Transitional Cell Carcinoma Of Urinary Bladder Research Articles

Fluid Shear Stress Induces Cell Cycle Arrest in Human Urinary Bladder Transitional Cell Carcinoma Through Bone Morphogenetic Protein Receptor-Smad1/5 Pathway.

Mechanical force generated from the interstitial fluid flow inside and surrounding tissue has been known to play a significant role in cancer pathophysiology. In this study, we aimed to investigate the role of laminar shear stress (LSS) in modulating the cell cycle of human bladder transitional carcinoma (BFTC-905) cells which are frequently stimulated by not only the interstitial fluid flow, but also the urine flow transported from kidney to bladder in the urinary tract. The BFTC-905 cells were subjected to 0-12 dynes cm-2 LSS for 1, 4, 8, or 12h, respectively, followed by cellular and molecular assays for investigations of cell cycle regulation protein expressions, cell growth rates, and the potential mechanism. The results showed that the LSS with ≥ 8 dynes cm-2 for ≥ 8h significantly increased protein expressions of cyclin B1, Wee1, p21, and p-CDK1(Tyr15) (p < 0.05 for each), but conversely decreased protein expressions of cyclin A2, D1, E1, and CDK-1, -2, -4, and -6 (p < 0.05 for each) in the BFTC-905 cells, indicating that a G2/M cell cycle arrest was obtained after shearing stimulation. Furthermore, our data demonstrated that the LSS-induced G2/M arrest and the corresponding changes in cell cycle regulatory protein expressions were modulated by bone morphogenetic protein (BMP) receptor-Smad1/5 signaling pathway. Our findings provided evidences for the effect of mechanical microenvironment on urothelial cancer pathobiology and generated insights into mechanism of LSS-regulated bladder tumor cell cycle.

Effect of Pretreatment of Morin on the Cisplatin-Induced Toxicity on LLC-PK1 and T24 Cells

Cisplatin is a chemotherapeutic drug broadly used in the treatment of solid tumors. However, patients under this chemotherapy develop severe adverse effects, being nephrotoxicity the most frequent. Cisplatin-induced nephrotoxicity has been associated with oxidative stress, inflammation and apoptosis. Morin, a rather abundant flavonoid, presents antioxidant properties and, at the same time, decreases viability in some tumor cells. Taking into account these facts, it has been hypothesized that morin could attenuate cisplatin-induced kidney injury without interfering with antineoplastic activity of cisplatin. The aim of this study was to evaluate the potential cytoprotective effect of morin against cisplatin-induced damage in the Lilly Laboratories cell-porcine kidney 1 (LLC-PK1) cell line. In addition, the effect of pretreatment with morin on the toxicity of cisplatin on human urinary bladder transitional cell carcinoma T24 cell line was investigated. It was found that 200 μM morin attenuates cisplatin-induced damage on LLC-PK1 cells in a heme oxygenase-1 (HO-1) dependent-way. Moreover, it was found that 200 μM morin alone, decreases T24 cell viability in the same proportion as cisplatin. However, when T24 cells were pretreated with morin, the cell viability did not change compared to the cells treated only with cisplatin.

Quantitative evaluation of canine urinary bladder transitional cell carcinoma using contrast-enhanced ultrasonography

BackgroundIn veterinary medicine, contrast-enhanced ultrasonography allowed the accurate quantification of liver, splenic and kidney vascularization in healthy dogs and the differentiation between malignant and benign hepatic, renal, and splenic nodules in dogs and cats based on perfusion patterns. The utility of contrast-enhanced ultrasonography in other applications is still under study.The aim of this study was to develop diagnostic criteria by contrast-enhanced ultrasonography in 8 client-owned adult dogs affected by urinary bladder transitional cell carcinoma with definitive diagnosis made by cytopathologic evaluation after suction biopsy. The contrast enhancement pattern and the quantification of blood flow parameters of this tumor were reported.ResultsExaminations with B-mode, Doppler ultrasonography and contrast-enhanced ultrasonography were performed in all not sedated dogs. Assessments of bladder masses and bladder wall infiltration were performed. Each dog received 2 bolus injections of sulfur hexafluoride during the contrast-enhanced ultrasonography. Quantitative analysis of the contrast-enhanced ultrasonography images were performed. For each dog, one region of interest was manually drawn around the entire tumor. Software analysis of contrast-enhanced time-intensity curves was used to identify peak enhancement, time to peak enhancement, regional blood volume, regional blood flow, and mean transit time.Contrast-enhanced ultrasonography showed an avid enhancement of the tumour tissue, with a heterogeneous or homogeneous pattern. The exam also showed the loss of planes between the lesion and the muscular layer. The presence of vascularized tissue through the bladder wall confirms the infiltrative feature of the tumour. Post-processing quantitative analysis showed a time-intensity curve with a rapid wash-in, a low level of signal intensity and a slow wash-out.ConclusionsContrast-enhanced ultrasonography provided useful clinical information and defined a vascular enhancement patterns and calculated parameters associated with TCC. It may be a useful, noninvasive and reproducible tool for detecting these tumors in dogs.

DIAGNOSIS AND SURGICAL TREATMENT OF A TRANSITIONAL CELL CARCINOMA IN THE BLADDER APEX OF A PET RABBIT (ORYCTOLAGUS CUNICULUS)

A 6-year-old, 1.9-kg female spayed lop-eared European rabbit (Oryctolagus cuniculus) was evaluated for acute hematuria and inappropriate urination and defecation of less than 12-hours duration. Abdominal ultrasonography revealed a suspected bladder mass. Ultrasound-guided cystocentesis was performed and the results of the urinalysis were unremarkable. An abdominal exploratory surgery revealed a nodular cystic mass at the cranial ventral apex of the bladder wall which measured 0.5cm × 0.5cm. Based on histopathologic evaluation, excision of the neoplasm was complete and the mass was diagnosed as transitional cell carcinoma of the bladder. This case suggests that urinary bladder transitional cell carcinoma should be considered in pet rabbits presenting with similar clinical signs.

Evaluation of Uracil, Sodium Ascorbate, and Rosiglitazone as Promoters of Urinary Bladder Transitional Cell Carcinomas in Male Sprague-Dawley Rats

The purpose of this study was to establish a 2-stage model of urinary bladder carcinogenesis in male Sprague-Dawley rats to identify tumor promoters. In phase 1 of the study, rats ( n = 170) were administered 100 mg/kg of the tumor initiator, N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN), twice weekly by oral gavage (po) for a period of 6 weeks. Phase 2 consisted of dividing rats into 4 groups ( n = 40 per group) and administering one of the following for 26 weeks to identify putative tumor promoters: (1) vehicle po, (2) 25 mg/kg/day rosiglitazone po, (3) 5% dietary sodium l-ascorbate, and (4) 3% dietary uracil. Rats were necropsied after 7.5 months, and urinary bladders were evaluated by histopathology. BBN/vehicle treatments induced the development of urothelial hyperplasia (83%) and papillomas (15%) but no transitional cell carcinomas (TCCs). Rosiglitazone increased the incidence and severity of papillomas (93%) and resulted in TCC in 10% of treated rats. Uracil was the most effective tumor promoter in our study and increased the incidence of papillomas (90%) and TCC (74%). Sodium ascorbate decreased the incidence of urothelial hyperplasia (63%) and did not increase the incidence of urothelial papillomas or TCC. These data confirm the capacity of our 2-stage model to identify urinary bladder tumor promoters.

Evaluation of two-dimensional ultrasonography and computed tomography in the mapping and measuring of canine urinary bladder tumors

Determining the dimensions of transitional cell carcinomas (TCCs) of the urinary bladder in dogs is important in assessing tumor progression and the response to treatment. The primary aim of this study was to evaluate the reliability of a standardized two-dimensional (2-D) ultrasound (US) protocol performed by a single experienced operator. Secondary aims were to compare World Health Organization (WHO) and Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, and to compare measurements by two operators following these guidelines. These were evaluated by inter-operator and intra-operator reliability using the concordance correlation coefficient (CCC) and Cohen’s κ statistics, which demonstrated substantial to better agreement by an experienced operator using either set of guidelines. It was demonstrated that 2-D US provides a reliable means to determine the dimensions of urinary bladder TCC when an experienced operator used a standardized protocol. In a subset of dogs, urinary bladder distension was varied, which resulted in differences in measurement with 2-D US and computed tomography.

Multiple primary malignancies

Two cases of multiple primary malignancies (two or more neoplasms without any relationship between them) are presented in this paper. The first case (65 years) was a male in whom follicular carcinoma of thyroid, metachronous neuroendocrine tumor of duodenum and urinary bladder transitional cell carcinoma were diagnosed within an eight-year period. The second case (65 years) was a female with synchronous dual malignancy of lung and urinary bladder diagnosed within a very short period of time.

Density of tumor-infiltrating granzyme B-positive cells predicts favorable prognosis in dogs with transitional cell carcinoma

Although tumor-infiltrating lymphocytes (TILs) play a key role in anti-tumor immunity, their involvement in canine transitional cell carcinoma (TCC) is not well-documented. The objective of this study was to investigate the association between TIL number and prognosis in dogs with urinary bladder TCC. Immunohistochemical analysis of CD3 and granzyme B was performed using canine TCC (n=32) and normal bladder (n=10) tissues. The numbers of CD3+ and granzyme B+ cells located in peritumoral stroma of canine TCC were significantly higher than those in normal controls. In TCC cases, the number of CD3+ TILs was not significantly related to prognosis, whereas the abundant granzyme B+ TILs were associated with favorable outcome. Since granzyme B+ TILs were not associated with the tumor stage, the presence of granzyme B+ TILs may be an independent prognostic factor. These results suggest that granzyme B+ TILs play a role in anti-tumor immunity and inhibit tumor progression in canine TCC.

Evaluation of cellular transformation and tumor aggressiveness factor expression in urinary bladder lesions and transitional cell carcinoma special variants in relation to bilharziasis

Evaluation of cellular transformation and tumor aggressiveness factor expression in urinary bladder lesions and transitional cell carcinoma special variants in relation to bilharziasis

Expression of HER2 and topoisomerase II α in urinary bladder transitional and squamous cell carcinoma

Expression of HER2 and topoisomerase II α in urinary bladder transitional and squamous cell carcinoma

78 - Immunohistochemical expression of c-Myc in patients with urinary bladder transitional cell carcinoma and correlation with tumor grade, stage and lymph node metastasis

78 - Immunohistochemical expression of c-Myc in patients with urinary bladder transitional cell carcinoma and correlation with tumor grade, stage and lymph node metastasis

Radical Cystectomy in Patients with Transitional Cell Carcinoma Urinary Bladder

Radical Cystectomy in Patients with Transitional Cell Carcinoma Urinary Bladder

Overexpression of UHRF1 gene correlates with the major clinicopathological parameters in urinary bladder cancer.

ABSTRACTIntroduction Recently, expression of the UHRF1 gene was found to be up-regulated in numerous neoplasms, including the urinary bladder transitional cell carcinoma (TCC).Objective The aim of our study was to determine if the expression levels of UHRF1 gene correlates with the major pathological characteristics of the tumor and patients’ clinical outcome.Materials and Methods In our study, we have analyzed the tissue samples derived from group of 70 patients with histologically confirmed TCC of the urinary bladder, while normal urinary bladder mucosa obtained from 40 patients with nonmalignant diseases was used as a negative control group. Expression of UHRF1 gene in each patient sample was determined using reverse transcriptase-polymerase chain reaction.Results UHRF1 gene expression was found to be app. 2.5 times higher in samples from patients with TCC in comparison with normal epithelium derived from control group patients. Analysis show that gene expression correlates with the malignancy of the tumor. A highly significant differences were found between the expression values of samples from low and high grade TCC, as well as between the high grade and control group. UHRF1 expression was higher in patients with non-muscle invasive disease than in those with muscle invasive disease.Conclusions The result of this study indicates that UHRF1 gene expression levels correlates with the major pathological characteristics of TCC samples and with the clinical outcome of those patients. Determination of UHRF1 gene expression could have a potential to be used as a sensitive molecular marker in patients with urinary bladder cancer.

Multiple primary cancers: Simultaneously occurring prostate cancer and other primary tumors-our experience and literature search.

Prostate cancer is a leading cause of death in men all over the world, and it is becoming an increasing public health burden in sub-Saharan Africa. In our practice, we identified that prostate cancer co-existed with other primary cancers even in noncontiguous regions of the body and this co-existence impacted on our management of these patients. We retrospectively studied a 2-year period (June 2012-July 2014), the records of patients in our hospital with prostate cancer, who in addition, had other primary cancers; and studied the management and outcomes of these patients. We also reviewed the existing literatures for possible biologic links between prostatic carcinoma and other primary tumors. There were six patients with multiple primary cancers who had prostate cancers. The age range was 60-84 years and the mean age of 72.2 ± 0.4 years. The primary tumors co-existing with prostate cancer were colonic adenocarcinoma, rectal adenocarcinoma, urinary bladder transitional cell carcinoma, primary liver cell carcinoma, and thyroid follicular carcinoma in both synchronous and metachronous relationships. Prostate cancers often co-exist with other cancers. The precise mechanism by which prostate cancer co-exists with another primary cancer is yet to be clearly defined. With more study of the syndromic cancers involving the prostate, definite associations could be identified, and this may help in managing these patients better.

The Prognostic Role of NEDD9 and P38 Protein Expression Levels in Urinary Bladder Transitional Cell Carcinoma

Background. The most common malignant tumor of the urinary bladder is transitional cell carcinoma (TCC). Neural precursor cell-expressed developmentally downregulated protein 9 (NEDD9) is found to be a cell adhesion mediator. P38 Mitogen-Activated Protein Kinase is a serine/threonine kinases member which can mediate carcinogenesis through intracellular signaling. Methods. To assess their prognostic role; NEDD9 and p38 protein were evaluated in sections from 50 paraffin blocks of TCC. Results. The high expressions of NEDD9 and p38 protein were significantly associated with grade, stage, distant metastasis (p < 0.001), number of tumors, lymph node metastasis, and tumor size (p < 0.001, 0.002; 0.018, <0.001; and 0.004, 0.007, respectively). High NEDD9 and p38 detection had a worse 3-year OS (p = 0.041 and <0.001, respectively). By multivariate analysis the NEDD9 and p38 protein expression levels and various clinicopathological criteria including gender, grade, stage of the tumor, and regional lymph node involvement were independent prognostic parameters of TCC of the urinary bladder patients' outcome. Conclusion. NEDD9 and p38 protein expressions were poor prognostic markers of TCC.

Histological Characterization of 100 Urinary Bladder and Urethral Transitional Cell Carcinomas in Dogs from the UK

Histological Characterization of 100 Urinary Bladder and Urethral Transitional Cell Carcinomas in Dogs from the UK

Evaluation of androgen receptor and HER2/neu receptor in tumor tissue of transitional cell carcinoma of urinary bladder and normal bladder mucosa

Background: Transitional cell carcinoma (TCC) is the most prevalent, singly accounting for 90% of all bladder cancer cases. Various markers involved in cell cycle but none of them proven its capacity as a prognostic indicator. The discovery of new biological markers may lead to early clinical prediction and may help in individualization of therapeutic approach in management of bladder cancer patients. The human epidermal growth factor receptors (EGFRs) – HER2/neu play a role in neoplastic cell growth and its role proven in breast and ovarian cancer while its role in bladder cancer still not explored its potential. Bladder cancer incidence is higher in male as compared to female. This gender related difference is still not clear in humans while it is proven in animal studies. In this study, we investigated the potential role and association of HER2/neu and androgen receptors (ARs) in etiology and prognosis of TCC. Patients and Methods: The study included 20 histopathologically confirmed cases of TCC of urinary bladder attending the Department of General Surgery, KGMU, Lucknow and 20 healthy individuals were taken as control. Immunohistochemical analysis for AR and HER2/neu receptor was done using paraffin-embedded tissue blocks treated with monoclonal mouse anti-human antibodies against AR and HER2/neu receptor, respectively. Results: HER2/neu over expression was observed in 14 (73%) of which 12 were males and 2 were females. Among these 16.7%, 33.3%, and 37.5% cases were in Grade I, II, and III, respectively. The AR overexpression was observed in 4 (20%) of which all were males. About 16.7% and 27.3% cases were in Grade II and III, respectively. Peak incidence was observed in the age group of 50–70 years (75%). Conclusions: We conclude that HER2/neu and AR can be considered as bad prognostic factor in TCC. These results suggested that targeting AR and HER2/neu may provide novel chemopreventive and therapeutic approaches for the management of bladder cancer.

Up and down staging of TCC using 18F-FDG PET/CT scan

ObjectiveThe purpose of this study was to investigate the ability of PET/CT to restage urinary bladder transitional cell carcinoma (TCC) whether up or down after initial staging by histopathology and other imaging modalities. Patients and methodsDuring three year duration 27 patients with urinary bladder TCC were prospectively evaluated. They were previously diagnosed by histopathology after biopsy and had prior imaging for initial staging. All patients underwent PET/CT examinations following a preset protocol. The images obtained were reconstructed using dedicated software and workstations. Results of PET/CT examinations were confirmed by histopathology. ResultsPrior imaging and PET/CT findings were matched in 17 patients (63%) with no changes regarding their initial TNM stages and differed in 10 patients (37%). Six patients (22.2%) showed new sites of distant metastasis and unchanged initial stages. Two patients (7.4%) were up staged and 2 patients (7.4%) were down staged for whom the plan of clinical management was justified. Conclusion18F-FDG PET/CT can up and down stage TCC and can detect new sites of nodal or distant metastasis leading to optimal therapy planning.

Risk of Osteosarcoma in Dogs After Open Fracture Fixation.

To critically evaluate whether open fracture fixation is a significant risk factor for latent osteosarcoma development. Case-control study. Dogs undergoing open fracture repair and dogs diagnosed with osteosarcoma. Records were retrieved from the Veterinary Medical Database VMDB (1970-2000) for dogs undergoing surgical repair of a fracture and dogs diagnosed with osteosarcoma. Dogs with open reduction of joint luxation, dogs diagnosed with bacterial cystitis, and dogs diagnosed with urinary bladder transitional cell carcinoma (UBTCC) were queried as comparison populations. Relative risk for osteosarcoma development was determined. From a population of 19,041 fractures treated surgically, 15 of those dogs subsequently appeared in the VMDB with osteosarcoma affecting the same bone. The relative risk of a fracture repair and associated orthopedic implants and osteosarcoma occurrence was equivalent to the relative risk of open joint reduction and osteosarcoma occurrence (95% confidence interval; 0.998-1.00). The relative risk of having bacterial cystitis and appearing again in the VMDB with UBTCC was higher than the risk of open fracture repair and a subsequent diagnosis of osteosarcoma (P < .02). The incidence of fracture-related osteosarcoma may be significantly less than previously estimated based on cases queried from the VMDB. Although possible cases of implant-associated osteosarcoma were identified, their occurrence was rare. Elective implant removal for the purpose of reducing the risk of osteosarcoma after fracture repair may not be warranted and merits further investigation.

Metastatic urinary bladder transitional cell carcinoma to the oral cavity and oropharynx

Background Distant metastasis from urinary bladder transitional cell carcinoma (TCC) is a well-reported phenomenon, most commonly occurring in osseous and pulmonary sites. In contrast, metastasis to oral and/or oropharyngeal soft tissues is extremely rare.