (e.g., as in skin cancer or cervical cancer). We report here specifically on its potential application in the detection of bladder cancer.« less

Expression analysis and clinical significance of CXCL16/CXCR6 in patients with bladder cancer.

PubMed

Lee, Jun Taik; Lee, Sang Don; Lee, Jeong Zoo; Chung, Moon Kee; Ha, Hong Koo

2013-01-01

The interactions between chemokines and their receptors are closely involved in the progression and metastasis of cancer. We hypothesized that the CXCL16-CXCR6 ligand-receptor system plays an important role in bladder cancer progression. To evaluate this hypothesis, the expression levels of CXCL16 and CXCR6 were evaluated in 160 patients, including 155 patients with bladder cancer and 5 patients with benign bladder disease. The tissues were analyzed by immunohistochemical (IHC) staining and real-time reverse-transcription polymerase chain reaction. We compared the expression of CXCL16/CXCR6 in bladder cancer and benign bladder disease. The expression of CXCR6 was increased in patients with bladder cancer compared with benign bladder disease in RT-PCR. The mRNA expression levels of CXCL16 and CXCR6 were 1.75×10(-2) and 1.99×10(-2) in benign bladder tissue and 1.39×10(-2) and 2.32×10(-2) in bladder cancer tissue, respectively. In IHC staining, the expression of CXCL16/CXCR6 in bladder cancer tissues was higher compared with benign bladder tissues. On multivariate analysis, the IHC staining of CXCL16 was correlated with the 2004 WHO grade and lymphovascular invasion (P=0.021 and P=0.011, respectively). CXCR6 was correlated with the 1973 WHO grade (P=0.001), 2004 WHO grade (P<0.001), pathological T stage (P=0.002) and perineural invasion (P=0.031). However, Cox regression analysis revealed that the expression of CXCL16 and CXCR6 was not correlated with cancer recurrence and cancer-specific survival (P=0.142 and P=0.324, respectively). The expression of CXCL16/CXCR6 was higher in bladder cancer compared to benign disease and correlated with aggressive cancer behavior. Based on our results, the CXCL16/CXCR6 axis appears to be important in the progression of bladder cancer. Thus, CXCL16 and CXCR6 serve as potential therapeutic targets.

Evidence of Nonuniformity in Urothelium Barrier Function between the Upper Urinary Tract and Bladder.

PubMed

Williams, Nicholas A; Barnard, Luke; Allender, Chris J; Bowen, Jenna L; Gumbleton, Mark; Harrah, Tim; Raja, Aditya; Joshi, Hrishi B

2016-03-01

We compared the relative permeability of upper urinary tract and bladder urothelium to mitomycin C. Ex vivo porcine bladder, ureters and kidneys were dissected out and filled with 1 mg ml(-1) mitomycin C. At 60 minutes the organs were emptied and excised tissue samples were sectioned parallel to the urothelium. Sectioned tissue was homogenized and extracted mitomycin C was quantified. Transurothelial permeation across the different urothelia was calculated by normalizing the total amount of drug extracted to the surface area of the tissue sample. Average mitomycin C concentrations at different tissue depths (concentration-depth profiles) were calculated by dividing the total amount of drug recovered by the total weight of tissue. Mitomycin C permeation across the ureteral urothelium was significantly greater than across the bladder and renal pelvis urothelium (9.07 vs 0.94 and 3.61 μg cm(-2), respectively). Concentrations of mitomycin C in the ureter and kidney were markedly higher than those achieved in the bladder at all tissue depths. Average urothelial mitomycin C concentrations were greater than 6.5-fold higher in the ureter and renal pelvis than in the bladder. To our knowledge we report for the first time that the upper urinary tract and bladder show differing permeability to a single drug. Ex vivo porcine ureter is significantly more permeable to mitomycin C than bladder urothelium and consequently higher mitomycin C tissue concentrations can be achieved after topical application. Data in this study correlate with the theory that mammalian upper tract urothelium represents a different cell lineage than that of the bladder and it is innately more permeable to mitomycin C. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Monitoring of permeability of different analytes in human normal and cancerous bladder tissues in vitro using optical coherence tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bingsong Lei; Xiaoyuan Deng; Huajiang Wei

2014-12-31

We report our preliminary results on quantification of glucose and dimethyl sulfoxide (DMSO) diffusion in normal and cancerous human bladder tissues in vitro by using a spectral domain optical coherence tomography (SD-OCT). The permeability coefficients (PCs) of a 30% aqueous solution of glucose are found to be (7.92 ± 0.81) × 10{sup -6} cm s{sup -1} and (1.19 ± 0.13) × 10{sup -5} cm s{sup -1} in normal and cancerous bladder tissues, respectively. The PCs of 50% DMSO are calculated to be (8.99 ± 0.93) × 10{sup -6} cm s{sup -1} and (1.43 ± 0.17) × 10{sup -5} cm s{supmore » -1} in normal and cancerous bladder tissues, respectively. The obtained results show a statistically significant difference in permeability of normal and cancerous tissue and indicate that the PC of 50% DMSO is about 1.13-and 1.21-fold higher than that of 30% glucose in normal bladder and cancerous bladder tissues, respectively. Thus, the quantitative measurements with the help of PCs from OCT images can be a potentially powerful method for bladder cancer detection. (optical coherence tomography)« less

Expression of the urothelial differentiation markers GATA3 and placental S100 (S100P) in female genital tract transitional cell proliferations.

PubMed

Esheba, Ghada E; Longacre, Teri A; Atkins, Kristen A; Higgins, John P

2009-03-01

The degree of urothelial differentiation in putative transitional (urothelial) proliferations in the female genital tract is still controversial. To further investigate the similarities (or dissimilarities) between female genital tract transitional proliferations and bladder urothelium, we evaluated the expression of S100P and GATA3, 2 proteins that we previously found to be strongly expressed in bladder urothelial tumors, in 25 benign ovarian Brenner tumors, 19 Walthard cell nests (17 tubal and 2 ovarian hilus), 1 mature teratoma with a benign urothelial proliferation, 2 proliferating (borderline) ovarian Brenner tumors, 1 malignant Brenner tumor, and 12 ovarian transitional cell carcinomas (TCC). Each lesion was also evaluated for p63 expression by immunohistochemistry. Immunostaining was performed on formalin-fixed, paraffin-embedded tissue sections using the avidin-biotin-peroxidase complex method. Eighty-eight percent of Brenner tumors were positive for S100P, whereas 96% and 100% were positive for GATA3 and p63, respectively. One of 2 proliferating Brenner tumors was positive for S100P, whereas both cases were positive for GATA3 and p63; the malignant Brenner tumor was positive for S100P and p63, but negative for GATA3. Only 17% of TCC were positive for S100p, whereas 33% and 50% of TCC were positive for GATA3 and p63, respectively. Tubal Walthard cell nests were either completely negative or showed only scattered positive staining for S100P; in contrast, 89.5% and 100% of Walthard nests, including the 2 ovarian cases were positive for GATA3 and p63. The teratoma-associated benign urothelial proliferation was also negative for S100P, but positive for GATA3 and p63. Although proliferating and malignant Brenner tumors may exhibit a more intermediate immunoprofile, expression of S100P, GATA3, and p63 by a majority of ovarian Brenner tumors underscores the similarity between these neoplasms and urothelial proliferations of bladder origin. The indeterminate phenotype seen in Walthard nests and ovarian TCC suggests that these proliferations may represent an incomplete or alternate form of differentiation.

Augmentation cystoplasty in neurogenic bladder

PubMed Central

Kocjancic, Ervin; Demirdağ, Çetin

2016-01-01

The aim of this review is to update the indications, contraindications, technique, complications, and the tissue engineering approaches of augmentation cystoplasty (AC) in patients with neurogenic bladder. PubMed/MEDLINE was searched for the keywords "augmentation cystoplasty," "neurogenic bladder," and "bladder augmentation." Additional relevant literature was determined by examining the reference lists of articles identified through the search. The update review of of the indications, contraindications, technique, outcome, complications, and tissue engineering approaches of AC in patients with neurogenic bladder is presented. Although some important progress has been made in tissue engineering AC, conventional AC still has an important role in the surgical treatment of refractory neurogenic lower urinary tract dysfunction. PMID:27617312

Experimental investigations on intracavity sonography. Part 2: Alteration of imaging by artificial alterations in the wall of isolated porcine urinary bladders.

PubMed

Jaeger, N; Vahlensieck, W

1986-01-01

Because the determination of the depth of urinary bladder tumors by means of intracavity sonography depends on several factors (tumor size, reflection behavior of the tumor etc.), we checked the imaging of this diagnostic technique in the isolated porcine urinary bladder under various experimental conditions. Different tissues of defined size were fixed on the inner or outer surface of the bladder wall; both the bladder mucosa and the foreign tissue were damaged thermally or by incision. The importance of a limited depth of sound penetration or of a sound shadow depending on the characteristics of the tissue under investigation was revealed; tissue types could not be distinguished unequivocally by the reflection pattern; above all, a sonographic diagnosis of the tumor was not possible in the presence of histo-pathologically detectable tissue changes due to thermal damage.

Ultrasound and Biomarker Tests in Predicting Cancer Aggressiveness in Tissue Samples of Patients With Bladder Cancer

ClinicalTrials.gov

2017-06-23

Bladder Papillary Urothelial Carcinoma; Stage 0a Bladder Urothelial Carcinoma; Stage 0is Bladder Urothelial Carcinoma; Stage I Bladder Cancer With Carcinoma In Situ; Stage I Bladder Urothelial Carcinoma; Stage II Bladder Urothelial Carcinoma; Stage III Bladder Urothelial Carcinoma; Stage IV Bladder Urothelial Carcinoma

Tissue engineering of urinary bladder - current state of art and future perspectives.

PubMed

Adamowicz, Jan; Kowalczyk, Tomasz; Drewa, Tomasz

2013-01-01

Tissue engineering and biomaterials science currently offer the technology needed to replace the urinary tract wall. This review addresses current achievements and barriers for the regeneration of the urinary blad- der based on tissue engineering methods. Medline was search for urinary bladder tissue engineering regenerative medicine and stem cells. Numerous studies to develop a substitute for the native urinary bladder wall us- ing the tissue engineering approach are ongoing. Stem cells combined with biomaterials open new treatment methods, including even de novo urinary bladder construction. However, there are still many issues before advances in tissue engineering can be introduced for clinical application. Before tissue engineering techniques could be recognize as effective and safe for patients, more research stud- ies performed on large animal models and with long follow-up are needed to carry on in the future.

Optical improvements in the diagnosis of bladder cancer: implications for clinical practice.

PubMed

Schubert, Tina; Rausch, Steffen; Fahmy, Omar; Gakis, Georgios; Stenzl, Arnulf

2017-11-01

For over 100 years white-light cystoscopy has remained the gold-standard technique for the detection of bladder cancer (BCa). Some limitations in the detection of flat lesions (CIS), the differentiation between inflammation and malignancy, the inaccurate determination of the tumor margin status as well as the tumor depth, have led to a variety of technological improvements. The aim of this review is to evaluate the impact of these improvements in the diagnosis of BCa and their effectiveness in clinical practice. A systematic literature search was conducted according to the PRISMA statement to identify studies reporting on imaging modalities in the diagnosis of NMIBC between 2000 and 2017. A two-stage selection process was utilized to determine eligible studies. A total of 74 studies were considered for final analysis. Optical imaging technologies have emerged as an adjunct to white-light cystoscopy and can be classified according to their scope as macroscopic, microscopic and molecular. Macroscopic techniques including photodynamic diagnosis (PDD), narrow-band imaging (NBI) and the Storz Professional Image Enhancement System (IMAGE1 S, formerly known as SPIES) are similar to white-light cystoscopy, but are superior in the detection of bladder tumors by means of contrast enhancement. Especially the detection rate of very mute lesions in the bladder mucosa (CIS) could be significantly increased by the use of these methods. Microscopic imaging techniques like confocal laser endomicroscopy and optical coherence tomography permit a real-time high-resolution assessment of the bladder mucosa at a cellular and sub-cellular level with spatial resolutions similar to histology, enabling the surgeon to perform an 'optical biopsy'. Molecular techniques are based on the combination of optical imaging technologies with fluorescence labeling of cancer-specific molecular agents like antibodies. This labeling is intended to favor an optical distinction between benign and malignant tissue. Optical improvements of the standard white-light cystoscopy have proven their benefit in the detection of BCa and have found their way into clinical practice. Especially the combination of macroscopic and microscopic techniques may improve diagnostic accuracy. Nevertheless, HAL-PDD guided cystoscopy is the only approach approved for routine use in the diagnosis of BCa by most urological associations in the EU and USA to date.

Carcinomas of the urinary bladder simulating malignant lymphoma. A report of five cases.

PubMed

Zukerberg, L R; Harris, N L; Young, R H

1991-06-01

We report five carcinomas of the urinary bladder, four of them transitional cell carcinomas and one undifferentiated carcinoma, with unusual features that have received little or no comment in the literature and may be the cause of diagnostic difficulty because of their possible confusion with malignant lymphoma. Four patients were male and one female. They ranged from 61 to 76 years of age. Three tumors from these patients had a prominent (2 cases) or massive (1 case) lymphoid infiltrate that partially obscured the invasive carcinoma in two cases and largely obscured it in the third case, which closely resembled a lymphoepithelioma. The diagnosis of malignant lymphoma was only excluded with confidence in the last case after thorough immunohistochemical study. The lymphoid infiltrate was composed of numerous T-cells (UCHL-1 and Leu 22 positive) and polytypic plasma cells with admixed eosinophils; occasional germinal centers were present in one case. The tumors were deeply invasive in two patients, one of whom is alive with no evidence of disease 4 years after treatment with chemotherapy and radiation therapy; the other two cases are too recent for meaningful follow-up. Two other transitional cell carcinomas had diffuse patterns that simulated lymphoma or plasmacytoma. Recognition of these patterns of vesical carcinoma is important in order to avoid the misdiagnosis of the very rare malignant lymphoma of the urinary bladder.

Quadruple primary urogenital cancers - A case report.

PubMed

Elec, Florin-Ioan; Zaharie, Andreea; Ene, Bogdan-Mihai; Ghervan, Liviu

2017-01-01

Urogenital cancers are not an uncommon occurrence in daily practice. Prostate cancer is the second most frequent cancer in men, kidney cancer accounts for 2.4% of all cancers and bladder cancers represent 3.1% of cancers in both men and women [1]. However, the cases of a simultaneous development of all three cancers, including one with a neuroendocrine component, are very few and far between. Our case report involves a case of a patient with prostate adenocarcinoma, clear-cell renal carcinoma, papillary renal carcinoma and small-cell bladder cancer. The patient was treated as if he had separate pathologies by a multidisciplinary team: surgical and oncological, performing radical cystoprostatectomy with left perifascial nephroureterectomy, right ureterostomy and adjuvant chemotherapy, with excellent outcome even four years after the initial diagnosis. The distinct features of this case are the occurence of four different malignancies of the urogenital system, the family history of colon cancer, the development of small-cell carcinoma of the bladder, which is extremely rare and the good outcome, despite the quadruple malignancies and the aggresivity of the small-cell carcinoma. Mutiple primary malignancies are a relatively rare pathology, but should be considered as a possibility in patients who already had a second malignancy. Cases of patients with MPMs should be supervised by a multidisciplinary team and should be followed closely. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Effects of shielded or unshielded laser and electrohydraulic lithotripsy on rabbit bladder.

PubMed

Bhatta, K M; Rosen, D I; Flotte, T J; Dretler, S P; Nishioka, N S

1990-04-01

The pulsed dye laser and electrohydraulic lithotriptor (EHL) are both effective devices for fragmenting urinary and biliary calculi. Both fragment stones by producing a plasma-mediated shockwave. Recently, a plasma shield consisting of a hollow spring and a metal end cap has been described for use with the laser and EHL devices in an attempt to minimize tissue damage without adversely affecting stone fragmentation rates. The tissue effects produced by a pulsed dye laser and an EHL device with and without plasma shields were examined and compared using rabbit urinary bladders. If blood was present, the unshielded laser perforated the bladder wall in two pulses. However, in the absence of blood, over 100 pulses were needed for the laser to perforate the bladder. A mean of six pulses were required to perforate the bladder wall with a shielded laser. The unshielded EHL perforated the bladder wall in two pulses, whereas, the shielded EHL required a mean of 35 pulses. Microscopically, areas of exposure revealed hemorrhage and tissue ablation. We conclude that all devices examined can produce significant tissue damage when discharged directly onto bladder epithelium.

Tissue engineering of bladder using vascular endothelial growth factor gene-modified endothelial progenitor cells.

PubMed

Chen, Bai-Song; Xie, Hua; Zhang, Sheng-Li; Geng, Hong-Quan; Zhou, Jun-Mei; Pan, Jun; Chen, Fang

2011-12-01

This study assessed the use of vascular endothelial growth factor (VEGF) gene-modified endothelial progenitor cells (EPCs) seeded onto bladder acellular matrix grafts (BAMGs), to enhance the blood supply in tissue-engineered bladders in a porcine model. Autologous porcine peripheral EPCs were isolated, cultured, expanded, characterized, and modified with the VEGF gene using an adenovirus vector. The expression of VEGF was examined using reverse transcriptase polymerase chain reaction (RT-PCR) and an enzyme-linked immunosorbent assay (ELISA). VEGF gene modified EPCs were seeded onto BAMG and cultured for 3 days before implantation into pigs for bladder tissue engineering. A partial bladder cystectomy was performed in 12 pigs. The experimental group (6 pigs) received VEGF gene-modified EPC-seeded BAMG. The control group (6 pigs) received BAMG without seeded EPCs. The resulting tissue-engineered bladders were subject to a general and histological analysis. Microvessel density (MVD) was assessed using immunohistochemistry. The ex vivo transfection efficiency of EPCs was greater than 60%-70% when concentrated adenovirus was used. The genetically modified cells expressed both VEGF and green fluorescent protein (GFP). Scanning electron microscopy (SEM) and Masson's trichrome staining of cross sections of the cultured cells seeded to BAMG showed cell attachment and proliferation on the surface of the BAMG. Histological examination revealed bladder regeneration in a time-dependent fashion. Significant increases in MVD were observed in the experimental group, in comparison with the control group. VEGF-modified EPCs significantly enhanced neovascularization, compared with BAMG alone. These results indicate that EPCs, combined with VEGF gene therapy, may be a suitable approach for increasing blood supply in the tissue engineering of bladders. Thus, a useful strategy to achieve a tissue-engineered bladder is indicated.

Nephrogenic Adenoma of the Urinary Bladder: A Review of the Literature

PubMed Central

Venyo, Anthony Kodzo-Grey

2015-01-01

Background. Nephrogenic adenoma of the urinary bladder (NAUB) is a rare lesion associated with nonspecific symptoms and could inadvertently be misdiagnosed. Aim. To review the literature. Methods. Various internet search engines were used. Results. NAUB is a benign tubular and papillary lesion of the bladder, is more common in men and adults, and has been associated with chronic inflammation/irritation, previous bladder surgery, diverticula, renal transplantation, and intravesical BCG; recurrences and malignant transformations have been reported. Differential diagnoses include clear cell adenocarcinoma, endocervicosis, papillary urothelial carcinoma, prostatic adenocarcinoma of bladder, and nested variant of urothelial carcinoma; most NAUBs have both surface papillary and submucosal tubular components; both the papillae and tubules tend to be lined by a single layer of mitotically inactive bland cells which have pale to clear cytoplasm. Diagnosis may be established by using immunohistochemistry (positive staining with racemase; PAX2; keratins stain positive with fibromyxoid variant), electron microscopy, DNA analysis, and cytological studies. Treatment. Endoscopic resection is the treatment but recurrences including sporadic malignant transformation have been reported. Conclusions. There is no consensus on best treatment. A multicentre study is required to identify the treatment that would reduce the recurrence rate, taking into consideration that intravesical BCG is associated with NAUB. PMID:27347540

Outlines on nanotechnologies applied to bladder tissue engineering.

PubMed

Alberti, C

2012-01-01

Tissue engineering technologies are more and more expanding as consequence of recent developments in the field of biomaterial science and nanotechnology research. An important issue in designing scaffold materials is that of recreating the ECM (extra-cellular matrix) functional features - particularly ECM-derived complex molecule signalling - to mimic its capability of directing cell-growth and neotissue morphogenesis. In this way the nanotechnology may offer intriguing chances, biomaterial nanoscale-based scaffold geometry behaving as nanomechanotransducer complex interacting with different cell nanosize proteins, especially with those of cell surface mechanoreceptors. To fabricate 3D-scaffold complex architectures, endowed with controlled geometry and functional properties, bottom-up approaches, based on molecular self-assembling of small building polymer units, are used, sometimes functionalizing them by incorporation of bioactive peptide sequences such as RDG (arginine - glycine - aspartic acid, a cell-integrin binding domain of fibronectin), whereas the top-down approaches are useful to fabricate micro/nanoscale structures, such as a microvasculature within an existing complex bioarchitecture. Synthetic polymer-based nanofibers, produced by electrospinning process, may be used to create fibrous scaffolds that can facilitate, given their nanostructured geometry and surface roughness, cell adhesion and growth. Also bladder tissue engineering may benefit by nanotechnology advances to achieve a better reliability of the bladder engineered tissue. Particularly, bladder smooth muscle cell adhesion to nanostructured polymeric surfaces is significantly enhanced in comparison with that to conventional biomaterials. Moreover nanostructured surfaces of bladder engineered tissue show a decreased calcium stone production. In a bladder tumor animal model, the dispersion of carbon nanofibers in a polymeric scaffold-based tissue engineered replacement neobladder, appears to inhibit a carcinogenic relapse in bladder prosthetic material. Facing the future, a full success of bladder tissue engineering will mainly depend on the progress of both biomaterial nanotechnologies and stem cell biology research.

Characterization of dynamic physiology of the bladder by optical coherence tomography

NASA Astrophysics Data System (ADS)

Yuan, Zhijia; Keng, Kerri; Pan, Rubin; Ren, Hugang; Du, Congwu; Kim, Jason; Pan, Yingtian

2012-03-01

Because of its high spatial resolution and noninvasive imaging capabilities, optical coherence tomography has been used to characterize the morphological details of various biological tissues including urinary bladder and to diagnose their alternations (e.g., cancers). In addition to static morphology, the dynamic features of tissue morphology can provide important information that can be used to diagnose the physiological and functional characteristics of biological tissues. Here, we present the imaging studies based on optical coherence tomography to characterize motion related physiology and functions of rat bladder detrusor muscles and compared the results with traditional biomechanical measurements. Our results suggest that optical coherence tomography is capable of providing quantitative evaluation of contractile functions of intact bladder (without removing bladder epithelium and connective tissue), which is potentially of more clinical relevance for future clinical diagnosis - if incorporated with cystoscopic optical coherence tomography.

Oncogene miR-187-5p is associated with cellular proliferation, migration, invasion, apoptosis and an increased risk of recurrence in bladder cancer.

PubMed

Li, Zuwei; Lin, Canbin; Zhao, Liwen; Zhou, Liang; Pan, Xiang; Quan, Jing; Peng, Xiqi; Li, Weiqing; Li, Hang; Xu, Jinling; Xu, Weijie; Guan, Xin; Chen, Yun; Lai, Yongqing

2018-06-05

Bladder cancer, the ninth-most-common malignancy worldwide with an estimated 356,000 new cases and 145,000 deaths annually, has a propensity to relapse, requiring lifelong monitoring after diagnosis. 75% patients diagnosed with BC are non-muscle invasive BC and over 50% of them experience recurrences within 6-12 years of initial diagnosis. miRNA are small, noncoding RNA and shown to be oncogenes or anti-oncogenes in bladder cancer, contributing to numerous BC cell processes, including cell proliferation, differentiation, migration and apoptosis. RT-qPCR were performed to detect the expression of miR-187-5p in tissues and cell lines, After which, clinicopathological variables and the prognostic value of altered miR-187-5p expression in BC was analyzed with the 48 formalin-fixed paraffin-embedded BC samples. Moreover, Cell functional assays (wound healing assay, CCK-8 assay, transwell assay and flow cytometry assay) were performed to explore the relationship between miR-187-5p expression and cell proliferation, migration, invasion and apoptosis in BC. Up-regulation of miR-187-5p was observed in BC tissues and BC cell lines. Cox proportional hazard regression analysis demonstrated that the patients with low expression of miR-187-5p experience lower risks of recurrence in the univariate and multivariate analysis. The Kaplan-Meier recurrence-free curves suggested that the patients with low expression of miR-187-5p experience lower risks of recurrence. Up-regulation of miR-187-5p promotes cell proliferation and mobility and inhibits the apoptosis of 5637 and UM-UC-3 cell, while down-regulation of miR-187-5p reverses these effects. The results of our study demonstrated that oncogene miR-187-5p is associated with cellular proliferation, migration, invasion, apoptosis and an increased risk of recurrence in bladder cancer. Copyright © 2018 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Clinical utility of kallikrein-related peptidases (KLK) in urogenital malignancies.

PubMed

Dorn, J; Bayani, J; Yousef, G M; Yang, F; Magdolen, V; Kiechle, M; Diamandis, E P; Schmitt, M

2013-09-01

Kallikrein-related peptidases (KLK), which represent a major tissue-associated proteolytic system, stand for a rich source of biomarkers that may allow molecular classification, early diagnosis and prognosis of human malignancies as well as prediction of response or failure to cancer-directed drugs. International research points to an important role of certain KLKs in female and male urogenital tract malignancies, in addition to cancers of the lung, brain, skin, head and neck, and the gastrointestinal tract. Regarding the female/male urogenital tract, remarkably, all of the KLKs are expressed in the normal prostate, testis, and kidney whereas the uterus, the ovary, and the urinary bladder are expressing a limited number of KLKs only. Most of the information regarding KLK expression in tumour-affected organs is available for ovarian cancer; all of the 12 KLKs tested so far were found to be elevated in the malignant state, depicting them as valuable biomarkers to distinguish between the normal and the cancerous phenotype. In contrast, for kidney cancer, a series of KLKs was found to be downregulated, while other KLKs were not expressed. Evidently, depending on the type of cancer or cancer stage, individual KLKs may show characteristics of a Janus-faced behaviour, by either expanding or inhibiting cancer progression and metastasis.

Expression analysis and clinical significance of CXCL16/CXCR6 in patients with bladder cancer

PubMed Central

LEE, JUN TAIK; LEE, SANG DON; LEE, JEONG ZOO; CHUNG, MOON KEE; HA, HONG KOO

2013-01-01

The interactions between chemokines and their receptors are closely involved in the progression and metastasis of cancer. We hypothesized that the CXCL16-CXCR6 ligand-receptor system plays an important role in bladder cancer progression. To evaluate this hypothesis, the expression levels of CXCL16 and CXCR6 were evaluated in 160 patients, including 155 patients with bladder cancer and 5 patients with benign bladder disease. The tissues were analyzed by immunohistochemical (IHC) staining and real-time reverse-transcription polymerase chain reaction. We compared the expression of CXCL16/CXCR6 in bladder cancer and benign bladder disease. The expression of CXCR6 was increased in patients with bladder cancer compared with benign bladder disease in RT-PCR. The mRNA expression levels of CXCL16 and CXCR6 were 1.75×10−2 and 1.99×10−2 in benign bladder tissue and 1.39×10−2 and 2.32×10−2 in bladder cancer tissue, respectively. In IHC staining, the expression of CXCL16/CXCR6 in bladder cancer tissues was higher compared with benign bladder tissues. On multivariate analysis, the IHC staining of CXCL16 was correlated with the 2004 WHO grade and lymphovascular invasion (P=0.021 and P=0.011, respectively). CXCR6 was correlated with the 1973 WHO grade (P=0.001), 2004 WHO grade (P<0.001), pathological T stage (P=0.002) and perineural invasion (P=0.031). However, Cox regression analysis revealed that the expression of CXCL16 and CXCR6 was not correlated with cancer recurrence and cancer-specific survival (P=0.142 and P=0.324, respectively). The expression of CXCL16/CXCR6 was higher in bladder cancer compared to benign disease and correlated with aggressive cancer behavior. Based on our results, the CXCL16/CXCR6 axis appears to be important in the progression of bladder cancer. Thus, CXCL16 and CXCR6 serve as potential therapeutic targets. PMID:23255926

CIP2A is a predictor of survival and a novel therapeutic target in bladder urothelial cell carcinoma.

PubMed

Xue, Yijun; Wu, Gengqing; Wang, Xiaoning; Zou, Xiaofeng; Zhang, Guoxi; Xiao, Rihai; Yuan, Yuanhu; Long, Dazhi; Yang, Jun; Wu, Yuting; Xu, Hui; Liu, Folin; Liu, Min

2013-03-01

Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified human oncoprotein that stabilizes the c-MYC protein. Herein, we aimed to investigate its expression pattern, clinical significance, and biological function in urothelial cell carcinoma (UCC) of the bladder. CIP2A expression was examined in 20 fresh bladder UCC tissues and paired adjacent normal bladder tissues by RT-PCR and Western blot. Immunohistochemistry for CIP2A was performed on additional 117 bladder UCC tissues. The clinical significance of CIP2A expression was analyzed. CIP2A downregulation was performed in bladder UCC cell line T24 with high abundance of CIP2A, and the effects of CIP2A silencing on cell proliferation, migration, invasion in vitro, and tumor growth in vivo were evaluated. We found that CIP2A expression was upregulated in bladder UCC tissues relative to adjacent normal bladder tissues. Clinicopathological analysis showed that CIP2A expression was significantly associated with tumor stage (P = 0.004), histological grade (P = 0.007), and lymph node status (P = 0.001). The Kaplan-Meier survival curves revealed that CIP2A expression was associated with poor prognosis in bladder UCC patients (log-rank value = 14.704, P < 0.001). CIP2A expression was an independent prognostic marker of overall patient survival in a multivariate analysis (P = 0.015). Knockdown of the CIP2A expression reduced cell proliferation, anchorage-independent growth, migration, invasion, and tumor growth in xenograft model mice. Our findings suggest that CIP2A is an independent predictor of poor prognosis of bladder UCC patients, and inhibition of its expression might be of therapeutic significance.

Relook TURBT in superficial bladder cancer: its importance and its correlation with the tumor ploidy.

PubMed

Dwivedi, Udai S; Kumar, Abhay; Das, Suren K; Trivedi, Sameer; Kumar, Mohan; Sunder, Shyam; Singh, Pratap B

2009-01-01

To evaluate various prognostic factor predictors of residual growth in Relook transurethral resection of bladder tumor (TURBT) in superficial bladder cancer. Also, to evaluate the role of Relook TURBT along with the ploidy for prediction of recurrence and stage progression in these patients. Fifty patients with superficial bladder cancer underwent TURBT after complete evaluation. Ploidy of the tumor specimen was evaluated by flow cytometry. After 4 to 6 weeks of initial TURBT, these patients underwent Relook TURBT. Final treatment was given after the results of the histological evaluation of these specimens. Patients who underwent bladder sparing treatment were followed-up. Of the patients, 28.5% had residual tumor in Relook TURBT. Growth was found to be at the same site in 66.7% and at a different site 33.3%; 75% had single while 25% had multiple residual growth. Residual malignant tissue had a statistically significant correlation with size of the tumor (>3 cm), appearance (solid tumor), number (>3), grade (high), and multiple previous resections. Overall, the up-migration of stage and grade leads to change in treatment in 41.6%; 5 underwent radical cystectomy and 1 opted for radiotherapy; in 2 patients, intravesical BCG was given. In follow-up of mean 11.5 months, 16.6% had recurrence. Presence of residual growth in Relook TURBT along with number, size, morphology, and multiple previous resections were found to have significant correlation with the recurrence in these patients. Ploidy and grade of the tumor were not found to have correlation. Multiple, more than 3 cm, solid high grade tumor with > 3 previous resections were predictors of presence of residual tumor in Relook TURBT. Presence of residual growth is a significant risk factor for recurrence. Ploidy was not found to be significantly correlated with recurrence.

Bovine papillomavirus type 2 (BPV-2) E5 oncoprotein binds to the subunit D of the V₁-ATPase proton pump in naturally occurring urothelial tumors of the urinary bladder of cattle.

PubMed

Roperto, Sante; Russo, Valeria; Borzacchiello, Giuseppe; Urraro, Chiara; Lucà, Roberta; Esposito, Iolanda; Riccardi, Marita Georgia; Raso, Cinzia; Gaspari, Marco; Ceccarelli, Dora Maria; Galasso, Rocco; Roperto, Franco

2014-01-01

Active infection by bovine papillomavirus type 2 (BPV-2) was documented for fifteen urinary bladder tumors in cattle. Two were diagnosed as papillary urothelial neoplasm of low malignant potential (PUNLMP), nine as papillary and four as invasive urothelial cancers. In all cancer samples, PCR analysis revealed a BPV-2-specific 503 bp DNA fragment. E5 protein, the major oncoprotein of the virus, was shown both by immunoprecipitation and immunohistochemical analysis. E5 was found to bind to the activated (phosphorylated) form of the platelet derived growth factor β receptor. PDGFβR immunoprecipitation from bladder tumor samples and from normal bladder tissue used as control revealed a protein band which was present in the pull-down from bladder cancer samples only. The protein was identified with mass spectrometry as "V₁-ATPase subunit D", a component of the central stalk of the V₁-ATPase vacuolar pump. The subunit D was confirmed in this complex by coimmunoprecipitation investigations and it was found to colocalize with the receptor. The subunit D was also shown to be overexpressed by Western blot, RT-PCR and immunofluorescence analyses. Immunoprecipitation and immunofluorescence also revealed that E5 oncoprotein was bound to the subunit D. For the first time, a tri-component complex composed of E5/PDGFβR/subunit D has been documented in vivo. Previous in vitro studies have shown that the BPV-2 E5 oncoprotein binds to the proteolipid c ring of the V₀-ATPase sector. We suggest that the E5/PDGFβR/subunit D complex may perturb proteostasis, organelle and cytosol homeostasis, which can result in altered protein degradation and in autophagic responses.

Adenocarcinoma of the urinary bladder

PubMed Central

Dadhania, Vipulkumar; Czerniak, Bogdan; Guo, Charles C

2015-01-01

Adenocarcinoma is an uncommon malignancy in the urinary bladder which may arise primarily in the bladder as well as secondarily from a number of other organs. Our aim is to provide updated information on primary and secondary bladder adenocarcinomas, with focus on pathologic features, differential diagnosis, and clinical relevance. Primary bladder adenocarcinoma exhibits several different growth patterns, including enteric, mucinous, signet-ring cell, not otherwise specified, and mixed patterns. Urachal adenocarcinoma demonstrates similar histologic features but it can be distinguished from bladder adenocarcinoma on careful pathologic examination. Secondary bladder adenocarcinomas may arise from the colorectum, prostate, endometrium, cervix and other sites. Immunohistochemical study is valuable in identifying the origin of secondary adenocarcinomas. Noninvasive neoplastic glandular lesions, adenocarcinoma in situ and villous adenoma, are frequently associated with bladder adenocarcinoma. It is also important to differentiate bladder adenocarcinoma from a number of nonneoplastic lesions in the bladder. Primary bladder adenocarcinoma has a poor prognosis largely because it is usually diagnosed at an advanced stage. Urachal adenocarcinoma shares similar histologic features with bladder adenocarcinoma, but it has a more favorable prognosis than bladder adenocarcinoma, partly due to the relative young age of patients with urachal adenocarcinoma. PMID:26309895

Nanotechnology in bladder cancer: current state of development and clinical practice

PubMed Central

Tomlinson, Ben; Lin, Tzu-yin; Dall'Era, Marc; Pan, Chong-Xian

2015-01-01

Nanotechnology is being developed for the diagnosis and treatment of both nonmyoinvasive bladder cancer (NMIBC) and invasive bladder cancer. The diagnostic applications of nanotechnology in NMIBC mainly focus on tumor identification during endoscopy to increase complete resection of bladder cancer while nanotechnology to capture malignant cells or their components continues to be developed. The therapeutic applications of nanotechnology in NMIBC are to reformulate biological and cytotoxic agents for intravesical instillation, combine both diagnostic and therapeutic application in one nanoformulation. In invasive and advanced bladder cancer, magnetic resonance imaging with supraparamagnetic iron oxide nanoparticles can improve the sensitivity and specificity in detecting small metastasis to lymph nodes. Nanoformulation of cytotoxic agents can potentially decrease the toxicity while increasing efficacy. PMID:25929573

Immunohistochemical study of parathyroid hormone-related protein in vesical transitional epithelium of patients with spinal cord injury.

PubMed

Vaidyanathan, S; McCreavy, D T; McDicken, I W; Soni, B M; Mansour, P; Wlodarski, B; Carron, J A; Fraser, W D; Singh, G; Sett, P; Gallagher, J A

1999-11-01

Parathyroid hormone-related protein (PTHrP), in addition to the well-established role in endochrondral bone development, is believed to be an important mediator of cellular growth and differentiation in a number of non-bony tissues. To compare the immunohistochemical staining of vesical transitional epithelium to antibodies raised to synthetic peptides of PTHrP composed of amino acid sequences 43 - 52 and 127 - 138 in patients with spinal cord injury (SCI) and neuropathic bladder (n=14), and control patients with intact neuraxis and no history of bladder cancer (n=10). Male SCI patients registered with Regional Spinal Injuries Centre, Southport, England. Endoscopic cold cup biopsy from the trigone of the urinary bladder was taken from patients with SCI while they were undergoing a therapeutic procedure in the urinary bladder. The control samples of bladder biopsies were taken from the archives of the Department of Histopathology, District General Hospital, Southport. Immunohistochemistry was performed using rabbit antibodies raised against synthetic peptides of human PTHrP (43 - 52) and PTHrP (127 - 138). The biopsies were examined for immunostaining of transitional epithelium. Of the 14 biopsies of SCI patients, positive immunostaining using antibodies to both the PTHrP peptides was found in four cases; five biopsies showed positive immunostaining only to anti-PTHrP (43 - 52); and five biopsies showed no immunostaining with either of the PTHrP peptides. In contrast, transitional epithelium in the biopsy specimens of ten control subjects with no history of bladder cancer showed no immunostaining with either of the PTHrP peptides. This study revealed that the transitional epithelium of neuropathic urinary bladder exhibits increased predilection for positive immunohistochemical staining for PTHrP (43 - 52), and to a lesser extent, to PTHrP (127 - 138), as compared to the vesical transitional epithelium of able bodied individuals with no history of vesical malignancy. The possible role of PTHrP in the cellular differentiation of urothelium of neuropathic bladder, and thereby, in the pathogenesis of cystitis in SCI patients, needs to be explored.

75 FR 10867 - Determinations Concerning Illnesses Discussed in the Institute of Medicine Report on Gulf War and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-09

... cancer; nervous system disease; reproductive or developmental dysfunction; non-malignant respiratory... nervous system cancers, stomach cancer, prostatic cancer and testicular cancer. The non-malignant diseases... and bladder cancer exists. G. Brain and Other Central Nervous System Cancers Of the 20 published...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Paul-Yann; Lin, Yung-Lun; Huang, Chin-Chin

Epidemiological studies have revealed that exposure to an arsenic-contaminated environment correlates with the incidence of bladder cancer. Bladder cancer is highly recurrent after intravesical therapy, and most of the deaths from this disease are due to invasive metastasis. In our present study, the role of inorganic arsenic in bladder carcinogenesis is characterized in a mouse model. This work provides the first evidence that inorganic arsenic in drinking water promotes N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced bladder tissue damage, including the urothelium and submucosal layer. This damage to the bladder epithelium induced by BBN includes thickening of the submucosal layer, the loss of the glycosaminoglycanmore » layer and an increase in both the deoxyguanosine oxidation and cytosine methylation levels in the DNA. Further, when 10 ppm inorganic arsenic is combined with BBN, the number of bladder submucosal capillaries is increased. In addition, inorganic arsenic also increases the deoxyguanosine oxidation level, alters the cytosine methylation state, decreases the activities of glutathione reductase and glucose-6-phosphate dehydrogenase, decreases the protein expression of NAD(P)H quinone oxidoreductase-1 (NQO-1) and increases the protein expression of specific protein 1 (Sp1) in bladder tissues. In summary, our data reveal that inorganic arsenic in drinking water promotes the BBN-induced pre-neoplastic damage of bladder tissue in mice, and that the 8-hydroxy-2′-deoxyguanosine, 5-methylcytosine, NQO-1 protein and Sp1 protein levels may be pre-neoplastic markers of bladder tumors. -- Highlights: ► The role of inorganic arsenic in bladder carcinogenesis is characterized in mice. ► We examine the changes in the histology and biochemistry of bladder tissues. ► Inorganic arsenic enhances BBN-induced DNA oxidation while decreases BBN-induced DNA methylation in the mouse bladder. ► Inorganic arsenic alters the activities of the anti-oxidant enzymes in the mouse bladder. ► Inorganic arsenic increases Sp1 while decreases NQO-1 protein expression in the mouse whole bladder.« less

[Using of cell biocomposite material in tissue engineering of the urinary bladder].

PubMed

Glybochko, P V; Olefir, Yu V; Alyaev, Yu G; Butnaru, D V; Bezrukov, E A; Chaplenko, A A; Zharikova, T M

2017-06-01

In a systematic review, to present an overview of the current situation in the field of tissue engineering of urinary bladder related to the use of cell lines pre-cultured on matrices. The selection of eligible publications was conducted according to the method described in the article Glybochko P.V. et al. "Tissue engineering of urinary bladder using acellular matrix." At the final stage, studies investigating the application of matrices with human and animal cell lines were analyzed. Contemporary approaches to using cell-based tissue engineering of the bladder were analyzed, including the formation of 3D structures from several types of cells, cell layers and genetic modification of injected cells. The most commonly used cell lines are urothelial cells, mesenchymal stem cells and fibroblasts. The safety and efficacy of any types of composite cell structures used in the cell-based bladder tissue engineering has not been proven sufficiently to warrant clinical studies of their usefulness. The results of cystoplasty of rat bladder are almost impossible to extrapolate to humans; besides, it is difficult to predict possible side effects. For the transition to clinical trials, additional studies on relevant animal models are needed.

Mast Cell IL-10 Drives Localized Tolerance in Chronic Bladder Infection

PubMed Central

Chan, Cheryl Y.; St. John, Ashley L.; Abraham, Soman N.

2013-01-01

The lower urinary tract’s virtually inevitable exposure to external microbial pathogens warrants efficient tissue-specialized defenses to maintain sterility. The observation that the bladder can become chronically infected in combination with clinical observations that antibody responses following bladder infections are not detectable, suggest defects in the formation of adaptive immunity and immunological memory. We have identified a broadly immunosuppressive transcriptional program specific to the bladder, but not the kidney, during infection of the urinary tract that is dependent on tissue-resident mast cells (MCs). This involves localized production of interleukin-10 and results in suppressed humoral and cell mediated responses and bacterial persistence. Therefore, in addition to the previously described role of MCs orchestrating the early innate immunity during bladder infection, they subsequently play a tissue-specific immunosuppressive role. These findings may explain the prevalent recurrence of bladder infections and suggest the bladder as a site exhibiting an intrinsic degree of MC-maintained immune privilege. PMID:23415912

Nitrative DNA damage and Oct3/4 expression in urinary bladder cancer with Schistosomahaematobium infection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, Ning; Thanan, Raynoo; Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie

Highlights: {yields} Oct3/4-positive cells increase in Schistosoma haematobium (SH)-associated bladder cancer. {yields} iNOS-dependent DNA lesion, 8-nitroguanine, was formed in Oct3/4-positive cells. {yields} 8-Nitroguanine formed in stem-like cells plays a role in SH-induced carcinogenesis. {yields} Mutant stem cells may participate in inflammation-related carcinogenesis. -- Abstract: To investigate whether mutant stem cells participate in inflammation-related carcinogenesis, we performed immunohistochemical analysis to examine nitrative and oxidative DNA lesions (8-nitroguanine and 8-oxodG) and a stem cell marker Oct3/4 in bladder tissues obtained from cystitis and bladder cancer patients infected with Schistosomahaematobium (S. haematobium). We also detected the expression of nuclear factor-{kappa}B (NF-{kappa}B) and induciblemore » nitric oxide synthase (iNOS), which lead to 8-nitroguanine formation. The staining intensity of 8-nitroguanine and 8-oxodG was significantly higher in bladder cancer and cystitis tissues than in normal tissues. iNOS expression was colocalized with NF-{kappa}B in 8-nitroguanine-positive tumor cells from bladder cancer patients. Oct3/4 expression was significantly increased in cells from S. haematobium-associated bladder cancer tissues in comparison to normal bladder and cancer tissues without infection. Oct3/4 was also expressed in epithelial cells of cystitis patients. Moreover, 8-nitroguanine was formed in Oct3/4-positive stem cells in S. haematobium-associated cystitis and cancer tissues. In conclusion, inflammation by S.haematobium infection may increase the number of mutant stem cells, in which iNOS-dependent DNA damage occurs via NF-{kappa}B activation, leading to tumor development.« less

Current status of tissue engineering applied to bladder reconstruction in humans.

PubMed

Gasanz, C; Raventós, C; Morote, J

2018-01-11

Bladder reconstruction is performed to replace or expand the bladder. The intestine is used in standard clinical practice for tissue in this procedure. The complications of bladder reconstruction range from those of intestinal resection to those resulting from the continuous contact of urine with tissue not prepared for this contact. In this article, we describe and classify the various biomaterials and cell cultures used in bladder tissue engineering and reviews the studies performed with humans. We conducted a review of literature published in the PubMed database between 1950 and 2017, following the principles of the PRISM declaration. Numerous in vitro and animal model studies have been conducted, but only 18 experiments have been performed with humans, with a total of 169 patients. The current evidence suggests that an acellular matrix, a synthetic polymer with urothelial and autologous smooth muscle cells attached in vitro or stem cells would be the most practical approach for experimental bladder reconstruction. Bladder replacement or expansion without using intestinal tissue is still a challenge, despite progress in the manufacture of biomaterials and the development of cell therapy. Well-designed studies with large numbers of patients and long follow-up times are needed to establish an effective clinical translation and standardisation of the check-up functional tests. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Orbital Metastasis: Rare Initial Presentation of an Occult Gall Bladder Carcinoma.

PubMed

Jain, Tarun Kumar; Parihar, Ashwin Singh; Sood, Ashwani; Basher, Rajender Kumar; Bollampally, Neeraja; Shekhawat, Amit Singh; Mittal, Bhagwant Rai

2018-03-01

Orbital metastases are known to arise from primary breast carcinoma followed by prostate, malignant melanoma, and lung carcinoma. We report a case of orbital metastasis as the initial presentation of an occult primary gall bladder carcinoma. The FDG PET/CT helped in localizing the occult distant primary site, which previously escaped detection, and also enabled the evaluation of orbital metastasis.

New clinical trial will test COXEN’s ability to choose best therapy for patients with advanced bladder cancer | Center for Cancer Research

Cancer.gov

The Genitourinary Malignancies Branch is now enrolling participants for a clinical trial that will evaluate whether analyzing a tumor’s genetic profile can identify which approved anticancer drugs are most likely to benefit individual patients whose bladder cancer has stopped responding to standard treatments. Learn more...

Magnetic Fluid Hyperthermia for Bladder Cancer: A Preclinical Dosimetry Study

PubMed Central

Oliveira, Tiago R.; Stauffer, Paul R.; Lee, Chen-Ting; Landon, Chelsea D.; Etienne, Wiguins; Ashcraft, Kathleen A.; McNerny, Katie L.; Mashal, Alireza; Nouls, John; Maccarini, Paolo F.; Beyer, Wayne F.; Inman, Brant; Dewhirst, Mark W.

2014-01-01

Purpose This paper describes a preclinical investigation of the feasibility of thermotherapy treatment of bladder cancer with Magnetic Fluid Hyperthermia (MFH), performed by analyzing the thermal dosimetry of nanoparticle heating in a rat bladder model. Materials and Methods The bladders of twenty-five female rats were instilled with magnetite-based nanoparticles, and hyperthermia was induced using a novel small animal magnetic field applicator (Actium Biosystems, Boulder, CO). We aimed to increase the bladder lumen temperature to 42°C in <10 min and maintain that temperature for 60 min. Temperatures were measured within the bladder lumen and throughout the rat with seven fiberoptic probes (OpSens Technologies, Quebec, Canada). An MRI analysis was used to confirm the effectiveness of the catheterization method to deliver and maintain various nanoparticle volumes within the bladder. Thermal dosimetry measurements recorded the temperature rise of rat tissues for a variety of nanoparticle exposure conditions. Results Thermal dosimetry data demonstrated our ability to raise and control the temperature of rat bladder lumen ≥1°C/min to a steady-state of 42°C with minimal heating of surrounding normal tissues. MRI scans confirmed the homogenous nanoparticle distribution throughout the bladder. Conclusion These data demonstrate that our MFH system with magnetite-based nanoparticles provide well-localized heating of rat bladder lumen with effective control of temperature in the bladder and minimal heating of surrounding tissues. PMID:24050253

HAMLET treatment delays bladder cancer development.

PubMed

Mossberg, Ann-Kristin; Hou, Yuchuan; Svensson, Majlis; Holmqvist, Bo; Svanborg, Catharina

2010-04-01

HAMLET is a protein-lipid complex that kills different types of cancer cells. Recently we observed a rapid reduction in human bladder cancer size after intravesical HAMLET treatment. In this study we evaluated the therapeutic effect of HAMLET in the mouse MB49 bladder carcinoma model. Bladder tumors were established by intravesical injection of MB49 cells into poly L-lysine treated bladders of C57BL/6 mice. Treatment groups received repeat intravesical HAMLET instillations and controls received alpha-lactalbumin or phosphate buffer. Effects of HAMLET on tumor size and putative apoptotic effects were analyzed in bladder tissue sections. Whole body imaging was used to study HAMLET distribution in tumor bearing mice compared to healthy bladder tissue. HAMLET caused a dose dependent decrease in MB49 cell viability in vitro. Five intravesical HAMLET instillations significantly decreased tumor size and delayed development in vivo compared to controls. TUNEL staining revealed selective apoptotic effects in tumor areas but not in adjacent healthy bladder tissue. On in vivo imaging Alexa-HAMLET was retained for more than 24 hours in the bladder of tumor bearing mice but not in tumor-free bladders or in tumor bearing mice that received Alexa-alpha-lactalbumin. Results show that HAMLET is active as a tumoricidal agent and suggest that topical HAMLET administration may delay bladder cancer development. Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

[Feasibility of using connective tissue prosthesis for autoplastic repair of urinary bladder wall defects (an experimental study)].

PubMed

Tyumentseva, N V; Yushkov, B G; Medvedeva, S Y; Kovalenko, R Y; Uzbekov, O K; Zhuravlev, V N

2016-12-01

Experiments on laboratory rats have shown the feasibility of autoplastic repair of urinary bladder wall defects using a connective-tissue capsule formed as the result of an inflammatory response to the presence of a foreign body. The formation of connective tissue prosthesis is characterized by developing fibrous connective tissue, ordering of collagen fibers, reducing the number of cells per unit area with a predominance of more mature cells - fibroblasts. With increasing time of observation, connective tissue prostheses were found to acquire a morphological structure similar to that of the urinary bladder wall. By month 12, the mucosa, the longitudinal and circular muscle layers were formed. The proposed method of partial autoplastic repair of urinary bladder wall is promising, has good long-term results, but requires further experimental studies.

[Epithelial intestine cells transdifferentiate into bladder urothelium in experiments in vivo].

PubMed

Popov, B K; Zaĭchik, A M; Bud'ko, M B; Zlobina, O V; Tolkunova, E N; Zhidkova, O V; Petrov, N S

2011-01-01

The autoplastic surgery by intestine tissue has been used for reconstructive therapy of the urinary tract since the middle of the last century; however, cell mechanisms of the urothelium engraftment are still obscure. Intestine stem cells possess plasticity and presumably enable after the autoplastic surgery to transdifferentiate into mature cells of urinary tract. Using the preliminary developed in vivo model for evaluation of somatic cells transdifferentiation into urothelium, we have found that the epithelial intestine cells producing Gfp transdifferentiate into the cryoinjured bladder urothelium of the syngenetic C57BL mice. Gfp was detected in the bladder tissue of mice-recipients using reverted polymerase chain reaction, primary fluorescence and immunofluorescence, while colocalization of the Gfp and Her-4 revealing similar to urothelium staining pattern was demonstrated in a few urothelium cells by double immunohistochemical staining of the bladder tissue with specific antibodies. The results obtained suggest that epithelial intestine cells enable to transdifferentiate into bladder urothelium, however the transdifferentiation level is low and presumably can not provide full functional urothelium engraftment in the case of autoplastic bladder surgery by intestine tissue.

Pattern of somatostatin receptors expression in normal and bladder cancer tissue samples.

PubMed

Karavitakis, Markos; Msaouel, Pavlos; Michalopoulos, Vassilis; Koutsilieris, Michael

2014-06-01

Known risks factors for bladder cancer progression and recurrence are limited regarding their prognostic ability. Therefore identification of molecular determinants of disease progression could provide with more specific prognostic information and could be translated into new approaches for biomarker development. In the present study we evaluated, the expression patterns of somatostatin receptors 1-5 (SSTRs) in normal and tumor bladder tissues. The expression of SSTR1-5 was characterized in 45 normal and bladder cancer tissue samples using reverse transcriptase-polymerase chain reaction (RT-PCR). SSTR1 was expressed in 24 samples, SSTR2 in 15, SSTR3 in 23, SSTR4 in 16 and SSTR5 in all but one sample. Bladder cancer tissue samples expressed lower levels of SSTR3. Co-expression of SSTRs was associated with superficial disease. Our results demonstrate, for the first time, that there is expression of SSTR in normal and bladder cancer urothelium. Further studies are required to evaluate the prognostic and therapeutic significance of these findings. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Advances in Imaging in Prostate and Bladder Cancer.

PubMed

Srivastava, Abhishek; Douglass, Laura M; Chernyak, Victoria; Watts, Kara L

2017-09-01

Recent advancements in urologic imaging techniques aim to improve the initial detection of urologic malignancies and subsequent recurrence and to more accurately stage disease. This allows the urologist to make better informed treatment decisions. In particular, exciting advances in the imaging of prostate cancer and bladder cancer have recently emerged including the use of dynamic, functional imaging with MRI and PET. In this review, we will explore these imaging modalities, in addition to new sonography techniques and CT, and how they hope to improve the diagnosis and management of prostate and bladder cancer.

New developments in fluorescence detection of ALA-induced protoporphyrin IX for cancer localization

NASA Astrophysics Data System (ADS)

Stepp, Herbert G.; Baumgartner, Reinhold; Betz, Christian; Bise, Karl; Brand, P.; Gamarra, Fernando; Haeussinger, Karl; Hillemanns, Peter; Huber, Rudolf M.; Knuechel, Ruth; Kriegmair, M.; Leunig, Andreas; Pichler, J.; Rick, Kai; Schulz, H.; Stanzel, F.; Stocker, Susanne; Wagner, Simon; Weigandt, H.

1997-12-01

After the very promising clinical results for the detection of bladder cancer in urology, preclinical and clinical studies on aminolevulinic acid (5-ALA) induced protoporphyrin IX (PPIX) are preformed in various disciplines now. This paper provides a brief overview of the progress on 5-ALA assisted fluorescence diagnosis in urology, pulmonology, neurosurgery, gynecology and ENT performed in collaboration with the Laser Research Laboratory at the Department of Urology of the Ludwig-Maximilians-University in Munich. Five-ALA can be applied either topically or systemically to induce an intracellular accumulation of fluorescing PPIX. With appropriate dosage of 5-ALA, malignant tissue can be stained selectively, and irradiation with violet light excites a bright red fluorescence of the tumor. Optical properties of the tissue tend to hamper the precise identification and demarcation of suspect areas in fluorescence images. Multicolor remission and fluorescence imaging, therefore, seems to be indispensable for a reliable tumor localization.

Latest results of 5-ALA-based fluorescence diagnosis and other medical disciplines

NASA Astrophysics Data System (ADS)

Baumgartner, Reinhold

1999-02-01

Preclinical and clinical studies on 5-aminolevulinic acid (5- ALA) induced Protoporphyrin IX (PPIX) are performed in various departments now following promising clinical results for the detection of bladder cancer in urology. This paper provides an overview on the progress of 5-ALA assisted fluorescence diagnosis in urology, pulmonology, neurosurgery, gynecology and ENT coordinated by the Laser Research Laboratory of the Ludwig-Maximilians-University in Munich. 5-ALA can be applied either topically or systematically to induce an intracellular accumulation of fluorescing PPIX. With appropriate dosage of 5-ALA, malignant tissue can be stained selectively, and irradiation with violet light excites a bright red fluorescence of the tumor visible with naked eyes. Optical properties of the tissue tend to hamper the precise identification and demarcation of suspect areas in fluorescence images. Multicolor remission and fluorescence imaging, therefore, should improve tumor localization in future.

Urothelial conversion of 5-aminolevulinic acid to protoporphyrin IX following oral or intravesical administration

NASA Astrophysics Data System (ADS)

Moore, Ronald B.; Miller, Gerald G.; Brown, Kevin; Bhatnagar, Rakesh; Tulip, John; McPhee, Malcolm S.

1995-03-01

Preferential conversion of 5-aminolevulinic acid (5-ALA) to protoporphyrin-IX (Pp-IX) occurs in malignant tissue, with accumulation to diagnostic and therapeutic levels. Recent studies have suggested selective conversion in epithelial tissue following oral or intravenous administration. Topical application avoids systemic photosensitization. However, the glycosaminoglycan (GAG) layer lining the urinary bladder is believed to be a protective barrier generally limiting mucosal absorption. Our objective was to evaluate uptake and conversion of 5-ALA following intravesical or oral administration. Using a rat model, Pp-IX content within epithelial and muscularis layers was quantitated by fluorescence confocal microscopy. Following intravesical administration, Pp-IX accumulated predominantly in the urothelium; whereas following oral administration, Pp-IX accumulated in both the urothelium and muscularis. Intravesical 5-ALA administration is feasible and may afford selective photosensitization of the urothelium for treatment of carcinoma in situ.

Adenocarcinoma arising in urinary bladder endocervicosis.

PubMed

Nakaguro, Masato; Tsuzuki, Toyonori; Shimada, Satoko; Taki, Tetsuro; Tsuchiyama, Mari; Kitamura, Atsuko; Suzuki, Yasuhiko; Nakano, Yojiro; Ono, Kenzo

2016-02-01

Endocervicosis is a rare benign condition characterized by the presence of endocervical-type mucinous glands. Urinary bladder endocervicosis forms an elevated lesion in the posterior wall of the urinary bladder and is sometimes misdiagnosed as a malignant tumor clinically and pathologically. Herein we describe the first case of adenocarcinoma arising in urinary bladder endocervicosis. The patient, a 58-year-old woman, presented with asymptomatic hematuria. Cystoscopy revealed a nodular mass measuring 4 cm in diameter in the posterior wall, and total cystectomy was performed. Histology revealed that the elevated lesion of the bladder wall was composed of haphazard proliferation of cystic glands lined by benign endocervical-type epithelium. An adenocarcinoma arose at the center of this endocervicosis. Mucin histochemistry revealed the presence of sulfomucin in both the endocervicosis and adenocarcinoma components. Immunohistochemically, the endocervicosis was positive for cytokeratin (CK) 7, AE1/AE3, CAM5.2, HBME1, CA19-9, and estrogen receptor (ER), and negative for CK20, CDX2, progesterone receptor (PR), MUC5AC, and β-catenin. The adenocarcinoma showed similar immunohistochemical results, except for loss of ER expression and a slight increase in the ratio of Ki-67-positive cells. This case indicates that endocervicosis, known as a benign lesion, harbors the possibility of malignant transformation. © 2016 The Authors. Pathology International published by Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

Mucoepidermoid carcinoma of lung masquerading as urothelial carcinoma of bladder

PubMed Central

Graham, Donna M.; O’Connor, Kate M.; Hinchion, John; Coate, Linda E.; Burke, Louise; Power, Derek G.

2013-01-01

Background Mucoepidermoid carcinoma (MEC) of the lung is a rare subtype of non-small cell lung cancer. There is no consensus regarding optimal management for this disease. Case report We present a case of MEC of the lung in a 75 year-old female with a history of superficial urothelial carcinoma of the bladder. The patient was found to have an asymptomatic lung mass. Initial biopsy suggested metastatic recurrence of urothelial carcinoma and therefore, cisplatin and gemcitabine chemotherapy was administered prior to surgical resection. Pathological analysis of the resected specimen confirmed a diagnosis of stage IIIA MEC with focal high-grade features including transitional cell-like areas. Adjuvant radiotherapy was administered due to a positive microscopic resection margin. No chemotherapy was given due to lack of supporting data. The patient developed widespread metastatic disease 3 months following completion of radiotherapy and died 1 month later. Conclusion This case demonstrates the possibility of dual pathology in cases where metastatic disease is suspected. The use of small tissue samples may complicate diagnosis due to the heterogeneity of malignant tumours. PMID:24936321

Predicting the failure of retrograde ureteral stent insertion for managing malignant ureteral obstruction in outpatients

PubMed Central

WANG, JIN-YOU; ZHANG, HAI-LIANG; ZHU, YAO; QIN, XIAO-JIAN; DAI, BO; YE, DING-WEI

2016-01-01

Malignant ureteral obstruction (MUO) is an unpropitious sign that is commonly observed in patients with advanced incurable cancer. The present study aimed to evaluate predictive factors for the failure of retrograde ureteral stent insertion in the management of MUO in outpatients. A total of 164 patients with MUO were retrospectively assessed in this study. Clinical factors, including age, gender, type of malignancy, level of obstruction, cause of obstruction, pre-operative creatinine level, degree of hydronephrosis, condition of the contralateral ureter, prior radiotherapy, Eastern Cooperative Oncology Group performance status (ECOG PS), bladder wall invasion and technical failure, were recorded for each case. Univariate and multivariate logistic regression analyses were used to investigate the risk factors for predicting the failure of retrograde ureteral stent insertion. In total, 38 out of 164 patients experienced bilateral obstruction, therefore, a total of 202 ureteral units were available for data analysis. The rate of insertion failure in MUO was 34.65%. Multivariate analyses identified ECOG PS, degree of hydronephrosis and bladder wall invasion as independent predictors for insertion failure. Overall, the present study found that rate of retrograde ureteral stent insertion failure is high in outpatients with MUO, and that ECOG PS, degree of hydronephrosis and bladder invasion are potential independent predictors of insertion failure. PMID:26870299

[Bladder pseudotumor in childhood].

PubMed

Fernández Arjona, M; Muñoz-Delgado Salmerón, J; Shihadei, S; Colomar, P J; García Estevez, J A

1997-01-01

Case report of a 10 year-old male with vesical mass suggestive of a rabdomiosarcoma based on the radiologic studies performed. The existence of an inflammatory process with no signs of malignancy was confirmed by transurethral resection. The serological studies were negative and the absence of malignant disease in further substantiated by immunohistochemistry. We want to emphasize that certain vesical masses. which appear to be malignant on the radiological study (Pseudotumours), may be just inflammatory processes.

Gamma-Klotho exhibits multiple roles in tumor growth of human bladder cancer.

PubMed

Hori, Shunta; Miyake, Makito; Tatsumi, Yoshihiro; Morizawa, Yosuke; Nakai, Yasushi; Onishi, Sayuri; Onishi, Kenta; Iida, Kota; Gotoh, Daisuke; Tanaka, Nobumichi; Fujimoto, Kiyohide

2018-04-13

Alpha-Klotho (KLα) and beta-Klotho (KLβ) have recently been reported to correlate with cancer prognosis in some malignancies and we previously reported the association between KLα, KLβ, and urothelial carcinoma of the bladder (UCB), indicating that KLβ acts as a tumor promoter. However, the association between gamma-Klotho (KLγ) and cancer prognosis remains unclear. In the present study, we evaluated the association between KLγ and UCB. To evaluate the effect of KLγ on human bladder cancer cell lines in vitro assays were performed. Exogenous KLγ increased the ability of human bladder cancer cells to proliferate, migrate, invade, form colonies, and provide anchorage-independent growth potential. In in vivo assays, eighteen mice bearing xenografts inoculated using UM-UC-3, were randomly divided into three groups and treated with a small interfering RNA (siRNA) by intratumoral administration once a week for four weeks. Knockdown of KLγ with siRNA led to a dramatic change in tumor growth and suggested that KLγ had effects on tumor growth, including promotion of cell proliferation, inhibition of apoptosis, and enhancement of the epithelial-mesenchymal transition. To confirm the study, human tissue samples were used and patients were divided into two groups according to KLγ expression level. High expression of KLγ was significantly associated with higher stage and grade cancer and the presence of lymphovascular invasion compared to patients with lower expression of KLγ. Our results suggest that KLγ plays an important role in tumor invasion and progression and these results may lead to the development of new therapies and diagnostic methods for UCB.

Gamma-Klotho exhibits multiple roles in tumor growth of human bladder cancer

PubMed Central

Hori, Shunta; Miyake, Makito; Tatsumi, Yoshihiro; Morizawa, Yosuke; Nakai, Yasushi; Onishi, Sayuri; Onishi, Kenta; Iida, Kota; Gotoh, Daisuke; Tanaka, Nobumichi; Fujimoto, Kiyohide

2018-01-01

Alpha-Klotho (KLα) and beta-Klotho (KLβ) have recently been reported to correlate with cancer prognosis in some malignancies and we previously reported the association between KLα, KLβ, and urothelial carcinoma of the bladder (UCB), indicating that KLβ acts as a tumor promoter. However, the association between gamma-Klotho (KLγ) and cancer prognosis remains unclear. In the present study, we evaluated the association between KLγ and UCB. To evaluate the effect of KLγ on human bladder cancer cell lines in vitro assays were performed. Exogenous KLγ increased the ability of human bladder cancer cells to proliferate, migrate, invade, form colonies, and provide anchorage-independent growth potential. In in vivo assays, eighteen mice bearing xenografts inoculated using UM-UC-3, were randomly divided into three groups and treated with a small interfering RNA (siRNA) by intratumoral administration once a week for four weeks. Knockdown of KLγ with siRNA led to a dramatic change in tumor growth and suggested that KLγ had effects on tumor growth, including promotion of cell proliferation, inhibition of apoptosis, and enhancement of the epithelial-mesenchymal transition. To confirm the study, human tissue samples were used and patients were divided into two groups according to KLγ expression level. High expression of KLγ was significantly associated with higher stage and grade cancer and the presence of lymphovascular invasion compared to patients with lower expression of KLγ. Our results suggest that KLγ plays an important role in tumor invasion and progression and these results may lead to the development of new therapies and diagnostic methods for UCB. PMID:29731962

Stokes polarimetry imaging of dog prostate tissue

NASA Astrophysics Data System (ADS)

Kim, Jihoon; Johnston, William K., III; Walsh, Joseph T., Jr.

2010-02-01

Prostate cancer is the second leading cause of death in the United States in 2009. Radical prostatectomy (complete removal of the prostate) is the most common treatment for prostate cancer, however, differentiating prostate tissue from adjacent bladder, nerves, and muscle is difficult. Improved visualization could improve oncologic outcomes and decrease damage to adjacent nerves and muscle important for preservation of potency and continence. A novel Stokes polarimetry imaging (SPI) system was developed and evaluated using a dog prostate specimen in order to examine the feasibility of the system to differentiate prostate from bladder. The degree of linear polarization (DOLP) image maps from linearly polarized light illumination at different visible wavelengths (475, 510, and 650 nm) were constructed. The SPI system used the polarization property of the prostate tissue. The DOLP images allowed advanced differentiation by distinguishing glandular tissue of prostate from the muscular-stromal tissue in the bladder. The DOLP image at 650 nm effectively differentiated prostate and bladder by strong DOLP in bladder. SPI system has the potential to improve surgical outcomes in open or robotic-assisted laparoscopic removal of the prostate. Further in vivo testing is warranted.

Identification of Carbonic Anhydrase IX as a Novel Target for Endoscopic Molecular Imaging of Human Bladder Cancer.

PubMed

Wang, Jiaqi; Fang, Ruizhe; Wang, Lu; Chen, Guang; Wang, Hongzhi; Wang, Zhichao; Zhao, Danfeng; Pavlov, Valentin N; Kabirov, Ildar; Wang, Ziqi; Guo, Pengyu; Peng, Li; Xu, Wanhai

2018-06-27

Emerging novel optical imaging techniques with cancer-specific molecular imaging agents offer a powerful and promising platform for cancer detection and resection. White-light cystoscopy and random bladder biopsies remain the most appropriate but nonetheless suboptimal diagnostic technique for bladder cancer, which is associated with high morbidity and recurrence. However, white-light cystoscopy has intrinsic shortcomings. Although current optical imaging technologies hold great potential for improved diagnostic accuracy, there are few imaging agents for specific molecular targeting. Carbonic anhydrase IX (CAIX) plays a pivotal role in tumorigenesis and tumor progression with potential value as an imaging target. Here, we investigated the feasibility of CAIX as a target and validated the diagnostic performance and significance of CAIX as an imaging agent. We first analyzed the data from The Cancer Genome Atlas (TCGA). Pairs of samples comprising bladder cancer and adjacent normal tissue were collected. All tissue samples were used for real-time PCR and immunohistochemistry to compare CAIX expression in normal and cancer tissue. Using blue-light cystoscopy, we observed the optical distribution of fluorescently labeled CAIX antibody in freshly excised human bladders and obtained random bladder biopsies to assess sensitivity and specificity. The TCGA data revealed that CAIX expression was significantly higher in bladder cancer specimens than in normal tissue. The outcome was similar in quantitative real-time PCR analysis. In immunohistochemical analysis, bladder cancer specimens classified in four pathological subtypes presented a variety of positive staining intensities, whereas no benign specimens showed CAIX staining. Using blue-light cystoscopy, we distinguished bladder cancers that were mainly papillary, some variants of urothelial carcinoma, and less carcinoma in situ, from benign tissue, despite the presence of suspicious-appearing mucosa. The sensitivity and specificity for CAIX-targeted imaging were 88.00% and 93.75%, respectively. CAIX-targeted molecular imaging could be a feasible and adaptive alternative approach for the accurate diagnosis and complete resection of bladder cancer. © 2018 The Author(s). Published by S. Karger AG, Basel.

Genome-wide screening and identification of long noncoding RNAs and their interaction with protein coding RNAs in bladder urothelial cell carcinoma.

PubMed

Wang, Longxin; Fu, Dian; Qiu, Yongbin; Xing, Xiaoxiao; Xu, Feng; Han, Conghui; Xu, Xiaofeng; Wei, Zhifeng; Zhang, Zhengyu; Ge, Jingping; Cheng, Wen; Xie, Hai-Long

2014-07-10

To understand lncRNAs expression profiling and their potential functions in bladder cancer, we investigated the lncRNA and coding RNA expression on human bladder cancer and normal bladder tissues. Bioinformatic analysis revealed thousands of significantly differentially expressed lncRNAs and coding mRNA in bladder cancer relative to normal bladder tissue. Co-expression analysis revealed that 50% of lncRNAs and coding RNAs expressed in the same direction. A subset of lncRNAs might be involved in mTOR signaling, p53 signaling, cancer pathways. Our study provides a large scale of co-expression between lncRNA and coding RNAs in bladder cancer cells and lays biological basis for further investigation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Clinical value and potential pathways of miR-183-5p in bladder cancer: A study based on miRNA-seq data and bioinformatics analysis

PubMed Central

Gao, Jia-Min; Huang, Lin-Zhen; Huang, Zhi-Guang; He, Rong-Quan

2018-01-01

The clinicopathological value and exploration of the potential molecular mechanism of microRNA-183-5p (miR-183-5p) have been investigated in various cancers; however, to the best of the author's knowledge, no similar research has been reported for bladder cancer. In the present study, it was revealed that the expression level of miR-183-5p was notably increased in bladder cancer tissues compared with adjacent non-cancerous tissues (P=0.001) and was markedly increased in the tissue samples of papillary, pathological T stage (T0-T2) and pathological stage (I–II) compared with tissue samples of their counterparts (P=0.05), according to data from The Cancer Genome Atlas. Receiver operating characteristic analysis revealed the robust diagnostic value of miR-183-5p for distinguishing bladder cancer from non-cancerous bladder tissues (area under curve=0.948; 95% confidence interval: 0.919–0.977). Amplification and deep deletion of miR-183-5p were indicated by cBioPortal, accounting for 1% (4/412) of bladder cancer cases. Data from YM500v3 demonstrated that compared with other cancers, bladder cancer exhibited high expression levels of miR-183-5p, and miR-183-5p expression in primary solid tumors was much higher compared with solid normal tissues. A meta-analysis indicated that miR-183-5p was more highly expressed in bladder cancer samples compared with normal counterparts. A total of 88 potential target genes of miR-183-5p were identified, 13 of which were discerned as hub genes by protein-protein interaction. The epithelial-to-mesenchymal transition pathway was the most significantly enriched pathway by FunRich (P=0.0001). In summary, miR-183-5p may participate in the tumorigenesis and development of bladder cancer via certain signaling pathways, particularly the epithelial-to-mesenchymal transition pathway. However, the exact molecular mechanism of miR-183-5p in bladder cancer must be validated by in vitro and in vivo experiments. PMID:29616090

Clinical value and potential pathways of miR-183-5p in bladder cancer: A study based on miRNA-seq data and bioinformatics analysis.

PubMed

Gao, Jia-Min; Huang, Lin-Zhen; Huang, Zhi-Guang; He, Rong-Quan

2018-04-01

The clinicopathological value and exploration of the potential molecular mechanism of microRNA-183-5p (miR-183-5p) have been investigated in various cancers; however, to the best of the author's knowledge, no similar research has been reported for bladder cancer. In the present study, it was revealed that the expression level of miR-183-5p was notably increased in bladder cancer tissues compared with adjacent non-cancerous tissues (P=0.001) and was markedly increased in the tissue samples of papillary, pathological T stage (T0-T2) and pathological stage (I-II) compared with tissue samples of their counterparts (P=0.05), according to data from The Cancer Genome Atlas. Receiver operating characteristic analysis revealed the robust diagnostic value of miR-183-5p for distinguishing bladder cancer from non-cancerous bladder tissues (area under curve=0.948; 95% confidence interval: 0.919-0.977). Amplification and deep deletion of miR-183-5p were indicated by cBioPortal, accounting for 1% (4/412) of bladder cancer cases. Data from YM500v3 demonstrated that compared with other cancers, bladder cancer exhibited high expression levels of miR-183-5p, and miR-183-5p expression in primary solid tumors was much higher compared with solid normal tissues. A meta-analysis indicated that miR-183-5p was more highly expressed in bladder cancer samples compared with normal counterparts. A total of 88 potential target genes of miR-183-5p were identified, 13 of which were discerned as hub genes by protein-protein interaction. The epithelial-to-mesenchymal transition pathway was the most significantly enriched pathway by FunRich (P=0.0001). In summary, miR-183-5p may participate in the tumorigenesis and development of bladder cancer via certain signaling pathways, particularly the epithelial-to-mesenchymal transition pathway. However, the exact molecular mechanism of miR-183-5p in bladder cancer must be validated by in vitro and in vivo experiments.

Bladder Smooth Muscle Cells Differentiation from Dental Pulp Stem Cells: Future Potential for Bladder Tissue Engineering

PubMed Central

Song, Bing; Jiang, Wenkai; Alraies, Amr; Liu, Qian; Gudla, Vijay; Oni, Julia; Wei, Xiaoqing; Sloan, Alastair; Ni, Longxing; Agarwal, Meena

2016-01-01

Dental pulp stem cells (DPSCs) are multipotent cells capable of differentiating into multiple cell lines, thus providing an alternative source of cell for tissue engineering. Smooth muscle cell (SMC) regeneration is a crucial step in tissue engineering of the urinary bladder. It is known that DPSCs have the potential to differentiate into a smooth muscle phenotype in vitro with differentiation agents. However, most of these studies are focused on the vascular SMCs. The optimal approaches to induce human DPSCs to differentiate into bladder SMCs are still under investigation. We demonstrate in this study the ability of human DPSCs to differentiate into bladder SMCs in a growth environment containing bladder SMCs-conditioned medium with the addition of the transforming growth factor beta 1 (TGF-β1). After 14 days of exposure to this medium, the gene and protein expression of SMC-specific marker (α-SMA, desmin, and calponin) increased over time. In particular, myosin was present in differentiated cells after 11 days of induction, which indicated that the cells differentiated into the mature SMCs. These data suggested that human DPSCs could be used as an alternative and less invasive source of stem cells for smooth muscle regeneration, a technology that has applications for bladder tissue engineering. PMID:26880982

Rhabdomyosarcoma of the urinary bladder in adults: predilection for alveolar morphology with anaplasia and significant morphologic overlap with small cell carcinoma.

PubMed

Paner, Gladell P; McKenney, Jesse K; Epstein, Jonathan I; Amin, Mahul B

2008-07-01

Rhabdomyosarcoma (RMS) represents the most common malignant soft tissue tumor in children and adolescents with the urinary bladder representing a frequent site. Most of these urinary bladder tumors are embryonal RMS, predominantly the botryoid subtype. RMSs of the urinary bladder in adults are distinctively rare and the subject of only case reports. We report the clinicopathologic features of 5 bladder neoplasms with rhabdomyosarcomatous differentiation in adults and emphasize the differential diagnosis in the adult setting. The patients, 4 men and 1 woman, ranged in age from 23 to 85 years (mean 65.4 y). Gross hematuria was the most common initial symptom, although 2 patients had metastatic disease at presentation. Four cases were pure primary RMSs of the bladder and 1 case was a sarcomatoid urothelial carcinoma with RMS representing the extensive heterologous component. All 5 cases demonstrated a diffuse growth pattern (ie, non-nested), of which 4 cases had nuclear anaplasia (Wilms criteria without the atypical mitotic figure requirement); only 1 case (the sarcomatoid carcinoma) showed obvious rhabdomyoblastic differentiation (ie, strap cells). Three cases were of the alveolar subtype (1 admixed with embryonal histology) and 2 were RMS, not further classified. Microscopically, all tumors had a primitive undifferentiated morphology with cells containing scant cytoplasm, varying round to fusiform nuclei with even chromatin distribution, and frequent mitoses. The degree of morphologic overlap with small cell carcinoma of the bladder, a relatively more common round cell tumor in adults, was striking. The epithelial component of the sarcomatoid carcinoma was high-grade invasive urothelial carcinoma with glandular differentiation. No other case had previous history of bladder cancer or concurrent carcinoma in situ or invasive urothelial carcinoma. All tumors showed immunohistochemical expression for desmin, myogenin, and/or MyoD1. Synaptophysin was performed in 4 cases, and 3 showed weak cytoplasmic immunoreactivity. Two patients received chemotherapy, 2 underwent cystectomy, and 1 had transurethral resection alone. Outcome data were available in 4 cases, and all 4 died of disease (1, 4, 8, and 8 mo). In conclusion, (1) RMS of the urinary bladder in adults more commonly presents as a primitive round blue cell neoplasm that has significant morphologic and immunohistochemical overlap with small cell carcinoma of the bladder. (2) Although RMS in children generally have a botryoid embryonal histology with favorable outcome, bladder RMS in adults frequently demonstrates alveolar or unclassified histology, commonly with anaplasia, and have a uniformly aggressive clinical course.

The Urinary Bladder Transcriptome and Proteome Defined by Transcriptomics and Antibody-Based Profiling

PubMed Central

Habuka, Masato; Fagerberg, Linn; Hallström, Björn M.; Pontén, Fredrik; Yamamoto, Tadashi; Uhlen, Mathias

2015-01-01

To understand functions and diseases of urinary bladder, it is important to define its molecular constituents and their roles in urinary bladder biology. Here, we performed genome-wide deep RNA sequencing analysis of human urinary bladder samples and identified genes up-regulated in the urinary bladder by comparing the transcriptome data to those of all other major human tissue types. 90 protein-coding genes were elevated in the urinary bladder, either with enhanced expression uniquely in the urinary bladder or elevated expression together with at least one other tissue (group enriched). We further examined the localization of these proteins by immunohistochemistry and tissue microarrays and 20 of these 90 proteins were localized to the whole urothelium with a majority not yet described in the context of the urinary bladder. Four additional proteins were found specifically in the umbrella cells (Uroplakin 1a, 2, 3a, and 3b), and three in the intermediate/basal cells (KRT17, PCP4L1 and ATP1A4). 61 of the 90 elevated genes have not been previously described in the context of urinary bladder and the corresponding proteins are interesting targets for more in-depth studies. In summary, an integrated omics approach using transcriptomics and antibody-based profiling has been used to define a comprehensive list of proteins elevated in the urinary bladder. PMID:26694548

Risks of secondary malignancies with heterotopic bone radiation therapy for patients younger than 40 years

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cadieux, Catherine L., E-mail: ccadieux@umail.iu.edu; DesRosiers, Colleen; McMullen, Kevin

Heterotopic ossification (HO) of the bone is defined as a benign condition in which abnormal bone formation occurs in soft tissue. One of the most common prophylactic treatments for HO is radiation therapy (RT). This study retrospectively reviewed 20 patients younger than the age of 40 who received radiation to prevent HO in a single fraction of 7 Gray. The purpose of this study is to assess the risk of a second malignancy in these patients by recreating their treatment fields and contouring organs at risk to estimate the radiation dose absorbed by normal tissues outside the radiation treatment field.more » Diagnostic computed tomography (CT) scans for each patient were used to recreate treatment fields and to calculate dose to structures of interest. The distance from the field edge to each structure and its depth was recorded. Dose measurements in a water phantom were performed for the range of depths, distances, and field sizes used in the actual treatment plans. Computer-generated doses were compared to estimates based on measurement. The structure dose recorded was the higher dose generated between the 2 methods. Scatter dose was recorded to the rectum, bladder, sigmoid colon, small bowel, ovaries and utero-cervix in female patients, and prostate and gonads in male patients. In some patients, there is considerable dose received by certain organs from scatter because of their proximity to the radiation field. The average dose to the ovarian region was 4.125 Gy with a range of 1.085 to 6.228 Gy. The risk estimate for these patients ranged from 0.16% to 0.93%. The average total lifetime risk estimate for the bladder in all patients is 0.22% and the average total lifetime risk estimate for the remainder organs in all patients is 1.25%. In conclusions, proper shielding created from multileaf collimators (MLCs), blocks, and shields should always be used when possible.« less

Bladder chondrosarcoma plus urothelial carcinoma in recurred transitional cell carcinoma of the upper urinary tract: a case report and literature review.

PubMed

Cho, Min Hyun; Kim, Sung Han; Park, Weon Seo; Joung, Jae Young; Seo, Ho Kyung; Chung, Jinsoo; Lee, Kang Hyun

2016-10-20

Sarcomatoid urothelial carcinoma (SUC) is a rare malignant neoplasm of the urinary bladder comprising 0.2-0.6 % of all histological bladder tumor subtypes. It presents as a high-stage malignancy and exhibits aggressive biological behavior, regardless of the treatment employed. It is defined as histologically indistinguishable from sarcoma and as a high-grade biphasic neoplasm with malignant epithelial and mesenchymal components. The mean age of patients presenting with SUC is 66 years, and the male-to-female ratio is 3:1. In addition, gross hematuria is usually present. The prognosis of SUC is poorer than that of typical urothelial carcinoma because of uncertainty concerning the optimal treatment regimen. We report the case of a 77-year-old woman with SUC containing a chondrosarcoma component who, 12 years previously, had undergone a nephroureterectomy for pT3N0M0 ureter cancer of the contralateral upper urinary tract. From the 4th year of follow-up after nephroureterectomy, multiple recurrent bladder tumors staged as Ta transitional cell carcinoma developed, and six transurethral resections of the bladder (TURB) with multiple intravesical instillations were performed without any evidence of metastases and upper tract recurrences. In 2015, a right partial distal ureterectomy and an additional TURB were performed due to a papillary mass at the right contralateral ureterovesical junction of the bladder, which was confirmed as a high-grade pT1 transitional cell carcinoma. After a further 2 years of follow-up, total pelvic exenteration with an ileal conduit diversion was performed to remove the mass, which was a pT4N0M0 tumor composed of carcinomatous and sarcomatous elements compatible with a sarcomatoid carcinoma including grade 3 transitional cell carcinoma and chondrosarcoma. Immunohistochemical examination showed that tumor cells were positive for vimentin and p63 and negative for NSE and Cd56 markers. In the first postoperative month, a metastatic lung nodule was detected on chest CT. The patient was scheduled for adjuvant gemcitabine-cisplatin chemotherapy. The present case was interesting because we cannot be sure if the SUC chondrosarcoma originated from the 12-year-ago proximal ureter tumor, the 2-year-ago contralateral distal ureter tumor, or a new primary bladder tumor. Genetic profiling might have been useful to determine the origin of the SUC chondrosarcoma.

ADVANCES IN IMAGING TECHNOLOGIES IN THE EVALUATION OF HIGH-GRADE BLADDER CANCER

PubMed Central

Zlatev, Dimitar V.; Altobelli, Emanuela; Liao, Joseph C.

2015-01-01

Bladder cancer is a heterogeneous disease that ranges from low-grade variant with an indolent course, to high-grade subtype with a recurrent, progressive, and potentially lethal outcome. Accurate assessment for individualized treatment depends critically on the diagnostic accuracy of white light cystoscopy. Despite its central role, white light cystoscopy has several well-documented shortcomings including difficult flat lesion detection, imprecise tumor delineation that limits complete resection, differentiation between inflammation and malignancy, and grade and stage determination. As the limitations of white light cystoscopy contribute to the risk of cancer persistence, recurrence, and progression, there is a need for improved visualization of flat, multifocal, high-grade, and muscle-invasive lesions. Optical imaging technologies have emerged as an adjunct to white light cystoscopy with the goal to guide more effective treatment by improving cancer detection and patient stratification on the basis of grade and stage. Photodynamic diagnosis and narrow band imaging are macroscopic imaging modalities similar to white light cystoscopy, but provide additional contrast enhancement of bladder tumors and have been shown to improve detection rates. Confocal laser endomicroscopy and optical coherence tomography are microscopic imaging technologies that enable real-time high resolution, subsurface tissue characterization with spatial resolutions similar to histology. Molecular imaging offers the potential for the combination of optical imaging technologies with cancer-specific molecular agents to improve the specificity of disease detection. PMID:25882557

Comprehensive Analysis of ETS Family Members in Melanoma by Fluorescence In Situ Hybridization Reveals Recurrent ETV1 Amplification

PubMed Central

Mehra, Rohit; Dhanasekaran, Saravana M; Palanisamy, Nallasivam; Vats, Pankaj; Cao, Xuhong; Kim, Jung H; Kim, David SL; Johnson, Timothy; Fullen, Douglas R; Chinnaiyan, Arul M

2013-01-01

E26 transformation-specific (ETS) transcription factors are known to be involved in gene aberrations in various malignancies including prostate cancer; however, their role in melanoma oncogenesis has yet to be fully explored. We have completed a comprehensive fluorescence in situ hybridization (FISH)-based screen for all 27 members of the ETS transcription factor family on two melanoma tissue microarrays, representing 223 melanomas, 10 nevi, and 5 normal skin tissues. None of the melanoma cases demonstrated ETS fusions; however, 6 of 114 (5.3%) melanomas were amplified for ETV1 using a break-apart FISH probe. For the six positive cases, locus-controlled FISH probes revealed that two of six cases were amplified for the ETV1 region, whereas four cases showed copy gains of the entire chromosome 7. The remaining 26 ETS family members showed no chromosomal aberrations by FISH. Quantitative polymerase chain reaction showed an average 3.4-fold (P value = .00218) increased expression of ETV1 in melanomas, including the FISH ETV1-amplified cases, when compared to other malignancies (prostate, breast, and bladder carcinomas). These data suggest that a subset of melanomas overexpresses ETV1 and amplification of ETV1 may be one mechanism for achieving high gene expression. PMID:23908683

Hemoglobin enhances tissue factor expression on human malignant cells.

PubMed

Siddiqui, F A; Amirkhosravi, A; Amaya, M; Meyer, T; Biggerstaff, J; Desai, H; Francis, J L

2001-04-01

Tissue Factor (TF) is a transmembrane glycoprotein that complexes with factor VII/activated factor VII to initiate blood coagulation. TF may be expressed on the surface of various cells including monocytes and endothelial cells. Over-expression of TF in human tumor cell lines promotes metastasis. We recently showed that hemoglobin (Hb) forms a specific complex with TF purified from human malignant melanoma cells and enhances its procoagulant activity (PCA). To further study this interaction, we examined the effect of Hb on the expression of TF on human malignant (TF+) cells and KG1 myeloid leukemia (TF-) cells. Human melanoma A375 and J82 bladder carcinoma cells, which express TF at moderate and relatively high levels, respectively, were incubated with varying concentrations (0-1.5 mg/ml) of Hb. After washing, cells were analyzed for Hb binding and TF expression using flow cytometry and confocal microscopy. Hb bound to the cells in a concentration-dependent manner, and increased both TF expression and PCA. The human A375 malignant melanoma cells incubated with Hb (1 mg/ml) expressed up to six times more TF antigen than cells without Hb. This increase in TF expression and PCA of intact cells incubated with Hb was significantly inhibited by cycloheximide at a concentration of 10 microg/ml (P < 0.01). An increase in total cellular TF antigen content was demonstrated by specific immunoassay. In contrast, Hb (5 mg/ml) did not induce TF expression and PCA on KG1 cells as determined by flow cytometry and TF (FXAA) activity. We conclude that Hb specifically binds to TF-bearing malignant cells and increases their PCA. This effect seems to be at least partly due to de novo synthesis of TF and increased surface expression. However, the exact mechanism by which Hb binds and upregulates TF expression remains to be determined.

Histogram analysis of apparent diffusion coefficient at 3.0 T in urinary bladder lesions: correlation with pathologic findings.

PubMed

Suo, Shi-Teng; Chen, Xiao-Xi; Fan, Yu; Wu, Lian-Ming; Yao, Qiu-Ying; Cao, Meng-Qiu; Liu, Qiang; Xu, Jian-Rong

2014-08-01

To investigate the potential value of histogram analysis of apparent diffusion coefficient (ADC) obtained at standard (700 s/mm(2)) and high (1500 s/mm(2)) b values on a 3.0-T scanner in the differentiation of bladder cancer from benign lesions and in assessing bladder tumors of different pathologic T stages and to evaluate the diagnostic performance of ADC-based histogram parameters. In all, 52 patients with bladder lesions, including benign lesions (n = 7) and malignant tumors (n = 45; T1 stage or less, 23; T2 stage, 7; T3 stage, 8; and T4 stage, 7), were retrospectively evaluated. Magnetic resonance examination at 3.0 T and diffusion-weighted imaging were performed. ADC maps were obtained at two b values (b = 700 and 1500 s/mm(2); ie, ADC-700 and ADC-1500). Parameters of histogram analysis included mean, kurtosis, skewness, and entropy. The correlations between these parameters and pathologic results were revealed. Receiver operating characteristic (ROC) curves were generated to determine the diagnostic value of histogram parameters. Significant differences were found in mean ADC-700, mean ADC-1500, skewness ADC-1500, and kurtosis ADC-1500 between bladder cancer and benign lesions (P = .002-.032). There were also significant differences in mean ADC-700, mean ADC-1500, and kurtosis ADC-1500 among bladder tumors of different pathologic T stages (P = .000-.046). No significant differences were observed in other parameters. Mean ADC-1500 and kurtosis ADC-1500 were significantly correlated with T stage, respectively (ρ = -0.614, P < .001; ρ = 0.374, P = .011). ROC analysis showed that the combination of mean ADC-1500 and kurtosis ADC-1500 has the maximal area under the ROC curve (AUC, 0.894; P < .001) in the differentiation of benign lesions and malignant tumors, with a sensitivity of 77.78% and specificity of 100%. AUCs for differentiating low- and high-stage tumors were 0.840 for mean ADC-1500 (P < .001) and 0.696 for kurtosis ADC-1500 (P = .015). Histogram analysis of ADC-1500 at 3.0 T can be useful in evaluation of bladder lesions. A combination of mean ADC-1500 and kurtosis ADC-1500 may be more beneficial in the differentiation of benign and malignant lesions. Mean ADC-1500 was the most promising parameter for differentiating low- from high-stage bladder cancer. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.

Radiological interventions in malignant biliary obstruction

PubMed Central

Madhusudhan, Kumble Seetharama; Gamanagatti, Shivanand; Srivastava, Deep Narayan; Gupta, Arun Kumar

2016-01-01

Malignant biliary obstruction is commonly caused by gall bladder carcinoma, cholangiocarcinoma and metastatic nodes. Percutaneous interventions play an important role in managing these patients. Biliary drainage, which forms the major bulk of radiological interventions, can be palliative in inoperable patients or pre-operative to improve liver function prior to surgery. Other interventions include cholecystostomy and radiofrequency ablation. We present here the indications, contraindications, technique and complications of the radiological interventions performed in patients with malignant biliary obstruction. PMID:27247718

Expression of CCK Receptors in Carcinoma Gallbladder and Cholelithiasis: A Pilot Study.

PubMed

Faridi, Mohammad Shazib; Jaiswal, Mahabir Saran Das; Goel, Sudhir K

2015-07-01

Gastrin and cholecystokinin (CCK) receptors are trophic for various gastrointestinal malignancies. Their role in gallbladder cancer has not been widely studied. To identify expression of CCK-A and CCK-B receptors in the tissue and blood of patients suffering from carcinoma (CA) gallbladder and gallstone disease and to compare expression of CCK A and B receptors in the gall bladder tissue and blood of healthy individuals and patients of CA gallbladder, and gallstone diseases. Forty nine subjects of both genders were recruited, comprising of 22 patients of CA gall bladder, 19 cases of cholelithiasis and, 8 normal gallbladders obtained from patients operated for trauma of the biliary system or Whipple's procedure. RNA extraction and cDNA formation for CCK-A and CCK-B receptors were carried out. Real Time PCR was performed on cDNA and threshold cycle (Ct) value of each sample was obtained and ΔCt was calculated. Chi-square test for comparing two groups and ANOVA test for comparing multiple groups were applied and if p<0.05 then Dunnett-C test was performed. Both CCK-A and CCK-B receptors were expressed irrespective of its origin in all tissues and blood samples studied; be it normal, Cholelithiasis or CA gallbladder and there was no difference among them (p>0.05). This preliminary study showed higher expression of CCK-A receptors in patients of cholelithiasis and decreased expression of CCK-A receptors in patients of CA gallbladder as compared to normal gallbladder although it did not rise to statistical significance.

Expression of CCK Receptors in Carcinoma Gallbladder and Cholelithiasis: A Pilot Study

PubMed Central

Jaiswal, Mahabir Saran Das; Goel, Sudhir K.

2015-01-01

Background: Gastrin and cholecystokinin (CCK) receptors are trophic for various gastrointestinal malignancies. Their role in gallbladder cancer has not been widely studied. Objectives: To identify expression of CCK-A and CCK-B receptors in the tissue and blood of patients suffering from carcinoma (CA) gallbladder and gallstone disease and to compare expression of CCK A and B receptors in the gall bladder tissue and blood of healthy individuals and patients of CA gallbladder, and gallstone diseases. Materials and Methods: Forty nine subjects of both genders were recruited, comprising of 22 patients of CA gall bladder, 19 cases of cholelithiasis and, 8 normal gallbladders obtained from patients operated for trauma of the biliary system or Whipple’s procedure. RNA extraction and cDNA formation for CCK-A and CCK-B receptors were carried out. Real Time PCR was performed on cDNA and threshold cycle (Ct) value of each sample was obtained and ΔCt was calculated. Chi-square test for comparing two groups and ANOVA test for comparing multiple groups were applied and if p<0.05 then Dunnett-C test was performed. Observation and Results: Both CCK-A and CCK-B receptors were expressed irrespective of its origin in all tissues and blood samples studied; be it normal, Cholelithiasis or CA gallbladder and there was no difference among them (p>0.05). Conclusion: This preliminary study showed higher expression of CCK-A receptors in patients of cholelithiasis and decreased expression of CCK-A receptors in patients of CA gallbladder as compared to normal gallbladder although it did not rise to statistical significance. PMID:26393162

Etiological role of human papillomavirus infection for inverted papilloma of the bladder.

PubMed

Shigehara, Kazuyoshi; Sasagawa, Toshiyuki; Doorbar, John; Kawaguchi, Shohei; Kobori, Yoshitomo; Nakashima, Takao; Shimamura, Masayoshi; Maeda, Yuji; Miyagi, Tohru; Kitagawa, Yasuhide; Kadono, Yoshifumi; Konaka, Hiroyuki; Mizokami, Atsushi; Koh, Eitetsu; Namiki, Mikio

2011-02-01

The status of human papillomavirus (HPV) infection in urothelial inverted papilloma was examined in the present study. Formalin-fixed and paraffin-embedded tissues from eight cases of inverted papilloma of the bladder were studied. The presence of HPV-DNA was examined by modified GP5/6+PCR using archival tissue sections by microdissection. HPV genotype was determined with a Hybri-Max HPV genotyping kit. Immunohistochemical analysis for p16-INK4a, mcm7, HPV-E4, and L1, and in situ hybridization for the HPV genome were performed. HPV was detected in seven of eight cases (87.5%) of inverted papilloma. Three cases were diagnosed as inverted papilloma with atypia, while the remaining five were typical cases. HPV-18 was detected in two cases, including one inverted papilloma with atypia, and HPV-16 was detected in four cases, including one inverted papilloma with atypia. Multiple HPV type infection was detected in one typical case and one atypical case. High-risk HPV was present in all HPV-positive cases. Cellular proteins, p16-INK4a and mcm7, which are surrogate markers for HPV-E7 expression, were detected in all HPV-positive cases, and their levels were higher in inverted papilloma with atypia than in typical cases. In contrast, HPV-E4 and L1, which are markers for HPV propagation, were observed in some parts of the typical inverted papilloma tissue. High-risk HPV infection may be one of the causes of urothelial inverted papilloma, and inverted papilloma with atypia may have malignant potential. 2010 Wiley-Liss, Inc.

The inhibitory effect of vitamin E on cigarette smoke-induced oxidative damage to the rat urothelium: can it prevent transitional cell carcinoma?

PubMed

Onol, Fikret Fatih; Demir, Aslan; Temiz, Yusuf; Yüksel, Meral; Eren, Funda; Türkeri, Levent N

2007-01-01

We aimed to detect reactive oxygen species (ROS) and assess subsequent carcinogenesis in terms of cellular proliferation in the bladder and kidney epithelial tissues of rats exposed to cigarette smoke (CS), and to investigate the changes following vitamin E treatment. Twenty-four male Sprague-Dawley rats were divided into 3 groups: group 1 was kept intact; group 2 was subjected to CS exposure for 8 weeks, and group 3 received intraperitoneal vitamin E injections (200 mg/kg/week) for 8 weeks in addition to CS exposure. Histological examination and Ki67 antigen expression measurements were made from bladder and renal pelvic tissue sections. Luminol-amplified chemiluminescence was used to measure ROS levels. All results were compared using a one-way ANOVA test. In CS-exposed rats, light microscopy of renal and bladder tissues revealed nonspecific epithelial changes; however, Ki67 expression was significantly increased in bladder tissues compared to other groups (17.5 +/- 4.7, 35 +/- 2.9 and 18.7 +/- 5.1% in groups 1, 2 and 3, respectively, p < 0.05). Chemiluminescence levels in bladder and renal tissues were also significantly higher in the CS-exposed animals (78.1 +/- 11.4, 148 +/- 13.3, 97.8 +/- 6.1 rlu/mg for the bladder, and 99.8 +/- 12.2, 176.1 +/- 27.9, 67.1 +/- 9 rlu/mg, for renal pelvic tissues, respectively, p < 0.05). Vitamin E can alleviate CS-induced oxidative damage in rat bladder and kidney epithelium suggesting a potential role for vitamin E in the prevention of CS-mediated carcinogenesis. 2007 S. Karger AG, Basel

PET/CT in renal, bladder and testicular cancer

PubMed Central

Bouchelouche, Kirsten; Physician, Chief; Choyke, Peter L.

2015-01-01

Imaging plays an important role in the clinical management of cancer patients. Hybrid imaging with PET/CT is having a broad impact in oncology, and in recent years PET/CT is beginning to have an impact in uro-oncology as well. In both bladder and renal cancer there is a need to study the efficacy of other tracers than F-18 fluorodeoxyglucose (FDG), particularly tracers with only limited renal excretion. Thus, new tracers are being introduced in these malignancies. This review focuses on the clinical role of FDG and other PET agents in renal, bladder and testicular cancer. PMID:26099672

Use of the holmium:YAG laser in urology

NASA Astrophysics Data System (ADS)

Mattioli, Stefano

1997-12-01

The Holmium-YAG is a versatile laser with multiple soft- tissue applications including tissue incision and vaporization, and pulsed-laser applications such as lithotripsy. At 2140 nanometers, the wavelength is highly absorbed by tissue water. Further, like CO2 laser, the Holmium produces immediate tissue vaporization while minimizing deep thermal damage to surrounding tissues. It is an excellent instrument for endopyelotomy, internal urethrotomy, bladder neck incisions and it can be used to resect the prostate. The Holmium creates an acute TUR defect which gives immediate results like the TURP. More than 50 patients were treated from Jan. 1996 to Jan. 1997 for obstructive symptoms due to benign prostatic hyperplasia, bladder neck stricture, urethral stenosis, and superficial bladder tumors.

Malakoplakia mimics urinary bladder cancer: a case report.

PubMed

Ristić-Petrović, Ana; Stojnev, Slavica; Janković-Velicković, Ljubinka; Marjanović, Goran

2013-06-01

Malakoplakia is an unusual and very rare chronic inflammatory disease. In bladder especially it can mimic malignancy and lead to serious misdiagnosis. We presented a case of a middle-aged woman with persistent macrohematuria and cystoscopically polypoid bladder mass that resembled a neoplastic process. The final diagnosis was based on cystoscopic biopsy and microscopic findings of acidophilic, foamy histiocytes with the presence of Michaelis-Gutmann inclusions which are characteristic for diagnosis of malakoplakia. Immunohistochemistry confirmed diagnosis by demonstrating CD68-positive macrophages. Urinary bladder malakoplakia should be considered in patients with persistent urinary tract infections and tumor mass at cystoscopy. Early identification with prompt antibiotic treatment can be helpful in avoiding unnecessary surgical interventions and in preventing development of possible complications.

A Murine Model of Inflammatory Bladder Disease: Cathelicidin Peptide Induced Bladder Inflammation and Treatment With Sulfated Polysaccharides

PubMed Central

Oottamasathien, Siam; Jia, Wanjian; McCoard, Lindsi; Slack, Sean; Zhang, Jianxing; Skardal, Aleksander; Job, Kathleen; Kennedy, Thomas P.; Dull, Randal O.; Prestwich, Glenn D.

2013-01-01

Purpose Studies show that LL-37 is a naturally occurring urinary defensin peptide that is up-regulated during urinary tract infections. Although normal urinary LL-37 levels are antimicrobial, we propose that increased LL-37 may trigger bladder inflammation. We further suggest that anti-inflammatory sulfated polysaccharides known as semi-synthetic glycosaminoglycan ether compounds can treat/prevent LL-37 mediated bladder inflammation. Materials and Methods C57BL/6 mice were catheterized/instilled with LL-37 (320 μM at 150 μl) for 45 minutes. Animals were sacrificed at 12 and 24 hours, and tissues were examined using hematoxylin and eosin. Separate experiments were performed for myeloperoxidase to quantify inflammation. GM-1111 semi-synthetic glycosaminoglycan ether treatments involved instillation of 10 mg/ml for 45 minutes directly before or after LL-37. Tissues were harvested at 24 hours. To compare semi-synthetic glycosaminoglycan ether efficacy experiments were performed using 10 mg/ml heparin. Finally, tissue localization of semi-synthetic glycosaminoglycan ether was examined using a fluorescent GM-1111-Alexa Fluor® 633 conjugate. Results Profound bladder inflammation developed after LL-37. Greater tissue inflammation occurred after 24 hours compared to that at 12 hours. Myeloperoxidase assays revealed a 21 and 61-fold increase at 12 and 24 hours, respectively. Semi-synthetic glycosaminoglycan ether treatment after LL-37 showed mild attenuation of inflammation with myeloperoxidase 2.5-fold below that of untreated bladders. Semi-synthetic glycosaminoglycan ether treatment before LL-37 demonstrated almost complete attenuation of inflammation. Myeloperoxidase results mirrored those in controls. In heparin treated bladders minimal attenuation of inflammation occurred. Finally, instillation of GM-1111-Alexa Fluor 633 revealed urothelial coating, significant tissue penetration and binding to endovasculature. Conclusions We developed what is to our knowledge a new model of inflammatory bladder disease by challenge with the naturally occurring urinary peptide LL-37. We also noted that a new class of anti-inflammatory sulfated polysaccharides prevents and mitigates bladder inflammation. PMID:21855919

In vivo fluorescence imaging of an orthotopic rat bladder tumor model indicates differential uptake of intravesically instilled near-infrared labeled 2-deoxyglucose analog by neoplastic urinary bladder tissues

NASA Astrophysics Data System (ADS)

Piao, Daqing; Davis, Carole A.; Hurst, Robert E.; Slaton, Joel W.

2017-02-01

Bladder cancer is one of the most expensive cancers to manage due to frequent recurrences requiring life-long surveillance and treatment. A near-infrared labeled 2-deoxy-d-glucose probe IRDye800CW-DG targeting glucose metabolism pathway has shown to enhance the sensitivity of diagnosing several types of cancers as tested on tumor models not including bladder tumor. This pilot study has explored differential uptake of intravesically administered IRDye800CW-DG in an orthotopic rat bladder tumor model. Twenty-five female Fischer rats were randomly grouped to four conditions: no-tumor-control (n=3), no-tumor-control intravesically instilled with IRDye800CWDG (n=6), rats bearing GFP-labeled AY-27 rat bladder urothelial cell carcinoma cells and washed with saline (n=5), and rats bearing AY-27 tumors and intravesically instilled with IRDye800CW-DG (n=11). Near-infrared fluorescence was measured from the opened bladder wall of anesthetized rat at an excitation wavelength of 750nm and an emission wavelength of 776nm, by using an in-house fluorescence imaging system. There is no statistically significant difference of the peak fluorescence intensity among the no-tumor-control bladders (n=3), the no-tumorcontrol bladders instilled with IRDye800CW-DG (n=6), and the GFP-labeled AY-27 treated bladders washed by saline (n=5). When compared to that of the no-tumor-control bladders instilled with IRDye800CW-DG (n=6), the fluorescence intensity of GFP-labeled AY-27 treated bladders instilled with IRDye800CW-DG and with histology confirmed neoplastic bladder tissue (n=11) was remarkably more intense (3.34 fold of over the former) and was also statistically significant (p<0.0001). The differential uptake of IRDye800CW-DG by the neoplastic urinary bladder tissues suggests the potential for cystoscopy-adaptation to enhance diagnosis and guiding surgical management of flat urinary bladder cancer.

Multimodal, 3D pathology-mimicking bladder phantom for evaluation of cystoscopic technologies (Conference Presentation)

NASA Astrophysics Data System (ADS)

Smith, Gennifer T.; Lurie, Kristen L.; Zlatev, Dimitar V.; Liao, Joseph C.; Ellerbee, Audrey K.

2016-02-01

Optical coherence tomography (OCT) and blue light cystoscopy (BLC) have shown significant potential as complementary technologies to traditional white light cystoscopy (WLC) for early bladder cancer detection. Three-dimensional (3D) organ-mimicking phantoms provide realistic imaging environments for testing new technology designs, the diagnostic potential of systems, and novel image processing algorithms prior to validation in real tissue. Importantly, the phantom should mimic features of healthy and diseased tissue as they appear under WLC, BLC, and OCT, which are sensitive to tissue color and structure, fluorescent contrast, and optical scattering of subsurface layers, respectively. We present a phantom posing the hollow shape of the bladder and fabricated using a combination of 3D-printing and spray-coating with Dragon Skin (DS) (Smooth-On Inc.), a highly elastic polymer to mimic the layered structure of the bladder. Optical scattering of DS was tuned by addition of titanium dioxide, resulting in scattering coefficients sufficient to cover the human bladder range (0.49 to 2.0 mm^-1). Mucosal vasculature and tissue coloration were mimicked with elastic cord and red dye, respectively. Urethral access was provided through a small hole excised from the base of the phantom. Inserted features of bladder pathology included altered tissue color (WLC), fluorescence emission (BLC), and variations in layered structure (OCT). The phantom surface and underlying material were assessed on the basis of elasticity, optical scattering, layer thicknesses, and qualitative image appearance. WLC, BLC, and OCT images of normal and cancerous features in the phantom qualitatively matched corresponding images from human bladders.

Distribution of mast cell subtypes in interstitial cystitis: implications for novel diagnostic and therapeutic strategies?

PubMed

Malik, Shabana T; Birch, Brian R; Voegeli, David; Fader, Mandy; Foria, Vipul; Cooper, Alan J; Walls, Andrew F; Lwaleed, Bashir A

2018-05-15

To identify the presence and geographical distribution of mast cell (MC) subtypes: MC T (tryptase positive-chymase negative) and MC TC (tryptase positive-chymase positive) in bladder tissue. Bladder tissue was obtained from patients with painful bladder syndrome/interstitial cystitis (n=14) and normal histology from University Hospital Southampton tissue bank. Sequential tissue slices were immunohistochemically stained for MC subtypes using anti-MC tryptase (for MC T and MC TC ) and anti-MC chymase (for MC TC ). Stained sections were photographed, and positively stained MCs were quantified using ImageJ. Data were analysed using descriptive statistics and individual paired t-tests. There was a significant difference in the density of MCs between each layer of the disease bladder, with the greatest accumulation within the detrusor (p<0.001). There was a significant increase in MC TC subtype in the lamina (p=0.009) in painful bladder syndrome/interstitial cystitis. Our results suggest that mastocytosis is present within all layers of disease bladder, especially the muscle layer. The varying increase in MC subtypes in the lamina and mucosa may explain the variability in painful bladder syndrome/interstitial cystitis symptoms. A high influx of MC TC in the mucosa of individuals who also had ulceration noted within their diagnostic notes may be of the Hunner's ulcer subclassification. These findings suggest a relationship between the pathogenesis of MC subtypes and the clinical presentation of painful bladder syndrome/interstitial cystitis. A cohort study would further elucidate the diagnostic and/or therapeutic potential of MCs in patients with painful bladder syndrome/interstitial cystitis. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Expression of ERβ and its co-regulators p300 and NCoR in human transitional cell bladder cancer.

PubMed

Kontos, Stylianos; Papatsoris, Athanasios; Kominea, Athina; Melachrinou, Maria; Tanoglidi, Anna; Kachrilas, Stefanos; Karavitakis, Markos; Balampani, Eleni; Sotiropoulou-Bonikou, Georgia

2011-01-01

Several data support a possible role of estrogens in bladder carcinogenesis, mediated mainly through estrogen receptor-β (ERβ). We study the expression of ERβ and its co-regulators p300 and nuclear co-repressor (NCoR) in patients with bladder cancer. One hundred and eleven consecutive patients (74 males and 37 females), aged 23-90 years (mean 70 ± 10) diagnosed with transitional cell bladder cancer were included in this study. The control group consisted of 29 patients that underwent transurethral prostatectomy and consented to simultaneous bladder biopsies. Immunohistochemical studies took place on formalin-fixed, paraffin-embedded sections from the TUR (transurethral resection) specimens. We studied the expression of ERβ, p300 and NCoR.χ(2) test was used to evaluate the relationship between the histological grade and ERβ expression, grade and co-regulators expression and grade and gender. Spearman rank correlation coefficient (r) was used in order to estimate the direction and strength of correlations between histological grade and ERβ-p300-NCoR expressions. The Cochran-Armitage test for trend was applied in order to examine possible trends across the ordered levels of histological grade. ERβ was more frequently expressed in the nucleus of normal bladder epithelium compared to malignant bladder epithelium with statistical significant association (r = -0.25, p = 0.003). The p300 was expressed only in the nucleus of bladder cancer cells and a positive correlation between molecular expression and cancer progression was demonstrated (r = 0.55, p < 0.001). NCoR immunostaining was demonstrated in the nuclei of bladder cells. Nuclear staining was significantly higher in normal tissue than in cancer cells (r = -0.33, p < 0.001), with negative correlation. Furthermore, its expression in grade I tumors was significantly higher than in grade II (r = -0.46, p < 0.001) and grade III tumors (r = -0.51, p < 0.001). Thus, like ERβ, NCoR expression in bladder epithelium decreased during cancer progression and loss of cell differentiation. There was no correlation between the levels of expression of the three proteins in normal bladder epithelium, but there was an inverse correlation between the nuclear expression of ERβ and p300 in carcinomas (r = -3.88, p = 0.042). Statistical significant association was established when correlating ERβ expression with NCoR expression (r = 0.273, p = 0.005), while co-regulators' nuclear expression did not correlate with each other (p > 0.05). In bladder carcinogenesis, we demonstrated inhibition in the expression of ERβ and its co-repressor NCoR as well as increased expression of the co-activator p300. Copyright © 2011 S. Karger AG, Basel.

Telomerase activity in solid transitional cell carcinoma, bladder washings, and voided urine.

PubMed

Lance, R S; Aldous, W K; Blaser, J; Thrasher, J B

1998-03-04

Telomerase activity has been detected in a wide variety of human malignancies. It appears to be one of the fundamental ingredients necessary for cellular immortality. We sought to determine the incidence of telomerase activity in solid transitional cell carcinoma (TCC) specimens, benign urothelium, bladder washings, and voided urine from patients with TCC identified cystoscopically compared with controls. Telomerase activity was measured in 26 solid bladder cancers and 13 benign urothelial specimens using the telomere repeat amplification protocol (TRAP), a polymerase chain reaction (PCR) based assay. Telomerase activity was further measured in the centrifuged cellular material obtained from the bladder washings of 26 patients with TCC and 40 with benign urologic disease found to have a normal cystoscopy. All patients with hematuria were additionally evaluated with an upper tract radiographic examination and found to be free of malignancy. Voided urine was likewise evaluated in 11 patients with TCC, 12 with benign urologic diseases, and 56 asymptomatic control subjects. Telomerase activity was detected in 25 of 26 (96%) solid specimens, 21 of 26 (81%) bladder washings, and 6 of 11 (54%) voided urine specimens from patients with histologically confirmed TCC. In the control group, 2 of 13 (15%) benign urothelial specimens and 2 of 56 (4%) voided urine specimens from the asymptomatic volunteer group demonstrated telomerase activity. Of those with benign urologic disease, 16 of 40 (40%) bladder barbotage specimens and 6 of 12 (50%) voided urine specimens demonstrated telomerase activity. Sensitivity and specificity of telomerase as a marker for TCC were 81% and 60%, respectively, in the bladder washings group and 54% and 50%, respectively, in voided urine. These data indicate that activation of telomerase is frequent in solid TCC and appears to be a sensitive marker in bladder washings of patients with TCC. We noted an unexpectedly high false positive detection rate in patients with benign urologic diseases, especially those with symptomatic benign prostatic hyperplasia. An additional study of a larger number of both bladder cancer patients and those at risk is necessary to determine if telomerase activity could play a role as a diagnostic and/or surveillance marker of TCC. Published by Elsevier Science Inc.

Evaluation of the biocompatibility of a coating material for an implantable bladder volume sensor.

PubMed

Kim, Su-Jin; Lee, Dong-Sup; Kim, In-Gul; Sohn, Dong-Wan; Park, Jung-Yul; Choi, Bum-Kyoo; Kim, Sae-Woong

2012-03-01

As the applications for implantable medical devices have increased, the need for biocompatible packaging materials has become important. Recently, we reported an implantable sensor for real-time monitoring of the changes in bladder volume, which necessitated finding a safe coating material for use in bladder tissue. At present, materials like polyethylene glycol (PEG), polydimethylsiloxane (PDMS) and parylene-C are used in biomedical devices or as coating materials, owing to their excellent safety in various medical fields. However, few studies have assessed their safety in bladder tissue, therefore, we evaluated the biocompatibility of PEG, PDMS and parylene-C in the bladder. All three materials turned out to be safe in in vitro tests of live/dead staining and cell viability. In vivo tests with hematoxylin and eosin and immunofluorescence staining with MAC387 showed no persistent inflammation. Therefore, we consider that the three materials are biocompatible in bladder tissue. Despite this safety, however, PEG has biodegradable characteristics and thus is not suitable for use as packaging. We suggest that PDMS and parylene-C can be used as safe coating materials for the implantable bladder volume sensor reported previously. Copyright © 2012. Published by Elsevier B.V.

A novel role for drebrin in regulating progranulin bioactivity in bladder cancer.

PubMed

Xu, Shi-Qiong; Buraschi, Simone; Morcavallo, Alaide; Genua, Marco; Shirao, Tomoaki; Peiper, Stephen C; Gomella, Leonard G; Birbe, Ruth; Belfiore, Antonino; Iozzo, Renato V; Morrione, Andrea

2015-05-10

We recently established a critical role for the growth factor progranulin in bladder cancer insofar as progranulin promotes urothelial cancer cell motility and contributes, as an autocrine growth factor, to the transformed phenotype by modulating invasion and anchorage-independent growth. In addition, progranulin expression is upregulated in invasive bladder cancer tissues compared to normal controls. However, the molecular mechanisms of progranulin action in bladder cancer have not been fully elucidated. In this study, we searched for novel progranulin-interacting proteins using pull-down assays with recombinant progranulin and proteomics. We discovered that drebrin, an F-actin binding protein, bound progranulin in urothelial cancer cells. We characterized drebrin function in urothelial cancer cell lines and showed that drebrin is critical for progranulin-dependent activation of the Akt and MAPK pathways and modulates motility, invasion and anchorage-independent growth. In addition, drebrin regulates tumor formation in vivo and its expression is upregulated in bladder cancer tissues compared to normal tissue controls. Our data are translationally relevant as indicate that drebrin exerts an essential functional role in the regulation of progranulin action and may constitute a novel target for therapeutic intervention in bladder tumors. In addition, drebrin may serve as novel biomarker for bladder cancer.

A microangiographic study of the effect of hyperthermia on the rabbit bladder

NASA Technical Reports Server (NTRS)

Hietala, S. O.; Howells, R.; Hazra, I. A.

1978-01-01

A model was used to study the effect of hyperthermia on a normal tissue. The model selected was the rabbit bladder and the end point measured was the changes in the micro-vasculature of the bladder wall. It was already demonstrated clinically that hot water bladder infusions produce regression in bladder tumors.

Synchrotron X-Ray Fluorescence Microscopy of Gallium in Bladder Tissue following Gallium Maltolate Administration during Urinary Tract Infection

PubMed Central

Sampieri, Francesca; Chirino, Manuel; Hamilton, Don L.; Blyth, Robert I. R.; Sham, Tsun-Kong; Dowling, Patricia M.; Thompson, Julie

2013-01-01

A mouse model of cystitis caused by uropathogenic Escherichia coli was used to study the distribution of gallium in bladder tissue following oral administration of gallium maltolate during urinary tract infection. The median concentration of gallium in homogenized bladder tissue from infected mice was 1.93 μg/g after daily administration of gallium maltolate for 5 days. Synchrotron X-ray fluorescence imaging and X-ray absorption spectroscopy of bladder sections confirmed that gallium arrived at the transitional epithelium, a potential site of uropathogenic E. coli infection. Gallium and iron were similarly but not identically distributed in the tissues, suggesting that at least some distribution mechanisms are not common between the two elements. The results of this study indicate that gallium maltolate may be a suitable candidate for further development as a novel antimicrobial therapy for urinary tract infections caused by uropathogenic E. coli. PMID:23877680

Tissue Specific Dysregulated Protein Subnetworks in Type 2 Diabetic Bladder Urothelium and Detrusor Muscle*

PubMed Central

Tomechko, Sara E.; Liu, Guiming; Tao, Mingfang; Schlatzer, Daniela; Powell, C. Thomas; Gupta, Sanjay; Chance, Mark R.; Daneshgari, Firouz

2015-01-01

Diabetes mellitus is well known to cause bladder dysfunction; however, the molecular mechanisms governing this process and the effects on individual tissue elements within the bladder are poorly understood, particularly in type 2 diabetes. A shotgun proteomics approach was applied to identify proteins differentially expressed between type 2 diabetic (TallyHo) and control (SWR/J) mice in the bladder smooth muscle and urothelium, separately. We were able to identify 1760 nonredundant proteins from the detrusor smooth muscle and 3169 nonredundant proteins from urothelium. Pathway and network analysis of significantly dysregulated proteins was conducted to investigate the molecular processes associated with diabetes. This pinpointed ERK1/2 signaling as a key regulatory node in the diabetes-induced pathophysiology for both tissue types. The detrusor muscle samples showed diabetes-induced increased tissue remodeling-type events such as Actin Cytoskeleton Signaling and Signaling by Rho Family GTPases. The diabetic urothelium samples exhibited oxidative stress responses, as seen in the suppression of protein expression for key players in the NRF2-Mediated Oxidative Stress Response pathway. These results suggest that diabetes induced elevated inflammatory responses, oxidative stress, and tissue remodeling are involved in the development of tissue specific diabetic bladder dysfunctions. Validation of signaling dysregulation as a function of diabetes was performed using Western blotting. These data illustrated changes in ERK1/2 phosphorylation as a function of diabetes, with significant decreases in diabetes-associated phosphorylation in urothelium, but the opposite effect in detrusor muscle. These data highlight the importance of understanding tissue specific effects of disease process in understanding pathophysiology in complex disease and pave the way for future studies to better understand important molecular targets in reversing bladder dysfunction. PMID:25573746

Tissue specific dysregulated protein subnetworks in type 2 diabetic bladder urothelium and detrusor muscle.

PubMed

Tomechko, Sara E; Liu, Guiming; Tao, Mingfang; Schlatzer, Daniela; Powell, C Thomas; Gupta, Sanjay; Chance, Mark R; Daneshgari, Firouz

2015-03-01

Diabetes mellitus is well known to cause bladder dysfunction; however, the molecular mechanisms governing this process and the effects on individual tissue elements within the bladder are poorly understood, particularly in type 2 diabetes. A shotgun proteomics approach was applied to identify proteins differentially expressed between type 2 diabetic (TallyHo) and control (SWR/J) mice in the bladder smooth muscle and urothelium, separately. We were able to identify 1760 nonredundant proteins from the detrusor smooth muscle and 3169 nonredundant proteins from urothelium. Pathway and network analysis of significantly dysregulated proteins was conducted to investigate the molecular processes associated with diabetes. This pinpointed ERK1/2 signaling as a key regulatory node in the diabetes-induced pathophysiology for both tissue types. The detrusor muscle samples showed diabetes-induced increased tissue remodeling-type events such as Actin Cytoskeleton Signaling and Signaling by Rho Family GTPases. The diabetic urothelium samples exhibited oxidative stress responses, as seen in the suppression of protein expression for key players in the NRF2-Mediated Oxidative Stress Response pathway. These results suggest that diabetes induced elevated inflammatory responses, oxidative stress, and tissue remodeling are involved in the development of tissue specific diabetic bladder dysfunctions. Validation of signaling dysregulation as a function of diabetes was performed using Western blotting. These data illustrated changes in ERK1/2 phosphorylation as a function of diabetes, with significant decreases in diabetes-associated phosphorylation in urothelium, but the opposite effect in detrusor muscle. These data highlight the importance of understanding tissue specific effects of disease process in understanding pathophysiology in complex disease and pave the way for future studies to better understand important molecular targets in reversing bladder dysfunction. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Tissue Permeability Effects Associated with the Use of Mucoadhesive Cationic Nanoformulations of Docetaxel in the Bladder.

PubMed

Pandey, Rakhi; Jackson, John K; Mugabe, Clement; Liggins, Richard; Burt, Helen M

2016-08-01

Recently, efficacy studies in mice have shown that amine-terminated cationic (CNP) nanoparticulate carriers of DTX offer an improved formulation of the drug for intravesical delivery. It is hypothesized that this improved efficacy may arise from a carrier mediated bladder exfoliation process that removes the urothelial barrier allowing for increased drug uptake into bladder tissue. The objective of this study was to investigate exfoliation processes in fresh pig's bladders (ex vivo) exposed to three cationic polyglycerols with increasing degrees of amination (denoted 350, 580 and 780). The study also compared the tissue depth profile of DTX uptake into these tissues using these different carriers. Aminated polyglycerols were synthesized and characterized in the laboratory with low (CNP-360), medium (CNP-580) and high (CNP-780) levels of amine content. CNP-based DTX solutions and commercial DTX solutions in polysorbate 80 (Taxotere®) were doped with (3)H-radiolabeled DTX and prepared by solvent evaporation from acetonitrile, followed by drying and reconstitution in pH 6.4 buffer. Sections of fresh pig's bladder tissue were clamped into Franz diffusion cells and the urothelial side was exposed to the DTX solutions for 2 h. Tissue sections were then frozen for sectioning by cryotome sectioning and subsequently processed for drug analysis by liquid scintillation counting. Alternatively tissue sections were fixed in 2% glutaraldehyde and 2% paraformaldehyde in 0.1 M sodium cacodylate buffer for the purposes of scanning electron microscopy (SEM). Exposure of the urothelial surface to the amine-terminated polyglycerol solutions resulted in the exfoliation of bladder tissues in a time- and concentration-dependent manner. Exfoliation was significantly more pronounced when using CNPs with a medium or high levels of amination whereas only minor levels of exfoliation were seen with low levels. Following incubation of tissues in Tween-based commercial formulations (Taxotere) of DTX (0.5 mg/mL) the drug was detectable at low levels (10-40 μg/g tissue) in all depths of tissue. Similar drug uptake was observed using the CNP-360 formulation. However drug uptake levels were increased to 60-100 μg/g tissue when samples were incubated with either the CNP-580 or CNP-780 formulations. The use of cationic polyglycerols with higher levels of amine termination allows for an enhanced uptake of DTX into bladder tissues as compared to commercial (Taxotere) formulations. These increased drug levels probably arise from exfoliation processes resulting in a temporary elimination of the urothelial permeability barrier and increased drug penetration into the tissue.

The mitochondrial C16069T polymorphism, not mitochondrial D310 (D-loop) mononucleotide sequence variations, is associated with bladder cancer.

PubMed

Shakhssalim, Nasser; Houshmand, Massoud; Kamalidehghan, Behnam; Faraji, Abolfazl; Sarhangnejad, Reza; Dadgar, Sepideh; Mobaraki, Maryam; Rosli, Rozita; Sanati, Mohammad Hossein

2013-12-05

Bladder cancer is a relatively common and potentially life-threatening neoplasm that ranks ninth in terms of worldwide cancer incidence. The aim of this study was to determine deletions and sequence variations in the mitochondrial displacement loop (D-loop) region from the blood specimens and tumoral tissues of patients with bladder cancer, compared to adjacent non-tumoral tissues. The DNA from blood, tumoral tissues and adjacent non-tumoral tissues of twenty-six patients with bladder cancer and DNA from blood of 504 healthy controls from different ethnicities were investigated to determine sequence variation in the mitochondrial D-loop region using multiplex polymerase chain reaction (PCR), DNA sequencing and southern blotting analysis. From a total of 110 variations, 48 were reported as new mutations. No deletions were detected in tumoral tissues, adjacent non-tumoral tissues and blood samples from patients. Although the polymorphisms at loci 16189, 16261 and 16311 were not significantly correlated with bladder cancer, the C16069T variation was significantly present in patient samples compared to control samples (p < 0.05). Interestingly, there was no significant difference (p > 0.05) of C variations, including C7TC6, C8TC6, C9TC6 and C10TC6, in D310 mitochondrial DNA between patients and control samples. Our study suggests that 16069 mitochondrial DNA D-Loop mutations may play a significant role in the etiology of bladder cancer and facilitate the definition of carcinogenesis-related mutations in human cancer.

[The role of telomerase activity in non-invasive diagnostics of bladder cancer].

PubMed

Glybochko, P V; Alyaev, J G; Potoldykova, N V; Polyakovsky, K A; Vinarov, A Z; Glukhov, A I; Gordeev, S A

2016-08-01

To evaluate the potentials of determining the telomerase activity (TA) in the cellular material of the urine for noninvasive diagnosis of bladder cancer (BC). Evaluation of TA was performed in the urine of 48 patients with bladder cancer (study group) before and after transurethral resection of the bladder wall (n=38), an open resection of the bladder (n=4), and cystectomy (n=6). TA was also evaluated in 48 tumor tissue samples obtained from these patients during removal of the bladder tumor. Each sample of the tumor tissue was separated into two parts, one of which was subjected to histological examination, and the latter was used to determine the telomerase activity. In all cases, the diagnosis of bladder cancer was confirmed morphologically. Determination of TA in the samples was performed by the modified TRAP-method (telomerase repeat amplification protocol), RT-PCR, PCR, and electrophoresis. As a control, cell material of the urine and tissue in 12 patients with chronic cystitis was investigated. TA before surgery was found in 45 (93.75%) of 48 samples of cellular material of the urine from patients with suspected bladder cancer. BC was histologically verified in all patients in this group. In the postoperative period, TA was not observed in the 48 samples of cellular material of the urine from patients with BC. In the control group of patients with histologically verified cystitis, weak TA was determined only in one sample of cellular material of the urine. The analysis indicates statistically significant predominance of patients with bladder cancer in case of TA in the urine (P=0.001). TA was detected in all samples of tumor tissue. We also analyzed the dependence of TA levels in urine and tissue on the degree of BC differentiation. In patients with highly differentiated BC, mean AT in the cellular materials of the urine was 0,61% (n=15), in patients with moderately differentiated BC - 0.95% (n=23), in patients with low-grade bladder cancer - 1.33% (n=10); in other words, increase in the TA levels with decreasing the degree of differentiation was observed. This finding can be used in the prognosis of the course of disease based on determining the TA level in these patients. Preliminary data indicate the possibility of use of determining the TA in cellular material of the urine for the diagnosis and monitoring of bladder cancer recurrence.

Mechanisms of Visceral Organ Crosstalk: Importance of Alterations in Permeability in Rodent Models

PubMed Central

Greenwood-Van Meerveld, B; Mohammadi, E; Tyler, K; Van Gordon, S; Parker, A; Towner, R; Hurst, R

2015-01-01

Purpose The pathophysiology of painful bladder syndrome (PBS) is poorly understood; however, there is evidence of female predominance and comorbidity with irritable bowel syndrome (IBS). Our hypothesis is that cross-sensitization between the bladder and colon is due to altered permeability in one organ affecting the other organ. Materials and methods Experiments were performed in anesthetized, ovariectomized (OVX) female rats. In separate groups, protamine sulfate was infused into the bladder or TNBS was infused into the colon, with untreated rats serving as controls. Both bladder and colonic tissue were harvested for all rats at 1, 3, and 5 days post-treatment. Permeability was assessed in vitro in Ussing chambers via measurements of transepithelial electrical resistance (TEER) and macromolecular flux of Fluorescein isothiocyanate (FITC)-4 dextran. Results Exposing the bladder to protamine sulfate induced a significant (p<0.05) decrease in bladder TEER and an increase in the translocation of FITC across the tissue compared to controls at 1 and 3 days. Colonic tissue from rats with enhanced bladder permeability exhibited a significant (p<0.05) decrease in TEER and increase in FITC when compared to untreated controls at all time points. Conversely, when colonic permeability was increased with TNBS, we observed an increase in bladder permeability in the absence of any changes to the bladder urothelium. Conclusions Changes in epithelial permeability may represent a novel mechanism for visceral organ crosstalk and may explain the overlapping symptomology of PBS and IBS. PMID:25776913

Long non-coding RNA ANRIL is up-regulated in bladder cancer and regulates bladder cancer cell proliferation and apoptosis through the intrinsic pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, Hongxue; Department of Urology, Hospital of Xinjiang Production and Construction Corps, Urumqi 830002; Li, Xuechao

Antisense non-coding RNA in the INK4 locus (ANRIL) is a member of long non-coding RNAs and has been reported to be dysregulated in several human cancers. However, the role of ANRIL in bladder cancer remains unclear. This present study aimed to investigate whether and how ANRIL involved in bladder cancer. Our results showed up-regulation of ANRIL in bladder cancer tissues versus the corresponding adjacent non-tumor tissues. To explore the specific mechanisms, ANRIL was silenced by small interfering RNA or short hairpin RNA transfection in human bladder cancer T24 and EJ cells. Knockdown of ANRIL repressed cell proliferation and increased cellmore » apoptosis, along with decreased expression of Bcl-2 and increased expressions of Bax, cytoplasmic cytochrome c and Smac and cleaved caspase-9, caspase-3 and PARP. However, no change of cleaved caspase-8 level was observed. Furthermore, in vivo experiment confirmed that knockdown of ANRIL inhibited tumorigenic ability of EJ cells in nude mice. Meanwhile, in accordance with in vitro study, knockdown of ANRIL inhibited expression of Bcl-2 and up-regulated expressions of Bax and cleaved caspase-9, but did not affect cleaved caspase-8 level. In conclusion, we first report that ANRIL possibly serves as an oncogene in bladder cancer and regulates bladder cancer cell proliferation and apoptosis through the intrinsic apoptosis pathway. - Highlights: • We first report the role of ANRIL in bladder cancer. • ANRIL is obviously up-regulated in bladder cancer tissues. • ANRIL regulates bladder cancer cell proliferation and cell apoptosis through the intrinsic pathway.« less

Transient receptor potential vanilloid type 2 (TRPV2) expression in normal urothelium and in urothelial carcinoma of human bladder: correlation with the pathologic stage.

PubMed

Caprodossi, Sara; Lucciarini, Roberta; Amantini, Consuelo; Nabissi, Massimo; Canesin, Giacomo; Ballarini, Patrizia; Di Spilimbergo, Adriana; Cardarelli, Marco Andrea; Servi, Lucilla; Mammana, Gabriele; Santoni, Giorgio

2008-09-01

To evaluate the expression of transient receptor potential vanilloid type 2 (TRPV2) in normal human bladder and urothelial carcinoma (UC) tissues. Bladder specimens were obtained by transurethral resection or radical cystectomy. TRPV2 mRNA expression in normal human urothelial cells (NHUCs), UC cell lines, and formalin-fixed paraffin-embedded normal (n=6) and cancer bladder tissues (n=58) was evaluated by polymerase chain reaction (PCR) and quantitative real-time PCR (RT-PCR). TRPV2 protein expression was assessed by cytofluorimetric and confocal microscopy analyses in NHUCs and UC cells and by Western blotting and immunohistochemistry in normal and UC tissues. Enhanced TRPV2 mRNA and protein expression was found in high-grade and -stage UC specimens and UC cell lines. Both the full-length TRPV2 (hTRPV2) and a short splice-variant (s-TRPV2) were detected in NHUC and normal bladder specimens, whereas a progressive decline of s-TRPV2 in pTa, pT1, and pT2 stages was observed, up to a complete loss in pT3 and pT4 UC specimens. Normal human urothelial cells and bladder tissue specimens express TRPV2 at both the mRNA and protein levels. A progressive loss of s-TRPV2 accompanied by a marked increase of hTRPV2 expression was found in high-grade and -stage UC tissues.

Analysis on pathogenesis of 50 cases of bladder proliferative lesions.

PubMed

Chen, Zhiqiang; Lan, Ruzhu; Ye, Zhangqun; Yang, Weimin

2003-01-01

In order to study the pathogenesis, clinical and pathological characteristics of proliferative lesions of the bladder, 50 cases of proliferative lesions of the bladder from 150 patients with complaints of frequency, urgency, hematuria and dysuria were subjected to cystoscopic biopsy of the suspicious foci in the bladder. In combination with the symptoms, urine and urodynamics, the relationship of proliferative lesions of the bladder to the inflammation and obstruction of the lower urinary tract was analyzed. Of the 50 cases of proliferative bladder lesions, 44 cases (88%) had lower urinary tract infection and 29 (58%) lower urinary tract obstruction. The patients with lower urinary tract obstruction were all complicated with infection. Three cases were associated with transitional cell carcinoma. Malignant cells were detected in 1 case by urinary cytologic examination. Proliferative lesions of the bladder, especially those without other obvious mucosa changes under cystoscopy, are common histological variants of urothelium in the patients with chronic inflammation and obstruction of the lower urinary tract. Chronic inflammation and obstruction of the lower urinary tract might be the causes for proliferative lesions of the bladder. It is suggested that different treatments should be applied according to the scope and histological type of the proliferative lesions.

Polyesterurethane and acellular matrix based hybrid biomaterial for bladder engineering.

PubMed

Horst, Maya; Milleret, Vincent; Noetzli, Sarah; Gobet, Rita; Sulser, Tullio; Eberli, Daniel

2017-04-01

Poly(lactic-co-glycolic acid) (PLGA) based biomaterials for soft tissue engineering have inherent disadvantages, such as a relative rigidity and a limited variability in the mechanical properties and degradation rates. In this study, a novel electrospun biomaterial based on degradable polyesterurethane (PEU) (DegraPol ® ) was investigated for potential use for bladder engineering in vitro and in vivo. Hybrid microfibrous PEU and PLGA scaffolds were produced by direct electrospinning of the polymer onto a bladder acellular matrix. The scaffold morphology of the scaffold was analyzed, and the biological performance was tested in vitro and in vivo using a rat cystoplasty model. Anatomical and functional outcomes after implantation were analyzed macroscopically, histologically and by cystometry, respectively. Scanning electron microscopy analysis showed that PEU samples had a lower porosity (p < 0.001) and were slightly thinner (p = 0.009) than the PGLA samples. Proliferation and survival of the seeded smooth muscle cells in vitro were comparable on PEU and PLGA scaffolds. After 8 weeks in vivo, the PEU scaffolds exhibited no shrinkage. However, cystometry of the reconstructed bladders exhibited a slightly greater functional bladder capacity in the PLGA group. Morphometric analyses revealed significantly better tissue healing (p < 0.05) and, in particular, better smooth muscle regeneration, as well as a lower rate of inflammatory responses at 8 weeks in the PEU group. Collectively, the results indicated that PEU-hybrid scaffolds promote bladder tissue formation with excellent tissue integration and a low inflammatory reaction in vivo. PEU is a promising biomaterial, particularly with regard to functional tissue engineering of the bladder and other hollow organs. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 658-667, 2017. © 2015 Wiley Periodicals, Inc.

CXCL5 knockdown expression inhibits human bladder cancer T24 cells proliferation and migration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Jiajia; Zhu, Xi; Zhang, Jie, E-mail: zhangjiebjmu@163.com

2014-03-28

Highlights: • We first demonstrated CXCL5 is highly expressed in human bladder tumor tissues and cells. • CXCL5 knockdown inhibits proliferation, migration and promotes apoptosis in T24 cells. • CXCL5 knockdown inhibits Snail, PI3K-AKT and ERK1/2 signaling pathways in T24 cells. • CXCL5 is critical for bladder tumor growth and progression. - Abstract: CXCL5 (epithelial neutrophil activating peptide-78) which acts as a potent chemoattractant and activator of neutrophil function was reported to play a multifaceted role in tumorigenesis. To investigate the role of CXCL5 in bladder cancer progression, we examined the CXCL5 expression in bladder cancer tissues by real-time PCRmore » and Western blot, additionally, we used shRNA-mediated silencing to generate stable CXCL5 silenced bladder cancer T24 cells and defined its biological functions. Our results demonstrated that mRNA and protein of CXCL5 is increased in human bladder tumor tissues and cell lines, down-regulation of CXCL5 in T24 cells resulted in significantly decreased cell proliferation, migration and increased cell apoptosis in vitro through Snail, PI3K-AKT and ERK1/2 signaling pathways. These data suggest that CXCL5 is critical for bladder tumor growth and progression, it may represent a potential application in cancer diagnosis and therapy.« less

A novel role for drebrin in regulating progranulin bioactivity in bladder cancer

PubMed Central

Morcavallo, Alaide; Genua, Marco; Shirao, Tomoaki; Peiper, Stephen C.; Gomella, Leonard G.; Birbe, Ruth; Belfiore, Antonino; Iozzo, Renato V.; Morrione, Andrea

2015-01-01

We recently established a critical role for the growth factor progranulin in bladder cancer insofar as progranulin promotes urothelial cancer cell motility and contributes, as an autocrine growth factor, to the transformed phenotype by modulating invasion and anchorage-independent growth. In addition, progranulin expression is upregulated in invasive bladder cancer tissues compared to normal controls. However, the molecular mechanisms of progranulin action in bladder cancer have not been fully elucidated. In this study, we searched for novel progranulin-interacting proteins using pull-down assays with recombinant progranulin and proteomics. We discovered that drebrin, an F-actin binding protein, bound progranulin in urothelial cancer cells. We characterized drebrin function in urothelial cancer cell lines and showed that drebrin is critical for progranulin-dependent activation of the Akt and MAPK pathways and modulates motility, invasion and anchorage-independent growth. In addition, drebrin regulates tumor formation in vivo and its expression is upregulated in bladder cancer tissues compared to normal tissue controls. Our data are translationally relevant as indicate that drebrin exerts an essential functional role in the regulation of progranulin action and may constitute a novel target for therapeutic intervention in bladder tumors. In addition, drebrin may serve as novel biomarker for bladder cancer. PMID:25839164

Endoscopic Optical Coherence Tomography in Urology

NASA Astrophysics Data System (ADS)

Pan, Yingtian; Waltzer, Wayne; Ye, Zhangqun

Clinical statistics has shown a stable prevalence of bladder cancer in recent years, which by far remains among the most common types of malignancy in the USA. With smoking as the most well-established risk factor, bladder cancer is the fourth most common cancer occurrences in male population [1]. In the year of 2014, an estimated 74,690 new cases are expected to occur with estimated 15,580 deaths. Bladder cancer often refers to transitional cell carcinoma (TCC) as it originates primarily from the epithelial cell layer (i.e., urothelium) of the bladder. Unlike prostate-specific antigen (PSA) for prostate cancer screening, there is currently no effective screening technique approved or recommended for the population at average risk [2-5]. As a result, hematuria (i.e., blood in the urine) is often the first clinical symptom of bladder cancer. Fortunately, urinary bladder is more accessible than prostate glands endoscopically; thus cytology following white-light cystoscopy has been the gold standard for current clinical detection of bladder cancer. This is important because bladder cancer if diagnosed prior to muscle invasion (e.g., superficial or at

Beclin-1 Expression in Normal Bladder and in Cd+2 and As+3 Exposed and Transformed Human Urothelial Cells (UROtsa)

PubMed Central

Larson, Jennifer L.; Somji, Seema; Zhou, Xu Dong; Sens, Mary Ann; Garrett, Scott H.; Sens, Donald A.; Dunlevy, Jane R.

2010-01-01

The expression of beclin-1 in normal human bladder and in Cd+2 and As+3 exposed and transformed urothelial cells (UROtsa) was examined in this study. It was shown using a combination of real time PCR, western analysis and immunohistochemistry that beclin-1 was expressed in the urothelial cells of the normal bladder. It was also demonstrated that the parental UROtsa cell line expressed beclin-1 mRNA and protein at levels similar to that of the in situ urothelium. The level of beclin-1 expression underwent only modest alterations when the UROtsa cells were malignantly transformed by Cd+2 or As+3 or when the parental cells were exposed acutely to Cd+2 or As+3. While there were instances of significant alterations at individual time points and within cell line-to-cell line comparisons there was no evidence of a dose response relationship or correlations to the phenotypic properties of the cell lines. Similar results were obtained for the expression of the Atg-5, Atg-7, Atg-12 and LC3B autophagy-related proteins. The findings provide initial evidence for beclin-1 expression in normal bladder and that large alterations in the expression of beclin-1 and associated proteins do not occur when human urothelial cells are malignantly transformed with, or exposed to, either Cd+2 or As+3. PMID:20206246

Readability of American online patient education materials in urologic oncology: a need for simple communication.

PubMed

Pruthi, Amanda; Nielsen, Matthew E; Raynor, Mathew C; Woods, Michael E; Wallen, Eric M; Smith, Angela B

2015-02-01

To determine the readability levels of reputable cancer and urologic Web sites addressing bladder, prostate, kidney, and testicular cancers. Online patient education materials (PEMs) for bladder, prostate, kidney, and testicular malignancies were evaluated from the American Cancer Society, American Society of Clinical Oncology, National Cancer Institute, Urology Care Foundation, Bladder Cancer Advocacy Network, Prostate Cancer Foundation, Kidney Cancer Association, and Testicular Cancer Resource Center. Grade level was determined using several readability indices, and analyses were performed on the basis of cancer type, Web site, and content area (general, causes, risk factors and prevention, diagnosis and staging, treatment, and post-treatment). Estimated grade level of online PEMs ranged from 9.2 to 14.2 with an overall mean of 11.7. Web sites for kidney cancer had the least difficult readability (11.3) and prostate cancer had the most difficult readability (12.1). Among specific Web sites, the most difficult readability levels were noted for the Urology Care Foundation Web site for bladder and prostate cancer and the Kidney Cancer Association and Testicular Cancer Resource Center for kidney and testes cancer. Readability levels within content areas varied on the basis of the disease and Web site. Online PEMs in urologic oncology are written at a level above the average American reader. Simplification of these resources is necessary to improve patient understanding of urologic malignancy. Copyright © 2015 Elsevier Inc. All rights reserved.

Is CD147 a New Biomarker Reflecting Histological Malignancy of Gliomas?

PubMed

Kong, Xiangyi; Wang, Yu; Dai, Congxin; Ma, Wenbin; Wang, Renzhi

2017-03-01

CD147 belongs to immunoglobulin superfamily and can stimulate the surrounding fibroblasts to secret matrix metalloproteinases (MMPs). Studies showed that when compared with their normal counterparts, CD47 expression level increased in lung carcinoma tissue, breast cancer tissue, and bladder cancer tissue. They increase in line with a tumor's malignant progression, invasiveness, and metastasis. However, the precise implications and utility of the presence of CD147 in the WHO grading system for gliomas have rarely been reported; in addition, the signal transduction pathways regarding CD147 remain unclear and controversial. Thus, in performing a meta-analysis, it is essential to reach a reliable conclusion. The related literatures were incorporated into the present meta-analysis after careful assessment, and odds ratios (ORs) with 95 % confidence intervals (95 % CIs) were calculated. Heterogeneity evaluation was estimated. Ten studies involving 615 patients were found to be eligible, nine of which were conducted in China and the remaining one in Japan. Analysis of eight studies involving dichotomous data revealed that CD147 overexpression in glioma tissue was related to higher WHO grading (III + IV; OR, 9.900; 95 % CI, 5.943, 16.491; P = 0.000) closely, whereas analysis of three studies of continuous data type indicated that there were no statistical associations (standard mean difference, -1.894; 95 % CI, -4.081, 0.293; P = 0.090). In accordance with funnel plot, Egger test, and Begg test, there was no publication bias. Considering that the continuous data make up only a small proportion of the overall analysis, we believe that our study indicates that CD147 overexpression is potentially related to higher WHO grade. Certainly, more data compiled based on evidence-based medicine are required to further support this conclusion.

Bladder tissue engineering through nanotechnology.

PubMed

Harrington, Daniel A; Sharma, Arun K; Erickson, Bradley A; Cheng, Earl Y

2008-08-01

The field of tissue engineering has developed in phases: initially researchers searched for "inert" biomaterials to act solely as replacement structures in the body. Then, they explored biodegradable scaffolds--both naturally derived and synthetic--for the temporary support of growing tissues. Now, a third phase of tissue engineering has developed, through the subcategory of "regenerative medicine." This renewed focus toward control over tissue morphology and cell phenotype requires proportional advances in scaffold design. Discoveries in nanotechnology have driven both our understanding of cell-substrate interactions, and our ability to influence them. By operating at the size regime of proteins themselves, nanotechnology gives us the opportunity to directly speak the language of cells, through reliable, repeatable creation of nanoscale features. Understanding the synthesis of nanoscale materials, via "top-down" and "bottom-up" strategies, allows researchers to assess the capabilities and limits inherent in both techniques. Urology research as a whole, and bladder regeneration in particular, are well-positioned to benefit from such advances, since our present technology has yet to reach the end goal of functional bladder restoration. In this article, we discuss the current applications of nanoscale materials to bladder tissue engineering, and encourage researchers to explore these interdisciplinary technologies now, or risk playing catch-up in the future.

Bladder segmentation in MR images with watershed segmentation and graph cut algorithm

NASA Astrophysics Data System (ADS)

Blaffert, Thomas; Renisch, Steffen; Schadewaldt, Nicole; Schulz, Heinrich; Wiemker, Rafael

2014-03-01

Prostate and cervix cancer diagnosis and treatment planning that is based on MR images benefit from superior soft tissue contrast compared to CT images. For these images an automatic delineation of the prostate or cervix and the organs at risk such as the bladder is highly desirable. This paper describes a method for bladder segmentation that is based on a watershed transform on high image gradient values and gray value valleys together with the classification of watershed regions into bladder contents and tissue by a graph cut algorithm. The obtained results are superior if compared to a simple region-after-region classification.

Correlation between messenger RNA expression and protein expression of immune checkpoint-associated molecules in bladder urothelial carcinoma: A retrospective study.

PubMed

Le Goux, Constance; Damotte, Diane; Vacher, Sophie; Sibony, Mathilde; Delongchamps, Nicolas Barry; Schnitzler, Anne; Terris, Benoit; Zerbib, Marc; Bieche, Ivan; Pignot, Géraldine

2017-05-01

Immunotherapy for bladder cancer seems to have promising results. Here, we evaluated the association between messenger RNA (mRNA) and protein levels and possible prognostic value of the programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) immune checkpoint pathways during bladder carcinogenesis. Tumor samples were obtained from 155 patients (84 with muscle-invasive bladder cancer [MIBC], and 71 non-muscle-invasive bladder cancer [NMIBC]) and normal bladder tissue from 15 patients. We evaluated the mRNA expression of 3 genes in the PD-1 pathway (PD-1, PD-L1, and PD-L2) and 4 in the CTLA4 pathway (CTLA4, CD28, CD80, and CD86) in normal and tumoral human bladder samples by quantitative real-time reverse transcription polymerase chain reaction, with immunohistochemistry used to evaluate the protein expression of PD-1 and PD-L1 in tumor and immune cells. Results of molecular analyses were compared with survival analyses. As compared with normal bladder tissue, MIBC tissue showed PD-1, PD-L1, CTLA4, and CD80 overexpression (59.5%, 60.7%, 84.5%, and 92.9%, respectively), whereas overexpression was lower in NMIBC tissue (22.5%, 4.2%, 35.2%, and 46.5%, respectively). The results of reverse transcription polymerase chain reaction analysis were confirmed by immunohistochemistry, with a high correlation between mRNA and protein expression. On multivariate analyses, overexpression of the studied genes was not associated with prognosis in relapse or progression of NMIBC or in recurrence-free and overall survival of MIBC. The CTLA4 pathway appears to be deregulated along with the PD-1/PD-L1 pathway in bladder carcinogenesis, with good correlation between mRNA and protein expression endorsing the useful role of immune checkpoints, especially for a large subgroup of MIBC. Copyright © 2017 Elsevier Inc. All rights reserved.

Bioadhesive drug delivery system using glyceryl monooleate for the intravesical administration of paclitaxel.

PubMed

Lee, Seung-Ju; Kim, Sae Woong; Chung, Hesson; Park, Yeong Taek; Choi, Young Wook; Cho, Yong-Hyun; Yoon, Moon Soo

2005-10-01

Many reports have shown that the efficacy of intravesical therapy for bladder cancer is in part limited by the poor penetration of drugs into the urothelium. The present study evaluated the effect of glyceryl monooleate (GMO) on the absorption of intravesically administered paclitaxel in a rabbit model of bladder cancer. Urine, plasma, and tissue pharmacokinetics were determined in rabbits treated for 120 min with paclitaxel (500 microg/20 ml) by intravesical instillation. Two formulations of GMO/paclitaxel were evaluated using different proportions of water, 15 and 30%, and Taxol was used as a control. Animals were observed for clinical signs of toxicity and necropsy was performed. 120 min after instillation, the bladder was emptied and excised. In the urine, paclitaxel concentration was decreased by 39.6 and 41.2% in the two experimental groups and by 25.2% in the control group. The paclitaxel concentrations in the urothelium were 53 and 56% of the urine concentration in both experimental groups, but 11% in the control group. The concentration then declined exponentially in the underlying capillary-perfused tissues, reaching equilibrium at a depth of 1,400-1,700 microm. The plasma concentrations were extremely low compared with concentrations in urine and bladder tissues and were not associated with clinical toxicity. We conclude that GMO has a significantly increased bioadhesiveness to bladder mucosa. Therefore, intravesical administration of GMO/paclitaxel/water provides a significant advantage for drugs targeting the bladder tissue, and paclitaxel represents a viable option for intravesical bladder cancer therapy. Copyright 2005 S. Karger AG, Basel.

Immunology of malignant diseases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Byers, V.S.; Baldwin, R.W.

1987-01-01

This book contains 11 chapters. Some of the chapter titles are: Immunoscintigraphy: tumor detection with radiolabelled antitumor monoclonal antibodies; Bone marrow transplantation; Immunomodulating agents; Immunology in bowel cancer; Melanoma; and Immunological features of human bladder cancer.

Parasites and malignancies, a review, with emphasis on digestive cancer induced by Cryptosporidium parvum (Alveolata: Apicomplexa)

PubMed Central

Benamrouz, S.; Conseil, V.; Creusy, C.; Calderon, E.; Dei-Cas, E.; Certad, G.

2012-01-01

The International Agency for Research on Cancer (IARC) identifies ten infectious agents (viruses, bacteria, parasites) able to induce cancer disease in humans. Among parasites, a carcinogenic role is currently recognized to the digenetic trematodes Schistosoma haematobium, leading to bladder cancer, and to Clonorchis sinensis or Opisthorchis viverrini, which cause cholangiocarcinoma. Furthermore, several reports suspected the potential association of other parasitic infections (due to Protozoan or Metazoan parasites) with the development of neoplastic changes in the host tissues. The present work shortly reviewed available data on the involvement of parasites in neoplastic processes in humans or animals, and especially focused on the carcinogenic power of Cryptosporidium parvum infection. On the whole, infection seems to play a crucial role in the etiology of cancer. PMID:22348213

Parasites and malignancies, a review, with emphasis on digestive cancer induced by Cryptosporidium parvum (Alveolata: Apicomplexa).

PubMed

Benamrouz, S; Conseil, V; Creusy, C; Calderon, E; Dei-Cas, E; Certad, G

2012-05-01

The International Agency for Research on Cancer (IARC) identifies ten infectious agents (viruses, bacteria, parasites) able to induce cancer disease in humans. Among parasites, a carcinogenic role is currently recognized to the digenetic trematodes Schistosoma haematobium, leading to bladder cancer, and to Clonorchis sinensis or Opisthorchis viverrini, which cause cholangiocarcinoma. Furthermore, several reports suspected the potential association of other parasitic infections (due to Protozoan or Metazoan parasites) with the development of neoplastic changes in the host tissues. The present work shortly reviewed available data on the involvement of parasites in neoplastic processes in humans or animals, and especially focused on the carcinogenic power of Cryptosporidium parvum infection. On the whole, infection seems to play a crucial role in the etiology of cancer.

Expression of chicken ovalbumin upstream promoter-transcription factor I (COUP-TFI) in bladder transitional cell carcinoma.

PubMed

Ham, Won Sik; Lee, Joo Hyoung; Yu, Ho Song; Choi, Young Deuk

2008-10-01

An analysis of differentially expressed genes (DEGs) between bladder transitional cell carcinoma (TCC) and the surrounding urothelium to help identify what lies behind the mechanism of multifocal tumor development has not yet been performed. We sought to find a new DEG related to the development of bladder TCC. Thirty-nine bladder TCC tissues paired with normal-appearing urothelium tissues obtained from the same patient were used as subjects. Initially, we compared the messenger RNA (mRNA) profiles between normal-appearing urothelium and TCC tissue of 1 patient by using annealing control primer (ACP)-based GeneFishing polymerase chain reaction (PCR) and selective amplification of family members (SAFM) PCR to identify potential DEGs. To validate the results of the ACP data, reverse transcriptase-polymerase chain reaction (RT-PCR) was performed on those of all 39 patients. Among the several DEGs discovered in the ACP data, 1 DEG was chosen as the candidate for the RT-PCR, that is present or markedly upregulated in normal-appearing urothelial tissue compared with TCC tissue. Gene sequence searching revealed that this DEG is chicken ovalbumin upstream promoter-transcription factor I (COUP-TFI). Downregulation of COUP-TFI mRNA expression in TCC tissue compared to normal-appearing urothelium tissue of the same patient, irrespective of tumor stage and grade, was confirmed by RT-PCR in 39 patients. Our results suggest that the loss of COUP-TFI may play a role in the transition from normal epithelium to TCC. Further characterization of the COUP-TFI gene is expected to give us informations about bladder TCC tumorigenesis.

Bladder augmentation and artificial sphincter implantation: urodynamic behavior and effects on continence.

PubMed

Rodó, Juan S; Cáceres, Freud A; Lerena, Javier R; Rossy, Enrica

2008-02-01

To quantify changes in bladder capacity, pressure and compliance after isolated bladder augmentation or augmentation associated with implantation of an artificial sphincter, and to compare the various types of augmentation. Preoperative and postoperative urodynamic studies were performed in a group of 38 patients (18 males and 20 females; age range 2-19 years), who underwent a type of bladder augmentation. The bladder improved in capacity in all patients (mean values: initial 137 ml, final 336 ml, individual increase 229 ml; 434%) except two, in which the augmentation was done with ureter. The mean pressure improved (initial 32 cm of H(2)O, final 14, decrease per patient 18 cm of H2O; 49%). The curve of compliance, progressively increasing typical of hyperreflexia and poor compliance, present in 70% of the cases preoperatively, improved in 78% cases postoperatively, although there were several different patterns. Urodynamic behavior was analyzed with regard to the tissue used for augmentation (ileum, ureter or sigmoid colon). In the sigmoid colon group, there were no significant differences in the urodynamic behavior of the bladder neo-reservoir in relation to the configuration used. With bladder augmentation comes an increase in bladder capacity, a reduction in pressure, and an improvement in compliance and continence. The level of change in capacity, pressure and compliance varies with the tissue used and the length and caliber of the insert. When the procedure is carried out using sigmoid colon tissue, there are no noteworthy differences among the various possible configurations.

Curcumin inhibits bladder cancer progression via regulation of β-catenin expression.

PubMed

Shi, Jing; Wang, Yunpeng; Jia, Zhuomin; Gao, Yu; Zhao, Chaofei; Yao, Yuanxin

2017-07-01

Bladder cancer has a considerable morbidity and mortality impact with particularly poor prognosis. Curcumin has been recently noticed as a polyphenolic compound separated from turmeric to regulate tumor progression. However, the precise molecular mechanism by which curcumin inhibits the invasion and metastasis of bladder cancer cells is not fully elucidated. In this study, we investigate the effect of curcumin on the bladder cancer as well as possible mechanisms of curcumin. The expression of β-catenin was detected by quantitative real-time polymerase chain reaction and immunohistochemical analysis in a series of bladder cancer tissues. In addition, bladder cancer cell lines T24 and 5637 cells were treated with different concentrations of curcumin. The cytotoxic effect of curcumin on cell proliferation of T24 and 5637 cells was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The migration and invasion capacity of T24 and 5637 cells were measured by transwell assay. The effects of curcumin on expression levels of β-catenin and epithelial-mesenchymal transition marker were determined by western blotting. The β-catenin expression was significantly upregulated in bladder cancer tissues when compared with corresponding peri-tumor tissues. Furthermore, curcumin inhibited the cell proliferation of T24 and 5637 cells, and curcumin reduced the migration and invasive ability of T24 and 5637 cells via regulating β-catenin expression and reversing epithelial-mesenchymal transition. Curcumin may be a new drug for bladder cancer.

A flowgraph model for bladder carcinoma

PubMed Central

2014-01-01

Background Superficial bladder cancer has been the subject of numerous studies for many years, but the evolution of the disease still remains not well understood. After the tumor has been surgically removed, it may reappear at a similar level of malignancy or progress to a higher level. The process may be reasonably modeled by means of a Markov process. However, in order to more completely model the evolution of the disease, this approach is insufficient. The semi-Markov framework allows a more realistic approach, but calculations become frequently intractable. In this context, flowgraph models provide an efficient approach to successfully manage the evolution of superficial bladder carcinoma. Our aim is to test this methodology in this particular case. Results We have built a successful model for a simple but representative case. Conclusion The flowgraph approach is suitable for modeling of superficial bladder cancer. PMID:25080066

Lymphotoxin β receptor activation promotes bladder cancer in a nuclear factor-κB-dependent manner.

PubMed

Shen, Mo; Duan, Xiuzhi; Zhou, Ping; Zhou, Wu; Wu, Xiuling; Xu, Siqi; Chen, Yuhua; Tao, Zhihua

2015-02-01

Bladder cancer (BCa) is the most common tumor of the urinary system. Chronic inflammation in the papillary urothelial neoplasm of low malignant potential (PUNLMP)may contribute to carcinogenesis, including that of BCa, via poorly understood mechanisms. In this study, we show that the lymphotoxin β receptor (LTβR) is upregulated in BCa via activation of the canonical and non-canonical nuclear factor-κB (NF-κB) pathways. The mRNA expression of LTβR in 81 BCa, 10 chronic cystitis and 23 healthy bladder mucosa tissues was investigated by reverse transcription-fluorescent quantitative polymerase chain reaction (RT-FQ-PCR), and protein expression was studied in 73 BCa, 30 cystitis and 15 healthy paraffin-embedded tissue sections by immunohistochemistry. Both LTβR mRNA and protein were upregulated in BCa and cystitis compared to the healthy group (P<0.05). The mRNA level of the downstream NF-κB canonical pathway p65 gene and of the non-canonical pathway RelB gene were higher in the BCa and cystitis groups compared to the healthy one. The level of phosphorylated p65 (p-p65) protein of the canonical NF-κB pathway and that of p52, a protein of the non-canonical NF-κB pathway, were also higher in the BCa and cystitis group compared to the healthy group. The levels of these proteins significantly correlated to the pathological grade, clinical stage and lymph node metastasis of BCa patients (P<0.05). In addition, there was a positive correlation between LTβR and NF-κB pathway proteins. Thus, LTβR signaling may be involved in promoting BCa through the NF-κB pathway, and which may represent the molecular link between inflammation and BCa.

Oncogenic PIK3CA mutations occur in epidermal nevi and seborrheic keratoses with a characteristic mutation pattern

PubMed Central

Hafner, Christian; López-Knowles, Elena; Luis, Nuno M.; Toll, Agustí; Baselga, Eulàlia; Fernández-Casado, Alex; Hernández, Silvia; Ribé, Adriana; Mentzel, Thomas; Stoehr, Robert; Hofstaedter, Ferdinand; Landthaler, Michael; Vogt, Thomas; Pujol, Ramòn M.; Hartmann, Arndt; Real, Francisco X.

2007-01-01

Activating mutations of the p110 α subunit of PI3K (PIK3CA) oncogene have been identified in a broad spectrum of malignant tumors. However, their role in benign or preneoplastic conditions is unknown. Activating FGF receptor 3 (FGFR3) mutations are common in benign skin lesions, either as embryonic mutations in epidermal nevi (EN) or as somatic mutations in seborrheic keratoses (SK). FGFR3 mutations are also common in low-grade malignant bladder tumors, where they often occur in association with PIK3CA mutations. Therefore, we examined exons 9 and 20 of PIK3CA and FGFR3 hotspot mutations in EN (n = 33) and SK (n = 62), two proliferative skin lesions lacking malignant potential. Nine of 33 (27%) EN harbored PIK3CA mutations; all cases showed the E545G substitution, which is uncommon in cancers. In EN, R248C was the only FGFR3 mutation identified. By contrast, 10 of 62 (16%) SK revealed the typical cancer-associated PIK3CA mutations E542K, E545K, and H1047R. The same lesions displayed a wide range of FGFR3 mutations. Corresponding unaffected tissue was available for four EN and two mutant SK: all control samples displayed a WT sequence, confirming the somatic nature of the mutations found in lesional tissue. Forty of 95 (42%) lesions showed at least one mutation in either gene. PIK3CA and FGFR3 mutations displayed an independent distribution; 5/95 lesions harbored mutations in both genes. Our findings suggest that, in addition to their role in cancer, oncogenic PIK3CA mutations contribute to the pathogenesis of skin tumors lacking malignant potential. The remarkable genotype–phenotype correlation as observed in this study points to a distinct etiopathogenesis of the mutations in keratinocytes occuring either during fetal development or in adult life. PMID:17673550

Infiltrating T Cells Promote Bladder Cancer Progression via Increasing IL1→Androgen Receptor→HIF1α→VEGFa Signals.

PubMed

Tao, Le; Qiu, Jianxin; Jiang, Ming; Song, Wenbin; Yeh, Shuyuan; Yu, Hong; Zang, Lijuan; Xia, Shujie; Chang, Chawnshang

2016-08-01

The tumor microenvironment impacts tumor progression and individual cells, including CD4(+) T cells, which have been detected in bladder cancer tissues. The detailed mechanism of how these T cells were recruited to the bladder cancer tumor and their impact on bladder cancer progression, however, remains unclear. Using a human clinical bladder cancer sample survey and in vitro coculture system, we found that bladder cancer has a greater capacity to recruit T cells than surrounding normal bladder tissues. The consequences of higher levels of recruited T cells in bladder cancer included increased bladder cancer metastasis. Mechanism dissection revealed that infiltrating T cells might function through secreting the cytokine IL1, which increases the recruitment of T cells to bladder cancer and enhances the bladder cancer androgen receptor (AR) signaling that results in increased bladder cancer cell invasion via upregulation of hypoxia-inducible factor-1α (HIF1α)/VEGFa expression. Interruption of the IL1→AR→HIF1α→VEGFa signals with inhibitors of HIF1α or VEGFa partially reversed the enhanced bladder cancer cell invasion. Finally, in vivo mouse models of xenografted bladder cancer T24 cells with CD4(+) T cells confirmed in vitro coculture studies and concluded that infiltrating CD4(+) T cells can promote bladder cancer metastasis via modulation of the IL1→AR→HIF1α→VEGFa signaling. Future clinical trials using small molecules to target this newly identified signaling pathway may facilitate the development of new therapeutic approaches to better suppress bladder cancer metastasis. Mol Cancer Ther; 15(8); 1943-51. ©2016 AACR. ©2016 American Association for Cancer Research.

Analysis of Tissue and Serum MicroRNA Expression in Patients with Upper Urinary Tract Urothelial Cancer

PubMed Central

Kriebel, Stephanie; Schmidt, Doris; Holdenrieder, Stefan; Goltz, Diane; Kristiansen, Glen; Moritz, Rudolf; Fisang, Christian; Müller, Stefan C.; Ellinger, Jörg

2015-01-01

Introduction MicroRNAs play an important role in many human malignancies; so far, their expression remains to be studied in upper urinary tract urothelial cancer (UUTUC). Materials and Methods The expression of eleven microRNAs (miR-10a, miR-21, miR-96, miR-135, miR-141, miR-182, miR-200b, miR-205, miR-429, miR-520b, miR-1244) formerly shown to be upregulated in urothelial bladder cancer were studied in corresponding normal and cancerous tissue samples of patients undergoing nephroureterectomy for UUTUC. Upregulated microRNAs were then measured in serum samples of patients with UUTUC and patients with non-malignant urological diseases to evaluate their potential as non-invasive biomarkers for UUTUC. Results MicroRNA expression allowed differentiation of normal and cancerous tissue: miR-21, miR-96, miR-135, miR-141, miR-182, miR-205, miR-429 and miR-520b were significantly overexpressed. Furthermore, miR-205 was upregulated in poorly differentiated UUTUC. The analysis of circulating RNA in serum demonstrated an increase of miR-141 in patients with UUTUC; receiver operator characteristic analysis demonstrated an area under the curve of 0.726 for miR-141 as a diagnostic biomarker. Furthermore, we observed lower levels of miR-10a and miR-135 in UUTUC patients. Conclusions MicroRNA expression is altered in UUTUC. The analysis of circulating miR-141 may be useful to identify patients with UUTUC. PMID:25629698

Analysis of tissue and serum microRNA expression in patients with upper urinary tract urothelial cancer.

PubMed

Kriebel, Stephanie; Schmidt, Doris; Holdenrieder, Stefan; Goltz, Diane; Kristiansen, Glen; Moritz, Rudolf; Fisang, Christian; Müller, Stefan C; Ellinger, Jörg

2015-01-01

MicroRNAs play an important role in many human malignancies; so far, their expression remains to be studied in upper urinary tract urothelial cancer (UUTUC). The expression of eleven microRNAs (miR-10a, miR-21, miR-96, miR-135, miR-141, miR-182, miR-200b, miR-205, miR-429, miR-520b, miR-1244) formerly shown to be upregulated in urothelial bladder cancer were studied in corresponding normal and cancerous tissue samples of patients undergoing nephroureterectomy for UUTUC. Upregulated microRNAs were then measured in serum samples of patients with UUTUC and patients with non-malignant urological diseases to evaluate their potential as non-invasive biomarkers for UUTUC. MicroRNA expression allowed differentiation of normal and cancerous tissue: miR-21, miR-96, miR-135, miR-141, miR-182, miR-205, miR-429 and miR-520b were significantly overexpressed. Furthermore, miR-205 was upregulated in poorly differentiated UUTUC. The analysis of circulating RNA in serum demonstrated an increase of miR-141 in patients with UUTUC; receiver operator characteristic analysis demonstrated an area under the curve of 0.726 for miR-141 as a diagnostic biomarker. Furthermore, we observed lower levels of miR-10a and miR-135 in UUTUC patients. MicroRNA expression is altered in UUTUC. The analysis of circulating miR-141 may be useful to identify patients with UUTUC.

Insights from animal models of bladder cancer: recent advances, challenges, and opportunities

PubMed Central

John, Bincy Anu; Said, Neveen

2017-01-01

Bladder cancer (urothelial cancer of the bladder) is the most common malignancy affecting the urinary system with increasing incidence and mortality. Treatment of bladder cancer has not advanced in the past 30 years. Therefore, there is a crucial unmet need for novel therapies, especially for high grade/stage disease that can only be achieved by preclinical model systems that faithfully recapitulate the human disease. Animal models are essential elements in bladder cancer research to comprehensively study the multistep cascades of carcinogenesis, progression and metastasis. They allow for the investigation of premalignant phases of the disease that are not clinically encountered. They can be useful for identification of diagnostic and prognostic biomarkers for disease progression and for preclinical identification and validation of therapeutic targets/candidates, advancing translation of basic research to clinic. This review summarizes the latest advances in the currently available bladder cancer animal models, their translational potential, merits and demerits, and the prevalent tumor evaluation modalities. Thereby, findings from these model systems would provide valuable information that can help researchers and clinicians utilize the model that best answers their research questions. PMID:28915710

Cabozantinib-s-malate and Nivolumab With or Without Ipilimumab in Treating Patients With Metastatic Genitourinary Tumors

ClinicalTrials.gov

2018-04-02

Clear Cell Renal Cell Carcinoma; Metastatic Malignant Neoplasm in the Bone; Metastatic Penile Carcinoma; Renal Pelvis Urothelial Carcinoma; Squamous Cell Carcinoma of the Penis; Stage III Bladder Adenocarcinoma AJCC v6 and v7; Stage III Bladder Squamous Cell Carcinoma AJCC v6 and v7; Stage III Bladder Urothelial Carcinoma AJCC v6 and v7; Stage III Penile Cancer AJCC v7; Stage III Renal Cell Cancer AJCC v7; Stage III Renal Pelvis Cancer AJCC v7; Stage III Ureter Cancer AJCC v7; Stage III Urethral Cancer AJCC v7; Stage IIIa Penile Cancer AJCC v7; Stage IIIb Penile Cancer AJCC v7; Stage IV Bladder Adenocarcinoma AJCC v7; Stage IV Bladder Squamous Cell Carcinoma AJCC v7; Stage IV Bladder Urothelial Carcinoma AJCC v7; Stage IV Penile Cancer AJCC v7; Stage IV Renal Cell Cancer AJCC v7; Stage IV Renal Pelvis Cancer AJCC v7; Stage IV Ureter Cancer AJCC v7; Stage IV Urethral Cancer AJCC v7; Ureter Urothelial Carcinoma; Urethral Urothelial Carcinoma

Biochemical and pathological changes in the male rat kidney and bladder following exposure to continuous 900-MHz electromagnetic field on postnatal days 22-59^.

PubMed

Türedi, Sibel; Kerimoğlu, Gökçen; Mercantepe, Tolga; Odacı, Ersan

2017-09-01

To investigate the effect on male rat kidney and bladder tissues of exposure to 900-megahertz (MHz) electromagnetic field (EMF) applied on postnatal days 22-59, inclusive. Twenty-four male Sprague Dawley rats, aged 21 days, were used. These were divided equally into one of three groups, control (CG), sham (SG) or EMF (EMFG). CG was not exposed to any procedure. SG rats were kept inside a cage, without being exposed to the effect of EMF, for 1 h a day on postnatal days 22-59, inclusive. EMFG rats were exposed to continuous 900-MHz EMF for 1 h a day under the same conditions as those for the SG rats. Rats were sacrificed on postnatal day 60, and the kidney and bladder tissues were removed. Tissues were stained with hematoxylin and eosin (H&E) and Masson trichrome for histomorphological evaluation. The TUNEL method was used to assess apoptosis. Transmission electron microscopy (TEM) was also used for the kidney tissue. Oxidant/antioxidant parameters were studied in terms of biochemical values. The findings showed that tissue malondialdehyde increased in EMFG compared to CG and SG in both kidney (p = 0.004 and p = 0.004, respectively) and bladder tissue (p = 0.004, p = 0.006, respectively), while catalase and glutathione levels decreased compared to CG (p = 0.004; p = 0.004, respectively) and SG (p = 0.004; p = 0.004, respectively). In the EMF group, pathologies such as dilatation and vacuolization in the distal and proximal tubules, degeneration in glomeruli and an increase in cells tending to apoptosis were observed in kidney tissue. In bladder tissue, degeneration in the transitional epithelium and stromal irregularity and an increase in cells tending to apoptosis were observed in EMFG. Additionally, EMFG samples exhibited glomerular capillary degeneration with capillary basement membranes under TEM. We conclude that continuous exposure to the effect of 900-MHz EMF for 1 h a day on postnatal days 22-59, inclusive, causes an increase in oxidative stress and various pathological changes in male rat kidney and bladder tissues.

68Ga-PSMA-HBED-CC-Avid Synchronous Urinary Bladder Paraganglioma in a Patient With Metastatic Prostate Carcinoma.

PubMed

Parihar, Ashwin Singh; Vadi, Shelvin Kumar; Mittal, Bhagwant Rai; Kumar, Rajender; Bal, Amanjit; Singh, Shrawan Kumar

2018-06-19

Ga-PSMA-HBED-CC PET/CT has proven to be a useful modality in patients with prostate carcinoma, especially in those with suspected recurrence and in detection of locoregional and distant metastases. However, with expanding use of this tracer, several recent reports of in vivo expression of PSMA in nonprostatic benign and malignant entities have been published. We report a patient with PSMA-avid synchronous urinary bladder paraganglioma and metastatic prostate carcinoma.

Photodynamic diagnosis of bladder cancer in ex vivo urine cytology

NASA Astrophysics Data System (ADS)

Fu, C. Y.; Ng, B. K.; Razul, S. Gulam; Olivo, Malini C.; Lau, Weber K. O.; Tan, P. H.; Chin, William

2006-02-01

Bladder cancer is the fourth common malignant disease worldwide, accounting for 4% of all cancer cases. In Singapore, it is the ninth most common form of cancer. The high mortality rate can be reduced by early treatment following precancerous screening. Currently, the gold standard for screening bladder tumors is histological examination of biopsy specimen, which is both invasive and time-consuming. In this study ex vivo urine fluorescence cytology is investigated to offer a timely and biopsy-free means for detecting bladder cancers. Sediments in patients' urine samples were extracted and incubated with a novel photosensitizer, hypericin. Laser confocal microscopy was used to capture the fluorescence images at an excitation wavelength of 488 nm. Images were subsequently processed to single out the exfoliated bladder cells from the other cells based on the cellular size. Intensity histogram of each targeted cell was plotted and feature vectors, derived from the histogram moments, were used to represent each sample. A difference in the distribution of the feature vectors of normal and low-grade cancerous bladder cells was observed. Diagnostic algorithm for discriminating between normal and low-grade cancerous cells is elucidated in this paper. This study suggests that the fluorescence intensity profiles of hypericin in bladder cells can potentially provide an automated quantitative means of early bladder cancer diagnosis.

Problems arising in the diagnosis of primary ovarian transitional cell carcinoma after the occurrence of a transitional cell carcinoma of the bladder: a report of a difficult case and a critical review of literature.

PubMed

Raspollini, Maria Rosaria; Paglierani, Milena; Taddei, Gian Luigi

2009-03-01

Transitional cell carcinoma (TCC) of the ovary is a recently recognized subtype of ovarian surface epithelial-stromal cancer that morphologically resembles a TCC of the bladder. The most frequent metastases to ovaries come from the gastrointestinal tract and from breast carcinoma, but metastatic TCCs from the urinary tract to the ovary have been reported. TCC of the bladder is the sixth most common cancer in European and North American countries and its incidence has been increasing. We recently observed a woman, who previously had undergone endoscopic resection of a TCC of the bladder. She was affected by an ovarian bilateral tumor with features of malignant transitional cell tumor, characterized by papillae with multilayered transitional epithelium infiltrating the ovarian stroma. In this study, we showed the utility of WT1 and a panel of immunohistochemical markers in the difficult differential diagnosis between bladder and ovarian TCC.

[Association of serum decoy receptor 3 protein level with the clinicopathologic features of bladder transitional cell carcinoma].

PubMed

Wang, Dong; Wang, Jian; Chen, Guojun

2013-12-01

To investigate the association of serum levels of decoy receptor 3(DcR3) protein and the clinicopathologic features of bladder transitional cell carcinoma. Enzyme-linked immunosorbent assay was used to examine the serum levels of DcR3 in patients with bladder transitional cell carcinoma for analysis of its association with the patients' age, gender, clinical stages and pathological classification. The patients with bladder transitional cell carcinoma showed a significantly elevated serum level of DcR3 (183.43 ∓78.45 pg/m1) compared with the normal level (116.65∓97.43 pg/m1, P<0.05). The serum level of DcR3 in the patients showed close correlations with the TNM stage and pathological classification of the tumor (P<0.05) but not with the patients' age or gender (P>0.05). In patients with bladder transitional cell carcinoma, a high serum level of DcR3 suggests a higher malignancy of the tumor.

Proceedings of the 3rd Annual Albert Institute for Bladder Cancer Research Symposium.

PubMed

Flaig, Thomas W; Kamat, Ashish M; Hansel, Donna; Ingersoll, Molly A; Barton Grossman, H; Mendelsohn, Cathy; DeGraff, David; Liao, Joseph C; Taylor, John A

2017-07-27

The Third Annual Albert Institute Bladder Symposium was held on September 8-10th, 2016, in Denver Colorado. Participants discussed several critical topics in the field of bladder cancer: 1) Best practices for tissue analysis and use to optimize correlative studies, 2) Modeling bladder cancer to facilitate understanding and innovation, 3) Targeted therapies for bladder cancer, 4) Tumor phylogeny in bladder cancer, 5) New Innovations in bladder cancer diagnostics. Our understanding of and approach to treating urothelial carcinoma is undergoing rapid advancement. Preclinical models of bladder cancer have been leveraged to increase our basic and mechanistic understanding of the disease. With the approval of immune checkpoint inhibitors for the treatment of advanced urothelial carcinoma, the treatment approach for these patients has quickly changed. In this light, molecularly-defined subtypes of bladder cancer and appropriate pre-clinical models are now essential to the further advancement and appropriate application of these therapeutic improvements. The optimal collection and processing of clinical urothelial carcinoma tissues samples will also be critical in the development of predictive biomarkers for therapeutic selection. Technological advances in other areas including optimal imaging technologies and micro/nanotechnologies are being applied to bladder cancer, especially in the localized setting, and hold the potential for translational impact in the treatment of bladder cancer patients. Taken together, advances in several basic science and clinical areas are now converging in bladder cancer. These developments hold the promise of shaping and improving the clinical care of those with the disease.

Prospective Clinical Trial of Bladder Filling and Three-Dimensional Dosimetry in High-Dose-Rate Vaginal Cuff Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stewart, Alexandra J.; Cormack, Robert A.; Lee, Hang

2008-11-01

Purpose: To investigate the effect of bladder filling on dosimetry and to determine the best bladder dosimetric parameter for vaginal cuff brachytherapy. Methods and Materials: In this prospective clinical trial, a total of 20 women underwent vaginal cylinder high-dose-rate brachytherapy. The bladder was full for Fraction 2 and empty for Fraction 3. Dose-volume histogram and dose-surface histogram values were generated for the bladder, rectum, and urethra. The midline maximal bladder point (MBP) and the midline maximal rectal point were recorded. Paired t tests, Pearson correlations, and regression analyses were performed. Results: The volume and surface area of the irradiated bladdermore » were significantly smaller when the bladder was empty than when full. Of the several dose-volume histogram and dose-surface histogram parameters evaluated, the bladder maximal dose received by 2 cm{sup 3} of tissue, volume of bladder receiving {>=}50% of the dose, volume of bladder receiving {>=}70% of the dose, and surface area of bladder receiving {>=}50% of the dose significantly predicted for the difference between the empty vs. full filling state. The volume of bladder receiving {>=}70% of the dose and the maximal dose received by 2 cm{sup 3} of tissue correlated significantly with the MBP. Bladder filling did not alter the volume or surface area of the rectum irradiated. However, an empty bladder did result in the nearest point of bowel being significantly closer to the vaginal cylinder than when the bladder was full. Conclusions: Patients undergoing vaginal cuff brachytherapy treated with an empty bladder have a lower bladder dose than those treated with a full bladder. The MBP correlated well with the volumetric assessments of bladder dose and provided a noninvasive method for reporting the MBP dose using three-dimensional imaging. The MBP can therefore be used as a surrogate for complex dosimetry in the clinic.« less

Intrafraction Bladder Motion in Radiation Therapy Estimated From Pretreatment and Posttreatment Volumetric Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Foroudi, Farshad, E-mail: farshad.foroudi@petermac.org; Pham, Daniel; Bressel, Mathias

2013-05-01

Purpose: The use of image guidance protocols using soft tissue anatomy identification before treatment can reduce interfractional variation. This makes intrafraction clinical target volume (CTV) to planning target volume (PTV) changes more important, including those resulting from intrafraction bladder filling and motion. The purpose of this study was to investigate the required intrafraction margins for soft tissue image guidance from pretreatment and posttreatment volumetric imaging. Methods and Materials: Fifty patients with muscle-invasive bladder cancer (T2-T4) underwent an adaptive radiation therapy protocol using daily pretreatment cone beam computed tomography (CBCT) with weekly posttreatment CBCT. A total of 235 pairs of pretreatmentmore » and posttreatment CBCT images were retrospectively contoured by a single radiation oncologist (CBCT-CTV). The maximum bladder displacement was measured according to the patient's bony pelvis movement during treatment, intrafraction bladder filling, and bladder centroid motion. Results: The mean time between pretreatment and posttreatment CBCT was 13 minutes, 52 seconds (range, 7 min 52 sec to 30 min 56 sec). Taking into account patient motion, bladder centroid motion, and bladder filling, the required margins to cover intrafraction changes from pretreatment to posttreatment in the superior, inferior, right, left, anterior, and posterior were 1.25 cm (range, 1.19-1.50 cm), 0.67 cm (range, 0.58-1.12 cm), 0.74 cm (range, 0.59-0.94 cm), 0.73 cm (range, 0.51-1.00 cm), 1.20 cm (range, 0.85-1.32 cm), and 0.86 cm (range, 0.73-0.99), respectively. Small bladders on pretreatment imaging had relatively the largest increase in pretreatment to posttreatment volume. Conclusion: Intrafraction motion of the bladder based on pretreatment and posttreatment bladder imaging can be significant particularly in the anterior and superior directions. Patient motion, bladder centroid motion, and bladder filling all contribute to changes between pretreatment and posttreatment imaging. Asymmetric expansion of CTV to PTV should be considered. Care is required in using image-guided radiation therapy protocols that reduce CTV to PTV margins based only on daily pretreatment soft tissue position.« less

Surgical technique for en bloc transurethral resection of bladder tumour with a Hybrid Knife(®).

PubMed

Islas-García, J J O; Campos-Salcedo, J G; López-Benjume, B I; Torres-Gómez, J J; Aguilar-Colmenero, J; Martínez-Alonso, I A; Gil-Villa, S A

2016-05-01

Bladder cancer is the second most common malignancy of the urinary tract and the 9th worldwide. Latin American has an incidence of 5.6 per 100,000 inhabitants per year. Seventy-five percent of newly diagnosed cases are nonmuscle invasive bladder cancer, and 25% of cases present as muscle invasive. The mainstay of treatment for nonmuscle invasive bladder cancer is loop transurethral resection. In 2013, the group led by Dr Mundhenk of the University Hospital of Tübingen, Germany, was the first to describe the Hybrid Knife(®) equipment for performing en bloc bladder tumour resection, with favourable functional and oncological results. To describe the surgical technique of en bloc bladder tumour resection with a Hybrid Knife(®) as an alternative treatment for nonmuscle invasive bladder tumours. A male patient was diagnosed by urotomography and urethrocystoscopy with a bladder tumour measuring 2×1cm on the floor. En bloc transurethral resection of the bladder tumour was performed with a Hybrid Knife(®). Surgery was performed for 35min, with 70 watts for cutting and 50 watts for coagulation, resecting and evacuating en bloc the bladder tumour, which macroscopically included the muscle layer of the bladder. There were no complications. The technique of en bloc bladder tumour resection with Hybrid Knife(®) is an effective alternative to bipolar loop transurethral resection. Resection with a Hybrid Knife(®) is a procedure with little bleeding and good surgical vision and minimises the risk of bladder perforation and tumour implants. The procedure facilitates determining the positivity of the neoplastic process, vascular infiltration and bladder muscle invasion in the histopathology study. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Sonography of tumors and tumor-like lesions that mimic carcinoma of the urinary bladder

PubMed Central

Szopiński, Tomasz; Gołąbek, Tomasz; Ostasz, Oksana; Bojko, Stefania

2014-01-01

One of the basic abdominal organs that is assessed during transabdominal ultrasound examination for urological reasons is the urinary bladder. The bladder must be filled with urine. This is a prerequisite for a reliable assessment and, at the same time, an acoustic window in examining adjacent structures and organs, for instance the prostate gland. In some cases, doubts occur with respect to the nature of lesions detected. The paper presents anatomic lesions, defects and pathologies which might be erroneously interpreted as tumors of the urinary bladder, i.e. transitional cell carcinoma of the urinary bladder. The following lesions are discussed: 1) anatomic defects (including urachus remnants, ligaments that stabilize the bladder or cyst in the opening of the ureter into the bladder – ureterocele); 2) tumor- like lesions in the lumen of the urinary bladder (such as blood clots, fungus balls, stones or foreign bodies); 3) bladder wall pathologies (i.e. cystitis or endometriosis), focal decidual transformation of stromal cells or inflammatory pseudotumor; 4) lesions impressing on the bladder from the outside (the mesentery of the sigmoid colon, the bowel, pathological lesions in organs adjacent to the urinary bladder, inflammatory infiltration, vasogenic compression of the bladder, pelvic lipomatosis, pathological lesions of the pubic symphysis); 5) postoperative lesions. All these lesions may mimic carcinoma of the urinary bladder in sonography. Bearing this fact in mind is significant in establishing a diagnosis. Due to the malignant character of carcinoma of the urinary bladder and the need for aggressive surgical treatment, a correct diagnosis of this disease is essential for patients, particularly because the lack of adequate treatment and delayed treatment considerably affect prognosis. PMID:26672732

Paraganglioma of the Urinary Bladder: A Rare Cause of Hypertension and Urinary Tract Infections.

PubMed

Chaaya, Gerard; Morales, Jorge; Castiglioni, Analia; Subhani, Noman; Asmar, Abdo

2018-02-01

Pheochromocytoma is a neoplasm, which develops from cells of the chromaffin tissues that are derived from the ectodermic neural system and mostly situated within the adrenal medulla. Approximately 15% of pheochromocytoma cases arise from extra-adrenal chromaffin tissue. Pheochromocytoma of the bladder is rare and accounts for less than 0.06% of all bladder neoplasms and less than 1% of all pheochromocytomas. We report a case of a young woman who presented with uncontrolled hypertension, recurrent urinary tract infections and micturition attacks and was found to have a metastatic bladder paraganglioma. In addition, we provide a summary table of the clinical manifestations of paragangliomas based on anatomic locations. Published by Elsevier Inc.

Unusual Presentation of Bladder Paraganglioma: Comparison of (131)I MIBG SPECT/CT and (68)Ga DOTANOC PET/CT.

PubMed

Jain, Tarun Kumar; Basher, Rajender Kumar; Gupta, Nitin; Shukla, Jaya; Singh, Shrawan Kumar; Mittal, Bhagwant Rai

2016-01-01

Extraadrenal chromaffin cell-related tumors or paragangliomas are rare, especially in the bladder, accounting for less than 1% of cases. We report a 16-year-old boy who presented with hematuria and paroxysmal headache and was found to have a prostatic growth infiltrating the urinary bladder on anatomical imaging. Iodine-131 ((131)I) metaiodobenzylguanidine (MIBG) whole-body scanning and subsequently gallium-68 ((68)Ga) DOTANOC positron emission tomography/computed tomography (PET/CT) were performed. The MIBG scan revealed a non-tracer-avid soft-tissue mass, while DOTANOC PET/CT revealed a tracer-avid primary soft-tissue mass involving the urinary bladder and prostate with metastasis to the iliac lymph nodes. He underwent surgical management; histopathology of the surgical specimen revealed a bladder paraganglioma, whereas the prostate was found to be free of tumor.

Epithelial-Mesenchymal Interactions in Urinary Bladder and Small Intestine and How to Apply Them in Tissue Engineering.

PubMed

Jerman, Urška Dragin; Kreft, Mateja Erdani; Veranič, Peter

2015-12-01

Reciprocal interactions between the epithelium and mesenchyme are essential for the establishment of proper tissue morphology during organogenesis and tissue regeneration as well as for the maintenance of cell differentiation. With this review, we highlight the importance of epithelial-mesenchymal cross talk in healthy tissue and further discuss its significance in engineering functional tissues in vitro. We focus on the urinary bladder and small intestine, organs that are often compromised by disease and are as such in need of research that would advance effective treatment or tissue replacement. To date, the understanding of epithelial-mesenchymal reciprocal interactions has enabled the development of in vitro biomimetic tissue equivalents that have provided many possibilities in treating defective, damaged, or even cancerous tissues. Although research of the past several years has advanced the field of bladder and small intestine tissue engineering, one must be aware of its current limitations in successfully and above all safely introducing tissue-engineered constructs into clinical practice. Special attention is in particular needed when treating cancerous tissues, as initially successful tumor excision and tissue reconstruction may later on result in cancer recurrence due to oncogenic signals originating from an altered stroma. Recent rather poor outcomes in pioneering clinical trials of bladder reconstructions should serve as a reminder that recreating a functional organ to replace a dysfunctional one is an objective far more difficult to reach than initially foreseen. When considering effective tissue engineering approaches for diseased tissues in humans, it is imperative to introduce animal models with dysfunctional or, even more importantly, cancerous organs, which would greatly contribute to predicting possible complications and, hence, reducing risks when translating to the clinic.

Dose Distribution in Bladder and Surrounding Normal Tissues in Relation to Bladder Volume in Conformal Radiotherapy for Bladder Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Majewski, Wojciech, E-mail: wmajewski1@poczta.onet.p; Wesolowska, Iwona; Urbanczyk, Hubert

2009-12-01

Purpose: To estimate bladder movements and changes in dose distribution in the bladder and surrounding tissues associated with changes in bladder filling and to estimate the internal treatment margins. Methods and Materials: A total of 16 patients with bladder cancer underwent planning computed tomography scans with 80- and 150-mL bladder volumes. The bladder displacements associated with the change in volume were measured. Each patient had treatment plans constructed for a 'partially empty' (80 mL) and a 'partially full' (150 mL) bladder. An additional plan was constructed for tumor irradiation alone. A subsequent 9 patients underwent sequential weekly computed tomography scanningmore » during radiotherapy to verify the bladder movements and estimate the internal margins. Results: Bladder movements were mainly observed cranially, and the estimated internal margins were nonuniform and largest (>2 cm) anteriorly and cranially. The dose distribution in the bladder worsened if the bladder increased in volume: 70% of patients (11 of 16) would have had bladder underdosed to <95% of the prescribed dose. The dose distribution in the rectum and intestines was better with a 'partially empty' bladder (volume that received >70%, 80%, and 90% of the prescribed dose was 23%, 20%, and 15% for the rectum and 162, 144, 123 cm{sup 3} for the intestines, respectively) than with a 'partially full' bladder (volume that received >70%, 80%, and 90% of the prescribed dose was 28%, 24%, and 18% for the rectum and 180, 158, 136 cm{sup 3} for the intestines, respectively). The change in bladder filling during RT was significant for the dose distribution in the intestines. Tumor irradiation alone was significantly better than whole bladder irradiation in terms of organ sparing. Conclusion: The displacements of the bladder due to volume changes were mainly related to the upper wall. The internal margins should be nonuniform, with the largest margins cranially and anteriorly. The changes in bladder filling during RT could influence the dose distribution in the bladder and intestines. The dose distribution in the rectum and bowel was slightly better with a 'partially empty' than with a 'full' bladder.« less

SPARC Gene Expression is Repressed in Human Urothelial Cells (UROtsa) Exposed to or Malignantly Transformed by Cadmium or Arsenite

PubMed Central

Larson, Jennifer; Yasmin, Tahmina; Sens, Donald A.; Zhou, Xu Dong; Sens, Mary Ann; Garrett, Scott H.; Dunlevy, Jane R.; Cao, Ling; Somji, Seema

2010-01-01

SPARC belongs to a class of extracellular matrix-associated proteins that have counteradhesive properties. The ability of SPARC to modulate cell-cell and cell-matrix interactions provides a strong rationale for studies designed to determine its expression in cancer. The objective of this study was to determine if SPARC expression was altered in cadmium (Cd+2) and arsenite (As+3) induced bladder cancer and if these alterations were present in archival specimens of human bladder cancer. The expression of SPARC was determined in human parental UROtsa cells, their Cd+2 and As+3 transformed counterparts and derived tumors, and in archival specimens of human bladder cancer using a combination of real time reverse transcriptase polymerase chain reaction, western blotting, immunofluoresence localization and immunohistochemical staining. It was demonstrated that SPARC expression was down-regulated in Cd+2 and As+3 transformed UROtsa cells. In addition, the malignant epithelial component of tumors derived from these cell lines were also down-regulated for SPARC expression, but the stromal cells recruited to these tumors was highly reactive for SPARC. This finding was shown to translate to specimens of human bladder cancer where tumor cells were SPARC negative, but stromal cells were positive. Acute exposure of UROtsa cells to both cadmium and arsenite reduced the expression of SPARC through a mechanism that did not involve changes in DNA methylation or histone acetylation. These studies suggest that environmental exposure to As+3 or Cd+2 can alter cell-cell and cell-matrix interactions in normal urothelial cells through a reduction in the expression of SPARC. The SPARC associated loss of cell-cell and cell-matrix contacts may participate in the multi-step process of bladder carcinogenesis. PMID:20837119

[Tissue engineering of urinary bladder using acellular matrix].

PubMed

Glybochko, P V; Olefir, Yu V; Alyaev, Yu G; Butnaru, D V; Bezrukov, E A; Chaplenko, A A; Zharikova, T M

2017-04-01

Tissue engineering has become a new promising strategy for repairing damaged organs of the urinary system, including the bladder. The basic idea of tissue engineering is to integrate cellular technology and advanced bio-compatible materials to replace or repair tissues and organs. of the study is the objective reflection of the current trends and advances in tissue engineering of the bladder using acellular matrix through a systematic search of preclinical and clinical studies of interest. Relevant studies, including those on methods of tissue engineering of urinary bladder, was retrieved from multiple databases, including Scopus, Web of Science, PubMed, Embase. The reference lists of the retrieved review articles were analyzed for the presence of the missing relevant publications. In addition, a manual search for registered clinical trials was conducted in clinicaltrials.gov. Following the above search strategy, a total of 77 eligible studies were selected for further analysis. Studies differed in the types of animal models, supporting structures, cells and growth factors. Among those, studies using cell-free matrix were selected for a more detailed analysis. Partial restoration of urothelium layer was observed in most studies where acellular grafts were used for cystoplasty, but no the growth of the muscle layer was observed. This is the main reason why cellular structures are more commonly used in clinical practice.

Dysregulation of miRNAs in bladder cancer: altered expression with aberrant biogenesis procedure

PubMed Central

Dong, Fan; Xu, Tianyuan; Shen, Yifan; Zhong, Shan; Chen, Shanwen; Ding, Qiang; Shen, Zhoujun

2017-01-01

Aberrant expression profiles of miRNAs are widely observed in the clinical tissue specimens and urine samples as well as the blood samples of bladder cancer patients. These profiles are closely related to the pathological features of bladder cancer, such as the tumour stage/grade, metastasis, recurrence and chemo-sensitivity. MiRNA biogenesis forms the basis of miRNA expression and function, and its dysregulation has been shown to be essential for variations in miRNA expression profiles as well as tumourigenesis and cancer progression. In this review, we summarize the up-to-date and widely reported miRNAs in bladder cancer that display significantly altered expression. We then compare the miRNA expression profiles among three different sample types (tissue, urine and blood) from patients with bladder cancer. Moreover, for the first time, we outline the dysregulated miRNA biogenesis network in bladder cancer from different levels and analyse its possible relationship with aberrant miRNA expression and the pathological characteristics of the disease. PMID:28187437

Biofabricated Structures Reconstruct Functional Urinary Bladders in Radiation-injured Rat Bladders.

PubMed

Imamura, Tetsuya; Shimamura, Mitsuru; Ogawa, Teruyuki; Minagawa, Tomonori; Nagai, Takashi; Silwal Gautam, Sudha; Ishizuka, Osamu

2018-05-08

The ability to repair damaged urinary bladders through the application of bone marrow-derived cells is in the earliest stages of development. We investigated the application of bone marrow-derived cells to repair radiation-injured bladders. We used a three-dimensional (3D) bioprinting robot system to biofabricate bone marrow-derived cell structures. We then determined if the biofabricated structures could restore the tissues and functions of radiation-injured bladders. The bladders of female 10-week-old Sprague-Dawley (SD) rats were irradiated with 2-Gy once a week for 5 weeks. Adherent and proliferating bone marrow-derived cells harvested from the femurs of male 17-week-old green fluorescence protein-transfected Tg-SD rats were cultured in collagen-coated flasks. Bone marrow-derived cell spheroids were formed in 96-well plates. Three layers of spheroids were assembled by the bioprinter onto a 9x9 microneedle array. The assembled spheroids were perfusion cultured for 7 days, and then the microneedle array was removed. Two weeks after the last radiation treatment, the biofabricated structures were transplanted into an incision on the anterior wall of the bladders (n=10). Control rats received the same surgery but without the biofabricated structures (sham-structure, n=12). At 2 and 4 weeks after surgery, the sham-structure control bladder tissues exhibited disorganized smooth muscle layers, decreased nerve cells, and significant fibrosis with increased presence of fibrosis-marker P4HB-positive cells and hypoxia-marker HIF1α-positive cells. The transplanted structures survived within the recipient tissues, and blood vessels extended within them from the recipient tissues. The bone marrow-derived cells in the structures differentiated into smooth muscle cells and formed smooth muscle clusters. The recipient tissues near the transplanted structures had distinct smooth muscle layers and reconstructed nerve cells, and only minimal fibrosis with decreased presence of P4HB- and HIF1α-positive cells. At 4 weeks after surgery, the sham-structure control rats exhibited significant urinary frequency symptoms with irregular and short voiding intervals, and low micturition volumes. In contrast, the structure-transplanted rats had regular micturition with longer voiding intervals and higher micturition volumes compared to the control rats. Further, the residual volume of the structure-transplanted rats was lower than for the controls. Therefore, transplantation of biofabricated bone marrow-derived cell structures reconstructed functional bladders.

Multiple Primary and Histology Coding Rules - SEER

Cancer.gov

Download the coding manual and training resources for cases diagnosed from 2007 to 2017. Sites included are lung, breast, colon, melanoma of the skin, head and neck, kidney, renal pelvis/ureter/bladder, benign brain, and malignant brain.

Correlation of gene expression with bladder capacity in interstitial cystitis/bladder pain syndrome.

PubMed

Colaco, Marc; Koslov, David S; Keys, Tristan; Evans, Robert J; Badlani, Gopal H; Andersson, Karl-Erik; Walker, Stephen J

2014-10-01

Interstitial cystitis and bladder pain syndrome are terms used to describe a heterogeneous chronic pelvic and bladder pain disorder. Despite its significant prevalence, our understanding of disease etiology is poor. We molecularly characterized interstitial cystitis/bladder pain syndrome and determined whether there are clinical factors that correlate with gene expression. Bladder biopsies from female subjects with interstitial cystitis/bladder pain syndrome and female controls without signs of the disease were collected and divided into those with normal and low anesthetized bladder capacity, respectively. Samples then underwent RNA extraction and microarray assay. Data generated by these assays were analyzed using Omics Explorer (Qlucore, Lund, Sweden), GeneSifter® Analysis Edition 4.0 and Ingenuity® Pathway Analysis to determine similarity among samples within and between groups, and measure differentially expressed transcripts unique to each phenotype. A total of 16 subjects were included in study. Principal component analysis and unsupervised hierarchical clustering showed clear separation between gene expression in tissues from subjects with low compared to normal bladder capacity. Gene expression in tissue from patients with interstitial cystitis/bladder pain syndrome who had normal bladder capacity did not significantly differ from that in controls without interstitial cystitis/bladder pain syndrome. Pairwise analysis revealed that pathways related to inflammatory and immune response were most involved. Microarray analysis provides insight into the potential pathological condition underlying interstitial cystitis/bladder pain syndrome. This pilot study shows that patients with this disorder who have low compared to normal bladder capacity have significantly different molecular characteristics, which may reflect a difference in disease pathophysiology. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Nanotechnology in Urology

PubMed Central

Jayasimha, Sudhindra

2017-01-01

Introduction: Nanotechnology has revolutionized our approach to medical diagnostics as well as therapeutics and has spanned an entirely new branch of research. This review addresses the potential applications of Nanotechnology in Urology. This article is based on the Dr. Sitharaman Best Essay award of the Urological Society of India for 2016. Methods: A PubMed search was performed for all relevant articles using the terms, “nanotechnology, nanoparticles, nanoshells, nanoscaffolds, and nanofibers.” Results: The developments in diagnostics include novel techniques of imaging of genitourinary malignancies, prostate-specific antigen measurement, early detection of mutations that are diagnostic for polycystic kidney disease. The potential applications of nanotechnology are in the targeted therapy of genitourinary malignancies, erectile dysfunction, overactive bladder, bladder reconstruction, construction of artificial kidneys and biodegradable stents as well as in robotic surgery. Conclusions: Nanotechnology is a rapidly emerging branch of research in urology with diverse and clinically significant applications in diagnostics as well as therapeutics. PMID:28197024

Bladder cancer exosomes contain EDIL-3/Del1 and facilitate cancer progression.

PubMed

Beckham, Carla J; Olsen, Jayme; Yin, Peng-Nien; Wu, Chia-Hao; Ting, Huei-Ju; Hagen, Fred K; Scosyrev, Emelian; Messing, Edward M; Lee, Yi-Fen

2014-08-01

High grade bladder cancer is an extremely aggressive malignancy associated with high rates of morbidity and mortality. Understanding how exosomes may affect bladder cancer progression could reveal novel therapeutic targets. Exosomes derived from human bladder cancer cell lines and the urine of patients with high grade bladder cancer were assessed for the ability to promote cancer progression in standard assays. Exosomes purified from the high grade bladder cancer cell line TCC-SUP and the nonmalignant urothelial cell line SV-HUC were submitted for mass spectrometry analysis. EDIL-3 was identified and selected for further analysis. Western blot was done to determine EDIL-3 levels in urinary exosomes from patients with high grade bladder cancer. shRNA gene knockdown and recombinant EDIL-3 were applied to study EDIL-3 function. Exosomes isolated from high grade bladder cancer cells and the urine of patients with high grade bladder cancer promoted angiogenesis and migration of bladder cancer cells and endothelial cells. We silenced EDIL-3 expression and found that shEDIL-3 exosomes did not facilitate angiogenesis, and urothelial and endothelial cell migration. Moreover, exosomes purified from the urine of patients with high grade bladder cancer contained significantly higher EDIL-3 levels than exosomes from the urine of healthy controls. EDIL-3 activated epidermal growth factor receptor signaling while blockade of epidermal growth factor receptor signaling abrogated this EDIL-3 induced bladder cell migration. Exosomes derived from the urine of patients with bladder cancer contains bioactive molecules such as EDIL-3. Identifying these components and their associated oncogenic pathways could lead to novel therapeutic targets and treatment strategies. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Location-dependent correlation between tissue structure and the mechanical behaviour of the urinary bladder.

PubMed

Morales-Orcajo, Enrique; Siebert, Tobias; Böl, Markus

2018-05-25

The mechanical properties of the urinary bladder wall are important to understand its filling-voiding cycle in health and disease. However, much remains unknown about its mechanical properties, especially regarding regional heterogeneities and wall microstructure. The present study aimed to assess the regional differences in the mechanical properties and microstructure of the urinary bladder wall. Ninety (n=90) samples of porcine urinary bladder wall (ten samples from nine different locations) were mechanically and histologically analysed. Half of the samples (n=45) were equibiaxially tested within physiological conditions, and the other half, matching the sample location of the mechanical tests, was frozen, cryosectioned, and stained with Picro-Sirius red to differentiate smooth muscle cells, extracellular matrix, and fat. The bladder wall shows a non-linear stress-stretch relationship with hysteresis and softening effects. Regional differences were found in the mechanical response and in the microstructure. The trigone region presents higher peak stresses and thinner muscularis layer compared to the rest of the bladder. Furthermore, the ventral side of the bladder presents anisotropic characteristics, whereas the dorsal side features perfect isotropic behaviour. This response matches the smooth muscle fibre bundle orientation within the tunica muscularis. This layer, comprising approximately 78% of the wall thickness, is composed of two fibre bundle arrangements that are cross-oriented, one with respect to the other, varying the angle between them across the organ. That is, the ventral side presents a 60°/120° cross-orientation structure, while the muscle bundles were oriented perpendicular in the dorsal side. In the present study, we demonstrate that the mechanical properties and the microstructure of the urinary bladder wall are heterogeneous across the organ. The mechanical properties and the microstructure of the urinary bladder wall within nine specific locations matching explicitly the mechanical and structural variations have been examined. On the one hand, the results of this study contribute to the understanding of bladder mechanics and thus to their functional understanding of bladder filling and voiding. On the other hand, they are relevant to the fields of constitutive formulation of bladder tissue, whole bladder mechanics, and bladder-derived scaffolds i.e., tissue-engineering grafts. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Unusual Presentation of Bladder Paraganglioma: Comparison of 131I MIBG SPECT/CT and 68Ga DOTANOC PET/CT

PubMed Central

Jain, Tarun Kumar; Basher, Rajender Kumar; Gupta, Nitin; Shukla, Jaya; Singh, Shrawan Kumar; Mittal, Bhagwant Rai

2016-01-01

Extraadrenal chromaffin cell-related tumors or paragangliomas are rare, especially in the bladder, accounting for less than 1% of cases. We report a 16-year-old boy who presented with hematuria and paroxysmal headache and was found to have a prostatic growth infiltrating the urinary bladder on anatomical imaging. Iodine-131 (131I) metaiodobenzylguanidine (MIBG) whole-body scanning and subsequently gallium-68 (68Ga) DOTANOC positron emission tomography/computed tomography (PET/CT) were performed. The MIBG scan revealed a non-tracer-avid soft-tissue mass, while DOTANOC PET/CT revealed a tracer-avid primary soft-tissue mass involving the urinary bladder and prostate with metastasis to the iliac lymph nodes. He underwent surgical management; histopathology of the surgical specimen revealed a bladder paraganglioma, whereas the prostate was found to be free of tumor. PMID:26912984

Radiation-induced second cancers: the impact of 3D-CRT and IMRT

NASA Technical Reports Server (NTRS)

Hall, Eric J.; Wuu, Cheng-Shie

2003-01-01

Information concerning radiation-induced malignancies comes from the A-bomb survivors and from medically exposed individuals, including second cancers in radiation therapy patients. The A-bomb survivors show an excess incidence of carcinomas in tissues such as the gastrointestinal tract, breast, thyroid, and bladder, which is linear with dose up to about 2.5 Sv. There is great uncertainty concerning the dose-response relationship for radiation-induced carcinogenesis at higher doses. Some animal and human data suggest a decrease at higher doses, usually attributed to cell killing; other data suggest a plateau in dose. Radiotherapy patients also show an excess incidence of carcinomas, often in sites remote from the treatment fields; in addition there is an excess incidence of sarcomas in the heavily irradiated in-field tissues. The transition from conventional radiotherapy to three-dimensional conformal radiation therapy (3D-CRT) involves a reduction in the volume of normal tissues receiving a high dose, with an increase in dose to the target volume that includes the tumor and a limited amount of normal tissue. One might expect a decrease in the number of sarcomas induced and also (less certain) a small decrease in the number of carcinomas. All around, a good thing. By contrast, the move from 3D-CRT to intensity-modulated radiation therapy (IMRT) involves more fields, and the dose-volume histograms show that, as a consequence, a larger volume of normal tissue is exposed to lower doses. In addition, the number of monitor units is increased by a factor of 2 to 3, increasing the total body exposure, due to leakage radiation. Both factors will tend to increase the risk of second cancers. Altogether, IMRT is likely to almost double the incidence of second malignancies compared with conventional radiotherapy from about 1% to 1.75% for patients surviving 10 years. The numbers may be larger for longer survival (or for younger patients), but the ratio should remain the same.

Expression of cyclooxygenase-1 and cyclooxygenase-2, syndecan-1 and connective tissue growth factor in benign and malignant breast tissue from premenopausal women.

PubMed

Fahlén, M; Zhang, H; Löfgren, L; Masironi, B; von Schoultz, E; von Schoultz, B; Sahlin, L

2017-05-01

Stromal factors have been identified as important for tumorigenesis and metastases of breast cancer. From 49 premenopausal women, samples were collected from benign or malignant tumors and the seemingly normal tissue adjacent to the tumor. The factors studied, with real-time polymerase chain reaction (PCR) and immunohistochemistry, were cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2), syndecan-1 (S-1) and connective tissue growth factor (CTGF). COX-1 and S-1 mRNA levels were higher in the malignant tumors than in normal and benign tissues. The COX-2 mRNA level was lower in the malignant tumor than in the normal tissue, while CTGF mRNA did not differ between the groups. COX-1 immunostaining was higher in stroma from malignant tumors than in benign tissues, whereas COX-2 immunostaining was higher in the malignant tissue. Glandular S-1 immunostaining was lower in malignant tumors compared to benign and normal tissues, and the opposite was found in stroma. Conclusively, mRNA levels of COX-1 and COX-2 were oppositely regulated, with COX-1 being increased in the malignant tumor while COX-2 was decreased. S-1 protein localization switched from glandular to stromal cells in malignant tissues. Thus, these markers are, in premenopausal women, localized and regulated differently in normal/benign breast tissue as compared to the malignant tumor.

In-vivo assessment of barbed suturing thread with regard to tissue reaction and material absorption in a rat model.

PubMed

Petrut, Bogdan; Hogea, Maximiliam; Fetica, Bogdan; Kozan, Andrei; Feflea, Dragos; Sererman, Gabriel; Goezen, Ali Serdar; Rassweiler, Jens

2013-01-01

The laparoscopic approach in urological surgery demands a high degree of skill in intracorporeal suturing and knot tying. In an effort to reduce the amount of time required to perform a suture, new materials have been developed that through selfanchorage distribute tension more evenly across the suture and also eliminate the need of knot tying. The goal of this study was to assess the in vivo tissue response to a novel material (V-Loc tm; Covidien) in comparison to established materials (Vicryl, PDS II), in the case of bladder suturing, in a rat model. The study included 48 male Wistar rats. All underwent a median abdominal incision, with a 1cm cystotomy, followed by a running suture. The suture material used was either V-Loc absorbable self anchoring thread, Vicryl threaded absorbable suture or monofilament absorbable suture. The abdominal cavity and the bladder suture were macroscopically evaluated at the rats' scheduled death at 3 and 6 weeks. The bladder wall was microscopically assessed by a pathologist, with regard to tissue reaction and suture material degradation. All rats survived the procedure, with the abdominal scar fully healed at week 2. There were no signs of infection or lithiasis during the observation. Macroscopically, at 3 weeks, the suture material was recognizable and visible in all cases, with special mention that the V-Loc thread was considerably more rigid, retaining its shape almost entirely, and provoked more adhesion of the surrounding tissue. At 6 weeks, the suture was indistinguishable in the bladder wall in the case of monofilament absorbable material, barely visible in the case of Vicryl, while the aspect of the V-Loc suture resembled the one at 3 weeks, with the material still clearly visible in the bladder wall, shape almost entirely maintained, and surrounding tissue adherence. Microscopically, at 3 weeks and 6 weeks, all bladder walls examined had regained their structure. At 3 weeks, the monofilament absorbable suture showed intense tissue reaction, with the material already in phagocytosis; at 6 weeks, no clear evidence of leftover material was observed. At 3 weeks, the Vicryl material showed moderate tissue reaction, with phagocytosis initiated between the strands of the material; at 6 weeks, the material was almost entirely absorbed, but with a clear leftover tissue reaction. In the case of the V-Loc suture, due to the hardness of the thread, the material itself could not be cut for analysis with the bladder wall, and the examination could only involve the bladder wall and marks of the thread. Thus, the tissue reaction was minimal, as was the presence of phagocytes at the suture site. The material showed little, if any, signs of absorption after 6 weeks. The materials tested all proved equally effective in suturing the bladder wall in a rat model. However, the novel barbed thread proved a consistently low in-vivo absorption rate, while maintaining its rigidity over time. More research is needed to assess the possible clinical implications of these findings.

In-vivo assessment of barbed suturing thread with regard to tissue reaction and material absorption in a rat model

PubMed Central

PETRUT, BOGDAN; HOGEA, MAXIMILIAM; FETICA, BOGDAN; KOZAN, ANDREI; FEFLEA, DRAGOS; SERERMAN, GABRIEL; GOEZEN, ALI SERDAR; RASSWEILER, JENS

2013-01-01

Aim The laparoscopic approach in urological surgery demands a high degree of skill in intracorporeal suturing and knot tying. In an effort to reduce the amount of time required to perform a suture, new materials have been developed that through selfanchorage distribute tension more evenly across the suture and also eliminate the need of knot tying. The goal of this study was to assess the in vivo tissue response to a novel material (V-Loc tm; Covidien) in comparison to established materials (Vicryl, PDS II), in the case of bladder suturing, in a rat model. Methods The study included 48 male Wistar rats. All underwent a median abdominal incision, with a 1cm cystotomy, followed by a running suture. The suture material used was either V-Loc absorbable self anchoring thread, Vicryl threaded absorbable suture or monofilament absorbable suture. The abdominal cavity and the bladder suture were macroscopically evaluated at the rats’ scheduled death at 3 and 6 weeks. The bladder wall was microscopically assessed by a pathologist, with regard to tissue reaction and suture material degradation. Results All rats survived the procedure, with the abdominal scar fully healed at week 2. There were no signs of infection or lithiasis during the observation. Macroscopically, at 3 weeks, the suture material was recognizable and visible in all cases, with special mention that the V-Loc thread was considerably more rigid, retaining its shape almost entirely, and provoked more adhesion of the surrounding tissue. At 6 weeks, the suture was indistinguishable in the bladder wall in the case of monofilament absorbable material, barely visible in the case of Vicryl, while the aspect of the V-Loc suture resembled the one at 3 weeks, with the material still clearly visible in the bladder wall, shape almost entirely maintained, and surrounding tissue adherence. Microscopically, at 3 weeks and 6 weeks, all bladder walls examined had regained their structure. At 3 weeks, the monofilament absorbable suture showed intense tissue reaction, with the material already in phagocytosis; at 6 weeks, no clear evidence of leftover material was observed. At 3 weeks, the Vicryl material showed moderate tissue reaction, with phagocytosis initiated between the strands of the material; at 6 weeks, the material was almost entirely absorbed, but with a clear leftover tissue reaction. In the case of the V-Loc suture, due to the hardness of the thread, the material itself could not be cut for analysis with the bladder wall, and the examination could only involve the bladder wall and marks of the thread. Thus, the tissue reaction was minimal, as was the presence of phagocytes at the suture site. The material showed little, if any, signs of absorption after 6 weeks. Conclusion The materials tested all proved equally effective in suturing the bladder wall in a rat model. However, the novel barbed thread proved a consistently low in-vivo absorption rate, while maintaining its rigidity over time. More research is needed to assess the possible clinical implications of these findings. PMID:26527981

Expression and significance of cyclooxygenase-2 mRNA in benign and malignant ascites

PubMed Central

Lu, Jing; Li, Xiao-Feng; Kong, Li-Xia; Ma, Lin; Liao, Su-Huan; Jiang, Chang-You

2013-01-01

AIM: To investigate the mRNA expression of cyclooxygensae-2 (COX-2) in benign and malignant ascites, and to explore the difference in COX-2 mRNA expression among different diseases. METHODS: A total of 36 samples were collected from the Fifth Affiliated Hospital of Sun Yat-Sen University and divided into two experimental groups: benign ascites (n = 21) and malignant ascites (n = 15). Benign ascites included cirrhotic ascites (n = 10) and tuberculous ascites (n = 5). Malignant ascites included oophoroma (n = 7), cancer of colon (n = 5), cancer of the liver (n = 6), gastric cancer (n = 2), and bladder carcinoma (n = 1). The mRNA expression of COX-2 in ascites was examined with reverse transcriptase polymerase chain reaction (RT-PCR) technology, and the positive rate of COX-2 mRNA was compared between different diseases. RESULTS: The positive rate of COX-2 mRNA in malignant ascites was 42.9% (9/21), which was significantly higher than in benign ascites, 6.7% (1/15), difference being significant between these two groups (χ2 = 4.051, P = 0.044). The proportion of the positive rate in the malignant ascites was as follows: ovarian cancers 57.1% (4/7), colon cancer 40.0% (2/5), liver cancer 33.3% (2/6), gastric cancer 50.0% (1/2), and bladder cancer 0.00% (0/1). However, there was no significant difference in COX-2 mRNA expression among various tumors with malignant ascites (χ2 = 1.614, P = 0.806). Among the benign ascites, COX-2 mRNA levels were different between the tuberculous ascites (0/5) and cirrhotic ascites (1/10), but there was no significant difference (P = 1.000). CONCLUSION: COX-2 mRNA, detected by RT-PCR, is useful in the differential diagnosis of benign and malignant ascites, which also has potential value in the clinical diagnosis of tumors. PMID:24187465

TRPV2 mediates adrenomedullin stimulation of prostate and urothelial cancer cell adhesion, migration and invasion.

PubMed

Oulidi, Agathe; Bokhobza, Alexandre; Gkika, Dimitra; Vanden Abeele, Fabien; Lehen'kyi, V'yacheslav; Ouafik, L'houcine; Mauroy, Brigitte; Prevarskaya, Natalia

2013-01-01

Adrenomedullin (AM) is a 52-amino acid peptide initially isolated from human pheochromocytoma. AM is expressed in a variety of malignant tissues and cancer cell lines and was shown to be a mitogenic factor capable of stimulating growth of several cancer cell types. In addition, AM is a survival factor for certain cancer cells. Some data suggest that AM might be involved in the progression cancer metastasis via angiogenesis and cell migration and invasion control. The Transient Receptor Potential channel TRPV2 is known to promote in prostate cancer cell migration and invasive phenotype and is correlated with the stage and grade of bladder cancer. In this work we show that AM induces prostate and urothelial cancer cell migration and invasion through TRPV2 translocation to plasma membrane and the subsequent increase in resting calcium level.

Non-alcoholic beverages and risk of bladder cancer in Uruguay

PubMed Central

De Stefani, Eduardo; Boffetta, Paolo; Deneo-Pellegrini, Hugo; Correa, Pelayo; Ronco, Alvaro L; Brennan, Paul; Ferro, Gilles; Acosta, Giselle; Mendilaharsu, María

2007-01-01

Background Bladder cancer is the fourth most frequent malignancy among Uruguayan men. A previous study from Uruguay suggested a high risk of bladder cancer associated with maté drinking. We conducted an additional case-control study in order to further explore the role of non-alcoholic beverages in bladder carcinogenesis. Methods In the time period 1996–2000, 255 incident cases with transitional cell carcinoma of the bladder and 501 patients treated in the same hospitals and in the same time period were frequency matched on age, sex, and residence. Both cases and controls were face-to-face interviewed on occupation, tobacco smoking, alcohol drinking and intake of maté, coffee, tea, and soft drinks. Statistical analysis was carried out by unconditional multiple logistic regression. Results Ever maté drinking was positively associated with bladder cancer (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.2–3.9) and the risk increased for increasing duration and amount of maté drinking. Both coffee and tea were strongly associated with bladder cancer risk (OR for coffee drinking 1.6, 95% CI 1.2–2.3; OR for tea drinking 2.3, 95% CI 1.5–3.4). These results were confirmed in a separate analysis of never-smokers. Conclusion Our results suggest that drinking of maté, coffee and tea may be risk factors for bladder carcinoma in Uruguay. PMID:17394632

Lymphocytic infiltration of bladder after local cellular immunotherapy.

PubMed

Ingram, M; Bishai, M B; Techy, G B; Narayan, K S; Saroufeem, R; Yazan, O; Marshall, C E

2000-01-01

This is a case report of a patient who received cellular immunotherapy, in the form of local injections of autologous stimulated lymphocytes (ASL) into individual tumors in the urinary bladder. A major consideration in cellular immunotherapy being the ability of immune cells to reach all target areas, we hypothesized that direct delivery of effector cells into individual bladder tumors might assure such access. ASL were generated by exposing the patient's PBL to phytohemagglutinin and culturing them in the presence of IL-2 to expand the population. ASL were injected into the base of individual bladder tumors three times at intervals of 3 weeks. The patient died of a myocardial infarct, unrelated to cell therapy, 20 days after the third injection. An autopsy was performed. Histological sections of the bladder showed extensive lymphocytic infiltration of virtually the entire organ. No conclusions about the therapeutic efficacy of local immunotherapy using ASL are possible. Nevertheless, the observations reported, taken together with reports of therapeutic efficacy of other immunotherapy regimens in the management of bladder cancer, suggest that ready access of stimulated lymphocytes to all regions of the organ may account, in part, for the relatively high rate of therapeutic success reported for various immunotherapy regimens for this malignancy.

Vitamin D Induction of the Human Antimicrobial Peptide Cathelicidin in the Urinary Bladder

PubMed Central

Hertting, Olof; Holm, Åsa; Lüthje, Petra; Brauner, Hanna; Dyrdak, Robert; Jonasson, Aino Fianu; Wiklund, Peter; Chromek, Milan; Brauner, Annelie

2010-01-01

The urinary tract is frequently being exposed to potential pathogens and rapid defence mechanisms are therefore needed. Cathelicidin, a human antimicrobial peptide is expressed and secreted by bladder epithelial cells and protects the urinary tract from infection. Here we show that vitamin D can induce cathelicidin in the urinary bladder. We analyzed bladder tissue from postmenopausal women for expression of cathelicidin, before and after a three-month period of supplementation with 25-hydroxyvitamin D3 (25D3). Cell culture experiments were performed to elucidate the mechanisms for cathelicidin induction. We observed that, vitamin D per se did not up-regulate cathelicidin in serum or in bladder tissue of the women in this study. However, when the bladder biopsies were infected with uropathogenic E. coli (UPEC), a significant increase in cathelicidin expression was observed after 25D3 supplementation. This observation was confirmed in human bladder cell lines, even though here, cathelicidin induction occurred irrespectively of infection. Vitamin D treated bladder cells exerted an increased antibacterial effect against UPEC and colocalization to cathelicidin indicated the relevance of this peptide. In the light of the rapidly growing problem of resistance to common urinary tract antibiotics, we suggest that vitamin D may be a potential complement in the prevention of UTI. PMID:21179490

Polythelia: simple atavistic remnant or a suspicious clinical sign for investigation?

PubMed

Galli-Tsinopoulou, Assimina; Stergidou, Dorothea

2014-03-01

Supernumerary nipples (or polythelia) usually appear along the embryonic milk lines or in other sites including the back, thigh, vulva, neck etc. The frequency of polythelia ranges from 0.2% to 5.6%. Despite the plethora of published cases concerning its association with other congenital malformations or syndromes with different patterns of inheritance, polythelia still remains a controversial and theoretical issue. Although most reports describe a link between supernumerary nipples and kidney/urinary tract anomalies, a potential relationship with other congenital anomalies or malignancies has also been speculated. Additionally, polythelia has been associated with genodermatoses, thus being related with an increased malignant potential, as well as with an increased risk for solid tumors such as renal adenocarcinoma, testicular cancer, prostate cancer, and urinary bladder carcinoma. The fact that the Scaramanga (ska) mutant mice presented with ectopic breast tissue imply that misregulation of the neuregulin-3 signaling pathway may be critical in the occurrence of polythelia. This is an attempt to review existing literature in order to (a) draw reliable conclusions whether polythelia is a manifestation of simple atavism or may be associated with concomitant severe conditions needing further investigation and/or management, (b) elucidate its aetiology and (c) establish appropriate clinical and laboratory approach.

Photodynamic therapy (PDT) and photodiagnosis (PD) using endogenous photosensitization induced by 5-aminolevulinic acid (ALA): current clinical and development status

NASA Astrophysics Data System (ADS)

Marcus, Stuart L.; Sobel, Russel S.; Golub, Allyn L.; Carroll, Ronald L.; Lundahl, Scott L.; Shulman, D. Geoffrey

1996-04-01

Exogenous provision of ALA to many tissues results in the accumulation of sufficient quantities of the endogenous photosensitizer protoporphyrin IX, (PpIX), to produce a photodynamic effect. Therefore, ALA may be considered the only current PDT agent in clinical development which is a biochemical precursor of a photosensitizer. Topical ALA application, followed by exposure to activating light (ALA PDT), has been reported effective for the treatment of a variety of dermatologic diseases including cutaneous T-cell lymphoma, superficial basal cell carcinoma, Bowen's disease, and actinic (solar) keratoses, and is also being examined for treatment of acne and hirsutism. PpIX induced by ALA application also may serve as a fluorescence detection marker for photodiagnosis (PD) of malignant and pre- malignant conditions of the urinary bladder and other organs. Local internal application of ALA has also been used for selective endometrial ablation in animal model systems and is beginning to be examined in human clinical studies. Systemic, oral administration of ALA has been used for ALA PDT of superficial head and neck cancer, various gastrointestinal cancers, and the condition known as Barrett's esophagus. This brief paper reviews the current clinical and development status of ALA PDT.

SU-E-J-214: Comparative Assessment On IGRT On Partial Bladder Cancer Treatment Between CT-On-Rails (CTOR) and KV Cone Beam CT (CBCT)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, T; Ma, C

2014-06-01

Purpose: Image-Guided radiation therapy(IGRT) depends on reliable online patient-specific anatomy information to address random and progressive anatomy changes. Large margins have been suggested to bladder cancer treatment due to large daily bladder anatomy variation. KV Cone beam CT(CBCT) has been used in IGRT localization prevalently; however, its lack of soft tissue contrast makes clinicians hesitate to perform daily soft tissue alignment with CBCT for partial bladder cancer treatment. This study compares the localization uncertainties of bladder cancer IGRT using CTon- Rails(CTOR) and CBCT. Methods: Three T2N0M0 bladder cancer patients (total of 66 Gy to partial bladder alone) were localized dailymore » with either CTOR or CBCT for their entire treatment course. A total of 71 sets of CTOR and 22 sets of CBCT images were acquired and registered with original planning CT scans by radiation therapists and approved by radiation oncologists for the daily treatment. CTOR scanning entailed 2mm slice thickness, 0.98mm axial voxel size, 120kVp and 240mAs. CBCT used a half fan pelvis protocol from Varian OBI system with 2mm slice thickness, 0.98axial voxel size, 125kVp, and 680mAs. Daily localization distribution was compared. Accuracy of CTOR and CBCT on partial bladder alignment was also evaluated by comparing bladder PTV coverage. Results: 1cm all around PTV margins were used in every patient except target superior limit margin to 0mm due to bowel constraint. Daily shifts on CTOR averaged to 0.48, 0.24, 0.19 mms(SI,Lat,AP directions); CBCT averaged to 0.43, 0.09, 0.19 mms(SI,Lat,AP directions). The CTOR daily localization showed superior results of V100% of PTV(102% CTOR vs. 89% CBCT) and bowel(Dmax 69.5Gy vs. 78Gy CBCT). CTOR images showed much higher contrast on bladder PTV alignment. Conclusion: CTOR daily localization for IGRT is more dosimetrically beneficial for partial bladder cancer treatment than kV CBCT localization and provided better soft tissue PTV identification.« less

Romidepsin in Treating Patients With Lymphoma, Chronic Lymphocytic Leukemia, or Solid Tumors With Liver Dysfunction

ClinicalTrials.gov

2018-04-02

Glioma; Lymphoma; Metastatic Malignant Solid Neoplasm; Neuroendocrine Neoplasm; Recurrent Adult Soft Tissue Sarcoma; Recurrent Bladder Carcinoma; Recurrent Breast Carcinoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Colorectal Carcinoma; Recurrent Head and Neck Carcinoma; Recurrent Lung Carcinoma; Recurrent Malignant Solid Neoplasm; Recurrent Melanoma; Recurrent Pancreatic Carcinoma; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Prostate Carcinoma; Recurrent Renal Cell Carcinoma; Recurrent Thyroid Gland Carcinoma; Refractory Chronic Lymphocytic Leukemia; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage III Breast Cancer AJCC v7; Stage III Colorectal Cancer AJCC v7; Stage III Cutaneous Melanoma AJCC v7; Stage III Lung Cancer AJCC v7; Stage III Pancreatic Cancer AJCC v6 and v7; Stage III Prostate Cancer AJCC v7; Stage III Renal Cell Cancer AJCC v7; Stage III Soft Tissue Sarcoma AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Breast Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Breast Cancer AJCC v6 and v7; Stage IV Colorectal Cancer AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7; Stage IV Lung Cancer AJCC v7; Stage IV Pancreatic Cancer AJCC v6 and v7; Stage IV Prostate Cancer AJCC v7; Stage IV Renal Cell Cancer AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7; Unresectable Solid Neoplasm

Thirty-five years of noninvasive bladder carcinoma: a plea for the use of papillary intraurothelial neoplasia as new terminology.

PubMed

Van der Kwast, Theodorus H; Zlotta, Alexandre R; Fleshner, Neil; Jewett, Michael; Lopez-Beltran, Antonio; Montironi, Roldolfo

2008-12-01

Since the introduction of the World Health Organization (WHO) 1973 terminology for bladder cancer, noninvasive epithelial bladder tumors have consistently been labeled bladder carcinomas. In the WHO 2004 classification the removal of the "carcinoma" label from a small subset of noninvasive bladder carcinomas with indolent behavior created the entity of papillary urothelial neoplasms of low malignant potential, but the remaining noninvasive carcinomas of the urothelial tract retained this label. In this overview, we analyze clinical, pathologic and molecular-genomic findings to support a more evidence-based nomenclature of papillary neoplastic lesions of the urinary tract. In line with the tendency during the last few decades to label flat precancerous lesions of various organs intraepithelial neoplasms, we may now also refer to dysplasia and carcinoma in situ of the urinary tract as low and high grade intraurothelial neoplasia, respectively. To harmonize nomenclature, we now propose that the terms low and high grade papillary urothelial carcinoma be replaced by low and high grade papillary intraurothelial neoplasiafor all noninvasive urothelial cancers.

Linearized texture of three-dimensional extracellular matrix is mandatory for bladder cancer cell invasion.

PubMed

Alfano, Massimo; Nebuloni, Manuela; Allevi, Raffaele; Zerbi, Pietro; Longhi, Erika; Lucianò, Roberta; Locatelli, Irene; Pecoraro, Angela; Indrieri, Marco; Speziali, Chantal; Doglioni, Claudio; Milani, Paolo; Montorsi, Francesco; Salonia, Andrea

2016-10-25

In the fields of biomaterials and tissue engineering simulating the native microenvironment is of utmost importance. As a major component of the microenvironment, the extracellular matrix (ECM) contributes to tissue homeostasis, whereas modifications of native features are associated with pathological conditions. Furthermore, three-dimensional (3D) geometry is an important feature of synthetic scaffolds favoring cell stemness, maintenance and differentiation. We analyzed the 3D structure, geometrical measurements and anisotropy of the ECM isolated from (i) human bladder mucosa (basal lamina and lamina propria) and muscularis propria; and, (ii) bladder carcinoma (BC). Next, binding and invasion of bladder metastatic cell line was observed on synthetic scaffold recapitulating anisotropy of tumoral ECM, but not on scaffold with disorganized texture typical of non-neoplastic lamina propria. This study provided information regarding the ultrastructure and geometry of healthy human bladder and BC ECMs. Likewise, using synthetic scaffolds we identified linearization of the texture as a mandatory feature for BC cell invasion. Integrating microstructure and geometry with biochemical and mechanical factors could support the development of an innovative synthetic bladder substitute or a tumoral scaffold predictive of chemotherapy outcomes.

Is radical oncosurgery justified for the treatment of primary malignant fibrous histiocytoma of the urinary bladder? Report of two cases and analyses of disease-specific survival rates based on a review of the literature.

PubMed

Gunia, Sven; May, Matthias; Koch, Stefan; Erbersdobler, Andreas

2011-01-01

Disease-specific survival (DSS) rates were evaluated in 20 patients with primary malignant fibrous histiocytoma (MFH) of the bladder. The most common pathologic finding was the pleomorphic subtype of MFH (55%) with a mean tumor size of 6.8 cm. 10 patients underwent surgery without and 6 patients with adjuvant therapy. Local and systemic rates of progression were 30 and 60% after surgery only compared with 16.7 and 50% after surgery with adjuvant therapy. Although none of the patients showed metastatic dissemination at the time of diagnosis, overall 1- and 2-year DSS rates of only 47.8 and 31.9% were observed. Hence, after the onset of clinical symptoms, the disease runs a very aggressive course regardless of the therapeutic options employed. Although distant dissemination seems to be rare at the time of diagnosis, the prognostic outcome is dismal. The rarity and inconsistency of the currently available case reports on MFH of the bladder hampers the development of therapeutic guidelines. Advanced studies enrolling a larger number of patients with appropriate clinical and pathological data are needed to compare the beneficial effects of various treatment options. Copyright © 2011 S. Karger AG, Basel.

Epigenetic mediated transcriptional activation of WNT5A participates in arsenical-associated malignant transformation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jensen, Taylor J.; Wozniak, Ryan J.; Arizona Cancer Center, University of Arizona, Tucson, AZ 85724

2009-02-15

Arsenic is a human carcinogen with exposure associated with cancer of the lung, skin, and bladder. Many potential mechanisms have been implicated as playing a role in the process of arsenical-induced malignancy including the perturbation of signaling pathways and aberrant epigenetic regulation. We initiated studies to examine the role of a member of the non-canonical WNT signaling pathway, WNT5A, in UROtsa cells and arsenite [URO-ASSC] and monomethylarsonous acid [URO-MSC] malignantly transformed variants. We present data herein that suggest that WNT5A is transcriptionally activated during arsenical-induced malignant transformation. This WNT5A transcriptional activation is correlated with the enrichment of permissive histone modificationsmore » and the reduction of repressive modifications in the WNT5A promoter region. The epigenetic activation of WNT5A expression and acetylation of its promoter remain after the removal of the arsenical, consistent with the maintenance of an anchorage independent growth phenotype in these cells. Additionally, treatment with epigenetic modifying drugs supports a functional role for these epigenetic marks in controlling gene expression. Reduction of WNT5A using lentiviral shRNA greatly attenuated the ability of these cells to grow in an anchorage independent fashion. Extension of our model into human bladder cancer cell lines indicates that each of the cell lines examined also express WNT5A. Taken together, these data suggest that the epigenetic remodeling of the WNT5A promoter is correlated with its transcriptional activation and this upregulation likely participates in arsenical-induced malignant transformation.« less

Multimodal fiber-probe spectroscopy for the diagnostics and classification of bladder tumors

NASA Astrophysics Data System (ADS)

Anand, Suresh; Cicchi, Riccardo; Fantechi, Riccardo; Gacci, Mauro; Nesi, Gabriella; Carini, Marco; Pavone, Francesco S.

2017-02-01

The gold standard for the detection of bladder cancer is white light cystoscopy, followed by an invasive biopsy and pathological examination. Tissue pathology is time consuming and often prone to sampling errors. Recently, optical spectroscopy techniques have evolved as promising techniques for the detection of neoplasia. The specific goal of this study is to evaluate the application of combined auto-fluorescence (excited using 378 nm and 445 nm wavelengths) and diffuse reflectance spectroscopy to discriminate normal bladder tissue from tumor at different grades. The fluorescence spectrum at both excitation wavelengths showed an increased spectral intensity in tumors with respect to normal tissues. Reflectance data indicated an increased reflectance in the wavelength range 610 nm - 700 nm for different grades of tumors, compared to normal tissues. The spectral data were further analyzed using principal component analysis for evaluating the sensitivity and specificity for diagnosing tumor. The spectral differences observed between various grades of tumors provides a strong genesis for the future evaluation on a larger patient population to achieve statistical significance. This study indicates that a combined spectroscopic strategy, incorporating fluorescence and reflectance spectroscopy, could improve the capability for diagnosing bladder tumor as well as for differentiating tumors in different grades.

The acellular matrix (ACM) for bladder tissue engineering: A quantitative magnetic resonance imaging study.

PubMed

Cheng, Hai-Ling Margaret; Loai, Yasir; Beaumont, Marine; Farhat, Walid A

2010-08-01

Bladder acellular matrices (ACMs) derived from natural tissue are gaining increasing attention for their role in tissue engineering and regeneration. Unlike conventional scaffolds based on biodegradable polymers or gels, ACMs possess native biomechanical and many acquired biologic properties. Efforts to optimize ACM-based scaffolds are ongoing and would be greatly assisted by a noninvasive means to characterize scaffold properties and monitor interaction with cells. MRI is well suited to this role, but research with MRI for scaffold characterization has been limited. This study presents initial results from quantitative MRI measurements for bladder ACM characterization and investigates the effects of incorporating hyaluronic acid, a natural biomaterial useful in tissue-engineering and regeneration. Measured MR relaxation times (T(1), T(2)) and diffusion coefficient were consistent with increased water uptake and glycosaminoglycan content observed on biochemistry in hyaluronic acid ACMs. Multicomponent MRI provided greater specificity, with diffusion data showing an acellular environment and T(2) components distinguishing the separate effects of increased glycosaminoglycans and hydration. These results suggest that quantitative MRI may provide useful information on matrix composition and structure, which is valuable in guiding further development using bladder ACMs for organ regeneration and in strategies involving the use of hyaluronic acid.

Microwave radiometry for non-invasive detection of vesicoureteral reflux (VUR) following bladder warming

NASA Astrophysics Data System (ADS)

Stauffer, Paul R.; Maccarini, Paolo F.; Arunachalam, Kavitha; De Luca, Valeria; Salahi, Sara; Boico, Alina; Klemetsen, Oystein; Birkelund, Yngve; Jacobsen, Svein K.; Bardati, Fernando; Tognolotti, Piero; Snow, Brent

2011-03-01

Background: Vesicoureteral reflux (VUR) is a serious health problem leading to renal scarring in children. Current VUR detection involves traumatic x-ray imaging of kidneys following injection of contrast agent into bladder via invasive Foley catheter. We present an alternative non-invasive approach for detecting VUR by radiometric monitoring of kidney temperature while gently warming the bladder. Methods: We report the design and testing of: i) 915MHz square slot antenna array for heating bladder, ii) EMI-shielded log spiral microstrip receive antenna, iii) high-sensitivity 1.375GHz total power radiometer, iv) power modulation approach to increase urine temperature relative to overlying perfused tissues, and v) invivo porcine experiments characterizing bladder heating and radiometric temperature of aaline filled 30mL balloon "kidney" implanted 3-4cm deep in thorax and varied 2-6°C from core temperature. Results: SAR distributions are presented for two novel antennas designed to heat bladder and monitor deep kidney temperatures radiometrically. We demonstrate the ability to heat 180mL saline in in vivo porcine bladder to 40-44°C while maintaining overlying tissues <38°C using time-modulated square slot antennas coupled to the abdomen with room temperature water pad. Pathologic evaluations confirmed lack of acute thermal damage in pelvic tissues for up to three 20min bladder heat exposures. The radiometer clearly recorded 2-6°C changes of 30mL "kidney" targets at depth in 34°C invivo pig thorax. Conclusion: A 915MHz antenna array can gently warm in vivo pig bladder without toxicity while a 1.375GHz radiometer with log spiral receive antenna detects >=2°C rise in 30mL "urine" located 3-4cm deep in thorax, demonstrating more than sufficient sensitivity to detect Grade 4-5 reflux of warmed urine for non-invasive detection of VUR.

Microwave Radiometry for Non-Invasive Detection of Vesicoureteral Reflux (VUR) Following Bladder Warming.

PubMed

Stauffer, Paul R; Maccarini, Paolo F; Arunachalam, Kavitha; De Luca, Valeria; Salahi, Sara; Boico, Alina; Klemetsen, Oystein; Birkelund, Yngve; Jacobsen, Svein K; Bardati, Fernando; Tognolatti, Piero; Snow, Brent

2011-01-01

BACKGROUND: Vesicoureteral reflux (VUR) is a serious health problem leading to renal scarring in children. Current VUR detection involves traumatic x-ray imaging of kidneys following injection of contrast agent into bladder via invasive Foley catheter. We present an alternative non-invasive approach for detecting VUR by radiometric monitoring of kidney temperature while gently warming the bladder. METHODS: We report the design and testing of: i) 915MHz square slot antenna array for heating bladder, ii) EMI-shielded log spiral microstrip receive antenna, iii) high-sensitivity 1.375GHz total power radiometer, iv) power modulation approach to increase urine temperature relative to overlying perfused tissues, and v) invivo porcine experiments characterizing bladder heating and radiometric temperature of aaline filled 30mL balloon "kidney" implanted 3-4cm deep in thorax and varied 2-6°C from core temperature. RESULTS: SAR distributions are presented for two novel antennas designed to heat bladder and monitor deep kidney temperatures radiometrically. We demonstrate the ability to heat 180mL saline in in vivo porcine bladder to 40-44°C while maintaining overlying tissues <38°C using time-modulated square slot antennas coupled to the abdomen with room temperature water pad. Pathologic evaluations confirmed lack of acute thermal damage in pelvic tissues for up to three 20min bladder heat exposures. The radiometer clearly recorded 2-6°C changes of 30mL "kidney" targets at depth in 34°C invivo pig thorax. CONCLUSION: A 915MHz antenna array can gently warm in vivo pig bladder without toxicity while a 1.375GHz radiometer with log spiral receive antenna detects ≥2°C rise in 30mL "urine" located 3-4cm deep in thorax, demonstrating more than sufficient sensitivity to detect Grade 4-5 reflux of warmed urine for non-invasive detection of VUR.

A review of Agent Orange and its associated oncologic risk of genitourinary cancers.

PubMed

Chang, Chrystal; Benson, Michael; Fam, Mina M

2017-11-01

Agent Orange is an herbicide sprayed widely in Vietnam that is linked to a variety of malignancies in as early as 1991.Since then, there has been concern for, and subsequent interest in studying, the potential connection between Agent Orange and other malignancies. In the past 2 decades, there have been significant changes in the opinion of the National Academy of Science regarding Agent Orange and certain genitourinary malignancies. Herein, we review the literature regarding the potential link between Agent Orange and various urological cancers, including prostate, bladder, testicular, and renal cancers. Copyright © 2017 Elsevier Inc. All rights reserved.

Expression of EphA2 and Ephrin A-1 in carcinoma of the urinary bladder.

PubMed

Abraham, Shaji; Knapp, Deborah W; Cheng, Liang; Snyder, Paul W; Mittal, Suresh K; Bangari, Dinesh S; Kinch, Michael; Wu, Lan; Dhariwal, Jay; Mohammed, Sulma I

2006-01-15

The EphA2 receptor tyrosine kinase is believed to play a role in tumor growth and metastasis. The clinical significance of the expression of EphA2 was observed in breast, prostate, colon, skin, cervical, ovarian, and lung cancers. The purpose of this work was to determine the expression of EphA2 and its ligand, Ephrin A-1, and E-cadherin in carcinoma of the urinary bladder, and determine EphA2 as a new target for therapy in bladder cancer. EphA2 mRNA and protein expression was investigated by reverse transcription-PCR and Western blot, respectively, in bladder cancer cell lines. In addition, the expression of EphA2, Ephrin A-1, and E-cadherin in tissues from patients with different stages of urinary bladder cancer was determined by immunohistochemistry. Furthermore, the ability of Ephrin A-1 to inhibit growth of bladder cancer cells was also investigated using an adenoviral delivery system. Western blot analysis showed high EphA2 expression in TCCSUP, T24, and UMUC-3 cell lines. In tissues, the staining intensity of EphA2 was less in normal urothelium but increased greatly in advancing stages of urothelial carcinoma (P < 0.05). Similarly, the staining intensity of Ephrin A-1 was low in normal tissues and high in cancerous tissues, but it was similar across the various stages of urothelial carcinoma (T(a)-T(4)). E-cadherin immunoreactivity decreased in urothelial cancer. Association of EphA2 and Ephrin A-1 expression was found to be significant between T(a) stage and T(1)-T(2) (P < 0.04) and T(a) and T(3)-T(4) stages (P < 0.0001). Adenovirus delivery of Ephrin A-1 inhibited proliferation of TCCSUP cells. EphA2 may serve as a novel target for bladder cancer therapy.

Unique Case Report of Pineal Gland Metastasis From Bladder Carcinoma.

PubMed

Li, Jun; Wang, Ping; Wang, Bin

2016-05-01

Pineal metastasis is uncommon and most metastatic pineal lesions are asymptomatic. To our knowledge the herein reported case is the first in which the pineal gland was confirmed as the metastatic site of a bladder carcinoma.The patient reported in this case is a 59-year-old man who suffered from headache and delirium for 4 days after surgical treatment for removal of a bladder carcinoma 1 year ago. Magnetic resonance imaging (MRI) revealed a solid tumor involving the pineal gland with significant enhancement.The patient underwent surgical treatment for removal of the neoplastic lesion in the pineal gland. Histopathological examination confirmed invasion of the pineal gland by metastatic urothelial carcinoma.This case highlighted that the presence of pineal lesions in patient with known malignancy should raise suspicion of metastatic involvement.

Using gene chips to identify organ-specific, smooth muscle responses to experimental diabetes: potential applications to urological diseases.

PubMed

Hipp, Jason D; Davies, Kelvin P; Tar, Moses; Valcic, Mira; Knoll, Abraham; Melman, Arnold; Christ, George J

2007-02-01

To identify early diabetes-related alterations in gene expression in bladder and erectile tissue that would provide novel diagnostic and therapeutic treatment targets to prevent, delay or ameliorate the ensuing bladder and erectile dysfunction. The RG-U34A rat GeneChip (Affymetrix Inc., Sunnyvale, CA, USA) oligonucleotide microarray (containing approximately 8799 genes) was used to evaluate gene expression in corporal and male bladder tissue excised from rats 1 week after confirmation of a diabetic state, but before demonstrable changes in organ function in vivo. A conservative analytical approach was used to detect alterations in gene expression, and gene ontology (GO) classifications were used to identify biological themes/pathways involved in the aetiology of the organ dysfunction. In all, 320 and 313 genes were differentially expressed in bladder and corporal tissue, respectively. GO analysis in bladder tissue showed prominent increases in biological pathways involved in cell proliferation, metabolism, actin cytoskeleton and myosin, as well as decreases in cell motility, and regulation of muscle contraction. GO analysis in corpora showed increases in pathways related to ion channel transport and ion channel activity, while there were decreases in collagen I and actin genes. The changes in gene expression in these initial experiments are consistent with the pathophysiological characteristics of the bladder and erectile dysfunction seen later in the diabetic disease process. Thus, the observed changes in gene expression might be harbingers or biomarkers of impending organ dysfunction, and could provide useful diagnostic and therapeutic targets for a variety of progressive urological diseases/conditions (i.e. lower urinary tract symptoms related to benign prostatic hyperplasia, erectile dysfunction, etc.).

Enhanced inhibition of urinary bladder cancer growth and muscle invasion by allyl isothiocyanate and celecoxib in combination

PubMed Central

Zhang, Yuesheng

2013-01-01

Allyl isothiocyanate (AITC) occurs in cruciferous vegetables that are commonly consumed by humans and has been shown to inhibit urinary bladder cancer growth and progression in previous preclinical studies. However, AITC does not significantly modulate cyclooxygenase-2 (Cox-2), whose oncogenic activity has been well documented in bladder cancer and other cancers. Celecoxib is a selective Cox-2 inhibitor and has been widely used for treatment of several diseases. Celecoxib has also been evaluated in bladder cancer patients, but its efficacy against bladder cancer as a single agent remains unclear. In a syngeneic rat model of orthotopic bladder cancer, treatment of the animals with the combination of AITC and celecoxib at low dose levels (AITC at 1mg/kg and celecoxib at 10mg/kg) led to increased or perhaps synergistic inhibition of bladder cancer growth and muscle invasion, compared with each agent used alone. The combination regime was also more effective than each single agent in inhibiting microvessel formation and stimulating microvessel maturation in the tumor tissues. The anticancer efficacy of the combination regime was associated with depletion of prostaglandin E2, a key downstream signaling molecule of Cox-2, caspase activation and downregulation of vascular endothelial growth factor in the tumor tissues. These data show that AITC and celecoxib complement each other for inhibition of bladder cancer and provide a novel combination approach for potential use for prevention or treatment of human bladder cancer. PMID:23946495

Pitfalls and Limitations of Diffusion-Weighted Magnetic Resonance Imaging in the Diagnosis of Urinary Bladder Cancer

PubMed Central

Lin, Wei-Ching; Chen, Jeon-Hor

2015-01-01

Adequately selecting a therapeutic approach for bladder cancer depends on accurate grading and staging. Substantial inaccuracy of clinical staging with bimanual examination, cystoscopy, and transurethral resection of bladder tumor has facilitated the increasing utility of magnetic resonance imaging to evaluate bladder cancer. Diffusion-weighted imaging (DWI) is a noninvasive functional magnetic resonance imaging technique. The high tissue contrast between cancers and surrounding tissues on DWI is derived from the difference of water molecules motion. DWI is potentially a useful tool for the detection, characterization, and staging of bladder cancers; it can also monitor posttreatment response and provide information on predicting tumor biophysical behaviors. Despite advancements in DWI techniques and the use of quantitative analysis to evaluate the apparent diffusion coefficient values, there are some inherent limitations in DWI interpretation related to relatively poor spatial resolution, lack of cancer specificity, and lack of standardized image acquisition protocols and data analysis procedures that restrict the application of DWI and reproducibility of apparent diffusion coefficient values. In addition, inadequate bladder distension, artifacts, thinness of bladder wall, cancerous mimickers of normal bladder wall and benign lesions, and variations in the manifestation of bladder cancer may interfere with diagnosis and monitoring of treatment. Recognition of these pitfalls and limitations can minimize their impact on image interpretation, and carefully applying the analyzed results and combining with pathologic grading and staging to clinical practice can contribute to the selection of an adequate treatment method to improve patient care. PMID:26055180

Spontaneously released substance P and bradykinin from isolated guinea-pig bladder.

PubMed

Saban, R; Franz, J; Bjorling, D E

1997-04-01

To investigate whether the isolated urinary bladder spontaneously releases substance P (SP) or bradykinin (BK), which can act as potent mediators of pain and inflammation of the urinary bladder, and whether peptidase inhibitors enhance peptide release. Urinary bladder segments (2 x 10 x 0.8-1 mm) were isolated from guinea pigs and studied in vitro; tissue contraction was assessed using force-displacement transducers and the release of peptides by specific enzyme immunoassays. In the absence of any exogenous agonists, the inhibition of neutral endopeptidase and angiotensin-converting enzyme by phosphoramidon and captopril, respectively, increased the frequency and magnitude of spontaneous motility of isolated bladder strips. Phosphoramidon increased the net release of SP-like immunoreactivity (SP-LI) and captopril increased the net release of SP-LI and BK-LI, concomitant with contraction. Peptide-LI was recovered primarily from bladder mucosa and to a lesser degree from detrusor smooth muscle. Similarly, peptidase inhibitors primarily affected the bladder mucosa; phosphoramidon induced a fourfold increase in SP-LI and captopril induced a significant increase of SP-LI and BK-LI from the mucosa. Tissues contracted in response to peptidase inhibitors in the presence of atropine and indomethacin, but contraction was reduced significantly by in vitro capsaicin desensitization or removal of bladder mucosa. BK stimulated SP-LI release from mucosa but not detrusor. SP stimulated increased BK-LI release from mucosa and detrusor. These findings indicate the basal release of peptide-like immunoreactivity by isolated bladder and further support the concept that peptidases located in the bladder mucosa are important in terminating the effects of endogenous peptides.

[Multiple bladder diverticula caused by occipital horn syndrome].

PubMed

Legros, L; Revencu, N; Nassogne, M-C; Wese, F-X; Feyaerts, A

2015-11-01

We report on the case of a child who presented with recurrent, multiple, and voluminous bladder diverticula. Bladder diverticula are defined as a herniation of the mucosa through the bladder muscle or the detrusor. Causes are numerous and diverticula can be classified into primary congenital diverticula (para-ureteral - or Hutch diverticula - and posterolateral diverticula); secondary diverticula (resulting from chronic mechanical obstruction or from neurological disease; and diverticula secondary to connective tissue or muscle fragility. The latter is seen in disease entities such as prune belly syndrome, Ehlers-Danlos syndrome, cutis laxa syndrome, OHS (occipital horn syndrome), Menkes disease, and Williams-Beuren syndrome. In this patient, the cause of these diverticula was OHS, a genetic, recessive X-chromosome-linked syndrome, responsible for abnormal tissue caused by a disorder in copper metabolism. This case reminds us of the importance of pushing the diagnostic workup when presented with multiple and/or large bladder diverticula, and in particular to search for rare malformation syndromes after exclusion of an obstacle. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Lipid peroxidation and antioxidants status in human malignant and non-malignant thyroid tumours.

PubMed

Stanley, J A; Neelamohan, R; Suthagar, E; Vengatesh, G; Jayakumar, J; Chandrasekaran, M; Banu, S K; Aruldhas, M M

2016-06-01

Thyroid epithelial cells produce moderate amounts of reactive oxygen species that are physiologically required for thyroid hormone synthesis. Nevertheless, when they are produced in excessive amounts, they may become toxic. The present study is aimed to compare the lipid peroxidation (LPO), antioxidant enzymes - superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and non-protein thiols (reduced glutathione (GSH)) in human thyroid tissues with malignant and non-malignant disorders. The study used human thyroid tissues and blood samples from 157 women (147 diseased and 10 normal). Thyroid hormones, oxidative stress markers and antioxidants were estimated by standard methods. LPO significantly increased in most of the papillary thyroid carcinoma (PTC: 82.9%) and follicular thyroid adenoma (FTA: 72.9%) tissues, whilst in a majority of nodular goitre (69.2%) and Hashimoto's thyroiditis (HT: 73.7%) thyroid tissues, it remained unaltered. GSH increased in PTC (55.3%), remained unaltered in FTA (97.3%) and all other goiter samples studied. SOD increased in PTC (51.1%) and all other malignant thyroid tissues studied. CAT remained unaltered in PTC (95.7%), FTA (97.3%) and all other non-malignant samples (HT, MNG, TMNG) studied. GPx increased in PTC (63.8%), all other malignant thyroid tissues and remained unaltered in many of the FTA (91.9%) tissues and all other non-malignant samples (HT, MNG, TMNG) studied. In the case of non-malignant thyroid tumours, the oxidant-antioxidant balance was undisturbed, whilst in malignant tumours the balance was altered, and the change in r value observed in the LPO and SOD pairs between normal and PTC tissues and also in many pairs with multi-nodular goitre (MNG)/toxic MNG tissues may be used as a marker to differentiate/detect different malignant/non-malignant thyroid tumours. © The Author(s) 2015.

Amyopathic Dermatomyositis: A Concise Review of Clinical Manifestations and Associated Malignancies.

PubMed

Udkoff, Jeremy; Cohen, Philip R

2016-10-01

Amyopathic dermatomyositis is a rare, idiopathic, connective tissue disease that presents with dermatologic lesions of classic dermatomyositis but lacks the myopathy of this disease. Cutaneous manifestations may include Gottron's sign, heliotrope rash, and characteristic patterns of poikiloderma. There is a substantial risk for developing interstitial lung disease or malignancy in patients with amyopathic dermatomyositis. A literature review of amyopathic dermatomyositis was performed using the PubMed medical database. The key features of amyopathic dermatomyositis, including autoantibodies, clinical presentation and dermatologic manifestations, epidemiology, history, associated malignancies, management, and pathogenesis, are summarized in this review. Cancer (solid tumor) (73/79, 89 %) and hematologic malignancies (9/79, 11 %) were reported in 79 patients, with three patients having more than one malignancy. In addition, there were six patients with amyopathic dermatomyositis who had tumor of unknown primary, and eight patients with cancer-associated amyopathic dermatomyositis for whom no additional details were provided. From the group of 73 tumors for whom primary origin and sex were available, malignancy of the genitourinary organs (24/73, 33 %), aerorespiratory organs (15/73, 21 %), and breast (14/73, 19 %) were the most commonly observed solid organ tumors. Tumors of the genitourinary organs (15/48, 31 %) and breast (14/48, 29 %) were the most frequent neoplasms in women, accounting for 29 of 48 (60 %) cancers, with the most common sites being breast (14/48, 29 %), ovary (8/48, 17 %), and cervix or uterus (5/48, 10 %). In men, tumors of the aerorespiratory (9/25, 36 %) and genitourinary (9/25, 36 %) tracts were the most common neoplasms, accounting for 72 % (18/25) of cancers; the most common sites of primary malignancy were nasopharyngeal (6/25, 24 %), bladder (4/25, 16 %), and either colorectal, lung or prostate cancer (three cancers each, 12 %). In summary, the search for an undiagnosed associated malignancy in patients with amyopathic dermatomyositis should focus towards the organs most frequently affected. Similar to classic dermatomyositis, ovarian and nasopharyngeal cancers are also common in amyopathic dermatomyositis. However, in contrast to lung cancer, which is the most frequent malignancy associated with classic dermatomyositis, breast cancer was the most common type of malignancy reported in patients with amyopathic dermatomyosotis.

The health economics of bladder cancer: an updated review of the published literature.

PubMed

Yeung, Christina; Dinh, Tuan; Lee, Joseph

2014-11-01

The purpose of this paper is to provide a current view of the economic burden of bladder cancer, with a focus on the cost effectiveness of available interventions. This review updates a previous systematic review and includes 72 new papers published between 2000 and 2013. Bladder cancer continues to be one of the most common and expensive malignancies. The annual cost of bladder cancer in the USA during 2010 was $US4 billion and is expected to rise to $US5 billion by 2020. Ten years ago, urinary markers held the potential to lower treatment costs of bladder cancer. However, subsequent real-world experiments have demonstrated that further work is necessary to identify situations in which these technologies can be applied in a cost-effective manner. Adjunct cytology remains a part of diagnostic standard of care, but recent research suggests that it is not cost effective due to its low diagnostic yield. Analysis of intravesical chemotherapy after transurethral resection of bladder tumor (TURBT), neo-adjuvant therapy for cystectomy, and robot-assisted laparoscopic cystectomy suggests that these technologies are cost effective and should be implemented more widely for appropriate patients. The existing literature on the cost effectiveness of bladder cancer treatments has improved substantially since 2000. The body of work now includes many new models, registry analyses, and real-world studies. However, there is still a need for new implementation guidelines, new risk modeling tools, and a better understanding of the empirical burden of bladder cancer.

Bladder cancer in patients with spinal cord injury.

PubMed

Hess, Marika J; Zhan, Ellen H; Foo, Dominic K; Yalla, Subbarao V

2003-01-01

The incidence of bladder cancer in spinal cord injury (SCI) is 16 to 28 times higher than that in the general population. The objective of this study was to investigate the characteristics of bladder cancer that are unique to the SCI population. Retrospective review. The charts of 16 patients diagnosed with bladder cancer from 1982 to 2001 were reviewed for type of cancer, exposure to risk factors, presenting symptoms, and survival time. The presenting manifestations were gross hematuria in 14 patients, papillary urethral growth in 1 patient, and acute obstructive renal failure in 1 patient. The diagnosis was made on initial cystoscopic evaluation in 16 patients; 3 patients required further evaluation. Eight of the 11 screening cytologies were suspicious for a malignancy prior to the diagnosis. Seven patients had transitional cell carcinoma, 6 patients had squamous cell carcinoma (SCCA), and 3 patients had both. The bladder wasmanaged with chronic indwelling catheter in 12 patients. Nine patients died of bladder cancer metastases and the remaining 3 patients died of other causes. Six patients survived 5 years or more; 4 were still alive at the completion of this study. Gross hematuria in individuals with SCI warrants aggressive assessment for bladder cancer. Chronic indwelling catheter, smoking, and renal and bladder stones are important risk factors for cancer. The incidence of SCCA in the SCI popullation is much higher than in the general population. Cystoscopic and cytologic evaluation in patients with advanced disease may fail to confirm the diagnosis in a high proportion of patients.

Effects of exposure to pile-driving sounds on the lake sturgeon, Nile tilapia and hogchoker

PubMed Central

Halvorsen, Michele B.; Casper, Brandon M.; Matthews, Frazer; Carlson, Thomas J.; Popper, Arthur N.

2012-01-01

Pile-driving and other impulsive sound sources have the potential to injure or kill fishes. One mechanism that produces injuries is the rapid motion of the walls of the swim bladder as it repeatedly contacts nearby tissues. To further understand the involvement of the swim bladder in tissue damage, a specially designed wave tube was used to expose three species to pile-driving sounds. Species included lake sturgeon (Acipenser fulvescens)—with an open (physostomous) swim bladder, Nile tilapia (Oreochromis niloticus)—with a closed (physoclistous) swim bladder and the hogchoker (Trinectes maculatus)—a flatfish without a swim bladder. There were no visible injuries in any of the exposed hogchokers, whereas a variety of injuries were observed in the lake sturgeon and Nile tilapia. At the loudest cumulative and single-strike sound exposure levels (SELcum and SELss respectively), the Nile tilapia had the highest total injuries and the most severe injuries per fish. As exposure levels decreased, the number and severity of injuries were more similar between the two species. These results suggest that the presence and type of swim bladder correlated with injury at higher sound levels, while the extent of injury at lower sound levels was similar for both kinds of swim bladders. PMID:23055066

Tissue responses to hexyl 5-aminolevulinate-induced photodynamic treatment in syngeneic orthotopic rat bladder cancer model: possible pathways of action

NASA Astrophysics Data System (ADS)

Arum, Carl-Jørgen; Gederaas, Odrun A.; Larsen, Eivind L. P.; Randeberg, Lise L.; Hjelde, Astrid; Krokan, Hans E.; Svaasand, Lars O.; Chen, Duan; Zhao, Chun-Mei

2011-02-01

Orthotopic bladder cancer model in rats mimics human bladder cancer with respect to urothelial tumorigenesis and progression. Utilizing this model at pT1 (superficial stage), we analyze the tissue responses to hexyl 5-aminolevulinate-induced photodynamic therapy (HAL-PDT). In comparison to untreated rats, HAL-PDT causes little change in tumor-free rat bladder but induces inflammatory changes with increased lymphocytes and mononuclear cell infiltration in rat bladders with tumor. Immunohistochemistry reveals that HAL-PDT is without effect on proliferating cell nuclear antigen expression within the tumor and increases caspase-3 expression in both normal urothelium and the tumor. Transmission electron microscopy reveals severe mitochondrial damage, formations of apoptotic bodies, vacuoles, and lipofuscin bodies, but no microvillus-formed niches in HAL-PDT-treated bladder cancer rats. Bioinformatics analysis of the gene expression profile indicates an activation of T-cell receptor signaling pathway in bladder cancer rats without PDT. HAL-PDT increases the expression of CD3 and CD45RA in the tumor (determined by immunohistochemistry). We suggest that pathways of action of HAL-PDT may include, at least, activations of mitochondrial apoptosis and autophagy, breakdown of cancer stem cell niches, and importantly, enhancement of T-cell activation.

Effects of exposure to pile-driving sounds on the lake sturgeon, Nile tilapia and hogchoker.

PubMed

Halvorsen, Michele B; Casper, Brandon M; Matthews, Frazer; Carlson, Thomas J; Popper, Arthur N

2012-12-07

Pile-driving and other impulsive sound sources have the potential to injure or kill fishes. One mechanism that produces injuries is the rapid motion of the walls of the swim bladder as it repeatedly contacts nearby tissues. To further understand the involvement of the swim bladder in tissue damage, a specially designed wave tube was used to expose three species to pile-driving sounds. Species included lake sturgeon (Acipenser fulvescens)--with an open (physostomous) swim bladder, Nile tilapia (Oreochromis niloticus)--with a closed (physoclistous) swim bladder and the hogchoker (Trinectes maculatus)--a flatfish without a swim bladder. There were no visible injuries in any of the exposed hogchokers, whereas a variety of injuries were observed in the lake sturgeon and Nile tilapia. At the loudest cumulative and single-strike sound exposure levels (SEL(cum) and SEL(ss) respectively), the Nile tilapia had the highest total injuries and the most severe injuries per fish. As exposure levels decreased, the number and severity of injuries were more similar between the two species. These results suggest that the presence and type of swim bladder correlated with injury at higher sound levels, while the extent of injury at lower sound levels was similar for both kinds of swim bladders.

Bladder Involvement in Stage I Endometriosis.

PubMed

Brady, Paula C; Missmer, Stacey A; Laufer, Marc R

2017-08-01

Endometriosis-the ectopic implantation of endometrial-like tissue-affects 10% of adolescent females and adults. Bladder involvement, causing dysuria and hematuria, occurs in a very small number of endometriosis patients. The patient presented at age 12 years with dysuria and pelvic pain. Laparoscopy revealed stage I endometriosis. Postoperatively, she reported persistent dysuria and passage of tissue in her urine. Cystoscopy showed diffuse erythema; urine cytology revealed glandular and spindle cells suggestive of endometriosis. She was transitioned from oral contraceptives to an intranasal gonadotropin-releasing hormone agonist, with symptom resolution. Intravesicular endometriosis coinciding with stage I disease supports a mechanism of endometriosis dissemination other than direct bladder infiltration. Patients with endometriosis who complain of urinary symptoms warrant assessment, because intravesicular bladder involvement cannot be excluded using pelviscopy. Copyright © 2017 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Increased autophagy contributes to impaired smooth muscle function in neurogenic lower urinary tract dysfunction.

PubMed

Eberli, Daniel; Horst, Maya; Mortezavi, Ashkan; Andersson, Karl-Erik; Gobet, Rita; Sulser, Tullio; Simon, Hans-Uwe; Salemi, Souzan

2018-05-24

To explore whether autophagy plays a role in the remodeling of bladder smooth muscle cells (SMCs) in children with neurogenic lower urinary tract dysfunction (NLUTD), we investigated the effect of autophagy in NLUTD in the paediatric population. Bladder biopsies were taken from children with NLUTD and healthy donors as controls. Samples were labeled with the SMC markers calponin, smoothelin, and the autophagy proteins LC3, ATG5, and Beclin1. The contractile ability of bladder derived SMCs was investigated. ATG5 gene and protein was upregulated in NLUTD muscle tissue compared to normal bladder. NLUTD muscle exhibited a punctated immunostaining pattern for LC3 in a subset of the SMCs, confirming the accumulation of autophagosomes. Pronounced elevation of ATG5 in the SMC in NLUTD tissue was associated with a downregulation of the key contractile proteins smoothelin and calponin. Pharmacological blocking of autophagy completely stopped the cells growth in normal bladder SMCs. Inhibition of autophagy in the NLUTD SMCs, with already elevated levels of ATG5, resulted in a reduction of ATG5 protein expression to the basal level found in normal controls. Our study suggests that autophagy is an important factor affecting the remodeling of SMCs and the alteration of functionality in bladder smooth muscle tissue in the NLUTD. Since autophagy can be influenced by oral medication, this finding might lead to novel strategies preventing the deterioration of NLUTD muscle. © 2018 Wiley Periodicals, Inc.

A new problem in inflammatory bladder diseases: use of mobile phones!

PubMed

Koca, Orhan; Gokce, Ali Murat; Akyuz, Mehmet; Ercan, Feriha; Yurdakul, Necati; Karaman, Muhammet Ihsan

2014-01-01

Technological developments provide a lot of conveniences to our lives. This issue is one of the risks that arise along with these conveniences. In our study we tried to understand the impact of electromagnetic waves from mobile phones on bladder tissue. Twenty-one adult male albino rats were divided into three equal groups. Group 1 was exposed to electromagnetic wave for 8 hours per day for 20 days and then their bladders were taken off immediately. Group 2 was firstly exposed to electromagnetic wave for 8 hours per day for 20 days then secondly another for 20 days without exposition to electromagnetic wave and then their bladders were taken off. Group 3 was the control group and they were not exposed to electromagnetic wave. Under microscopic examination of bladder tissue, in the first group severe inflammatory cell infiltration was seen in lamina propria and muscle layer in contrast to intact urothelium. In the second group mild inflammatory cell infiltration was seen in lamina propria and muscle layer. The mean scores for the three groups were 5.5 ± 2.5, 0.8 ± 1.3 and 1.2 ± 1.5 respectively. Mean score of group 1 was statistically higher than others (p = 0.001). Intensive use of mobile phones has negative impact on bladder tissue as well as the other organs. Keeping a minimum level of mobile phone use makes it easy to be kept under control of diseases in which inflammation is an etiologic factor.

Immunohistochemical analysis of the role and relationship between Notch-1 and Oct-4 expression in urinary bladder carcinoma.

PubMed

Abdou, Asmaa Gaber; El-Wahed, Moshira Mohammed Abd; Kandil, Mona Abd-Elhalim; Samaka, Rehab Monir; Elkady, Noha

2013-10-01

Most tumors contain a minor population of cancer stem cells that are responsible for tumor heterogeneity, resistance to therapy and recurrence. Oct-4 is a transcription factor responsible for self-renewal of stem cells, whereas the Notch family of receptors and ligands may play a pivotal role in the regulation of stem cell maintenance and differentiation. This study aimed at an evaluation of Oct-4 and Notch-1 expression in both carcinoma and stromal cells of 83 cases of primary bladder carcinoma and to study the relationship between them. Notch-1 was expressed in carcinoma and stromal cells of all malignant cases, where expression in both cell types was correlated with parameters indicating differentiation, such as low grade (p < 0.05) and less proliferation (p < 0.05). However, Notch-1 expression in stromal cells was associated with nodal metastasis (p = 0.016) and advanced stage (p = 0.030). 56.6 and 75.9% of carcinoma and stromal cells of malignant cases showed Oct-4 expression, respectively. Oct-4 expression in carcinoma cells or stromal cells was associated with aggressive features of bladder carcinoma, such as poor differentiation (p = 0.001), high proliferation (p < 0.001, 0.030), and liability for recurrence (p = 0.010, p < 0.001). There was an inverse relationship between Notch-1 and Oct-4 expression in carcinoma cells (p = 0.002), but stromal expression of Notch-1 was found to be associated with a nuclear pattern of Oct-4 expression in carcinoma cells (p = 0.030). Oct-4 as a stem cell marker is expressed in carcinoma cells and in stromal cells of bladder carcinoma, where they may cooperate in the progression of bladder carcinoma by acquiring aggressive features, such as a liability for recurrence and dissemination. Notch-1 is also expressed in both carcinoma cells and stromal cells of bladder carcinoma. Although they could share in enhancing differentiation, stromal expression of Notch-1 may have a bad impact, possibly through up-regulation of the active nuclear form of Oct-4 in carcinoma cells. © 2013 APMIS Published by Blackwell Publishing Ltd.

[The Predictive Factors of Stent Failure in the Treatment of Malignant Extrinsc Ureteral Obstruction Using Internal Ureteral Stents].

PubMed

Matsuura, Hiroshi; Arase, Shigeki; Hori, Yasuhide; Tochigi, Hiromi

2017-12-01

In this study, we retrospectively reviewed the experiences at our single institute in the treatment of malignant extrinsic ureteral obstruction (MUO) using ureteral stents to investigate the clinical outcomes and the predictive factors of stent failure. In 52 ureters of 38 patients who had radiologically significant hydronephrosis due to MUO, internal ureteral stents (The BARD(R) INLAY(TM) ureteral stent set) were inserted. The median follow-up interval after the initial stent insertion was 124.5 days (4-1,120). Stent failure occurred in 8 ureters (15.4%) of the 7 patients. The median interval from the first stent insertion to stent failure was 88 days (1-468). A Cox regression multivariate analysis showed that the significant predictors of stent failure were bladder invasion. Based on the possibility of stent failure, the adaptation of the internal ureteral stent placement should be considered especially in a patient with MUO combined with bladder invasion.

Variant hairy cell leukemia following papillary urothelial neoplasm of bladder.

PubMed

Beyan, Cengiz; Kaptan, Kürsat

2014-03-01

A 65 years old man was admitted with multiple lymphadenopathy, weight loss, night sweats and fatigue for 2 months. He had been treated for bladder cancer 2 years ago. Leukocyte count was 37.9 x10(9)/l. Peripheral blood smear had 91% lymphocytes. Lymphocytes had large nuclei with prominent nucleoli, heterogeneous appearance, and large cytoplasm with hairy projections. Flow cytometric immunophenotyping revealed CD20, CD22, CD24, CD45 and HLA-DR positivity. Atypical lymphocytes were stained with tartrate resistant acid phosphatase. Increased metabolic activity was detected in multiple lymph nodes, bone marrow and extremely enlarged spleen with positron emission tomography-computed tomography. Excisional biopsy of the left axillary lymph node revealed infiltration with diffuse B-cell leukemia/lymphoma. Immunohistochemistry showed CD20 positive atypical cells with weak expression of CD11c. The patient was diagnosed as a case of variant hairy cell leukemia and cladribine was administered. A probable second primary malignancy should be kept in mind in cases with a defined malignancy in the presence of unusual symptoms.

Targeting Hsp90 in urothelial carcinoma

PubMed Central

Skotnicki, Kamil; Landas, Steve; Bratslavsky, Gennady; Bourboulia, Dimitra

2015-01-01

Urothelial carcinoma, or transitional cell carcinoma, is the most common urologic malignancy that carries significant morbidity, mortality, recurrence risk and associated health care costs. Despite use of current chemotherapies and immunotherapies, long-term remission in patients with muscle-invasive or metastatic disease remains low, and disease recurrence is common. The molecular chaperone Heat Shock Protein-90 (Hsp90) may offer an ideal treatment target, as it is a critical signaling hub in urothelial carcinoma pathogenesis and potentiates chemoradiation. Preclinical testing with Hsp90 inhibitors has demonstrated reduced proliferation, enhanced apoptosis and synergism with chemotherapies and radiation. Despite promising preclinical data, clinical trials utilizing Hsp90 inhibitors for other malignancies had modest efficacy. Therefore, we propose that Hsp90 inhibition would best serve as an adjuvant treatment in advanced muscle-invasive or metastatic bladder cancers to potentiate other therapies. An overview of bladder cancer biology, current treatments, molecular targeted therapies, and the role for Hsp90 inhibitors in the treatment of urothelial carcinoma is the focus of this review. PMID:25909217

Primary malignant melanoma of the urinary bladder: clinical, morphological, and molecular analysis of five cases.

PubMed

Karabulut, Yasemin Y; Erdogan, Seyda; Sayar, Hamide; Ergen, Ali; Ertoy Baydar, Dilek

2016-12-01

The aim of our study was to evaluate the clinical and morphological features of primary malignant melanomas of the urinary bladder. We obtained information on five such cases from three different institutions. These were three men and two women between 52 and 76 years of age. Three tumors presented with hematuria, one with dysuria, and one was discovered incidentally on imaging studies. All were invasive to muscularis propria on transuretral resections performed for diagnosis. Neoplastic cells showed variable patterns (large cell epithelioid, small cell diffuse, storiform, or mixed) in different tumors. Pigmentation was prominent in all except one case. Each case was labeled diffusely for S-100, HMB-45, and Melan-A. Pan-cytokeratin showed a perinuclear dot-like reaction in two tumors. Three cases showed the BRAF mutation in molecular studies. Two patients were already metastatic at the time of diagnosis. Two patients died, one is alive with disease after 15 months, and two patients are disease free at 1 and 5 years of surveillance.

Sex disparities in diagnosis of bladder cancer after initial presentation with hematuria: a nationwide claims-based investigation.

PubMed

Cohn, Joshua A; Vekhter, Benjamin; Lyttle, Christopher; Steinberg, Gary D; Large, Michael C

2014-02-15

Women have disproportionately higher mortality rates relative to incidence for bladder cancer. Multiple etiologies have been proposed, including delayed diagnosis and treatment. Guidelines recommend ruling out malignancy in men and women presenting with hematuria. This study sought to determine the difference in timing from presentation with hematuria to diagnosis of bladder cancer in women versus men. This is a retrospective population-based study examining the timing from presentation with hematuria to diagnosis of bladder cancer, based on data from the MarketScan databases, which include enrollees of more than 100 health insurance plans of approximately 40 large US employers from 2004 through 2010. All study patients presented with hematuria and were subsequently diagnosed with bladder cancer. The primary outcome measure was number of days between initial presentation with hematuria and diagnosis of bladder cancer by sex. A total of 5416 men and 2233 women met inclusion criteria. Mean days from initial hematuria claim to bladder cancer claim was significantly longer in women (85.4 versus 73.6 days, P < .001), and the proportion of women with >6 month delay in bladder cancer diagnosis was significantly higher (17.3% versus 14.1%, P < .001). Women were more likely to be diagnosed with urinary tract infection (odds ratio = 2.32, 95% confidence interval = 2.07-2.59) and less likely to undergo abdominal or pelvic imaging (odds ratio = 0.80, 95% confidence interval = 0.71-0.89). Both men and women experience significant delays between presentation with hematuria and diagnosis of bladder cancer, with longer delays for women. This may be partly responsible for the sex-based discrepancy in outcomes associated with bladder cancer. © 2013 American Cancer Society.

Inflammation and Tissue Remodeling in the Bladder and Urethra in Feline Interstitial Cystitis

PubMed Central

Kullmann, F. Aura; McDonnell, Bronagh M.; Wolf-Johnston, Amanda S.; Lynn, Andrew M.; Getchell, Samuel E.; Ruiz, Wily G.; Zabbarova, Irina V.; Ikeda, Youko; Kanai, Anthony J.; Roppolo, James R.; Bastacky, Sheldon I.; Apodaca, Gerard; Buffington, C. A. Tony; Birder, Lori A.

2018-01-01

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating chronic disease of unknown etiology. A naturally occurring disease termed feline interstitial cystitis (FIC) reproduces many features of IC/BPS patients. To gain insights into mechanisms underlying IC/BPS, we investigated pathological changes in the lamina propria (LP) of the bladder and proximal urethra in cats with FIC, using histological and molecular methods. Compared to control cat tissue, we found an increased number of de-granulated mast cells, accumulation of leukocytes, increased cyclooxygenase (COX)-1 expression in the bladder LP, and increased COX-2 expression in the urethra LP from cats with FIC. We also found increased suburothelial proliferation, evidenced by mucosal von Brunn’s nests, neovascularization and alterations in elastin content. Scanning electron microscopy revealed normal appearance of the superficial urethral epithelium, including the neuroendocrine cells (termed paraneurons), in FIC urethrae. Together, these histological findings suggest the presence of chronic inflammation of unknown origin leading to tissue remodeling. Since the mucosa functions as part of a “sensory network” and urothelial cells, nerves and other cells in the LP are influenced by the composition of the underlying tissues including the vasculature, the changes observed in the present study may alter the communication of sensory information between different cellular components. This type of mucosal signaling can also extend to the urethra, where recent evidence has revealed that the urethral epithelium is likely to be part of a signaling system involving paraneurons and sensory nerves. Taken together, our data suggest a more prominent role for chronic inflammation and tissue remodeling than previously thought, which may result in alterations in mucosal signaling within the urinary bladder and proximal urethra that may contribute to altered sensations and pain in cats and humans with this syndrome. PMID:29706873

Androgen receptor activation: a prospective therapeutic target for bladder cancer?

PubMed

Mizushima, Taichi; Tirador, Kathleen A; Miyamoto, Hiroshi

2017-03-01

Patients with non-muscle-invasive or muscle-invasive bladder cancer undergoing surgery and currently available conventional therapy remain having a high risk of tumor recurrence or progression, respectively. Novel targeted molecular therapy is therefore expected to improve patient outcomes. Meanwhile, substantially higher incidence of bladder cancer in men has prompted research on androgen-mediated androgen receptor (AR) signaling in this malignancy. Indeed, preclinical evidence has suggested that AR signaling plays an important role in urothelial carcinogenesis and tumor outgrowth as well as resistance to some of the currently available conventional non-surgical therapies. Areas covered: We summarize and discuss available data suggesting the involvement of AR and its potential downstream targets in the development and progression of bladder cancer. Associations between AR signaling and sensitivity to cisplatin/doxorubicin or bacillus Calmette-Guérin treatment are also reviewed. Expert opinion: AR activation is likely to correlate with the promotion of urothelial carcinogenesis and cancer outgrowth as well as resistance to conventional therapies. Molecular therapy targeting the AR may thus provide effective chemopreventive and therapeutic approaches for urothelial cancer. Accordingly, bladder cancer can now be considered as an endocrine-related neoplasm. Clinical application of various anti-AR therapies available for AR-dependent prostate cancer to bladder cancer patients is anticipated.

TRPV2 Mediates Adrenomedullin Stimulation of Prostate and Urothelial Cancer Cell Adhesion, Migration and Invasion

PubMed Central

Vanden Abeele, Fabien; Lehen’kyi, V’yacheslav; Ouafik, L’Houcine; Mauroy, Brigitte; Prevarskaya, Natalia

2013-01-01

Adrenomedullin (AM) is a 52-amino acid peptide initially isolated from human pheochromocytoma. AM is expressed in a variety of malignant tissues and cancer cell lines and was shown to be a mitogenic factor capable of stimulating growth of several cancer cell types. In addition, AM is a survival factor for certain cancer cells. Some data suggest that AM might be involved in the progression cancer metastasis via angiogenesis and cell migration and invasion control. The Transient Receptor Potential channel TRPV2 is known to promote in prostate cancer cell migration and invasive phenotype and is correlated with the stage and grade of bladder cancer. In this work we show that AM induces prostate and urothelial cancer cell migration and invasion through TRPV2 translocation to plasma membrane and the subsequent increase in resting calcium level. PMID:23741410

[DAB2IP expression in bladder transitional cell carcinoma and its correlation with clinical outcome].

PubMed

Zhu, Jian-Ning; Wu, Kai-Jie; Guan, Zhen-Feng; Liu, Li-Xia; Ning, Zhong-Yun; Zhou, Jian-Cheng; Wang, Xin-Yang; Fan, Jin-Hai

2014-07-01

To investigate the expression of DAB2IP in bladder transitional cell carcinoma (BTCC) and its correlation with clinical characteristics and prognosis of BTCC patients. Immunohistochemical staining was applied to detect DAB2IP protein level in 79 cases of TCCB tissues and 11 cases of normal bladder tissues, and the relationships of the staining results with pathological grade, stage, lymph node metastasis, gender, age and the 3-year survival rate of the patients were analyzed. The expression of DAB2IP in BTCC tissues was significantly lower than that in normal bladder epithelium, and the expression score and rate of DAB2IP in the high-grade, invasive and metastatic BTCC were significantly lower than those in low-grade, superficial and non-metastatic BTCC (P < 0.05). The 3-year survival rate of the patients with high DAB2IP expression was significantly higher than that of the patients with low DAB2IP expression. DAB2IP may be one of the important inhibitory factors during the occurrence and progression of BTCC.

Androgen receptor signals regulate UDP-glucuronosyltransferases in the urinary bladder: a potential mechanism of androgen-induced bladder carcinogenesis.

PubMed

Izumi, Koji; Zheng, Yichun; Hsu, Jong-Wei; Chang, Chawnshang; Miyamoto, Hiroshi

2013-02-01

UDP-glucuronosyltransferases (UGTs), major phase II drug metabolism enzymes, play an important role in urinary bladder cancer initiation by detoxifying carcinogens. We aimed to determine if androgens regulate UGT expression via the androgen receptor (AR) pathway in the bladder. Real-time reverse transcription-polymerase chain reaction and Western blot analyses were used to assess UGT1A levels in the normal urothelium SVHUC cell line stably expressed with AR and in bladder tissues from AR knockout (ARKO) and castrated male mice. Immunohistochemistry was also performed in radical cystectomy specimens. Dihydrotestosterone (DHT) treatment in SVHUC-AR reduced mRNA expression of all the UGT1A subtypes (19-75% decrease), and hydroxyflutamide antagonized the DHT effects. In contrast, DHT showed only marginal effects on UGT1A expression in SVHUC-Vector. Of note were higher expression levels of UGT1As in SVHUC-Vector than in SVHUC-AR. In ARKO mice, all the Ugt1a subtypes were up-regulated, compared to wild-type littermates. In wild-type male mice, castration increased the expression of Ugt1a8, Ugt1a9, and Ugt1a10. Additionally, wild-type female mice had higher levels of Ugt1a than wild-type males. Immunohistochemical studies showed strong (3+) UGT1A staining in 11/24 (46%) cancer tissues, which was significantly lower than in corresponding benign tissues [17/18 (94%) cases (P = 0.0009)]. These results suggest that androgen-mediated AR signals promote bladder carcinogenesis by down-regulating the expression of UGTs in the bladder. Copyright © 2011 Wiley Periodicals, Inc.

Tumour front inflammation and necrosis are independent prognostic predictors in high-grade urothelial carcinoma of the bladder.

PubMed

Hodgson, Anjelica; Xu, Bin; Satkunasivam, Raj; Downes, Michelle R

2018-02-01

Inflammation and necrosis have been associated with prognosis in multiple epithelial malignancies. Our objective was to evaluate inflammation and necrosis in a cohort of patients with high-grade urothelial carcinomas of the bladder to determine their association with pathological parameters and their prognostic effect on relapse-free and disease-specific survival. A retrospective cohort that underwent radical cystectomy for urothelial carcinomas (n=235) was evaluated for invasive front and central inflammation using the Klintrup-Makinen assessment method. Necrosis was scored using a four-point scale. The relationship of inflammation and necrosis with stage, nodal status, carcinoma in situ, tumour size, margin status and vascular space invasion and the impact on relapse-free and disease-specific survival were calculated using appropriate statistical tests. On multivariate analysis, invasive front inflammation (p=0.003) and necrosis (p=0.000) were independent predictors of relapse-free survival. Both invasive front inflammation (p=0.009) and necrosis (p=0.002) again were independent predictors of disease-specific survival. For pathological features, low invasive front inflammation was associated with lymphovascular space invasion (p=0.008), a positive soft tissue margin (p=0.028) and carcinoma in situ (p=0.042). Necrosis was statistically associated with tumours >3 cm in size (p=0.013) and carcinoma in situ (p<0.001). Necrosis and invasive front inflammation are additional histological variables with independent prognostic relevance in high-grade urothelial carcinoma of the bladder. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Hypoxia enhances the malignant nature of bladder cancer cells and concomitantly antagonizes protein O-glycosylation extension

PubMed Central

Lima, Luís; Azevedo, Rita; Soares, Janine; Cotton, Sofia; Parreira, Beatriz; Neves, Manuel; Amaro, Teresina; Tavares, Ana; Teixeira, Filipe; Palmeira, Carlos; Rangel, Maria; Silva, André M.N.; Reis, Celso A.; Santos, Lúcio Lara; Oliveira, Maria José; Ferreira, José Alexandre

2016-01-01

Invasive bladder tumours express the cell-surface Sialyl-Tn (STn) antigen, which stems from a premature stop in protein O-glycosylation. The STn antigen favours invasion, immune escape, and possibly chemotherapy resistance, making it attractive for target therapeutics. However, the events leading to such deregulation in protein glycosylation are mostly unknown. Since hypoxia is a salient feature of advanced stage tumours, we searched into how it influences bladder cancer cells glycophenotype, with emphasis on STn expression. Therefore, three bladder cancer cell lines with distinct genetic and molecular backgrounds (T24, 5637 and HT1376) were submitted to hypoxia. To disclose HIF-1α-mediated events, experiments were also conducted in the presence of Deferoxamine Mesilate (Dfx), an inhibitor of HIF-1α proteasomal degradation. In both conditions all cell lines overexpressed HIF-1α and its transcriptionally-regulated protein CA-IX. This was accompanied by increased lactate biosynthesis, denoting a shift toward anaerobic metabolism. Concomitantly, T24 and 5637 cells acquired a more motile phenotype, consistent with their more mesenchymal characteristics. Moreover, hypoxia promoted STn antigen overexpression in all cell lines and enhanced the migration and invasion of those presenting more mesenchymal characteristics, in an HIF-1α-dependent manner. These effects were reversed by reoxygenation, demonstrating that oxygen affects O-glycan extension. Glycoproteomics studies highlighted that STn was mainly present in integrins and cadherins, suggesting a possible role for this glycan in adhesion, cell motility and invasion. The association between HIF-1α and STn overexpressions and tumour invasion was further confirmed in bladder cancer patient samples. In conclusion, STn overexpression may, in part, result from a HIF-1α mediated cell-survival strategy to adapt to the hypoxic challenge, favouring cell invasion. In addition, targeting STn-expressing glycoproteins may offer potential to treat tumour hypoxic niches harbouring more malignant cells. PMID:27542232

A large-scale measurement of dielectric properties of normal and malignant colorectal tissues obtained from cancer surgeries at Larmor frequencies.

PubMed

Li, Zhou; Deng, Guanhua; Li, Zhe; Xin, Sherman Xuegang; Duan, Song; Lan, Maoying; Zhang, Sa; Gao, Yixin; He, Jun; Zhang, Songtao; Tang, Hongming; Wang, Weiwei; Han, Shuai; Yang, Qing X; Zhuang, Ling; Hu, Jiani; Liu, Feng

2016-11-01

Knowledge of dielectric properties of malignant human tissues is necessary for the recently developed magnetic resonance (MR) technique called MR electrical property tomography. This technique may be used in early tumor detection based on the obvious differentiation of the dielectric properties between normal and malignant tissues. However, the dielectric properties of malignant human tissues in the scale of the Larmor frequencies are not completely available in the literature. In this study, the authors focused only on the dielectric properties of colorectal tumor tissue. The dielectric properties of 504 colorectal malignant samples excised from 85 patients in the scale of the Larmor frequencies were measured using the precision open-ended coaxial probe method. The obtained complex-permittivity data were fitted to the single-pole Cole-Cole model. The median permittivity and conductivity for the malignant tissue sample were 79.3 and 0.881 S/m at 128 MHz, which were 14.6% and 17.0% higher, respectively, than those of normal tissue samples. Significant differences between normal and malignant tissues were found for the dielectric properties (p < 0.05). Experimental results indicated that the dielectric properties were significantly different between normal and malignant tissues for colorectal tissue. This large-scale clinical measurement provides more subtle base data to validate the technique of MR electrical property tomography.

Incidence of Second Primary Malignancies Following Colorectal Cancer: A Distinct Pattern of Occurrence Between Colon and Rectal Cancers and Association of Co-Morbidity with Second Primary Malignancies in a Population-Based Cohort of 98,876 Patients in Taiwan

PubMed Central

Lee, Yu-Ting; Liu, Chia-Jen; Hu, Yu-Wen; Teng, Chung-Jen; Tzeng, Cheng-Hwai; Yeh, Chiu-Mei; Chen, Tzeng-Ji; Lin, Jen-Kou; Lin, Chun-Chi; Lan, Yuan-Tzu; Wang, Huann-Sheng; Yang, Shung-Haur; Jiang, Jeng-Kai; Chen, Wei-Shone; Lin, Tzu-Chen; Chang, Shih-Ching; Chen, Ming-Huang; Teng, Hao-Wei; Liu, Jin-Hwang; Yen, Chueh-Chuan

2015-01-01

Abstract The purpose of this study is to determine the features of second primary malignancies (SPMs) among patients with prior colorectal cancer (CRC) using a nationwide population-based dataset. Patients with CRC newly diagnosed between 1996 and 2011, and >1 year of follow-up were recruited from the Taiwan National Health Insurance database. Standardized incidence ratios (SIRs) of SPMs in patients with CRC were calculated. During the 16-year study period, 4259 SPMs developed among 98,876 CRC patients. The median duration of follow-up was 4.03 years. The SIR for all SPMs was 1.13 (95% confidence interval = 1.10–1.17). Compared with the general population, a higher incidence of thyroid, prostate, ovarian, and hematologic malignancies developed among patients with colon cancer, whereas the risk for bone and soft tissue cancers increased among patients with rectal cancer. The risk for breast, bladder, kidney, lung, and uterine cancers was significantly higher in patients with colon and rectal cancers than the general population. The risk for liver and biliary tract cancers declined in patients with rectal cancer. Based on multivariate analysis among patients with CRC, age ≥70 years, men, chronic obstructive pulmonary disease (COPD), cirrhosis, and dyslipidemia were independent predictors of an SPM. In conclusion, patients with CRC were at increased risk for a second cancer. The pattern of SPMs was distinct between patients with colon and rectal cancer. Age, men, COPD, cirrhosis, and dyslipidemia were independent risk factors for SPMs. Surveillance and education should be provided for survivors with respect to risk for SPMs. PMID:26131831

A probable risk factor of female breast cancer: study on benign and malignant breast tissue samples.

PubMed

Rehman, Sohaila; Husnain, Syed M

2014-01-01

The study reports enhanced Fe, Cu, and Zn contents in breast tissues, a probable risk factor of breast cancer in females. Forty-one formalin-fixed breast tissues were analyzed using atomic absorption spectrophotometry. Twenty malignant, six adjacent to malignant and 15 benign tissues samples were investigated. The malignant tissues samples were of grade 11 and type invasive ductal carcinoma. The quantitative comparison between the elemental levels measured in the two types of specimen (benign and malignant) tissues (removed after surgery) suggests significant elevation of these metals (Fe, Cu, and Zn) in the malignant tissue. The specimens were collected just after mastectomy of women aged 19 to 59 years from the hospitals of Islamabad and Rawalpindi, Pakistan. Most of the patients belong to urban areas of Pakistan. Findings of study depict that these elements have a promising role in the initiation and development of carcinoma as consistent pattern of elevation for Fe, Cu, and Zn was observed. The results showed the excessive accumulation of Fe (229 ± 121 mg/L) in malignant breast tissue samples of patients (p < 0.05) to that in benign tissues samples (49.1 ± 11.4 mg/L). Findings indicated that excess accumulation of iron in malignant tissues can be a risk factor of breast cancer. In order to validate our method of analysis, certified reference material muscle tissue lyophilized (IAEA) MA-M-2/TM was analyzed for metal studied. Determined concentrations were quite in good agreement with certified levels. Asymmetric concentration distribution for Fe, Cu, and Zn was observed in both malignant and benign tissue samples.

Silibinin suppresses bladder cancer cell malignancy and chemoresistance in an NF-κB signal-dependent and signal-independent manner.

PubMed

Sun, Yi; Guan, Zhenfeng; Zhao, Wencai; Jiang, Yazhuo; Li, Qing; Cheng, Yongyi; Xu, Yonggang

2017-10-01

Because bladder cancer (BCa) is the 9th most common malignant tumor and 13th leading cause of death due to cancer, therapeutic approaches have attracted a great deal of attention from both clinicians and BCa patients. Although the development of surgery and targeted drugs has brought new challenges for the traditional concept of BCa therapy, various types of chemotherapy remain the final treatment method for many BCa patients. However, chemoresistance inevitably appears, leading to the failure of chemotherapy. Silibinin, a polyphenolic flavonoid component isolated from the fruits or seeds of milk thistle, has been reported to play important roles in inhibiting tumor chemoresistance in breast cancer and head and neck squamous cell carcinomas. Our previous study indicated that silibinin inhibited BCa progression in some mechanisms but with no conclusion of chemoresistance inhibition. Therefore, in the present study, we dissected the role of silibinin in BCa progression and chemoresistance. Our results revealed that in BCa, chemodrug-induced chemoresistance was reversed in the presence of silibinin. Further mechanistic study indicated that silibinin suppressed chemoresistance and BCa malignancy in an NF-κB-dependent and -independent manner. In addition, all of the inhibitory effects were dose‑dependent. Thus, our results provide a potential use for silibinin in BCa therapeutics.

Wnt5a / planar cell polarity signaling pathway in urothelial carcinoma, a potential prognostic biomarker

PubMed Central

Saling, Mark; Duckett, Jordan K; Ackers, Ian; Coschigano, Karen; Jenkinson, Scott; Malgor, Ramiro

2017-01-01

Bladder cancer is the fourth most common cancer in men and the most common malignancy of the urinary tract. Bladder cancers detected at an early stage have a very high five-year survival rate, but when detected after local metastasis the rate is only about 50%. Our group recently reported a positive correlation between the expression of Wnt5a, a member of the Wnt proteins family, and histopathological grade and stage of urothelial carcinoma (UC). The objective of this study was to analyze UC cases reported in Athens, Ohio and investigate the major components of Wnt5a / planar cell polarity (PCP) signaling pathway in UC human tissue samples and UC cell lines. Formalin fixed and paraffin embedded transurethral resection tissues were immunostained for Wnt5a, Ror-2, CTHRC1 and E-cadherin. In addition, in vitro studies using UC cell lines were investigated for Wnt5a/PCP signaling and epithelial mesenchymal transition (EMT) gene expression. The IHC results showed a correlation between the expression of Wnt5a, Ror2 and CTHRC1 with high histological grade of the tumor, while E-cadherin showed an opposite trend of expression. Real time RT-PCR results showed that RNA expression of the Wnt5a/ PCP pathway genes vary in low and high grade UC cell lines and that the high grade cell lines exhibited signs of EMT. These findings support that Wnt5a-Ror2 signaling plays a role in UC, support the potential use of Wnt5a as a prognostic marker and provide evidence that Wnt5a signaling may be used as an effective molecular target for novel therapeutic tools. PMID:28427201

Cixutumumab and Doxorubicin Hydrochloride in Treating Patients With Unresectable, Locally Advanced, or Metastatic Soft Tissue Sarcoma

ClinicalTrials.gov

2016-05-16

Adult Angiosarcoma; Adult Desmoplastic Small Round Cell Tumor; Adult Epithelioid Sarcoma; Adult Extraskeletal Myxoid Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Mesenchymoma; Adult Malignant Peripheral Nerve Sheath Tumor; Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Adult Undifferentiated High Grade Pleomorphic Sarcoma of Bone; Childhood Angiosarcoma; Childhood Desmoplastic Small Round Cell Tumor; Childhood Epithelioid Sarcoma; Childhood Fibrosarcoma; Childhood Leiomyosarcoma; Childhood Liposarcoma; Childhood Malignant Mesenchymoma; Childhood Malignant Peripheral Nerve Sheath Tumor; Childhood Pleomorphic Rhabdomyosarcoma; Childhood Rhabdomyosarcoma With Mixed Embryonal and Alveolar Features; Childhood Synovial Sarcoma; Dermatofibrosarcoma Protuberans; Malignant Adult Hemangiopericytoma; Malignant Childhood Hemangiopericytoma; Metastatic Childhood Soft Tissue Sarcoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Untreated Childhood Rhabdomyosarcoma

Adipose-derived stem-cell-implanted poly(ϵ-caprolactone)/chitosan scaffold improves bladder regeneration in a rat model.

PubMed

Zhou, Zhe; Yan, Hao; Liu, Yidong; Xiao, Dongdong; Li, Wei; Wang, Qiong; Zhao, Yang; Sun, Kang; Zhang, Ming; Lu, Mujun

2018-04-01

The study investigated the feasibility of seeding adipose-derived stem cells (ASCs) onto a poly(ϵ-caprolactone)/chitosan (PCL/CS) scaffold for bladder reconstruction using a rat model of bladder augmentation. In the experimental group, the autologous ASCs were seeded onto the PCL/CS scaffold for bladder augmentation. An unseeded scaffold was used for bladder augmentation as control group. The sham group was also set. 8 weeks after implantation, more densely smooth muscles were detected in the experimental group with a larger bladder capacity and more intensive blood vessels. Immunofluorescence staining demonstrated that some of the smooth muscle cells were transdifferentiated from the ASCs. Our findings indicated that ASC-seeded PCL/CS may be a potential scaffold for bladder tissue engineering.

High expression of insulin receptor on tumour-associated blood vessels in invasive bladder cancer predicts poor overall and progression-free survival.

PubMed

Roudnicky, Filip; Dieterich, Lothar C; Poyet, Cedric; Buser, Lorenz; Wild, Peter; Tang, Dave; Camenzind, Peter; Ho, Chien Hsien; Otto, Vivianne I; Detmar, Michael

2017-06-01

Bladder cancer is a frequently recurring disease with a very poor prognosis once progressed to invasive stages, and tumour-associated blood vessels play a crucial role in this process. In order to identify novel biomarkers associated with progression, we isolated blood vascular endothelial cells (BECs) from human invasive bladder cancers and matched normal bladder tissue, and found that tumour-associated BECs greatly up-regulated the expression of insulin receptor (INSR). High expression of INSR on BECs of invasive bladder cancers was significantly associated with shorter progression-free and overall survival. Furthermore, increased expression of the INSR ligand IGF-2 in invasive bladder cancers was associated with reduced overall survival. INSR may therefore represent a novel biomarker to predict cancer progression. Mechanistically, we observed pronounced hypoxia in human bladder cancer tissue, and found a positive correlation between the expression of the hypoxia marker gene GLUT1 and vascular INSR expression, indicating that hypoxia drives INSR expression in tumour-associated blood vessels. In line with this, exposure of cultured BECs and human bladder cancer cell lines to hypoxia led to increased expression of INSR and IGF-2, respectively, and IGF-2 increased BEC migration through the activation of INSR in vitro. Taken together, we identified vascular INSR expression as a potential biomarker for progression in bladder cancer. Furthermore, our data suggest that IGF-2/INSR mediated paracrine crosstalk between bladder cancer cells and endothelial cells is functionally involved in tumour angiogenesis and may thus represent a new therapeutic target. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Diagnostic and Prognostic Significance of Serum and Tissue Galectin 3 Expression in Patients with Carcinoma of the Bladder

PubMed Central

Gendy, Hoda El; Madkour, Bothina; Abdelaty, Sara; Essawy, Fayza; Khattab, Dina; Hammam, Olfat; Nour, Hani H.

2014-01-01

Background Galectins are group of proteins found in the cytoplasm, nucleus, cell surface and extracellular matrix. Galectin 3 (Gal-3) displays pathological expression in a variety of processes such as tumorigenesis. Patients and Method 70 patients classified into the control group, cystitis group, transitional cell carcinoma group, and squamous cell carcinoma group were enrolled in this study which aimed to detect the serum level and the intensity of tissue expression of Gal-3. Results Both serum level and tissue expression of Gal-3 were statistically higher in bladder cancer patients compared to the other groups. Gal-3 level expression increased from low to high grade urothelial tumors, with a statistically significant increase of its level and expression between muscle invasive and non-muscle invasive Ta urothelial tumors. Conclusion The serum Gal-3 level is sensitive and specific for the diagnosis of bladder cancer. The prognostic significance of tissue expression is to be confirmed. PMID:26195948

Homing peptide guiding optical molecular imaging for the diagnosis of bladder cancer

NASA Astrophysics Data System (ADS)

Yang, Xiao-feng; Pang, Jian-zhi; Liu, Jie-hao; Zhao, Yang; Jia, Xing-you; Li, Jun; Liu, Reng-xin; Wang, Wei; Fan, Zhen-wei; Zhang, Zi-qiang; Yan, San-hua; Luo, Jun-qian; Zhang, Xiao-lei

2014-11-01

Background: The limitations of primary transurethral resection of bladder tumor (TURBt) have led the residual tumors rates as high as 75%. The intraoperative fluorescence imaging offers a great potential for improving TURBt have been confirmed. So we aim to distinguish the residual tumors and normal mucosa using fluorescence molecular imaging formed by conjugated molecule of the CSNRDARRC bladder cancer homing peptide with fluorescent dye. The conjugated molecule was abbreviated FIuo-ACP. In our study, we will research the image features of FIuo-ACP probe targeted bladder cancer for fluorescence molecular imaging diagnosis for bladder cancer in vivo and ex vivo. Methods: After the FIuo-ACP probe was synthetized, the binding sites, factors affecting binding rates, the specificity and the targeting of Fluo-ACP labeled with bladder cancer cells were studied respectively by laser scanning confocal microscope (LSCM), immunofluorescence and multispectral fluorescence ex vivo optical molecular imaging system. Results: The binding sites were located in nucleus and the binding rates were correlated linearly with the dose of probe and the grade of pathology. Moreover, the probe has a binding specificity with bladder cancer in vivo and ex vivo. Tumor cells being labeled by the Fluo-ACP, bright green spots were observed under LSCM. The tissue samples and tumor cells can be labeled and identified by fluorescence microscope. Optical molecular imaging of xenograft tumor tissues was exhibited as fluorescent spots under EMCCD. Conclusion: The CSNRDARRC peptides might be a useful bladder cancer targeting vector. The FIuo-ACP molecular probe was suitable for fluorescence molecular imaging diagnosis for bladder cancer in vivo and ex vivo.

Carcinoma transverse colon masquerading as carcinoma gall bladder

PubMed Central

Kumar, Ashwani; Singh, Harnam; Singh, Gurpreet; Singh, Bimaljot; Chauhan, Mahak

2014-01-01

Colorectal cancer is one of the most common cancer worldwide .Its incidence is reported to be increasing in developing countries. It commonly presents with weight loss, anaemia, lump abdomen, change of bowel habit, obstruction or fresh rectal bleeding. Beside these common modes of presentations, there are some rare manifestations which masqueraded as different disease like obstructive jaundice, empyema gall bladder or cholecystitis. A 60-year-old male presented to hospital with right sided pain abdomen. On abdominal examination mild tenderness was present in right hypochondrium. Intra operatively gall bladder was separated from the adjoining gut, peritoneum and liver bed and was removed. On further exploration, there was a large mass in the vicinity of the gall bladder related to transverse colon. Extended right hemicolectomy was done. Histopathological examination of gut mass revealed adenocarcinoma of transverse colon with free margins and gall bladder showed cholecystitis with no evidence of malignancy. We present an interesting case of colon cancer colon that caused diagnostic confusion by mimicking as cholecystitis. Colorectal cancer constitutes a major public health issue globally. Therefore, public awareness, screening of high-risk populations, early diagnosis and effective treatment and follow-up will help to reduce its occurance and further complications. PMID:24772345

Carcinoma transverse colon masquerading as carcinoma gall bladder.

PubMed

Munghate, Anand; Kumar, Ashwani; Singh, Harnam; Singh, Gurpreet; Singh, Bimaljot; Chauhan, Mahak

2014-04-01

Colorectal cancer is one of the most common cancer worldwide .Its incidence is reported to be increasing in developing countries. It commonly presents with weight loss, anaemia, lump abdomen, change of bowel habit, obstruction or fresh rectal bleeding. Beside these common modes of presentations, there are some rare manifestations which masqueraded as different disease like obstructive jaundice, empyema gall bladder or cholecystitis. A 60-year-old male presented to hospital with right sided pain abdomen. On abdominal examination mild tenderness was present in right hypochondrium. Intra operatively gall bladder was separated from the adjoining gut, peritoneum and liver bed and was removed. On further exploration, there was a large mass in the vicinity of the gall bladder related to transverse colon. Extended right hemicolectomy was done. Histopathological examination of gut mass revealed adenocarcinoma of transverse colon with free margins and gall bladder showed cholecystitis with no evidence of malignancy. We present an interesting case of colon cancer colon that caused diagnostic confusion by mimicking as cholecystitis. Colorectal cancer constitutes a major public health issue globally. Therefore, public awareness, screening of high-risk populations, early diagnosis and effective treatment and follow-up will help to reduce its occurance and further complications.

Bladder welding in rats using controlled temperature CO2 laser system.

PubMed

Lobik, L; Ravid, A; Nissenkorn, I; Kariv, N; Bernheim, J; Katzir, A

1999-05-01

Laser tissue welding has potential advantages over conventional suture closure of surgical wounds. It is a noncontact technique that introduces no foreign body and limits the possibility of infections and complications. The closure could be immediately watertight and the procedure may be less traumatic, faster and easier. In spite of these positives laser welding has not yet been approved for wide use. The problem in the clinical implementation of this technique arises from the difficulty in defining the conditions under which a highly reliable weld is formed. We have assumed that the successful welding of tissues depends on the ability to monitor and control the surface temperature during the procedure, thereby avoiding underheating or overheating. The purpose of this work was to develop a laser system for reliable welding of urinary tract tissues under good temperature control. We have developed a "smart" laser system that is capable of a dual role: transmitting CO2 laser power for tissue heating, and noncontact (radiometric) temperature monitoring and control. Bladder opening (cystotomy) was performed in 38 rats. Thirty-three animals underwent laser welding. In 5 rats (control group) the bladder wound was closed with one layer of continuous 6-0 dexon sutures. Reliable welding was obtained when the surface temperature was kept at 71 + 5C. Quality of weld was controlled immediately after operation. The rats were sacrificed on days 2, 10 and 30 for histological study. Bladder closure using the laser welding system was successful in 31/33 (94%) animals. Histological examination revealed an excellent welding and healing of the tissue. Efficiency of laser welding of urinary bladder in rats was confirmed by high survival rate and quality of scar that was demonstrated by clinical and histological examinations. In the future, optimal laser welding conditions will be studied in larger animals, using CO2 lasers and other lasers, with deeper radiation penetration into tissues.

In vivo magnetic resonance imaging of type I collagen scaffold in rat: improving visualization of bladder and subcutaneous implants.

PubMed

Sun, Yi; Geutjes, Paul; Oosterwijk, Egbert; Heerschap, Arend

2014-12-01

Noninvasive monitoring of implanted scaffolds is important to understand their behavior and role in tissue engineering, in particular to follow their degradation and interaction with host tissue. Magnetic resonance imaging (MRI) is well suited for this goal, but its application is often hampered by the low contrast of scaffolds that are prepared from biomaterials such as type I collagen. The aim of this study was to test iron oxide particles incorporation in improving their MRI contrasts, and to follow their degradation and tissue interactions. Scaffolds with and without iron oxide particles were implanted either subcutaneously or on the bladder of rats. At predetermined time points, in vivo MRI were obtained and tissues were then harvested for histology analysis and transmission electron microscopy. The result showed that the incorporation of iron oxide particles improved MRI contrast of the implants, providing information on their location, shapes, and degradation. Second, the host tissue reaction to the type I collagen implants could be observed in both MRI and histology. Finally, MRI also revealed that the degradation and host tissue reaction of iron particles-loaded scaffolds differed between subcutaneous and bladder implantation, which was substantiated by histology.

Differential diagnosis between benign and malignant soft tissue tumors utilizing ultrasound parameters.

PubMed

Morii, Takeshi; Kishino, Tomonori; Shimamori, Naoko; Motohashi, Mitsue; Ohnishi, Hiroaki; Honya, Keita; Aoyagi, Takayuki; Tajima, Takashi; Ichimura, Shoichi

2018-01-01

Preoperative discrimination between benign and malignant soft tissue tumors is critical for the prevention of excess application of magnetic resonance imaging and biopsy as well as unplanned resection. Although ultrasound, including power Doppler imaging, is an easy, noninvasive, and cost-effective modality for screening soft tissue tumors, few studies have investigated reliable discrimination between benign and malignant soft tissue tumors. To establish a modality for discrimination between benign and malignant soft tissue tumors using ultrasound, we extracted the significant risk factors for malignancy based on ultrasound information from 40 malignant and 56 benign pathologically diagnosed soft tissue tumors and established a scoring system based on these risk factors. The maximum size, tumor margin, and vascularity evaluated using ultrasound were extracted as significant risk factors. Using the odds ratio from a multivariate regression model, a scoring system was established. Receiver operating characteristic analyses revealed a high area under the curve value (0.85), confirming the accuracy of the scoring system. Ultrasound is a useful modality for establishing the differential diagnosis between benign and malignant soft tissue tumors.

Frequency of CD4+CD25+Foxp3+ cells in peripheral blood in relation to urinary bladder cancer malignancy indicators before and after surgical removal.

PubMed

Jóźwicki, Wojciech; Brożyna, Anna A; Siekiera, Jerzy; Slominski, Andrzej T

2016-03-08

Tumor cells communicate with stromal cells, including cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs), to form microenvironment inhibiting immune responses. Regulatory T cells (Tregs, CD4+CD25+FoxP3+) stimulate immune tolerance and facilitate tumor progression. We analyzed the changes in Treg frequencies assessed using flow cytometry in the peripheral blood of patients with urothelial bladder cancer before and after tumor-removal. Changes in Treg frequency were investigated in relation to clinicopathomorphological indicators of tumor malignancy and expression of RCAS1 on CAFs and TAMs. Higher Treg frequencies were observed in early phase of tumor growth (pTa-pT2), in larger tumors, with more aggressive type of invasion, and with expression of RCAS1. The later phase of tumor development, accompanied by a nonclassic differentiations and pT3-pT4 advancement, had lower number of tumor infiltrating lymphocytes (TILs) and lower Treg frequency. Furthermore, in pT2-pT4 tumors, a decreased post-surgery Treg frequency was associated with poorer prognosis: patients with the lowest frequency of Tregs died first. These findings strongly suggest that the Treg frequencies at later phase of tumor growth, associated with a low anti-tumor response, represent a new and important prognostic indicator in urinary bladder cancer.

[Bladder-conserving treatment for bladder cancer: potential of and developments in radiotherapy].

PubMed

Hulshof, Maarten C C M; Pieters, Bradley R; Koning, Caro C E

2013-01-01

The standard treatment for muscle-invasive bladder cancer is surgical removal of the bladder and construction of a neobladder. Recently, important improvements have been made in the potential for bladder-conserving treatment using radiotherapy. External beam radiotherapy has undergone technological improvements, as a result of which it is possible to radiate the tumour more precisely while decreasing radiation to healthy tissue. Radiochemotherapy improves local recurrence-free and overall survival compared with radiotherapy alone. The results of this combined treatment are comparable with those of surgery. Additionally, Dutch radiotherapy departments have collected data in a national database of 1040 selected patients with confined bladder cancer. These patients were treated with external beam radiation, limited surgery and brachytherapy. The 5-year local recurrence-free survival was 75%. Bladder conserving treatment options for muscle-invasive bladder cancer should be discussed during the multidisciplinary meeting.

Observation, Radiation Therapy, Combination Chemotherapy, and/or Surgery in Treating Young Patients With Soft Tissue Sarcoma

ClinicalTrials.gov

2017-09-07

Adult Alveolar Soft-part Sarcoma; Adult Angiosarcoma; Adult Epithelioid Sarcoma; Adult Extraskeletal Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Fibrous Histiocytoma; Adult Malignant Hemangiopericytoma; Adult Malignant Mesenchymoma; Adult Neurofibrosarcoma; Adult Synovial Sarcoma; Childhood Alveolar Soft-part Sarcoma; Childhood Angiosarcoma; Childhood Epithelioid Sarcoma; Childhood Fibrosarcoma; Childhood Leiomyosarcoma; Childhood Liposarcoma; Childhood Malignant Mesenchymoma; Childhood Neurofibrosarcoma; Childhood Synovial Sarcoma; Dermatofibrosarcoma Protuberans; Metastatic Childhood Soft Tissue Sarcoma; Nonmetastatic Childhood Soft Tissue Sarcoma; Stage I Adult Soft Tissue Sarcoma; Stage II Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

Dosimetric comparison of intensity modulated radiotherapy and three-dimensional conformal radiotherapy in patients with gynecologic malignancies: a systematic review and meta-analysis

PubMed Central

2012-01-01

Background To quantitatively evaluate the safety and related-toxicities of intensity modulated radiotherapy (IMRT) dose–volume histograms (DVHs), as compared to the conventional three-dimensional conformal radiotherapy (3D-CRT), in gynecologic malignancy patients by systematic review of the related publications and meta-analysis. Methods Relevant articles were retrieved from the PubMed, Embase, and Cochrane Library databases up to August 2011. Two independent reviewers assessed the included studies and extracted data. Pooled average percent irradiated volumes of adjacent non-cancerous tissues were calculated and compared between IMRT and 3D-CRT for a range of common radiation doses (5-45Gy). Results In total, 13 articles comprised of 222 IMRT-treated and 233 3D-CRT-treated patients were included. For rectum receiving doses ≥30 Gy, the IMRT pooled average irradiated volumes were less than those from 3D-CRT by 26.40% (30 Gy, p = 0.004), 27.00% (35 Gy, p = 0.040), 37.30% (40 Gy, p = 0.006), and 39.50% (45 Gy, p = 0.002). Reduction in irradiated small bowel was also observed for IMRT-delivered 40 Gy and 45 Gy (by 17.80% (p = 0.043) and 17.30% (p = 0.012), respectively), as compared with 3D-CRT. However, there were no significant differences in the IMRT and 3D-CRT pooled average percent volumes of irradiated small bowel or rectum from lower doses, or in the bladder or bone marrow from any of the doses. IMRT-treated patients did not experience more severe acute or chronic toxicities than 3D-CRT-treated patients. Conclusions IMRT-delivered high radiation dose produced significantly less average percent volumes of irradiated rectum and small bowel than 3D-CRT, but did not differentially affect the average percent volumes in the bladder and bone marrow. PMID:23176540

Polymorphic Expression of a Human Superficial Bladder Tumor Antigen Defined by Mouse Monoclonal Antibodies

NASA Astrophysics Data System (ADS)

Fradet, Yves; Islam, Nazrul; Boucher, Lucie; Parent-Vaugeois, Carmen; Tardif, Marc

1987-10-01

Three mouse monoclonal antibodies (mAbs), which define a highly restricted antigen, were obtained by simultaneous immunizations with superficial papillary bladder tumor cells and mouse polyclonal serum against normal urothelium. The antigen was detected by the avidin/biotin/peroxidase method in 30/44 superficial bladder tumors (68%) but in only 4/27 infiltrating urothelial cancers (with much less intensity). No normal adult or fetal tissues tested expressed the antigen, including normal urothelium from 40 individuals, 13 of whom had a bladder tumor positive for the antigen. Only 1 of 45 nonbladder tumors showed some reactivity with one of the three mAbs. Serological tests on a large panel of human cancer cell lines and normal cultured cells were negative. The antigen is highly stable and well preserved on paraffin-embedded tissues. Electrophoretic transfer blot experiments with fresh tumor extracts showed that all three mAbs react with a determinant on a component of 300,000 Mr (pI 9.5) and 62,000 Mr (pI 6.5). The antigen shows polymorphic expression at the cellular level on tissue sections and also at a molecular level on immunoblots where the two bands are differentially detected on extracts of a series of tumors but are not visualized on normal urothelium extracts. The characteristics of this antigenic system suggest that it may provide some insights about the biology of bladder cancer. Specific detection of the antigen on 70% of superficial bladder tumors with normal cytology may be useful for their diagnosis and follow-up.

Tissue engineering for human urethral reconstruction: systematic review of recent literature.

PubMed

de Kemp, Vincent; de Graaf, Petra; Fledderus, Joost O; Ruud Bosch, J L H; de Kort, Laetitia M O

2015-01-01

Techniques to treat urethral stricture and hypospadias are restricted, as substitution of the unhealthy urethra with tissue from other origins (skin, bladder or buccal mucosa) has some limitations. Therefore, alternative sources of tissue for use in urethral reconstructions are considered, such as ex vivo engineered constructs. To review recent literature on tissue engineering for human urethral reconstruction. A search was made in the PubMed and Embase databases restricted to the last 25 years and the English language. A total of 45 articles were selected describing the use of tissue engineering in urethral reconstruction. The results are discussed in four groups: autologous cell cultures, matrices/scaffolds, cell-seeded scaffolds, and clinical results of urethral reconstructions using these materials. Different progenitor cells were used, isolated from either urine or adipose tissue, but slightly better results were obtained with in vitro expansion of urothelial cells from bladder washings, tissue biopsies from the bladder (urothelium) or the oral cavity (buccal mucosa). Compared with a synthetic scaffold, a biological scaffold has the advantage of bioactive extracellular matrix proteins on its surface. When applied clinically, a non-seeded matrix only seems suited for use as an onlay graft. When a tubularized substitution is the aim, a cell-seeded construct seems more beneficial. Considerable experience is available with tissue engineering of urethral tissue in vitro, produced with cells of different origin. Clinical and in vivo experiments show promising results.

A case of large cell neuroendocrine carcinoma of the bladder with prolonged spontaneous remission

PubMed Central

Chong, Vincent; Zwi, Jonathan; Hanning, Fritha; Lim, Remy; Cadwallader, Jon

2017-01-01

Abstract Large cell neuroendocrine carcinoma (LCNEC) of the urinary bladder are rare. We present a case of a 72-year-old man who presented with back pain and acute renal failure. Ultrasound showed a soft tissue mass in the base of the bladder causing bilateral ureteric obstruction. Subsequent biopsy of this mass demonstrated neuroendocrine carcinoma. He was commenced on neoadjuvant chemotherapy (carboplatin/etoposide) and proceeded to a radical cysto-prostatectomy. Histology revealed a LCNEC involving the bladder, T4a with invasion through to adipose tissue and posteriorly at perivesical resection margins. In addition, there was a Gleason score 9 prostatic adenocarcinoma, distinct from the neuroendocrine carcinoma. Following surgery, the patient developed gross local-regional recurrence and refused further systemic therapy. However, 1 year following referral to palliative care, a further CT-PET showed complete spontaneous remission of his disease. There are only few case reports of LCNEC of the urinary bladder therefore the pathogenesis and treatment protocol are still unclear. This case report highlights the unpredictable nature of this disease. PMID:28560016

A case of large cell neuroendocrine carcinoma of the bladder with prolonged spontaneous remission.

PubMed

Chong, Vincent; Zwi, Jonathan; Hanning, Fritha; Lim, Remy; Williams, Andrew; Cadwallader, Jon

2017-05-01

Large cell neuroendocrine carcinoma (LCNEC) of the urinary bladder are rare. We present a case of a 72-year-old man who presented with back pain and acute renal failure. Ultrasound showed a soft tissue mass in the base of the bladder causing bilateral ureteric obstruction. Subsequent biopsy of this mass demonstrated neuroendocrine carcinoma. He was commenced on neoadjuvant chemotherapy (carboplatin/etoposide) and proceeded to a radical cysto-prostatectomy. Histology revealed a LCNEC involving the bladder, T4a with invasion through to adipose tissue and posteriorly at perivesical resection margins. In addition, there was a Gleason score 9 prostatic adenocarcinoma, distinct from the neuroendocrine carcinoma. Following surgery, the patient developed gross local-regional recurrence and refused further systemic therapy. However, 1 year following referral to palliative care, a further CT-PET showed complete spontaneous remission of his disease. There are only few case reports of LCNEC of the urinary bladder therefore the pathogenesis and treatment protocol are still unclear. This case report highlights the unpredictable nature of this disease.

An Optimized Set of Fluorescence In Situ Hybridization Probes for Detection of Pancreatobiliary Tract Cancer in Cytology Brush Samples.

PubMed

Barr Fritcher, Emily G; Voss, Jesse S; Brankley, Shannon M; Campion, Michael B; Jenkins, Sarah M; Keeney, Matthew E; Henry, Michael R; Kerr, Sarah M; Chaiteerakij, Roongruedee; Pestova, Ekaterina V; Clayton, Amy C; Zhang, Jun; Roberts, Lewis R; Gores, Gregory J; Halling, Kevin C; Kipp, Benjamin R

2015-12-01

Pancreatobiliary cancer is detected by fluorescence in situ hybridization (FISH) of pancreatobiliary brush samples with UroVysion probes, originally designed to detect bladder cancer. We designed a set of new probes to detect pancreatobiliary cancer and compared its performance with that of UroVysion and routine cytology analysis. We tested a set of FISH probes on tumor tissues (cholangiocarcinoma or pancreatic carcinoma) and non-tumor tissues from 29 patients. We identified 4 probes that had high specificity for tumor vs non-tumor tissues; we called this set of probes pancreatobiliary FISH. We performed a retrospective analysis of brush samples from 272 patients who underwent endoscopic retrograde cholangiopancreatography for evaluation of malignancy at the Mayo Clinic; results were available from routine cytology and FISH with UroVysion probes. Archived residual specimens were retrieved and used to evaluate the pancreatobiliary FISH probes. Cutoff values for FISH with the pancreatobiliary probes were determined using 89 samples and validated in the remaining 183 samples. Clinical and pathologic evidence of malignancy in the pancreatobiliary tract within 2 years of brush sample collection was used as the standard; samples from patients without malignancies were used as negative controls. The validation cohort included 85 patients with malignancies (46.4%) and 114 patients with primary sclerosing cholangitis (62.3%). Samples containing cells above the cutoff for polysomy (copy number gain of ≥2 probes) were classified as positive in FISH with the UroVysion and pancreatobiliary probes. Multivariable logistic regression was used to estimate associations between clinical and pathology findings and results from FISH. The combination of FISH probes 1q21, 7p12, 8q24, and 9p21 identified cancer cells with 93% sensitivity and 100% specificity in pancreatobiliary tissue samples and were therefore included in the pancreatobiliary probe set. In the validation cohort of brush samples, pancreatobiliary FISH identified samples from patients with malignancy with a significantly higher level of sensitivity (64.7%) than the UroVysion probes (45.9%) (P < .001) or routine cytology analysis (18.8%) (P < .001), but similar specificity (92.9%, 90.8%, and 100.0% respectively). Factors significantly associated with detection of carcinoma, in adjusted analyses, included detection of polysomy by pancreatobiliary FISH (P < .001), a mass by cross-sectional imaging (P < .001), cancer cells by routine cytology (overall P = .003), as well as absence of primary sclerosing cholangitis (P = .011). We identified a set of FISH probes that detects cancer cells in pancreatobiliary brush samples from patients with and without primary sclerosing cholangitis with higher levels of sensitivity than UroVysion probes. Cytologic brushing test results and clinical features were independently associated with detection of cancer and might be used to identify patients with pancreatobiliary cancers. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Oncogenic Activation of Fibroblast Growth Factor Receptor-3 and RAS Genes as Non-Overlapping Mutual Exclusive Events in Urinary Bladder Cancer.

PubMed

Pandith, Arshad A; Hussain, Aashaq; Khan, Mosin S; Shah, Zafar A; Wani, M Saleem; Siddiqi, Mushtaq A

2016-01-01

Urinary bladder cancer is a common malignancy in the West and ranks as the 7th most common cancer in our region of Kashmir, India. FGFR3 mutations are frequent in superficial urothelial carcinoma (UC) differing from the RAS gene mutational pattern. The aim of this study was to analyze the frequency and association of FGFR3 and RAS gene mutations in UC cases. Paired tumor and adjacent normal tissue specimens of 65 consecutive UC patients were examined. DNA preparations were evaluated for the occurrence of FGFR3 and RAS gene mutations by PCR-SCCP and DNA sequencing. Somatic point mutations of FGFR3 were identified in 32.3% (21 of 65). The pattern and distribution were significantly associated with low grade/stage (<0.05). The overall mutations in exon 1 and 2 in all the forms of RAS genes aggregated to 21.5% and showed no association with any clinic-pathological parameters. In total, 53.8% (35 of 65) of the tumors studied had mutations in either a RAS or FGFR3 gene, but these were totally mutually exclusive in and none of the samples showed both the mutational events in mutually exclusive RAS and FGFR3. We conclude that RAS and FGFR3 mutations in UC are mutually exclusive and non-overlapping events which reflect activation of oncogenic pathways through different elements.

Vesicoureteral reflux in children: a phantom study of microwave heating and radiometric thermometry of pediatric bladder.

PubMed

Birkelund, Yngve; Klemetsen, Øystein; Jacobsen, Svein K; Arunachalam, Kavitha; Maccarini, Paolo; Stauffer, Paul R

2011-11-01

We have investigated the use of microwave heating and radiometry to safely heat urine inside a pediatric bladder. The medical application for this research is to create a safe and reliable method to detect vesicoureteral reflux, a pediatric disorder, where urine flow is reversed and flows from the bladder back up into the kidney. Using fat and muscle tissue models, we have performed both experimental and numerical simulations of a pediatric bladder model using planar dual concentric conductor microstrip antennas at 915 MHz for microwave heating. A planar elliptical antenna connected to a 500 MHz bandwidth microwave radiometer centered at 3.5 GHz was used for noninvasive temperature measurement inside tissue. Temperatures were measured in the phantom models at points during the experiment with implanted fiberoptic sensors, and 2-D distributions in cut planes at depth in the phantom with an infrared camera at the end of the experiment. Cycling between 20 s with 20 Watts power for heating, and 10 s without power to allow for undisturbed microwave radiometry measurements, the experimental results show that the target tissue temperature inside the phantom increases fast and that the radiometer provides useful measurements of spatially averaged temperature of the illuminated volume. The presented numerical and experimental results show excellent concordance, which confirms that the proposed system for microwave heating and radiometry is applicable for safe and reliable heating of pediatric bladder.

A Dose Escalation Study in Adult Patients With Advanced Solid Malignancies

ClinicalTrials.gov

2018-06-05

Advanced Solid Tumors With Alterations of FGFR1, 2 and or 3; Squamous Lung Cancer With FGFR1 Amplification; Bladder Cancer With FGFR3 Mutation or Fusion; Advanced Solid Tumors With FGFR1 Amplication; Advanced Solid Tumors With FGFR2 Amplication; Advanced Solid Tumors With FGFR3 Mutation

Dielectric properties of human normal, malignant and cirrhotic liver tissue: in vivo and ex vivo measurements from 0.5 to 20 GHz using a precision open-ended coaxial probe.

PubMed

O'Rourke, Ann P; Lazebnik, Mariya; Bertram, John M; Converse, Mark C; Hagness, Susan C; Webster, John G; Mahvi, David M

2007-08-07

Hepatic malignancies have historically been treated with surgical resection. Due to the shortcomings of this technique, there is interest in other, less invasive, treatment modalities, such as microwave hepatic ablation. Crucial to the development of this technique is the accurate knowledge of the dielectric properties of human liver tissue at microwave frequencies. To this end, we characterized the dielectric properties of in vivo and ex vivo normal, malignant and cirrhotic human liver tissues from 0.5 to 20 GHz. Analysis of our data at 915 MHz and 2.45 GHz indicates that the dielectric properties of ex vivo malignant liver tissue are 19 to 30% higher than normal tissue. The differences in the dielectric properties of in vivo malignant and normal liver tissue are not statistically significant (with the exception of effective conductivity at 915 MHz, where malignant tissue properties are 16% higher than normal). Also, the dielectric properties of in vivo normal liver tissue at 915 MHz and 2.45 GHz are 16 to 43% higher than ex vivo. No statistically significant differences were found between the dielectric properties of in vivo and ex vivo malignant tissue (with the exception of effective conductivity at 915 MHz, where malignant tissue properties are 28% higher than normal). We report the one-pole Cole-Cole parameters for ex vivo normal, malignant and cirrhotic liver tissue in this frequency range. We observe that wideband dielectric properties of in vivo liver tissue are different from the wideband dielectric properties of ex vivo liver tissue, and that the in vivo data cannot be represented in terms of a Cole-Cole model. Further work is needed to uncover the mechanisms responsible for the observed wideband trends in the in vivo liver data.

Tissue-mimicking bladder wall phantoms for evaluating acoustic radiation force-optical coherence elastography systems.

PubMed

Ejofodomi, O'tega A; Zderic, Vesna; Zara, Jason M

2010-04-01

Acoustic radiation force-optical coherence elastography (ARF-OCE) systems are novel imaging systems that have the potential to simultaneously quantify and characterize the optical and mechanical properties of in vivo tissues. This article presents the construction of bladder wall phantoms for use in ARF-OCE systems. Mechanical, acoustic, and optical properties are reported and compared to published values for the urinary bladder. The phantom consisted of 0.2000 +/- 0.0089 and 6.0000 +/- 0.2830 microm polystyrene microspheres (Polysciences Inc., Warrington, PA, Catalog Nos. 07304 and 07312), 7.5 +/- 1.5 microm copolymer microspheres composed of acrylonitrile and vinylidene chloride, (Expancel, Duluth, GA, Catalog No. 461 DU 20), and bovine serum albumin within a gelatin matrix. Young's modulus was measured by successive compression of the phantom and obtaining the slope of the resulting force-displacement data. Acoustic measurements were performed using the transmission method. The phantoms were submerged in a water bath and placed between transmitting and receiving 13 mm diameter unfocused transducers operating at a frequency of 3.5 MHz. A MATLAB algorithm to extract the optical scattering coefficient from optical coherence tomography (OCT) images of the phantom was used. The phantoms possess a Young's modulus of 17.12 +/- 2.72 kPa, a mass density of 1.05 +/- 0.02 g/cm3, an acoustic attenuation coefficient of 0.66 +/- 0.08 dB/cm/MHz, a speed of sound of 1591 +/- 8.76 m/s, and an optical scattering coefficient of 1.80 +/- 0.23 mm(-1). Ultrasound and OCT images of the bladder wall phantom are presented. A material that mimics the mechanical, optical, and acoustic properties of healthy bladder wall has been developed. This tissue-mimicking bladder wall phantom was developed as a control tool to investigate the feasibility of using ARF-OCE to detect the mechanical and optical changes that may be indicative of the onset or development of cancer in the urinary bladder. By following the methods used in this article, phantoms matching the optical, acoustic, and mechanical properties of other biological tissues can also be constructed.

Incidence analyses of bladder cancer in the Nile delta region of Egypt

PubMed Central

Fedewa, Stacey A.; Soliman, Amr S.; Ismail, Kadry; Hablas, Ahmed; Seifeldin, Ibrahim A.; Ramadan, Mohamed; Omar, Hoda G.; Nriagu, Jerome; Wilson, Mark L.

2009-01-01

Bladder cancer is the most common malignancy among Egyptian males and previously has been attributed to Schistosoma infection, a major risk factor for squamous cell carcinoma (SCC). Recently, transitional cell carcinoma (TCC) incidence has been increasing while SCC has declined. To investigate this shift, we analyzed the geographical patterns of all bladder cancers cases recorded in Egypt’s Gharbiah Population-Based Cancer Registry from 1999 through 2002. Data on tumor grade, stage, and morphology, as well as smoking, community of residence, age and sex, were collected on 1,209 bladder cancer cases. Age-adjusted incidence rates were calculated for males, females, and the total population for the eight administrative Districts and 316 communities in Gharbiah. Incidence Rate Ratios (IRR) and 95% Confidence Intervals (CI) were computed using Poisson Regression. The male age-adjusted incidence rate (IR) in Gharbiah Province was 13.65/100,000 person years (PY). The District of Kotour had the highest age-adjusted IR 28.96/100,000 among males. The District of Kotour also had the highest IRR among all Districts, IRR=2.15 95% CI (1.72, 2.70). Kotour’s capital city had the highest bladder cancer incidence among the 316 communities (IR=73.11/100,000 PY). Future studies on sources and types of environmental pollution and exposures in relation to the spatial patterns of bladder cancer, particularly in Kotour District, may improve our understating of risk factors for bladder cancer in the region. PMID:19762298

Clinical utility of urinary soluble Fas in screening for bladder cancer.

PubMed

Srivastava, Anupam Kumar; Singh, Pankaj Kumar; Singh, Dhramveer; Dalela, Divakar; Rath, Srikanta Kumar; Bhatt, Madan Lal Brahma

2016-06-01

Early diagnosis of carcinoma of urinary bladder remains a challenge. Urine cytology, as an adjunct to cystoscopy, is less sensitive for low-grade tumors. Soluble Fas (sFas), a cell-surface receptor and member of the tumor necrosis factor superfamily, is frequently expressed in urinary bladder carcinoma. The objective of this study was to investigate the urinary sFas for diagnosis of transitional cell carcinoma (TCC) of urinary bladder. We examined urinary sFas concentration in 74 controls and 117 cases of TCC, both primary and recurrent disease, by using enzyme-linked immunosorbent assay and compared it with urinary cytology. Urinary sFas concentration was found to be significantly higher in the patient as compared to control group (P < 0.05). An optimal cutoff value of 174.0 pg/mL was proposed. The urinary sFas level was found to have an approximate sensitivity and specificity of 88.03% and 89.19% (P < 0.001), whereas urine cytology had sensitivity of 66.67% and specificity of 95.95%. sFas had better sensitivity in higher grade and both primary and recurrent cases of urinary bladder cancer in comparison with cytology. Out of 15 node positive bladder cancer cases, 13 had high urinary sFas levels, whereas 12 were urinary cytology positive for malignancy. Urinary sFas can be used as a non-invasive diagnostic biomarker for TCC of urinary bladder, both for primary and recurrent disease. © 2014 Wiley Publishing Asia Pty Ltd.

Clinical significance and biological roles of CARMA3 in human bladder carcinoma.

PubMed

Man, Xiaojun; He, Jiani; Kong, Chuize; Zhu, Yuyan; Zhang, Zhe

2014-05-01

Caspase recruitment domain and membrane-associated guanylate kinase-like domain protein 3 (CARMA3) was reported as an oncoprotein overexpressed in several cancers. The expression pattern of CARMA3 and its clinical significance in human bladder cancer have not been well characterized. In the present study, CARMA3 expression was analyzed in 90 archived bladder cancer specimens using immunohistochemistry, and the correlation between CARMA3 expression and clinicopathological parameters was evaluated. We found that CARMA3 was overexpressed in 35 of 90 (38.8%) bladder cancer specimens. Significant association was observed between CARMA3 overexpression with tumor status (p = 0.081) and tumor grade (p = 0.027). To further explore the biological functions of CARMA3 in bladder cancer, we depleted CARMA3 in T24 and 5637 cell lines using small interfering RNA (siRNA). Using cell counting kit-8 (CCK8) assay and colony formation assay, we were able to show that CARMA3 depletion inhibited cell proliferation and colony number. Further study demonstrated that CARMA3 depletion decreased an expression of nuclear factor kappa B (NF-κB) targets cyclin D1 and Bcl-2 expression, as well as IκB phosphorylation. Luciferase reporter assay showed that CARMA3 depletion could downregulate NF-κB reporter activity. In conclusion, CARMA3 is overexpressed in bladder cancer and regulates malignant cell growth and NF-κB signaling, which makes CARMA3 a candidate therapeutic target for bladder cancer.

Histone deacetylases (HDACs) in XPC gene silencing and bladder cancer

PubMed Central

2011-01-01

Bladder cancer is one of the most common malignancies and causes hundreds of thousands of deaths worldwide each year. Bladder cancer is strongly associated with exposure to environmental carcinogens. It is believed that DNA damage generated by environmental carcinogens and their metabolites causes development of bladder cancer. Nucleotide excision repair (NER) is the major DNA repair pathway for repairing bulk DNA damage generated by most environmental carcinogens, and XPC is a DNA damage recognition protein required for initiation of the NER process. Recent studies demonstrate reduced levels of XPC protein in tumors for a majority of bladder cancer patients. In this work we investigated the role of histone deacetylases (HDACs) in XPC gene silencing and bladder cancer development. The results of our HDAC inhibition study revealed that the treatment of HTB4 and HTB9 bladder cancer cells with the HDAC inhibitor valproic acid (VPA) caused an increase in transcription of the XPC gene in these cells. The results of our chromatin immunoprecipitation (ChIP) studies indicated that the VPA treatment caused increased binding of both CREB1 and Sp1 transcription factors at the promoter region of the XPC gene for both HTB4 and HTB9 cells. The results of our immunohistochemistry (IHC) staining studies further revealed a strong correlation between the over-expression of HDAC4 and increased bladder cancer occurrence (p < 0.001) as well as a marginal significance of increasing incidence of HDAC4 positivity seen with an increase in severity of bladder cancer (p = 0.08). In addition, the results of our caspase 3 activation studies demonstrated that prior treatment with VPA increased the anticancer drug cisplatin-induced activation of caspase 3 in both HTB4 and HTB9 cells. All of these results suggest that the HDACs negatively regulate transcription of the XPC gene in bladder cancer cells and contribute to the severity of bladder tumors. PMID:21507255

Expression of parathyroid hormone/parathyroid hormone-related peptide receptor 1 in normal and diseased bladder detrusor muscles: a clinico-pathological study.

PubMed

Nishikawa, Nobuyuki; Yago, Rie; Yamazaki, Yuichiro; Negoro, Hiromitsu; Suzuki, Mari; Imamura, Masaaki; Toda, Yoshinobu; Tanabe, Kazunari; Ogawa, Osamu; Kanematsu, Akihiro

2015-01-21

To investigate the expression of parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor 1 (PTH1R) in clinical specimens of normal and diseased bladders. PTHrP is a unique stretch-induced endogenous detrusor relaxant that functions via PTH1R. We hypothesized that suppression of this axis could be involved in the pathogenesis of bladder disease. PTH1R expression in clinical samples was examined by immunohistochemistry. Normal kidney tissue from a patient with renal cancer and bladder specimens from patients undergoing ureteral reimplantation for vesicoureteral reflux or partial cystectomy for urachal cyst were examined as normal control organs. These were compared with 13 diseased bladder specimens from patients undergoing bladder augmentation. The augmentation patients ranged from 8 to 31 years old (median 15 years), including 9 males and 4 females. Seven patients had spinal disorders, 3 had posterior urethral valves and 3 non-neurogenic neurogenic bladders (Hinman syndrome). Renal tubules, detrusor muscle and blood vessels in normal control bladders stained positive for PTH1R. According to preoperative urodynamic studies of augmentation patients, the median percent bladder capacity compared with the age-standard was 43.6% (range 1.5-86.6%), median intravesical pressure at maximal capacity was 30 cmH2O (range 10-107 cmH2O), and median compliance was 3.93 ml/cmH2O (range 0.05-30.3 ml/cmH2O). Detrusor overactivity was observed in five cases (38.5%). All augmented bladders showed negative stainings in PTH1R expression in the detrusor tissue, but positive staining of blood vessels in majority of the cases. Downregulation of PTH1R may be involved in the pathogenesis of human end-stage bladder disease requiring augmentation.

Commentary on "tissue-specific mutagenesis by N-butyl-N-(4-hydroxybutyl) nitrosamine as the basis for urothelial cell carcinogenesis." He Z, Kosinska W, Zhao ZL, Wu XR, Guttenplan JB, Department of Basic Science, New York University Dental College, NY, USA.: Mutat Res 2012;742(1-2):92-5 [Epub 2011 Dec 4].

PubMed

Scherr, Douglas S

2014-02-01

Bladder cancer is one of the few cancers that have been linked to carcinogens in the environment and tobacco smoke. Of the carcinogens tested in mouse chemical carcinogenesis models, N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) is one that reproducibly causes high-grade, invasive cancers in the urinary bladder, but not in any other tissues. However, the basis for such a high-level tissue-specificity has not been explored. Using mutagenesis in lacI (Big Blue™) mice, we show here that BBN is a potent mutagen and it causes high-level of mutagenesis specifically in the epithelial cells (urothelial) of the urinary bladder. After a 2-6-week treatment of 0.05% BBN in the drinking water, mutagenesis in urothelial cells of male and female mice was about two orders of magnitude greater than the spontaneous mutation background. In contrast, mutagenesis in smooth muscle cells of the urinary bladder was about five times lower than in urothelial tissue. No appreciable increase in mutagenesis was observed in kidney, ureter, liver or forestomach. In lacI (Big Blue™) rats, BBN mutagenesis was also elevated in urothelial cells, albeit not nearly as profoundly as in mice. This provides a potential explanation as to why rats are less prone than mice to the formation of aggressive form of bladder cancer induced by BBN. Our results suggest that the propensity to BBN-triggered mutagenesis of urothelial cells underlies its heightened susceptibility to this carcinogen and that mutagenesis induced by BBN represents a novel model for initiation of bladder carcinogenesis. Copyright © 2014 Elsevier Inc. All rights reserved.

An integral theory of female urinary incontinence. Experimental and clinical considerations.

PubMed

Petros, P E; Ulmsten, U I

1990-01-01

In this Theory paper, the complex interplay of the specific structures involved in female urinary continence are analyzed. In addition the effects of age, hormones, and iatrogenically induced scar tissue on these structures, are discussed specifically with regard to understanding the proper basis for treatment of urinary incontinence. According to the Theory stress and urge symptoms may both derive, for different reasons from the same anatomical defect, a lax vagina. This laxity may be caused by defects within the vaginal wall itself, or its supporting structures i.e. ligaments, muscles, and their connective tissue insertions. The vagina has a dual function. It mediates (transmits) the various muscle movements involved in bladder neck opening and closure through three separate closure mechanisms. It also has a structural function, and prevents urgency by supporting the hypothesized stretch receptors at the proximal urethra and bladder neck. Altered collagen/elastin in the vaginal connective tissue and/or its ligamentous supports may cause laxity. This dissipates the muscle contraction, causing stress incontinence, and/or activation of an inappropriate micturition reflex, ("bladder instability") by stimulation of bladder base stretch receptors. The latter is manifested by symptoms of frequency, urgency, nocturia with or without urine loss.

Vasculogenic mimicry in bladder cancer and its association with the aberrant expression of ZEB1

PubMed Central

Li, Baimou; Mao, Xiaopeng; Wang, Hua; Su, Guanyu; Mo, Chengqiang; Cao, Kaiyuan; Qiu, Shaopeng

2018-01-01

The aim of the present study was to investigate the associations between vasculogenic mimicry (VM) and zinc finger E-box binding homeobox 1 (ZEB1) in bladder cancer. VM structure and ZEB1 expression were analyzed by cluster of differentiation 34/periodic acid Schiff (PAS) double staining and immunohistochemical staining in 135 specimens from patients with bladder cancer, and a further 12 specimens from normal bladder tissues. Three-dimensional (3-D) culture was used to detect VM formation in the bladder transitional cancer cell lines UM-UC-3 and J82, and the immortalized human bladder epithelium cell line SV-HUC-1 in vitro. ZEB1 expression in these cell lines was compared by reverse transcription-quantitative polymerase chain reaction and western blot assays. In addition, small interfering RNA was used to inhibit ZEB1 in UM-UC-3 and J82 cells, followed by 3-D culturing of treated cell lines. As a result, VM was observed in 31.1% of specimens from bladder cancer tissues, and cases with high ZEB1 expression accounted for 60.0% of patients with bladder cancer. In addition, ZEB1 expression was closely associated with VM (r=0.189; P<0.05), and also increased as the grade and stage of the tumor developed. In an in vitro assay, UM-UC-3 and J82 cells exhibited VM formation, however, SV-HUC-1 did not. Furthermore, VM-forming cancer cell lines UM-UC-3 and J82 exhibited higher ZEB1 expression. Notably, VM formation was inhibited following knockdown of ZEB1. In conclusion, ZEB1 may be associated with VM in bladder cancer and serve an important role in the process of VM formation. However, its detailed mechanism requires further study. PMID:29552157

The Rare Togetherness of Bladder Leiomyoma and Neurofibromatosis.

PubMed

Yucel, Cem; Budak, Salih; Kisa, Erdem; Celik, Orcun; Kozacioglu, Zafer

2018-01-01

Neurofibromatosis Type 1 (Von Recklinghausen disease) is a common, autosomal dominant hereditary disorder characterized by involvement of multiple tissues derived from the neural crest. Urinary system involvement in neurofibromatosis is a rare condition. Leiomyoma of the bladder is a rare benign mesenchymal tumor. In this case, our experience and approach regarding the bladder leiomyoma development in a patient diagnosed with neurofibromatosis are presented and the literature data has been reviewed.

Fluorescence cystoscopy in the management of bladder cancer: a help for the urologist!

PubMed

Jichlinski, Patrice; Leisinger, Hans-Jurg

2005-01-01

As a disease characterized by a nature polymorphic and fluctuant in its evolution, superficial transitional cell carcinoma of the bladder remains a perpetual therapeutic challenge, and raises a great interest in the development of new diagnostic and surveillance techniques. This paper reviews 10 years of experience of fluorescence cystoscopy, a simple technique perfectly adapted to the current endoscopic equipment. Its principle is to enhance the visual contrast between benign and malignant cells. Three photosensitizing agents are available, two prodrugs: delta-aminolevulinic acid or hexaminolevulinate, and a natural substance: hypericin. With a detection rate of over 90% for carcinoma in situ and a real potential for detecting small tumors overlooked by standard cystoscopy, fluorescence cystoscopy may be clearly recommended in clinical practice. This technique favors a standardization of superficial bladder cancer endoscopic management and is susceptible to have a real impact on the disease recurrence and progression rate.

The role of micronutrients in the risk of urinary tract cancer

PubMed Central

Bukowczan, Jakub; Sobczynski, Robert; Leszczyszyn, Jaroslaw; Chlosta, Piotr L.

2016-01-01

Prostate, bladder and kidney cancers remain the most common urological malignancies worldwide, and the prevention and treatment of these diseases pose a challenge to clinicians. In recent decades, many studies have been conducted to assess the association between supplementation with selected vitamins and elements and urinary tract tumour initiation and development. Here, we review the relationship between vitamins A, B, D, and E, in addition to calcium, selenium, and zinc, and the risk of developing prostate, kidney and bladder cancer. A relatively consistent body of evidence suggests that large daily doses of calcium (> 2,000 mg/day) increase the risk of prostate cancer. Similarly, supplementation with 400 IU/day of vitamin E carries a significant risk of prostate cancer. However, there have been many conflicting results regarding the effect of these nutrients on kidney and bladder neoplasms. Moreover, the role of other compounds in urinary tract carcinogenesis needs further clarification. PMID:27186192

Multilayered disease-mimicking bladder phantom with realistic surface topology for optical coherence tomography

NASA Astrophysics Data System (ADS)

Smith, Gennifer T.; Lurie, Kristen L.; Khan, Saara A.; Liao, Joseph C.; Ellerbee, Audrey K.

2014-03-01

Optical coherence tomography (OCT) has shown potential as a complementary modality to white light cystoscopy (WLC), the gold standard for imaging bladder cancer. OCT can visualize sub-surface details of the bladder wall, which enables it to stage cancers and detect tumors that are otherwise invisible to WLC. Currently, OCT systems have too slow a speed and too small a field of view for comprehensive bladder imaging, which limits its clinical utility. Validation and feasibility testing of technological refinements aimed to provide faster imaging and wider fields of view necessitates a realistic bladder phantom. We present a novel process to fabricate the first such phantom that mimics both the optical and morphological properties of layers of the healthy and pathologic bladder wall as they characteristically appear with OCT. The healthy regions of the silicone-based phantom comprises three layers: the urothelium, lamina propria and muscularis propria, each containing an appropriate concentration of titanium dioxide to mimic its distinct scattering properties. As well, the layers each possess a unique surface appearance imposed by a textured mold. Within this phantom, pathologic tissue-mimicking regions are created by thickening specific layers or creating inclusions that disrupt the layered appearance of the bladder wall, as is characteristic of bladder carcinomas. This phantom can help to evaluate the efficacy of new OCT systems and software for tumor localization. Moreover, the procedure we have developed is highly generalizable for the creation of OCT-relevant, multi-layer phantoms for tissues that incorporate diseased states characterized by the loss of layered structures.

Functional expression of KCNQ (Kv7) channels in guinea pig bladder smooth muscle and their contribution to spontaneous activity

PubMed Central

Anderson, U A; Carson, C; Johnston, L; Joshi, S; Gurney, A M; McCloskey, K D

2013-01-01

Background and Purpose The aim of the study was to determine whether KCNQ channels are functionally expressed in bladder smooth muscle cells (SMC) and to investigate their physiological significance in bladder contractility. Experimental Approach KCNQ channels were examined at the genetic, protein, cellular and tissue level in guinea pig bladder smooth muscle using RT-PCR, immunofluorescence, patch-clamp electrophysiology, calcium imaging, detrusor strip myography, and a panel of KCNQ activators and inhibitors. Key Results KCNQ subtypes 1–5 are expressed in bladder detrusor smooth muscle. Detrusor strips typically displayed TTX-insensitive myogenic spontaneous contractions that were increased in amplitude by the KCNQ channel inhibitors XE991, linopirdine or chromanol 293B. Contractility was inhibited by the KCNQ channel activators flupirtine or meclofenamic acid (MFA). The frequency of Ca2+-oscillations in SMC contained within bladder tissue sheets was increased by XE991. Outward currents in dispersed bladder SMC, recorded under conditions where BK and KATP currents were minimal, were significantly reduced by XE991, linopirdine, or chromanol, and enhanced by flupirtine or MFA. XE991 depolarized the cell membrane and could evoke transient depolarizations in quiescent cells. Flupirtine (20 μM) hyperpolarized the cell membrane with a simultaneous cessation of any spontaneous electrical activity. Conclusions and Implications These novel findings reveal the role of KCNQ currents in the regulation of the resting membrane potential of detrusor SMC and their important physiological function in the control of spontaneous contractility in the guinea pig bladder. PMID:23586426

Increased expression of sex determining region Y-box 11 (SOX11) in cutaneous malignant melanoma.

PubMed

Jian, Jiao; Guoying, Wang; Jing, Zhao

2013-08-01

To observe sex determining region Y-box 11 (SOX11) gene expression in cutaneous malignant melanoma and its effect on tumour cell proliferation. Clinicopathological data and tissue samples from patients with cutaneous malignant melanoma, together with tissue samples from healthy volunteers (controls), were retrospectively reviewed. Protein levels of SOX11 and the antigen identified by monoclonal antibody Ki-67 (Ki-67) in skin lesions were analysed using immunohistochemistry. The correlation between protein levels and clinipathological parameters was investigated. Out of 40 patient samples, 25 (62.5%) were positive for SOX11 protein in malignant melanoma tissue. This was significantly higher than in 40 control tissue samples, in which no SOX11 protein was detected. Presence of SOX11 protein was positively related to the proliferation index of cutaneous malignant melanoma tumour cells. Presence of SOX11 protein in cutaneous malignant melanoma was related to tumour type, tumour location, lymph node metastasis and 5-year survival rate. Human cutaneous malignant melanoma tissues expressed high levels of SOX11 compared with healthy controls, suggesting that SOX11 may be a new prognostic marker for malignant melanoma.

Correlation of the cell surface antigens with stage and grade in cancer of the bladder.

PubMed

Emmott, R C; Javadpour, N; Bergman, S M; Soares, T

1979-01-01

We examined 76 bladder tumors of various stages and grades for the presence of the ABO (H) cell surface antigen, using the specific red cell adherence technique. Of the grade I lesions studied 70 per cent were positive for the cell surface antigen and none of the 26 grade III tumors retained the antigens. When correlated with clinical stage the tumors showed no antigens for those of stages B1 to D, while 12 of 16 stage A lesions were positive for the antigen. When stage A lesions were studied and the findings were correlated with recurrence and metastasis/invasion rates the cell surface antigen was present on the initial tumor in only 1 lesion that recurred at an invasive stage. The findings of this study show that the specific red cell adherence technique may be valuable for predicting malignant potential in low grade, low stage cancer of the bladder. If supported by further investigation this technique may offer the capability of selecting low grade, low stage bladder tumors that are destined to invade or metastasize while they are at curable stages.

A rare case of metastatic squamous urachal carcinoma.

PubMed

Andrei, S; Andrei, A; Rusu Muntean, G; Ungureanu, M; Herlea, V; Becheanu, G; Popescu, I

2013-01-01

Squamous cell carcinoma is a very rare type of urachal malignancy, only a few cases being reported in the medical literature. We present the case of a 49-year-old male patient diagnosed with infected squamous cell urachal carcinoma with multiple pulmonary metastases, after complaints of lower abdominal pain, abdominal mass and fever, without respiratory symptoms. The abdominal ultrasonography and the CT scan revealed a tumoral mass in the lower abdomen in contact with the abdominal wall and the urinary bladder dome, displacing the small bowel. Pulmonary nodular lesions were described in the left lobe pyramid. The intraoperative diagnosis was necrotic urachal tumor with urinary bladder dome invasion and suspected pulmonary metastases, and tumor ablation with bladder dome resection and suture of the bladder were performed. The histopathological result was poorly differentiated squamous cell carcinoma (G3), with negative resection margins. The patient recovered well after surgery, but the prognosis is very poor due to the metastatic stage in which the tumor was diagnosed, no standard chemotherapy regimen for the treatment of metastatic urachal carcinoma being known as effective until now. Celsius.

A place for precision medicine in bladder cancer: targeting the FGFRs.

PubMed

di Martino, Erica; Tomlinson, Darren C; Williams, Sarah V; Knowles, Margaret A

2016-10-01

Bladder tumors show diverse molecular features and clinical outcome. Muscle-invasive bladder cancer has poor prognosis and novel approaches to systemic therapy are urgently required. Non-muscle-invasive bladder cancer has good prognosis, but high recurrence rate and the requirement for life-long disease monitoring places a major burden on patients and healthcare providers. Studies of tumor tissues from both disease groups have identified frequent alterations of FGFRs, including mutations of FGFR3 and dysregulated expression of FGFR1 and FGFR3 that suggest that these may be valid therapeutic targets. We summarize current understanding of the molecular alterations affecting these receptors in bladder tumors, preclinical studies validating them as therapeutic targets, available FGFR-targeted agents and results from early clinical trials in bladder cancer patients.

A place for precision medicine in bladder cancer: targeting the FGFRs

PubMed Central

di Martino, Erica; Tomlinson, Darren C; Williams, Sarah V; Knowles, Margaret A

2016-01-01

Bladder tumors show diverse molecular features and clinical outcome. Muscle-invasive bladder cancer has poor prognosis and novel approaches to systemic therapy are urgently required. Non-muscle-invasive bladder cancer has good prognosis, but high recurrence rate and the requirement for life-long disease monitoring places a major burden on patients and healthcare providers. Studies of tumor tissues from both disease groups have identified frequent alterations of FGFRs, including mutations of FGFR3 and dysregulated expression of FGFR1 and FGFR3 that suggest that these may be valid therapeutic targets. We summarize current understanding of the molecular alterations affecting these receptors in bladder tumors, preclinical studies validating them as therapeutic targets, available FGFR-targeted agents and results from early clinical trials in bladder cancer patients. PMID:27381494

The Diagnostic and Prognostic Value of Hematological and Chemical Abnormalities in Soft Tissue Sarcoma: A Comparative Study in Patients with Benign and Malignant Soft Tissue Tumors.

PubMed

Ariizumi, Takashi; Kawashima, Hiroyuki; Ogose, Akira; Sasaki, Taro; Hotta, Tetsuo; Hatano, Hiroshi; Morita, Tetsuro; Endo, Naoto

2018-01-01

The value of routine blood tests in malignant soft tissue tumors remains uncertain. To determine if these tests can be used for screening, the routine pretreatment blood test findings were retrospectively investigated in 359 patients with benign and malignant soft tissue tumors. Additionally, the prognostic potential of pretreatment blood abnormalities was evaluated in patients with soft tissue sarcomas. We compared clinical factors and blood tests findings between patients with benign and malignant soft tissue tumors using univariate and multivariate analysis. Subsequently, patients with malignant tumors were divided into two groups based on blood test reference values, and the prognostic significance of each parameter was evaluated. In the univariate analysis, age, tumor size, and tumor depth were significant clinical diagnostic factors. Significant increases in the granulocyte count, C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), and γ-glutamyl transpeptidase (γ-GTP) levels were found in patients with malignant soft tissue tumors. Multiple logistic regression showed that tumor size and ESR were independent factors that predicted malignant soft tissue tumors. The Kaplan-Meier survival analysis revealed that granulocyte counts, γ-GTP levels, and CRP levels correlated significantly with overall survival. Thus, pretreatment routine blood tests are useful diagnostic and prognostic markers for diagnosing soft tissue sarcoma. © 2018 by the Association of Clinical Scientists, Inc.

Endometrial stem cell differentiation into smooth muscle cell: a novel approach for bladder tissue engineering in women.

PubMed

Shoae-Hassani, Alireza; Sharif, Shiva; Seifalian, Alexander M; Mortazavi-Tabatabaei, Seyed Abdolreza; Rezaie, Sassan; Verdi, Javad

2013-10-01

To investigate manufacturing smooth muscle cells (SMCs) for regenerative bladder reconstruction from differentiation of endometrial stem cells (EnSCs), as the recent discovery of EnSCs from the lining of women's uteri, opens up the possibility of using these cells for tissue engineering applications, such as building up natural tissue to repair prolapsed pelvic floors as well as building urinary bladder wall. Human EnSCs that were positive for cluster of differentiation 146 (CD146), CD105 and CD90 were isolated and cultured in Dulbecco's modified Eagle/F12 medium supplemented with myogenic growth factors. The myogenic factors included: transforming growth factor β, platelet-derived growth factor, hepatocyte growth factor and vascular endothelial growth factor. Differentiated SMCs on bioabsorbable polyethylene-glycol and collagen hydrogels were checked for SMC markers by real-time reverse-transcriptase polymerase chain reaction (RT-PCR), western blot (WB) and immunocytochemistry (ICC) analyses. Histology confirmed the growth of SMCs in the hydrogel matrices. The myogenic growth factors decreased the proliferation rate of EnSCs, but they differentiated the human EnSCs into SMCs more efficiently on hydrogel matrices and expressed specific SMC markers including α-smooth muscle actin, desmin, vinculin and calponin in RT-PCR, WB and ICC experiments. The survival rate of cultures on the hydrogel-coated matrices was significantly higher than uncoated cultures. Human EnSCs were successfully differentiated into SMCs, using hydrogels as scaffold. EnSCs may be used for autologous bladder wall regeneration without any immunological complications in women. Currently work is in progress using bioabsorbable nanocomposite materials as EnSC scaffolds for developing urinary bladder wall tissue. © 2013 The Authors. BJU International © 2013 BJU International.

Feasibility of Raman spectroscopy in vitro after 5-ALA-based fluorescence diagnosis in the bladder

NASA Astrophysics Data System (ADS)

Grimbergen, M. C. M.; van Swol, C. F. P.; van Moorselaar, R. J. A.; Mahadevan-Jansen, A.,; Stone, N.

2006-02-01

Photodynamic diagnosis (PDD) has become popular in bladder cancer detection. Several studies have however shown an increased false positive biopsies rate under PDD guidance compared to conventional cystoscopy. Raman spectroscopy is an optical technique that utilizes molecular specific, inelastic scattering of light photons to interrogate biological tissues, which can successfully differentiate epithelial neoplasia from normal tissue and inflammations in vitro. This investigation was performed to show the feasibility of NIR Raman spectroscopy in vitro on biopsies obtained under guidance of 5-ALA induced PPIX fluorescence imaging. Raman spectra of a PPIX solution was measured to obtain a characteristic signature for the photosensitzer without contributions from tissue constituents. Biopsies were obtained from patients with known bladder cancer instilled with 50ml, 5mg 5-ALA two hours prior to trans-urethral resection of tumor (TURT). Additional biopsies were obtained at a fluorescent and non-fluorescent area, snap-frozen in liquid nitrogen and stored at -80 °C. Each biopsy was thawed before measurements (10sec integration time) with a confocal Raman system (Renishaw Gloucestershire, UK). The 830 nm excitation (300mW) source is focused on the tissue by a 20X ultra-long-working-distance objective. Differences in fluorescence background between the two groups were removed by means of a special developed fluorescence subtraction algorithm. Raman spectra from ALA biopsies showed different fluorescence background which can be effectively removed by a fluorescence subtraction algorithm. This investigation shows that the interaction of the ALA induced PPIX with Raman spectroscopy in bladder samples. Combination of these techniques in-vivo may lead to a viable method of optical biopsies in bladder cancer detection.

GENE EXPRESSION CHANGES IN MOUSE BLADDER TISSUE IN RESPONSE TO INORGANIC ARSENIC

EPA Science Inventory

Chronic human exposures to high arsenic concentrations are associated with lung, skin, and bladder cancer. Considerable controversy exists concerning arsenic mode of action and low dose extrapolation. This investigation was designed to identify dose-response changes in gene expre...

Benefits of nanoencapsulation for the hypercin-mediated photodetection of ovarian micrometastases.

PubMed

Zeisser-Labouèbe, Magali; Delie, Florence; Gurny, Robert; Lange, Norbert

2009-02-01

The high recurrence and lethality of ovarian cancer at advanced stages is problematic, especially due to the development of numerous micrometastases scattered throughout the abdominal cavity. Fluorescence photodetection (PD) used in combination with surgical resection of malignant tissues has been suggested to improve recovery. Based on promising in vivo results for the detection of bladder cancer, hypericin (Hy), a natural photosensitizer (PS), stands as a good candidate for the photodetection of ovarian cancer. However, due to its hydrophobicity, systemic administration of Hy is problematic. Polymeric nanoparticles (NPs) help to overcome these delivery and stability problems and enable intravenous administration of Hy. In this study, Hy-loaded NPs of polylactic acid were produced with the following properties: (i) mean size of 268 nm, (ii) negative zeta potential, (iii) low residual surfactant and (iv) drug loading of 3.7 % (w/w). The potential of hypericin-loaded nanoparticles for the fluorescence photodetection of ovarian metastases in Fischer 344 rats bearing ovarian tumours was compared to free drug. The selectivity of Hy administered with both formulations was assessed first by fluorescence endoscopy, and then quantified after tissue extraction. The results showed an improved selective accumulation of Hy in ovarian micrometastases when NPs were used.

Cascade Bioassay Evidence for the Existence of Urothelium-Derived Inhibitory Factor in Guinea Pig Urinary Bladder

PubMed Central

Guan, Na N.; Thor, Anna; Hallén, Katarina; Wiklund, N. Peter; Gustafsson, Lars E.

2014-01-01

Our aim was to investigate whether guinea pig urothelium-derived bioactivities compatible with the existence of urothelium-derived inhibitory factor could be demonstrated by in vitro serial bioassay and whether purinergic P1 receptor agonists, nitric oxide, nitrite or prostaglandins might explain observed activities. In a cascade superfusion system, urothelium-denuded guinea pig ureters were used as bioassay tissues, recording their spontaneous rhythmic contractions in presence of scopolamine. Urothelium-intact or -denuded guinea pig urinary bladders were used as donor tissues, stimulated by intermittent application of carbachol before or during the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), the adenosine/P1 nucleoside receptor antagonist 8-(p-sulfophenyl)theophylline (8-PST) or the cyclo-oxygenase inhibitor diclofenac infused to bath donor and bioassay tissues. The spontaneous contractions of bioassay ureters were unaltered by application of carbachol 1–5 µM in the presence of scopolamine 5–30 µM. When carbachol was applied over the urothelium-denuded bladder, the assay ureter contraction rate was unaltered. Introducing carbachol over the everted urothelium-intact bladder significantly inhibited the contraction frequency of the assay ureter, suggesting the transfer of an inhibitory activity from the bladder to the assay ureter. The transmissible inhibitory activity was not markedly antagonized by L-NAME, 8-PST or diclofenac, while L-NAME nearly abolished nitrite release from the urothelium-intact bladder preparations. We suggest that urothelium-derived inhibitory factor is a transmissible entity over a significant distance as demonstrated in this novel cascade superfusion assay and seems less likely to be nitric oxide, nitrite, an adenosine receptor agonist or subject to inhibition by administration of a cyclo-oxygenase inhibitor. PMID:25084114

Cascade bioassay evidence for the existence of urothelium-derived inhibitory factor in Guinea pig urinary bladder.

PubMed

Guan, Na N; Thor, Anna; Hallén, Katarina; Wiklund, N Peter; Gustafsson, Lars E

2014-01-01

Our aim was to investigate whether guinea pig urothelium-derived bioactivities compatible with the existence of urothelium-derived inhibitory factor could be demonstrated by in vitro serial bioassay and whether purinergic P1 receptor agonists, nitric oxide, nitrite or prostaglandins might explain observed activities. In a cascade superfusion system, urothelium-denuded guinea pig ureters were used as bioassay tissues, recording their spontaneous rhythmic contractions in presence of scopolamine. Urothelium-intact or -denuded guinea pig urinary bladders were used as donor tissues, stimulated by intermittent application of carbachol before or during the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), the adenosine/P1 nucleoside receptor antagonist 8-(p-sulfophenyl)theophylline (8-PST) or the cyclo-oxygenase inhibitor diclofenac infused to bath donor and bioassay tissues. The spontaneous contractions of bioassay ureters were unaltered by application of carbachol 1-5 µM in the presence of scopolamine 5-30 µM. When carbachol was applied over the urothelium-denuded bladder, the assay ureter contraction rate was unaltered. Introducing carbachol over the everted urothelium-intact bladder significantly inhibited the contraction frequency of the assay ureter, suggesting the transfer of an inhibitory activity from the bladder to the assay ureter. The transmissible inhibitory activity was not markedly antagonized by L-NAME, 8-PST or diclofenac, while L-NAME nearly abolished nitrite release from the urothelium-intact bladder preparations. We suggest that urothelium-derived inhibitory factor is a transmissible entity over a significant distance as demonstrated in this novel cascade superfusion assay and seems less likely to be nitric oxide, nitrite, an adenosine receptor agonist or subject to inhibition by administration of a cyclo-oxygenase inhibitor.

Protective effect of ketamine against hemorrhagic cystitis in rats receiving ifosfamide

PubMed Central

Ozguven, Ali A.; Yılmaz, Omer; Taneli, Fatma; Ulman, Cevval; Vatansever, Seda; Onag, Ali

2014-01-01

Objective: To investigate the possible protective effect of a single dose of ketamine and the synergistic effect between ketamine and 2-mercaptoethane sulfonate (mesna) against ifosfamide-induced hemorrhagic cystitis. Materials and Methods: 35 adult female wistar rats were divided into five groups and pretreated with ketamine at 10 mg/kg and/or mesna 400 mg/kg 30 minutes before intraperitoneal injection of IFS (400 mg/kg) or with saline (control group). Hemorrhagic cystitis was evaluated 24 hours after IFS injection according to bladder wet weight (BWW), and microscopic changes, i.e. edema, hemorrhage, cellular infiltration, and urothelial desquamation. The markers of oxidative damage including nitric oxide (NO) and malondialdehyde (MDA) levels and the expressions of tumor necrosis factor alpha (TNF-α), interleukin 1-beta (IL-1β), inducible nitric oxide synthase (i-NOS) and endothelial nitric oxide synthase (e-NOS) were also assayed in the bladder tissues. Results: Pretreatment with ketamine alone or ketamine in combination with mesna reduced the IFS-induced increase of BWW (58,47% and 63,33%, respectively, P < 0.05). IFS- induced microscopic alterations were also prevented by ketamine with or without mesna (P < 0.05). In addition, also statistically insignificant, the bladder tissue expressions of IL-1β were lower in ketamine and/or mesna-receiving groups (P > 0,05). The parameters of oxidative stress, the NO and the MDA contents of the bladder tissues of the study groups were not different. Conclusion: The results of the present study suggest that a single dose of ketamine pretreatment attenuates experimental IFS-induced bladder damage. It is therefore necessary to investigate ketamine locally and systematically with various dosing schedulesin order to reduce the bladder damage secondary to oxazaphosphorine-alkylating agents and these results may widen the spectrum of ketamine. PMID:24741183

LncRNA AWPPH inhibits SMAD4 via EZH2 to regulate bladder cancer progression.

PubMed

Zhu, Feng; Zhang, Xinjun; Yu, Qinnan; Han, Guangye; Diao, Fengxia; Wu, Chunlei; Zhang, Yan

2018-06-01

This study aimed to investigate the effect and underlying mechanism of lncRNA AWPPH in bladder cancer (BC). A total of 20 Ta-T1 stage BC tissues, 20 T2-T4 stage BC tissues, and 20 normal bladder tissues, as well as human bladder epithelial cell line SV-HUC-1, human BC cell lines RT4, and T24 were obtained to detect the levels of AWPPH, enhancer of zeste homolog 2 (EZH2) and SMAD4 using RT-qPCR or Western blotting. RT4 cells were transfected with pc-AWPPH, pc-EZH2, or pc-control and T24 cells were transfected with si-AWPPH, si-EZH2, si-control, or pc-AWPPH + pc-SMAD4, respectively. Then, cell proliferation, apoptosis, autophagy, and migration, were detected using MTT assay, colony formation assay, Annexin V-FITC/PI method, Western blotting, and Transwell analysis, respectively. The relationship of AWPPH and EZH2 or SMAD4 was evaluated by RNA immunoprecipitation (RIP) assay or Chromatin immunoprecipitation (ChIP) assay. Compared with normal bladder tissues or cells, the levels of AWPPH and EZH2 were overexpressed, while SMAD4 was down-regulated in BC tissues or cells (all P < 0.01). Cell viability, colony number, and migration were significantly increased, while cell apoptosis ratio was reduced in cells with pc-AWPPH compared with cells with pc-control (all P < 0.05), meanwhile, these effects were reversed by the treatment of pc-SMAD4. Then, RIP assay revealed that AWPPH could bind to EZH2 and ChIP assay showed SMAD4 was regulated by EZH2. LncRNA AWPPH can promote cell proliferation, autophagy, and migration, as well as inhibit cell apoptosis in BC by inhibiting SMAD4 via EZH2. © 2017 Wiley Periodicals, Inc.

Intravesical application of rebamipide promotes urothelial healing in a rat cystitis model.

PubMed

Funahashi, Yasuhito; Yoshida, Masaki; Yamamoto, Tokunori; Majima, Tsuyoshi; Takai, Shun; Gotoh, Momokazu

2014-12-01

Rebamipide is used as a topical therapeutic agent for various organs. We examined the healing effects of intravesical rebamipide on damaged urothelium in a rat model of chemically induced cystitis. Hydrochloride was injected in the bladder of female Sprague Dawley® rats to induce cystitis. On days 1 and 4 rebamipide (1 or 10 mM) or vehicle was administered in the bladder and maintained for 1 hour. Histopathology, urothelial permeability, cystometrogram and nociceptive behaviors were evaluated on day 7. Also, tissue rebamipide concentrations after the 1-hour bladder instillation were quantified using high performance liquid chromatography. Intravesically administered rebamipide permeated the bladder, particularly in hydrochloride treated rats, and the pharmacologically effective tissue dose remained for greater than 6 hours. Bladder histological evaluation revealed polymorphological inflammatory cell infiltration and decreased positive staining for uroplakin 3A in hydrochloride treated rats. Scanning electron microscopy showed damaged tight junctions in the hydrochloride group. Evans blue absorption in the bladder wall was increased in hydrochloride treated rats. These findings, which were associated with urothelial injury and increased permeability, were dependently suppressed by the rebamipide treatment dose. Cystometrogram demonstrated that the intercontraction interval was shorter in hydrochloride treated rats but prolonged by rebamipide. The increased nociceptive behaviors observed after intravesical resiniferatoxin administration were also suppressed by rebamipide. Intravesical rebamipide accelerated the repair of damaged urothelium, protected urothelial barrier function and suppressed bladder overactivity and nociception. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

The Rare Togetherness of Bladder Leiomyoma and Neurofibromatosis

PubMed Central

Celik, Orcun; Kozacioglu, Zafer

2018-01-01

Neurofibromatosis Type 1 (Von Recklinghausen disease) is a common, autosomal dominant hereditary disorder characterized by involvement of multiple tissues derived from the neural crest. Urinary system involvement in neurofibromatosis is a rare condition. Leiomyoma of the bladder is a rare benign mesenchymal tumor. In this case, our experience and approach regarding the bladder leiomyoma development in a patient diagnosed with neurofibromatosis are presented and the literature data has been reviewed. PMID:29736289

Bladder tissue regeneration using acellular bi-layer silk scaffolds in a large animal model of augmentation cystoplasty.

PubMed

Tu, Duong D; Chung, Yeun Goo; Gil, Eun Seok; Seth, Abhishek; Franck, Debra; Cristofaro, Vivian; Sullivan, Maryrose P; Di Vizio, Dolores; Gomez, Pablo; Adam, Rosalyn M; Kaplan, David L; Estrada, Carlos R; Mauney, Joshua R

2013-11-01

Acellular scaffolds derived from Bombyx mori silk fibroin were investigated for their ability to support functional tissue regeneration in a porcine model of augmentation cystoplasty. Two bi-layer matrix configurations were fabricated by solvent-casting/salt leaching either alone (Group 1) or in combination with silk film casting (Group 2) to yield porous foams buttressed by heterogeneous surface pore occlusions or homogenous silk films, respectively. Bladder augmentation was performed with each scaffold group (6 × 6 cm(2)) in juvenile Yorkshire swine for 3 m of implantation. Augmented animals exhibited high rates of survival (Group 1: 5/6, 83%; Group 2: 4/4, 100%) and voluntary voiding over the course of the study period. Urodynamic evaluations demonstrated mean increases in bladder capacity over pre-operative levels (Group 1: 277%; Group 2: 153%) which exceeded nonsurgical control gains (144%) encountered due to animal growth.In addition, animals augmented with both matrix configurations displayed increases in bladder compliance over pre-operative levels(Group 1: 357%; Group 2: 338%) similar to growth-related elevations observed in non-surgical controls (354%) [corrected]. Gross tissue evaluations revealed that both matrix configurations supported extensive de novo tissue formation throughout the entire original implantation site which exhibited ultimate tensile strength similar to nonsurgical counterparts. Histological and immunohistochemical analyses showed that both implant groups promoted comparable extents of smooth muscle regeneration and contractile protein (α-smooth muscle actin and SM22α) expression within defect sites similar to controls. Parallel evaluations demonstrated the formation of a transitional, multi-layered urothelium with prominent cytokeratin, uroplakin, and p63 protein expression in both matrix groups. De novo innervation and vascularization processes were evident in all regenerated tissues indicated by synaptophysin-positive neuronal cells and vessels lined with CD31 expressing endothelial cells. Ex vivo organ bath studies demonstrated that regenerated tissues supported by both silk matrices displayed contractile responses to carbachol, α,β-methylene-ATP, KCl, and electrical field stimulation similar to controls. Our data detail the ability of acellular silk scaffolds to support regeneration of innervated, vascularized smooth muscle and urothelial tissues within 3 m with structural, mechanical, and functional properties comparable to native tissue in a porcine model of bladder repair. © 2013 Elsevier Ltd. All rights reserved.

ATP is released from rabbit urinary bladder epithelial cells by hydrostatic pressure changes--a possible sensory mechanism?

PubMed Central

Ferguson, D R; Kennedy, I; Burton, T J

1997-01-01

1. The responses of rabbit urinary bladder to hydrostatic pressure changes and to electrical stimulation have been investigated using both the Ussing chamber and a superfusion apparatus. These experiments enabled us to monitor changes in both ionic transport across the tissue and cellular ATP release from it. 2. The urinary bladder of the rabbit maintains an electrical potential difference across its wall as a result largely of active sodium transport from the urinary (mucosal) to the serosal surface. 3. Small hydrostatic pressure differences produced by removal of bathing fluid from one side of the tissue caused reproducible changes in both potential difference and short-circuit current. The magnitude of these changes increases as the volume of fluid removed increases. 3. Amiloride on the mucosal (urinary), but not the serosal, surface of the membrane reduces the transepithelial potential difference and short-circuit current with an IC50 of 300 nM. Amiloride reduces the size of, but does not abolish, transepithelial potential changes caused by alterations in hydrostatic pressure. 4. Field electrical stimulation of strips of bladder tissue produces a reproducible release of ATP. Such release was demonstrated to occur largely from urothelial cells and is apparently non-vesicular as it increases in the absence of calcium and is not abolished by tetrodotoxin. 5. It is proposed that ATP is released from the urothelium as a sensory mediator for the degree of distension of the rabbit urinary bladder and other sensory modalities. PMID:9423189

[The diagnostic value of microsatellite LOH analysis and the prognostic relevance of angiogenic gene expression in urinary bladder cancer].

PubMed

Szarvas, Tibor

2009-12-01

Bladder cancer is the second most common malignancy affecting the urinary system. Currently, histology is the only tool that determines therapy and patients' prognosis. As the treatment of non-invasive (Ta/T1) and muscle invasive (T2-T4) bladder tumors are completely different, correct staging is important, although it is often hampered by disturbing factors. Molecular methods offer new prospects for early disease detection, confirmation of unclear histological findings and prognostication. Applying molecular biological methods, the present study is searching for answers to current diagnostic and prognostic problems in bladder carcinoma. We analyzed tumor, blood and/or urine samples of 334 bladder cancer patients and 117 control individuals. Genetic alterations were analyzed in urine samples of patients and controls, both by PCR-based microsatellite loss of heterozigosity (LOH) analysis using 12 fluorescently labeled primers and by DNA hybridization based UroVysion FISH technique using 4 probes, to assess the diagnostic values of these methods. Whole genome microsatellite analysis (with 400 markers) was performed in tumor and blood specimens of bladder cancer patients to find chromosomal regions, the loss of which may be associated with tumor stage. Furthermore, we assessed the prognostic value of Tie2, VEGF, Angiopoietin-1 and -2. We concluded that DNA analysis of voided urine samples by microsatellite analysis and FISH are sensitive and non-invasive methods to detect bladder cancer. Furthermore, we established a panel of microsatellite markers that could differentiate between non-invasive and invasive bladder cancer. However, further analyses in a larger cohort of patients are needed to assess their specificity and sensitivity. Finally, we identified high Ang-2 and low Tie2 gene expression as significant and independent risk factors of tumor recurrence and cancer related survival.

Detecting DNA methylation of the BCL2, CDKN2A and NID2 genes in urine using a nested methylation specific polymerase chain reaction assay to predict bladder cancer.

PubMed

Scher, Michael B; Elbaum, Michael B; Mogilevkin, Yakov; Hilbert, David W; Mydlo, Jack H; Sidi, A Ami; Adelson, Martin E; Mordechai, Eli; Trama, Jason P

2012-12-01

Detection of methylated DNA has been shown to be a good biomarker for bladder cancer. Bladder cancer has the highest recurrence rate of any cancer and, as such, patients are regularly monitored using invasive diagnostic techniques. As urine is easily attainable, bladder cancer is an optimal cancer to detect using DNA methylation. DNA methylation is highly specific in cancer detection. However, it is difficult to detect because of the limited amount of DNA present in the urine of patients with bladder cancer. Therefore, an improved, sensitive and noninvasive diagnostic test is needed. We developed a highly specific and sensitive nested methylation specific polymerase chain reaction assay to detect the presence of bladder cancer in small volumes of patient urine. The genes assayed for DNA methylation are BCL2, CDKN2A and NID2. The regions surrounding the DNA methylation sites were amplified in a methylation independent first round polymerase chain reaction and the amplification product from the first polymerase chain reaction was used in a real-time methylation specific polymerase chain reaction. Urine samples were collected from patients receiving treatment at Wolfson Medical Center in Holon, Israel. In a pilot clinical study using patient urine samples we were able to differentiate bladder cancer from other urogenital malignancies and nonmalignant conditions with a sensitivity of 80.9% and a specificity of 86.4%. We developed a novel methylation specific polymerase chain reaction assay for the detection and monitoring of bladder cancer using DNA extracted from patient urine. The assay may also be combined with other diagnostic tests to improve accuracy. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Efficacy and safety of hexaminolevulinate fluorescence cystoscopy in the diagnosis of bladder cancer.

PubMed

Lee, Jae Seung; Lee, Seo Yeon; Kim, Woo Jung; Seo, Seong Il; Jeon, Seong Soo; Lee, Hyun Moo; Choi, Han Yong; Jeong, Byong Chang

2012-12-01

The aim of this study was to evaluate the efficacy and safety of hexaminolevulinate fluorescence cystoscopy in the diagnosis of bladder cancer. In a prospective design, we included patients who had a bladder lesion suggesting bladder cancer. Patients with massive hematuria, urethral Foley catheter insertion, chronic retention state, or urinary tract infection were excluded. After the bladder was emptied, hexaminolevulinate was gently administered into the bladder. One hour later, cystoscopy under white light and blue light was performed. After marking the lesions confirmed with white light or blue light, transurethral resection of the bladder lesion and pathologic confirmation were done. Transurethral resection of the lesions that were negative in both white and blue light was also performed. From April 2010 to September 2010, 30 patients were enrolled. From the total of 30 patients (25 men and 5 women; mean age, 60.4±9.22 years), 134 specimens were extracted. Among these, 101 specimens showed positive results by blue light cystoscopy (BLC). The sensitivity of BLC and white light cystoscopy (WLC) was 92.3% and 80.8%, respectively (p=0.021). The specificity of BLC and WLC was 48% and 49.1%, respectively (p>0.05). The positive and negative predictive values of BLC were 71.2% and 81.8%, respectively, whereas those of WLC were 72.0% and 68.6%, respectively. With WLC, 48 specimens showed negative findings, but of that group, 15 specimens (31.2%) were revealed to be malignant with BLC. There were no significant side effects in the 24 hours after the instillation of hexaminolevulinate. Photodynamic diagnosis with hexaminolevulinate helps to find tumors that could be missed by use of WLC only. Photodynamic diagnosis might be valuable in complete resection as well as for more accurate diagnosis of bladder tumor.

Role of imaging techniques in the diagnosis and follow-up of muscle-invasive bladder carcinoma.

PubMed

Mesa, A; Nava, E; Fernández Del Valle, A; Argüelles, B; Menéndez-Del Llano, R; Sal de Rellán, S

2017-10-10

Muscle-invasive bladder malignancies represent 20-30% of all bladder cancers. These patients require imaging tests to determine the regional and distant staging. To describe the role of various imaging tests in the diagnosis, staging and follow-up of muscle-invasive bladder cancer. To assess recent developments in radiology aimed at improving the sensitivity and specificity of local staging and treatment response. We conducted an updated literature review. Computed tomography and magnetic resonance imaging (MRI) are the tests of choice for performing proper staging prior to surgery. Computed tomography urography is currently the most widely used technique, although it has limitations in local staging. Ultrasonography still has a limited role. Recent developments in MRI have improved its capacity for local staging. MRI has been suggested as the test of choice for the follow-up, with promising results in assessing treatment response. Positron emission tomography could improve the detection of adenopathies and extrapelvic metastatic disease. Imaging tests are essential for the diagnosis, staging and follow-up of muscle-invasive bladder cancer. Recent technical developments represent important improvements in local staging and have opened the possibility of assessing treatment response. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Roles of polyuria and hyperglycemia in bladder dysfunction in diabetes.

PubMed

Xiao, Nan; Wang, Zhiping; Huang, Yexiang; Daneshgari, Firouz; Liu, Guiming

2013-03-01

Diabetes mellitus causes diabetic bladder dysfunction. We identified the pathogenic roles of polyuria and hyperglycemia in diabetic bladder dysfunction in rats. A total of 72 female Sprague-Dawley® rats were divided into 6 groups, including age matched controls, and rats with sham urinary diversion, urinary diversion, streptozotocin induced diabetes mellitus after sham urinary diversion, streptozotocin induced diabetes mellitus after urinary diversion and 5% sucrose induced diuresis after sham urinary diversion. Urinary diversion was performed by ureterovaginostomy 10 days before diabetes mellitus induction. Animals were evaluated 20 weeks after diabetes mellitus or diuresis induction. We measured 24-hour drinking and voiding volumes, and cystometry. Bladders were harvested to quantify smooth muscle, urothelium and collagen. We measured nitrotyrosine and Mn superoxide dismutase in the bladder. Diabetes and diuresis caused increases in drinking and voiding volume, and bladder weight. Bladder weight decreased in the urinary diversion group and the urinary diversion plus diabetes group. The intercontractile interval, voided volume and compliance increased in the diuresis and diabetes groups, decreased in the urinary diversion group and further decreased in the urinary diversion plus diabetes group. Total cross-sectional tissue, smooth muscle and urothelium areas increased in the diuresis and diabetes groups, and decreased in the urinary diversion and urinary diversion plus diabetes groups. As a percent of total tissue area, collagen decreased in the diuresis and diabetes groups, and increased in the urinary diversion and urinary diversion plus diabetes groups. Smooth muscle and urothelium decreased in the urinary diversion and urinary diversion plus diabetes groups. Nitrotyrosine and Mn superoxide dismutase increased in rats with diabetes and urinary diversion plus diabetes. Polyuria induced bladder hypertrophy, while hyperglycemia induced substantial oxidative stress in the bladder, which may have a pathogenic role in late stage diabetic bladder dysfunction. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Masked urinary bladder injury with a bullet expulsed spontaneously during voiding.

PubMed

Calışkan, Müjgan; Evren, Ismail; Kabak, Ismail; Atak, Ibrahim; Gökcan, Recai

2011-09-01

We report a case with gunshot to the pelvis. The injury site was the soft tissue between the rectum and urinary bladder. Several days later, the bullet was expulsed spontaneously during voiding. In the literature, only a few case reports have described spontaneous expulsion of an intravesical bullet. A 19-year-old male was wounded on the left hip by gunshot. Radiographic examinations showed a bullet in the pelvis, which was localized in the soft tissue between the rectum and urinary bladder, with no accompanying visceral injury on abdominopelvic computerized tomography. Macroscopic hematuria was noticed after urethral catheterization. Rectosigmoidoscopy and retrograde cystoscopic examinations were both negative. The patient was monitored closely and treated conservatively with no surgical intervention. The urinary catheter was removed on the fifth postoperative day, and the bullet was expulsed spontaneously via the urethra during normal voiding three hours after catheter removal. Thereafter, a retrograde urethrography was performed, which showed no evidence of urinary tract or bladder injury.

Causes and risk factors of urinary incontinence: Avicenna's point of view vs. contemporary findings.

PubMed

Nojavan, Fatemeh; Sharifi, Hossein; Ghanbari, Zinat; Kamalinejad, Mohammad; Mokaberinejad, Roshanak; Emami, Maryam

2015-02-22

To extract the causes and risk factors of urinary incontinence from an old medical text by Avicenna entitled "Canon of Medicine" and comparing it with contemporary studies. In this study, etiology and risk factors of urinary incontinence were extracted from Avicenna's "Canon of Medicine". Commentaries written on this book and other old reliable medical texts about bladder and its diseases were also studied. Then the achieved information was compared with contemporary findings of published articles. Urinary incontinence results from bladder dysfunction in reservoir phase. Bladder's involuntary muscles and voluntary external sphincter are two main components which are involved in this process. Urinary incontinence can exist without obvious structural and neuronal etiologies. According to Avicenna, distemperment of muscular tissue of bladder and external sphincter is the cause for urinary incontinence in such cases. Distemperment is the result of bothering qualities in tissue, i.e.: "wet" and "cold". They are the two bothering qualities which are caused by extracorporeal and intracorporeal factors. Interestingly, the positive associations of some of these factors with urinary incontinence have been shown in recent researches. "Cold" and "wet" distemperment of bladder and external sphincter can be independent etiologies of urinary incontinence which should be investigated. 

Viruses and interstitial cystitis: adenovirus genomes cannot be demonstrated in urinary bladder biopsies.

PubMed

Hukkanen, V; Haarala, M; Nurmi, M; Klemi, P; Kiilholma, P

1996-01-01

Microbes may be involved in the pathogenesis of interstitial cystitis (IC). Adenoviruses and BK virus (BKV) can infect epithelial cells in urinary bladder and they are causative agents for hemorrhagic cystitis. We therefore studied the presence of adenovirus and BKV genomes in urinary bladder tissue specimens of patients with IC using polymerase chain reaction (PCR) and in situ hybridization (ISH). Controls were specimens from cases with transitional cell carcinoma of the bladder. Nucleic acids were extracted from paraffin sections of the bladder tissue for PCR. Primers detecting all adenovirus types were used. In situ hybridization was carried out for the paraffin sections using digoxigenin-labeled DNA probes for adenovirus and BKV. The adenovirus DNA PCR was able to detect one to two infected cells/specimen. All the seven IC cases studied and six controls were negative for adenovirus DNA by PCR and ISH. The ISH test for BKV genomes was also considered negative in IC cases and controls. The specimens which were negative in PCR tests yielded a signal with beta-globin primers, thus being amplifiable. We conclude that adenovirus and BKV do not play a major pathogenetic role in interstitial cystitis.

Concentrations of cadmium and selected essential elements in malignant large intestine tissue

PubMed Central

Dziki, Adam; Kilanowicz, Anna; Sapota, Andrzej; Duda-Szymańska, Joanna; Daragó, Adam

2015-01-01

Introduction Colorectal cancer is one of the most common cancers worldwide. Incidence rates of large intestine cancer indicate a role of environmental and occupational factors. The role of essential elements and their interaction with toxic metals can contribute to the explanation of a complex mechanism by which large intestine cancer develops. Bearing this in mind, determining the levels of essential and toxic elements in tissues (organs), as well as in body fluids, seems to shed light on their role in the mode of action in malignant disease. Aim Determination of the levels of cadmium, zinc, copper, selenium, calcium, magnesium, and iron in large intestine malignant tissue. Material and methods Two intraoperative intestine sections were investigated: one from the malignant tissue and the other one from the normal tissue, collected from each person with diagnosed large intestine cancer. Cadmium, zinc, copper, calcium, magnesium, and iron levels were determined with atomic absorption spectrometry, and selenium levels by spectrofluorimetric method. Results The levels of copper, selenium, and magnesium were higher in the malignant than in normal tissues. In addition, the zinc/copper and calcium/magnesium relationship was altered in malignant tissue, where correlations were lower compared to non-malignant tissue. Conclusions The results seems to demonstrate disturbed homeostasis of some essential elements. However, it is hard to confirm their involvement in the aetiology of colorectal cancer. PMID:27110307

The effect of bladder outlet obstruction on tissue oxygen tension and blood flow in the pig bladder.

PubMed

Greenland, J E; Hvistendahl, J J; Andersen, H; Jörgensen, T M; McMurray, G; Cortina-Borja, M; Brading, A F; Frøkiaer, J

2000-06-01

To investigate the effect of partial bladder outlet obstruction on detrusor blood flow and oxygen tension (PdetO2) in female pigs. Detrusor-layer oxygen tension and blood flow were measured using oxygen-sensitive electrode and radiolabelled microsphere techniques in five female Large White pigs with a partial urethral obstruction and in five sham-operated controls. The effects of chronic outlet obstruction on bladder weight, and cholinergic nerve density and distribution, are also described. In the obstructed bladders, blood flow and oxygen tension were, respectively, 54.9% and 74.3% of control values at low bladder volume, and 47.5% and 42.5% at cystometric capacity. Detrusor blood flow declined by 27.8% and 37.5% in the control and obstructed bladders, respectively, as a result of bladder filling, whilst PdetO2 did not decrease in the controls, but fell by 42.7% in the obstructed bladders. Bladder weight increased whilst cholinergic nerve density decreased in the obstructed animals. In pigs with chronic bladder outlet obstruction, blood flow and oxygen tension in the detrusor layer were lower than in control animals. In addition, increasing detrusor pressure during filling caused significantly greater decreases in blood flow and oxygen tension in the obstructed than in the control bladders.

Efficacy and Safety of Blue Light Flexible Cystoscopy with Hexaminolevulinate in the Surveillance of Bladder Cancer: A Phase III, Comparative, Multicenter Study.

PubMed

Daneshmand, Siamak; Patel, Sanjay; Lotan, Yair; Pohar, Kamal; Trabulsi, Edouard; Woods, Michael; Downs, Tracy; Huang, William; Jones, Jeffrey; O'Donnell, Michael; Bivalacqua, Trinity; DeCastro, Joel; Steinberg, Gary; Kamat, Ashish; Resnick, Matthew; Konety, Badrinath; Schoenberg, Mark; Jones, J Stephen

2018-05-01

We compared blue light flexible cystoscopy with white light flexible cystoscopy for the detection of bladder cancer during surveillance. Patients at high risk for recurrence received hexaminolevulinate intravesically before white light flexible cystoscopy and randomization to blue light flexible cystoscopy. All suspicious lesions were documented. Patients with suspicious lesions were referred to the operating room for repeat white and blue light cystoscopy. All suspected lesions were biopsied or resected and specimens were examined by an independent pathology consensus panel. The primary study end point was the proportion of patients with histologically confirmed malignancy detected only with blue light flexible cystoscopy. Additional end points were the false-positive rate, carcinoma in situ detection and additional tumors detected only with blue light cystoscopy. Following surveillance 103 of the 304 patients were referred, including 63 with confirmed malignancy, of whom 26 had carcinoma in situ. In 13 of the 63 patients (20.6%, 95% CI 11.5-32.7) recurrence was seen only with blue light flexible cystoscopy (p <0.0001). Five of these cases were confirmed as carcinoma in situ. Operating room examination confirmed carcinoma in situ in 26 of 63 patients (41%), which was detected only with blue light cystoscopy in 9 of the 26 (34.6%, 95% CI 17.2-55.7, p <0.0001). Blue light cystoscopy identified additional malignant lesions in 29 of the 63 patients (46%). The false-positive rate was 9.1% for white and blue light cystoscopy. None of the 12 adverse events during surveillance were serious. Office based blue light flexible cystoscopy significantly improves the detection of patients with recurrent bladder cancer and it is safe when used for surveillance. Blue light cystoscopy in the operating room significantly improves the detection of carcinoma in situ and detects lesions that are missed with white light cystoscopy. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Antitumor potential of 1-thiocarbamoyl-3,5-diaryl-4,5-dihydro-1H-pyrazoles in human bladder cancer cells.

PubMed

Tessmann, Josiane Weber; Buss, Julieti; Begnini, Karine Rech; Berneira, Lucas Moraes; Paula, Favero Reisdorfer; de Pereira, Claudio Martin Pereira; Collares, Tiago; Seixas, Fabiana Kömmling

2017-10-01

Bladder cancer is a genitourinary malignant disease common worldwide. Current chemotherapy is often limited mainly due to toxicity and drug resistance. Thus, there is a continued need to discover new therapies. Recently evidences shows that pyrazoline derivatives are promising antitumor agents in many types of cancers, but there are no studies with bladder cancer. In order to find potent and novel chemotherapy drugs for bladder cancer, a series of pyrazoline derivatives 2a-2d were tested for their antitumor activity in two human bladder cancer cell lines 5647 and T24. The MTT assay showed that the compounds 1-thiocarbamoyl-3,5-diphenyl-4,5-dihydro-1H-pyrazole (2a) and 1-thiocarbamoyl-5-(4-chlorophenyl)-3-phenyl-4,5-dihydro-1H-pyrazole (2c) decrease the cell viability of 5637 cells. Molecular modeling indicated that these compounds had a good oral bioavailability and low toxicities. Clonogenic assay and flow cytometric analysis were used to assess colony formation, apoptosis induction and cell cycle distribution. Overall, our results suggest that pyrazoline 2a and 2c, with the substituents hydrogen and chlorine respectively, may decrease cell viability and colony formation of bladder cancer 5637 cell line by inhibition of cell cycle progression, and for pyrazoline 2a, by induction of apoptosis. As indicated by the physicochemical properties of these compounds, the steric factor influences the activity. Therefore, these pyrazoline derivatives can be considered promising anticancer agents for the treatment of bladder cancer. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Age-Related Alterations in Regeneration of the Urinary Bladder after Subtotal Cystectomy

DTIC Science & Technology

2013-11-01

buffer. The bladders were cut into approximately equally sized strips along the longitudinal axis. The strips were denuded of the urothelium and sub... urothelium and then were attached to tissue holds at one end and to force transducers at the other end in an organ bath system (Danish Myo Technology...of the urothelium and the bladder wall to reseal immediately after STC in old animals. This suppo- sition is consistent with the decreased PCNA

The Ethanol Extract of the Inner Bark of Caesalpinia pyramidalis (Tul.) Reduces Urinary Bladder Damage during Cyclophosphamide-Induced Cystitis in Rats

PubMed Central

Moraes, Janaína P.; Pereira, Denyson S.; Matos, Alexandre S.; Santana, Danielle G.; Santos, Cliomar A.; Estevam, Charles S.; Fakhouri, Ricardo; de Lucca Junior, Waldecy; Camargo, Enilton A.

2013-01-01

Hemorrhagic cystitis (HC) is a common side effect of cyclophosphamide therapy, which deserves new therapeutic strategies, such as those based on natural products. The ethanol extract of the inner bark of Caesalpinia pyramidalis (Tul.) (EECp) possesses anti-inflammatory, antinociceptive, and antioxidant activities as previously showed by our group. We have investigated the effect of EECp on the cyclophosphamide-induced HC. Cystitis was induced in male Wistar rats by the injection of cyclophosphamide. These animals were pretreated with EECp (100–400 mg/kg), vehicle, or mesna. Myeloperoxidase activity and malondialdehyde formation were measured in urinary bladder and other tissues. Bladder edema and histopathological alterations and serum nitric oxide metabolites concentration NOx − were also evaluated. Treatment with EECp (100–400 mg/kg) or mesna impaired the increase of myeloperoxidase activity in urinary bladder and the serum NOx − induced by cyclophosphamide but did not reduce edema in this tissue, as did mesna. Total histological score was reduced by EECp (100 mg/kg). Lung myeloperoxidase activity, which was increased by cyclophosphamide, was decreased significantly by EECp (400 mg/kg). EECp also diminished the malondialdehyde formation in bladder, lung, and spleen, although these parameters were not affected by cyclophosphamide. These results indicate that EECp reduced urinary bladder damage during cyclophosphamide-induced HC in rats. PMID:24348180

Acrolein- and 4-Aminobiphenyl-DNA adducts in human bladder mucosa and tumor tissue and their mutagenicity in human urothelial cells

PubMed Central

Weng, Mao-wen; Hu, Yu; Chen, Wei-sheng; Chou, David; Liu, Yan; Donin, Nicholas; Huang, William C.; Lepor, Herbert; Wu, Xue-Ru; Wang, Hailin; Beland, Frederick A.; Tang, Moon-shong

2014-01-01

Tobacco smoke (TS) is a major cause of human bladder cancer (BC). Two components in TS, 4-aminobiphenyl (4-ABP) and acrolein, which also are environmental contaminants, can cause bladder tumor in rat models. Their role in TS related BC has not been forthcoming. To establish the relationship between acrolein and 4-ABP exposure and BC, we analyzed acrolein-deoxyguanosine (dG) and 4-ABP-DNA adducts in normal human urothelial mucosa (NHUM) and bladder tumor tissues (BTT), and measured their mutagenicity in human urothelial cells. We found that the acrolein-dG levels in NHUM and BTT are 10-30 fold higher than 4-ABP-DNA adduct levels and that the acrolein-dG levels in BTT are 2 fold higher than in NHUM. Both acrolein-dG and 4-ABP-DNA adducts are mutagenic; however, the former are 5 fold more mutagenic than the latter. These two types of DNA adducts induce different mutational signatures and spectra. We found that acrolein inhibits nucleotide excision and base excision repair and induces repair protein degradation in urothelial cells. Since acrolein is abundant in TS, inhaled acrolein is excreted into urine and accumulates in the bladder and because acrolein inhibits DNA repair and acrolein-dG DNA adducts are mutagenic, we propose that acrolein is a major bladder carcinogen in TS. PMID:24939871

Roles of Polyuria and Hyperglycemia on Bladder Dysfunction in Diabetes

PubMed Central

Xiao, Nan; Wang, Zhiping; Huang, Yexiang; Daneshgari, Firouz; Liu, Guiming

2014-01-01

Purpose Diabetes mellitus (DM) causes diabetic bladder dysfunction (DBD). We aimed to identify the pathogenic roles of polyuria and hyperglycemia on DBD in rats. Materials and Methods Seventy-two female Sprague-Dawley rats were divided: age-matched controls (control), sham urinary diversion (sham), urinary diversion (UD), streptozotocin-induced diabetes after sham UD (DM), streptozotocin-induced diabetes after UD (UD+DM), and 5% sucrose-induced diuresis after sham UD (DIU). UD was performed by ureterovaginostomy 10d before DM induction. Animals were evaluated 20 wks after DM or diuresis induction. We measured 24-hr drinking and voiding volumes and cystometry (CMG). Bladders were harvested for quantification of smooth muscle, urothelium, and collagen. We measured nitrotyrosine and manganese superoxide dismutase (MnSOD) in bladder. Results Diabetes and diuresis caused increases in drinking volume, voiding volume and bladder weight. Bladder weights decreased in the UD and UD+DM groups. Intercontractile intervals, voided volume, and compliance increased in the DIU and DM groups, decreased in the UD, and further decreased in the UD+DM group. The total cross-sectional tissue, smooth muscle and urothelium areas increased in the DIU and DM groups, and decreased in the UD and UD+DM groups. As percentages of total tissue area, collagen decreased in the DIU and DM groups, and increased in the UD and UD+DM groups, and smooth muscle and urothelium decreased in the UD and UD+DM groups. Nitrotyrosine and MnSOD increased in DM and UD+DM rats. Conclusions Polyuria induced bladder hypertrophy, while hyperglycemia induced substantial oxidative stress in the bladder, which may play a pathogenic role in late stage DBD. PMID:22999997

Identification of an unintended consequence of Nrf2-directed cytoprotection against a key tobacco carcinogen plus a counteracting chemopreventive intervention

PubMed Central

Paonessa, Joseph D.; Ding, Yi; Randall, Kristen L.; Munday, Rex; Argoti, Dayana; Vouros, Paul; Zhang, Yuesheng

2011-01-01

Nrf2 is a major cytoprotective gene and is a key chemopreventive target against cancer and other diseases. Here we show that Nrf2 faces a dilemma in defense against 4-aminobiphenyl (ABP), a major human bladder carcinogen from tobacco smoke and other environmental sources. While Nrf2 protected mouse liver against ABP (which is metabolically activated in liver), the bladder level of N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-ABP), the predominant ABP-DNA adduct formed in bladder cells and tissues, was markedly higher in Nrf2+/+ mice than in Nrf2−/− mice after ABP exposure. Notably, Nrf2 protected bladder cells against ABP in vitro. Mechanistic investigations showed that the dichotomous effects of Nrf2 could be explained at least partly by upregulation of UDP-glucuronosyltransferase (UGT). Nrf2 promoted conjugation of ABP with glucuronic acid in the liver, increasing urinary excretion of the conjugate. While glucuronidation of ABP and its metabolites is a detoxification process, these conjugates, which are excreted in urine, are known to be unstable in acidic urine, leading to delivery of the parent compounds to bladder. Hence, while higher liver UGT activity may protect the liver against ABP it increases bladder exposure to ABP. These findings raise concerns of potential bladder toxicity when Nrf2-activating chemopreventive agents are used in humans exposed to ABP, especially in smokers. We further demonstrate that 5,6-dihydrocyclopenta[c][1,2]-dithiole-3(4H)-thione (CPDT) significantly inhibits dG-C8-ABP formation in bladder cells and tissues, but does not appear to significantly modulate ABP-catalyzing UGT in liver. Thus, CPDT exemplifies a counteracting solution to the dilemma posed by Nrf2. PMID:21487034

Differentiation of malignant from benign soft tissue tumours: use of additive qualitative and quantitative diffusion-weighted MR imaging to standard MR imaging at 3.0 T.

PubMed

Lee, So-Yeon; Jee, Won-Hee; Jung, Joon-Yong; Park, Michael Y; Kim, Sun-Ki; Jung, Chan-Kwon; Chung, Yang-Guk

2016-03-01

To determine the added value of diffusion-weighted imaging (DWI) to standard magnetic resonance imaging (MRI) to differentiate malignant from benign soft tissue tumours at 3.0 T. 3.0 T MR images including DWI in 63 patients who underwent surgery for soft tissue tumours were retrospectively analyzed. Two readers independently interpreted MRI for the presence of malignancy in two steps: standard MRI alone, standard MRI and DWI with qualitative and quantitative analysis combined. There were 34 malignant and 29 non-malignant soft tissue tumours. In qualitative analysis, hyperintensity relative to skeletal muscle was more frequent in malignant than benign tumours on DWI (P=0.003). In quantitative analysis, ADCs of malignant tumours were significantly lower than those of non-malignant tumours (P≤0.002): 759±385 vs. 1188±423 μm(2)/sec minimum ADC value, 941±440 vs. 1310±440 μm(2)/sec average ADC value. The mean sensitivity, specificity and accuracy of both readers were 96%, 72%, and 85% on standard MRI alone and 97%, 90%, and 94% on standard MRI with DWI. The addition of DWI to standard MRI improves the diagnostic accuracy for differentiation of malignant from benign soft tissue tumours at 3.0 T. DWI has added value for differentiating malignant from benign soft tissue tumours. Addition of DWI to standard MRI at 3.0 T improves the diagnostic accuracy. Measurements of both ADC min within solid portion and ADC av are helpful.

Is photodynamic therapy a selective treatment? Analysis of local complications after endoscopic photodynamic therapy of early stage tumors of gastrointestinal, tracheobronchial, and urinary tracts

NASA Astrophysics Data System (ADS)

Spinelli, Pasquale; Dal Fante, Marco; Mancini, Andrea

1995-03-01

Selectivity is the most emphasized advantage of photodynamic therapy (PDT). However, at drug and light doses used for clinical applications, response from normal tissue surrounding the tumor reduces the real selectivity of the drug-light system and increases the surface of the area responding to the treatment. It is now evident that light irradiation of a sensitized patient produces damage at a various degree not only in the tumor but also in non-neoplastic tissues included in the field of irradiation. We report our experience in endoscopic PDT of early stage tumors in tracheobronchial, gastrointestinal and urinary tracts, describing early and late local complications caused by the damage of normal tissues adjacent to the tumors and included in the field of light irradiation. Among 44 patients treated, local complications, attributable to a poor selectivity of the modality, occurred in 6 patients (14%). In particular, the rate of local complications was 9% in patients treated for esophageal tumors, 14% in patients with gastric tumors, 9% in patients with tracheobronchial tumors, and 67% in bladder cancer patients. Clinical pictures as well as endoscopic findings at various intervals from treatment showed that mucositis is a common event following endoscopic PDT. It causes exudation and significant tissue inflammatory response, whose consequences are different in the various organs treated. Photoradiation must be, as much as possible, limited to the malignant area.

Epigenetic regulation of EFEMP1 in prostate cancer: biological relevance and clinical potential

PubMed Central

Almeida, Mafalda; Costa, Vera L; Costa, Natália R; Ramalho-Carvalho, João; Baptista, Tiago; Ribeiro, Franclim R; Paulo, Paula; Teixeira, Manuel R; Oliveira, Jorge; Lothe, Ragnhild A; Lind, Guro E; Henrique, Rui; Jerónimo, Carmen

2014-01-01

Epigenetic alterations are common in prostate cancer (PCa) and seem to contribute decisively to its initiation and progression. Moreover, aberrant promoter methylation is a promising biomarker for non-invasive screening. Herein, we sought to characterize EFEMP1 as biomarker for PCa, unveiling its biological relevance in prostate carcinogenesis. Microarray analyses of treated PCa cell lines and primary tissues enabled the selection of differentially methylated genes, among which EFEMP1 was further validated by MSP and bisulfite sequencing. Assessment of biomarker performance was accomplished by qMSP. Expression analysis of EFEMP1 and characterization of histone marks were performed in tissue samples and cancer cell lines to determine the impact of epigenetic mechanisms on EFEMP1 transcriptional regulation. Phenotypic assays, using transfected cell lines, permitted the evaluation of EFEMP1’s role in PCa development. EFEMP1 methylation assay discriminated PCa from normal prostate tissue (NPT; P < 0.001, Kruskall–Wallis test) and renal and bladder cancers (96% sensitivity and 98% specificity). EFEMP1 transcription levels inversely correlated with promoter methylation and histone deacetylation, suggesting that both epigenetic mechanisms are involved in gene regulation. Phenotypic assays showed that EFEMP1 de novo expression reduces malignant phenotype of PCa cells. EFEMP1 promoter methylation is prevalent in PCa and accurately discriminates PCa from non-cancerous prostate tissues and other urological neoplasms. This epigenetic alteration occurs early in prostate carcinogenesis and, in association with histone deacetylation, progressively leads to gene down-regulation, fostering cell proliferation, invasion and evasion of apoptosis. PMID:25211630

In vivo electric conductivity of cervical cancer patients based on B₁⁺ maps at 3T MRI.

PubMed

Balidemaj, E; de Boer, P; van Lier, A L H M W; Remis, R F; Stalpers, L J A; Westerveld, G H; Nederveen, A J; van den Berg, C A T; Crezee, J

2016-02-21

The in vivo electric conductivity (σ) values of tissue are essential for accurate electromagnetic simulations and specific absorption rate (SAR) assessment for applications such as thermal dose computations in hyperthermia. Currently used σ-values are mostly based on ex vivo measurements. In this study the conductivity of human muscle, bladder content and cervical tumors is acquired non-invasively in vivo using MRI. The conductivity of 20 cervical cancer patients was measured with the MR-based electric properties tomography method on a standard 3T MRI system. The average in vivo σ-value of muscle is 14% higher than currently used in human simulation models. The σ-value of bladder content is an order of magnitude higher than the value for bladder wall tissue that is used for the complete bladder in many models. Our findings are confirmed by various in vivo animal studies from the literature. In cervical tumors, the observed average conductivity was 13% higher than the literature value reported for cervical tissue. Considerable deviations were found for the electrical conductivity observed in this study and the commonly used values for SAR assessment, emphasizing the importance of acquiring in vivo conductivity for more accurate SAR assessment in various applications.

Dynamic Real-time Microscopy of the Urinary Tract Using Confocal Laser Endomicroscopy

PubMed Central

Wu, Katherine; Liu, Jen-Jane; Adams, Winifred; Sonn, Geoffrey A.; Mach, Kathleen E.; Pan, Ying; Beck, Andrew H.; Jensen, Kristin C.; Liao, Joseph C.

2014-01-01

OBJECTIVES To develop the diagnostic criteria for benign and neoplastic conditions of the urinary tract using probe-based confocal laser endomicroscopy (pCLE), a new technology for dynamic, in vivo imaging with micron-scale resolution. The suggested diagnostic criteria will formulate a guide for pCLE image interpretation in urology. METHODS Patients scheduled for transurethral resection of bladder tumor (TURBT) or nephrectomy were recruited. After white-light cystoscopy (WLC), fluorescein was administered as contrast. Different areas of the urinary tract were imaged with pCLE via direct contact between the confocal probe and the area of interest. Confocal images were subsequently compared with standard hematoxylin and eosin analysis. RESULTS pCLE images were collected from 66 participants, including 2 patients who underwent nephrectomy. We identified key features associated with different anatomic landmarks of the urinary tract, including the kidney, ureter, bladder, prostate, and urethra. In vivo pCLE of the bladder demonstrated distinct differences between normal mucosa and neoplastic tissue. Using mosaicing, a post hoc image-processing algorithm, individual image frames were juxtaposed to form wideangle views to better evaluate tissue microarchitecture. CONCLUSIONS In contrast to standard pathologic analysis of fixed tissue with hematoxylin and eosin, pCLE provides real time microscopy of the urinary tract to enable dynamic interrogation of benign and neoplastic tissues in vivo. The diagnostic criteria developed in this study will facilitate adaptation of pCLE for use in conjunction with WLC to expedite diagnosis of urinary tract pathology, particularly bladder cancer. PMID:21601243

Cigarette side-stream smoke lung and bladder carcinogenesis: inducing mutagenic acrolein-DNA adducts, inhibiting DNA repair and enhancing anchorage-independent-growth cell transformation

PubMed Central

Chin, Chiu; Huang, William; Lepor, Herbert; Wu, Xue-Ru; Rom, William N.; Chen, Lung-Chi; Tang, Moon-shong

2015-01-01

Second-hand smoke (SHS) is associated with 20–30% of cigarette-smoke related diseases, including cancer. Majority of SHS (>80%) originates from side-stream smoke (SSS). Compared to mainstream smoke, SSS contains more tumorigenic polycyclic aromatic hydrocarbons and acrolein (Acr). We assessed SSS-induced benzo(a)pyrene diol epoxide (BPDE)- and cyclic propano-deoxyguanosine (PdG) adducts in bronchoalveolar lavage (BAL), lung, heart, liver, and bladder-mucosa from mice exposed to SSS for 16 weeks. In SSS exposed mice, Acr-dG adducts were the major type of PdG adducts formed in BAL (p < 0.001), lung (p < 0.05), and bladder mucosa (p < 0.001), with no significant accumulation of Acr-dG adducts in heart or liver. SSS exposure did not enhance BPDE-DNA adduct formation in any of these tissues. SSS exposure reduced nucleotide excision repair (p < 0.01) and base excision repair (p < 0.001) in lung tissue. The levels of DNA repair proteins, XPC and hOGG1, in lung tissues of exposed mice were significantly (p < 0.001 and p < 0.05) lower than the levels in lung tissues of control mice. We found that Acr can transform human bronchial epithelial and urothelial cells in vitro. We propose that induction of mutagenic Acr-DNA adducts, inhibition of DNA repair, and induction of cell transformation are three mechanisms by which SHS induces lung and bladder cancers. PMID:26431382

[Study of susceptibility weighted imaging on MR and pathologic findings to distinguish benign or malignant soft tissue tumor].

PubMed

Liu, J; Chen, Y; Bao, X M; Ling, X L; Ding, J P; Zhang, Z K

2017-05-23

Objective: To explore the diagnostic performance of susceptibility weighted imaging (SWI)in distinguishing benign or malignant soft tissue tumor, and to study pathological observation. Methods: Sixty-eight patients with soft tissue tumor, who received no previous treatment or invasive examination, received routine preoperative MRI examination and SWI scanning. The graduation and distribution of intratumoral susceptibility signal intensity(ITSS) and proportion of tumor volume were observed.The pathological results were also included for comparative analysis. Results: Fourty of 68 patients were benign and 28 were malignant. 72.5% (29/40) patients with benign soft tissue tumors were ITSS grade 1 and ITSS grade 3 (hemangioma). 89.3%(25/28) patients with malignant soft tissue tumors were ITSS grade 2 and ITSS grade 3. The difference was statistically significant ( P <0.01). The distribution of ITSS in patients with benign soft tissue tumors was dominated by peripheral distribution and diffuse distribution (hemangioma), accounting for 90.0% (36/40). The distribution of ITSS in patients with malignant soft tissue tumors mainly distributed in the central region, accounting for 78.6% (22 /28). The difference was statistically significant ( P <0.01). The proportion of tumor volume occupied by ITSS in benign soft tissue tumors was <1/3 and> 2/3 (hemangioma), accounting for 90.0% (36/40). The volume of malignant soft tissue tumors were predominantly <1/3 , accounting for 82.1% (23/28). The difference was statistically significant ( P <0.01). Conclusion: SWI is sensitive in displaying the vein and blood metabolites in soft tissue lesions, which is helpful for the differential diagnosis of benign and malignant tumors in soft tissue.

Quality of life in patients with muscle invasive and non-muscle invasive bladder cancer.

PubMed

Singer, S; Ziegler, C; Schwalenberg, T; Hinz, A; Götze, H; Schulte, T

2013-05-01

Compared to the literature on other malignancies, data on quality of life (QoL) in bladder cancer are sparse. This study sought answers to the following questions: In what QoL domains do patients with bladder cancer differ from the general population? Do patients with radical cystectomy differ in QoL compared to those who received conservative treatment? Do patients with neobladder generally have better QoL compared to patients with other diversion methods? At the beginning of inpatient rehabilitation, N = 823 patients with bladder cancer were assessed. Data of a representative community sample (N = 2037) were used for comparison. The questionnaire EORTC QLQ-C30 was used to measure QoL. Multivariate linear regression models were computed to investigate differences between groups. Patients with both non-muscle invasive and muscle invasive bladder cancer reported significantly more problems and worse functioning than the general population. Radiotherapy is associated with clinically relevant more pain, dyspnoea, constipation, appetite loss and decreased social functioning while chemotherapy is associated more with dyspnoea. Cystectomy patients reported more fatigue, appetite loss and decreased role functioning. Male patients ≥70 years with conduit experienced more sleep and emotional problems. These effects of urinary diversion were not observed in women and younger patients. Patients with bladder cancer experience various QoL concerns at the beginning of inpatient rehabilitation. These problems can partly be explained by the type of treatment the patients receive. Type of urinary diversion is relevant for QoL in subgroups of patients.

[A case of eosinophilic cystitis mimicking an invasive bladder cancer].

PubMed

Okazaki, Satoshi; Hori, Jun-Ichi; Kita, Masafumi; Yamaguchi, Satoshi; Kawakami, Norihiro; Kakizaki, Hidehiro

2014-12-01

A 60-year-old woman was referred to our hospital because of gross hematuria, right lumbar pain and lower abdominal pain. Computed tomography (CT) scan revealed hydronephrosis of the right kidney, irregular bladder wall thickening at the right lateral and posterior portion and external iliac lymph node swelling of the right side. Laboratory data revealed disseminated intravascular coagulation syndrome (DIC) and eosinophilia. Because she developed a high fever that was caused by acute obstructive pyelonephritis of the right kidney, percutaneous nephrostomy was placed and the therapy for DIC was initiated. Pathological examination of transurethral resection of bladder tumor performed twice showed no malignancy but inflammatory infiltration of many eosinocytes, leading to the diagnosis of eosinophilic cystitis (EC). We considered the possibility of allergic reaction to the drugs she was taking as the etiology of EC and discontinued all drugs. Although eosinophilia was resolved afterward, she then developed brain infarction, followed by cerebral hemorrhage. She was transferred to a rehabilitation hospital for long-term care. CT scan that was performed 4 months after the initial presentation showed the resolution of hydronephrosis of the right kidney and external iliac lymph node swelling and the improvement of bladder wall thickness. Hydronephrosis of the right kidney has not recurred after removing the nephrostomy catheter. EC is a rare condition that could mimic an invasive bladder cancer. EC should be considered if bladder tumor is associated with eosinophilia. Therapeutic consideration for thromboembolic events should be made in patients with EC.

Bladder leiomyoma presenting as dyspareunia: Case report and literature review.

PubMed

Xin, Jun; Lai, Hai-Ping; Lin, Shao-Kun; Zhang, Qing-Quan; Shao, Chu-Xiao; Jin, Lie; Lei, Wen-Hui

2016-07-01

Leiomyoma of the bladder is a rare tumor arising from the submucosa. Most patients with bladder leiomyoma may present with urinary frequency or obstructive urinary symptoms. However, there are a few cases of bladder leiomyoma coexisting with uterine leiomyoma presenting as dyspareunia. We herein report an unusual case of coexisting bladder leiomyoma and uterine leiomyoma presenting as dyspareunia. A 44-year-old Asian female presented to urologist and complained that she had experienced dyspareunia over the preceding several months. A pelvic ultrasonography revealed a mass lesion located in the trigone of urinary bladder. The mass lesion was confirmed on contrast-enhanced computed tomography (CT). The CT scan also revealed a lobulated and enlarged uterus consistent with uterine leiomyoma. Then, the biopsies were then taken with a transurethral resection (TUR) loop and these biopsies showed a benign proliferation of smooth muscle in a connective tissue stroma suggestive of bladder leiomyoma. An open local excision of bladder leiomyoma and hysteromyomectomy were performed successfully. Histological examination confirmed bladder leiomyoma coexisting with uterine leiomyoma. This case highlights a rare presentation of bladder leiomyoma, dyspareunia, as the chief symptom in a patient who had coexisting uterine leiomyoma. Bladder leiomyomas coexisting with uterine leiomyomas are rare and can present with a wide spectrum of complaints including without symptoms, irritative symptoms, obstructive symptoms, or even dyspareunia.

Hybrid phosphorescence and fluorescence native spectroscopy for breast cancer detection.

PubMed

Alimova, Alexandra; Katz, A; Sriramoju, Vidyasagar; Budansky, Yuri; Bykov, Alexei A; Zeylikovich, Roman; Alfano, R R

2007-01-01

Fluorescence and phosphorescence measurements are performed on normal and malignant ex vivo human breast tissues using UV LED and xenon lamp excitation. Tryptophan (trp) phosphorescence intensity is higher in both normal glandular and adipose tissue when compared to malignant tissue. An algorithm based on the ratio of trp fluorescence intensity at 345 nm to phosphorescence intensity at 500 nm is successfully used to separate normal from malignant tissue types. Normal specimens consistently exhibited a low I(345)I(500) ratio (<10), while for malignant specimens, the I(345)I(500) ratio is consistently high (>15). The ratio analysis correlates well with histopathology. Intensity ratio maps with a spatial resolution of 0.5 mm are generated in which local regions of malignancy could be identified.

CureOne Registry: Advanced Malignancy or Myelodysplasia, Tested by Standard Sequencing and Treated by Physician Choice

ClinicalTrials.gov

2017-10-02

Neoplasms; Lung Neoplasms; Colon Neoplasms; Breast Neoplasms; Pancreatic Neoplasms; Prostate Neoplasms; Kidney Neoplasms; Liver Neoplasms; Rectal Neoplasms; Hematologic Neoplasms; Multiple Myeloma; Myelodysplastic Syndromes; Ovarian Neoplasms; Bladder Neoplasms; Testicular Neoplasms; Endometrial Neoplasms; Brain Neoplasms; Biliary Tract Neoplasms; Head and Neck Neoplasms; Uterine Cervical Neoplasms; Skin Neoplasms; Melanoma; Gastric Neoplasms; Anal Neoplasms; Sarcoma

Is whole-body fluorine-18 fluorodeoxyglucose PET/CT plus additional pelvic images (oral hydration-voiding-refilling) useful for detecting recurrent bladder cancer?

PubMed

Yang, Zhongyi; Cheng, Jingyi; Pan, Lingling; Hu, Silong; Xu, Junyan; Zhang, Yongping; Wang, Mingwei; Zhang, Jianping; Ye, Dingwei; Zhang, Yingjian

2012-08-01

Because of the urinary excretion of fluorine-18 fluorodeoxyglucose ((18)F-FDG), FDG-PET or PET/CT is thought of little value in patients with bladder cancer. The purpose of our study was to investigate the value of (18)F-FDG PET/CT with additional pelvic images in detection of recurrent bladder cancers. From December 2006 to August 2010, 35 bladder cancer patients (median age 56 years old, ranging from 35 to 96) underwent routine (18)F-FDG PET/CT. To better detect bladder lesions, a new method called as oral hydration-voiding-refilling was introduced, which included that all the patients firstly received oral hydration, then were required to void frequently and finally were demanded to hold back urine when the additional pelvic images were scanned. Lesions were confirmed by either histopathology or clinical follow-up for at least 6 months. Finally, 12 recurrent cases of 35 patients were confirmed by cystoscope. PET/CT correctly detected 11 of them. Among these 11 true positive patients, 5 patients (45.5 %) were detected only after additional pelvic images. Lichenoid lesions on the bladder wall were missed, which caused 1 false negative result. All three false positive cases were testified to be inflammatory tissues by cystoscope. Therefore, the sensitivity, specificity and accuracy of PET/CT were 91.7 % (11/12), 87.0 % (20/23) and 88.6 % (31/35), respectively. PET/CT with additional pelvic images can highly detect recurrent lesions in residual bladder tissues. Our method with high accuracy and better endurance could be potentially applied.

Monitoring of lower urinary tract function in patients with spinal cord injury using near infrared spectroscopy

NASA Astrophysics Data System (ADS)

Shadgan, Babak; Macnab, Andrew; Nigro, Mark; Stothers, Lynn

2012-02-01

Background: One of the most important conditions where there is loss of normal bladder function is spinal cord injury (SCI). Currently, evaluation of bladder function is limited to periodic invasive urodynamic testing (UDS). The purpose of this study was to assess the feasibility and usefulness of near-infrared spectroscopy (NIRS) in monitoring bladder function in patients with SCI during bladder filling and emptying and to investigate the correlations of NIRS measures with simultaneous UDS parameters. NIRS is a non-invasive optical method to study tissue oxygenation, hemodynamics and function by monitoring changes in the chromophore concentrations of oxygenated (O2Hb), deoxygenated (HHb) and total hemoglobin (tHb). Methods: 10 adult paraplegic patients with neurogenic bladder dysfunction who were referred for regular urodynamic evaluation were recruited. Changes in O2Hb, HHb and tHb, and tissue saturation index (TSI%) in the detrusor were monitored and recorded by a wireless NIRS system during the urodynamic evaluation. Time points of urgency and urinary leakage were marked and patterns of change in NIRS parameters were compared to standard urodynamic pressure tracings. Results: Strong consistency between changes in NIRS-derived tHb and changes in intravesical pressure were observed during filling across the subjects. During bladder filling a gradual increase in O2Hb and tHb with minimal changes in HHb was observed. Interestingly, a drop in TSI% was detected seconds before strong urgency and urinary leakage. Conclusions: Our preliminary data suggest a relationship between noninvasive NIRS measures and UDS parameters during bladder filling in SCI patients.

[Correlation of infection with the physical and chemical characteristics of gall bladder contents].

PubMed

Sulaberidze, G T; Rachvelishvili, B Kh; Gelbakhiani, G P; Barbakadze, G G; Kapanadze, A G

2005-06-01

The aim of the study was to investigate pH and viscosity (h) of gall bladder contents during cholelithiasis and establishment of their correlation with bacterial and HBV infections. Seventy-eight patients undergone the planned cholecystectomy were investigated. 5 healthy persons (control group) were also involved into the study. In all cases the markers of HBV (Anti-HB core IgG, Anti-HB core IgM, HBsAg) in blood were detected, also bacteriological analysis of gall bladder tissue was performed. In 78 cases (I group) pH of gall bladder contents was measured, in 29 cases (II group), also viscosity of gall was studied. In the control group pH and viscosity were detected. Statistical analysis was performed using ANOVA method. Bacteriological study revealed presence of bacterial infection in gall bladder tissue in 34 cases (43,6%), in 30 patients Anti-HB core antibodies were found in the blood, in 13 cases (16,7%) coincidence of bacterial and HBV infection was documented. Mean indexes of pH and viscosity appeared to be significantly higher in the operated group (pH--7,30, h 2,1 mm(2)/sec), then in the control group (pH--6,74, h--1,34 mm(2)/sec); this indexes were highest in the infected patients. Thus, according to results of the study, changes of pH and viscosity of gall bladder contents could be considered as the useful indexes of initial stage of cholelithiasis and their values depend on the presence of bacterial or HBV infection of gall bladder.

Layer-dependent role of collagen recruitment during loading of the rat bladder wall.

PubMed

Cheng, Fangzhou; Birder, Lori A; Kullmann, F Aura; Hornsby, Jack; Watton, Paul N; Watkins, Simon; Thompson, Mark; Robertson, Anne M

2018-04-01

In this work, we re-evaluated long-standing conjectures as to the source of the exceptionally large compliance of the bladder wall. Whereas these conjectures were based on indirect measures of loading mechanisms, in this work we take advantage of advances in bioimaging to directly assess collagen fibers and wall architecture during biaxial loading. A custom biaxial mechanical testing system compatible with multiphoton microscopy was used to directly measure the layer-dependent collagen fiber recruitment in bladder tissue from 9 male Fischer rats (4 adult and 5 aged). As for other soft tissues, the bladder loading curve was exponential in shape and could be divided into toe, transition and high stress regimes. The relationship between collagen recruitment and loading curves was evaluated in the context of the inner (lamina propria) and outer (detrusor smooth muscle) layers. The large extensibility of the bladder was found to be possible due to folds in the wall (rugae) that provide a mechanism for low resistance flattening without any discernible recruitment of collagen fibers throughout the toe regime. For more extensible bladders, as the loading extended into the transition regime, a gradual coordinated recruitment of collagen fibers between the lamina propria layer and detrusor smooth muscle layer was found. A second important finding was that wall extensibility could be lost by premature recruitment of collagen in the outer wall that cut short the toe region. This change was correlated with age. This work provides, for the first time, a mechanistic understanding of the role of collagen recruitment in determining bladder extensibility and capacitance.

The Activity of Class I-IV Alcohol Dehydrogenase Isoenzymes and Aldehyde Dehydrogenase in Bladder Cancer Cells.

PubMed

Orywal, Karolina; Jelski, Wojciech; Werel, Tadeusz; Szmitkowski, Maciej

2018-01-02

The aim of this study was to determine the differences in the activity of Alcohol Dehydrogenase (ADH) isoenzymes and Aldehyde Dehydrogenase (ALDH) in normal and cancerous bladder cells. Class III, IV of ADH and total ADH activity were measured by the photometric method and class I, II ADH and ALDH activity by the fluorometric method. Significantly higher total activity of ADH was found in both, low-grade and high-grade bladder cancer, in comparison to healthy tissues. The increased activity of total ADH in bladder cancer cells may be the cause of metabolic disorders in cancer cells, which may intensify carcinogenesis.

Hormone replacement therapy and risk of malignancy.

PubMed

Diamanti-Kandarakis, Evanthia

2004-02-01

The fact that today our concern is oriented towards the risks rather than the benefits of hormone replacement therapy could be the clearest message about our current position. The safety of hormone replacement therapy, an estrogen-progestin combination which has been sympathetic to and supportive of disturbing menopausal symptoms of women, is seriously challenged. Four randomized trials have now reported on the results of hormone replacement therapy in major potentially fatal conditions, in more than 20,000 women studied for about 5 years. The main concern regarding the increased risk of malignancy in healthy postmenopausal women in western countries has been breast cancer. It is estimated to cause an extra case in about six per 1000 users aged 50-59 and 12 per 1000 aged 60-69. Over the same period the estimated risk of endometrial cancer rates are not increased, with a relative risk of 0.76 per 1000 users aged 50-59. Overall, however, the increased incidence of malignancies is greater than any reduction, one per 230 users aged 50-59 and one per 150 aged 60-69. Randomized trials examining other important but rarer malignancies, like ovarian, gall bladder and urinary bladder cancer, are either nonexistent or too small to reliably describe any effects of hormone replacement therapy. Conclusively epidemiological evidence suggests that hormone replacement therapy is associated with a small but substantial increase in breast cancer risk and combined estrogen-progesterone regimens further increase this hazard. Additionally, the evidence from the recent double blind placebo controlled randomized trial on the slight increase in the incidence of adverse cardiovascular events, has turned our orientation away from hormone replacement therapy as a long term therapy in postmenopausal women. In this review, the effort is to approach comprehensively and globally the information on the risks of hormone replacement therapy on several cancer sites.

N-acetyltransferase 1*10 genotype in bladder cancer patients.

PubMed

Höhne, Svetlana; Gerullis, Holger; Blaszkewicz, Meinolf; Selinski, Silvia; Hengstler, Jan G; Otto, Thomas; Golka, Klaus

2017-01-01

In a large bladder cancer study in the greater Berlin area with 425 cases and 343 controls, the haplotype N-acetyltransferase 1*10 (NAT1*10) was associated with a decreased bladder cancer risk. In a recently published meta-analysis, results of the studies were found to be inconclusive. Therefore, the aim of this study was to investigate the frequency of NAT1*10 in bladder cancer patients and controls recruited in an area without industries reported to be associated with increased bladder cancer risk. Rs1057126 (1088 T > A) and rs15561 (1095 C > A) were determined in 412 bladder cancer patients and 415 controls without a known history of malignancies. With these two single-nucleotide polymorphisms (SNP), it was possible to distinguish between NAT1*4 (wild type), NAT1*3 (1095 C > A), and NAT1*10 (1088 T > A, 1095C > A). The frequencies of the determined NAT1 haplotypes did not differ markedly between cases and controls: NAT1*4: 74%, NAT1*3: 6%, NAT1*10: 20%. Bladder cancer risk was not significantly modulated by NAT1*10/*10 (OR 1.03, 95% CI 0.71-1.48) but was higher for NAT1*3/*3 genotypes (OR 2.05, 95% CI 1.32-3.21). In contrast to the Berlin study from 2001, data in present study demonstrated that NAT1*10 haplotype was not associated with a significantly decreased bladder cancer risk. This may be due to local effects in the greater Berlin area, particularly at the time of investigation. The findings of the present study are in agreement with observations of a recently published meta-analysis which also showed no relevant impact of NAT1*10 haplotype on bladder cancer risk. The impact of the rare NAT1*3/*3 genotype was significant but this may be attributed to rarity without major practical relevance.

Effect of coffee drinking on cell proliferation in rat urinary bladder epithelium.

PubMed

Lina, B A; Rutten, A A; Woutersen, R A

1993-12-01

A possible effect of freshly brewed drip coffee on urinary bladder carcinogenesis was investigated in male Wistar rats using cell proliferation in urinary bladder epithelium as the indicator of tumour promotion. Male rats were given either undiluted coffee brew (100% coffee), coffee diluted 10 times (10% coffee) or tap water (controls), as their only source of drinking fluid for 2 or 6 wk. Uracil, known to induce cell proliferation in urinary bladder epithelium, was included in the study as a positive control. In rats receiving 100% coffee, body weights, liquid intake and urinary volume were decreased. Neither histopathological examination of urinary bladder tissue nor the bromodeoxyuridine labelling index revealed biologically significant differences between rats receiving coffee and the tap water controls. Uracil increased the labelling index and induced hyperplasia of the urinary bladder epithelium, as expected. It was concluded that these results produced no evidence that drinking coffee predisposes to tumour development in the urinary bladder.

[Concomitant oncopathological changes in the prostate of urinary bladder cancer patients undergoing radical cystoprostateectomy].

PubMed

Komyakov, B K; Sergeev, A V; Fadeev, V A; Ismailov, K I; Ulyanov, A Yu; Shmelev, A Yu; Onoshko, M V

2017-09-01

To determine the incidence of spreading bladder transitional cell carcinoma and primary adenocarcinoma to the prostate in patients with bladder cancer undergoing radical cystectomy. From 1995 to 2016, 283 men underwent radical cystectomy with removal of the bladder, perivesical tissue, prostate, seminal vesicles and pelvic lymph nodes. Prostate sparing cystectomy was performed in 45 (13.7%) patients. The whole prostate and the apex of the prostate were preserved in 21 (6.4%) and 24 (7.3%) patients, respectively. The spread of transitional cell cancer of the bladder to the prostate occurred in 50 (15.2%) patients. Twelve (3.6%) patients were found to have primary prostate adenocarcinoma. Clinically significant prostate cancer was diagnosed in 4 (33.3%) patients. We believe that the high oncological risk of prostate sparing cystectomy, despite some functional advantages, dictates the need for complete removal of the prostate in the surgical treatment of bladder cancer.

miR-1182 inhibits growth and mediates the chemosensitivity of bladder cancer by targeting hTERT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Jun; Dai, Wenbin, E-mail: daiwenbin271@163.com; Song, Jianming

2016-02-05

microRNAs (miRNAs) have been demonstrated to contribute to tumor progression and metastasis and proposed to be key regulators of diverse biological processes. In this study, we report that miR-1182 is deregulated in bladder cancer tissues and cell lines. To characterize the role of miR-1182 in bladder cancer cells, we performed functional assays. The overexpression of miR-1182 significantly inhibits bladder cancer cell proliferation, colony formation, and invasion. Moreover, its up-regulation induced cell cycle arrest and apoptosis and mediated chemosensitivity to cisplatin in bladder cancer. Furthermore, a luciferase reporter assay and a rescue experiment indicated that miR-1182 directly targets hTERT by bindingmore » its 3′UTR. In conclusion, these results demonstrate that miR-1182 acts as a tumor suppressor and may be a potential biomarker for bladder cancer diagnosis and treatment.« less

Bone dissemination of prostate cancer after holmium laser enucleation of the prostate: a case report and a review of the literature.

PubMed

Koguchi, Dai; Nishi, Morihiro; Satoh, Takefumi; Shitara, Toshiya; Matsumoto, Kazumasa; Fujita, Tetsuo; Yoshida, Kazunari; Iwamura, Masatsugu

2014-02-01

We report a case of dissemination of prostate cancer after holmium laser enucleation of the prostate in an 80-year-old patient. The patient presented at hospital because of nocturia. Transrectal ultrasound-guided biopsy was carried out because of high serum prostate-specific antigen (3.55 ng/mL), but it showed no malignancies. Benign prostate hyperplasia was diagnosed, and he was started on an α1-blocker. Although the urinary symptom improved with silodosin, acute urinary retention occurred 3 years after therapy began. Holmium laser enucleation of the prostate for relief of bladder outlet obstruction enabled discharge of urine. Pathological examination of the resected tissue found adenocarcinoma with a high Gleason score, 4 + 5. Serum alkaline phosphatase increased rapidly after holmium laser enucleation, and bone scintigraphy confirmed multiple bone metastases. Prostate cancer, T1bN0M1b, was diagnosed. © 2013 The Japanese Urological Association.

Temperature-responsive grafted polymer brushes obtained from renewable sources with potential application as substrates for tissue engineering

NASA Astrophysics Data System (ADS)

Raczkowska, Joanna; Stetsyshyn, Yurij; Awsiuk, Kamil; Lekka, Małgorzata; Marzec, Monika; Harhay, Khrystyna; Ohar, Halyna; Ostapiv, Dmytro; Sharan, Mykola; Yaremchuk, Iryna; Bodnar, Yulia; Budkowski, Andrzej

2017-06-01

The novel temperature-responsive poly(cholesteryl methacylate) (PChMa) coatings derived from renewable sources were synthesized and characterized. Temperature induced changes in wettability were accompanied by surface roughness modifications, traced with AFM. Topographies recorded for temperatures increasing from 5 to 25 °C showed a slight but noticeable increase of calculated root mean square (RMS) roughness by a factor of 1.5, suggesting a horizontal rearrangement in the structure of PChMa coatings. Another structural reordering was observed in the 55-85 °C temperature range. The recorded topography changed noticeably from smooth at 55 °C to very structured and rough at 60 °C and returned eventually to relatively smooth at 85 °C. In addition, temperature transitions of PChMa molecules were revealed by DSC measurements. The biocompatibility of the PChMa-grafted coatings was shown for cultures of granulosa cells and a non malignant bladder cancer cell (HCV29 line) culture.

Recent advances in photodynamic diagnosis of gastric cancer using 5-aminolevulinic acid.

PubMed

Koizumi, Noriaki; Harada, Yoshinori; Minamikawa, Takeo; Tanaka, Hideo; Otsuji, Eigo; Takamatsu, Tetsuro

2016-01-21

Photodynamic diagnosis based on 5-aminolevulinic acid-induced protoporphyrin IX has been clinically applied in many fields based upon its evidenced efficacy and adequate safety. In order to establish a personalized medicine approach for treating gastric cancer patients, rapid intraoperative detection of malignant lesions has become important. Feasibility of photodynamic diagnosis using 5-aminolevulinic acid for gastric cancer patients has been investigated, especially for the detection of peritoneal dissemination and lymph node metastasis. This method enables intraoperative real-time fluorescence detection of peritoneal dissemination, exhibiting higher sensitivity than white light observation without histopathological examination. The method also enables detection of metastatic foci within excised lymph nodes, exhibiting a diagnostic accuracy comparable to that of a current molecular diagnostics technique. Although several complicating issues still need to be resolved, such as the effect of tissue autofluorescence and the insufficient depth penetration of excitation light, this simple and rapid method has the potential to become a useful diagnostic tool for gastric cancer, as well as urinary bladder cancer and glioma.

Neurogenic bladder in spinal cord injury patients

PubMed Central

Taweel, Waleed Al; Seyam, Raouf

2015-01-01

Neurogenic bladder dysfunction due to spinal cord injury poses a significant threat to the well-being of patients. Incontinence, renal impairment, urinary tract infection, stones, and poor quality of life are some complications of this condition. The majority of patients will require management to ensure low pressure reservoir function of the bladder, complete emptying, and dryness. Management typically begins with anticholinergic medications and clean intermittent catheterization. Patients who fail this treatment because of inefficacy or intolerability are candidates for a spectrum of more invasive procedures. Endoscopic managements to relieve the bladder outlet resistance include sphincterotomy, botulinum toxin injection, and stent insertion. In contrast, patients with incompetent sphincters are candidates for transobturator tape insertion, sling surgery, or artificial sphincter implantation. Coordinated bladder emptying is possible with neuromodulation in selected patients. Bladder augmentation, usually with an intestinal segment, and urinary diversion are the last resort. Tissue engineering is promising in experimental settings; however, its role in clinical bladder management is still evolving. In this review, we summarize the current literature pertaining to the pathology and management of neurogenic bladder dysfunction in patients with spinal cord injury. PMID:26090342

Effects of fasudil, a Rho-kinase inhibitor, on contraction of pig bladder tissues with or without urothelium.

PubMed

Tatsumiya, Katsuhisa; Yamanishi, Tomonori; Watanabe, Miho; Masuda, Akinori; Mizuno, Tomoya; Kamai, Takao; Yoshida, Ken-Ichiro

2009-12-01

To investigate the effects of fasudil, a Rho-associated serine-threonine protein kinase inhibitor, on contraction of the pig urinary bladder tissues with or without urothelium. Cumulative concentration-response curves (CRCs) to carbachol were obtained with and without 3-10 microM fasudil. Drug effects were evaluated in detrusor with and without urothelium. Inhibitory responses to fasudil were also examined in tissues precontracted with KCl and carbachol, and in response to electrical field stimulation, in pig bladder with and without urothelium. In detrusor without urothelium, maximum contraction (E(max)) decreased after administration of fasudil at 3 or 10 micromol/L (both P < 0.01), or 30 micromol/L (72.5 + or - 7.43%, 58.4 + or - 8.04% and 68.4 + or - 9.6%, respectively, of the first curve). In detrusor with urothelium, E(max) decreased significantly (all P < 0.05) after the addition of 3, 10 or 30 micromol/L of fasudil (84.9 + or - 6.7%, 67.9 + or - 5.2% and 35.2 + or - 4.1%, respectively). In tissues precontracted with 80 mmol/L KCl or 100 micromol/L carbachol, tension after administration of fasudil (1 nmol/L to 100 micromol/L) decreased (by approximately 40%), only after administration of fasudil at high concentration (>1 micromol/L), in detrusor both with and without urothelium. In tissues with and without urothelium, responses to electrical field stimulation at 1-50 Hz decreased significantly in a concentration-dependent manner after addition of fasudil (3 to 30 micromol/L). Fasudil seems to provoke relaxation of the bladder detrusor via both urothelium-dependent and independent pathways.

Low amplitude rhythmic contraction frequency in human detrusor strips correlates with phasic intravesical pressure waves.

PubMed

Colhoun, Andrew F; Speich, John E; Cooley, Lauren F; Bell, Eugene D; Barbee, R Wayne; Guruli, Georgi; Ratz, Paul H; Klausner, Adam P

2017-08-01

Low amplitude rhythmic contractions (LARC) occur in detrusor smooth muscle and may play a role in storage disorders such as overactive bladder and detrusor overactivity. The purpose of this study was to determine whether LARC frequencies identified in vitro from strips of human urinary bladder tissue correlate with in vivo LARC frequencies, visualized as phasic intravesical pressure (p ves ) waves during urodynamics (UD). After IRB approval, fresh strips of human urinary bladder were obtained from patients. LARC was recorded with tissue strips at low tension (<2 g) and analyzed by fast Fourier transform (FFT) to identify LARC signal frequencies. Blinded UD tracings were retrospectively reviewed for signs of LARC on the p ves tracing during filling and were analyzed via FFT. Distinct LARC frequencies were identified in 100% of tissue strips (n = 9) obtained with a mean frequency of 1.97 ± 0.47 cycles/min (33 ± 8 mHz). Out of 100 consecutive UD studies reviewed, 35 visually displayed phasic p ves waves. In 12/35 (34%), real p ves signals were present that were independent of abdominal activity. Average UD LARC frequency was 2.34 ± 0.36 cycles/min (39 ± 6 mHz) which was similar to tissue LARC frequencies (p = 0.50). A majority (83%) of the UD cohort with LARC signals also demonstrated detrusor overactivity. During UD, a subset of patients displayed phasic p ves waves with a distinct rhythmic frequency similar to the in vitro LARC frequency quantified in human urinary bladder tissue strips. Further refinements of this technique may help identify subsets of individuals with LARC-mediated storage disorders.

Soft-tissue applications of the holmium:YAG laser in urology

NASA Astrophysics Data System (ADS)

Denstedt, John D.; Razvi, Hassan A.; Chun, Samuel S.; Sales, Jack L.

1995-05-01

The ideal surgical laser for the treatment of soft tissue pathology should possess both ablative and hemostatic abilities. As well, for use in urologic conditions the laser must also be suitable for endoscopic use. The Holmium:YAG laser possesses these qualities and in preliminary clinical use has demonstrated a variety of potential urologic applications. In this study we review our initial experience with the Holmium:YAG laser over a 18 month period. A total of 51 patients underwent 53 procedures for a variety of soft tissue conditions including: bladder tumor ablation (25), incision of ureteral stricture (15), incision of urethral stricture (6), treatment of ureteropelvic junction obstruction (3), incision of bladder neck contracture (2), and ablation of a ureteral tumor (2). Satisfactory hemostasis was achieved in all cases. Procedures were considered successful (no further intervention being required to treat the condition) in 81% of the cases. Two patients with dense bladder neck contractures required electroincision under the same anesthetic for completion of the procedure. A single complication, that of urinary extravasation following incision of a urethral stricture resolved with conservative management. In summary, the Holmium:YAG laser has demonstrated safety and proficiency in the treatment of a variety of urologic soft tissue conditions.

Trimodal spectra for high discrimination of benign and malignant prostate tissue

NASA Astrophysics Data System (ADS)

Al Salhi, Mohamad; Masilamani, Vadivel; Trinka, Vijmasi; Rabah, Danny; Al Turki, Mohammed R.

2011-02-01

High false positives and over diagnosis is a major problem with management of prostate cancer. A non-invasive or a minimally invasive technique to accurately distinguish malignant prostate cancers from benign tumors will be extremely helpful to overcome this problem. In this paper, we had used three different fluorescence spectroscopy techniques viz., Fluorescence Emission Spectrum (FES), Stokes' Shift Spectrum (SSS) and Reflectance Spectrum (RS) to discriminate benign prostate tumor tissues (N=12) and malignant prostate cancer tissues (N=8). These fluorescence techniques were used to determine the relative concentration of naturally occurring biomolecules such as tryptophan, elastin, NADH and flavin which are found to be out of proportion in cancer tissues. Our studies show that combining all three techniques, benign and malignant prostate tissues could be classified with accuracy greater than 90%. This preliminary report is based on in vitro spectroscopy analysis. However, by employing fluorescence endoscopy techniques, this can be extended to in vivo analysis as well. This technique has the potential to identify malignant prostate tissues without surgery.

Skull infarction in a patient with malignant fibrous histiocytoma.

PubMed

Nagle, C E; Morayati, S J; LeDuc, M A

1987-09-01

The authors describe a case of a skull infarction initially suspected to be an isolated, remote metastasis in a patient diagnosed with soft tissue malignant fibrous histiocytoma. Osseous malignant fibrous histiocytoma has been reported to occur within a bone infarction but the presence of a benign bone infarction remote from a soft tissue malignant fibrous histiocytoma has not been reported previously. Bone infarctions and malignant fibrous histiocytomas are briefly reviewed.

NF-κB pathways are involved in M1 polarization of RAW 264.7 macrophage by polyporus polysaccharide in the tumor microenvironment

PubMed Central

Liu, Chun-Ping; Zhang, Xian; Tan, Qing-Long; Xu, Wen-Xing; Zhou, Chang-Yuan; Luo, Min; Li, Xiong; Zeng, Xing

2017-01-01

Bladder cancer is one of the most malignant tumors closely associated with macrophages. Polyporus polysaccharide (PPS) has shown excellent efficacy in treating bladder cancer with minimal side effects. However, the molecular mechanisms underlying the effects of PPS in inhibiting bladder cancer remain unclear. In this study, we used macrophages cultured alone or with T24 human bladder cancer cell culture supernatant as study models. We found that PPS enhanced the activities of IFN-γ-stimulated RAW 264.7 macrophages, as shown by the release of inducible nitric oxide synthase (INOS), secretion of tumor necrosis factor (TNF)-α and interleukin (IL)-6, phagocytosis activity, as well as expression of M1 phenotype indicators, such as CD40, CD284 and CD86. PPS acted upstream in activation cascade of nuclear factor (NF)-κB signaling pathways by interfering with IκB phosphorylation. In addition, PPS regulated NF-κB (P65) signaling by interfering with Toll-like receptor (TLR)-4, INOS and cyclooxygenase (COX)-2. Our results indicate that PPS activates macrophages through TLR4/NF-κB signaling pathways. PMID:29155869

Differential Expression of Glypican-3 and Insulin–Like Growth Factor-II mRNAs and Alpha-Fetoprotein and Ki-67 Markers in HCV Related Hepatocellular Carcinomas In Egyptian Patients

PubMed

Saber, Mohamed A; MM AbdelHafiz, Samah; Khorshed, Fatma E; Aboushousha, Tarek S; Hamdy, Hussam EM; Seleem, Mohamed I; Soliman, Amira H

2017-01-01

Background: Increasing evidence indicates that in hepatocellular carcinomas (HCCs) abnormal gene expression, for example of glypican-3 (GPC-3) and insulin-like growth factor-II (IGF-II), are associated with the occurrence and progression of HCC. The objective of this study was to evaluate the differential expression of GPC-3 and IGF-II mRNAs in HCC tissues with a background of chronic hepatitis C virus (HCV) genotype 4 cirrhosis, in relation to Ki-67 and alpha-feto protein (AFP) tissue markers. Methods: One hundred and five patients with HCCs who had undergone hepatectomy, were included, after obtaining informed consent. Total RNA was extracted from malignant and corresponding peri-malignant liver tissues, and GPC-3 and IGF-II mRNAs in addition to beta-actin mRNA as an internal control, were evaluated in all samples by reverse transcriptase-polymerase chain reactions (RT-PCR). Routine histopathological diagnosis as well as immunohistochemical (IHC) staining using monoclonal antibodies for Ki-67 and AFP were also performed. Result: Expression of GPC-3 mRNA was positive in all HCC malignant tissue, with overexpression in 86/105 (81.9%); in respect to the grade of the tumor (1-3 grades), while in peri-malignant tissue it was over expressed only in 20/105 (19%). The IGF-II mRNA was over expressed in only 10/105 (9.5%) malignant and peri-malignant samples. AFP was expressed in 33.3% of malignant samples but absent in peri-malignant tissues. Ki-67 expression was significantly increased in malignant compared to peri-malignant tissue. Conclusion: GPC-3 and IGF II mRNAs may be good molecular markers for HCC, especially with a background of cirrhosis due to chronic HCV infection. Significant correlations were noted with the pattern of AFP and Ki-67 expression. Creative Commons Attribution License

Machine learning aided diagnosis of hepatic malignancies through in vivo dielectric measurements with microwaves.

PubMed

Yilmaz, Tuba; Kılıç, Mahmut Alp; Erdoğan, Melike; Çayören, Mehmet; Tunaoğlu, Doruk; Kurtoğlu, İsmail; Yaslan, Yusuf; Çayören, Hüseyin; Arkan, Akif Enes; Teksöz, Serkan; Cancan, Gülden; Kepil, Nuray; Erdamar, Sibel; Özcan, Murat; Akduman, İbrahim; Kalkan, Tunaya

2016-06-20

In the past decade, extensive research on dielectric properties of biological tissues led to characterization of dielectric property discrepancy between the malignant and healthy tissues. Such discrepancy enabled the development of microwave therapeutic and diagnostic technologies. Traditionally, dielectric property measurements of biological tissues is performed with the well-known contact probe (open-ended coaxial probe) technique. However, the technique suffers from limited accuracy and low loss resolution for permittivity and conductivity measurements, respectively. Therefore, despite the inherent dielectric property discrepancy, a rigorous measurement routine with open-ended coaxial probes is required for accurate differentiation of malignant and healthy tissues. In this paper, we propose to eliminate the need for multiple measurements with open-ended coaxial probe for malignant and healthy tissue differentiation by applying support vector machine (SVM) classification algorithm to the dielectric measurement data. To do so, first, in vivo malignant and healthy rat liver tissue dielectric property measurements are collected with open-ended coaxial probe technique between 500 MHz to 6 GHz. Cole-Cole functions are fitted to the measured dielectric properties and measurement data is verified with the literature. Malign tissue classification is realized by applying SVM to the open-ended coaxial probe measurements where as high as 99.2% accuracy (F1 Score) is obtained.

SU-E-J-206: Adaptive Radiotherapy for Gynecological Malignancies with MRIGuided Cobolt-60 Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lamb, J; Kamrava, M; Agazaryan, N

Purpose: Even in the IMRT era, bowel toxicity and bone marrow irradiation remain concerns with pelvic irradiation. We examine the potential gain from an adaptive radiotherapy workflow for post-operative gynecological patients treated to pelvic targets including lymph nodes using MRI-guided Co-60 radiation therapy. Methods: An adaptive workflow was developed with the intent of minimizing time overhead of adaptive planning. A pilot study was performed using retrospectively analyzed images from one patient’s treatment. The patient’s treated plan was created using conventional PTV margins. Adaptive treatment was simulated on the patient’s first three fractions. The daily PTV was created by removing non-targetmore » tissue, including bone, muscle and bowel, from the initial PTV based on the daily MRI. The number of beams, beam angles, and optimization parameters were kept constant, and the plan was re-optimized. Normal tissue contours were not adjusted for the re-optimization, but were adjusted for evaluation of plan quality. Plan quality was evaluated based on PTV coverage and normal tissue DVH points per treatment protocol. Bowel was contoured as the entire bowel bag per protocol at our institution. Pelvic bone marrow was contoured per RTOG protocol 1203. Results: For the clinically treated plan, the volume of bowel receiving 45 Gy was 380 cc, 53% of the rectum received 30 Gy, 35% of the bladder received 45 Gy, and 28% of the pelvic bone marrow received 40 Gy. For the adaptive plans, the volume of bowel receiving 45 Gy was 175–201 cc, 55–62% of the rectum received 30 Gy, 21– 27% of the bladder received 45 Gy, and 13–17% of the pelvic bone marrow received 40 Gy. Conclusion: Adaptive planning led to a large reduction of bowel and bone marrow dose in this pilot study. Further study of on-line adaptive techniques for the radiotherapy of pelvic lymph nodes is warranted. Dr. Low is a member of the scientific advisory board of ViewRay, Inc.« less

Bladder cancer mortality trends and patterns in Córdoba, Argentina (1986-2006).

PubMed

Pou, Sonia Alejandra; Osella, Alberto Ruben; Diaz, Maria Del Pilar

2011-03-01

Bladder cancer is common worldwide and the fourth most commonly diagnosed malignancy in men in Argentina. To describe bladder cancer mortality trends in Córdoba (1986-2006), considering the effect of age, period, and cohort, and to estimate the effect of arsenic exposure on bladder cancer, and its interaction with sex, while controlling by smoking habits and space and time variation of the rates. A joinpoint regression was performed to compute the estimated annual percentage changes (EAPC) of the age-standardized mortality rates (ASMR) in an adult population from Córdoba, Argentina. A Poisson model was fitted to estimate the effect of age, period, and cohort. The influence of gender, tobacco smoking (using lung cancer ASMR as surrogate), and arsenic in drinking water was examined using a hierarchical model. A favorable trend (1986-2006) in bladder cancer ASMR in both sexes was found: EAPC of -2.54 in men and -1.69 in women. There was a decreasing trend in relative risk (RR) for cohorts born in 1931 or after. The multilevel model showed an increasing risk for each increase in lung cancer ASMR unit (RR = 1.001) and a biological interaction between sex and arsenic exposure. RR was higher among men exposed to increasing As-exposure categories (RR male low exposure 3.14, RR male intermediate exposure 4.03, RR male high exposure 4.71 versus female low exposure). A non-random space-time distribution of the rates was observed. There has been a decreasing trend in ASMR for bladder cancer in Córdoba. This study confirms that bladder cancer is associated with age, gender, smoking habit, and exposure to arsenic. Moreover, an effect measure modification between exposure to arsenic and sex was found.

Gemcitabine Hydrochloride With or Without Pazopanib Hydrochloride in Treating Patients With Refractory Soft Tissue Sarcoma

ClinicalTrials.gov

2017-11-01

Adult Alveolar Soft Part Sarcoma; Adult Angiosarcoma; Adult Desmoplastic Small Round Cell Tumor; Adult Epithelioid Hemangioendothelioma; Adult Epithelioid Sarcoma; Adult Extraskeletal Myxoid Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Mesenchymoma; Adult Malignant Peripheral Nerve Sheath Tumor; Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Adult Undifferentiated Pleomorphic Sarcoma; Malignant Adult Hemangiopericytoma; Recurrent Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

Depsipeptide (Romidepsin) in Treating Patients With Metastatic or Unresectable Soft Tissue Sarcoma

ClinicalTrials.gov

2017-05-18

Adult Alveolar Soft-part Sarcoma; Adult Angiosarcoma; Adult Epithelioid Sarcoma; Adult Extraskeletal Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Fibrous Histiocytoma; Adult Malignant Hemangiopericytoma; Adult Malignant Mesenchymoma; Adult Neurofibrosarcoma; Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Gastrointestinal Stromal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Adult Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

A large-scale study of the ultrawideband microwave dielectric properties of normal, benign and malignant breast tissues obtained from cancer surgeries

NASA Astrophysics Data System (ADS)

Lazebnik, Mariya; Popovic, Dijana; McCartney, Leah; Watkins, Cynthia B.; Lindstrom, Mary J.; Harter, Josephine; Sewall, Sarah; Ogilvie, Travis; Magliocco, Anthony; Breslin, Tara M.; Temple, Walley; Mew, Daphne; Booske, John H.; Okoniewski, Michal; Hagness, Susan C.

2007-10-01

The development of microwave breast cancer detection and treatment techniques has been driven by reports of substantial contrast in the dielectric properties of malignant and normal breast tissues. However, definitive knowledge of the dielectric properties of normal and diseased breast tissues at microwave frequencies has been limited by gaps and discrepancies across previously published studies. To address these issues, we conducted a large-scale study to experimentally determine the ultrawideband microwave dielectric properties of a variety of normal, malignant and benign breast tissues, measured from 0.5 to 20 GHz using a precision open-ended coaxial probe. Previously, we reported the dielectric properties of normal breast tissue samples obtained from reduction surgeries. Here, we report the dielectric properties of normal (adipose, glandular and fibroconnective), malignant (invasive and non-invasive ductal and lobular carcinomas) and benign (fibroadenomas and cysts) breast tissue samples obtained from cancer surgeries. We fit a one-pole Cole-Cole model to the complex permittivity data set of each characterized sample. Our analyses show that the contrast in the microwave-frequency dielectric properties between malignant and normal adipose-dominated tissues in the breast is considerable, as large as 10:1, while the contrast in the microwave-frequency dielectric properties between malignant and normal glandular/fibroconnective tissues in the breast is no more than about 10%.

Bladder Tumor in Women with Microscopic Hematuria: An Iranian Experience and a Review of the Literature

PubMed Central

Abbaszadeh, Shahin; Taheri, Saeed; Nourbala, Mohammad Hossein

2009-01-01

Aim. In this study we report our experience with microhematuria and its relation with bladder tumors in Iranian women. Materials and Methods. Overall 249 women were evaluated. Microscopic hematuria was defined as three or more red blood cells per high-power field on at least two different occasions. Patients with a history of gross hematuria or coagulation disorders, having organic diseases, urinary stones, urinary tract infections, nephrological diseases, and local lesions such as urethral caruncle were excluded from the study population. Final diagnosis of malignant tumors was done with cystoscopy and biopsy specimen pathological assessment in all cases. Results. Age for the study population was 49.7 ± 11.8 years. 95 (38%) of patients were identified during routine check up and presenting symptoms in other patients were frequency, dysuria, stress urge incontinence, urge incontinence, feeling of incomplete urine emptying, and flunk pain, respectively. Finally, 7 (2.8%) of study subjects were confirmed as having bladder tumors. One of tumor cases was diagnosed 24 months after initial assessments. Patients with bladder tumor were significantly older; more frequently had diverticulum in their bladder wall (P < .05). Conclusion. Female microscopic hematuria is relevant and deserves evaluations, especially in elderly patients. Patients whose reason for microhematuria would not be diagnosed at the initial evaluations should be followed. PMID:19639044

Study of dosimetric variation due to interfraction organ movement in High Dose Rate Interstital (MUPIT) brachytherapy for gynecologic malignancies

NASA Astrophysics Data System (ADS)

Velmurugan, Thanigaimalai; Sukumar, Prabakar; Krishnappan, Chokkalingam; Boopathy, Raghavendiran

2010-01-01

Ten patients with cancer of uterine cervix who underwent interstitial brachytherapy using MUPIT templates were CT scanned (CT1) using which bladder, rectum and CTV were delineated. The treatment plan PCT1 was generated and optimized geometrically on the volume. CT scan (CT2) was repeated before the second fraction of the treatment CTV and critical organs were delineated. The plan (PCT2) was created by reproducing the Plan PCT1 in the CT2 images and compared with PCT1. Bladder, Rectum and CTV percentage volume variation ranges from +28.6% to -34.3%, 38.4% to -14.9% and 8.5% to -15.2% respectively. Maximum dose variation in bladder was +17.1%, in rectum was up to +410% and in CTV was -13.0%. The dose to these structures varies independently with no strong correlation with the volume variation. Hence it is suggested that repeat CT and re-planning is mandatory before second fraction execution.

Advances in Therapeutic Development for Radiation Cystitis.

PubMed

Rajaganapathy, Bharathi Raja; Jayabalan, Nirmal; Tyagi, Pradeep; Kaufman, Jonathan; Chancellor, Michael B

2014-01-01

Radiation treatment for pelvic malignancies is typically associated with radiation injury to urinary bladder that can ultimately lead to radiation cystitis (RC). The late sequelae of radiation therapy may take many years to develop and include bothersome storage symptoms such as hematuria, which may be life-threatening in severe cases of hemorrhagic cystitis. Although no definitive treatment is currently available, various interventions are used for radiation and hemorrhagic cystitis including blood transfusion, bladder irrigation, intravesical instillation of substances such as alum, silver nitrate, prostaglandins or formalin, and fulguration of intravesical bleeding sites and surgery options such as supravesical urinary diversions and cystectomy. Effects of non-surgical treatments for radiation and hemorrhagic cystitis are of modest success and studies are lacking to control the effects caused by RC. When such measures have proven ineffective, use of bladder botulinum toxin injection has been reported. New therapy, such as intravesical immunosuppression with local tacrolimus formulation is being developed for the treatment of radiation hemorrhagic cystitis. © 2013 Wiley Publishing Asia Pty Ltd.

A novel single compartment in vitro model for electrophysiological research using the perfluorocarbon FC-770.

PubMed

Choudhary, M; Clavica, F; van Mastrigt, R; van Asselt, E

2016-06-20

Electrophysiological studies of whole organ systems in vitro often require measurement of nerve activity and/or stimulation of the organ via the associated nerves. Currently two-compartment setups are used for such studies. These setups are complicated and require two fluids in two separate compartments and stretching the nerve across one chamber to the other, which may damage the nerves. We aimed at developing a simple single compartment setup by testing the electrophysiological properties of FC-770 (a perfluorocarbon) for in vitro recording of bladder afferent nerve activity and electrical stimulation of the bladder. Perflurocarbons are especially suitable for such a setup because of their high oxygen carrying capacity and insulating properties. In male Wistar rats, afferent nerve activity was recorded from postganglionic branches of the pelvic nerve in vitro, in situ and in vivo. The bladder was stimulated electrically via the efferent nerves. Organ viability was monitored by recording spontaneous contractions of the bladder. Additionally, histological examinations were done to test the effect of FC-770 on the bladder tissue. Afferent nerve activity was successfully recorded in a total of 11 rats. The bladders were stimulated electrically and high amplitude contractions were evoked. Histological examinations and monitoring of spontaneous contractions showed that FC-770 maintained organ viability and did not cause damage to the tissue. We have shown that FC-770 enables a simple, one compartment in vitro alternative for the generally used two compartment setups for whole organ electrophysiological studies.

Characterization of the Olfactory Receptor OR10H1 in Human Urinary Bladder Cancer.

PubMed

Weber, Lea; Schulz, Wolfgang A; Philippou, Stathis; Eckardt, Josephine; Ubrig, Burkhard; Hoffmann, Michéle J; Tannapfel, Andrea; Kalbe, Benjamin; Gisselmann, Günter; Hatt, Hanns

2018-01-01

Olfactory receptors (ORs) are a large group of G-protein coupled receptors predominantly found in the olfactory epithelium. Many ORs are, however, ectopically expressed in other tissues and involved in several diseases including cancer. In this study, we describe that one OR, OR10H1, is predominantly expressed in the human urinary bladder with a notably higher expression at mRNA and protein level in bladder cancer tissues. Interestingly, also significantly higher amounts of OR10H1 transcripts were detectable in the urine of bladder cancer patients than in the urine of control persons. We identified the sandalwood-related compound Sandranol as a specific agonist of OR10H1. This deorphanization allowed the functional characterization of OR10H1 in BFTC905 bladder cancer cells. The effect of receptor activation was morphologically apparent in cell rounding, accompanied by changes in the cytoskeleton detected by β-actin, T-cadherin and β-Catenin staining. In addition, Sandranol treatment significantly diminished cell viability, cell proliferation and migration and induced a limited degree of apoptosis. Cell cycle analysis revealed an increased G1 fraction. In a concentration-dependent manner, Sandranol application elevated cAMP levels, which was reduced by inhibition of adenylyl cyclase, and elicited intracellular Ca 2+ concentration increase. Furthermore, activation of OR10H1 enhanced secretion of ATP and serotonin. Our results suggest OR10H1 as a potential biomarker and therapeutic target for bladder cancer.

Proteomic analysis of urine in patients with intestinal segments transposed into the urinary tract.

PubMed

Nabi, Ghulam; N'Dow, James; Hasan, Tahseen S; Booth, Ian R; Cash, Phil

2005-04-01

Intestinal segments are used to replace or reconstruct the urinary bladder when it has become dysfunctional or develops life-threatening disease such as cancer. The quality of life in patients with intestinal segments used to either enlarge or completely replace the native bladder is adversely affected by recurrent urinary tract infections, excessive mucus production and the occasional development of malignancy. At present, there is no reliable method of predicting or noninvasively monitoring these patients for the development of these complications. The characterisation of proteins secreted into urine from the transposed intestinal segments could serve as important indicators of these clinical complications. Urine is an ideal source of material in which to search for biomarkers, since it bathes the affected tissues and can be obtained relatively easily by noninvasive methods. The urinary proteome of patients with intestinal segments transposed into the urinary tract is unknown and we present the first global description of the urinary protein profile in these patients. Sample preparation is a critical step in achieving accurate and reliable data. We describe a method to prepare urinary proteins that was compatible with their subsequent analysis using two-dimensional polyacrylamide gel electrophoresis. This method helped to overcome some of the technical problems encountered in analysing urine from this patient cohort. The method was used to analyse urinary proteins recovered from five healthy controls and ten patients with intestinal segments transposed into the urinary tract. Four low molecular weight proteins were found to be present in nine out of ten for the patient group but for none of the healthy controls. The four proteins were identified as lithostathine-1 alpha precursor, pancreatitis associated protein-1 precursor, liver fatty acid binding protein and testis expressed protein-12. The role of these proteins as potential biomarkers of intestinal cell activity within the reconstructed bladder is discussed.

Prostaglandins as mediators of acidification in the urinary bladder of Bufo marinus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frazier, L.W.; Yorio, T.

1990-05-01

Experiments were performed to determine whether prostaglandins (PG) play a role in H+ and NH4+ excretion in the urinary bladder of Bufo marinus. Ten paired hemibladders from normal toads were mounted in chambers. One was control and the other hemibladder received PGE2 in the serosal medium (10(-5) M). H+ excretion was measured by change in pH in the mucosal fluid and reported in units of nmol (100 mg tissue)-1 (min)-1. NH4+ excretion was measured colorimetrically and reported in the same units. The control group H+ excretion was 8.4 +/- 1.67, while the experimental group was 16.3 +/- 2.64 (P lessmore » than 0.01). The NH4+ excretion in the experimental and control group was not significantly different. Bladders from toads in a 48-hr NH4+Cl acidosis (metabolic) did not demonstrate this response to PGE2 (P greater than 0.30). Toads were put in metabolic acidosis by gavaging with 10 ml of 120 mM NH4+Cl 3 x day for 2 days. In another experiment, we measured levels of PG in bladders from control (N) and animals placed in metabolic acidosis (MA). Bladders were removed from the respective toad, homogenized, extracted, and PG separated using high-pressure liquid chromatography and quantified against PG standards. The results are reported in ng (mg tissue)-1. PGE2 fraction in N was 1.09 +/- 0.14 and in MA was 3.21 +/- 0.63 (P less than 0.01). PGF1 alpha, F2 alpha and I2 were not significantly different in N and MA toads. Bladders were also removed from N and MA toads, and incubated in Ringer's solution containing (3H)arachidonic acid (0.2 microCi/ml) at 25 degrees C for 2 hr. Bladders were then extracted for PG and the extracts separated by thin layer chromatography. PG were identified using standards and autoradiography, scraped from plates, and counted in a scintillation detector. The results are reported in cpm/mg tissue x hr +/- SEM.« less

Uterine Prolapse

MedlinePlus

... during bowel movements Family history of weakness in connective tissue Being Hispanic or white Complications Uterine prolapse is ... You might experience: Anterior prolapse (cystocele). Weakness of connective tissue separating the bladder and vagina may cause the ...

Spectral grading and Gleason grading of malignant prostate tissue using Stokes shift spectra

NASA Astrophysics Data System (ADS)

Al Salhi, M.; Masilamani, V.; Rabah, D.; Farhat, K.; Liu, C. H.; Pu, Y.; Alfano, R. R.

2012-01-01

Gleason score is the most common method of grading the virulence of prostate malignancy and is based on the pathological assessment of morphology of cellular matrix. Since this involves the excision of the tissue, we are working on a new, minimally invasive, non contact, procedure of spectral diagnosis of prostate malignancy. In this preliminary in vitro study reported here, we have analyzed 27 tissue samples (normal control =7: benign=8: malignant =12) by Stokes' shift spectra (SSS) to establish a one- to- one correlation between spectral grading and Gleason grading.

Urine cytology of nonurothelial malignancies-a 10-year experience in a large multihospital healthcare system.

PubMed

Savant, Deepika; Bajaj, Jaya; Gimenez, Cecilia; Rafael, Oana C; Mirzamani, Neda; Chau, Karen; Klein, Melissa; Das, Kasturi

2017-01-01

Urine cytology is the most frequently utilized test to detect urothelial cancer. Secondary bladder neoplasms need to be recognized as this impacts patient management. We report our experience on nonurothelial malignancies (NUM) detected in urine cytology over a 10-year period. A 10-year retrospective search for patients with biopsy-proven NUM to the urothelial tract yielded 25 urine samples from 14 patients. Two cytopathologists blinded to the original cytology diagnosis reviewed the cytology and histology slides. The incidence, cytomorphologic features, diagnostic accuracy, factors influencing the diagnostic accuracy, and clinical impact of the cytology result were studied. The incidence of NUM was <1%. The male:female ratio was 1.3. An abnormality was detected in 60% of the cases; however, in only 4% of the cases, a primary site was identified accurately. Of the false negatives, 96% was deemed as sampling errors and 4% was interpretational. Patient management was not impacted in any of the false-negative cases due to concurrent or past tissue diagnosis. Colon cancer was the most frequent secondary tumor. Sampling error attributed to the false-negative results. Necrosis and dirty background was often associated with metastatic lesions from colon. Obtaining history of a primary tumor elsewhere was a key factor in diagnosis of a metastatic lesion. Hematopoietic malignancies remain to be a diagnostic challenge. Cytospin preparations were superior for evaluating nuclear detail and background material as opposed to monolayer (Thinprep) technology. Diagnostic accuracy was improved by obtaining immunohistochemistry. Diagn. Cytopathol. 2016. © 2016 Wiley Periodicals, Inc. Diagn. Cytopathol. 2017;45:22-28. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Secondary Primary Malignancy Risk in Patients With Cervical Cancer in Taiwan: A Nationwide Population-Based Study.

PubMed

Teng, Chung-Jen; Huon, Leh-Kiong; Hu, Yu-Wen; Yeh, Chiu-Mei; Chao, Yee; Yang, Muh-Hwa; Chen, Tzeng-Ji; Hung, Yi-Ping; Liu, Chia-Jen

2015-10-01

To evaluate the risk of secondary primary malignancy (SPM) in patients with cervical cancer using a nationwide population-based dataset.Patients newly diagnosed with cervical cancer between 1997 and 2011 were identified using Taiwan's National Health Insurance database. Patients with antecedent malignancies were excluded. Standardized incidence ratios (SIRs) for SPM were calculated by comparing with the cancer incidence in the general population. Risk factors for cancer development were analyzed using Cox proportional hazard models.During the 14-year study period (follow-up of 223,062 person-years), 2004 cancers developed in 35,175 patients with cervical cancer. The SIR for all cancers was 1.56 (95% confidence interval, 1.50-1.63, P < 0.001). SIRs for follow-up periods of >10, 5 to 10, 1 to 5, and <1 year were 1.37, 1.51, 1.34, and 2.59, respectively. After the exclusion of SPM occurring within 1 year of cervical cancer diagnosis, SIRs were significantly higher for cancers of the esophagus (2.05), stomach (1.38), colon, rectum, and anus (1.36); lung and mediastinum (2.28), bone and soft tissue (2.23), uterus (3.76), bladder (2.26), and kidneys (1.41). Multivariate analysis showed that age ≥60 was a significant SPM risk factor (hazard ratio [HR] 1.59). Different treatments for cervical cancer, including radiotherapy (HR 1.41) and chemotherapy (HR 1.27), had different impacts on SPM risk. Carboplatin and fluorouracil independently increased SPM risk in cervical cancer patients.Patients with cervical cancer are at increased risk of SPM development. Age ≥60 years, chemotherapy, and radiotherapy are independent risk factors. Carboplatin and fluorouracil also increased SPM risk independently. Close surveillance of patients at high risk should be considered for the early detection of SPMs.

Female laundry and dry cleaning workers in Wisconsin: a mortality analysis.

PubMed Central

Katz, R M; Jowett, D

1981-01-01

The mortality patterns of 671 female laundry and dry cleaning workers for the period 1963--1977 were analyzed, using Wisconsin death certificate data. Results fail to show an overall increase in malignant neoplasms, but elevated risk was found for cancers of the kidney and genitals (unspecified), along with a smaller excess of bladder and skin cancer and lymphosarcoma. PMID:7468868

Cost analysis of open radical cystectomy versus robot-assisted radical cystectomy.

PubMed

Mmeje, Chinedu O; Martin, Aaron D; Nunez-Nateras, Rafael; Parker, Alexander S; Thiel, David D; Castle, Erik P

2013-02-01

Bladder cancer is the fourth and ninth most common malignancy in males and females, respectively, in the U.S. and one of the most costly cancers to manage. With the current economic condition, physicians will need to become more aware of cost-effective therapies for the treatment of various malignancies. Robot-assisted radical cystectomy (RARC) is the latest minimally invasive surgical option for muscle-invasive bladder cancer. Current reports have shown less blood loss, a shorter hospital stay, and a lower morbidity with RARC, as compared with the traditional open radical cystectomy (ORC), although long-term oncologic results of RARC are still maturing. There are few studies that have assessed the cost outcomes of RARC as compared with ORC. Currently, ORC appears to offer a direct cost advantage due to the high purchase and maintenance cost of the robotic platform, although when the indirect costs of complications and extended hospital stay with ORC are considered, RARC may be less expensive than the traditional open procedure. In order to accurately evaluate the cost effectiveness of RARC versus ORC, prospective randomized trials between the two surgical techniques with long-term oncologic efficacy are needed.

Deformable structure registration of bladder through surface mapping.

PubMed

Xiong, Li; Viswanathan, Akila; Stewart, Alexandra J; Haker, Steven; Tempany, Clare M; Chin, Lee M; Cormack, Robert A

2006-06-01

Cumulative dose distributions in fractionated radiation therapy depict the dose to normal tissues and therefore may permit an estimation of the risk of normal tissue complications. However, calculation of these distributions is highly challenging because of interfractional changes in the geometry of patient anatomy. This work presents an algorithm for deformable structure registration of the bladder and the verification of the accuracy of the algorithm using phantom and patient data. In this algorithm, the registration process involves conformal mapping of genus zero surfaces using finite element analysis, and guided by three control landmarks. The registration produces a correspondence between fractions of the triangular meshes used to describe the bladder surface. For validation of the algorithm, two types of balloons were inflated gradually to three times their original size, and several computerized tomography (CT) scans were taken during the process. The registration algorithm yielded a local accuracy of 4 mm along the balloon surface. The algorithm was then applied to CT data of patients receiving fractionated high-dose-rate brachytherapy to the vaginal cuff, with the vaginal cylinder in situ. The patients' bladder filling status was intentionally different for each fraction. The three required control landmark points were identified for the bladder based on anatomy. Out of an Institutional Review Board (IRB) approved study of 20 patients, 3 had radiographically identifiable points near the bladder surface that were used for verification of the accuracy of the registration. The verification point as seen in each fraction was compared with its predicted location based on affine as well as deformable registration. Despite the variation in bladder shape and volume, the deformable registration was accurate to 5 mm, consistently outperforming the affine registration. We conclude that the structure registration algorithm presented works with reasonable accuracy and provides a means of calculating cumulative dose distributions.

Production of the Escherichia coli Common Pilus by Uropathogenic E. coli Is Associated with Adherence to HeLa and HTB-4 Cells and Invasion of Mouse Bladder Urothelium

PubMed Central

Carrillo-Casas, Erika Margarita; Durán, Laura; Zhang, Yushan; Hernández-Castro, Rigoberto; Puente, José L.; Daaka, Yehia; Girón, Jorge A.

2014-01-01

Uropathogenic Escherichia coli (UPEC) strains cause urinary tract infections and employ type 1 and P pili in colonization of the bladder and kidney, respectively. Most intestinal and extra-intestinal E. coli strains produce a pilus called E. coli common pilus (ECP) involved in cell adherence and biofilm formation. However, the contribution of ECP to the interaction of UPEC with uroepithelial cells remains to be elucidated. Here, we report that prototypic UPEC strains CFT073 and F11 mutated in the major pilin structural gene ecpA are significantly deficient in adherence to cultured HeLa (cervix) and HTB-4 (bladder) epithelial cells in vitro as compared to their parental strains. Complementation of the ecpA mutant restored adherence to wild-type levels. UPEC strains produce ECP upon growth in Luria-Bertani broth or DMEM tissue culture medium preferentially at 26°C, during incubation with cultured epithelial cells in vitro at 37°C, and upon colonization of mouse bladder urothelium ex vivo. ECP was demonstrated on and inside exfoliated bladder epithelial cells present in the urine of urinary tract infection patients. The ability of the CFT073 ecpA mutant to invade the mouse tissue was significantly reduced. The presence of ECP correlated with the architecture of the biofilms produced by UPEC strains on inert surfaces. These data suggest that ECP can potentially be produced in the bladder environment and contribute to the adhesive and invasive capabilities of UPEC during its interaction with the host bladder. We propose that along with other known adhesins, ECP plays a synergistic role in the multi-step infection of the urinary tract. PMID:25036370

Production of the Escherichia coli common pilus by uropathogenic E. coli is associated with adherence to HeLa and HTB-4 cells and invasion of mouse bladder urothelium.

PubMed

Saldaña, Zeus; De la Cruz, Miguel A; Carrillo-Casas, Erika Margarita; Durán, Laura; Zhang, Yushan; Hernández-Castro, Rigoberto; Puente, José L; Daaka, Yehia; Girón, Jorge A

2014-01-01

Uropathogenic Escherichia coli (UPEC) strains cause urinary tract infections and employ type 1 and P pili in colonization of the bladder and kidney, respectively. Most intestinal and extra-intestinal E. coli strains produce a pilus called E. coli common pilus (ECP) involved in cell adherence and biofilm formation. However, the contribution of ECP to the interaction of UPEC with uroepithelial cells remains to be elucidated. Here, we report that prototypic UPEC strains CFT073 and F11 mutated in the major pilin structural gene ecpA are significantly deficient in adherence to cultured HeLa (cervix) and HTB-4 (bladder) epithelial cells in vitro as compared to their parental strains. Complementation of the ecpA mutant restored adherence to wild-type levels. UPEC strains produce ECP upon growth in Luria-Bertani broth or DMEM tissue culture medium preferentially at 26°C, during incubation with cultured epithelial cells in vitro at 37°C, and upon colonization of mouse bladder urothelium ex vivo. ECP was demonstrated on and inside exfoliated bladder epithelial cells present in the urine of urinary tract infection patients. The ability of the CFT073 ecpA mutant to invade the mouse tissue was significantly reduced. The presence of ECP correlated with the architecture of the biofilms produced by UPEC strains on inert surfaces. These data suggest that ECP can potentially be produced in the bladder environment and contribute to the adhesive and invasive capabilities of UPEC during its interaction with the host bladder. We propose that along with other known adhesins, ECP plays a synergistic role in the multi-step infection of the urinary tract.

Application of 1,2-diethyl-3-hydroxypyridin-4-one to enhance tissue selectivity for photodynamic therapy of the bladder

NASA Astrophysics Data System (ADS)

Chang, Shi-Chung; MacRobert, Alexander J.; Porter, John B.; Bown, Stephen G.

1995-03-01

Five-aminolaevulinic acid (ALA) induced protoporphyrin IX (PpIX) has proven to be a useful photosensitizer for photodynamic therapy (PDT). In living cells, the conversion of PpIX to photoinactive haem is catalyzed by ferrochelatase in the presence of tissue iron and inhibition of this final committed step results in increased accumulation of PpIX. The in vivo effect of a new iron chelator, 1,2-diethyl-3-hydroxypyridin-4-one (CP94), on the buildup of PpIX in different bladder layers was evaluated. In CP94 treated rats, 5 - 7 hours after intravesical instillation of ALA solution, the fluorescence intensity of PpIX in the urothelium was doubled whilst in the muscle layer it remained low at a similar level to those seen without the iron chelator. With CP94, further reduction of skin photosensitization is possible as a similar photodynamic effect on the bladder could be achieved at lower ALA concentration. The addition of CP94 seems an effective and convenient way to potentiate ALA induced PpIX tissue selectivity.

Flexible cystoscopic bladder biopsies: a technique for outpatient evaluation of the lower urinary tract urothelium.

PubMed

Beaghler, M; Grasso, M

1994-11-01

Routine urothelial biopsies of the lower urinary tract are obtained using the cold cup biopsy technique. This procedure is most often performed in the surgical suite and requires rigid endoscopic access and the use of biopsy forceps and Bugbee electrodes to obtain tissue for histologic examination. A new single-step biopsy forceps has been used through the flexible cystoscope. Using a 16 F actively deflectable, flexible cystoscope and the 5.4 F Therma Jaw Hot Urologic Forceps, bladder biopsies were obtained in 27 patients for a variety of indications. This biopsy forceps allows simultaneous tissue sampling and electrocoagulation of the biopsy site, thus eliminating the need for exchange of instruments through the flexible cystoscope. Tissue samples are somewhat protected from thermal changes during coagulation through the use of a Faraday cage. Biopsies were frequently obtained in an outpatient setting, requiring only local topical anesthesia (2% lidocaine jelly). Carcinoma in situ, transitional cell carcinoma, acute and chronic inflammation, and normal bladder mucosa were differentiated histologically. Using this technique, lower urinary tract urothelial mapping can be performed safely in the office with minimal patient discomfort.

Tissue reactions under piezoelectric shockwave application for the fragmentation of biliary calculi.

PubMed Central

Ell, C; Kerzel, W; Heyder, N; Rödl, W; Langer, H; Mischke, U; Giedl, J; Domschke, W

1989-01-01

The tissue reactions that occurred during piezoelectric shockwaves for the fragmentation of biliary calculi were investigated in 10 surgically removed stone containing human gall bladders and in acute (six dogs) and chronic (six dogs) animal experiments. Before and after shockwave (500, 1500 or 3000) in the anaesthetised dogs, computed tomography (CT), magnetic imaging (MRI) and laboratory tests were done; treatment was carried out under continuous ultrasonographic control. Shockwave applications to the human gall bladders resulted in disintegration of the stones with no macroscopically or microscopically detectable tissue changes. In acute animal experiments, small haematomas were observed in all six animals at surfaces, but also inside the liver and gall bladder (max diameter 25 mm). Perforation or intra-abdominal or pleural bleeding did not occur. In chronic experiments, no macroscopic, and only slight microscopic residual lesions (haemosiderin deposits) were seen three weeks after shockwave. In almost all instances, the lesions were detected by CT, MRI, and ultrasonography, while laboratory tests were negative. Images Fig 1 Figs. 2-4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 PMID:2731762

[Perivascular epithelioid cell tumor, not otherwise specified: a clinicopathologic and immunohistochemical analysis of 31 cases].

PubMed

Cai, Jun-Na; Shi, Min; Wang, Jian

2011-04-01

To study the clinicopathologic characteristics of perivascular epithelioid cell tumor (PEComa), not otherwise specified (NOS) and to evaluate the diagnostic criteria for malignancy. The clinical and pathologic features of 31 cases of PEComa-NOS were reviewed. The follow-up data available were analyzed. There were a total of 24 females and 7 males. The age of the patients ranged from 13 to 66 years (mean = 40 years). The site of tumor occurrence included gynecologic organs (n = 12), intraabdominal/peritoneal soft tissue (n = 10), gastrointestinal tract (n = 4), thigh (n = 2), mediastinum (n = 1), left groin (n = 1) and urinary bladder (n = 1). None of the cases was associated with tuberous sclerosis complex. Histologic examination showed that 23 cases (74%) were clear cell sugar tumor-like, 4 cases (13%) were clear cell myomelanocytic tumor-like and 4 cases (13%) were of mixed epithelioid-spindled morphology. According to the classification system proposed by Folpe et al, 19 cases (61%) were classified as malignant, 7 cases (23%) as PEComa of uncertain malignant potential and 5 cases (16%) as benign. The expression rates of HMB45, smooth muscle actin and desmin in tested cases were 100% (31/31), 67% (14/21) and 6/18, respectively. Follow-up data (1 to 56 months) were available in 23 cases (74%). Amongst the 16 cases of malignant PEComa, 7 patients were still alive with no evidence of disease, 6 patients were alive with unresectable or recurrent/metastatic disease and 3 patients died of the disease. The local recurrence and metastasis in those 16 cases were 6 cases and 5 cases, respectively. One of the 4 patients with PEComa of uncertain malignant potential died, while the remaining 3 patients and all of the patients with benign PEComa had an uneventful clinical course. The classification system of PEComas proposed by Folpe et al. is reliable in routine practice. Correlation with the clinical and radiologic findings however is prudent when dealing with core biopsy specimens or sampling from exploration laparotomy. Owing to the histologic heterogeneity of this entity, thorough understanding of the morphologic spectrum is essential in arriving at a correct diagnosis.

Intravesical Toll-like receptor 7 agonist R-837: Optimization of its formulation in an orthotopic mouse model of bladder cancer

PubMed Central

Hayashi, Tomoko; Crain, Brian; Corr, Maripat; Chan, Michael; Cottam, Howard B; Maj, Roberto; Barberis, Alcide; Leoni, Lorenzo; Carson, Dennis A

2013-01-01

Objective To study the immune response caused by the intravesical administration of the immunomodulator R-837 in various formulations and to estimate its therapeutic potential for bladder cancer. Methods Female C57BL/6 mice were intravesically treated with different formulations of R-837, a Toll-like receptor 7 agonist used for treating genital warts and skin malignancy. The tested formulation mixtures contained different ratios of lactic acid, a thermosensitive poloxamer polymer (Lutrol F127) and 2-(hydroxypropyl)-β-cyclodextrin (HPβCD). Induction of tumor necrosis factor α (TNFα) and keratinocyte-derived chemokine (KC) was analyzed by Luminex microbeads assay. The therapeutic potential of intravesical administration of R-837 was assessed in an orthotopic, syngeneic mouse model of bladder cancer using MB49 cells. Results Intravesical administration of R-837 in lactic acid alone induced systemic and bladder TNFα and KC in a dose-dependent manner. Formulations including poloxamer decreased systemic absorption of R-837 and significantly reduced systemic and local induction of KC. Addition of HPβCD in the poloxamer formulation particularly reversed levels of systemic and local levels of TNFα and KC. Histological examination showed that poloxamer-HPβCD formulation allowed infiltration of mononuclear cells into urothelium and lamina propria. In studies using orthotopic mouse bladder cancer, the tumor loads in R-837-treated mice were significantly lower than those in vehicle-treated or non-treated mice. Conclusion The optimized poloxamer-HPβCD formulation of R-837 shows therapeutic potential for bladder cancer while avoiding adverse side-effects. PMID:20337728

Mucinous adenocarcinoma of the bladder associated with long term suprapubic tube: a case report.

PubMed

Bauman, Tyler M; Potretzke, Theodora A; Potretzke, Aaron M; Siegel, Cary L; Brandes, Steven B

2015-12-03

Chronic indwelling catheters may induce histologic changes within the bladder, and these changes are sometimes pre-malignant. There are many documented cases of squamous cell carcinoma associated with indwelling catheters, but only three cases of catheter-associated adenocarcinoma have been reported. In this case report, we present radiographic findings of a case of mucinous adenocarcinoma of the bladder and suprapubic (SP) tract in a quadriplegic patient. A 71-year-old male with a history of spinal cord injury presented with hematuria and SP discharge after SP catheterization for 51 years. CT urography was performed and revealed an irregular, infiltrative, and heterogeneous mass arising from the anterior bladder at the level of the suprapubic catheter and extending along the SP tube tract. Cystoscopy and biopsy revealed an adenocarcinoma of the anterior bladder and stoma with extensive associated mucin production and a background of acute and chronic inflammation. Surgical therapy included cystoprostatectomy, abdominal wall resection, ileal conduit creation, and abdominal wall reconstruction. The final diagnosis was a high-grade, T2a/N0/M0 (Stage II) mucinous adenocarcinoma of the bladder. There has been no evidence of tumor recurrence over the previous 5 years. Few cases of adenocarcinoma associated with long term indwelling catheter have been reported in the literature, and due to the rarity of this disease process, the prognosis with surgical therapy is not well known. The patient described herein has been free of recurrence for the previous five years, suggesting that surgery is a viable management option for these patients.

Use of pneumocystoplasty for overinflation of the swim bladder in a goldfish.

PubMed

Britt, Tara; Weisse, Chick; Weber, E Scott; Matzkin, Zach; Klide, Alan

2002-09-01

A Ryukin goldfish was evaluated because of a 6-month history of progressive abdominal distention and positive buoyancy. Overinflation of the swim bladder was diagnosed, and the fish was anesthetized with tricaine methanesulfonate. Archimedes' principle was used to determine the volume of swim bladder that was removed surgically. The caudal swim bladder was exteriorized through an abdominal incision and 2 surgical clips were placed across it to limit its size. After surgery, the fish remained in a state of negative buoyancy in sternal and lateral recumbency on the bottom of the tank. Sutures were removed 15 days after surgery, but the fish died 24 days after surgery. A full necropsy could not be performed because of autolysis of the tissues, but the surgical clips and the swim bladder appeared unremarkable. Pneumocystoplasty may be a viable treatment for this condition.

AR Signaling in Human Malignancies: Prostate Cancer and Beyond.

PubMed

Antonarakis, Emmanuel S

2018-01-18

The notion that androgens and androgen receptor (AR) signaling are the hallmarks of prostate cancer oncogenesis and disease progression is generally well accepted. What is more poorly understood is the role of AR signaling in other human malignancies. This special issue of Cancers initially reviews the role of AR in advanced prostate cancer, and then explores the potential importance of AR signaling in other epithelial malignancies. The first few articles focus on the use of novel AR-targeting therapies in castration-resistant prostate cancer and the mechanisms of resistance to novel antiandrogens, and they also outline the interaction between AR and other cellular pathways, including PI3 kinase signaling, transcriptional regulation, angiogenesis, stromal factors, Wnt signaling, and epigenetic regulation in prostate cancer. The next several articles review the possible role of androgens and AR signaling in breast cancer, bladder cancer, salivary gland cancer, and hepatocellular carcinoma, as well as the potential treatment implications of using antiandrogen therapies in these non-prostatic malignancies.

Preventive Effect of Hydrogen Water on the Development of Detrusor Overactivity in a Rat Model of Bladder Outlet Obstruction.

PubMed

Miyazaki, Nozomu; Yamaguchi, Osamu; Nomiya, Masanori; Aikawa, Ken; Kimura, Junko

2016-03-01

Bladder ischemia and oxidative stress contribute to the pathogenesis of bladder dysfunction caused by bladder outlet obstruction. H2 reportedly acts as an effective antioxidant. We investigated whether oral ingestion of H2 water would have a beneficial effect on bladder function in a rat model of bladder outlet obstruction. H2 water was made by dissolving H2 gas in ordinary drinking water using a hydrogen water producing apparatus. The bladder outlet obstruction model was surgically induced in male rats. Rats with obstruction were fed H2 water or ordinary drinking water. On week 4 postoperatively cystometry was performed. Oxidative stress markers and the bladder nerve growth factor level were determined. Bladder tissues were processed for pharmacological studies and histological analysis. The micturition interval and micturition volume significantly decreased in obstructed rats given ordinary drinking water. These decreases were significantly suppressed by oral ingestion of H2 water. Increased post-void residual volume in obstructed rats was significantly reduced by H2 water. Obstruction led to a significant increase in bladder weight, oxidative stress markers and nerve growth factor. H2 water significantly suppressed these increases without affecting bladder weight. There was no significant difference in histological findings between rats with bladder obstruction given H2 water and ordinary drinking water. Decreased responses of detrusor muscle strips from obstructed bladders to KCl, carbachol and electrical field stimulation were reversed by H2 water ingestion. Results suggest that H2 water could ameliorate bladder dysfunction secondary to bladder outlet obstruction by attenuating oxidative stress. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Combination Chemotherapy in Treating Patients With Previously Untreated Rhabdomyosarcoma

ClinicalTrials.gov

2013-06-13

Adult Malignant Mesenchymoma; Adult Rhabdomyosarcoma; Alveolar Childhood Rhabdomyosarcoma; Childhood Malignant Mesenchymoma; Embryonal Childhood Rhabdomyosarcoma; Embryonal-botryoid Childhood Rhabdomyosarcoma; Nonmetastatic Childhood Soft Tissue Sarcoma; Previously Untreated Childhood Rhabdomyosarcoma; Stage I Adult Soft Tissue Sarcoma; Stage II Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma

Automatic T1 bladder tumor detection by using wavelet analysis in cystoscopy images

NASA Astrophysics Data System (ADS)

Freitas, Nuno R.; Vieira, Pedro M.; Lima, Estevão; Lima, Carlos S.

2018-02-01

Correct classification of cystoscopy images depends on the interpreter’s experience. Bladder cancer is a common lesion that can only be confirmed by biopsying the tissue, therefore, the automatic identification of tumors plays a significant role in early stage diagnosis and its accuracy. To our best knowledge, the use of white light cystoscopy images for bladder tumor diagnosis has not been reported so far. In this paper, a texture analysis based approach is proposed for bladder tumor diagnosis presuming that tumors change in tissue texture. As is well accepted by the scientific community, texture information is more present in the medium to high frequency range which can be selected by using a discrete wavelet transform (DWT). Tumor enhancement can be improved by using automatic segmentation, since a mixing with normal tissue is avoided under ideal conditions. The segmentation module proposed in this paper takes advantage of the wavelet decomposition tree to discard poor texture information in such a way that both steps of the proposed algorithm segmentation and classification share the same focus on texture. Multilayer perceptron and a support vector machine with a stratified ten-fold cross-validation procedure were used for classification purposes by using the hue-saturation-value (HSV), red-green-blue, and CIELab color spaces. Performances of 91% in sensitivity and 92.9% in specificity were obtained regarding HSV color by using both preprocessing and classification steps based on the DWT. The proposed method can achieve good performance on identifying bladder tumor frames. These promising results open the path towards a deeper study regarding the applicability of this algorithm in computer aided diagnosis.

Radiation Therapy With or Without Combination Chemotherapy or Pazopanib Hydrochloride Before Surgery in Treating Patients With Newly Diagnosed Non-rhabdomyosarcoma Soft Tissue Sarcomas That Can Be Removed by Surgery

ClinicalTrials.gov

2018-06-20

Adult Fibrosarcoma; Alveolar Soft Part Sarcoma; Angiomatoid Fibrous Histiocytoma; Atypical Fibroxanthoma; Clear Cell Sarcoma of Soft Tissue; Epithelioid Malignant Peripheral Nerve Sheath Tumor; Epithelioid Sarcoma; Extraskeletal Myxoid Chondrosarcoma; Extraskeletal Osteosarcoma; Fibrohistiocytic Neoplasm; Glomus Tumor of the Skin; Inflammatory Myofibroblastic Tumor; Intimal Sarcoma; Leiomyosarcoma; Liposarcoma; Low Grade Fibromyxoid Sarcoma; Low Grade Myofibroblastic Sarcoma; Malignant Cutaneous Granular Cell Tumor; Malignant Peripheral Nerve Sheath Tumor; Malignant Triton Tumor; Mesenchymal Chondrosarcoma; Myxofibrosarcoma; Myxoid Chondrosarcoma; Myxoinflammatory Fibroblastic Sarcoma; Nerve Sheath Neoplasm; PEComa; Pericytic Neoplasm; Plexiform Fibrohistiocytic Tumor; Sclerosing Epithelioid Fibrosarcoma; Stage IB Soft Tissue Sarcoma AJCC v7; Stage IIB Soft Tissue Sarcoma AJCC v7; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Synovial Sarcoma; Undifferentiated (Embryonal) Sarcoma; Undifferentiated High Grade Pleomorphic Sarcoma of Bone

p16 expression is not associated with human papillomavirus in urinary bladder squamous cell carcinoma.

PubMed

Alexander, Riley E; Hu, Yingchuan; Kum, Jennifer B; Montironi, Rodolfo; Lopez-Beltran, Antonio; Maclennan, Gregory T; Idrees, Muhammad T; Emerson, Robert E; Ulbright, Thomas M; Grignon, David G; Eble, John N; Cheng, Liang

2012-11-01

Squamous cell carcinoma of the urinary bladder is unusual and of unknown etiology. There is a well-established association between human papillomavirus (HPV) infection and the development of cervical and head/neck squamous cell carcinomas. However, the role of HPV in the pathogenesis of squamous cell carcinoma of the urinary bladder is uncertain. The purposes of this study were to investigate the possible role of HPV in the development of squamous cell carcinoma of the urinary bladder and to determine if p16 expression could serve as a surrogate marker for HPV in this malignancy. In all, 42 cases of squamous cell carcinoma of the urinary bladder and 27 cases of urothelial carcinoma with squamous differentiation were investigated. HPV infection was analyzed by both in situ hybridization at the DNA level and immunohistochemistry at the protein level. p16 protein expression was analyzed by immunohistochemistry. HPV DNA and protein were not detected in 42 cases of squamous cell carcinoma (0%, 0/42) or 27 cases of urothelial carcinoma with squamous differentiation (0%, 0/15). p16 expression was detected in 13 cases (31%, 13/42) of squamous cell carcinoma and 9 cases (33%, 9/27) of urothelial carcinoma with squamous differentiation. There was no correlation between p16 expression and the presence of HPV infection in squamous cell carcinoma of the bladder or urothelial carcinoma with squamous differentiation. Our data suggest that HPV does not play a role in the development of squamous cell carcinoma of the urinary bladder or urothelial carcinoma with squamous differentiation. p16 expression should not be used as a surrogate marker for evidence of HVP infection in either squamous cell carcinoma of the urinary bladder or urothelial carcinoma with squamous differentiation as neither HVP DNA nor protein is detectable in these neoplasms.

Contouring and Constraining Bowel on a Full-Bladder Computed Tomography Scan May Not Reflect Treatment Bowel Position and Dose Certainty in Gynecologic External Beam Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yaparpalvi, Ravindra, E-mail: ryaparpa@montefiore.org; Mehta, Keyur J.; Bernstein, Michael B.

Purpose: To evaluate, in a gynecologic cancer setting, changes in bowel position, dose-volume parameters, and biological indices that arise between full-bladder (FB) and empty-bladder (EB) treatment situations; and to evaluate, using cone beam computed tomography (CT), the validity of FB treatment presumption. Methods and Materials: Seventeen gynecologic cancer patients were retrospectively analyzed. Empty-bladder and FB CTs were obtained. Full-bladder CTs were used for planning and dose optimization. Patients were given FB instructions for treatment. For the study purpose, bowel was contoured on the EB CTs for all patients. Bowel position and volume changes between FB and EB states were determined.more » Full-bladder plans were applied on EB CTs for determining bowel dose-volume changes in EB state. Biological indices (generalized equivalent uniform dose and normal tissue complication probability) were calculated and compared between FB and EB. Weekly cone beam CT data were available in 6 patients to assess bladder volume at treatment. Results: Average (±SD) planned bladder volume was 299.7 ± 68.5 cm{sup 3}. Median bowel shift in the craniocaudal direction between FB and EB was 12.5 mm (range, 3-30 mm), and corresponding increase in exposed bowel volume was 151.3 cm{sup 3} (range, 74.3-251.4 cm{sup 3}). Absolute bowel volumes receiving 45 Gy were higher for EB compared with FB (mean 328.0 ± 174.8 vs 176.0 ± 87.5 cm{sup 3}; P=.0038). Bowel normal tissue complication probability increased 1.5× to 23.5× when FB planned treatments were applied in the EB state. For the study, the mean percentage value of relative bladder volume at treatment was 32%. Conclusions: Full-bladder planning does not necessarily translate into FB treatments, with a patient tendency toward EB. Given the uncertainty in daily control over bladder volume for treatment, we strongly recommend a “planning-at-risk volume bowel” (PRV{sub B}owel) concept to account for bowel motion between FB and EB that can be tailored for the individual patient.« less

Muscarinic Receptor Binding in Rat Bladder Urothelium and Detrusor Muscle by Intravesical Solifenacin.

PubMed

Ito, Yoshihiko; Kashiwabara, Michishi; Yoshida, Akira; Hikiyama, Eriko; Onoue, Satomi; Yamada, Shizuo

2016-01-01

Solifenacin is an antimuscarinic agent used to treat symptoms of overactive bladder. Pharmacologically significant amounts of solifenacin were excreted in the urine of humans taking a clinical dose of this drug. The aim of this study is to measure muscarinic receptor binding in the bladder urothelium and detrusor muscles of rats following the intravesical instillation of solifenacin. Muscarinic receptors were measured by radioreceptor assay using [N-methyl-(3)H]scopolamine methyl chloride ([(3)H]NMS), a selective radioligand of muscarinic receptors. Solifenacin showed concentration-dependent inhibition of specific [(3)H]NMS binding in the bladder urothelium and detrusor muscle of rats, with no significant difference in Ki values or Hill coefficients between these tissues. Following the intravesical instillation of solifenacin, there was significant muscarinic receptor binding (increase in Kd for specific [(3)H]NMS binding) in the bladder urothelium and detrusor muscle of rats. Similar bladder muscarinic receptor binding was observed by the intravesical instillation of oxybutynin, but not with trospium. In conclusion, the present study has demonstrated that solifenacin binds muscarinic receptors not only in the detrusor muscle but also in the bladder urothelium with high affinity. These bladder muscarinic receptors may be significantly affected by solifenacin excreted in the urine.

Deregulation of HIF1-alpha and hypoxia-regulated pathways in hepatocellular carcinoma and corresponding non-malignant liver tissue--influence of a modulated host stroma on the prognosis of HCC.

PubMed

Simon, Frank; Bockhorn, Maximilian; Praha, Christian; Baba, Hideo A; Broelsch, Christoph E; Frilling, Andrea; Weber, Frank

2010-04-01

The aim of this study was to elucidate the role of HIF1A expression in hepatocellular carcinoma (HCC) and the corresponding non-malignant liver tissue and to correlate it with the clinical outcome of HCC patients after curative liver resection. HIF1A expression was determined by quantitative RT-PCR in HCC and corresponding non-malignant liver tissue of 53 patients surgically treated for HCC. High-density gene expression analysis and pathway analysis was performed on a selected subset of patients with high and low HIF1A expression in the non-malignant liver tissue. HIF1A over-expression in the apparently non-malignant liver tissue was a predictor of tumor recurrence and survival. The estimated 1-year and 5-year disease-free survival was significantly better in patients with low HIF1A expression in the non-malignant liver tissue when compared to those patients with high HIF1 expression (88.9% vs. 67.9% and 61.0% vs. 22.6%, respectively, p = 0.008). Based on molecular pathway analysis utilizing high-density gene-expression profiling, HIF1A related molecular networks were identified that contained genes involved in cell migration, cell homing, and cell-cell interaction. Our study identified a potential novel mechanism contributing to prognosis of HCC. The deregulation of HIF1A and its related pathways in the apparently non-malignant liver tissue provides for a modulated environment that potentially enhances or allows for HCC recurrence after curative resection.

Expression of Leukemia/Lymphoma-Related Factor (LRF/POKEMON) in Human Breast Carcinoma and Other Cancers

PubMed Central

Aggarwal, Anshu; Hunter, William J.; Aggarwal, Himanshu; Silva, Edibaldo D.; Davey, Mary S.; Murphy, Richard F.; Agrawal, Devendra K.

2010-01-01

The POK family of proteins plays an important role in not only embryonic development and cell differentiation, but also in oncogenesis. Leukemia/lymphoma-related factor (LRF) belongs to the POK family of transcriptional repressors and is also known as POK erythroid myeloid ontogenic factor (POKEMON), which binds to short transcripts of HIV-1 (FBI-1) and TTF-1 interacting peptide (TIP21). Its oncogenic role is known only in lymphoma, non-small cell lung carcinoma, and malignant gliomas. The functional expression of LRF in human breast carcinoma has not yet been confirmed. The aim of this study was to investigate and compare the expression of LRF in human breast cancer tissues and other human tumors. The expression of LRF mRNA transcripts and protein was observed in twenty human benign and malignant breast biopsy tissues. Expression of LRF was observed in several formalin-fixed tissues by immunohistochemistry and immunofluorescence. All malignant breast tissues expressed mRNA transcripts and protein for LRF. However, 40% and 15% benign breast biopsy tissues expressed LRF mRNA transcripts and protein, respectively. The overall expression of LRF mRNA transcripts and total protein was significantly more in malignant breast tissues than the benign breast tissues. LRF expression was also observed in the nuclei of human colon, renal, lung, hepatocellular carcinomas and thymoma tumor cells. In general, a significantly higher expression of LRF was seen in malignant tissues than in the corresponding benign or normal tissue. Further studies are warranted to determine the malignant role of LRF in human breast carcinoma. PMID:20471975

Fluorescence lifetime of normal, benign, and malignant thyroid tissues

NASA Astrophysics Data System (ADS)

Brandao, Mariana; Iwakura, Ricardo; Basilio, Fagne; Haleplian, Kaique; Ito, Amando; de Freitas, Luiz Carlos Conti; Bachmann, Luciano

2015-06-01

Fine-needle aspiration cytology is the standard technique to diagnose thyroid pathologies. However, this method results in a high percentage of inconclusive and false negatives. The use of time-resolved fluorescence techniques to detect biochemical composition and tissue structure alterations could help to develop a portable, minimally invasive, and nondestructive method to assist during surgical procedures. This study aimed to use fluorescence lifetimes to differentiate healthy and benign tissues from malignant thyroid tissue. The thyroid tissue was excited at 298-300 nm and the fluorescence decay registered at 340 and 450 nm. We observed fluorescence lifetimes at 340 nm emission of 0.80±0.26 and 3.94±0.47 ns for healthy tissue; 0.90±0.24 and 4.05±0.46 ns for benign lesions; and 1.21±0.14 and 4.63±0.25 ns for malignant lesions. For 450 nm emissions, we obtain lifetimes of 0.25±0.18 and 3.99±0.39 ns for healthy tissue, 0.24±0.17 and 4.20±0.48 ns for benign lesions, 0.33±0.32 and 4.55±0.55 ns for malignant lesions. Employing analysis of variance, we differentiate malignant lesions from benign and healthy tissues. In addition, we use quadratic discriminant analysis to distinguish malignant from benign and healthy tissues with an accuracy of 76.1%, sensitivity of 74.7%, and specificity of 83.3%. These results indicate that time-resolved fluorescence can assist medical evaluation of thyroid pathologies during surgeries.

Combination Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Rhabdomyosarcoma

ClinicalTrials.gov

2017-06-27

Adult Malignant Mesenchymoma; Adult Rhabdomyosarcoma; Childhood Alveolar Rhabdomyosarcoma; Childhood Botryoid-Type Embryonal Rhabdomyosarcoma; Childhood Embryonal Rhabdomyosarcoma; Childhood Malignant Mesenchymoma; Non-Metastatic Childhood Soft Tissue Sarcoma; Stage I Adult Soft Tissue Sarcoma; Stage II Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Untreated Childhood Rhabdomyosarcoma

FGF2-mediated reciprocal tumor cell-endothelial cell interplay contributes to the growth of chemoresistant cells: a potential mechanism for superficial bladder cancer recurrence.

PubMed

Chen, Yule; Zhu, Guodong; Wu, Kaijie; Gao, Yang; Zeng, Jin; Shi, Qi; Guo, Peng; Wang, Xinyang; Chang, Luke S; Li, Lei; He, Dalin

2016-04-01

Patients with superficial bladder cancer can be definitively cured by one single transurethral resection (TUR) with additional intravesical chemotherapy; however, up to 75 % of cases display frequent and multiple recurrences. One of the major causes of recurrence is that chemotherapeutic drugs used in intravesical regimens may induce chemoresistance. However, the mechanisms by which these chemoresistant cells develop into recurrent tumors remain unclear. Recent clinical evidence revealed that the expression of pro-angiogenic factor FGF2 was associated with early local relapse in patients with superficial bladder cancer. In this study, we conducted a preliminary investigation of the mechanisms of chemoresistant cells mediated bladder cancer recurrence, focusing on FGF2-initiated tumor cell-endothelial cell interaction on chemoresistant cancer cell growth. We found that the expression of FGF2 was increased in chemoresistant bladder cell lines and in bladder tissues after intravesical chemotherapy. Although chemoresistant bladder cells grow slower than parental cells, chemoresistant bladder cancer cells had stronger ability than parental cells to stimulate endothelial cell migration, growth, and tube formation by producing FGF2. Inversely, endothelial cells significantly promoted chemoresistant bladder cancer growth in vitro and in vivo. Thus, targeting chemotherapy-induced FGF2 upregulation may provide a promising approach to manage the recurrence of superficial bladder cancer.

Neurosurgical sapphire handheld probe for intraoperative optical diagnostics, laser coagulation and aspiration of malignant brain tissue

NASA Astrophysics Data System (ADS)

Shikunova, Irina A.; Zaytsev, Kirill I.; Stryukov, Dmitrii O.; Dubyanskaya, Evgenia N.; Kurlov, Vladimir N.

2017-07-01

In this paper, a handheld contact probe based on sapphire shaped crystal was developed for the intraoperative optical diagnosis and aspiration of malignant brain tissue combined with the laser hemostasis. Such a favorable combination of several functions in a single instrument significantly increases its clinical relevance. It makes possible highly-accurate real-time detection and removal of either large-scale malignancies or even separate invasive cancer cells. The proposed neuroprobe was integrated into the clinical neurosurgical workflow for the intraoperative fluorescence identification and removal of malignant tissues of the brain.

Cytoplasmatic and Nuclear YAP1 and pYAP1 Staining in Urothelial Bladder Cancer.

PubMed

Latz, Stefan; Umbach, Tine; Goltz, Diane; Kristiansen, Glen; Müller, Stephan C; Ellinger, Jörg

2016-01-01

Yes-associated protein 1 (YAP1), the nuclear effector of the Hippo pathway, plays an important role in many tumor entities. We evaluated staining and clinical significance of YAP1 and phosphorylated YAP1 (pYAP1) in urothelial bladder cancer (BCA). We used a tissue micorarray with samples of patients with muscle-invasive bladder cancer (MIBC, n = 192), non-muscle-invasive bladder cancer (NMIBC, n = 192) and normal urothelial bladder tissue (CTRL, n = 38) to determine the immunhistochemical staining of YAP1 and pYAP1. Cytoplasmatic and nuclear levels were evaluated. The t test was used for comparative analysis. Overall survival and progression-free survival were evaluated by Kaplan-Meier estimates and the Cox proportional hazard regression model. Nuclear YAP1 as well as cytoplasmatic pYAP1 levels were higher in CTRL than in BCA, whereby both--NMIBC and MIBC--had lower levels than CTRL. Among patients with MIBC, cytoplasmatic YAP1 and pYAP1 staining decreased with advanced stage. YAP1 and pYAP1 staining did not correlate with the recurrence rate, progression-free, cancer-specific or overall survival. Immunhistochemical staining and subcellular localization of YAP1 and pYAP1 are different for BCA, NMIBC, MIBC and CTRL, indicating that the Hippo pathway is involved in urothelial carcinogenesis. © 2015 S. Karger AG, Basel.

Lipid Profiles of Canine Invasive Transitional Cell Carcinoma of the Urinary Bladder and Adjacent Normal Tissue by Desorption Electrospray Ionization Imaging Mass Spectrometry

PubMed Central

Dill, Allison L.; Ifa, Demian R.; Manicke, Nicholas E.; Costa, Anthony B.; Ramos-Vara, José A.; Knapp, Deborah W.; Cooks, R. Graham

2009-01-01

Desorption electrospray ionization (DESI) mass spectrometry (MS) was used in an imaging mode to interrogate the lipid profiles of thin tissue sections of canine spontaneous invasive transitional cell carcinoma (TCC) of the urinary bladder (a model of human invasive bladder cancer) as well as adjacent normal tissue from four different dogs. The glycerophospholipids and sphingolipids that appear as intense signals in both the negative ion and positive ion modes were identified by tandem mass spectrometry (MS/MS) product ion scans using collision-induced dissociation. Differences in the relative distributions of the lipid species were present between the tumor and adjacent normal tissue in both the negative and positive ion modes. DESI-MS images showing the spatial distributions of particular glycerophospholipids, sphinoglipids and free fatty acids in both the negative and positive ion modes were compared to serial tissue sections that were stained with hematoxylin and eosin (H&E). Increased absolute and relative intensities for at least five different glycerophospholipids and three free fatty acids in the negative ion mode and at least four different lipid species in the positive ion mode were seen in the tumor region of the samples in all four dogs. In addition, one sphingolipid species exhibited increased signal intensity in the positive ion mode in normal tissue relative to the diseased tissue. Principal component analysis (PCA) was also used to generate unsupervised statistical images from the negative ion mode data and these images are in excellent agreement with the DESI images obtained from the selected ions and also the H&E stained tissue PMID:19810710

SESN2/sestrin 2 induction-mediated autophagy and inhibitory effect of isorhapontigenin (ISO) on human bladder cancers.

PubMed

Liang, Yuguang; Zhu, Junlan; Huang, Haishan; Xiang, Daimin; Li, Yang; Zhang, Dongyun; Li, Jingxia; Wang, Yulei; Jin, Honglei; Jiang, Guosong; Liu, Zeyuan; Huang, Chuanshu

2016-08-02

Isorhapontigenin (ISO) is a new derivative of stilbene isolated from the Chinese herb Gnetum cleistostachyum. Our recent studies have revealed that ISO treatment at doses ranging from 20 to 80 μM triggers apoptosis in multiple human cancer cell lines. In the present study, we evaluated the potential effect of ISO on autophagy induction. We found that ISO treatment at sublethal doses induced autophagy effectively in human bladder cancer cells, which contributed to the inhibition of anchorage-independent growth of cancer cells. In addition, our studies revealed that ISO-mediated autophagy induction occurred in a SESN2 (sestrin 2)-dependent and BECN1 (Beclin 1, autophagy related)-independent manner. Furthermore, we identified that ISO treatment induced SESN2 expression via a MAPK8/JNK1 (mitogen-activated protein kinase 8)/JUN-dependent mechanism, in which ISO triggered MAPK8-dependent JUN activation and facilitated the binding of JUN to a consensus AP-1 binding site in the SESN2 promoter region, thereby led to a significant transcriptional induction of SESN2. Importantly, we found that SESN2 expression was dramatically downregulated or even lost in human bladder cancer tissues as compared to their paired adjacent normal tissues. Collectively, our results demonstrate that ISO treatment induces autophagy and inhibits bladder cancer growth through MAPK8-JUN-dependent transcriptional induction of SESN2, which provides a novel mechanistic insight into understanding the inhibitory effect of ISO on bladder cancers and suggests that ISO might act as a promising preventive and/or therapeutic drug against human bladder cancer.

Next generation of optical diagnostics for bladder cancer using probe-based confocal laser endomicroscopy

NASA Astrophysics Data System (ADS)

Liu, Jen-Jane; Chang, Timothy C.; Pan, Ying; Hsiao, Shelly T.; Mach, Kathleen E.; Jensen, Kristin C.; Liao, Joseph C.

2012-02-01

Real-time imaging with confocal laser endomicroscopy (CLE) probes that fit in standard endoscopes has emerged as a clinically feasible technology for optical biopsy of bladder cancer. Confocal images of normal, inflammatory, and neoplastic urothelium obtained with intravesical fluorescein can be differentiated by morphologic characteristics. We compiled a confocal atlas of the urinary tract using these diagnostic criteria to be used in a prospective diagnostic accuracy study. Patients scheduled to undergo transurethral resection of bladder tumor underwent white light cystoscopy (WLC), followed by CLE, and histologic confirmation of resected tissue. Areas that appeared normal by WLC were imaged and biopsied as controls. We imaged and prospectively analyzed 135 areas in 57 patients. We show that CLE improves the diagnostic accuracy of WLC for diagnosing benign tissue, low and high grade cancer. Interobserver studies showed a moderate level of agreement by urologists and nonclinical researchers. Despite morphologic differences between inflammation and cancer, real-time differentiation can still be challenging. Identification of bladder cancer-specific contrast agents could provide molecular specificity to CLE. By using fluorescently-labeled antibodies or peptides that bind to proteins expressed in bladder cancer, we have identified putative molecular contrast agents for targeted imaging with CLE. We describe one candidate agent - anti-CD47 - that was instilled into bladder specimens. The tumor and normal urothelium were imaged with CLE, with increased fluorescent signal demonstrated in areas of tumor compared to normal areas. Thus, cancer-specificity can be achieved using molecular contrast agents ex vivo in conjunction with CLE.

Urinary Retention, Incontinence, and Dysregulation of Muscarinic Receptors in Male Mice Lacking Mras.

PubMed

Ehrhardt, Annette; Wang, Bin; Yung, Andrew C; Wang, Yanni; Kozlowski, Piotr; van Breemen, Cornelis; Schrader, John W

2015-01-01

Here we show that male, but not female mice lacking expression of the GTPase M-Ras developed urinary retention with distention of the bladder that exacerbated with age but occurred in the absence of obvious anatomical outlet obstruction. There were changes in detrusor morphology in Mras-/- males: Smooth muscle tissue, which exhibited a compact organization in WT mice, appeared disorganized and became increasingly 'layered' with age in Mras-/- males, but was not fibrotic. Bladder tissue near the apex of bladders of Mras-/- males exhibited hypercontractility in response to the cholinergic agonist carbachol in in vitro, while responses in Mras-/- females were normal. In addition, spontaneous phasic contractions of detrusors from Mras-/- males were increased, and Mras-/- males exhibited urinary incontinence. We found that expression of the muscarinic M2 and M3 receptors that mediate the cholinergic contractile stimuli of the detrusor muscle was dysregulated in both Mras-/- males and females, although only males exhibited a urinary phenotype. Elevated expression of M2R in young males lacking M-Ras and failure to upregulate M3R with age resulted in significantly lower ratios of M3R/M2R expression that correlated with the bladder abnormalities. Our data suggests that M-Ras and M3R are functionally linked and that M-Ras is an important regulator of male bladder control in mice. Our observations also support the notion that bladder control is sexually dimorphic and is regulated through mechanisms that are largely independent of acetylcholine signaling in female mice.

Urinary Retention, Incontinence, and Dysregulation of Muscarinic Receptors in Male Mice Lacking Mras

PubMed Central

Ehrhardt, Annette; Wang, Bin; Yung, Andrew C.; Wang, Yanni; Kozlowski, Piotr; van Breemen, Cornelis; Schrader, John W.

2015-01-01

Here we show that male, but not female mice lacking expression of the GTPase M-Ras developed urinary retention with distention of the bladder that exacerbated with age but occurred in the absence of obvious anatomical outlet obstruction. There were changes in detrusor morphology in Mras -/- males: Smooth muscle tissue, which exhibited a compact organization in WT mice, appeared disorganized and became increasingly ‘layered’ with age in Mras -/- males, but was not fibrotic. Bladder tissue near the apex of bladders of Mras -/- males exhibited hypercontractility in response to the cholinergic agonist carbachol in in vitro, while responses in Mras -/- females were normal. In addition, spontaneous phasic contractions of detrusors from Mras -/- males were increased, and Mras -/- males exhibited urinary incontinence. We found that expression of the muscarinic M2 and M3 receptors that mediate the cholinergic contractile stimuli of the detrusor muscle was dysregulated in both Mras -/- males and females, although only males exhibited a urinary phenotype. Elevated expression of M2R in young males lacking M-Ras and failure to upregulate M3R with age resulted in significantly lower ratios of M3R/M2R expression that correlated with the bladder abnormalities. Our data suggests that M-Ras and M3R are functionally linked and that M-Ras is an important regulator of male bladder control in mice. Our observations also support the notion that bladder control is sexually dimorphic and is regulated through mechanisms that are largely independent of acetylcholine signaling in female mice. PMID:26516777

Differential diagnosis of breast masses in South Korean premenopausal women using diffuse optical spectroscopic imaging

NASA Astrophysics Data System (ADS)

Leproux, Anaïs; Kim, You Me; Min, Jun Won; McLaren, Christine E.; Chen, Wen-Pin; O'Sullivan, Thomas D.; Lee, Seung-ha; Chung, Phil-Sang; Tromberg, Bruce J.

2016-07-01

Young patients with dense breasts have a relatively low-positive biopsy rate for breast cancer (˜1 in 7). South Korean women have higher breast density than Westerners. We investigated the benefit of using a functional and metabolic imaging technique, diffuse optical spectroscopic imaging (DOSI), to help the standard of care imaging tools to distinguish benign from malignant lesions in premenopausal Korean women. DOSI uses near-infrared light to measure breast tissue composition by quantifying tissue concentrations of water (ctH2O), bulk lipid (ctLipid), deoxygenated (ctHHb), and oxygenated (ctHbO2) hemoglobin. DOSI spectral signatures specific to abnormal tissue and absent in healthy tissue were also used to form a malignancy index. This study included 19 premenopausal subjects (average age 41±9), corresponding to 11 benign and 10 malignant lesions. Elevated lesion to normal ratio of ctH2O, ctHHb, ctHbO2, total hemoglobin (THb=ctHHb+ctHbO2), and tissue optical index (ctHHb×ctH2O/ctLipid) were observed in the malignant lesions compared to the benign lesions (p<0.02). THb and malignancy index were the two best single predictors of malignancy, with >90% sensitivity and specificity. Malignant lesions showed significantly higher metabolism and perfusion than benign lesions. DOSI spectral features showed high discriminatory power for distinguishing malignant and benign lesions in dense breasts of the Korean population.

Autofluorescence guided diagnostic evaluation of suspicious oral mucosal lesions: opportunities, limitations, and pitfalls

NASA Astrophysics Data System (ADS)

Vigneswaran, Nadarajah

2011-03-01

Wide-filed autofluorescence examination is currently considered as a standard of care for screening and diagnostic evaluation of early neoplastic changes of the skin, cervix, lung, bladder, gastrointestinal tract and oral cavity. Naturally occurring fluorophores within the tissue absorb UV and visible light and can re-emit some of this light at longer wavelengths in the form of fluorescence. This non-invasive tissue autofluorescence imaging is used in optical diagnostics, especially in the early detection of cancer. Usually, malignant transformation is associated with thickening of the epithelium, enhanced cellular density due to increased nuclear cytoplasmic ratio which may attenuate the excitation leading to a decrease in collagen autofluorescence. Hence, dysplastic and cancerous tissues often exhibit decreased blue-green autofluorescence and appear darker compared to uninvolved mucosa. Currently, there are three commercially available devices to examine tissue autofluorescence in the oral cavity. In this study we used the oral cancer screening device IdentafiTM 3000 to examine the tissue reflectance and autofluorescence of PML and confounding lesions of the oral cavity. Wide-field autofluorescence imaging enables rapid inspection of large mucosal surfaces, to aid in recognition of suspicious lesions and may also help in discriminate the PML (class 1) from some of the confounding lesions (class II). However, the presence of inflammation or pigments is also associated with loss of stromal autofluorescence, and may give rise to false-positive results with widefield fluorescence imaging. Clinicians who use these autofluorescence based oral cancer screening devices should be aware about the benign oral mucosal lesions that may give false positivity so that unnecessary patient's anxiety and the need for scalpel biopsy can be eliminated.

The Role of Genetically Modified Mesenchymal Stem Cells in Urinary Bladder Regeneration.

PubMed

Snow-Lisy, Devon C; Diaz, Edward C; Bury, Matthew I; Fuller, Natalie J; Hannick, Jessica H; Ahmad, Nida; Sharma, Arun K

2015-01-01

Recent studies have demonstrated that mesenchymal stem cells (MSCs) combined with CD34+ hematopoietic/stem progenitor cells (HSPCs) can function as surrogate urinary bladder cells to synergistically promote multi-faceted bladder tissue regeneration. However, the molecular pathways governing these events are unknown. The pleiotropic effects of Wnt5a and Cyr61 are known to affect aspects of hematopoiesis, angiogenesis, and muscle and nerve regeneration. Within this study, the effects of Cyr61 and Wnt5a on bladder tissue regeneration were evaluated by grafting scaffolds containing modified human bone marrow derived MSCs. These cell lines were engineered to independently over-express Wnt5a or Cyr61, or to exhibit reduced expression of Cyr61 within the context of a nude rat bladder augmentation model. At 4 weeks post-surgery, data demonstrated increased vessel number (~250 vs ~109 vessels/mm2) and bladder smooth muscle content (~42% vs ~36%) in Cyr61OX (over-expressing) vs Cyr61KD (knock-down) groups. Muscle content decreased to ~25% at 10 weeks in Cyr61KD groups. Wnt5aOX resulted in high numbers of vessels and muscle content (~206 vessels/mm2 and ~51%, respectively) at 4 weeks. Over-expressing cell constructs resulted in peripheral nerve regeneration while Cyr61KD animals were devoid of peripheral nerve regeneration at 4 weeks. At 10 weeks post-grafting, peripheral nerve regeneration was at a minimal level for both Cyr61OX and Wnt5aOX cell lines. Blood vessel and bladder functionality were evident at both time-points in all animals. Results from this study indicate that MSC-based Cyr61OX and Wnt5aOX cell lines play pivotal roles with regards to increasing the levels of functional vasculature, influencing muscle regeneration, and the regeneration of peripheral nerves in a model of bladder augmentation. Wnt5aOX constructs closely approximated the outcomes previously observed with the co-transplantation of MSCs with CD34+ HSPCs and may be specifically targeted as an alternate means to achieve functional bladder regeneration.

Microcirculation and structural reorganization of the bladder mucosa in chronic cystitis under conditions of ozone therapy.

PubMed

Neimark, A I; Nepomnyashchikh, L M; Lushnikova, E L; Bakarev, M A; Abdullaev, N A; Sizov, K A

2014-01-01

Structural reorganization of the bladder mucosa in chronic cystitis and its correction by ozone therapy were studied. A relationship between the epithelial layer restructuring of different kinds (dystrophy, metaplasia, and degeneration), level of cell proliferation, and ultrastructural organization of urotheliocytes was detected. This complex of structural reactions was combined with dysregulation of tissue bloodflow in the bladder mucosa, shown by laser Doppler flowmetry. Positive structural changes were most marked in intravesical and less so in parenteral ozone therapy added to the therapeutic complex and manifested in reduction of inflammation and alteration in parallel with more intense reparative reactions. A special feature of parenteral ozone therapy was a significant improvement of microcirculation in the bladder mucosa.

Isorhapontigenin (ISO) Inhibits Invasive Bladder Cancer Formation In Vivo and Human Bladder Cancer Invasion In Vitro by Targeting STAT1/FOXO1 Axis.

PubMed

Jiang, Guosong; Wu, Amy D; Huang, Chao; Gu, Jiayan; Zhang, Liping; Huang, Haishan; Liao, Xin; Li, Jingxia; Zhang, Dongyun; Zeng, Xingruo; Jin, Honglei; Huang, Haojie; Huang, Chuanshu

2016-07-01

Although our most recent studies have identified Isorhapontigenin (ISO), a novel derivative of stilbene that isolated from a Chinese herb Gnetum cleistostachyum, for its inhibition of human bladder cancer growth, nothing is known whether ISO possesses an inhibitory effect on bladder cancer invasion. Thus, we addressed this important question in current study and discovered that ISO treatment could inhibit mouse-invasive bladder cancer development following bladder carcinogen N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) exposure in vivo We also found that ISO suppressed human bladder cancer cell invasion accompanied by upregulation of the forkhead box class O 1 (FOXO1) mRNA transcription in vitro Accordingly, FOXO1 was profoundly downregulated in human bladder cancer tissues and was negatively correlated with bladder cancer invasion. Forced expression of FOXO1 specifically suppressed high-grade human bladder cancer cell invasion, whereas knockdown of FOXO1 promoted noninvasive bladder cancer cells becoming invasive bladder cancer cells. Moreover, knockout of FOXO1 significantly increased bladder cancer cell invasion and abolished the ISO inhibition of invasion in human bladder cancer cells. Further studies showed that the inhibition of Signal transducer and activator of transcription 1 (STAT1) phosphorylation at Tyr701 was crucial for ISO upregulation of FOXO1 transcription. Furthermore, this study revealed that metalloproteinase-2 (MMP-2) was a FOXO1 downstream effector, which was also supported by data obtained from mouse model of ISO inhibition BBN-induced mouse-invasive bladder cancer formation. These findings not only provide a novel insight into the understanding of mechanism of bladder cancer's propensity to invasion, but also identify a new role and mechanisms underlying the natural compound ISO that specifically suppresses such bladder cancer invasion through targeting the STAT1-FOXO1-MMP-2 axis. Cancer Prev Res; 9(7); 567-80. ©2016 AACR. ©2016 American Association for Cancer Research.

[Myofibroblasts and afferent signalling in the urinary bladder. A concept].

PubMed

Neuhaus, J; Scholler, U; Freick, K; Schwalenberg, T; Heinrich, M; Horn, L C; Stolzenburg, J U

2008-09-01

Afferent signal transduction in the urinary bladder is still not clearly understood. An increasing body of evidence supports the view of complex interactions between urothelium, suburothelial myofibroblasts, and sensory nerves. Bladder tissue from tumour patients was used in this study. Methods included confocal immunofluorescence, polymerase chain reaction, calcium imaging, and fluorescence recovery after photobleaching (FRAP).Myofibroblasts express muscarinic and purinergic receptors. They show constitutive spontaneous activity in calcium imaging, which completely depends on extracellular calcium. Stimulation with carbachol and ATP-evoked intracellular calcium transients also depend on extracellular calcium. The intensive coupling between the cells is significantly diminished by incubation with TGF-beta 1. Myofibroblasts form an important cellular element within the afferent signalling of the urinary bladder. They possess all features required to take part in the complex interactions with urothelial cells and sensory nerves. Modulation of their function by cytokines may provide a pathomechanism for bladder dysfunction.

Altered RECQL5 expression in urothelial bladder carcinoma increases cellular proliferation and makes RECQL5 helicase activity a novel target for chemotherapy

PubMed Central

Patterson, Karl; Arya, Lovleen; Bottomley, Sarah; Morgan, Susan; Cox, Angela; Catto, James; Bryant, Helen E.

2016-01-01

RECQ helicases are a family of enzymes with both over lapping and unique functions. Functional autosomal recessive loss of three members of the family BLM, WRN and RECQL4, results in hereditary human syndromes characterized by cancer predisposition and premature aging, but despite the finding that RECQL5 deficient mice are cancer prone, no such link has been made to human RECQL5. Here we demonstrate that human urothelial carcinoma of the bladder (UCC) has increased expression of RECQL5 compared to normal bladder tissue and that increasing RECQL5 expression can drive proliferation of normal bladder cells and is associated with poor prognosis. Further, by expressing a helicase dead RECQL5 and by depleting bladder cancer cells of RECQL5 we show that inhibition of RECQL5 activity has potential as a new target for treatment of UCC. PMID:27764811

Giant cell arteritis mimicking a testicular tumour.

PubMed

Sundaram, S; Smith, D H

2001-07-01

Giant cell arteritis involving the testis was identified incidentally upon orchidectomy of a right testicular mass. The mass looked like a malignant process on ultrasound. The patient also had generalised disease and was treated appropriately. Giant cell arteritis involving the bladder, prostate, uterus, and adnexa have been described before. To our knowledge, this is the first described case of giant cell arteritis affecting the testis.

The ESR1 and GPX1 gene expression level in human malignant and non-malignant breast tissues.

PubMed

Król, Magdalena B; Galicki, Michał; Grešner, Peter; Wieczorek, Edyta; Jabłońska, Ewa; Reszka, Edyta; Morawiec, Zbigniew; Wąsowicz, Wojciech; Gromadzińska, Jolanta

2018-01-01

The aim of this study was to establish whether the gene expression of estrogen receptor alpha (encoded by ESR1) correlates with the expression of glutathione peroxidase 1 (encoded by GPX1) in the tumor and adjacent tumor-free breast tissue, and whether this correlation is affected by breast cancer. Such relationships may give further insights into breast cancer pathology with respect to the status of estrogen receptor. We used the quantitative real-time PCR technique to analyze differences in the expression levels of the ESR1 and GPX1 genes in paired malignant and non-malignant tissues from breast cancer patients. ESR1 and GPX1 expression levels were found to be significantly down-regulated by 14.7% and 7.4% (respectively) in the tumorous breast tissue when compared to the non-malignant one. Down-regulation of these genes was independent of the tumor histopathology classification and clinicopathological factors, while the ESR1 mRNA level was reduced with increasing tumor grade (G1: 103% vs. G2: 85.8% vs. G3: 84.5%; p<0.05). In the non-malignant and malignant breast tissues, the expression levels of ESR1 and GPX1 were significantly correlated with each other (Rs=0.450 and Rs=0.360; respectively). Our data suggest that down-regulation of ESR1 and GPX1 was independent of clinicopathological factors. Down-regulation of ESR1 gene expression was enhanced by the development of the disease. Moreover, GPX1 and ESR1 gene expression was interdependent in the malignant breast tissue and further work is needed to determine the mechanism underlying this relationship.

Positron emission tomography-computed tomography and 4-hydroxynonenal-histidine immunohistochemistry reveal differential onset of lipid peroxidation in primary lung cancer and in pulmonary metastasis of remote malignancies.

PubMed

Živković, Nevenka Piskač; Petrovečki, Mladen; Lončarić, Čedna Tomasović; Nikolić, Igor; Waeg, Georg; Jaganjac, Morana; Žarković, Kamelija; Žarković, Neven

2017-04-01

The Aim of the study was to reveal if PET-CT analysis of primary and of secondary lung cancer could be related to the onset of lipid peroxidation in cancer and in surrounding non-malignant lung tissue. Nineteen patients with primary lung cancer and seventeen patients with pulmonary metastasis were involved in the study. Their lungs were analyzed by PET-CT scanning before radical surgical removal of the cancer. Specific immunohistochemistry for the major bioactive marker of lipid peroxidation, 4-hydroxynonenal (HNE), was done for the malignant and surrounding non-malignant lung tissue using genuine monoclonal antibody specific for the HNE-histidine adducts. Both the intensity of the PET-CT analysis and the HNE-immunohistochemistry were in correlation with the size of the tumors analyzed, while primary lung carcinomas were larger than the metastatic tumors. The intensity of the HNE-immunohistochemistry in the surrounding lung tissue was more pronounced in the metastatic than in the primary tumors, but it was negatively correlated with the cancer volume determined by PET-CT. The appearance of HNE was more pronounced in non-malignant surrounding tissue than in cancer or stromal cells, both in case of primary and metastatic tumors. Both PET-CT and HNE-immunohistochemistry reflect the size of the malignant tissue. However, lipid peroxidation of non-malignant lung tissue in the vicinity of cancer is more pronounced in metastatic than in primary malignancies and might represent the mechanism of defense against cancer, as was recently revealed also in case of human liver cancer. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Laparoscopic cholecystectomy in the treatment of gallbladder polypoid lesions--15 years of experience.

PubMed

Matłok, Maciej; Migaczewski, Marcin; Major, Piotr; Pędziwiatr, Michał; Budzyński, Piotr; Winiarski, Marek; Ostachowski, Mateusz; Budzyński, Andrzej; Rembiasz, Kazimierz

2013-11-01

Due to the constant increase of public health awareness and widespread "cancerophobia", the progressively larger number of incidentally diagnosed gall-bladder polyps became the source of anxiety, which leads patients and physicians to undertake therapeutic decisions, despite the absence of symptoms. The majority of gall-bladder polyps are benign. It is estimated that only 3 to 5% of polyps are malignant. Currently, there is lack of randomized control trials based on which the clear-cut criteria of qualification of patients with gall-bladder polyps for surgical procedure can be created. The aim of the study was to analyze gall-bladder polyps in patients who underwent laparoscopic cholecystectomy in the 2nd Department of General Surgery, Jagiellonian University Collegium Medicum. The retrospective study was conducted on 5369 patients who underwent laparoscopic cholecystectomy in the 2nd Department of General Surgery, Jagiellonian University Collegium Medicum with special attention to 152 (2.8%) patients in whom gall-bladder polyps were diagnosed preoperatively. Qualification criteria for surgery, surgical treatment results, and histopathological examination results were also analyzed. Amongst the 5369 patients qualified for laparoscopic cholecystectomy, 152 (2.8%) were diagnosed with gall-bladder polyps during the preoperative ultrasound examinations. Postoperative histopathological examinations of 41 (27%) patients confirmed the presence of gall-bladder polyps. In 102 (67%) patients, only gall-stones were diagnosed without previously described polyps during the ultrasound examination. Analysis of the histopathological examination results revealed the presence of benign lesions in 35 (23.35%) patients. In 5 (3%) patients the presence of an adenoma, and in one (0.65%) the presence of adenocarcinoma were confirmed. Based on the conducted study and previous personal experience in the treatment of patients with gall-bladder polyps, we believe that due to the potential risk of neoplastic transformation, patients with polyps larger than 10 mm in diameter and polyps of proven rapid growth should be qualified for laparoscopic cholecystectomy. Indications for surgical treatment also seem reasonable in case of patients with present polyps and coexisting right upper quadrant pain, even though the above-mentioned is connected with gall-bladder deposits.

DNA BINDING AND ADDUCT FORMATION OF AFLATOXIN B1 IN CULTURED HUMAN AND ANIMAL TRACHEOBRONCHIAL AND BLADDER TISSUES

EPA Science Inventory

DNA binding and adduct formation of aflatoxin B1 (AFB1) was studied in cultured bladder and tracheobronchial explants from human, monkey, dog, hamster and rat. Explants were exposed to (3H)AFB1 (1 micrometer final concentration) in PFHR-4 medium (pH 7.4) without serum for 24 h, a...

INTERSPECIES COMPARISONS OF BENZO(A)PYRENE METABOLISM AND DNA-ADDUCT FORMATION IN CULTURED HUMAN AND ANIMAL BLADDER AND TRACHEOBRONCHIAL TISSUES

EPA Science Inventory

Cultured bladder and tracheobronchial explants from human, monkey, dog, hamster, and rat were used to study the metabolism, covalent binding to DNA, and DNA:adduct formation of (3H0benzo(a)pyrene (BP). Both organs from all species formed large amounts (40 to 70% of total 3H in th...

MBCP - Approach - Advanced Surgery | Center for Cancer Research

Cancer.gov

Advanced Surgery We have the expertise to do complex reconstructive procedures with robotic assistance. This results in: smaller incisions, less blood loss, and shorter stays in the hospital In the most challenging of cases of radical cystectomy, we remove the bladder and replace it with a bladder that we construct from bowel tissue. This is standard-of-care for advanced cases.

How does the urothelium affect bladder function in health and disease?

PubMed Central

Birder, L.A.; Ruggieri, M.; Takeda, M.; van Koeveringe, G.; Veltkamp, S.A.; Korstanje, C.; Parsons, B.A.; Fry, C.H.

2011-01-01

The urothelium is a multifunctional tissue that not only acts as a barrier between the vesical contents of the lower urinary tract and the underlying tissues but also acts as a sensory organ by transducing physical and chemical stresses to the attendant afferent nervous system and underlying smooth muscle. This review will consider the nature of the stresses that the urothelium can transduce; the transmitters that mediate the transduction process; and how lower urinary pathologies, including overactive bladder syndrome, painful bladder syndrome and bacterial infections, are associated with alterations to this sensory system. In particular, the role of muscarinic receptors and the TRPV channels system will be discussed in this context. The urothelium also influences the contractile state of detrusor smooth muscle, both through modifying its contractility and the extent of spontaneous activity; potential pathways are discussed. The potential role that the urothelium may play in bladder underactivity is introduced, as well as potential biomarkers for the condition that may cross the urothelium to the urine. Finally consideration is given to vesical administration of therapeutic agents that influence urinary tract function and how the properties of the urothelium may determine the effectiveness of this mode of delivery. PMID:22275289

Effect of furosemide on ion transport in the turtle bladder: evidence for direct inhibition of active acid-base transport.

PubMed

Ehrenspeck, G; Voner, C

1985-07-25

The diuretic furosemide inhibits acid-base transport in the short-circuited turtle bladder. It inhibits luminal acidification when present in either mucosal or serosal bathing fluids, but decreases alkalinization only from the serosal side of the tissue. The inhibition of both acid-base transport processes is independent of ambient Cl-; and the disulfonic stilbene, SITS, an inhibitor of Cl--HCO3- exchange, fails to prevent the furosemide-elicited inhibition of alkalinization. These results preclude an absolute requirement of a furosemide-sensitive Cl--HCO3- exchange by these transport processes. The drug also interferes with the CO2-induced stimulation of acidification and alkalinization. The inhibition of the residual acidification in acetazolamide-treated, acidotic bladders, however, suggests an action at sites other than cytosolic carbonic anhydrase. Although active Na+ and Cl- reabsorption and tissue oxygen uptake are also decreased by furosemide, the rate of oxygen consumption uncoupled by 2,4-dinitrophenol is not diminished, indicating a primary inhibition of the various ion transport processes, not of metabolism. It is proposed that inhibition of transepithelial acid-base transport by furosemide in the turtle bladder includes inhibition of the acid-base pumps.

Neoadjuvant chemotherapy for primary adenocarcinomas of the urinary bladder: a single-site experience.

PubMed

Yu, Bin; Zhou, Jin; Cai, Hongzhou; Xu, Ting; Xu, Zicheng; Zou, Qing; Gu, Min

2015-01-28

Adenocarcinoma of the urinary bladder is a rare malignancy. Radical surgery is suggested as the best available treatment for early-stage disease, but there is currently no consensus on standard chemotherapy regimen for advanced stage. We assessed the feasibility and effect of neoadjuvant chemotherapy with gemcitabine and cisplatin (GC) plus S-1 for patients with locally advanced primary adenocarcinomas of the urinary bladder. Six patients with locally advanced urachal or non-urachal (n = 3, each) primary adenocarcinoma of the bladder were treated from October 2010 to October 2013 at a single center. All the patients were treated with 3 cycles (21d, each) of GC plus S-1 (gemcitabine, 1000 mg/m2, days 1 and 8; cisplatin, 70 mg/m2, day 2; and S-1, 50 mg bid, day 1-14). After neoadjuvant chemotherapy, patients with urachal cancer were treated with en bloc radical cystectomy and umbilectomy; the remaining 3 patients were treated with cystectomy. All patients successfully completed the neoadjuvant chemotherapy without serious side effects. Two patients were assessed as complete response, 2 as partial response, 1 as stable disease and 1 as progressive disease. Despite the limitations of a small study population, the GC plus S-1 regimen for locally advanced primary adenocarcinoma of the urinary bladder was effective, and facilitated the success of surgery to a certain extent. Short follow-up time was also a limitation of our study. More studies are needed to evaluate the results.

Evaluation of transurethral and transperineal tin ethyl etiopurpurin-photodynamic therapy on the canine prostate one week after drug injection

NASA Astrophysics Data System (ADS)

Selman, Steven H.; Keck, Rick W.; Kondo, Sandy; Albrecht, Detlef

1999-06-01

We have been investigating the potential applicability of photodynamic therapy for the treatment of benign and malignant disease of the prostate. Both transurethral and transperineal approaches to the delivery of light to the tin ethyl etiopurpurin sensitized canine prostate have been studied. Pharmacologic studies were performed and suggested that delaying light treatment for 7 days after drug administration would maximize the desired effect on the targeted prostatic tissue while minimizing the damage to surrounding bladder and rectum. A total of 12 dogs were treated with transurethral light alone (n=6) or the combination of transurethral light and transperineal light one week after tin ethyl etiopurpurin administration. (Previous studies have shown that light alone has no effect on prostate size or histology.) Animals were euthanized 48 hours and 3 weeks after completion of treatment (drug, 1mg/kg day 0, light [400mw/750sec]day 7). Tissue response was determined by gross and microscopic examination. Additionally, pre- and post- treatment transrectal ultrasounds were compared to assess changes in prostate volume and tissue echogenicity. The combination of transurethral and transperineal light results in extensive destruction of glandular epithelium with minimal damage to surrounding structures. Prostate volumes decreased by an average of 52%. Untreated areas were found to lie greater than 0.5 cm from the light diffuser. These studies have encouraged us to continue to investigate this modality as a technique for total ablation of prostatic glandular epithelium.

Determination of the Chronic Mammalian Toxicological Effects of RDX. Twenty-Four Month Chronic Toxicity/Carcinogenicity Study of Hexahydro-1,3,5-Trinitro-1,3,5-Triazine (RDX) in the B6C3F1 Hybrid Mouse. Phase 4, Volume 3, Appendix 11: Final Pathology Report

DTIC Science & Technology

1984-04-01

bladder 1 muscle, s k e l e t a l 5 bone marrow smear --- 3 nasal t u rb ina tes *ti ~ s u e masses ,- and any o the r t i ssues w i t h...Lymphoma, lymphocytic type .__ - __ __ ___ .____. . _ - --- Fibrosarcoma , me ta s t a t i c - __ .._._- _ __._ - - .- Granulosa-cell Carcinoma... Fibrosarcoma , m e t a s t a t i c . -- RENAL LYMPH NODE -- E ’ L - --.I- t Malignant Lymphoma, mixed type Malignant

Noninvasive identification of bladder cancer with subsurface backscattered light

NASA Astrophysics Data System (ADS)

Bigio, Irving J.; Mourant, Judith R.; Boyer, James D.; Johnson, Tamara M.; Shimada, Tsutomu; Conn, Richard L.

1994-05-01

We have developed and are testing early prototypes of an optical biopsy system (OBS) for detection of cancer and other tissue pathologies. The OBS invokes a unique approach to optical diagnosis of tissue pathologies based on the elastic scattering properties, over a wide range of wavelengths, of the microscopic structure of the tissue. Absorption bands in the tissue also add useful complexity to the spectral data collected. The data acquisition and storage/display time with the OBS instrument is approximately 1 second. Thus, in addition to the reduced invasiveness of this technique compared with current state-of- the-art methods, the OBS offers the possibility of impressively faster diagnostic assessment. The OBS employs a small fiber-optic probe that is amendable to use with any endoscope, catheter or hypodermic, or to direct surface examination (e.g., as in skin cancer or cervical cancer). We report here specifically on its potential application in the detection of bladder cancer.

[Transurethral resection of bladder tumors and prostate enlargement in physiological saline solution (TURIS). A prospective study].

PubMed

Rose, A; Suttor, S; Goebell, P J; Rossi, R; Rübben, H

2007-09-01

Transurethral resection in a conductive irrigant medium is a new procedure in the surgical therapy of bladder tumors and prostate enlargement. In this prospective randomized trial we compared conventional TUR with TUR in saline regarding safety and efficiency. Between November 2004 and February 2005 a total number of 128 patients were included in this study. After randomization 58 patients were treated by conventional TUR and 70 patients by TURIS (Olympus, SurgMasterSystem). We evaluated resection time, weight of resected tissue, complications, blood loss, changes in serum sodium, and duration of catheterization. Among the tested procedures no statistically significant difference could be observed concerning blood loss, change of serum sodium, and complications. The mean weight of resected tissue of the prostate per time was 0.9 g/min with the TUR procedure and 0.8 g/min with the TURIS procedure. Severe complications like TUR syndrome or perforation of the bladder were not observed at all. In the TURIS group time until catheter removal was longer but also the mean weight of resected tissue of the prostate was higher in the TURIS group (42 g) than in the conventional TUR group (31 g). Transurethral resection in a conductive irrigant medium (TURIS) can be considered as a safe and effective surgical procedure in the treatment of BPH and superficial urothelial carcinoma. Moreover the risk of TUR syndrome and perforation of the bladder due to nerve stimulation is reduced.

Advances in stem cell therapy for the lower urinary tract.

PubMed

Lin, Ching-Shwun

2010-02-26

Lower urinary tract diseases are emotionally and financially burdensome to the individual and society. Current treatments are ineffective or symptomatic. Conversely, stem cells (SCs) are regenerative and may offer long-term solutions. Among the different types of SCs, bone marrow SCs (BMSCs) and skeletal muscle-derived SCs (SkMSCs) have received the most attention in pre-clinical and clinical trial studies concerning the lower urinary tract. In particular, clinical trials with SkMSCs for stress urinary incontinence have demonstrated impressive efficacy. However, both SkMSCs and BMSCs are difficult to obtain in quantity and therefore neither is optimal for the eventual implementation of SC therapy. On the other hand, adipose tissue-derived SCs (ADSCs) can be easily and abundantly obtained from "discarded" adipose tissue. Moreover, in several head-on comparison studies, ADSCs have demonstrated equal or superior therapeutic potential compared to BMSCs. Therefore, across several different medical disciplines, including urology, ADSC research is gaining wide attention. For the regeneration of bladder tissues, possible differentiation of ADSCs into bladder smooth muscle and epithelial cells has been demonstrated. For the treatment of bladder diseases, specifically hyperlipidemia and associated overactive bladder, ADSCs have also demonstrated efficacy. For the treatment of urethral sphincter dysfunction associated with birth trauma and hormonal deficiency, ADSC therapy was also beneficial. Finally, ADSCs were able to restore erectile function in various types of erectile dysfunction (ED), including those associated with diabetes, hyperlipidemia, and nerve injuries. Thus, ADSCs have demonstrated remarkable therapeutic potentials for the lower urinary tract.

Time-resolved laser-induced fluorescence spectroscopy as a diagnostic instrument in head and neck carcinoma.

PubMed

Meier, Jeremy D; Xie, Hongtao; Sun, Yang; Sun, Yinghua; Hatami, Nisa; Poirier, Brian; Marcu, Laura; Farwell, D Gregory

2010-06-01

The objectives of this study were to 1) determine differences in lifetime fluorescence between normal and malignant tissue of the upper aerodigestive tract, and 2) evaluate the potential of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) as a diagnostic instrument for head and neck squamous cell carcinoma (HNSCC). Cross-sectional study. University-based medical center. Nine patients with suspected HNSCC were included. In the operating room, a nitrogen pulse laser (337 nm, 700-picosecond pulse width) was used to induce tissue autofluorescence of normal tissue and suspected malignant lesions. Spectral intensities and time-domain measurements were obtained and compared with the histopathology at each site. A total of 53 sites were measured. The fluorescence parameters that provided the most discrimination were determined. Differences in spectral intensities allowed for discrimination between malignant and normal tissue. The spectral intensity of malignant tissue was lower than that of normal tissue, and a shift of peak intensity to a longer wavelength was observed in the normalized spectrum of malignant tissue in the range of 360 to approximately 660 nm. Multiple time-resolved fluorescence parameters provided the best diagnostic discrimination between normal tissue and carcinoma, including average lifetimes (i.e., at 390 nm: 1.7 +/- 0.06 ns [not significant] for normal and 1.3 +/- 0.06 ns for tumor, P = 0.0025) and the second-order Laguerre expansion coefficient (LEC-2) (i.e., at 460 nm: 0.135 +/- 0.001 for normal and 0.155 +/- 0.007 for tumor, P < 0.05). These findings highlight some of the differences in lifetime fluorescence between normal and malignant tissue. TR-LIFS has potential as a noninvasive diagnostic technique for HNSCC. Copyright 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. Published by Mosby, Inc. All rights reserved.

Time-resolved laser-induced fluorescence spectroscopy as a diagnostic instrument in head and neck carcinoma

PubMed Central

Meier, Jeremy D.; Xie, Hongtao; Sun, Yang; Sun, Yinghua; Hatami, Nisa; Poirier, Brian; Marcu, Laura; Farwell, D. Gregory

2011-01-01

OBJECTIVE 1) Determine differences in lifetime fluorescence between normal and malignant tissue of the upper aerodigestive tract. 2) Evaluate the potential of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) as a diagnostic instrument for head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN Cross-sectional study. SETTING University-based medical center. SUBJECTS AND METHODS Nine patients with suspected HNSCC were included. In the operating room, a nitrogen pulse laser (337 nm, 700 ps pulse width) was used to induce tissue autofluorescence of normal tissue and suspected malignant lesions. Spectral intensities and time-domain measurements were obtained and compared to the histopathology at each site. A total of 53 sites were measured. The fluorescence parameters that provided the most discrimination were determined. RESULTS Differences in spectral intensities allowed for discrimination between malignant and normal tissue. The spectral intensity of malignant tissue was lower than the normal tissue, and a shift of peak intensity to a longer wavelength was observed in the normalized spectrum of malignant tissue in the range of 360~660 nm. Multiple time-resolved fluorescence parameters provided the best diagnostic discrimination between normal tissue and carcinoma, including average lifetimes (i.e., at 390 nm: 1.7±0.06 ns for normal and 1.3±0.06 ns for tumor, P=0.0025), and the Laguerre coefficients, LEC-2 (i.e., at 460 nm: 0.135±0.001 for normal and 0.155±0.007 for tumor, P<0.05). CONCLUSION These findings highlight some of the differences in lifetime fluorescence between normal and malignant tissue. TR-LIFS has potential as a non-invasive diagnostic technique for HNSCC. PMID:20493355

Atezolizumab and Bevacizumab in Rare Solid Tumors

ClinicalTrials.gov

2018-05-25

Malignant Neoplasms of Digestive Organs; Malignant Neoplasms of Lip Oral Cavity and Pharynx; Malignant Neoplasms of Mesothelial and Soft Tissue; Malignant Neoplasms of Respiratory and Intrathoracic Organs

Assessment of normal tissue complications following prostate cancer irradiation: Comparison of radiation treatment modalities using NTCP models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takam, Rungdham; Bezak, Eva; Yeoh, Eric E.

2010-09-15

Purpose: Normal tissue complication probability (NTCP) of the rectum, bladder, urethra, and femoral heads following several techniques for radiation treatment of prostate cancer were evaluated applying the relative seriality and Lyman models. Methods: Model parameters from literature were used in this evaluation. The treatment techniques included external (standard fractionated, hypofractionated, and dose-escalated) three-dimensional conformal radiotherapy (3D-CRT), low-dose-rate (LDR) brachytherapy (I-125 seeds), and high-dose-rate (HDR) brachytherapy (Ir-192 source). Dose-volume histograms (DVHs) of the rectum, bladder, and urethra retrieved from corresponding treatment planning systems were converted to biological effective dose-based and equivalent dose-based DVHs, respectively, in order to account for differences inmore » radiation treatment modality and fractionation schedule. Results: Results indicated that with hypofractionated 3D-CRT (20 fractions of 2.75 Gy/fraction delivered five times/week to total dose of 55 Gy), NTCP of the rectum, bladder, and urethra were less than those for standard fractionated 3D-CRT using a four-field technique (32 fractions of 2 Gy/fraction delivered five times/week to total dose of 64 Gy) and dose-escalated 3D-CRT. Rectal and bladder NTCPs (5.2% and 6.6%, respectively) following the dose-escalated four-field 3D-CRT (2 Gy/fraction to total dose of 74 Gy) were the highest among analyzed treatment techniques. The average NTCP for the rectum and urethra were 0.6% and 24.7% for LDR-BT and 0.5% and 11.2% for HDR-BT. Conclusions: Although brachytherapy techniques resulted in delivering larger equivalent doses to normal tissues, the corresponding NTCPs were lower than those of external beam techniques other than the urethra because of much smaller volumes irradiated to higher doses. Among analyzed normal tissues, the femoral heads were found to have the lowest probability of complications as most of their volume was irradiated to lower equivalent doses compared to other tissues.« less

Effects of ageing and streptozotocin-induced diabetes on connexin43 and P2 purinoceptor expression in the rat corpora cavernosa and urinary bladder.

PubMed

Suadicani, Sylvia O; Urban-Maldonado, Marcia; Tar, Moses T; Melman, Arnold; Spray, David C

2009-06-01

To investigate whether ageing and diabetes alter the expression of the gap junction protein connexin43 (Cx43) and of particular purinoceptor (P2R) subtypes in the corpus cavernosum and urinary bladder, and determine whether changes in expression of these proteins correlate with development of erectile and bladder dysfunction in diabetic and ageing rats. Erectile and bladder function of streptozotocin (STZ)-induced diabetic, insulin-treated and age-matched control Fischer-344 rats were evaluated 2, 4 and 8 months after diabetes induction by in vivo cystometry and cavernosometry. Corporal and bladder tissue were then isolated at each of these sample times and protein expression levels of Cx43 and of various P2R subtypes were determined by Western blotting. In the corpora of control rats ageing was accompanied by a significant decrease in Cx43 and P2X(1)R, and increase in P2X(7)R expression. There was decreased Cx43 and increased P2Y(4)R expression in the ageing control rat bladder. There was a significant negative correlation between erectile capacity and P2X(1)R expression levels, and a positive correlation between bladder spontaneous activity and P2Y(4)R expression levels. There was already development of erectile dysfunction and bladder overactivity at 2 months after inducing diabetes, the earliest sample measured in the study. The development of these urogenital complications was accompanied by significant decreases in Cx43, P2Y(2)R, P2X(4)R and increase in P2X(1)R expression in the corpora, and by a doubling in Cx43 and P2Y(2)R, and significant increase in P2Y(4)R expression in the bladder. Changes in Cx43 and P2R expression were largely prevented by insulin therapy. Ageing and diabetes mellitus markedly altered the expression of the gap junction protein Cx43 and of particular P2R subtypes in the rat penile corpora and urinary bladder. These changes in Cx43 and P2R expression provide the molecular substrate for altered gap junction and purinergic signalling in these tissues, and thus probably contribute to the early development of erectile dysfunction and higher detrusor activity in ageing and in diabetic rats.

[Support vector machine?assisted diagnosis of human malignant gastric tissues based on dielectric properties].

PubMed

Zhang, Sa; Li, Zhou; Xin, Xue-Gang

2017-12-20

To achieve differential diagnosis of normal and malignant gastric tissues based on discrepancies in their dielectric properties using support vector machine. The dielectric properties of normal and malignant gastric tissues at the frequency ranging from 42.58 to 500 MHz were measured by coaxial probe method, and the Cole?Cole model was used to fit the measured data. Receiver?operating characteristic (ROC) curve analysis was used to evaluate the discrimination capability with respect to permittivity, conductivity, and Cole?Cole fitting parameters. Support vector machine was used for discriminating normal and malignant gastric tissues, and the discrimination accuracy was calculated using k?fold cross? The area under the ROC curve was above 0.8 for permittivity at the 5 frequencies at the lower end of the measured frequency range. The combination of the support vector machine with the permittivity at all these 5 frequencies combined achieved the highest discrimination accuracy of 84.38% with a MATLAB runtime of 3.40 s. The support vector machine?assisted diagnosis is feasible for human malignant gastric tissues based on the dielectric properties.

Production of urothelium from pluripotent stem cells for regenerative applications.

PubMed

Osborn, Stephanie L; Kurzrock, Eric A

2015-01-01

As bladder reconstruction strategies evolve, a feasible and safe source of transplantable urothelium becomes a major consideration for patients with advanced bladder disease, particularly cancer. Pluripotent stem cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), are attractive candidates from which to derive urothelium as they renew and proliferate indefinitely in vitro and fulfill the non-autologous and/or non-urologic criteria, respectively, that is required for many patients. This review presents the latest advancements in differentiating urothelium from pluripotent stem cells in vitro in the context of current bladder tissue engineering strategies.

Hypomethylation of DNA from Benign and Malignant Human Colon Neoplasms

NASA Astrophysics Data System (ADS)

Goelz, Susan E.; Vogelstein, Bert; Hamilton, Stanley R.; Feinberg, Andrew P.

1985-04-01

The methylation state of DNA from human colon tissue displaying neoplastic growth was determined by means of restriction endonuclease analysis. When compared to DNA from adjacent normal tissue, DNA from both benign colon polyps and malignant carcinomas was substantially hypomethylated. With the use of probes for growth hormone, γ -globin, α -chorionic gonadotropin, and γ -crystallin, methylation changes were detected in all 23 neoplastic growths examined. Benign polyps were hypomethylated to a degree similar to that in malignant tissue. These results indicate that hypomethylation is a consistent biochemical characteristic of human colonic tumors and is an alteration in the DNA that precedes malignancy.

Molecular genetics and genomics progress in urothelial bladder cancer.

PubMed

Netto, George J

2013-11-01

The clinical management of solid tumor patients has recently undergone a paradigm shift as the result of the accelerated advances in cancer genetics and genomics. Molecular diagnostics is now an integral part of routine clinical management in lung, colon, and breast cancer patients. In a disappointing contrast, molecular biomarkers remain largely excluded from current management algorithms of urologic malignancies. The need for new treatment alternatives and validated prognostic molecular biomarkers that can help clinicians identify patients in need of early aggressive management is pressing. Identifying robust predictive biomarkers that can stratify response to newly introduced targeted therapeutics is another crucially needed development. The following is a brief discussion of some promising candidate biomarkers that may soon become a part of clinical management of bladder cancers. © 2013 Published by Elsevier Inc.

High (18)F-FDG uptake in urinary calculi on PET/CT: An unrecognized non-malignant accumulation.

PubMed

Fu, Zhanli; Li, Ziao; Huang, Jia; Zhang, Jin; Liu, Meng; Li, Qian; Li, Yi

2016-08-01

To assess the high (18)F-fluorodeoxyglucose ((18)F-FDG) uptake in urinary calculi on positron-emission tomography/computed tomography (PET/CT). In this study, (18)F-FDG PET/CT examinations were retrospectively reviewed from November 2013 to February 2016 in a single center, and patients with high (18)F-FDG uptake in urinary calculi were identified. The following data were collected from each patient, including age, sex, primary disease, method to verify the urinary calculus, and imaging characteristics of the calculus. A total of 2758 PET/CT studies (2567 patients) were reviewed, and 52 patients with urinary calculi were identified, in which 6 (11.5%, 6/52) patients (5 males, 1 female, age 34-73 years, median age 60.5 years) demonstrated high (18)F-FDG uptake in the urinary calculi. Among the 6 patients, 3 patients had bladder calculi, 2 patients had renal calculi, and 1 patient had both bladder and renal calculi. The size of the urinary calculi varied from sandy to 19mm on CT. The maximal Hounsfield units of the calculi ranged from 153 to 1078. The SUVmax of the calculi on the routine PET/CT scan ranged from 11.7 to 143.0. Delayed PET/CT scans were performed on 4 patients, which showed the calculi SUVmax increasing in 2 patients, while decreasing in the other 2 patients. One patient with bladder calculus underwent a follow-up PET/CT, which showed enlargement of the calculus as well as the increased SUVmax. This study shows an uncommon high (18)F-FDG uptake in urinary calculi. Recognition of this non-malignant accumulation in urinary calculi is essential for correct interpretation of PET/CT findings. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Value of the Strain Ratio on Ultrasonic Elastography for Differentiation of Benign and Malignant Soft Tissue Tumors.

PubMed

Hahn, Seok; Lee, Young Han; Lee, Seung Hyun; Suh, Jin-Suck

2017-01-01

The purpose of this study was to evaluate whether the strain ratio provides additional value to conventional visual elasticity scores in the differentiation of benign and malignant soft tissue tumors by ultrasonic elastography. The Institutional Review Board approved the protocol of this retrospective review. Seventy-three patients who underwent elastography and had a soft tissue mass pathologically confirmed by ultrasound-guided core biopsy or surgical excision were enrolled from April 2012 through October 2014. On elastography, elasticity scores were determined with a 5-point visual scale, and the strain ratio to adjacent soft tissue at the same depth was calculated. Tumors were divided into benign and malignant groups according to the pathologic diagnoses. Elasticity scores and strain ratios were compared between benign and malignant groups, and diagnostic performance was evaluated by receiver operating characteristic curves. Of the 73 patients, 40 had benign tumors, and 33 had malignant tumors. Strain ratios (P = .003) and elasticity scores (P = .048) were significantly different between pathologic results. The areas under the receiver operating characteristic curves were 0.700 (95% confidence interval, 0.581-0.802) for the strain ratio and 0.623 (95% confidence interval, 0.515-0.746) for elastography. The strain ratios of malignant soft tissue tumors were lower than those of benign tumors and showed better diagnostic performance than did elasticity scores. The strain ratio can be used as a diagnostic indicator to predict the malignant potential of soft tissue tumors. © 2016 by the American Institute of Ultrasound in Medicine.

Raman spectroscopy of normal oral buccal mucosa tissues: study on intact and incised biopsies

NASA Astrophysics Data System (ADS)

Deshmukh, Atul; Singh, S. P.; Chaturvedi, Pankaj; Krishna, C. Murali

2011-12-01

Oral squamous cell carcinoma is one of among the top 10 malignancies. Optical spectroscopy, including Raman, is being actively pursued as alternative/adjunct for cancer diagnosis. Earlier studies have demonstrated the feasibility of classifying normal, premalignant, and malignant oral ex vivo tissues. Spectral features showed predominance of lipids and proteins in normal and cancer conditions, respectively, which were attributed to membrane lipids and surface proteins. In view of recent developments in deep tissue Raman spectroscopy, we have recorded Raman spectra from superior and inferior surfaces of 10 normal oral tissues on intact, as well as incised, biopsies after separation of epithelium from connective tissue. Spectral variations and similarities among different groups were explored by unsupervised (principal component analysis) and supervised (linear discriminant analysis, factorial discriminant analysis) methodologies. Clusters of spectra from superior and inferior surfaces of intact tissues show a high overlap; whereas spectra from separated epithelium and connective tissue sections yielded clear clusters, though they also overlap on clusters of intact tissues. Spectra of all four groups of normal tissues gave exclusive clusters when tested against malignant spectra. Thus, this study demonstrates that spectra recorded from the superior surface of an intact tissue may have contributions from deeper layers but has no bearing from the classification of a malignant tissues point of view.

Receptors, channels, and signalling in the urothelial sensory system in the bladder

PubMed Central

Merrill, Liana; Gonzalez, Eric J.; Girard, Beatrice M.; Vizzard, Margaret A.

2017-01-01

The storage and periodic elimination of urine, termed micturition, requires a complex neural control system to coordinate the activities of the urinary bladder, urethra, and urethral sphincters. At the level of the lumbosacral spinal cord, lower urinary tract reflex mechanisms are modulated by supraspinal controls with mechanosensory input from the urothelium, resulting in regulation of bladder contractile activity. The specific identity of the mechanical sensor is not yet known, but considerable interest exists in the contribution of transient receptor potential (TRP) channels to the mechanosensory functions of the urothelium. The sensory, transduction, and signalling properties of the urothelium can influence adjacent urinary bladder tissues including the suburothelial nerve plexus, interstitial cells of Cajal, and detrusor smooth muscle cells. Diverse stimuli, including those that activate TRP channels expressed by the urothelium, can influence urothelial release of chemical mediators (such as ATP). Changes to the urothelium are associated with a number of bladder pathologies that underlie urinary bladder dysfunction. Urothelial receptor and/or ion channel expression and the release of signalling molecules (such as ATP and nitric oxide) can be altered with bladder disease, neural injury, target organ inflammation, or psychogenic stress. Urothelial receptors and channels represent novel targets for potential therapies that are intended to modulate micturition function or bladder sensation. PMID:26926246

Kindlin-2 Expression in Arsenite and Cadmium Transformed Bladder Cancer Cell Lines and in Archival Specimens of Human Bladder Cancer

PubMed Central

Talaat, Sherine; Somji, Seema; Toni, Conrad; Garrett, Scott H.; Zhou, Xu Dong; Sens, Mary Ann; Sens, Donald A.

2011-01-01

Objective The goal of this study was to confirm a microarray study that suggested that Kindlin-2 might play a role in the development and progression of bladder cancer. There has been no previous examination of Kindlin-2 expression in human bladder cancer. Methods A combination of real time PCR, western analysis and immunohistochemistry was used to characterize Kindlin-2 expression in arsenite (As+3) and cadmium (Cd+2) transformed human cell lines, their tumor transplants in immune-compromised mice, and in archival specimens of human bladder and bladder cancer. Results The results show that the Kindlin-2 expression patterns in the cell lines were not duplicated in the tumor tissues. However, it was shown that Kindlin-2 was expressed in the stromal element of all the transplanted tumors and archival specimens of human bladder cancer. It was also shown that a small number of high grade invasive urothelial cancers have focal expression of Kindlin-2 in the tumor cells. Conclusion Kindlin-2 is expressed in the stromal component of most, if not all, human bladder cancers. Kindlin-2 is not expressed in normal urothelium. Kindlin-2 is expressed in a small subset of high grade invasive bladder cancers and may have potential as a prognostic marker for tumor progression. PMID:21624607

Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations (A Pediatric MATCH Treatment Trial)

ClinicalTrials.gov

2018-06-20

Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Childhood Hodgkin Lymphoma; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; EZH2 Gain of Function; EZH2 Gene Mutation; Histiocytosis; Loss of BRG1 Protein Expression; Loss of INI 1 Protein Expression; Low Grade Glioma; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Childhood Ependymoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Hodgkin Lymphoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Glioma; Recurrent Malignant Solid Neoplasm; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdoid Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Refractory Central Nervous System Neoplasm; Refractory Hodgkin Lymphoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Glioma; Refractory Medulloblastoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Rhabdoid Tumor; Refractory Soft Tissue Sarcoma; Rhabdoid Tumor; SMARCA4 Gene Inactivation; SMARCB1 Gene Inactivation; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Wilms Tumor

Suppression of progranulin expression inhibits bladder cancer growth and sensitizes cancer cells to cisplatin.

PubMed

Buraschi, Simone; Xu, Shi-Qiong; Stefanello, Manuela; Moskalev, Igor; Morcavallo, Alaide; Genua, Marco; Tanimoto, Ryuta; Birbe, Ruth; Peiper, Stephen C; Gomella, Leonard G; Belfiore, Antonino; Black, Peter C; Iozzo, Renato V; Morrione, Andrea

2016-06-28

We have recently demonstrated a critical role for progranulin in bladder cancer. Progranulin contributes, as an autocrine growth factor, to the transformed phenotype by modulating Akt-and MAPK-driven motility, invasion and anchorage-independent growth. Progranulin also induces F-actin remodeling by interacting with the F-actin binding protein drebrin. In addition, progranulin is overexpressed in invasive bladder cancer compared to normal tissue controls, suggesting that progranulin might play a key role in driving the transition to the invasive phenotype of urothelial cancer. However, it is not established whether targeting progranulin could have therapeutic effects on bladder cancer. In this study, we stably depleted urothelial cancer cells of endogenous progranulin by shRNA approaches and determined that progranulin depletion severely inhibited the ability of tumorigenic urothelial cancer cells to migrate, invade and grow in anchorage-independency. We further demonstrate that progranulin expression is critical for tumor growth in vivo, in both xenograft and orthotopic tumor models. Notably, progranulin levels correlated with response to cisplatin treatment and were upregulated in bladder tumors. Our data indicate that progranulin may constitute a novel target for therapeutic intervention in bladder tumors. In addition, progranulin may serve as a novel biomarker for bladder cancer.

Suppression of progranulin expression inhibits bladder cancer growth and sensitizes cancer cells to cisplatin

PubMed Central

Stefanello, Manuela; Moskalev, Igor; Morcavallo, Alaide; Genua, Marco; Tanimoto, Ryuta; Birbe, Ruth; Peiper, Stephen C.; Gomella, Leonard G.; Belfiore, Antonino; Black, Peter C.; Iozzo, Renato V.; Morrione, Andrea

2016-01-01

We have recently demonstrated a critical role for progranulin in bladder cancer. Progranulin contributes, as an autocrine growth factor, to the transformed phenotype by modulating Akt-and MAPK-driven motility, invasion and anchorage-independent growth. Progranulin also induces F-actin remodeling by interacting with the F-actin binding protein drebrin. In addition, progranulin is overexpressed in invasive bladder cancer compared to normal tissue controls, suggesting that progranulin might play a key role in driving the transition to the invasive phenotype of urothelial cancer. However, it is not established whether targeting progranulin could have therapeutic effects on bladder cancer. In this study, we stably depleted urothelial cancer cells of endogenous progranulin by shRNA approaches and determined that progranulin depletion severely inhibited the ability of tumorigenic urothelial cancer cells to migrate, invade and grow in anchorage-independency. We further demonstrate that progranulin expression is critical for tumor growth in vivo, in both xenograft and orthotopic tumor models. Notably, progranulin levels correlated with response to cisplatin treatment and were upregulated in bladder tumors. Our data indicate that progranulin may constitute a novel target for therapeutic intervention in bladder tumors. In addition, progranulin may serve as a novel biomarker for bladder cancer. PMID:27220888

Supra-vesical urinary diversion and ureteric re-implantation for malignant disease.

PubMed

Woodhouse, C R J

2010-11-01

Supra-vesical diversion or ureteric reconstruction is indicated for fistulae from the bladder or ureter, urinary incontinence, painful frequency and for end-stage renal failure due to obstructive uropathy. In a palliative setting, conservative measures, such as an indwelling catheter or ureteric stents, should be tried first. Open or laparoscopic surgery should be considered if these measures fail. For a patient who is leaking urine or has a very painful bladder, such surgery may well be justified, even very close to the end of life, as the symptoms are so unpleasant. When the problem is of end-stage renal failure that may be symptomless, the decision is more difficult; the patient may only gain a few months of life with no change in symptoms in return for the major surgery. The options available include cutaneous diversion either by ureterostomy or conduit and reconstruction either by re-implanting a ureter into the bladder or transuretero-ureterostomy. A laparoscopic approach may be possible in many cases. Copyright © 2010 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Ten Years of Complete Remission of Pulmonary Metastasis after Post-Cystectomy Palliative Cisplatin-Gemcitabine Chemotherapy with Gefitinib for Muscle Invasive Bladder Cancer: A Case Report.

PubMed

Fahmy, Omar; Scharpf, Marcus; Schubert, Tina; Feyerabend, Susan; Stenzl, Arnulf; Schwentner, Christian; Fend, Falko; Gakis, Georgios

2016-01-01

Muscle-invasive bladder cancer (MIBC) is considered one of the most lethal malignancies with high metastatic potential. Usually, metastatic bladder cancer carries worse prognosis with a median survival rate of approximately 6 months, which can be prolonged for up to 14 months with palliative systemic chemotherapy. We present the case of a 61-year-old male patient diagnosed with localized MIBC 10 years ago. He underwent nerve-sparing radical cystectomy with ileal neobladder, but developed pulmonary metastatic disease 7 months postoperatively. Six cycles of gemcitabine/cisplatin combination chemotherapy with an addition of gefitinib as daily oral medication were administered within a randomized phase II clinical trial; this resulted in complete remission of the pulmonary metastases. Until now, the patient is still on gefitinib daily without any side effects. Although, the addition of gefitinib to standard systemic chemotherapy has not been shown to improve the survival in metastatic urothelial cancer, this case represents a very pleasant albeit uncommon long-term outcome. © 2016 S. Karger AG, Basel.