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Sample records for bladder urothelial carcinoma

  1. Unusual presentation of cutaneous metastasis from bladder urothelial carcinoma

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    Chin-Pao Chang; I-Yen Lee; Hung-Jen Shih

    2013-01-01

    Cutaneous metastases from urothelial carcinoma of the bladder are a rare disease.In previous reports,the most common metastatic cutaneous lesions were non-tender nodules on the abdominal skin.We report a patient with bladder urothelial carcinoma with cutaneous metastases initially presenting as right leg and suprapubic lymphedema.Bladder tumor was the incidental finding by magnetic resonance venography.Urothelial carcinoma (clinical stage Ⅳ) was diagnosed,and chemotherapy was performed.Extensive painful erythematous plaques with an erysipelas-like appearance located on the suprapubic area,chest and abdomen were noted,and cutaneous metastases were confirmed by histopathology.Subsequently,extensive scrotal and prepuce ulcerative changes developed.This paper reports a rare case of extensive cutaneous metastasis of bladder urothelial carcinoma who presented an interesting clinical course.

  2. Isolated cardiac metastasis from plasmacytoid urothelial carcinoma of the bladder

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    Peck Joshua R

    2012-06-01

    Full Text Available Abstract A 57-year-old male with a history of hypertension presented with shortness of breath, intermittent substernal chest pain, subjective fevers, and a 30-pound weight loss. He was found to have a bladder mass four months prior to presentation, for which he underwent cystoscopy and surgical removal. Pathology demonstrated high-grade superficial plasmacytoid urothelial carcinoma extending into the submucosa but not the muscularis propria. Given the superficial nature of his bladder cancer, a cystectomy was deferred. He was subsequently lost to follow-up care. On arrival, physical exam was notable for tachycardia, tachypnea, and distant heart sounds. An ECG showed an incomplete right bundle branch block and sinus tachycardia. Computed tomography pulmonary angiography revealed a three-cm pericardial effusion. Transthoracic echocardiography confirmed this finding and revealed a mass in the right ventricle (RV extending into the outflow tract and infiltrating the free wall. The RV was dilated with an estimated RV systolic pressure of 37 mmHg. Pericardiocentesis yielded nearly one liter of serosanguinous fluid with non-diagnostic cytology. Partial median sternotomy with biopsy showed pathologic findings consistent with metastatic urothelial carcinoma, plasmacytoid variant. A PET scan showed increased uptake exclusively in the heart. The oncology team discussed options with the patient including chemotherapy and palliative care. The patient decided to withhold further therapy and went home with hospice care. He died two months later. Discussion Bladder cancer is the fourth most common cancer in men in the United States. Most patients (69% with metastatic bladder cancer have multiple organs involved; conversely, our patient had a PET scan indicating his disease was localized to the heart. Plasmacytoid urothelial carcinoma is a rare subtype of bladder cancer, and is estimated to make up less than three percent of all invasive bladder carcinomas. At

  3. Experimental rat bladder urothelial cell carcinoma models

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    Arentsen, Harm C.; Hendricksen, Kees; Oosterwijk, Egbert; Witjes, J Alfred

    2009-01-01

    Bladder cancer is a major public health problem. Currently available therapeutic options seem to be unable to prevent bladder cancer recurrence and progression. To enable preclinical testing of new intravesical therapeutic agents, a suitable bladder tumor model that resembles human disease is highly desirable. The aim of this topic paper was to discuss the problems associated with current in vivo animal bladder tumor models, focusing on the orthotopic syngeneic rat bladder tumor model. In the...

  4. Multicystic urothelial carcinoma of the bladder with gland-like lumina and with signet-ring cells. A case report

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    Hes Ondrej

    2008-09-01

    Full Text Available Abstract We present the case of 80-year-old male with superficial papillary urothelial carcinoma of the urinary bladder with striking multicystic architecture with a combination of features of urothelial carcinoma with gland-like lumina, with signet-ring cell differentiation and microcystic pattern. However, the tumor shared the morphologic features of several variants of urothelial carcinoma, the most important differential diagnosis covered so-called florid Brunneriosis, cystitis cystica, and primary adenocarcinomas of the urinary bladder.

  5. Recurrence of Urothelial Bladder Carcinoma in the Colon Presenting as Hematochezia

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    Krzyzak, Michael; Barakat, Iskandar; Deeb, Liliane

    2016-01-01

    Patients with superficial bladder cancers remain clinically indolent after treatment with even a modicum of urologic intervention. However, with more invasive disease, the majority of patients experience recurrence. The conventional route of metastasis and recurrence in primary urothelial cell carcinoma is through lymphatic system, with regional lymph nodes, lungs, liver, brain, and bone being the most common sites. Isolated intraluminal colonic recurrence in the absence of local invasion is extremely rare. We report a unique case of urothelial cell carcinoma presenting with an isolated colonic mass, which unexpectedly, on immunohistostaining, proved to be primarily of urothelial rather than colonic origin.

  6. Chromosomal imbalances in successive moments of human bladder urothelial carcinoma

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    Nascimento e Pontes, Merielen Garcia; da Silveira, Sara Martorelli; Trindade Filho, José Carlos de Souza;

    2013-01-01

    OBJECTIVE: To understand developmental characteristics of urinary bladder carcinomas (UBC) by evaluating genomic alterations and p53 protein expression in primary tumors, their recurrences, and in the morphologically normal urothelium of UBC patients. METHODS: Tumors and their respective recurren...

  7. Metastatic Urothelial Carcinoma of the Prepuce and Glans Penis: Suspected Implantation of Non-Muscle-Invasive Bladder Cancer via Urine

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    Makino, Tomoyuki; Kitagawa, Yasuhide; Namiki, Mikio

    2014-01-01

    Abstract Cutaneous metastatic implantation of non-muscle-invasive urothelial carcinoma via urine is a rare finding, and only few cases have been reported in the literature. Here, we present a case of metastatic urothelial carcinoma of the prepuce and glans penis, which was suspected to be an implantation of non-muscle-invasive bladder cancer via urine. The patient had pseudophimosis of the penis, and contact with urine containing urothelial carcinoma cells was considered to be the cause of th...

  8. Immunohistochemical determination of ETS-1 oncoprotein expression in urothelial carcinomas of the urinary bladder.

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    Sari, Aysegul; Calli, Aylin; Gorgel, Sacit Nuri; Altinboga, Aysegul Aksoy; Kara, Cengiz; Dincel, Cetin; Cakalagaoglu, Fulya

    2012-03-01

    ETS-1 protooncogene is an important transcription factor that plays a role in the regulation of physiological processes, such as cell proliferation and differentiation. ETS-1 is thought to be related to the growth of carcinoma cells by its regulation of the transcription of matrix metalloproteinases and urokinase-type plasminogen activator. In this study, we aimed to investigate the expression pattern of ETS-1 oncoprotein in urothelial carcinomas of the urinary bladder and determine its relationship with histopathologic parameters, including tumor grade and stage. One hundred six specimens of urothelial carcinoma and a total of 14 normal urothelium were analyzed immunohistochemically with anti-ETS-1 monoclonal antibody. The normal urothelium showed positive ETS-1 immunostaining. ETS-1 expression remained high in low-grade and noninvasive tumors, whereas it frequently decreased in high-grade or invasive carcinomas. Interestingly, ETS-1 was highly expressed in the basal cell layer of the noninvasive urothelial carcinomas. ETS-1 expression showed a strong negative correlation with the tumor grade (PETS-1 expression than the muscle-invasive tumors (pT2; PETS-1 expression is significantly associated with high grade and advanced stage in urothelial carcinomas of the urinary bladder, and that the downregulation of ETS-1 expression may be a marker of the aggressiveness of such malignancies.

  9. Metastatic Urothelial Carcinoma of the Prepuce and Glans Penis: Suspected Implantation of Non-Muscle-Invasive Bladder Cancer via Urine

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    Tomoyuki Makino

    2014-07-01

    Full Text Available Cutaneous metastatic implantation of non-muscle-invasive urothelial carcinoma via urine is a rare finding, and only few cases have been reported in the literature. Here, we present a case of metastatic urothelial carcinoma of the prepuce and glans penis, which was suspected to be an implantation of non-muscle-invasive bladder cancer via urine. The patient had pseudophimosis of the penis, and contact with urine containing urothelial carcinoma cells was considered to be the cause of the metastatic implantation.

  10. Bladder extramedullary plasmacytoma and synchronous bladder urothelial transitional cell carcinoma: A case report and review of the literature

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    Karan Wadhwa

    2011-02-01

    Full Text Available Karan Wadhwa, Raj Singh, Lemke Z SolomonDepartment of Urology, Queen Alexandra Hospital, Portsmouth, UKAbstract: A 69-year-old man presented with sudden onset of macroscopic hematuria. While an ultrasound of the bladder revealed a posterior bladder mass, subsequent flexible cystoscopy demonstrated only an area of irregular urothelium. Initial general anesthetic cytoscopy and biopsy revealed conventional G2/3 T1 TCC. Histology of a further formal resection of this irregular area revealed carcinoma-in-situ and population of atypical cells with enlarged nuclei, prominent nucleoli, and varying quantities of cytoplasm showing plasma cell features. The immunohistochemistry was consistent with a plasmacytoma. There must be a high index of suspicion when ultrasound demonstrates a mass not detected by flexible cystoscopy, and biopsies/resection are advised to exclude extramedullary plasmacytoma (EMP as the cause. EMP of the urinary bladder is a rare entity with only 21 cases reported in the literature. In this report we describe a further case of EMP of the bladder associated with synchronous transitional cell carcinoma (TCC of the urothelium. We also highlight the important histopathological findings and review the current literature to report the outcomes of existing approaches to management of this rare form of bladder cancer. We believe this to be the first case reported in which a patient presented concurrently with bladder EMP and urothelial TCC. EMPs are highly radiosensitive tumors and in the case of head/neck disease, survival at 10 years is in the order of 65% following radical radiotherapy. Given the paucity of reported cases of primary bladder EMP, the optimal treatment regime remains unclear. In keeping with other anatomical sites current treatment is based to the assumed benefit of radical radiotherapy and prognosis appears to be better in those with no evidence of systemic disease.Keywords: bladder cancer, extramedullary plasmacytoma

  11. Bladder cancer will grow anywhere: report of a urothelial carcinoma drop metastasis to the vagina and literature review.

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    Uhlman, Matthew A; Bevill, Mark D; Goodheart, Michael J; Brown, James A; O'Donnell, Michael A

    2016-08-01

    Urothelial carcinoma is the 2nd most common cancer of the urinary tract and accounts for the majority of cases of bladder cancer. Metastases are not infrequently encountered, increasing with disease stage and are most commonly seen in the bones and lungs. Many other sites have been described including the omentum, liver, and ovaries. An extremely rare site of metastatic disease however is within the vagina. Here we present a case of a probable vaginal 'drop metastasis' from previously treated urothelial carcinoma in the ureter and bladder. PMID:27544563

  12. Urothelial Carcinoma of the Bladder Metastatic to Bone Marrow Presenting as Isolated Thrombocytopenia

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    Robert C. Chan

    2007-01-01

    Full Text Available The skeletal system is a frequent site for metastases of urothelial carcinoma (UC of the bladder (22–37%. Of those cases involving bone, the marrow is infiltrated in 27% of patients. Imaging modalities, such as X-ray and CT, will detect gross skeletal lesions in the vast majority of these patients with bone marrow involvement, however, most patients with bone involvement are symptomatic at presentation. Additionally, there have been few reports in the literature of bone marrow metastases from UC presenting with isolated thrombocytopenia.

  13. Resolution of hypercalcemia of malignancy following radical cystectomy in a patient with paraneoplastic syndrome associated with urothelial carcinoma of the bladder

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    Alfredo Harb-De La Rosa

    2015-01-01

    Full Text Available Hypercalcemia of malignancy is a common finding associated with different types of cancers; however, its association with urothelial carcinoma of the bladder is rare. We report a case of a 69-year-old male with nonmetastatic urothelial carcinoma of the bladder who developed hypercalcemia that failed to respond to medical management, but resolved completely after undergoing resection of the tumor through radical cystectomy.

  14. Clear-cell variant urothelial carcinoma of the bladder: a case report and review of the literature

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    Hossein Tezval

    2012-10-01

    Full Text Available Clear cell variants of transitional cell carcinomas (TCC of the bladder are extremely rare tumors. Only 6 cases have been reported until now. We report of a 67 year old man who presented with fast growing tumor disease. While initial diagnosis showed localized bladder tumor, final histopathology revealed pT4, G3, L1 urothelial carcinoma with clear cell differentiation. No more than 14 weeks after initial diagnosis the patient died from multi-organ failure after unsuccessful salvage laparotomy which showed massive tumor burden within the pelvis and peritoneal carcinosis. This case demonstrated an extremely fast tumor growth. Therefore, patients with clear cell urothelial carcinoma should be treated vigorously and without time delay. We present a case of clear cell variant of TCC which exhibited an extremely aggressive behavior. To our knowledge this is the fifth report of this rare disease.

  15. ROS generation via NOX4 and its utility in the cytological diagnosis of urothelial carcinoma of the urinary bladder

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    Fujimoto Kiyohide; Anai Satoshi; Fujii Tomomi; Shimada Keiji; Konishi Noboru

    2011-01-01

    Abstract Background Reactive oxygen species (ROS) production via NADPH oxidase (NOX) contributes to various types of cancer progression. In the present research, we examined the pathobiological role of NADPH oxidase (NOX)4-mediated generation of reactive oxygen species (ROS) in urothelial carcinoma (UC) of the urinary bladder, and demonstrated the utility of ROS labeling in urine cytology. Methods NOX4 gene was silenced in vivo and in vitro by NOX4 siRNA transfection with or without atlocolla...

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

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    2016-06-09

    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

  17. Characterization of HGF/Met Signaling in Cell Lines Derived From Urothelial Carcinoma of the Bladder

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    Lee, Young H. [Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Apolo, Andrea B. [Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Agarwal, Piyush K.; Bottaro, Donald P., E-mail: dbottaro@helix.nih.gov [Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

    2014-11-25

    There is mounting evidence of oncogenic hepatocyte growth factor (HGF)/Met signaling in urothelial carcinoma (UC) of the bladder. The effects of three kinase inhibitors, cabozantinib, crizotinib and EMD1214063, on HGF-driven signaling and cell growth, invasion and tumorigenicity were analyzed in cultured UC cell lines. SW780 xenograft growth in SCID and human HGF knock-in SCID (hHGF/SCID) mice treated with cabozantinib or vehicle, as well as tumor levels of Met and pMet, were also determined. Met content was robust in most UC-derived cell lines. Basal pMet content and effector activation state in quiescent cells were low, but significantly enhanced by added HGF, as were cell invasion, proliferation and anchorage independent growth. These HGF-driven effects were reversed by Met inhibitor treatment. Tumor xenograft growth was significantly higher in hHGF/SCID mice vs. SCID mice and significantly inhibited by cabozantinib, as was tumor phospho-Met content. These studies indicate the prevalence and functionality of the HGF/Met signaling pathway in UC cells, suggest that paracrine HGF may contribute to UC tumor growth and progression, and that support further preclinical investigation of Met inhibitors for the treatment of UC is warranted.

  18. A Combined Clinicopathologic Analysis of 658 Urothelial Carcinoma Cases of Urinary Bladder

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    Hui-zhi Zhang; Chao-fu Wang; Juan-juan Sun; Bao-hua Yu

    2012-01-01

    To study the clinicopathological features of patients with urothelial carcinoma of the urinary bladder (UCB),and analyze the association of clinicopathological characteristics with tumor recurrence and progression.Methods Altogether 658 UCB cases in Fudan University Shanghai Cancer Center were collected from January 2006 to December 2010.The histopathologic materials and the clinical records were reviewed.Univariate and multivariate analyses were preformed to detect the association.Results The mean age of the patients was 61.97±12.97 years (range,20-90 years).Male to female ratio was about 5∶1.A total of 517 cases (78.6%) were superficial at the time of diagnosis (stage Ta/T1).The mean follow-up period was 22.36±24.92 months.Twenty-five patients lacking follow-up information were excluded in calculating recurrence and progression rates,the recurrence rate was about 37.0%(234/633),and progression rate about 6.2% (39/633).Three variables (grade,tumor growth pattern,and pathological stage) were found to be significant risk factors for tumor progression in univariate and multivariate analyses (P<0.05).Conclusions Most of the newly diagnosed UCB cases may be superficial diseases.Grade,tumor growth pattern,and pathological stage are associated with tumor progression of UCB.

  19. Unusual manifestations of secondary urothelial carcinoma

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    Chaohui Lisa Zhao

    2016-03-01

    Full Text Available High-grade papillary urothelial carcinoma regularly invades the bladder wall, adjacent prostate, seminal vesicles, ureters, vagina, rectum, retroperitoneum, and regional lymph nodes. In advanced stages, it may disseminate to the liver, lungs, and bone marrow. On rare occasions, unusual metastatic foci like skin have been reported. The incidence of urothelial carcinoma has increased with associated rise in variants of urothelial carcinoma and unusual metastatic foci. It is imperative that urologists and pathologists are aware of the unusual variants and unusual metastatic locations to expedite the diagnostic process. Hereby we report an unusual case of secondary involvement of spinal nerve by conventional urothelial carcinoma. Also a second case of rhabdoid variant of urothelial carcinoma showing synchronous involvement of bladder and subcutaneous tissue of upper extremity is presented.

  20. ARID1A immunohistochemistry improves outcome prediction in invasive urothelial carcinoma of urinary bladder.

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    Faraj, Sheila F; Chaux, Alcides; Gonzalez-Roibon, Nilda; Munari, Enrico; Ellis, Carla; Driscoll, Tina; Schoenberg, Mark P; Bivalacqua, Trinity J; Shih, Ie-Ming; Netto, George J

    2014-11-01

    AT-rich interactive domain 1A (ARID1A) is tumor suppressor gene that interacts with BRG1 adenosine triphosphatase to form a SWI/SNF chromatin remodeling protein complex. Inactivation of ARID1A has been described in several neoplasms, including epithelial ovarian and endometrial carcinomas, and has been correlated with prognosis. In the current study, ARID1A expression in urothelial carcinoma (UC) of the bladder and its association with clinicopathological parameters and outcome are addressed. Five tissue microarrays were constructed from 136 cystectomy specimens performed for UC at our institution. Nuclear ARID1A staining was evaluated using immunohistochemistry. An H-score was calculated as the sum of the products of intensity (0-3) multiplied by extent of expression (0%-100%). Average H-score per case was used for statistical analysis. ARID1A expression was categorized in low and high using Youden index to define the cut point. ARID1A expression significantly increased from normal to noninvasive UC to invasive UC. For both tumor progression and cancer death, Youden index yielded an H-score of 288 as the optimal cut point for ARID1A expression. Low ARID1A expression showed a tendency for lower risk of tumor progression and cancer mortality. Adding ARID1A expression to pathologic features offers a better model for predicting outcome than pathologic features alone. Low ARID1A expression was more frequently seen in earlier stage disease. There was a tendency for low ARID1A expression to predict better outcome. More importantly, the findings indicate that adding ARID1A expression to pathologic features increases the goodness of fit of the predictive model. PMID:25175170

  1. Tailored Selection of First-Line Cisplatin-Based Chemotherapy in Patients with Metastatic Urothelial Carcinoma of Bladder

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    Hsieh, Meng-Che; Huang, Cheng-Hua; Chiang, Po-Hui; Chen, Yen-Yang; Tang, Yeh; Su, Yu-Li

    2016-01-01

    Purpose: Methotrexate, vinblastine, doxorubicin plus cisplatin (MVAC) and gemcitabine plus cisplatin (GC) are both effective first-line chemotherapy. We explore the responsive variables of MVAC and GC for patients with metastatic urothelial carcinoma of bladder (mUCB). Materials and Methods: Patients who were initially diagnosed to have mUCB and received MVAC or GC as metastatic first-line chemotherapy between 2000 and 2014 at Kaohsiung Chang Gung Memorial Hospital were reviewed. Totally, 130 patients were enrolled into our study. Univariable Cox proportional hazard models were constructed for OS. Hazard ratio (HR) and 95% confidence intervals (CIs) was also presented. Results: There were 50 patients (38%) in the MVAC group and 80 patients (62%) in the GC group. The median OS was insignificantly different between MVAC and GC groups, accounting for 17.0 and 14.4 months (P = 0.214), respectively. OS of MVAC group was significantly longer with regard to age ≦ 60 years (HR: 0.38, 95% CI: 0.12-0.97, P = 0.036), pure urothelial carcinoma (HR: 0.56, 95% CI: 0.34-0.90, P = 0.015), > 1 metastatic sites (HR: 0.19, 95% CI: 0.08-0.44, P = 3(HR: 0.45, 95% CI: 0.25-0.81, P = 0.006), while OS with GC group was significantly longer with regard to variant urothelial carcinoma (HR: 0.56, 95% CI: 0.34-0.90, P = 0.015). Conclusions: Our study disclosed the predictive factors of different regimen for mUCB. These results have clinical implication for physicians who treat patients with mUCB. PMID:27390610

  2. uPAR Expression Pattern in Patients with Urothelial Carcinoma of the Bladder

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    Dohn, Line Hammer; Pappot, Helle; Iversen, Benedikte Richter;

    2015-01-01

    The objective of the present study was to confirm the expression and localisation pattern of the urokinase-type plasminogen activator receptor (uPAR) focusing on its possible clinical relevance in patients with urothelial neoplasia of the bladder. uPAR is a central molecule in tissue remodelling...... or positive as well as by the actual score. Separate scores were obtained for cancer cells, macrophages and myofibroblasts at the invasive front and in tumour core. We were able to confirm, in an independent patient cohort, the tissue expression and localisation pattern of uPAR as investigated...... investigations have generated new and valuable biological information about the cell types being involved in tumour invasion and progression through the plasminogen activation system....

  3. Synchronous papillary urothelial carcinoma of urinary bladder and adenocarcinoma of stomach in a middle-aged man: An extremely rare association with therapeutic dilemma

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    Dodul Mondal

    2013-01-01

    Full Text Available Synchronous occurrence of urinary bladder carcinoma and gastric carcinoma is very rare. A middle-aged Asian man presented with complaints of hematuria which was diagnosed due to muscle invasive papillary urothelial carcinoma of urinary bladder. Metastatic work-up revealed simultaneous presence of locally advanced gastric adenocarcinoma. He was treated with TURBT for the bladder cancer and was planned for radical gastric resection followed by radiation to urinary bladder and stomach with concurrent chemotherapy. However, due to very advanced nature of the gastric tumor patient was treated only with palliative gastric resection followed by palliative radiation to both urinary bladder and stomach due to his poor performance status. Lack of published English literature and evidence related to such clinical entity made this an extremely rare clinical entity and treatment decision difficult.

  4. ROS generation via NOX4 and its utility in the cytological diagnosis of urothelial carcinoma of the urinary bladder

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    Fujimoto Kiyohide

    2011-10-01

    Full Text Available Abstract Background Reactive oxygen species (ROS production via NADPH oxidase (NOX contributes to various types of cancer progression. In the present research, we examined the pathobiological role of NADPH oxidase (NOX4-mediated generation of reactive oxygen species (ROS in urothelial carcinoma (UC of the urinary bladder, and demonstrated the utility of ROS labeling in urine cytology. Methods NOX4 gene was silenced in vivo and in vitro by NOX4 siRNA transfection with or without atlocollagen. Cell cycle and measurement of ROS were analyzed by flowcytometry. Orthotopic implantation animal model was used in vivo experiment. NOX4 expression in urothelial carcinoma cells was observed by immunohistochemical analysis using surgical specimens of human bladder cancer. Urine cytology was performed after treatment with ROS detection reagents in addition to Papanicolaou staining. Results NOX4 was overexpressed in several UC cell lines and the NOX inhibitor, diphenylene iodonium reduced intracellular ROS and induced p16-dependent cell cycle arrest at the G1 phase. Moreover, silencing of NOX4 by siRNA significantly reduced cancer cell growth in vivo as assessed in an orthotopic mouse model. Immunohistochemistry demonstrated high expression of NOX4 in low grade/non-invasive and high grade/invasive UC including precancerous lesions such as dysplasia but not in normal urothelium. Then, we assessed the usefulness of cytological analysis of ROS producing cells in urine (ROS-C. Urine samples obtained from UC cases and normal controls were treated with fluorescent reagents labeling the hydrogen peroxide/superoxide anion and cytological atypia of ROS positive cells were analyzed. As a result, the sensitivity for detection of low grade, non-invasive UC was greatly increased (35% in conventional cytology (C-C vs. 75% in ROS-C, and the specificity was 95%. Through ROS-C, we observed robust improvement in the accuracy of follow-up urine cytology for cases with previously

  5. Prognostic Value of Beta-Tubulin-3 and c-Myc in Muscle Invasive Urothelial Carcinoma of the Bladder

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    Massari, Francesco; Bria, Emilio; Ciccarese, Chiara; Munari, Enrico; Modena, Alessandra; Zambonin, Valentina; Sperduti, Isabella; Artibani, Walter; Cheng, Liang; Martignoni, Guido; Tortora, Giampaolo; Brunelli, Matteo

    2015-01-01

    Background To date, putative prognostic biomarkers have shown limited utility from the clinical perspective for bladder urothelial carcinoma. Herein, the expression of beta-tubulin-3 and c-Myc was evaluated to determine their prognostic potential. Methods In formalin fixed-paraffin embedded blocks, immunohistochemical expression of c-Myc and beta-tubulin-3 was evaluated. H score ranging from 0 to 300 was obtained by multiplying the percentage of positive cells by intensity (0–3); c-Myc and beta-tubulin-3 expression was defined: 0: negative, 1: weakly positive, 2: strongly positive. Results beta-tubulin-3 and c-Myc immunoexpression was available for 46 cases. At the univariate analysis, node-involvement, beta-tubulin-3 and c-Myc overexpression discriminate shorter DFS (HR 2.19, p = 0.043; HR 3.10, p = 0.24 and HR 3.05, p = 0.011, respectively); 2-yrs DFS log-rank analysis according to low versus high level of immunoexpression were statistically significant; beta-tubulin-3, 53% low vs 12.7% high (p = value 0.02) and c-Myc 28 low vs 8 high (p-value 0.007). Patients displaying negative beta-tubulin-3/c-Myc had statistically significant better 2-yrs DFS than those with mixed expression or double positivity (54.5% versus 18.7% versus 0%, log-rank p = 0.006). Conclusions c-Myc and beta-tubulin-3 show improvement for prognostic risk stratification in patients with muscle invasive bladder urothelial carcinoma. These molecular pathways may also be candidate to improve predictiveness to targeted therapies. PMID:26046361

  6. Prognostic Value of Beta-Tubulin-3 and c-Myc in Muscle Invasive Urothelial Carcinoma of the Bladder.

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    Francesco Massari

    Full Text Available To date, putative prognostic biomarkers have shown limited utility from the clinical perspective for bladder urothelial carcinoma. Herein, the expression of beta-tubulin-3 and c-Myc was evaluated to determine their prognostic potential.In formalin fixed-paraffin embedded blocks, immunohistochemical expression of c-Myc and beta-tubulin-3 was evaluated. H score ranging from 0 to 300 was obtained by multiplying the percentage of positive cells by intensity (0-3; c-Myc and beta-tubulin-3 expression was defined: 0: negative, 1: weakly positive, 2: strongly positive.beta-tubulin-3 and c-Myc immunoexpression was available for 46 cases. At the univariate analysis, node-involvement, beta-tubulin-3 and c-Myc overexpression discriminate shorter DFS (HR 2.19, p = 0.043; HR 3.10, p = 0.24 and HR 3.05, p = 0.011, respectively; 2-yrs DFS log-rank analysis according to low versus high level of immunoexpression were statistically significant; beta-tubulin-3, 53% low vs 12.7% high (p = value 0.02 and c-Myc 28 low vs 8 high (p-value 0.007. Patients displaying negative beta-tubulin-3/c-Myc had statistically significant better 2-yrs DFS than those with mixed expression or double positivity (54.5% versus 18.7% versus 0%, log-rank p = 0.006.c-Myc and beta-tubulin-3 show improvement for prognostic risk stratification in patients with muscle invasive bladder urothelial carcinoma. These molecular pathways may also be candidate to improve predictiveness to targeted therapies.

  7. Pembrolizumab and Docetaxel or Gemcitabine Hydrochloride in Treating Patients Urothelial Cancer

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    2016-08-31

    Metastatic Urothelial Carcinoma of the Renal Pelvis and Ureter; Recurrent Bladder Carcinoma; Recurrent Urothelial Carcinoma of the Renal Pelvis and Ureter; Regional Urothelial Carcinoma of the Renal Pelvis and Ureter; Stage III Bladder Urothelial Carcinoma; Stage III Urethral Cancer; Stage IV Bladder Urothelial Carcinoma; Stage IV Urethral Cancer; Urethral Urothelial Carcinoma

  8. Impact of lymphovascular invasion on recurrence and progression rates in patients with pT1 urothelial carcinoma of bladder after transurethral resection

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    Sha N

    2015-11-01

    Full Text Available Nan Sha,* Linguo Xie,* Tao Chen,* Chen Xing, Xiaoteng Liu, Yu Zhang, Zhonghua Shen, Hao Xu, Zhouliang Wu, Hailong Hu, Changli Wu Department of Urology, Tianjin Key Laboratory of Urology, Tianjin Institute of Urology, Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of China *These authors contributed equally to this work Objective: To evaluate the clinical significance of lymphovascular invasion (LVI on recurrence and progression rates in patients with pT1 urothelial carcinoma of bladder after transurethral resection.Methods: This retrospective study was performed with 155 patients with newly diagnosed pT1 urothelial carcinoma of bladder who were treated with transurethral resection of bladder tumor at our institution from January 2006 to January 2010. The presence or absence of LVI was examined by pathologists. Chi-square test was performed to identify the correlations between LVI and other clinical and pathological features. Kaplan–Meier method was used to estimate the recurrence-free survival (RFS and progression-free survival curves and difference was determined by the log-rank test. Univariate and multivariate analyses were performed to determine the predictive factors through a Cox proportional hazards analysis model.Results: LVI was detected in a total of 34 patients (21.9%. While LVI was associated with high-grade tumors (P<0.001 and intravesical therapy (P=0.009. Correlations with age (P=0.227, sex (P=0.376, tumor size (P=0.969, tumor multiplicity (P=0.196, carcinoma in situ (P=0.321, and smoking (P=0.438 were not statistically significant. There was a statistically significant tendency toward higher recurrence rate and shorter RFS time in LVI-positive patients. However, no statistically significant differences were observed in progression rate between the two groups. Moreover, multivariate Cox proportional hazards analysis revealed that LVI, tumor size, and smoking were independent prognostic predictors of

  9. Prognostic Impact of Thrombospodin-2 (THBS2) Overexpression on Patients with Urothelial Carcinomas of Upper Urinary Tracts and Bladders

    Science.gov (United States)

    Chang, I-Wei; Li, Chien-Feng; Lin, Victor Chia-Hsiang; He, Hong-Lin; Liang, Per-In; Wu, Wen-Jeng; Li, Ching-Chia; Huang, Chun-Nung

    2016-01-01

    Purpose: Urothelial carcinoma (UC) is a type of tumor, especially of the urinary bladder, that affects people worldwide. Clarification of its detailed tumor biology and discovery of potential targets for developing treatment strategies are imperative because of frequent recurrences and poor prognosis of advanced UCs. By data mining a published dataset of UC of bladder (UCB) transcriptome (GSE31684) from Gene Expression Omnibus, National Center of Biotechnology Information (GEO, NCBI), we identified that THBS2 was the most significantly upregulated gene among those related to structural molecule activity (GO:0005198). Therefore, we evaluated the clinical significance and prognostic impact of thrombospondin-2 (THBS2) protein, A.K.A. TSP2, which encoded by THBS2 gene. Materials and Methods: THBS2 immunostaining was performed in 340 UCs of upper urinary tract (UC-UUTs) and 295 UCBs; subsequently, both groups were dichotomized into high- and low-expression subgroups. Moreover, statistical analyses were performed to correlate the association between THBS2 expression and clinicopathological parameters with two survival indexes: disease-specific survival (DSS) and metastasis-free survival (MeFS). Results: High THBS2 immunoexpression was significantly associated with advanced primary tumor status, nodal metastasis, and vascular invasion in both UC-UUT and UCB groups (all P ≤ .001). In addition, THBS2 overexpression was linked to adverse DSS and MeFS in univariate analyses and served as an independent prognosticator indicating poor outcomes in both groups in multivariate analyses. Conclusion: THBS2 may play a crucial role in UC progression and may be a novel prognostic marker. Additional investigations to elucidate the molecular pathway are necessary for developing potential THBS2-targeted therapies for UCs. PMID:27471570

  10. The prognostic role of lymphovascular invasion in urothelial carcinoma of the bladder.

    Science.gov (United States)

    Mathieu, Romain; Lucca, Ilaria; Rouprêt, Morgan; Briganti, Alberto; Shariat, Shahrokh F

    2016-08-01

    Outcome prediction in patients with bladder cancer has improved through the development of nomograms and predictive models. However, integration of further characteristics such as lymphovascular invasion (LVI) might increase the accuracy and clinical utility of these instruments. Assessment and reporting of LVI in specimens from transurethral resection of the bladder tumour (TURBT) or biopsy in patients with non-muscle-invasive bladder cancer (NMIBC) or muscle-invasive bladder cancer (MIBC) might enable improved staging, prognostication and clinical decision-making. In NMIBC, presence of LVI in TURBT and biopsy samples seems to be associated with understaging and increased risks of disease recurrence and progression. In MIBC, presence of LVI is associated with features of aggressive disease and predicts recurrence and survival. Integration of LVI status into predictive models might aid clinical decision-making regarding intravesical instillation schedules and regimens, early radical cystectomy in patients with high-grade T1 disease and perioperative chemotherapy. However, LVI assessment is hampered by insufficient reproducibility and reliability, lack of routine evaluation and limited concordance between findings in TURBT and radical cystectomy specimens. Standardization of the pathological criteria defining LVI is warranted to improve its reporting in routine clinical practice and its utility as a care-changing prognostic marker. PMID:27431340

  11. Artificial intelligence for predicting recurrence-free probability of non-invasive high-grade urothelial bladder cell carcinoma.

    Science.gov (United States)

    Cai, Tommaso; Conti, Gloria; Nesi, Gabriella; Lorenzini, Matteo; Mondaini, Nicola; Bartoletti, Riccardo

    2007-10-01

    The objective of our study was to define a neural network for predicting recurrence and progression-free probability in patients affected by recurrent pTaG3 urothelial bladder cancer to use in everyday clinical practice. Among all patients who had undergone transurethral resection for bladder tumors, 143 were finally selected and enrolled. Four follow-ups for recurrence, progression or survival were performed at 6, 9, 12 and 108 months. The data were analyzed by using the commercially available software program NeuralWorks Predict. These data were compared with univariate and multivariate analysis results. The use of Artificial Neural Networks (ANN) in recurrent pTaG3 patients showed a sensitivity of 81.67% and specificity of 95.87% in predicting recurrence-free status after transurethral resection of bladder tumor at 12 months follow-up. Statistical and ANN analyses allowed selection of the number of lesions (multiple, HR=3.31, p=0.008) and the previous recurrence rate (>or=2/year, HR=3.14, p=0.003) as the most influential variables affecting the output decision in predicting the natural history of recurrent pTaG3 urothelial bladder cancer. ANN applications also included selection of the previous adjuvant therapy. We demonstrated the feasibility and reliability of ANN applications in everyday clinical practice, reporting a good recurrence predicting performance. The study identified a single subgroup of pTaG3 patients with multiple lesions, >or=2/year recurrence rate and without any response to previous Bacille Calmette-Guérin adjuvant therapy, that seem to be at high risk of recurrence.

  12. Pathogenic and Diagnostic Potential of BLCA-1 and BLCA-4 Nuclear Proteins in Urothelial Cell Carcinoma of Human Bladder

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    Matteo Santoni

    2012-01-01

    Full Text Available Transitional cell carcinoma (TCC of the bladder is one of the most common malignancies of genitourinary tract. Patients with bladder cancer need a life-long surveillance, directly due to the relatively high recurrence rate of this tumor. The use of cystoscopy represents the gold standard for the followup of previously treated patients. Nevertheless, several factors, including cost and invasiveness, render cystoscopy not ideal for routine controls. Advances in the identification of specific alterations in the nuclear structure of bladder cancer cells have opened novel diagnostic landscapes. The members of nuclear matrix protein family BLCA-1 and BLCA-4, are currently under evaluation as bladder cancer urinary markers. They are involved in tumour cell proliferation, survival, and angiogenesis. In this paper, we illustrate the role of BLCA-1 and BLCA-4 in bladder carcinogenesis and their potential exploitation as biomarkers in this cancer.

  13. MORPHOMETRY, DENSITOMETRY AND PATTERN-ANALYSIS OF PLASTIC-EMBEDDED HISTOLOGIC MATERIAL FROM UROTHELIAL CELL-CARCINOMA OF THE BLADDER

    NARCIS (Netherlands)

    VANDERPOEL, HG; BOON, ME; KOK, LP; VANDERMEULEN, EA; VANCAUBERGH, RD; DEBRUIJN, WC; DEBRUYNE, FMJ

    1991-01-01

    An image analysis method of grading histologic sections of bladder carcinoma was tested. The method was new in four respects. First, fixation of the biopsies a coagulant fixative was used. Second, 2-mu-m plastic sections were used to ensure the reproductibility of nuclear imaging. Third, a new stere

  14. Correlation between Urothelial Differentiation and Sensory Proteins P2X3, P2X5, TRPV1, and TRPV4 in Normal Urothelium and Papillary Carcinoma of Human Bladder

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    Igor Sterle

    2014-01-01

    Full Text Available Terminal differentiation of urothelium is a prerequisite for blood-urine barrier formation and enables normal sensory function of the urinary bladder. In this study, urothelial differentiation of normal human urothelium and of low and high grade papillary urothelial carcinomas was correlated with the expression and localization of purinergic receptors (P2X3, and P2X5 and transient receptor potential vanilloid channels (TRPV1, and TRPV4. Western blotting and immunofluorescence of uroplakins together with scanning electron microscopy of urothelial apical surface demonstrated terminal differentiation of normal urothelium, partial differentiation of low grade carcinoma, and poor differentiation of high grade carcinoma. P2X3 was expressed in normal urothelium as well as in low grade carcinoma and in both cases immunolabeling was stronger in the superficial cells. P2X3 expression decreased in high grade carcinoma. P2X5 expression was detected in normal urothelium and in high grade carcinoma, while in low grade carcinoma its expression was diminished. The expression of TRPV1 decreased in low grade and even more in high grade carcinoma when compared with normal urothelium, while TRPV4 expression was unchanged in all samples. Our results suggest that sensory proteins P2X3 and TRPV1 are in correlation with urothelial differentiation, while P2X5 and TRPV4 have unique expression patterns.

  15. Microcystic Variant of Urothelial Carcinoma

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    Anthony Kodzo-Grey Venyo

    2013-01-01

    Full Text Available Background. Microcystic variant of urothelial carcinoma is one of the new variants of urothelial carcinoma that was added to the WHO classification in 2004. Aims. To review the literature on microcystic variant of urothelial carcinoma. Methods. Various internet search engines were used to identify reported cases of the tumour. Results. Microscopic features of the tumour include: (i Conspicuous intracellular and intercellular lumina/microcysts encompassed by malignant urothelial or squamous cells. (ii The lumina are usually empty; may contain granular eosinophilic debris, mucin, or necrotic cells. (iii The cysts may be variable in size; round, or oval, up to 2 mm; lined by urothelium which are either flattened cells or low columnar cells however, they do not contain colonic epithelium or goblet cells; are infiltrative; invade the muscularis propria; mimic cystitis cystica and cystitis glandularis; occasionally exhibit neuroendocrine differentiation. (iv Elongated and irregular branching spaces are usually seen. About 17 cases of the tumour have been reported with only 2 patients who have survived. The tumour tends to be of high-grade and high-stage. There is no consensus opinion on the best option of treatment of the tumour. Conclusions. It would prove difficult at the moment to be dogmatic regarding its prognosis but it is a highly aggressive tumour. New cases of the tumour should be reported in order to document its biological behaviour.

  16. Urothelial Bladder Cancer with Cavitary Lung Metastases

    OpenAIRE

    Anil Kurian; Jason Lee; Abraham Born

    2011-01-01

    Transitional cell carcinoma (TCC) of the bladder tends to remain superficial; however, in 5% to 20% of cases, it progresses to muscle invasion and, more rarely, can metastasize. TCC of the bladder primarily spreads via regional lymphatics. The most common sites of distant metastases of TCC are the liver, lung, mediastinum and bone. Long-term survival of patients with metastatic bladder cancer is rare. Patterns of pulmonary metastasis include multiple nodules, a solitary mass or interstitial m...

  17. 膀胱尿路上皮癌及正常膀胱组织microRNA21、205表达研究%Expression of miR-21 and miR-205 in urothelial cell carcinoma of bladder and normal bladder mucosa

    Institute of Scientific and Technical Information of China (English)

    马杰; 姜宁; 王国增; 郑景存; 贺伟; 刁海彦

    2012-01-01

    目的 探讨microRNAs (miRNAs)在膀胱尿路上皮癌与正常膀胱组织中的表达差异性及意义.方法 采用基于2-△△cT的实时定量PCR(Real-time PCR)方法 检测50例膀胱尿路上皮癌与21例正常膀胱组织中miR-21及miR-205的表达情况.结果 与正常组织相比,癌组织miR-21表达上调(P<0.01),miR-205表达下调(P<o.o1).癌组织中miR-21与miR-205表达量的比值约3.6倍于正常组织中表达量的比值.结论 miR-21高表达、miR-205低表达可能参与膀胱尿路上皮癌的发生、发展.%Objective To detect the expression of miR-21 and miR-205 in urothelial cell carcinoma of bladder and normal bladder mucosa and explore the relationship between microRNAs (miRNAs) and urothelial cell carcinoma of bladder. Methods 2△△CT Real-time PCR method was used for quantitative analysis of the expression of miR-21 and miR-205 in 50 urothelial cell carcinoma of bladder and 21 normal bladder tissues. Results Compared with normal bladder mucosa, the urothelial cell carcinoma of bladder tissues showed significant miR-21 over-expression (P<0. 01) and miR-205 down-regulation (P <0. 01). Cancer tissue showed miR-21: miR-205 ratio at least 3.6-fold higher than the quantitative ratio obtained from normal bladder tissue. Conclusion The over expression of miR-21 and lower expression of miR-205 may participate in recurrence urothelial cell carcinoma of bladder.

  18. Comparative Gene Expression Analyses Identify Luminal and Basal Subtypes of Canine Invasive Urothelial Carcinoma That Mimic Patterns in Human Invasive Bladder Cancer.

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    Deepika Dhawan

    Full Text Available More than 160,000 people are expected to die from invasive urothelial carcinoma (iUC this year worldwide. Research in relevant animal models is essential to improving iUC management. Naturally-occurring canine iUC closely resembles human iUC in histopathology, metastatic behavior, and treatment response, and could provide a relevant model for human iUC. The molecular characterization of canine iUC, however, has been limited. Work was conducted to compare gene expression array results between tissue samples from iUC and normal bladder in dogs, with comparison to similar expression array data from human iUC and normal bladder in the literature. Considerable similarities between enrichment patterns of genes in canine and human iUC were observed. These included patterns mirroring basal and luminal subtypes initially observed in human breast cancer and more recently noted in human iUC. Canine iUC samples also exhibited enrichment for genes involved in P53 pathways, as has been reported in human iUC. This is particularly relevant as drugs targeting these genes/pathways in other cancers could be repurposed to treat iUC, with dogs providing a model to optimize therapy. As part of the validation of the results and proof of principal for evaluating individualized targeted therapy, the overexpression of EGFR in canine bladder iUC was confirmed. The similarities in gene expression patterns between dogs and humans add considerably to the value of naturally-occurring canine iUC as a relevant and much needed animal model for human iUC. Furthermore, the finding of expression patterns that cross different pathologically-defined cancers could allow studies of dogs with iUC to help optimize cancer management across multiple cancer types. The work is also expected to lead to a better understanding of the biological importance of the gene expression patterns, and the potential application of the cross-species comparisons approach to other cancer types as well.

  19. Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma

    DEFF Research Database (Denmark)

    Hedegaard, Jakob; Lamy, Philippe; Nordentoft, Iver;

    2016-01-01

    Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease with widely different outcomes. We performed a comprehensive transcriptional analysis of 460 early-stage urothelial carcinomas and showed that NMIBC can be subgrouped into three major classes with basal- and luminal-like charac......Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease with widely different outcomes. We performed a comprehensive transcriptional analysis of 460 early-stage urothelial carcinomas and showed that NMIBC can be subgrouped into three major classes with basal- and luminal...... cytoskeletal functions. Furthermore, mutations in well-known cancer driver genes (e.g., TP53 and ERBB2) were primarily found in high-risk tumors, together with APOBEC-related mutational signatures. The identification of subclasses in NMIBC may offer better prognostication and treatment selection based on...

  20. Value of positron emission tomography in diagnosing synchronous penile metastasis from urothelial bladder cancer

    OpenAIRE

    Rouanne, M.; Alhammadi, A.; Vilain, D.; Radulescu, C.; Lebret, T.

    2015-01-01

    Metastases to the penis are extremely rare events. Most frequently, penile metastases come from the urogenital system (bladder, prostate) or the rectum-sigmoid colon. Usually painful, penile lesions may be asymptomatic, making diagnosis more challenging. Hence, we report the adding value of 18F-fludeoxyglucose–positron emission tomography/computed tomography (18F-FDG PET/CT) in the detection of penile metastases originating from urothelial carcinoma of the bladder. Arguably, penile metastases...

  1. Urothelial carcinoma involving the distal penis

    OpenAIRE

    Dason, Shawn; Sheikh, Adeel; Wang, Jing Gennie; Tauqir, Syeda; Davies, Timothy O.; Shayegan, Bobby

    2012-01-01

    Urothelial carcinoma (UC) rarely metastasizes to the penis and skin. We report the case of a 73-year-old man with UC metastases to the corpus spongiosum and dermis of the distal penis. We also review the clinicopathologic characteristics and management options for UC metastasizing to the penis. The patient presented with priapism and edema of the genital region. This follows a 5-year history of urothelial carcinoma in situ that progressed to invasive cancer despite intravesical immunotherapy....

  2. Impact of surgery and epirubicin intravesical chemotherapy on peripheral blood dendritic cell subsets in patients with superficial urothelial carcinoma of the bladder

    Institute of Scientific and Technical Information of China (English)

    FENG Lang; MA Lin-lin; ZHANG Yu-hai; TIAN Ye; QU Chen-xue; WANG Yang

    2012-01-01

    Background Superficial urothelial carcinoma (SUC) of the bladder is a common urinary tract tumor in China.There is a high recurrence rate of this tumor even after surgery and intravesical instillation.Previous reports have described a suppression of the immune system in cancer patients.Dendritic cells (DCs) play a pivotal role in the induction of an effective antitumor immune response.The aim of this study was to investigate the effects of surgery and epirubicin intravesical chemotherapy (IC) on peripheral blood DCs in subsets of patients with bladder SUC.@@Methods A total of 66 SUC patients and 38 healthy controls were enrolled in this study.All the patients had undergone transurethral resection (TUR) of their cancer and adjunctive IC after tumor removal.The patients were divided into a non-recurrence group (n=40) and a recurrence group (n=26) based on the presence or absence of tumor recurrence.Blood samples were taken preoperatively (PreOP),on postoperative days (POD) 1 and 7,and at postoperative month (POM) 3.Flow cytometric analysis was used for the determination and quantitation of the surface markers CD80 and CD86 in circulating DC subsets.@@Results The preoperative percentages of myeloid dendritic cells (mDCs) and expression of CD80 and CD86 were impaired in SUC patients compared to healthy controls (P <0.05).The percentages of mDCs and these surface markers decreased significantly on POD 1 and increased on POD 7,remaining higher than the preoperative values in POM 3 (P <0.05).The percentages of mDCs,and CD80 and CD86 in the non-recurrence group on PreOP,POD 7,and POM 3 were higher than those in recurrence group.@@Conclusions Surgical removal of SUC and adjunctive IC were associated with improved circulating mDC counts and function.Persistent depression of mDC counts and function after treatment in recurrence patients indicated lower antitumor immunity that may lead to tumor recurrence.

  3. Urothelial bladder cancer with cavitary lung metastases.

    Science.gov (United States)

    Kurian, Anil; Lee, Jason; Born, Abraham

    2011-01-01

    Transitional cell carcinoma (TCC) of the bladder tends to remain superficial; however, in 5% to 20% of cases, it progresses to muscle invasion and, more rarely, can metastasize. TCC of the bladder primarily spreads via regional lymphatics. The most common sites of distant metastases of TCC are the liver, lung, mediastinum and bone. Longterm survival of patients with metastatic bladder cancer is rare. Patterns of pulmonary metastasis include multiple nodules, a solitary mass or interstitial micronodule. When multiple nodules are present, they are round and well-circumscribed, without calcification or cavitation. An unusual case of rapidly metastatic TCC to the lung causing large cavitary masses and nodules is presented. Imaging performed after the patient began chemotherapy revealed widespread necrosis of the metastatic cavitary masses causing moderate volume hemoptysis. PMID:21766082

  4. Urothelial Bladder Cancer with Cavitary Lung Metastases

    Directory of Open Access Journals (Sweden)

    Anil Kurian

    2011-01-01

    Full Text Available Transitional cell carcinoma (TCC of the bladder tends to remain superficial; however, in 5% to 20% of cases, it progresses to muscle invasion and, more rarely, can metastasize. TCC of the bladder primarily spreads via regional lymphatics. The most common sites of distant metastases of TCC are the liver, lung, mediastinum and bone. Long-term survival of patients with metastatic bladder cancer is rare. Patterns of pulmonary metastasis include multiple nodules, a solitary mass or interstitial micronodule. When multiple nodules are present, they are round and well-circumscribed, without calcification or cavitation. An unusual case of rapidly metastatic TCC to the lung causing large cavitary masses and nodules is presented. Imaging performed after the patient began chemotherapy revealed widespread necrosis of the metastatic cavitary masses causing moderate volume hemoptysis.

  5. Upper Tract Urothelial Carcinomas in Patients with Chronic Kidney Disease: Relationship with Diagnostic Challenge

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    Li-Jen Wang

    2014-01-01

    Full Text Available Chronic kidney disease and upper tract urothelial carcinomas display a bidirectional relationship. Review of the literature indicates that early diagnosis and correct localization of upper tract urothelial carcinomas in dialysis patients and kidney transplant recipients are important but problematic. Urine cytology and cystoscopy have limited sensitivity for the diagnosis of upper tract urothelial carcinomas in dialysis patients. Enhanced computed tomography and magnetic resonance imaging could prove useful for the detection and staging of upper tract urothelial carcinomas in dialysis patients. Renal ultrasound can detect hydronephrosis caused by upper tract urothelial carcinomas in kidney transplant recipients but cannot visualize the carcinomas themselves. High detection rates for upper tract urothelial carcinomas in kidney transplant recipients have recently been demonstrated using computed tomography urography, which appears to be a promising tool. To detect carcinomas in dialysis patients and kidney transplant recipients as early as possible, regular screening in asymptomatic patients and diagnostic work-up in symptomatic patients should be performed using a combination of urological and imaging methods. Careful assessment of subsequent recurrence within the contralateral upper urinary tract and the urinary bladder is necessary for dialysis patients and kidney transplant recipients with upper tract urothelial carcinomas.

  6. Upper tract urothelial carcinomas in patients with chronic kidney disease: relationship with diagnostic challenge.

    Science.gov (United States)

    Wang, Li-Jen; Lee, Shen-Yang; Teh, Bin Tean; Chuang, Cheng-Keng; Nortier, Joëlle

    2014-01-01

    Chronic kidney disease and upper tract urothelial carcinomas display a bidirectional relationship. Review of the literature indicates that early diagnosis and correct localization of upper tract urothelial carcinomas in dialysis patients and kidney transplant recipients are important but problematic. Urine cytology and cystoscopy have limited sensitivity for the diagnosis of upper tract urothelial carcinomas in dialysis patients. Enhanced computed tomography and magnetic resonance imaging could prove useful for the detection and staging of upper tract urothelial carcinomas in dialysis patients. Renal ultrasound can detect hydronephrosis caused by upper tract urothelial carcinomas in kidney transplant recipients but cannot visualize the carcinomas themselves. High detection rates for upper tract urothelial carcinomas in kidney transplant recipients have recently been demonstrated using computed tomography urography, which appears to be a promising tool. To detect carcinomas in dialysis patients and kidney transplant recipients as early as possible, regular screening in asymptomatic patients and diagnostic work-up in symptomatic patients should be performed using a combination of urological and imaging methods. Careful assessment of subsequent recurrence within the contralateral upper urinary tract and the urinary bladder is necessary for dialysis patients and kidney transplant recipients with upper tract urothelial carcinomas.

  7. Further characterization of the muscle layers and lamina propria of the urinary bladder by systematic histologic mapping: implications for pathologic staging of invasive urothelial carcinoma.

    Science.gov (United States)

    Paner, Gladell P; Ro, Jae Y; Wojcik, Eva M; Venkataraman, Girish; Datta, Milton W; Amin, Mahul B

    2007-09-01

    bundles were noted in deep LP situated between the more typical slender MM layer and the MP. In conclusion, there are additional patterns of MM other than previously described. Awareness of the occasionally hyperplastic appearance of MM muscle is important to prevent overstaging of invasive urothelial carcinoma. In transurethral resection specimens, lack of orientation may preclude distinction of the hyperplastic MM from true MP in these rare situations. The number and orientation of muscle bundles, relationship to urothelium and vascular plexus, and comparison with more characteristic MP, if present, would be helpful; isolated bundles immediately adjacent to the urothelium with loose haphazard fiber orientation and irregular outlines favor MM over MP muscle. The hyperplastic MM mimicking MP may be more challenging; isolated muscle bundles immediately adjacent to the urothelium would favor hyperplastic pattern of MM over MP muscle. Topographical variations exist among the subsites, the more superficial location of the MP and the rarity of MM in the trigone, relative abundance of hyperplastic MM in dome, and presence of the more superficial ureteral MP at its insertion in the bladder complicate the traditional pT stage evaluation of invasion in these regions. The inconsistency of a distinct MM layer and variations in the LP vascular plexus indicate that substaging of pT1 would be problematic and thus provides further support to the World Health Organization/International Society of Urological Pathology 1998 and World Health Organization 2004 recommendation against its implementation at the current time. PMID:17721199

  8. MANAGEMENT OF CARCINOMA BLADDER: A REVIEW LITERATURE

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    Gurinderjit Singh

    2014-12-01

    Full Text Available Carcinoma of the bladder is a disease of the elderly. Bladder cancer is three times more common in males than in females and more common in whites than in blacks. Patients with bladder cancer have a 1% to 4% incidence of synchronous or metachronous upper t ract urothelial tumors. There are many risk factors for urothelial cancer, classified into (1 Genetic (2 chemical exposure, and (3 chronic irritation. Genetic abnormalities associated with CIS include alterations in the retinoblastoma gene (Rb, p53, an d PTEN. Chemical exposure has the most epidemiologic evidence to support it as an inciting agent (Aromatic amines, aniline dyes, and nitrites and nitrates. Chronic irritants include catheters, recurrent urinary track infections, Schistosoma haematobium, a nd irradiation. There are many studies that suggest high water consumption, vitamin intake, and various diets that are beneficial in preventing bladder cancer. However, none of these have shown any clear benefit with respect to prevention.

  9. URACHAL CARCINOMA IN BLADDER

    Institute of Scientific and Technical Information of China (English)

    薛丽燕; 吕宁; 何祖根; 林冬梅; 刘秀云

    2004-01-01

    Objective: To investigate the clinicopathologic features and diagnostic criteria of urachal carcinoma in the bladder.Methods: Seven cases of urachal carcinoma in the bladder were analyzed retrospectively. Results: All the tumors were found locating in the dome of bladder. Of them, 4 were mucinous adenocarcinoma, one was well differentiated papillary enteric adenocarcinoma, one was well differentiated squamous carcinoma, and one was neuroendocrine carcinoma. Cystomorphous urachal remnants were found in 4 cases. The main complaint was hematuria and all patients underwent partial excision of bladder and urachus. Conclusion: Mucinous adenocarcinoma is the main histo-pathological type, and cystomorphous urachal remnants are often accompanied with urachal carcinoma in the bladder. The key diagnostic criteria of urachal carcinoma in bladder are site and histopathology. And to examine the specimens carefully to find the urachal remnants is important.

  10. Diagnosis and treatment in primary bladder small cell carcinoma: Literature review

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    Orcun Celik

    2016-03-01

    Full Text Available Small cell bladder carcinoma is a rare and frequently fatal disease. It can be distinguished from classical urothelial carcinoma microscopically and immunohistochemically. Small cell bladder carcinoma has histologically similar properties with other small cell carcinomas in other organs. It has a worse prognosis when compared to urothelial bladder cancer. Multimodal treatments are recommended although there is no widely accepted consensus regarding to the treatment algorithm because of its rarity. In this review, clinical properties and diagnosis of small cell bladder carcinoma, its histopathological and immunohistochemical properties and treatment modalities are examined.

  11. Urothelial neoplasm of the bladder in childhood and adolescence: a rare disease

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    Haci Polat

    2016-04-01

    Full Text Available ABSTRACT Purpose: Bladder tumors are rare in children and adolescents. For this reason, the diagnosis is sometimes delayed in pediatric patients. We aimed to describe the diagnosis, treatment, and follow-up methods of bladder urothelial neoplasms in children and adolescents. Materials and Methods: We carried out a retrospective multicenter study involving patients who were treated between 2008 and 2014. Eleven patients aged younger than 18 years were enrolled in the study. In all the patients, a bladder tumor was diagnosed using ultrasonography and was treated through transurethral resection of the bladder (TURBT. Results: Nine of the 11 patients (82% were admitted with gross hematuria. The average delay in diagnosis was 3 months (range, 0–16 months until the ultrasonographic diagnosis was performed from the first episodes of macroscopic hematuria. A single exophytic tumor (1–4cm was present in each patient. The pathology of all patients was reported as superficial urothelial neoplasm: two with papilloma, one with papillary urothelial neoplasm of low malignant potential (PUNLMP, four with low grade pTa, and four with low grade pT1. No recurrence was observed during regular cystoscopic and ultrasonographic follow-up. Conclusions: Regardless of the presence of hematuria, bladder tumors in children are usually not considered because urothelial carcinoma in this population is extremely rare, which causes a delay in diagnosis. Fortunately, the disease has a good prognosis and recurrences are infrequent. Cystoscopy may be unnecessary in the follow-up of children with bladder tumors. We believe that ultrasonography is sufficient in follow-up.

  12. Bovine Papillomavirus Type 2 Infection and Microscopic Patterns of Urothelial Tumors of the Urinary Bladder in Water Buffaloes

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    Paola Maiolino

    2013-01-01

    Full Text Available Microscopic patterns of thirty-four urothelial tumors of the urinary bladder of water buffaloes from the Marmara and Black Sea Regions of Turkey are here described. All the animals grazed on lands rich in bracken fern. Histological diagnosis was assessed using morphological parameters recently suggested for the urinary bladder tumors of cattle. Papillary carcinoma was the most common neoplastic lesion (22/34 observed in this study, and low-grade carcinoma was more common (seventeen cases than high-grade carcinoma (five cases. Papilloma, papillary urothelial neoplasm of low malignant potential (PUNLMP, and invasive carcinomas were less frequently seen. Carcinoma in situ (CIS was often detected associated with some papillary and invasive carcinomas. De novo (primary CIS was rare representing 3% of tumors of this series. A peculiar feature of the most urothelial tumors was the presence in the tumor stroma of immune cells anatomically organized in tertiary lymphoid organs (TLOs. Bovine papillomavirus type-2 (PV-2 E5 oncoprotein was detected by molecular and immunohistochemistry procedures. Early protein, E2, and late protein, L1, were also detected by immunohistochemical studies. Morphological and molecular findings show that BPV-2 infection contributes to the development of urothelial bladder carcinogenesis also in water buffaloes.

  13. Does urothelial cancer of bladder behave differently in young patients?

    Institute of Scientific and Technical Information of China (English)

    WANG Zhi-hua; LI You-yuan; HU Zhi-quan; ZHU Hui; ZHUANG Qian-yuan; QI Yong; YE Zhang-qun

    2012-01-01

    Background Bladder urothelial cancer has been diagnosed at an increasing rate among young adults in China while the clinical outcomes remain highly controversial.To optimize the management of young patients with bladder cancer,we examined whether bladder urothelial cancer in young patients behaved differently from that in the elder patients.Methods From 1994 to 2008,a database of bladder urothelial cancer patients at a major tertiary medical center was retrospectively reviewed.The clinical and pathological parameters of patients who were less than 40 years of age and a series of patients older than 40 years of age as the control group during the same period were compared.A survival analysis was performed using the Kaplan-Meier method and log-rank test,and Cox regression was performed to identify clinical parameters that affected the clinic outcomes.Results Young bladder cancer patients had a lower male-to-female ratio and were less likely to have advanced stages and high-grade cancers at the initial diagnosis.Tumors in young bladder cancer patients tended to be less multifocal at diagnosis.In addition,young patients had a lower recurrence rate and longer recurrence interval than older patients.The Kaplan-Meier curve and Log-rank test showed that young patients had significantly better cancer specific survival than old patients.The univariats and multivariate Cox regression analysis revealed that tumor grade is the sole predictor for tumor recurrence in young patients.Conclusions Young patients with bladder cancer have favorable pathological features and clinical outcomes than older patients.These findings argue for more conservative management approaches for young patients with bladder cancer.

  14. Pure primary small cell carcinoma of urinary bladder: A rare diagnostic entity

    Directory of Open Access Journals (Sweden)

    Sonia Gon

    2013-01-01

    Full Text Available Small cell carcinoma of the bladder is a rare, aggressive, poorly differentiated neuroendocrine neoplasm accounting for only 0.3-0.7% of all bladder tumors. Since the tumor is very rare, pathogenesis is uncertain. Small cell carcinomas of the urinary bladder are mixed with classic urothelial carcinomas or adenocarcinomas of the bladder in 68% cases, making pure primary small cell carcinoma even a rarer entity. The unknown etiology and natural history of small cell carcinoma of the urinary bladder represent a challenge both to the pathologist and urologists for its diagnosis and treatment, respectively.

  15. Screening for Bladder and Other Urothelial Cancers

    Science.gov (United States)

    ... Using tobacco , especially smoking cigarettes. Having a family history of bladder cancer. Having certain changes in the genes . Being exposed to paints, dyes, metals or petroleum products in the workplace. Past treatment with radiation therapy to the pelvis or with certain anticancer drugs, ...

  16. Pure Lymphoepithelioma-Like Carcinoma Originating from the Urinary Bladder

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    Takashi Nagai

    2016-03-01

    Full Text Available Lymphoepithelioma-like carcinoma of the urinary bladder (LELCB is a rare variant of infiltrating urothelial carcinoma. We report a case of LELCB in a 43-year-old man. Ultrasonography and cystoscopy revealed two bladder tumors, one on the left side of the trigone and the other on the right side of the trigone. Transurethral resection of the bladder tumors was performed and pathological analysis revealed undifferentiated carcinoma. We therefore performed radical cystectomy and urinary diversion. Immunohistochemically the tumor cells were positive for cytokeratin, but negative for Epstein-Barr virus-encoded small RNA in situ hybridization as found for previous cases of LELCB. The final pathological diagnosis was a lymphoepithelioma-like variant of urothelial carcinoma with perivesical soft tissue invasion. For adjuvant systemic chemotherapy, three courses of cisplatin were administered. The patient subsequently became free of cancer 72 months postoperatively. Based on the literature, pure or predominant LELCB types show favorable prognoses due to their sensitivity to chemotherapy or radiotherapy. An analysis of the apparent diffusion coefficient (ADC values of bladder tumors examined in our institution revealed that the ADC value measured for this LELCB was relatively low compared to conventional urothelial carcinomas. This suggests that measuring the ADC value of a lymphoepithelioma-like carcinoma prior to operation may be helpful in predicting LELCB.

  17. Trastuzumab therapy in metastatic bladder carcinoma: The proof of concept

    Directory of Open Access Journals (Sweden)

    Moussaid Y

    2014-08-01

    Full Text Available About 10% of metastatic urothelial carcinoma overexpress oncogenic HER2/neu receptor. Recent preliminary data suggest that patients with this particular molecular subset could benefit from trastuzumab therapy, which specifically targets the receptor and thus inhibits downstream activation pathway. Here we report a case illustrating this clinical benefit, with complete response reported as third line therapy in a heavily pretreated patient with diffuse metastatic urothelial carcinoma of the bladder. It also highlights the usefulness of 18-Fluorodeoxyglucose Positron Emission Tomography (18-FDG PET as a biomarker for response to trastuzumab.

  18. IMMUNOHISTOCHEMICAL ANALYSIS OF UROTHELIAL BLADDER CANCERS

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    Katarina Bevizova

    2013-01-01

    Full Text Available Malignant cancers of urinary bladder are the second most common malignancy of the urinary tract and the fourth most common malignancy in general, especially in men. The aim of this study was a retrospective analysis of selected markers (p53, Ki-67 and E-cadherin of urinary bladder cancers from the Department of Urology in Bratislava, Slovak Republic between years 2007 and 2009. We analysed 244 patients (202 males, 42 females with diagnosed bladder cancer via cystoscopy and subsequent transurethral resection. Patients’ age varied from 36 to 98 years. Obtained samples were fixed by 10% buffered formalin for 24 to 48 h. Subsequently, they were dehydrated in ascending ethanol series and embedded in paraffin. The parafin sections of 5 µm were prepared by microtome and they were stained by haematoxylin and eosin. The antibodies against to p53, Ki-67 and E-cadherin were used in immunohistochemical analysis. Statistical evaluation was performed via SPSS using non-parametric Kruskal-Wallis test and p values<0.05 were considered statistically significant. No significant differences in the expression of selected markers were found between genders. Expression of p53 and Ki-67, in G1 and G2 of low grade tumours was lower in comparison to their expression in G3 tumors. Expression of E-cadherin was the opposite in this case. The expression of p53 and Ki-67 positively correlated with tumor’s depth of invasion, while the expression of E-cadherin significantly decreased. In case of T4 tumors, the expression of all markers exhibited consistently high values. When analysing tumor multiplicity, the expression of p53 and Ki-67 significantly decreased, while the expression of E-cadherin significantly increased. Based on the obtained results it can be concluded that the analysis of p53, Ki-67 and E-cadherin expression is essential for diagnostics and prognostics of bladder cancer and should be routinely used in daily practise together with

  19. Review of Topical Treatment of Upper Tract Urothelial Carcinoma

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    Kenneth G. Nepple

    2009-01-01

    Full Text Available A select group of patients with upper tract urothelial carcinoma may be appropriate candidates for minimally invasive management. Organ-preserving endoscopic procedures may be appropriate for patients with an inability to tolerate major surgery, solitary kidney, bilateral disease, poor renal function, small tumor burden, low-grade disease, or carcinoma in situ. We review the published literature on the use of topical treatment for upper tract urothelial carcinoma and provide our approach to treatment in the office setting.

  20. Disease-free survival at 2 and 3 years is a significant early surrogate marker predicting the 5-year overall survival in patients treated with radical cystectomy for urothelial carcinoma of the bladder: external evaluation and validation in a cohort of Korean patients

    Directory of Open Access Journals (Sweden)

    Hyung Suk eKim

    2015-10-01

    Full Text Available Purpose: We aimed to externally validate the association of 2- and 3-year disease-free survival with 5-year overall survival in patients treated with radical cystectomy for urothelial carcinoma of the bladder. Materials and Methods: We reviewed the clinical data of 422 patients who underwent radical cystectomy for urothelial carcinoma of the bladder in our institution between 1991 and 2012. Survival curves were plotted with the Kaplan–Meier method. The Kappa statistic and Kendall tau-b test were used to assess the agreements between 2- and 3-year disease free survival and 5-year overall survival. Results: In the entire study population, 2- and 3-year disease free and 5-year overall survival rates were 76.4%, 71.5%, and 67.4%, respectively. All Kappa and Kendall’s tau-b test values for agreements between 2- and 3-year disease free and 5-year overall survival were more than 0.40, indicating moderate agreement for all patients and in each patient subgroup selected according to specific variables (all p values <0.05. Kaplan–Meier analysis for disease free survival and Cox-proportional hazard models for landmark analysis at each time point indicated that most recurrences occurred within 3 years after surgery. The 5-year overall survival rates of patients who were recurrence free at each time point gradually increased to more than 95% in an extended recurrence-free interval of 12–36 months.Conclusions: Our external validation results support the existing finding that 2- and 3-year disease free survival can be a valid early surrogate end point to predict 5-year overall survival after radical cystectomy in patients with urothelial carcinoma of the bladder.

  1. Cytological Findings of the Micropapillary Variant of Urothelial Carcinoma: A Comparison with Typical High-Grade Urothelial Carcinoma

    OpenAIRE

    Kim, Kyu-Ho; Choi, Chang-Hwan; Han, Jee-Young; Kim, Lucia; Choi, Suk-Jin; Park, In-Suh; Kim, Joon-Mee; Chu, Young-Chae

    2013-01-01

    Background Micropapillary variant of urothelial carcinoma (MPUC) showed distinct pathologic features and aggressive behavior. The cytologic findings of MPUC are still indistinct. In this study, we evaluated the cytological findings of MPUC compared with those of high-grade urothelial carcinoma (HGUC). Methods The voided urine cytology of 8 cases of MPUC and 8 cases of HGUC was reviewed. Following cytological parameters were evaluated: cellularity, background, number of small, tight papillary ...

  2. Fruit and vegetable consumption and risk of aggressive and non-aggressive urothelial cell carcinomas in the European prospective investigation into cancer and nutrition

    NARCIS (Netherlands)

    Ros, M.; Bueno-de-Mesquita, H.B.; Kampman, E.; Büchner, F.L.; Aben, K.K.; Egevad, L.; Overvad, K.; Tjonneland, A.; Roswall, N.; Clavel-Chapelon, F.; Boutron-Ruault, M.C.; Moiros, S.; Kaaks, R.; Teucher, B.; Weikert, S.; Ruesten, A.V.; Trichopoulou, A.; Naska, A.; Benetou, V.; Saieva, C.; Pala, V.; Ricceri, F.; Tumino, R.; Mattiello, A.; Peeters, P.H.M.; Gils, van C.H.; Gram, I.T.; Engeset, D.; Chirlaque, M.D.; Ardanazx, E.; Rodriguez, L.

    2012-01-01

    Background - Many epidemiological studies have examined fruit and vegetable consumption in relation to the risk of urothelial cell carcinoma (UCC) of the bladder, but results are inconsistent. The association between fruit and vegetable consumption and UCC risk may vary by bladder tumour aggressiven

  3. Loss of the urothelial differentiation marker FOXA1 is associated with high grade, late stage bladder cancer and increased tumor proliferation.

    Directory of Open Access Journals (Sweden)

    David J DeGraff

    Full Text Available Approximately 50% of patients with muscle-invasive bladder cancer (MIBC develop metastatic disease, which is almost invariably lethal. However, our understanding of pathways that drive aggressive behavior of MIBC is incomplete. Members of the FOXA subfamily of transcription factors are implicated in normal urogenital development and urologic malignancies. FOXA proteins are implicated in normal urothelial differentiation, but their role in bladder cancer is unknown. We examined FOXA expression in commonly used in vitro models of bladder cancer and in human bladder cancer specimens, and used a novel in vivo tissue recombination system to determine the functional significance of FOXA1 expression in bladder cancer. Logistic regression analysis showed decreased FOXA1 expression is associated with increasing tumor stage (p<0.001, and loss of FOXA1 is associated with high histologic grade (p<0.001. Also, we found that bladder urothelium that has undergone keratinizing squamous metaplasia, a precursor to the development of squamous cell carcinoma (SCC exhibited loss of FOXA1 expression. Furthermore, 81% of cases of SCC of the bladder were negative for FOXA1 staining compared to only 40% of urothelial cell carcinomas. In addition, we showed that a subpopulation of FOXA1 negative urothelial tumor cells are highly proliferative. Knockdown of FOXA1 in RT4 bladder cancer cells resulted in increased expression of UPK1B, UPK2, UPK3A, and UPK3B, decreased E-cadherin expression and significantly increased cell proliferation, while overexpression of FOXA1 in T24 cells increased E-cadherin expression and significantly decreased cell growth and invasion. In vivo recombination of bladder cancer cells engineered to exhibit reduced FOXA1 expression with embryonic rat bladder mesenchyme and subsequent renal capsule engraftment resulted in enhanced tumor proliferation. These findings provide the first evidence linking loss of FOXA1 expression with histological subtypes

  4. Australian and New Zealand Faculty of Radiation Oncology Genito-Urinary Group: 2011 consensus guidelines for curative radiotherapy for urothelial carcinoma of the bladder

    International Nuclear Information System (INIS)

    Curative radiotherapy, with or without concurrent chemotherapy, is recognized as a standard treatment option for muscle-invasive bladder cancer. It is commonly used for two distinct groups of patients: either for those medically unfit for surgery, or as part of a 'bladder preserving' management plan incorporating the possibility of salvage cystectomy. However, in both situations, the approach to radiotherapy varies widely around the world. The Australian and New Zealand Faculty of Radiation Oncology Genito-Urinary Group recognised a need to develop consistent, evidence-based guidelines for patient selection and radiotherapy technique in the delivery of curative radiotherapy. Following a workshop convened in May 2009, a working party collated opinions and conducted a wide literature appraisal linking each recommendation with the best available evidence. This process was subject to ongoing re-presentation to the Faculty of Radiation Oncology Genito-Urinary Group members prior to final endorsement. These Guidelines include patient selection, radiation target delineation, dose and fractionation schedules, normal tissue constraints and investigational techniques. Particular emphasis is given to the rationale for the target volumes described. These Guidelines provide a consensus-based framework for the delivery of curative radiotherapy for muscle-invasive bladder cancer. Widespread input from radiation oncologists treating bladder cancer ensures that these techniques are feasible in practice. We recommend these Guidelines be adopted widely in order to encourage a uniformly high standard of radiotherapy in this setting, and to allow for better comparison of outcomes.

  5. Expression of metastasis-associated protein 1 and Ezrin in bladder urothelial carcinoma%转移相关蛋白1和埃兹蛋白在膀胱尿路上皮癌中的表达

    Institute of Scientific and Technical Information of China (English)

    潘兆君; 黄伟佳; 瞿虎; 邹自灏; 高兴成

    2010-01-01

    Objective To detect the expression of metastasis- associated protein 1 (MTA- 1) and Ezrin in bladder urothelial carcinoma (BUC) and normal bladder mucosa, and to investigate their correlation with clinical pathology and prognosis. Methods The expression of MTA- 1 and Ezrin proteins was detected in 65 specimens of surgically resected BUC tissue and 30 of normal bladder mucosa with immunohistochemistry. The correlation of MTA- 1 and Ezrin expressions in BUC with clinicopathological parameters, the correlation between MTA-1 and Ezrin protein expressions and their effects on prognosis were also analyzed. Results In 65 specimens of BUC tissue, the positive rates of MTA- 1 and Ezrin expression were 72.3% (n=47) and 89.2% (n=58) , respectively, in contrast to 0% for both MTA- 1 and Ezrin expressions in 30 specimens of normal bladder mucosa, which reached the level of statistical difference (all P<0.01). The expression of MTA- 1 in BUC tissue was closely related to the clinical stages, tumor pathological grading, metastasis and recurrence (all P<0.01 ) , while the expression of Ezrin was closely related to the clinical stages, metastasis and recurrence (all P<0.01 ), and the expression of MTA-1 was positively correlated with Ezrin expression (r=0.742, P<0.01 ). The disease free survival (DFS) in patients with combined expression was significantly lower than that in those with negative expression of MTA- 1 and Ezrin (P<0.01). Conclusion The high expression of MTA-1 and Ezrin is related to the occurrence,progression, as well as invasion and metastasis of BUC.%目的 检测转移相关蛋白1(MTA-1)、埃兹蛋白(Ezrin)在膀胱尿路上皮癌(BUC)组织及正常膀胱黏膜组织中的表达,探讨两者与患者临床病理及预后之间的关系.方法 采用免疫组化法检测65例手术切除的BUC组织和30例正常膀胱黏膜组织中MTA-1和Ezrin蛋白表达,分析MTA-1和Ezrin在BUC中的表达与患者临床病理参数的关系,分析MTA-1和Ezrin

  6. The Role of Structural Extracellular Matrix Proteins in Urothelial Bladder Cancer

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    Andrea Brunner

    2007-01-01

    Full Text Available The extracellular matrix (ECM plays a key role in the modulation of cancer cell invasion. In urothelial carcinoma of the bladder (UC the role of ECM proteins has been widely studied. The mechanisms, which are involved in the development of invasion, progression and generalization, are complex, depending on the interaction of ECM proteins with each other as well as with cancer cells. The following review will focus on the pathogenetic role and prognostic value of structural proteins, such as laminins, collagens, fi bronectin (FN, tenascin (Tn-C and thrombospondin 1 (TSP1 in UC. In addition, the role of integrins mediating the interaction of ECM molecules and cancer cells will be addressed, since integrin-mediated FN, Tn-C and TSP1 interactions seem to play an important role during tumor cell invasion and angiogenesis.

  7. High expression of KPNA2 defines poor prognosis in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy

    International Nuclear Information System (INIS)

    To analyze the expression of karyopherin alpha 2 (KPNA2) in upper tract urothelial carcinoma (UTUC) and to investigate whether the KPNA2 expression provides additional prognostic information following radical nephroureterectomy (RNU). A tissue microarray (TMA) containing samples from 176 patients with UTUC who underwent RNU at our institute was analyzed for KPNA2 expression using immunohistochemistry. KPNA2 expression in normal urothelial cell line and urothelial carcinoma cell lines was evaluated by western blot analysis. Using RNA interference in vitro, the effects of KPNA2 inhibition on cellular viability, migration and apoptosis were determined. KPNA2 expression was significantly upregulated in the UTUC samples compared with the adjacent normal urothelial tissues. High KPNA2 immunoreactivity was identified as a predictor of bladder recurrence (hazard ratio [HR]: 2.017, 95% CI 1.13-3.61, p = 0.018), poor disease-free survival (DFS, HR: 2.754, 95% CI 1.68-4.51, p = 0.001) and poor overall survival (OS, HR: 4.480, 95% CI 1.84-10.89, p = 0.001) for patients with UTUC after RNU. Furthermore, high KPNA2 immunoreactivity was independent of the conventional predictive factors in a multivariate analysis. Additional in vitro experiments revealed that KPNA2 expression was higher in urothelial carcinoma cell lines than in normal urothelial cell line. KPNA2 inhibition with a specific siRNA decreased cell viability and migration and increased apoptosis in urothelial carcinoma cell lines. KPNA2 is a novel independent prognostic marker for bladder recurrence, DFS and OS of UTUC patients who have undergone RNU. Moreover, these data suggest that KPNA2 may be a promising therapeutic target for UTUC

  8. A Small-Molecule Inhibitor of PIM Kinases as a Potential Treatment for Urothelial Carcinomas

    Directory of Open Access Journals (Sweden)

    Jason M. Foulks

    2014-05-01

    Full Text Available The proto-oncogene proviral integration site for moloney murine leukemia virus (PIM kinases (PIM-1, PIM-2, and PIM-3 are serine/threonine kinases that are involved in a number of signaling pathways important to cancer cells. PIM kinases act in downstream effector functions as inhibitors of apoptosis and as positive regulators of G1-S phase progression through the cell cycle. PIM kinases are upregulated in multiple cancer indications, including lymphoma, leukemia, multiple myeloma, and prostate, gastric, and head and neck cancers. Overexpression of one or more PIM family members in patient tumors frequently correlates with poor prognosis. The aim of this investigation was to evaluate PIM expression in low- and high-grade urothelial carcinoma and to assess the role PIM function in disease progression and their potential to serve as molecular targets for therapy. One hundred thirty-seven cases of urothelial carcinoma were included in this study of surgical biopsy and resection specimens. High levels of expression of all three PIM family members were observed in both noninvasive and invasive urothelial carcinomas. The second-generation PIM inhibitor, TP-3654, displays submicromolar activity in pharmacodynamic biomarker modulation, cell proliferation studies, and colony formation assays using the UM-UC-3 bladder cancer cell line. TP-3654 displays favorable human ether-à-go-go-related gene and cytochrome P450 inhibition profiles compared with the first-generation PIM inhibitor, SGI-1776, and exhibits oral bioavailability. In vivo xenograft studies using a bladder cancer cell line show that PIM kinase inhibition can reduce tumor growth, suggesting that PIM kinase inhibitors may be active in human urothelial carcinomas.

  9. Metastatic Prostate Cancer to the Urethra Masquerading as Urothelial Carcinoma

    OpenAIRE

    Ibrahim Zardawi; Peter Chong

    2016-01-01

    Tumors of the urethra, whether primary or metastatic, are very rare. The true nature of urethral neoplasm is not always obvious clinically nor in routine histological sections. Immunostains should be performed on such lesions because of management implications. We present a case of multiple metastases to the urethra from a prostatic carcinoma, masquerading as multiple urothelial carcinomas. Pathologists and urologists should be aware of the possibility of metastasis from the prostate.

  10. The prognostic value of pretreatment of systemic inflammatory responses in patients with urothelial carcinoma undergoing radical cystectomy

    OpenAIRE

    Ku, J H; Kang, M.; Kim, H S; Jeong, C. W.; Kwak, C; H.H. Kim

    2015-01-01

    Background: Systemic inflammatory response (SIR) is important in the relationship between the tumour, the host, and outcome in cancer patients. However, limited data exist regarding the prognostic significance of SIR in bladder cancer. We investigate the utility of pretreatment SIR in patients with urothelial carcinoma undergoing radical cystectomy. Methods: The study cohort consisted of 419 patients with a median follow-up of 37.7 months. The SIRs used for each described prognostic nomogram ...

  11. Unique Case Report of Pineal Gland Metastasis From Bladder Carcinoma.

    Science.gov (United States)

    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. PMID:27149501

  12. Clinical Application of {sup 18}F-FDG PET in Urothelial Carcinoma, Vulva and Vaginal Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Pai, Moon Sun [Kwandong University College of Medicine, Koyang (Korea, Republic of)

    2008-12-15

    Clinical experience on FDG PET in urothelial tumors, vulva and vaginal carcinoma is still limited. The main interest of this review is to study a bibliographic review and applications of PET for urothelial tumors, vulva and vaginal carcinoma. The role of positron emission tomography (PET) is still evolving but is likely to be most important in determining early spread of disease in patients with aggressive tumors and for monitoring response to therapy. More extensive clinical investigations are necessary to support this indications.

  13. Clinical Application of 18F-FDG PET in Urothelial Carcinoma, Vulva and Vaginal Carcinoma

    International Nuclear Information System (INIS)

    Clinical experience on FDG PET in urothelial tumors, vulva and vaginal carcinoma is still limited. The main interest of this review is to study a bibliographic review and applications of PET for urothelial tumors, vulva and vaginal carcinoma. The role of positron emission tomography (PET) is still evolving but is likely to be most important in determining early spread of disease in patients with aggressive tumors and for monitoring response to therapy. More extensive clinical investigations are necessary to support this indications

  14. [Urothelial carcinoma related to exposure to aromatic amines].

    Science.gov (United States)

    Naito, S; Kumazawa, J

    1989-12-01

    Clinical and statistical observations were made on a group of 438 persons who had worked with aromatic amines (benzidine, 2-naphthylamine, 1-naphthylamine and dianisidine) with reference to their carcinogenic properties in the urinary tract. Urinary tract tumors developed in 68 (15.5%), with an average latent period of 22 years and 11 months. In these 68 cases, upper urinary tract tumors were found in 16 cases, 8 of which had bilateral lesions. The average age of onset was 48.1 ranging from 24 to 79. The incidence of tumors increased with the length of exposure to the amines. There was no finding that smoking habit increased the incidence of tumors in this group. Of the 49 new patients with bladder tumor, urine cytology was positive in 24 (49.0%) and suspicious of malignancy in 10 (20.4%), respectively. This indicated that it could be a useful screening test. Transurethral surgery was most frequently performed as an initial treatment. Recurrence occurred in 50 cases (73.5%), but 5-, 10- and 20-year-survival rates were 89.0 79.3 and 64.7%, respectively, showing a good prognosis. Malignant tumors in other organs developed in 18 (4.1%) of the 438 workers. The incidence of such malignant tumors was significantly higher in the workers who had been exposed to 2-naphthylamine than in others. Our data indicate that close observation is still necessary for early detection of patient with new or recurrent urothelial carcinoma in this group. PMID:2618901

  15. Upper Tract Urothelial Carcinomas in Patients with Chronic Kidney Disease: Relationship with Diagnostic Challenge

    OpenAIRE

    Li-Jen Wang; Shen-Yang Lee; Bin Tean Teh; Cheng-Keng Chuang; Joëlle Nortier

    2014-01-01

    Chronic kidney disease and upper tract urothelial carcinomas display a bidirectional relationship. Review of the literature indicates that early diagnosis and correct localization of upper tract urothelial carcinomas in dialysis patients and kidney transplant recipients are important but problematic. Urine cytology and cystoscopy have limited sensitivity for the diagnosis of upper tract urothelial carcinomas in dialysis patients. Enhanced computed tomography and magnetic resonance imaging cou...

  16. Molecular markers for urothelial bladder cancer prognosis: Toward implementation in clinical practice

    NARCIS (Netherlands)

    Rhijn, B.W. van; Catto, J.W.; Goebell, P.J.; Knuchel, R.; Shariat, S.F.; Poel, H.G. van der; Sanchez-Carbayo, M.; Thalmann, G.N.; Schmitz-Drager, B.J.; Kiemeney, L.A.L.M.

    2014-01-01

    OBJECTIVES: To summarize the current status of clinicopathological and molecular markers for the prediction of recurrence or progression or both in non-muscle-invasive and survival in muscle-invasive urothelial bladder cancer, to address the reproducibility of pathology and molecular markers, and to

  17. Optimizing oncologic outcomes in upper tract urothelial carcinoma.

    Science.gov (United States)

    Hutchinson, Ryan C; Margulis, Vitaly

    2016-08-01

    Upper tract urothelial carcinoma is a disease with rapidly changing management. Though rare, recent multi-institutional collaborations have allowed for study of its biology and treatment outcomes in greater detail than ever before. In coming years physicians treating ureteral cancers will have an expanded armamentarium of treatment options and better data on which to base treatment decisions. Currently there is exciting work underway both in terms of developmental therapies, including neoadjuvant chemotherapy, as well as improved prognostics allowing for better utilization of nephron-sparing approaches where applicable. We present a review of current management techniques and the data on which to base management choices for surgeons treating upper tract urothelial carcinoma. The ultimate goal is improving outcomes for patients; with recent developments and current work in the field, there is reason to be optimistic for the future in this rare, challenging disease. PMID:26756501

  18. Metastatic Transitional Cell Carcinoma of the Bladder to the Testis: A Case Report

    Directory of Open Access Journals (Sweden)

    Gregory N. Kozak

    2012-01-01

    Full Text Available An 84-year-old gentleman presented with onset of gross hematuria in September 2010. Follow-up investigations revealed T1 superficially invasive, poorly differentiated, papillary urothelial carcinoma. He subsequently had GreenLight laser for BPH and bladder neck contracture on two occasions. He developed a right hydrocele 16 months after initial presentation and during his hydrocelectomy, a rock-hard right epididymis and testicle were discovered. Pathology revealed metastatic urothelial carcinoma replacing nearly the entire testis with lymphovascular invasion.

  19. Expression of thymidylate synthase in bladder urothelial carcinoma and its prognostic value%胸苷酸合成酶在膀胱尿路上皮癌中的表达及预后价值

    Institute of Scientific and Technical Information of China (English)

    赵伟; 孙茸; 赵守国; 赵南

    2011-01-01

    目的 探讨胸苷酸合成酶(TS)在膀胱尿路上皮癌(BUC)的表达情况及临床意义,评价TS预后价值,为肿瘤预后判断及治疗方案的选择提供帮助.方法 采用免疫组织化学染色(SP法)的方法检测54例BUC组织及15例正常膀胱组织的TS表达,通过回顾性随访,了解患者术后情况.以TS表达水平、临床病理变量及两个预后变量[无复发生存率(RFS)和总生存率(OS)]作为研究对象,探讨它们之间的关系,绘制生存曲线,进行Cox回归分析.结果 54例肿瘤标本中TS高表达率为46.30%(25/54),其中G1级为29.41%(5/17),G2级为46.43%(13/28),G3级为77.78%(7/9);Ta期为21.43%(3/14),T1期为26.32%(5/19),T2期为86.67%(13/15),T3期为66.67%(2/3),T4期为66.67%(2/3);TS表达水平与肿瘤分级、分期呈正相关(Kruskal-Wallis H,P=0.03,P<0.001).TS高表达患者术后复发率、病死率分别为60.00%(15/25)和44.00%(11/25),经生存分析和Cox回归分析,肿瘤的TS表达水平是术后复发(RR为2.65,95%CI 0.80~8.81,P<0.05)、死亡(RR为1.42,95%CI0.36~5.58,P<0.05)的独立预后因素.结论 随着TS表达水平升高,BUC发生恶性进展和复发的概率增加,测定其表达水平有助于选择恰当的治疗和随访方案.%Objective To investigate the expression of thymidylate synthase (TS) in bladder urothelial carcinoma(BUC) and its clinical significance, and to evaluate its prognostic value, thus to help predict the prognosis and choose therapy protocal. Methods The expression of TS was assessed by immunohistochemistry in 54 BUC and 15 normal bladder specimens, and all these clinical data were retrospectively analyzed after surgery. Expression of TS,clinicopathologic findings and two prognostic variances (relapse-free survival (RFS) and overall survival (OS)) were determined. The prognostic value of TS was estimated by survival curve and Cox proportional hazards model. Results Immunohistochemistry showed that 25 of 54 BUC cases (46. 30%) had high TS

  20. Transcriptional profiling of the bladder in urogenital schistosomiasis reveals pathways of inflammatory fibrosis and urothelial compromise.

    Directory of Open Access Journals (Sweden)

    Debalina Ray

    Full Text Available Urogenital schistosomiasis, chronic infection by Schistosoma haematobium, affects 112 million people worldwide. S. haematobium worm oviposition in the bladder wall leads to granulomatous inflammation, fibrosis, and egg expulsion into the urine. Despite the global impact of urogenital schistosomiasis, basic understanding of the associated pathologic mechanisms has been incomplete due to the lack of suitable animal models. We leveraged our recently developed mouse model of urogenital schistosomiasis to perform the first-ever profiling of the early molecular events that occur in the bladder in response to the introduction of S. haematobium eggs. Microarray analysis of bladders revealed rapid, differential transcription of large numbers of genes, peaking three weeks post-egg administration. Many differentially transcribed genes were related to the canonical Type 2 anti-schistosomal immune response, as reflected by the development of egg-based bladder granulomata. Numerous collagen and metalloproteinase genes were differentially transcribed over time, revealing complex remodeling and fibrosis of the bladder that was confirmed by Masson's Trichrome staining. Multiple genes implicated in carcinogenesis pathways, including vascular endothelial growth factor-, oncogene-, and mammary tumor-related genes, were differentially transcribed in egg-injected bladders. Surprisingly, junctional adhesion molecule, claudin and uroplakin genes, key components for maintaining the urothelial barrier, were globally suppressed after bladder exposure to eggs. This occurred in the setting of urothelial hyperplasia and egg shedding in urine. Thus, S. haematobium egg expulsion is associated with intricate modulation of the urothelial barrier on the cellular and molecular level. Taken together, our findings have important implications for understanding host-parasite interactions and carcinogenesis in urogenital schistosomiasis, and may provide clues for novel therapeutic

  1. miR-145 induces caspase-dependent and -independent cell death in urothelial cancer cell lines with targeting of an expression signature present in Ta bladder tumors

    DEFF Research Database (Denmark)

    Ostenfeld, Marie Stampe; Bramsen, Jesper Bertram; Lamy, Philippe;

    2010-01-01

    Downregulation of miR-145 in a variety of cancers suggests a possible tumor suppressor function for this microRNA. Here, we show that miR-145 expression is reduced in bladder cancer and urothelial carcinoma in situ, compared with normal urothelium, using transcription profiling and in situ...... hybridization. Ectopic expression of miR-145 induced extensive apoptosis in urothelial carcinoma cell lines (T24 and SW780) as characterized by caspase activation, nuclear condensation and fragmentation, cellular shrinkage, and detachment. However, cell death also proceeded upon caspase inhibition by the...... pharmacological inhibitor zVAD-fmk and ectopic expression of anti-apoptotic Bcl-2, indicating the activation of an alternative caspase-independent death pathway. Microarray analysis of transcript levels in T24 cells, before the onset of cell death, showed destabilization of mRNAs enriched for miR-145 7mer target...

  2. Application of urinary proteomics in early diagnosis of bladder urothelial carcinoma%尿液蛋白质组学在膀胱尿路上皮癌早期诊断中的应用

    Institute of Scientific and Technical Information of China (English)

    李宏杰; 李常颖; 张婷; 王世鑫; 畅继武; 蒋守芳; 章广玲; 李建民

    2013-01-01

    Objective To investigate the difference in urinary proteome between patients with bladder urothelial carcinoma (BUC) and healthy volunteers and to provide a basis for the early diagnosis of BUC.Methods The urine samples from BUC patients and healthy volunteers (controls) were treated by 25%ethanol precipitation and two-dimensional gel electrophoresis (2-DE),and the obtained urinary proteins were subjected to Coomassie brilliant blue staining and analysis by PDQuest 8.0 (2-DE image analysis software); the differentially expressed proteins were sequenced by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry and identified using the Swiss-Prot database; the differential expression of these proteins was verified by western blot.Results High-resolution and high-reproducibility 2-DE images were obtained from the urine samples of BUC patients and controls,with 789 ±18 and 762 ±14 protein spots,respectively.Compared with the control group,the BUC grouPhad significantly decreased expression of 6 protein spots and significantly increased expression of 11 protein spots.The mass spectrometry revealed five proteins with increased expression in the BUC group,including fibrinogen,lactate dehydrogenase B,apolipoprotein A1,clusterin,and haptoglobin,and the results were confirmed by western blot.Conclusion There is significant difference in urinary proteome between BUC patients and healthy volunteers; the identification of differentially expressed proteins in urine lays the foundation for identifying potential molecular markers in early diagnosis of BUC.%目的 寻找膀胱尿路上皮癌(BUC)患者与健康志愿者尿液蛋白质组学差异,为BUC的早期诊断奠定基础.方法 采用25%乙醇沉淀法制备尿液双向电泳样品,尿液蛋白经双向凝胶电泳(2-DE)分离后行考马斯亮蓝染色,利用PDQuest8.0 2D凝胶图像分析软件进行分析,所得差异蛋白点用基质辅助激光解吸电离飞行时间串联

  3. Compensatory Paracrine Mechanisms That Define The Urothelial Response to Injury in Partial Bladder Outlet Obstruction

    Energy Technology Data Exchange (ETDEWEB)

    Bassuk, James; Lendvay, Thomas S.; Sweet, Robert; Han, Chang-Hee; Soygur, Tarkan; Cheng, Jan-Fang; Plaire, J. Chadwick; Charleston, Jay S.; Charleston, Lynne B.; Bagai, Shelly; Cochrane, Kimberly; Rubio, Eric; Bassuk, James A.; Fuchs, Elaine

    2007-06-21

    Diseases and conditions affecting the lower urinary tract are a leading cause of dysfunctional sexual health, incontinence, infection, and kidney failure. The growth, differentiation, and repair of the bladder's epithelial lining are regulated, in part, by fibroblast growth factor (FGF)-7 and -10 via a paracrine cascade originating in the mesenchyme (lamina propria) and targeting the receptor for FGF-7 and -10 within the transitional epithelium (urothelium). The FGF-7 gene is located at the 15q15-q21.1 locus on chromosome 15 and four exons generate a 3.852-kb mRNA. Five duplicated FGF-7 gene sequences that localized to chromosome 9 were predicted not to generate functional protein products, thus validating the use of FGF-7-null mice as an experimental model. Recombinant FGF-7 and -10 induced proliferation of human urothelial cells in vitro and transitional epithelium of wild-type and FGF-7-null mice in vivo.To determine the extent that induction of urothelial cell proliferation during the bladder response to injury is dependent on FGF-7, an animal model of partial bladder outlet obstruction was developed. Unbiased stereology was used to measure the percentage of proliferating urothelial cells between obstructed groups of wild-type and FGF-7-null mice. The stereological analysis indicated that a statistical significant difference did not exist between the two groups, suggesting that FGF-7 is not essential for urothelial cell proliferation in response to partial outlet obstruction. In contrast, a significant increase in FGF-10 expression was observed in the obstructed FGF-7-null group, indicating that the compensatory pathway that functions in this model results in urothelial repair.

  4. Urothelial carcinoma with an inverted growth pattern can be distinguished from inverted papilloma by fluorescence in situ hybridization, immunohistochemistry, and morphologic analysis.

    Science.gov (United States)

    Jones, Timothy D; Zhang, Shaobo; Lopez-Beltran, Antonio; Eble, John N; Sung, Ming-Tse; MacLennan, Gregory T; Montironi, Rodolfo; Tan, Puay-Hoon; Zheng, Suqin; Baldridge, Lee Ann; Cheng, Liang

    2007-12-01

    Inverted papilloma of the urinary bladder and urothelial carcinoma with an inverted (endophytic) growth pattern may be difficult to distinguish histologically, especially in small biopsies. The distinction is important as these lesions have very different biologic behaviors and are treated differently. We examined histologic features and undertook immunohistochemical staining and UroVysion fluorescence in situ hybridization (FISH) to determine whether these methods could aid in making this distinction. We examined histologic sections from 15 inverted papillomas and 29 urothelial carcinomas with an inverted growth pattern. Each tumor was stained with antibodies to Ki-67, p53, and cytokeratin 20. In addition, each tumor was examined with UroVysion FISH for gains of chromosomes 3, 7, and 17 and for loss of chromosome 9p21 signals. None of the inverted papillomas stained positively for Ki-67 or for cytokeratin 20. Only 1 of 15 inverted papillomas stained positively for p53. By contrast, 66%, 59%, and 59% of urothelial carcinomas with an inverted growth pattern stained positively for Ki-67, p53, and cytokeratin 20, respectively. Only 3 of the urothelial carcinomas stained negatively for all 3 immunohistochemical markers. UroVysion FISH produced normal results for all cases of inverted papilloma. By contrast, 21 of 29 cases (72%) of urothelial carcinoma with an inverted growth pattern demonstrated chromosomal abnormalities typical of urothelial cancer and were considered positive by UroVysion FISH criteria. Morphologic features, as well as immunohistochemical stains (including stains for Ki-67, p53, and cytokeratin 20) and/or UroVysion FISH can help to distinguish inverted papilloma from urothelial carcinoma with an inverted growth pattern. PMID:18043040

  5. Upper tract urothelial carcinoma: epidemiology, high risk populations and detection.

    Science.gov (United States)

    Redrow, Grant P; Matin, Surena F

    2016-08-01

    Upper tract urothelial carcinoma (UTUC) is a rare but highly morbid genitourinary malignancy. In 2014 approximately 15,000 new cases were diagnosed in the United States. It accounts for approximately 5-10% of all urothelial cell carcinomas, and 10% of renal tumors. Recent research has increased understanding of the epidemiology of this disease, including several high-risk populations. Environmental exposure to tobacco as well as aristolochic acid, and other carcinogens significantly increase the development of UTUC. Additionally, the genetic condition of hereditary nonpolyposis colorectal carcinoma (HNPCC), also known as Lynch Syndrome (LS) is linked to development of UTUC. Advances in imaging, ureteroscopy, cytological techniques and pathological recognition have allowed for improved detection of primary tumors and recurrent disease. Non-invasive imaging with computed tomography (CT) and magnetic resonance imaging (MRI) now represent the gold standard in imaging detection and surveillance, while technological advances in ureteroscopy allow for minimally invasive approaches to obtain pathologic diagnosis anywhere within the upper tracts. This review will highlight these recent improvements to allow better understanding of who is affected by this rare and morbid disease, as well as the latest developments in detection and surveillance. PMID:27008468

  6. Renal Embolization and Urothelial Sclerotherapy for Recurrent Obstructive Urosepsis and Intractable Haematuria from Upper Tract Urothelial Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Nicholas, E-mail: nibrown@cantab.net [St Vincent’s Hospital, Department of Interventional Radiology (Australia); Olayos, Elizabeth; Elmer, Sandra; Wong, Lih-Ming [St Vincent’s Hospital, Department of Urology (Australia); Brooks, Duncan M; Jhamb, Ashu [St Vincent’s Hospital, Department of Interventional Radiology (Australia)

    2016-03-15

    Management of intractable haematuria and obstructive urosepsis from upper tract urothelial carcinoma can be problematic in patients not suitable for surgery, chemotherapy or radiotherapy. Interventional radiology techniques provide alternative approaches in this setting, such as complete kidney embolization to cease urine output, percutaneous nephrostomy, antegrade injection of sclerotherapy agents and sterilisation of the upper collecting system. Related approaches have been successfully employed to sclerose renal cysts, lymphoceles, chyluria and intractable lower tract haemorrhage. No reports of percutaneous, antegrade sclerotherapy in the upper urinary tract have previously been published. We present a case of recurrent haematuria and obstructive urosepsis caused by invasive upper tract urothelial carcinoma in a non-operative patient, which was treated with renal embolisation and percutaneous upper tract urothelial sclerotherapy.

  7. Urine cytology of micropapillary carcinoma of the urinary bladder.

    Science.gov (United States)

    Sakuma, Takahiko; Furuta, Michiko; Mimura, Akihiro; Tanigawa, Naoto; Takamizu, Ryuichi; Kawano, Kiyoshi

    2011-11-01

    A case of micropapillary carcinoma (MPC) of urinary bladder is presented, in which the urine smear was studied in detail in an attempt to better characterize the cytologic findings of MPC. When the voided urine was examined in low power, cancer cells were scattered in the specimens as compact papillary/spheroidal clusters composed of pleomorphic cancer cells. Solitary carcinoma cells were occasionally observed. High power view of the smear revealed that the papillae/spheroids consisted of high-grade urothelial carcinoma cells. The cancer cells had pleomorphic nuclei with coarsely granular chromatin and thickened, irregular nuclear membrane, and thick cytoplasm. Histologically, the tumor in the resected bladder appeared as small nests with surrounding hallo both in the luminal surface and in the site of wall involvement. These tightly bound papillary/spheroidal clusters comprised of highly atypical cancer cells were the most specific cytologic finding in the urine of MPC, which were considered as a key diagnostic clue of MPC. The background of the urine smear showed numerous granulocytes and bacilli compatible with cystitis, which is a previously known complication of MPC. Differential diagnoses of MPC from those with pertinent cytologic findings such as conventional UC (including glandular differentiation), and primary/secondary adenocarcinoma of urinary bladder are discussed with a brief review of literature.

  8. Bladder cancer cell in co-culture induces human stem cell differentiation to urothelial cells through paracrine FGF10 signaling

    OpenAIRE

    Chung, Seyung S.; Koh, Chester J.

    2013-01-01

    FGF10 is required for embryonic epidermal morphogenesis including brain development, lung morphogenesis, and initiation of limb bud formation. In this study, we investigated the role of FGF10 as a lead induction factor for stem cell differentiation toward urothelial cell. To this end, human multi-potent stem cell in vitro system was employed. Human amniotic fluid stem cells were co-cultured with immortalized bladder cancer lines to induce directed differentiation into urothelial cells. Urothe...

  9. Does subdivision of the "atypical" urine cytology increase predictive accuracy for urothelial carcinoma?

    Science.gov (United States)

    Bostwick, David G; Hossain, Deloar

    2014-12-01

    Urine cytology is routinely used for early diagnosis and monitoring of patients with hematuria or a history of urothelial carcinoma, but its clinical utility is greatly diminished by a high frequency of "atypical" specimens, reportedly around 20% in the literature. We compared our results with double-stained urine cytology specimens (papanicolaou and acid hematoxylin stains) with published results with only a single or double papanicolaou stain. The acid hematoxylin stain enhanced nuclear chromatin staining, eliminated significant background debris, and improved visibility of diagnostic cells in the presence of obscuring blood. Medical records of all urine cytologies received between 2005 and 2012 in our laboratories were reviewed. The study group consisted of all cases with bladder biopsy follow-up within one year of cytology. Of 43,131 urine cytologies diagnosed in our laboratories, biopsy follow-up results were available within one year in 10,473 cases, including 852 for symptoms and 1,461 for follow-up of bladder cancer. An additional 6,427 cases had cystoscopy results in which no biopsy was obtained. Cases were classified as negative (81.6%), atypical, favor reactive (2.9%), atypical, favor neoplastic (7.3%), suspicious (5.7%), and malignant (2.5%), with subsequent frequencies for urothelial cancer on biopsy of 13.3%, 31.1%, 37.6%, 53.6%, and 74.3%, respectively. No significant difference was found if atypical was subdivided into two categories: favor reactive and favor neoplastic. Subdivision of the atypical category did not improve diagnostic accuracy. Addition of the acid hematoxylin stain decreased the incidence of atypical urine cytologies from about 20% to 10.2%. PMID:24838797

  10. Evaluation of the depth of infiltration of urothelial carcinoma in the vesical wall obtained by transurethral intravesical echotomography

    Directory of Open Access Journals (Sweden)

    Milošević Radovan

    2007-01-01

    Full Text Available Background/Aim. Transitional cell carcinoma (TCC is the most frequent tumor of the bladder and represents 95−98% of blader neoplasams and 2−3% of all carcinomas in the body. In urogenital oncology more frequent is only prostatic cancer. Evaluation of the depth of infiltration of urothelial carcinoma in the vesical wall represents the clinical base in treatment planning and prognosis. Clinical investigation and convential radiological procedures have a low level of accuracy in estimating the local growth of the tumor. The aims of our investigation were to determine the depth of infiltration of urothelial carcinoma in the vesical wall in the investigated group of patients by transurethral intravesical echotomography (TIE and computerised tomography (CT scan and to compare results obtained by both methods with pathohistological (PH results, and, based on the difference of the results determine which method was more accurate in the evaluation of the depth of infiltration of urothelial carcinoma in the vesical wall. Methods. Thirty patients with TCC of the bladder both genders, aged 51−81 years were involved in our investigation. In all of these patients, radical cystectomy (RC was performed. This was neccessary to provide the defintive PH result. Transurethral intravesical echotomography was performed by ultrasound scanner type 1846 Bruel and Kjaer, sond type 1850, and the CT scan was perfomed by Pace plus, General Electric, U.S.A. The specimen for the definitive PH result obtained by RC includes all standards of the TNM classification. Results. Using CT scan, the most frequent was T1 stage (17 patients or 56.68%. Using TIE, the most frequent was T2 stage (22 patients or 73.33%. After RC the most frequent was T2 stage (21 patients or 70%. The Kolmogorov-Smirnov test, showed a high significant difference between the results obtained using CT and definitive PH results after RC. The same test showed no statistically significant difference between

  11. Immunohistochemistry and Fluorescence In Situ Hybridization Can Inform the Differential Diagnosis of Low-Grade Noninvasive Urothelial Carcinoma with an Inverted Growth Pattern and Inverted Urothelial Papilloma

    OpenAIRE

    Juan-Juan Sun; Yong Wu; Yong-Ming Lu; Hui-Zhi Zhang; Tao Wang; Xiao-Qun Yang; Meng-Hong Sun; Chao-Fu Wang

    2015-01-01

    Urothelial carcinoma (UC) comprises a heterogeneous group of epithelial neoplasms with diverse biological behaviors and variable clinical outcomes. Distinguishing UC histological subtypes has become increasingly important because prognoses and therapy can dramatically differ among subtypes. In clinical work, overlapping morphological findings between low-grade noninvasive UC (LGNUC), which exhibits an inverted growth pattern, and inverted urothelial papilloma (IUP) can make subclassification ...

  12. Bladder Cancer and Urothelial Impairment: The Role of TRPV1 as Potential Drug Target

    Directory of Open Access Journals (Sweden)

    Francesco Mistretta

    2014-01-01

    Full Text Available Urothelium, in addition to its primary function of barrier, is now understood to act as a complex system of cell communication that exhibits specialized sensory properties in the regulation of physiological or pathological stimuli. Furthermore, it has been hypothesized that bladder inflammation and neoplastic cell growth, the two most representative pathological conditions of the lower urinary tract, may arise from a primary defective urothelial lining. Transient receptor potential vanilloid channel 1 (TRPV1, a receptor widely distributed in lower urinary tract structures and involved in the physiological micturition reflex, was described to have a pathophysiological role in inflammatory conditions and in the genesis and development of urothelial cancer. In our opinion new compounds, such as curcumin, the major component of turmeric Curcuma longa, reported to potentiate the effects of the chemotherapeutic agents used in the management of recurrent urothelial cancer in vitro and also identified as one of several compounds to own the vanillyl structure required to work like a TRPV1 agonist, could be thought as complementary in the clinical management of both the recurrences and the inflammatory effects caused by the endoscopic resection or intravesical chemotherapy administration or could be combined with adjuvant agents to potentiate their antitumoral effect.

  13. [A CASE OF ADVANCED BLADDER NEUROENDOCRINE CARCINOMA (SMALL CELL CARCINOMA) SIGNIFICANTLY IMPROVED BY LOW DOSE OF ORAL TEGAFUR-URACIL].

    Science.gov (United States)

    Nomi, Hayahito; Takahara, Kiyoshi; Minami, Koichiro; Maenosono, Ryoichi; Matsunaga, Tomohisa; Yoshikawa, Yuki; Tsujino, Takuya; Hirano, Hajime; Inamoto, Teruo; Yamamoto, Ikuhisa; Tsuji, Motomu; Kiyama, Satoshi; Azuma, Haruhito

    2015-10-01

    A 81-old-woman underwent a transurethral resection of bladder tumor (TURBT) at a nearby hospital in April 2011. The diagnosis was invasive urothelial carcinoma, G3 with a component of bladder small cell carcinoma, T1 or more. She was recommended to visit our hospital for combined modality therapy of bladder cancer, but she refused the treatment for over one year. In May 2012, she came to our hospital with the chief complaint of pain at urination. Cystoscopy revealed non-papillary sessile tumor in the top of the bladder, and CT scan demonstrated the presence of the right obturator lymph nodes swollen up to 1.2 cm in size. The second TURBT was performed and the diagnosis was bladder small cell carcinoma (pT3N2M0) according to urothelial cancer guidelines of the Japanese Urological Association (JUA). Because she strongly refused hospitalization anymore, we started daily oral intake of low dose Tegafur-Uracil (100 mg) for the treatment. After one month, the serum Neuron-Specific Enolase (NSE; tumor maker of small cell cancer) level was elevated to 27.6 ng/ml and the right obturator lymph node was enlarged up to 1.9 cm. Therefore, the Trgafur-Uracil dose was increased to 200 mg daily. After then, the serum NSE level was decreased to 15.5 ng/ml following reduction in size of the obturator lymph nodes with partial response in December 2013. After two years of follow-up period, her regular urine test showed normal findings, and no apparent recurrence was detected on urinary bladder with MRI and Cystoscopy. This is a case of advanced bladder small cell carcinoma significantly improved by oral administration of Tegafur-Uracil 200 mg/day for over 2 years. PMID:26717786

  14. Triple cancer: chronic lymphocytic leukemia with bladder and prostate carcinoma.

    Science.gov (United States)

    Gajendra, Smeeta; Sharma, Rashi; Sahoo, Manas Kumar

    2015-08-01

    B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a common lymphoproliferative disorder with an increased risk of developing subsequent neoplasms of epithelial and mesenchymal origin. The decreased immunity and B-cell dysfunction in CLL probably accounts for this emergence of second malignancies. We report a case of synchronous bladder transitional cell carcinoma (TCC) and prostatic carcinoma with CLL. A 74-year-old male who underwent transurethral resection of the prostate (TURP) for benign prostatic hyperplasia 2 years before, presented with recurrent urinary tract infection. Peripheral blood smear revealed leukocytosis with absolute lymphocytosis (absolute lymphocyte count: 37870 cells/mm³). Flow cytometric immunophenotyping revealed 75% abnormal lymphoid cells which were positive for CD 19, CD5, CD23, CD22, CD200, CD20 (moderate) with lambda light chain restriction and negative for CD3, CD10, FMC7, CD38, CD138, IgM, CD103, CD123. F Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) showed increased metabolic activity of the left lateral wall of the urinary bladder extending to the left UV junction, adjacent part of trigone and bladder neck region along with multiple heterogeneous enhancing areas with increased FDG avidity within the prostate. Transurethral resection of the bladder tumour by cystoscopy was performed. Histopathology showed high grade, muscle invasive urothelial carcinoma. Due to presence of uptake in the prostate, transurethral resection of the prostate was done and histopathology revealed adenocarcinoma of prostate (prostate specific antigen- positive), Gleason grade III+III and Gleason score 6. A high index of suspicion is required to detect synchronous and metachronous malignancies. Ancillary studies such as immunohistochemistry, flow cytometry and PET/CT are often essential for detection and an accurate diagnosis. PMID:26277675

  15. The genetic difference between Western and Chinese urothelial cell carcinomas: infrequent FGFR3 mutation in Han Chinese patients

    Science.gov (United States)

    Liu, Li; Liu, Tiantian; Ge, Nan; Kong, Feng; Yang, Liu; Björkholm, Magnus; Fan, Yidong; Zhao, Shengtian; Xu, Dawei

    2016-01-01

    Urothelial cell carcinoma (UCC) includes urothelial bladder carcinoma (UBC), renal pelvic carcinoma (RPC) and ureter carcinoma (UC), and its incidence varies dependent on geographical areas and tumor locations, which indicates different oncogenic mechanisms and/or different genetic susceptibility/environment exposure. The activating mutations of the fibroblast growth factor receptor 3 (FGFR3) gene and telomerase reverse transcriptase (TERT) promoter are the most frequent genetic events in UCCs. These mutations have clinical utilities in UCC initial diagnostics, prognosis, recurrence monitoring and management. However, the vast majority of the results are obtained from studies of UCC patients in Western countries, and little has been known about these in Han Chinese patients. In the present study, we screened the FGFR3 gene and TERT promoter for mutations in 116 UBC, 91 RPC and 115 UC tumors from Han Chinese patients by using Sanger Sequencing. TERT promoter mutations occurred at a high frequency in these UCC patients, comparable with that seen in Western patients, however, the FGFR3 mutation was surprisingly lower, only 9.4% for UBCs, 8.8% for RPCs and 2.6% for UCs, respectively. Taken together, the FGFR3 gene is an infrequent target in the pathogenesis of Han Chinese UCCs, and its mutation detection and targeted therapy have limited clinical utility in these patients. Our results underscore the need for extensive characterization of cancer genomes from diverse patient populations, thereby contributing to precision medicine for cancer treatment and prevention. PMID:27029078

  16. The genetic difference between Western and Chinese urothelial cell carcinomas: infrequent FGFR3 mutation in Han Chinese patients.

    Science.gov (United States)

    Yuan, Xiaotian; Liu, Cheng; Wang, Kun; Liu, Li; Liu, Tiantian; Ge, Nan; Kong, Feng; Yang, Liu; Björkholm, Magnus; Fan, Yidong; Zhao, Shengtian; Xu, Dawei

    2016-05-01

    Urothelial cell carcinoma (UCC) includes urothelial bladder carcinoma (UBC), renal pelvic carcinoma (RPC) and ureter carcinoma (UC), and its incidence varies dependent on geographical areas and tumor locations, which indicates different oncogenic mechanisms and/or different genetic susceptibility/environment exposure. The activating mutations of the fibroblast growth factor receptor 3 (FGFR3) gene and telomerase reverse transcriptase (TERT) promoter are the most frequent genetic events in UCCs. These mutations have clinical utilities in UCC initial diagnostics, prognosis, recurrence monitoring and management. However, the vast majority of the results are obtained from studies of UCC patients in Western countries, and little has been known about these in Han Chinese patients. In the present study, we screened the FGFR3 gene and TERT promoter for mutations in 116 UBC, 91 RPC and 115 UC tumors from Han Chinese patients by using Sanger Sequencing. TERT promoter mutations occurred at a high frequency in these UCC patients, comparable with that seen in Western patients, however, the FGFR3 mutation was surprisingly lower, only 9.4% for UBCs, 8.8% for RPCs and 2.6% for UCs, respectively. Taken together, the FGFR3 gene is an infrequent target in the pathogenesis of Han Chinese UCCs, and its mutation detection and targeted therapy have limited clinical utility in these patients. Our results underscore the need for extensive characterization of cancer genomes from diverse patient populations, thereby contributing to precision medicine for cancer treatment and prevention.

  17. Skeletal Muscle Metastases to the Flexor Digitorum Superficialis and Profundus from Urothelial Cell Carcinoma and Review of the Literature.

    Science.gov (United States)

    Guidi, Marco; Fusetti, Cesare; Lucchina, Stefano

    2016-01-01

    Urothelial cell carcinoma (UCC) metastases to skeletal muscle are extremely rare and usually found in patients with advanced stage cancer. The most common sites of bladder cancer metastases are lymph nodes, lung, liver, and bones. Muscle is an unusual site of metastases from a distant primary cancer, due to several protective factors. We present a rare case of 76-year-old patient with metastases in the flexor digitorum superficialis (FDS) and flexor digitorum profundus (FDP) muscles, 2 years after a radical cystectomy for invasive UCC of the bladder. This case is the first description of a forearm lesion, with an extensive infiltration of the volar compartments of the forearm, and the first one with a clear functional impairment. PMID:27648338

  18. Hematuria in a 12-year-old child, a rare case of urothelial papilloma of the urinary bladder

    OpenAIRE

    Alexis Litchinko; Blaise Julien Meyrat; Antoine Nobile; Lara Raffoul; Gezim Dushi; Vanina Estremadoyro

    2016-01-01

    We describe a case of a 12-year-old boy with an isolated macroscopic hematuria. A urinary ultrasound revealed a bladder tumor next to the right ureteric orifice. A biopsy revealed a urothelial papilloma. He underwent a successful resection by cystostomy. This benign tumor is extremely rare in children and its management remains controversial.

  19. The significance of loss of 3q26. 1 small fragment in urothelial carcinoma of th bladder%膀胱癌组织中染色体3q26.1小片段高频率缺失及其意义

    Institute of Scientific and Technical Information of China (English)

    郑阳; 寿建忠; 蔡雄伟; 郑闪; 刘宇; 毕新刚; 柏景乔; 高燕宁

    2011-01-01

    Objective To investigate the copy number changes on chromosome 3q26. 1 in urothelial carcinoma of the bladder, and to explore its potential clinical significance. Methods The microarray-based comparative genomic hybridization (Array-CGH) approach was used to analyze the genome-wide copy number changes of 35 tumor tissue samples of bladder cancer. To confirm the loss of a small fragment in 3q26. 1 detected by Array-CGH, real-time fluorescent quantitative polymerase chain reaction (real-time PCR) was performed with 57 frozen tumor tissue samples and 34 formalinfixed paraffin-embedded (FFPE) tumor tissue samples. The urine sediment cells collected from 15 healthy volunteers and 29 bladder cancer patients were checked as above. Results The Array-CGH data showed that the copy number loss of a small fragment in 3q26. 1 was detected in 77.1% (27/35)of the tumor tissue samples investigated. Real-time PCR analysis validated this loss of a small fragment of 3q26.1 with high frequencies in both 57 frozen tumor samples and 34 FFPE tumor samples.The percentage of samples exhibiting loss was 78.9% (45/57) and 100. 0% (34/34) respectively.Furthermore, the relative copy number of the 3q26.1 small fragment was significantly lower in the urinary sediment cells of the patients (median=0. 0020), comparing with that of healthy controls (median=0. 0030) (P<0.01). Conclusions Loss of the small fragment in 3q26.1 could be a characteristic genetic change of urothelial carcinoma of the bladder. It may serve as a potential molecular marker for bladder cancer.%目的 探讨人膀胱尿路上皮癌组织中染色体3q26.1小片段拷贝数改变及其临床意义.方法 采用微阵列比较基因组杂交(array comparative genomic hybridization,Array-CGH)技术分析35例膀胱癌组织(Ta~T118例,T2~T417例)基因组DNA(区段/基因)拷贝数改变.采用实时荧光定量PCR验证57例冻存膀胱癌组织(Ta~T125例,T2~T4 32例),34例甲醛固定石

  20. Small cell carcinoma of the urinary bladder--a new case report.

    Science.gov (United States)

    Petrescu, Amelia; Berdan, Gabriela; Hulea, Ionela; Gaitanidis, Raluca; Ambert, V; Jinga, V; Damian, D; Codreanu, O; Andrei, F; Niculescu, L

    2007-01-01

    Primary pure small cell carcinoma of the urinary bladder is an extremely rare and highly aggressive tumor with an average five-year survival rate of less than 10% as cited by multiple case reports. It accounts for about 0.5-1% of all bladder tumors. We present the case of a 44-years-old man, smoker (10 cigarettes/day) hospitalized in the Department of Urology, from the "Prof. dr. Th. Burghele" Hospital, Bucharest, for one month intermittent hematuria. Ultrasonography showed a sessile tumoral mass, sized 37/30mm. Transurethral resection of the tumor mass was performed and tissue fragments were sent to the pathologic lab to establish the histologic type, the degree of differentiation and invasion. Fragments of the tumor were fixed in 10% formaldehyde, paraffin embedded and processed as standard technique; the sections were stained with HE, VG and immunohistochemically with: CROMO, EMA, NSE, CD56, NK1, p53 and betaHCG. The microscopic examination reveled a tumor proliferation composed of two distinct components: extensive small cells areas and foci of typical low grade (G2) papillary urothelial carcinoma. The small cell are uniformly, round, with increased nucleo-cytoplasmic ratio, eosinophyl cytoplasm, hyperchromatic nuclei, finely granular chromatin and inconspicuous nucleoli. Immunohistochemical stains showed diffuse positive staining of the small cell component for CROMO, EMA, NSE, CD56, NK1 and urothelial carcinoma component stained focally for betaHCG. The rate of cell proliferation was increased (p53 - 80% positive reaction). Conclusions. A diagnosis of small cell carcinoma coexisting with low-grade urothelial carcinoma was established. Because of aggressive behavior and distinct treatment, the pathologist should watch out for the presence of small cell carcinoma component. PMID:17914502

  1. Longitudinal change in renal function after nephroureterectomy in patients with upper tract urothelial carcinoma

    Directory of Open Access Journals (Sweden)

    Chih-Yuan Chou

    2015-06-01

    Conclusion: In this study, it was found that the average renal function of the patients with upper tract urothelial carcinoma is not as good as the general population. More than half of the normal renal function patients have new onset chronic kidney disease after surgery. For preventing further deterioration of renal function, the implication of partial nephrectomy or segmental ureterectomy for selected patients with localized urothelial carcinoma should be re-examined. Besides, neoadjuvant chemotherapy should be considered for those who are not good candidates for local treatment.

  2. Association of urothelial carcinoma of the renal pelvis with papillary and medullary thyroid carcinomas. A new sporadic neoplastic syndrome?

    Science.gov (United States)

    Albores-Saavedra, Jorge; Dorantes-Heredia, Rita; Chablé-Montero, Fredy; Córdova-Ramón, Juan Carlos; Henson, Donald E

    2014-10-01

    We describe 2 adult women (72 and 54 years), 1 with a low-grade noninvasive papillary urothelial carcinoma of the renal pelvis, who 14 years later developed a papillary carcinoma in 1 thyroid lobe and a medullary carcinoma in the contralateral lobe. Both neoplasms were similar in size and appeared symmetrical. Despite its small size, the medullary carcinoma metastasized in multiple cervical lymph nodes. The second patient had a high-grade invasive papillary urothelial carcinoma of the renal pelvis that infiltrated the renal parenchyma and metastasized in one of the lungs. Five months later, a papillary carcinoma was discovered in the thyroid gland. The 2 papillary thyroid carcinomas were of the follicular variant. Adjacent to 1 papillary carcinoma, there was a dominant nodule of a colloid and adenomatous goiter. The medullary carcinoma contained stromal amyloid and was immunoreactive for calcitonin and carcinoembryonic antigen. There was no C-cell hyperplasia (medullary carcinoma in situ). The 2 patients are alive, 1 is living with pulmonary metastasis from the high-grade urothelial carcinoma. Twelve cases of this neoplastic association were registered in the Survey, Epidemiology, and End Results Program from 1980 to 2009. We believe that the combination of these unusual neoplasms in the same patient may represent a new sporadic neoplastic syndrome.

  3. Xp11 Translocation Renal Cell Carcinoma: Unusual Variant Masquerading as Upper Tract Urothelial Cell Carcinoma

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    Arash Akhavein

    2014-05-01

    Full Text Available Xp11 translocation renal cell carcinoma (TRCC is a rare subtype of renal cell carcinoma characterized by chromosomal translocations involving the TFE3 gene located at the Xp11.2 locus. Initial cases were more common in children, but cases in older adults have begun to accrue and suggest a relatively more aggressive course. We report a case of Xp11 TRCC in a 63-year-old female patient with initial presentation mimicking upper urinary tract urothelial cell carcinoma, with biopsy proving TRCC. She underwent a radical nephrectomy and paracaval lymph node dissection and is followed up with the intent to initiate vascular endothelial growth factor–targeted therapy in case of recurrence.

  4. Hypercalcemia in Upper Urinary Tract Urothelial Carcinoma: A Case Report and Literature Review

    Science.gov (United States)

    McHugh, Jonathan B.; Miller, David C.; Esfandiari, Nazanene H.

    2013-01-01

    Objective. We here report a patient with upper urinary tract urothelial carcinoma with hypercalcemia likely due to elevated 1,25-dihydroxyvitamin D. Methods. We present a clinical case and a summary of literature search. Results. A 57-year-old man, recently diagnosed with a left renal mass, for which a core biopsy showed renal cell carcinoma, was admitted for hypercalcemia of 11.0 mg/mL He also had five small right lung nodules with a negative bone scan. Both intact parathyroid hormone and parathyroid hormone-related peptide were appropriately low, and 1,25-dihydroxyvitamin D was elevated at 118 pg/dL. The patient's calcium was normalized after hydration, and he underwent radical nephrectomy. On the postoperative day 6, a repeat 1,25-dihydroxyvitamin D was 24 pg/mL with a calcium of 8.1 mg/dL. Pathology showed a 6 cm high-grade urothelial carcinoma with divergent differentiation. We identified a total of 27 previously reported cases with hypercalcemia and upper tract urothelial carcinoma in English. No cases have a documented elevated 1,25-dihydroxyvitamin D level. Conclusion. This clinical course suggests that hypercalcemia in this case is from the patient's tumor, which was likely producing 1,25-dihydroxyvitamin D. Considering the therapeutic implications, hypercalcemia in patients with upper urinary tract urothelial carcinoma should be evaluated with 1,25-dihydroxyvitamin D. PMID:23476827

  5. Sarcopenia as a prognostic biomarker of advanced urothelial carcinoma.

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    Hiroshi Fukushima

    Full Text Available OBJECTIVES: Sarcopenia, a novel concept reflecting the degenerative loss of skeletal muscle mass, is an objective indicator of cancer cachexia. We investigated its role as a prognostic biomarker in advanced urothelial carcinoma (UC patients. METHODS: This retrospective study consisted of 88 UC patients with cT4 and/or metastases to lymph nodes/distant organs. Skeletal muscle index (SMI, an indicator of whole-body muscle mass, was measured from computed tomography (CT images at the diagnosis. Sarcopenia was defined as SMIs of <43 cm(2/m(2 for males with body mass index (BMI <25 cm(2/m(2, <53 cm(2/m(2 for males with BMI ≥ 25 cm(2/m(2, and <41 cm(2/m(2 for females. Predictors of overall survival (OS were examined using Cox proportional hazard models. RESULTS: Sixty-seven patients (76% died during the median follow-up of 13 months. The median OS rate was 13 months. Multivariate analysis revealed that SMI was a significant and independent predictor of shorter OS (hazard ratio (HR 0.90, P <0.001. In the present cohort, 53 (60% were diagnosed with sarcopenia. The median OS rates were 11 and 31 months for sarcopenic and non-sarcopenic patients, respectively (P <0.001. On multivariate analysis, sarcopenia was a significant and independent predictor of shorter OS (HR 3.36, P <0.001, along with higher C-reactive protein (CRP (P = 0.001, upper urinary tract cancer (P = 0.007, higher lactate dehydrogenase (LDH (P = 0.047, and higher alkaline phosphatase (ALP (P = 0.048. CONCLUSION: Sarcopenia, which is readily evaluated on routine CT scans, is a useful prognostic biomarker of advanced UC. Non-sarcopenic patients can expect long-term survival. Evaluating sarcopenia can be helpful for decision-making processes in the management of advanced UC patients.

  6. CA 19-9 as a serum marker in urothelial carcinoma

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    Mahander Pall

    2012-01-01

    Conclusions: Serum CA19-9 is a marker of aggressiveness of urothelial carcinoma and is almost invariably raised in patients with metastatic disease. Thus, it may be used as a prognostic marker but not as a screening tool due to its low sensitivity.

  7. Detection of mitochondrial deoxyribonucleic acid alterations in urine from urothelial cell carcinoma patients.

    NARCIS (Netherlands)

    Dasgupta, S.; Shao, C.; Keane, T.E.; Duberow, D.P.; Mathies, R.A.; Fisher, P.B.; Kiemeney, L.A.L.M.; Sidransky, D.

    2012-01-01

    Our study aims at understanding the timing and nature of mitochondrial deoxyribonucleic acid (mtDNA) alterations in urothelial cell carcinoma (UCC) and their detection in urine sediments. The entire 16.5 kb mitochondrial genome was sequenced in matched normal lymphocytes, tumor and urine sediments f

  8. Absence of karyotype abnormalities in patients with familial urothelial cell carcinoma.

    NARCIS (Netherlands)

    Aben, K.K.H.; Macville, M.V.E.; Smeets, D.F.C.M.; Schoenberg, M.P.; Witjes, J.A.; Kiemeney, L.A.L.M.

    2001-01-01

    OBJECTIVES: In a previous pilot study, a constitutional balanced translocation t(5;20)(p15;q11) was identified in a family with urothelial cell carcinoma (UCC). The purpose of this study was to find (additional) constitutional chromosomal abnormalities in selected families to obtain an indication fo

  9. HLA class I expression in bladder carcinomas.

    Science.gov (United States)

    Cabrera, T; Pedrajas, G; Cozar, J M; Garrido, A; Vicente, J; Tallada, M; Garrido, F

    2003-10-01

    HLA class I molecules are frequently lost in a large variety of human carcinomas, possibly because of T-cell immune selection of major histocompatibility complex class I deficient tumor variants. We report that this phenomenon is also a frequent event in bladder carcinomas. Of a total of 72 bladder carcinomas, 72% of the tumors had at least one alteration in HLA class I expression. These altered HLA class I phenotypes were classified as total HLA class I loss (25%; phenotype I); HLA-A or/and HLA-B locus-specific loss (12%; phenotype III); and HLA class I allelic loss (35%; phenotype II or IV). Comparison of histopathological parameters with HLA class I expression showed a statistically significant relationship with the degree of differentiation and tumor recurrence.

  10. HERV-K and LINE-1 DNA methylation and reexpression in urothelial carcinoma

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    Ulrike eKreimer

    2013-09-01

    Full Text Available Changes in DNA methylation frequently accompany cancer development. One prominent change is an apparently genome-wide decrease in methylcytosine that is often ascribed to DNA hypomethylation at retroelements comprising nearly half the genome. DNA hypomethylation may allow reactivation of retroelements, enabling retrotransposition and causing gene expression disturbances favoring tumor development. However, neither the extent of hypomethylation nor of retroelement reactivation are precisely known. We therefore assessed DNA methylation and expression of three major classes of retroelements (LINE-1, HERV-K and AluY in human urinary bladder cancer tissues and cell lines by pyrosequencing and quantitative reverse transcription–polymerase chain reaction, respectively. We found substantial global LINE-1 DNA hypomethylation in bladder cancer going along with a shift towards full-length LINE-1 expression. Thus, pronounced differences in LINE-1 expression were observed, which may be promoted, among others, by LINE-1 hypomethylation. Significant DNA hypomethylation was found at the HERV-K_22q11.23 proviral long terminal repeat (LTR in bladder cancer tissues but without reactivation of its expression. DNA methylation of HERVK17, essentially absent from normal urothelial cells, was elevated in cell lines from invasive bladder cancers. Accordingly, the faint expression of HERVK17 in normal urothelial cells disappeared in such cancer cell lines. Of 16 additional HERV-Ks, expression of 7 could be detected in the bladder, albeit generally at low levels. Unlike in prostate cancers, none of these showed significant expression changes in bladder cancer. In contrast, expression of the AluYb8 but not of the AluYa5 family was significantly increased in bladder cancer tissues. Collectively, our findings demonstrate a remarkable specificity of changes in expression and DNA methylation of retroelements in bladder cancer with a significantly different pattern from that

  11. Germline single nucleotide polymorphisms associated with response of urothelial carcinoma to platinum-based therapy: the role of the host.

    LENUS (Irish Health Repository)

    Gallagher, D J

    2013-09-01

    Variations in urothelial carcinoma (UC) response to platinum chemotherapy are common and frequently attributed to genetic and epigenetic variations of somatic DNA. We hypothesized that variations in germline DNA may contribute to UC chemosensitivity.

  12. Carcinoma Gall Bladder: Past, Present, and Future

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    Ghosh Y

    2014-12-01

    Full Text Available Carcinoma gall bladder is a very aggressive disease with poor outcomes. Despite achievements in the field of advanced imaging techniques, there is a very high mortality rate of the disease Cancer is the second most common disease in India responsible for maximum mortality with about 0.3 million deaths per year. The magnitude of cancer problem in the Indian Sub-continent (sheer numbers is increasing due to poor to moderate living standards and inadequate medical facilities. Women are more commonly affected than men. The peak incidence occurs in people in their 60s, but the disease age range is from 29 to 90 years of age and there is great geographic and ethnic variation. Carcinoma gall bladder, a disease of old age, is now found in the younger age group and presents with greater ferocity.

  13. Pathological Characteristics of Primary Bladder Carcinoma Treated at a Tertiary Care Hospital and Changing Demographics of Bladder Cancer in Sri Lanka.

    Science.gov (United States)

    Sasikumar, S; Wijayarathna, K S N; Karunaratne, K A M S; Gobi, U; Pathmeswaran, A; Abeygunasekera, Anuruddha M

    2016-01-01

    Objectives. The aim was to compare demographics and pathological features of bladder carcinoma treated in a urology unit with findings of previous studies done in Sri Lanka. Materials and Methods. Data of newly diagnosed patients with bladder cancer in a tertiary referral centre from 2011 to 2014 were analysed. Data on bladder cancers diagnosed from 1993 to 2014 were obtained from previous publications and Sri Lanka Cancer Registry. Results. There were 148 patients and mean age was 65 years. Male to female ratio was 4.1 : 1. Urothelial carcinoma (UC) was found in 89.2% of patients. Muscle invasion was noted in 35% of patients compared to 48.4% two decades ago. In patients with UC, 16.5% were found to have pT1 high grade tumour. It was 5.3% from 1993 to 2000. Pure squamous cell carcinoma was found in 8.1% of patients while primary or de novo carcinoma in situ (not associated with high grade pT1 tumours) was seen in one patient only. Conclusions. The percentage of squamous carcinoma is higher among Sri Lankan patients while primary carcinoma in situ is a rarity. The percentage of muscle invasive disease has decreased while the percentage of pT1 high grade tumours has increased during the last two decades in Sri Lanka. PMID:26884756

  14. A Case with Significant Proteinuria Caused by Secreted Protein from Urothelial Carcinoma

    Science.gov (United States)

    Sakakima, Masanori; Fujigaki, Yoshihide; Yasuda, Hideo; Togawa, Akashi; Fujikura, Tomoyuki; Otsuka, Atsushi; Ozono, Seiichiro; Hishida, Akira

    2011-01-01

    58-year-old female was admitted to our hospital complaining isolated proteinuria of 1.7 g/day. Abdominal echography showed right-sided unilateral hydronephrosis, and computed tomography pointed out a tumor of the right renal pelvis, suggesting cancer of renal pelvis. The right nephroureterectomy was carried out. Pathological diagnosis was urothelial carcinoma. Renal tissue revealed no apparent glomerulopathy with tubular atrophy, interstitial fibrosis, and mildly-to-moderately interstitial mononuclear cell infiltration. Immunofluorescence study showed no deposition of immunoreactanct, and electron microscopy showed almost normal glomerulus without electron dense deposit. Proteinuria disappeared within 6 days after the operation. Moderate amount of proteinuria in our patient was probably caused by secreted protein from urothelial carcinoma. This condition is rare but should be taken into account in patients with even moderate amount of proteinuria. PMID:24533189

  15. A Case with Significant Proteinuria Caused by Secreted Protein from Urothelial Carcinoma

    Directory of Open Access Journals (Sweden)

    Masanori Sakakima

    2011-01-01

    Full Text Available 58-year-old female was admitted to our hospital complaining isolated proteinuria of 1.7 g/day. Abdominal echography showed right-sided unilateral hydronephrosis, and computed tomography pointed out a tumor of the right renal pelvis, suggesting cancer of renal pelvis. The right nephroureterectomy was carried out. Pathological diagnosis was urothelial carcinoma. Renal tissue revealed no apparent glomerulopathy with tubular atrophy, interstitial fibrosis, and mildly-to-moderately interstitial mononuclear cell infiltration. Immunofluorescence study showed no deposition of immunoreactanct, and electron microscopy showed almost normal glomerulus without electron dense deposit. Proteinuria disappeared within 6 days after the operation. Moderate amount of proteinuria in our patient was probably caused by secreted protein from urothelial carcinoma. This condition is rare but should be taken into account in patients with even moderate amount of proteinuria.

  16. A Case with Significant Proteinuria Caused by Secreted Protein from Urothelial Carcinoma

    OpenAIRE

    Masanori Sakakima; Yoshihide Fujigaki; Hideo Yasuda; Akashi Togawa; Tomoyuki Fujikura; Atsushi Otsuka; Seiichiro Ozono; Akira Hishida

    2011-01-01

    58-year-old female was admitted to our hospital complaining isolated proteinuria of 1.7 g/day. Abdominal echography showed right-sided unilateral hydronephrosis, and computed tomography pointed out a tumor of the right renal pelvis, suggesting cancer of renal pelvis. The right nephroureterectomy was carried out. Pathological diagnosis was urothelial carcinoma. Renal tissue revealed no apparent glomerulopathy with tubular atrophy, interstitial fibrosis, and mildly-to-moderately interstitial mo...

  17. Detection of bladder transitional cell carcinoma: urinary hTERT assay versus urine cytology

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    Yahyazadeh SR

    2009-04-01

    Full Text Available "nBackground: Transitional Cell Carcinoma (TCC of bladder is the second most common urogenital malignancy and because of its high rate of recurrence (two third of tumors recur vigilant surveillance is necessary. There have been a lot of efforts to find a proper biomarker for detecting urothelial cancers because available methods are expensive and invasive (like cystoscopy or have a low degree of sensitivity (like urine cytology. Urothelial malignancies, like other cancers tend to express a large amount of telomerase. The aim of this study was to evaluate the possible application of voided urine human telomerase reverse transcriptase (hTERT mRNA assay in detecting low-grade bladder carcinoma in comparison with urine cytology. "nMethods: Voided urine samples were collected from 49 patients who were supposed to go under operation. Samples were examined by both Quantitative Real-time RT-PCR (for measuring hTERT mRNA level and cytology; the results were then compared to the final pathologic studies. "nResults: Regardless of clinical stage and or pathological grade of tumor, sensitivity of telomerase test and urine cytology was 74% and 16% respectively. There was a strong correlation between results of urine cytology and stage and/or grade of tumor; however, sensitivity of telomerase test was acceptable regardless of stage and or grade of tumor. There was a statistically significant difference between sensitivity of urine cytology and telomerase test (p<0.001. "nConclusion: Detection of hTERT-mRNA can potentially be used as a non-invasive method for diagnosis and follow up of bladder carcinoma instead of urine cytology.

  18. HpD Photobiology And Photodynamic Therapy Of Bladder Carcinoma

    Science.gov (United States)

    Lin, Chi-Wei

    1988-02-01

    Bladder carcinoma is considered one of the most favorable targets for the application of photodynamic therapy (PDT) due to the accessibility of the bladder for light delivery. Examination of the bladder and surgical procedures are routinely performed by the insertion of an optical instrument called cystoscope through the urethra. Thus, the treatment of bladder cancer by PDT can be conducted through the cystoscope with minimal invasion. However, to achieve optimal results from this treatment, one must consider both the structure of the bladder and the nature of the carcinoma.

  19. Loss of Sh3gl2/Endophilin A1 Is a Common Event in Urothelial Carcinoma that Promotes Malignant Behavior

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    Shyama Majumdar

    2013-07-01

    Full Text Available Urothelial carcinoma (UC causes substantial morbidity and mortality worldwide. However, the molecular mechanisms underlying urothelial cancer development and tumor progression are still largely unknown. Using informatics analysis, we identified Sh3gl2 (endophilin A1 as a bladder urothelium-enriched transcript. The gene encoding Sh3gl2 is located on chromosome 9p, a region frequently altered in UC. Sh3gl2 is known to regulate endocytosis of receptor tyrosine kinases implicated in oncogenesis, such as the epidermal growth factor receptor (EGFR and c-Met. However, its role in UC pathogenesis is unknown. Informatics analysis of expression profiles as well as immunohistochemical staining of tissue microarrays revealed Sh3gl2 expression to be decreased in UC specimens compared to nontumor tissues. Loss of Sh3gl2 was associated with increasing tumor grade and with muscle invasion, which is a reliable predictor of metastatic disease and cancer-derived mortality. Sh3gl2 expression was undetectable in 19 of 20 human UC cell lines but preserved in the low-grade cell line RT4. Stable silencing of Sh3gl2 in RT4 cells by RNA interference 1 enhanced proliferation and colony formation in vitro, 2 inhibited EGF-induced EGFR internalization and increased EGFR activation, 3 stimulated phosphorylation of Src family kinases and STAT3, and 4 promoted growth of RT4 xenografts in subrenal capsule tissue recombination experiments. Conversely, forced re-expression of Sh3gl2 in T24 cells and silenced RT4 clones attenuated oncogenic behaviors, including growth and migration. Together, these findings identify loss of Sh3gl2 as a frequent event in UC development that promotes disease progression.

  20. The expression of P504S in prostate adenocarcinoma, renal cell carcinoma and bladder urothelial carcinoma and its clinical significances%P504S在前列腺癌、肾细胞癌和膀胱尿路上皮癌中的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    马志伟; 董丹丹; 龚百生; 邱明星

    2015-01-01

    Objective:To evaluate the expression and clinical significance of P504S in prostate cancer (Pca), renal cell carcinoma (RCC) and bladder transitional cell carcinoma (BTCC). Methods:Immunohistochemical labeled dextran polymer (LDP) methods were used to detect the expressions of P504S in Pca, RCC and BTCC, and also to analyze the difference of expressions in benign prostatic hyperplasia tissue, normal renal tissue and normal bladder tissues. Results:The positive expression rates of P504S in Pca, RCC and BTCC tissues were 93.10%,65.28%and 46.07%respectively, but in BPH tissue, normal renal tissue and normal bladder tissue were 0%, 6.67%and 6.25%respectively, the expression was significantly different (P<0.01). The positive expression levels of P504S were positively correlated to tumor pathological grades and tumor clinical stages (P<0.05) of Pca, RCC and BTCC. It was also closely correlated with the prognosis of tumor. Conclusion:It suggested that P504S might play a role in the biological behavior of Pca, RCC and BTCC and might serve as an important indicator of the invasion, development and prognosis of these tumors.%目的:探讨肿瘤标记物P504S在前列腺癌(prostate cancer,Pca)、肾细胞癌(renal cell carcinoma, RCC)和膀胱尿路上皮癌(bladder transitional cell carcinoma,BTCC)组织中的表达及临床意义。方法:采用免疫组织化学标记菌葡萄聚糖聚合物法(labeled dextran polymer,LDP),检测P504S在前列腺癌、肾细胞癌和膀胱尿路上皮癌组织中的表达情况,探讨其在前列腺增生(benign prostatic hyperplasia,BPH)组织、正常肾组织和正常膀胱组织中的表达并作相应比较。结果:P504S在Pca、RCC和BTCC组织中阳性表达率分别为93.10%、65.28%和46.07%,而在BPH、正常肾组织和正常膀胱组织分别为0%、6.67%和6.25%,各组间差异均有统计学意义(P<0.01);P504S阳性表达水平与Pca、RCC及BTCC病理分级和临床分期均呈正相关(P<0.05)

  1. Penile-preserving surgery for primary urothelial carcinoma of male urethra

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    Haoping Tai

    2015-06-01

    Full Text Available Primary urethral carcinoma is a rare cancer, comprising <1% of all malignancies. The location of this lesion presents a certain dilemma of treatment between efficacy and quality of life. We report an 84-year-old male patient, with a history of chronic hepatitis C, hypertension, and transient ischemic accident, who presented with dysuria and acute urinary retention. The intravenous urography showed mild prostatic enlargement, but no stone or filling defect was noted in the upper urinary tract. On urethrocystoscopy, multiple papillary tumors were found at the pendulous urethra, and the pathology of biopsy confirmed urothelial carcinoma. The patient was admitted, and electroresection with fulguration of urethral tumors was performed owing to the patient's old age and poor performance status. Intraurethral and intravesical chemotherapy with mitomycin C was regularly given at the outpatient clinic. Recurrent urothelial carcinomas were noted twice in the first 2 years of follow up, and repeated transurethral resections were done. Unfortunately, liver cirrhosis with hepatocellular carcinoma was diagnosed last June, for which he received transcatheter arterial chemoembolization. No recurrence of urethral cancer has been found on semiannual cystoscopy in the past 3 years. Penile-preserving surgery is a reasonable surgical option for elderly primary urethral carcinoma patients with acceptable oncological outcome and good quality of life.

  2. ILEOCYSTOPLASTY IN INVASIVE URINARY BLADDER CARCINOMA

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    V. N. Pavlov

    2009-01-01

    Full Text Available Objective: to assess the results of surgical treatment of patients with the intestinal urinary bladder, to characterize its early and late postoperative complications, and to develop their correction tactics.  Subjects and methods. The results of treatment in 198 patients who had undergone ileocystoplasty were analyzed.  Results. The developed diagnostic approach and the determined examination periods could reduce the number of late postoperative complications of ileocystoplasty: acute and chronic pyelonephritis from 19.4 to 7.6%, urolithiasis from 17.2 to 1.9%, bladder dysfunction from 25.8 to 7.6%, and metabolic acidosis from 4.3 to 1.9%, and prevent the development of ureterovesical anastomosis stricture.  Conclusion. Radical cystectomy with the ileoplasty using an isolated segment of the ileum in patients with invasive urinary bladder carcinoma has been the operation of choice no longer; it has become an essential surgical adjunct. This method permits overall 5-year survival to be achieved in 69.7% of patients.  

  3. Dynamic contrast enhanced MRI-derived parameters are potential biomarkers of therapeutic response in bladder carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Chakiba, Camille [Department of Medical Oncology, Bergonié Cancer Institute, Bordeaux (France); Cornelis, François [Department of Radiology, Pellegrin Hospital, Bordeaux (France); Descat, Edouard [Department of Radiology, Saint-Augustin Clinic, Bordeaux (France); Gross-Goupil, Marine [Department of Medical Oncology, Bergonié Cancer Institute, Bordeaux (France); Sargos, Paul [Department of Radiotherapy, Bergonié Cancer Institute, Bordeaux (France); Roubaud, Guilhem [Department of Medical Oncology, Bergonié Cancer Institute, Bordeaux (France); Houédé, Nadine, E-mail: nadine.houede@chu-nimes.fr [Department of Medical Oncology, Bergonié Cancer Institute, Bordeaux (France); Department of Medical Oncology, Nimes University Hosptital, Nîmes (France)

    2015-06-15

    Highlights: • DCE-MRI parameters could be useful biomarker for patients with localized bladder carcinoma. • Rate of relapse is lower for good responders assessed by DCE-MRI. • The use of DCE-MRI parameters may improve the standardization of patients’ selection before surgery. - Abstract: Objectives: To evaluate the performance of dynamic contrast enhanced (DCE) magnetic resonance (MR) imaging to assess the histological response after chemotherapy on bladder carcinoma. Methods: From 2008 to 2010, 12 patients presenting localized urothelial carcinoma of the bladder were prospectively evaluated by DCE-MR imaging before and after two courses of cisplatin-based neoadjuvant chemotherapy. Size and thickness of tumours were measured. Relative enhancement at the arterial (rSI{sub 35s}) and venous phases (rSI{sub 80s}) of each tumour was obtained. Histological response was assessed and outcomes were recorded. Results: Histological examination after neoadjuvant chemotherapy concluded as pathological complete response (pCR) for 6 out of 12 patients. Five patients developed recurrences (4/6 no pCR and 1/6 pCR). Significant differences, between before and after treatment, were found for patients with complete pathological response after chemotherapy for all MR quantitative values. Tumours decreased in size and thickness (both P = 0.03). After treatment, rSI{sub 80s} was significantly different between pCR and non-pCR patients (P = 0.04) with a cut-off value of 40%. For this cut-off, sensitivity, specificity and accuracy were 83.33%. Similar recurrence free survivals were obtained if applying the MR cut-off value or the histopathological findings. Conclusion: Our results suggest that DCE-MR imaging may be a useful biomarker for patients with localized bladder carcinoma, improving selection before surgery.

  4. Polymorphism of inflammatory genes and arsenic methylation capacity are associated with urothelial carcinoma

    International Nuclear Information System (INIS)

    Chronic exposure to arsenic can generate reactive oxidative species, which can induce certain proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8). TNF-α, IL-6 and IL-8 have been shown to be involved in the development and progression of various cancers, including bladder cancer. This study aimed to investigate the joint effect of the polymorphism of TNF-α − 308 G/A, IL-6 − 174 G/C, IL-8 − 251 T/A and urinary arsenic profiles on urothelial carcinoma (UC) risk. This study evaluated 300 pathologically-confirmed cases of UC and 594 cancer-free controls. Urinary arsenic species were detected using high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. The polymorphism of TNF-α − 308 G/A, IL-6 − 174 G/C and IL-8 − 251 T/A was determined using polymerase chain reaction-restriction fragment length polymorphism. The joint effects on UC risk were estimated by odds ratios and 95% confidence intervals using unconditional logistic regression. We found that the TNF-α − 308 A/A and IL-8 − 251 T/T polymorphisms were significantly associated with UC. Moreover, significant dose–response joint effect of TNF-α − 308 A/A or IL-8 − 251 T/T genotypes and arsenic methylation indices were seen to affect UC risk. The present results also showed a significant increase in UC risk in subjects with the IL-8 − 251 T/T genotype for each SD increase in urinary total arsenic and MMA%. In contrast, a significant decrease in UC risk was found in subjects who carried the IL-8 − 251 T/T genotype for each SD increase in DMA%. - Highlights: • Joint effect of the TNF-α -308 A/A genotype and urinary total arsenic affected UC. • Joint effect of the IL-8 -251 T/T genotype and urinary total arsenic affected UC. • Urinary total arsenic level, TNF-α -308 A/A and IL-8 -251 T/T genotype affected UC

  5. Polymorphism of inflammatory genes and arsenic methylation capacity are associated with urothelial carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Chia-Chang [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Department of Urology, Taipei Medical University—Shuang Ho Hospital, Taipei, Taiwan (China); Huang, Yung-Kai [School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan (China); Chung, Chi-Jung [Department of Health Risk Management, College of Public Health, China Medical University and Hospital, Taichung, Taiwan (China); Department of Medical Research, China Medical University Hospital, Taichung, Taiwan (China); Huang, Chao-Yuan; Pu, Yeong-Shiau [Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan (China); Shiue, Horng-Sheng [Department of Chinese Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan (China); Lai, Li-An [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Lin, Ying-Chin [Department of Family Medicine, Shung Ho Hospital, Taipei Medical University, Taipei, Taiwan (China); Department of Health Examination, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan (China); Su, Chien-Tien [Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan (China); Hsueh, Yu-Mei, E-mail: ymhsueh@tmu.edu.tw [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China)

    2013-10-01

    Chronic exposure to arsenic can generate reactive oxidative species, which can induce certain proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8). TNF-α, IL-6 and IL-8 have been shown to be involved in the development and progression of various cancers, including bladder cancer. This study aimed to investigate the joint effect of the polymorphism of TNF-α − 308 G/A, IL-6 − 174 G/C, IL-8 − 251 T/A and urinary arsenic profiles on urothelial carcinoma (UC) risk. This study evaluated 300 pathologically-confirmed cases of UC and 594 cancer-free controls. Urinary arsenic species were detected using high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. The polymorphism of TNF-α − 308 G/A, IL-6 − 174 G/C and IL-8 − 251 T/A was determined using polymerase chain reaction-restriction fragment length polymorphism. The joint effects on UC risk were estimated by odds ratios and 95% confidence intervals using unconditional logistic regression. We found that the TNF-α − 308 A/A and IL-8 − 251 T/T polymorphisms were significantly associated with UC. Moreover, significant dose–response joint effect of TNF-α − 308 A/A or IL-8 − 251 T/T genotypes and arsenic methylation indices were seen to affect UC risk. The present results also showed a significant increase in UC risk in subjects with the IL-8 − 251 T/T genotype for each SD increase in urinary total arsenic and MMA%. In contrast, a significant decrease in UC risk was found in subjects who carried the IL-8 − 251 T/T genotype for each SD increase in DMA%. - Highlights: • Joint effect of the TNF-α -308 A/A genotype and urinary total arsenic affected UC. • Joint effect of the IL-8 -251 T/T genotype and urinary total arsenic affected UC. • Urinary total arsenic level, TNF-α -308 A/A and IL-8 -251 T/T genotype affected UC.

  6. Massive Upper Gastrointestinal Bleeding Secondary to Duodenal Metastasis of Transitional Cell Carcinoma of the Urinary Bladder

    Directory of Open Access Journals (Sweden)

    Carlos H.F. Chan

    2011-04-01

    Full Text Available Acute upper gastrointestinal (UGI bleeding is a common problem in our clinical practice and is often due to peptic ulcer diseases. Occasionally, malignancy may be implicated in these situations. Here we report a rare case of UGI bleeding secondary to metastatic transitional cell carcinoma (TCC of the urinary bladder. A 62-year-old man with a history of stage IIIb TCC of the urinary bladder presented with hematemesis. Endoscopy showed a large tumor in the second stage of the duodenum that occupied 40% of the duodenal circumference, over 7 cm in length. Biopsies revealed a poorly differentiated malignant neoplasm consistent with metastasis from urothelial carcinoma that was identical to the previous surgical specimen of the urinary bladder. He was treated with supportive therapy and intravenous proton pump inhibitor and was discharged home 2 weeks later. Two weeks after discharge, the patient returned to the hospital with a painful swelling of the floor of his mouth. Biopsy again showed the same cancer type. He had unremitting bleeding from his mouth requiring multiple transfusions and a course of palliative radiation therapy. He progressively deteriorated in his cardiopulmonary and neurological functions and expired with cardiopulmonary arrest one month later.

  7. Overactive and Underactive Bladder Dysfunction is Reflected by Alterations in Urothelial ATP and NO Release

    OpenAIRE

    Munoz, Alvaro; Smith, Christopher P.; Boone, Timothy B.; Somogyi, George T.

    2010-01-01

    ATP and NO are released from the urothelium in the bladder. Detrusor Overactivity (DO) following spinal cord injury results in higher ATP and lower NO release from the bladder urothelium. Our aim was to study the relationship between ATP and NO release in 1) early diabetic bladders, an overactive bladder model; and 2) in “diuretic” bladders, an underactive bladder model. To induce diabetes mellitus female rats received 65 mg/kg streptozocin (i.v.). To induce chronic diuresis rats were fed wit...

  8. Lynch syndrome and exposure to aristolochic acid in upper-tract urothelial carcinoma: its clinical impact?

    Science.gov (United States)

    Colin, Pierre; Seisen, Thomas; Mathieu, Romain; Shariat, Sharohkh F.

    2016-01-01

    The purpose of the current review was to describe the clinical risk for Lynch syndrome (LS) after exposure to aristolochic acid (AA) in cases of upper urinary-tract urothelial carcinoma (UTUC). A systematic review of the scientific literature was performed using the Medline database (National Library of Medicine, PubMed) using the following keywords: epidemiology, risk factor, AA, Balkan nephropathy (BNe), LS, hereditary cancer, hereditary non-polyposis colorectal cancer (HNPCC), mismatch repair genes, urothelial carcinomas, upper urinary tract, renal pelvis, ureter, Amsterdam criteria, genetic counselling, mismatch repair genes, genetic instability, microsatellite, and Bethesda guidelines. LS is a specific risk for UTUC, which is the third most frequent cancer (in its tumor spectrum) after colon and uterine lesions. Mutation of the MSH2 gene is the most commonly described cause of UTUC in LS. Diagnosis is based on clinical suspicion and is guided by Bethesda and Amsterdam criteria. It is secondarily confirmed by immunohistochemical analyses of the tumor and a search for gene mutations. The presence of LS in patients with UTUC is a favorable prognosis factor for survival during follow-ups. AA is a specific environmental risk factor for UTUC and tubulo-interstitial nephropathy. It has been involved in the development of nephropathies in link with the Balkan disease and intake of Chinese herbal medicine. More broadly, the use of traditional plant medicines from the genus Aristolochia has created worldwide public-health concerns. UTUCs share common risk factors with other urothelial carcinomas such as tobacco or occupational exposure. However, these tumors have also specific risk factors such as AA exposure and LS that clinicians should be aware of because of their clinical implication in further management and follow-up.

  9. [Risk factors for urothelial carcinoma: drinking measures, smoking and other life style-related risk factors--results of the Berlin Urothelial Study (BUS)].

    Science.gov (United States)

    Helmert, U; Bronder, E; Klimpel, A; Molzahn, M; Pommer, W

    2000-05-01

    With the exception of smoking and several occupational exposures there is little knowledge about risk factors for urothelial cancer. A case control study in the area of former West Berlin was performed from 1990-1995 to investigate the role of several lifestyle risk factors, such as smoking, drinking behaviour and regular intake of analgesics and laxatives. The study includes 647 hospital-based incident cases with bladder cancer (n = 571), renal pelvis cancer (n = 51), and ureter cancer (n = 25), and 647 population-based controls which were matched individually by sex and age. Data analyses were carried out using standard methods for case control studies (conditional multiple logistic regression analysis). Odds ratios (OR) and 95% confidence intervals (CI) were applied as effect parameter. Statistically significantly increased odds ratios were observed for current smoking (OR: 3.46, 95% CI: 2.50-4.78), previous but now abandoned smoking (OR: 1.51, 95% CI: 1.09-2.81), and for regular intake of laxatives (OR: 2.52, 95% CI: 1.56-4.09). Furthermore, an increased risk for urothelial cancer was observed for daily consumption of three and more litres of cold drinks (OR: 2.65 95% CI: 1.12-6.24). The results underline that lifestyle factors other than smoking may contribute to a higher risk of urothelial cancer. PMID:10893874

  10. Expression of OCT4A: The First Step to the Next Stage of Urothelial Bladder Cancer Progression

    Directory of Open Access Journals (Sweden)

    Wojciech Jóźwicki

    2014-09-01

    Full Text Available OCT4 (octamer-binding transcription factor is a transcription factor responsible for maintaining the pluripotent properties of embryonic stem cells. In this paper, we present the results of studies to investigate the role of the OCT4 splicing variant in urothelial bladder cancer and the relationship between the OCT4 phenotype and the morphological parameters of tumor malignancy. Ninety patients who received a cystectomy for bladder cancer were enrolled. The expression of OCT4 protein was analyzed by immunohistochemistry. The ratio of OCT4-positive cells was the lowest in pT1 (pathological assessment (p—tumor extent confined to mucosa (T1 tumors and the highest in pTis (non-papillary tumor extent confined to urothelium and pT2 (tumor extent including muscularis propria tumors. Information about the percentage of OCT4A-positive tumor cells could facilitate choosing the treatment mode in borderline pTis–pT1 (crossing the border of the basement membrane; the first stage of progression and pT1–pT2 (crossing the border of the muscularis propria; the second stage of progression cases: a higher percentage of OCT4A-positive cells should support more radical therapy. A significantly higher percentage of cases with moderate OCT4 intensity was found in metastasizing (the third stage of progression cases with >2 positive lymph nodes. The percentage of OCT4-positive cells was significantly higher for cancers with a high grade, higher non-classic differentiation number and greater aggressiveness of invasion. The differentiation, maturation and aggressiveness of tumor invasion appear to depend on the expression of the OCT4 phenotype in cancer cells, similar to the successive stages of malignancy progression in urothelial cancer.

  11. Radionuclide targeting with particular emphasis on urinary bladder carcinoma

    CERN Document Server

    Sjöström, A

    2001-01-01

    primary bladder carcinoma tumours was investigated. Both receptors were expressed in the majority of metastases and primary tumours. Targeting the EGF receptor and/or HER-2 in urinary bladder carcinoma is an exciting new concept The incidence of urinary bladder carcinoma is increasing and many patients die every year of this disease despite assumed radical therapy. Thus, there is a need for improved methods of diagnosis and therapy. Radionuclide targeting is based on achieving specific delivery of radioactive nuclides to tumour cells with minimal damage to surrounding normal tissues. Two possible target structures are the epidermal growth factor (EGF) receptor and the related receptor HER-2. Cellular binding and retention of sup 1 sup 2 sup 5 I-EGF-dextran conjugates was investigated in two bladder carcinoma cell lines. The conjugate bound specifically to the EGF receptor with delayed maximum binding, limited intracellular degradation and prolonged cellular retention compared to sup 1 sup 2 sup 5 I-EGF. EGF w...

  12. Calpain3 is expressed in a proteolitically active form in papillomavirus-associated urothelial tumors of the urinary bladder in cattle.

    Directory of Open Access Journals (Sweden)

    Sante Roperto

    Full Text Available BACKGROUND: Calpain 3 (Capn3, also named p94, is a skeletal muscle tissue-specific protein known to be responsible for limb-girdle muscular dystrophy type 2A (LGMD2A. Recent experimental studies have hypothesized a pro-apoptotic role of Capn3 in some melanoma cell lines. So far the link between calpain3 and tumors comes from in vitro studies. The objective of this study was to describe Capn3 activation in naturally occurring urothelial tumors of the urinary bladder in cattle. METHODS AND FINDINGS: Here we describe, for the first time in veterinary and comparative oncology, the activation of Capn3 in twelve urothelial tumor cells of the urinary bladder of cattle. Capn3 protein was initially identified with nanoscale liquid chromatography coupled with tandem mass spectrometry (nano LC-MS/MS in a co-immunoprecipitation experiment on E2F3, known to be a transcription factor playing a crucial role in bladder carcinogenesis in humans. Capn3 expression was then confirmed by reverse transcription polymerase chain reaction (RT-PCR. Finally, the Ca(2+-dependent proteolytic activity of Capn3 was assayed following ion exchange chromatography. Morphologically, Capn3 expression was documented by immunohistochemical methods. In fact numerous tumor cells showed an intracytoplasmic immunoreactivity, which was more rarely evident also at nuclear level. In urothelial tumors, bovine papillomavirus type 2 (BPV-2 DNA was amplified by PCR and the expression of E5 protein, the major oncogenic protein of BVP-2, was detected by western blotting, immunohistochemistry, and immunofluorescence. E2F3 overexpression and pRb protein downregulation were shown by western blotting. CONCLUSION: The role of capn3 protein in urothelial cancer of the urinary bladder remains to be elucidated: further studies would be required to determine the precise function of this protease in tumor development and progression. However, we suggest that activated Capn3 may be involved in molecular

  13. Transitional Cell Carcinoma within a Portion of Inguinally Herniated Bladder

    Directory of Open Access Journals (Sweden)

    Matthew A. Uhlman

    2013-01-01

    Full Text Available Bladder herniation within the inguinal canal is a relatively uncommon finding. We report an even less-common occurrence of transitional cell carcinoma located within a portion of inguinally herniated bladder. Fewer than 20 reports exist in the literature describing this scenario.

  14. Clinico-pathological pattern, classification and staging of urinary bladder carcinomas - a five years experience at a tertiary care hospital in central punjab

    International Nuclear Information System (INIS)

    In Pakistan, urinary bladder carcinoma is the 8th commonest malignancy while being the fourth commonest cancer in men. The relative occurrence of a particular histological type of bladder carcinoma depends on the clinical setting. Both grade and stage of these cancers are highly correlated with recurrence, progression and patient survival rates. Methods: This cross-sectional study comprised of 122 patients with newly diagnosed operable primary bladder carcinomas who underwent cystoscopy associated transurethral resection of bladder tumour at the Urology Department of Punjab Employees Social Security Hospital, Lahore. All participants completed a detailed questionnaire and underwent an in-depth interview to obtain data. The surgical specimens were referred to the Pathology department. Gross observations of the tumour recorded. Result: A total of 114 cases, classified according to WHO/ISUP criteria, low-grade papillary lesions, comprising Papillary Urothelial Neoplasm of Low Malignant Potential (PUNLMP) and Papillary Low Grade carcinomas, accounted for 43% of tumours. Male to female ratio being 5.3:1 (74%). Lateral walls were involved in 44%, posterior wall in 25.3%, trigone in 10.7%, bladder neck in 7.2%, dome in 5.8%, ureteric orifice in 4.13%, anterior wall in 2% and left ureter in 0.87% cases. Tumour staging revealed an overall 11.5% of tumours with stage Ta and 31.5% with stage T3-4. About 29% tumours were non invasive. About n=13 of low-grade carcinomas and n=68 of high-grade carcinomas were invasive. For tumours classified by WHO/ISUP criteria, the percentage of women was larger for PUNLMP than for the other categories of urothelial tumours (p-value 0.006); no statistically significant difference was found by age or gender with respect to tumour stage (p-value 0.138 and 0.452). Conclusion: Transitional Cell Carcinoma (TCC) is the commonest among middle aged men. (author)

  15. Geographic Variation of Chronic Kidney Disease Prevalence: Correlation with the Incidence of Renal Cell Carcinoma or Urothelial Carcinoma?

    Directory of Open Access Journals (Sweden)

    Yit-Sheung Yap

    2015-01-01

    Full Text Available Background. The aim of this study is to evaluate whether geographic variations in the prevalence of late-stage chronic kidney disease (CKD exist and are associated with incidence rates of renal cell carcinoma (RCC, upper tract urothelial carcinoma (UTUC, or lower tract urothelial carcinoma (LTUC. Methods. Prevalence rates of late-stage CKD for 366 townships (n>30 in Taiwan were calculated for 1,518,241 and 1,645,151 subjects aged 40 years or older in years 2010 and 2009, respectively. Late-stage CKD prevalence in year 2010 was used as a training set and its age-adjusted standardized morbidity rates (ASMR were divided into three groups as defined <1.76%, 1.76% ≤ ASMR < 2.64%, and ≥2.64%, respectively. Year 2009, defined as the validation set, was used to validate the results. Results. The ASMR of late-stage CKD in years 2010 and 2009 were 1.76%, and 2.09%, respectively. Geographic variations were observed, with notably higher rates of disease in areas of the central, southwestern mountainside, and southeastern seaboard. There were no significant differences among different combined risk groups of RCC, UTUC, and LTUC incidence. Conclusion. The substantial geographic variations in the prevalence of late-stage CKD exist, but are not correlated with RCC, UTUC, or LTUC incidence.

  16. Pooled analysis of phase II trials evaluating weekly or conventional cisplatin as first-line therapy for advanced urothelial carcinoma

    DEFF Research Database (Denmark)

    Maughan, Benjamin L; Agarwal, Neeraj; Hussain, Syed A;

    2013-01-01

    Weekly gemcitabine with GC every 3-4 weeks is considered conventional first-line chemotherapy for advanced urothelial carcinoma (UC). Weekly split-dose cisplatin with wGC might be less toxic and have similar activity, but has not been compared with GC. We pooled published phase II trials of GC...

  17. Immunohistochemical profile of the penile urethra and differential expression of GATA3 in urothelial versus squamous cell carcinomas of the penile urethra.

    Science.gov (United States)

    Chaux, Alcides; Han, Jeong S; Lee, Stephen; Gonzalez-Roibon, Nilda; Sharma, Rajni; Burnett, Arthur L; Cubilla, Antonio L; Netto, George J

    2013-12-01

    The penile urethra has a distinctive morphology not yet fully characterized by immunohistochemistry. In addition, both urothelial and squamous cell carcinomas have been reported in the penile urethra, and the distinction between these 2 tumors might be difficult. The purposes of this study are to assess the histology and immunohistochemical profile (CK20, CK7, p63, and GATA3) of the penile urethra and to assess the usefulness of Trans-acting T-cell-specific transcription factor (GATA3) and human papillomavirus detection in distinguishing urothelial versus squamous cell carcinomas. Normal penile urethra was evaluated in 11 total penectomies. The penile urethra was lined by 2 cell layers: a superficial single layer of CK7+, CK20-, and p63- columnar cells and a deep stratified layer of CK7-, CK20-, and p63+ cubical cells. Both layers were GATA3+, supporting urothelial differentiation. In addition, 2 tissue microarrays and 6 surgical specimens of primary tumors of the penile urethra (3 urothelial and 3 squamous cell carcinomas) were evaluated for GATA3 expression. In the tissue microarrays, 22 of 25 upper tract urothelial carcinomas and 0 of 38 penile squamous cell carcinomas were GATA3+. In the surgical specimens, GATA3 was positive in all urothelial carcinomas and negative in all squamous cell carcinomas. Human papillomavirus was detected in 2 of 3 squamous cell carcinomas and in 0 of 3 of the urothelial carcinomas. In conclusion, the penile urethra is covered by epithelial cells that are unique in morphology and immunohistochemical profile. In addition, our study suggests that GATA3 and human papillomavirus detection are useful markers for distinguishing urothelial carcinomas from squamous cell carcinomas of the penile urethra.

  18. Enterovesical fistula caused by a bladder squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Chun-Hsiang Ou Yang; Keng-Hao Liu; Tse-Ching Chen; Phei-Lang Chang; Ta-Sen Yeh

    2009-01-01

    Enterovesical fistulas are not uncommon in patients with inflammatory or malignant colonic disease, however,fistulas secondary to primary bladder carcinomas are extremely rare. We herein reported a patient presenting with intractable urinary tract infection due to enterovesical fistula formation caused by a squamous cell carcinoma of the urinary bladder. This patient underwent en bloc resection of the bladder dome and involved ileum, and recovered uneventfully without urinary complaint. To the best of our knowledge, this is the first case reported in the literature.

  19. Penile metastasis of urothelial carcinoma diagnosed by fine-needle aspiration

    Directory of Open Access Journals (Sweden)

    Santos Gilda

    2009-01-01

    Full Text Available Penile neoplasms are rare and can be primary or represent metastasis or local recurrence. The most common primary cancer of the penis is squamous cell carcinoma, accounting for 95% of all cancers. In spite of the rich vascularity of the organ, penile metastases are uncommon. Cutaneous metastasis of urothelial carcinoma (UC is extremely rare and generally accepted as the late manifestation of a systemic spread. By 1998, approximately 500 cases of penile metastasis had been reported worldwide. However, only few case reports and series of fine-needle aspiration cytology (FNAC of penile tumors have been documented. We report a case of penile metastasis from UC diagnosed by FNAC and describe the cytomorphological findings with an emphasis on cercariform cells. Although not commonly used, FNA of penile nodules can be effective in diagnosing recurrence or metastasis and avoiding surgical procedures, thus being an excellent initial procedure in the diagnostic approach.

  20. Immunohistochemistry and Fluorescence In Situ Hybridization Can Inform the Differential Diagnosis of Low-Grade Noninvasive Urothelial Carcinoma with an Inverted Growth Pattern and Inverted Urothelial Papilloma.

    Science.gov (United States)

    Sun, Juan-Juan; Wu, Yong; Lu, Yong-Ming; Zhang, Hui-Zhi; Wang, Tao; Yang, Xiao-Qun; Sun, Meng-Hong; Wang, Chao-Fu

    2015-01-01

    Urothelial carcinoma (UC) comprises a heterogeneous group of epithelial neoplasms with diverse biological behaviors and variable clinical outcomes. Distinguishing UC histological subtypes has become increasingly important because prognoses and therapy can dramatically differ among subtypes. In clinical work, overlapping morphological findings between low-grade noninvasive UC (LGNUC), which exhibits an inverted growth pattern, and inverted urothelial papilloma (IUP) can make subclassification difficult. We propose a combination of immunohistochemistry (IHC) and molecular cytogenetics for subtyping these clinical entities. In our study, tissue microarray immunohistochemical profiles of Ki-67, p53, cytokeratin 20 (CK20) and cyclinD1 were assessed. Molecular genetic alterations such as the gain of chromosomes 3, 7 or 17 or the homozygous loss of 9p21 were also assessed for their usefulness in differentiating these conditions. Based on our analysis, Ki-67 and CK20 may be useful for the differential diagnosis of these two tumor types. Fluorescence in situ hybridization (FISH) can also provide important data in cases in which the malignant nature of an inverted urothelial neoplasm is unclear. LGNUC with an inverted growth pattern that is negative for both Ki-67 and CK20 can be positively detected using FISH. PMID:26208279

  1. Immunohistochemistry and Fluorescence In Situ Hybridization Can Inform the Differential Diagnosis of Low-Grade Noninvasive Urothelial Carcinoma with an Inverted Growth Pattern and Inverted Urothelial Papilloma.

    Directory of Open Access Journals (Sweden)

    Juan-Juan Sun

    Full Text Available Urothelial carcinoma (UC comprises a heterogeneous group of epithelial neoplasms with diverse biological behaviors and variable clinical outcomes. Distinguishing UC histological subtypes has become increasingly important because prognoses and therapy can dramatically differ among subtypes. In clinical work, overlapping morphological findings between low-grade noninvasive UC (LGNUC, which exhibits an inverted growth pattern, and inverted urothelial papilloma (IUP can make subclassification difficult. We propose a combination of immunohistochemistry (IHC and molecular cytogenetics for subtyping these clinical entities. In our study, tissue microarray immunohistochemical profiles of Ki-67, p53, cytokeratin 20 (CK20 and cyclinD1 were assessed. Molecular genetic alterations such as the gain of chromosomes 3, 7 or 17 or the homozygous loss of 9p21 were also assessed for their usefulness in differentiating these conditions. Based on our analysis, Ki-67 and CK20 may be useful for the differential diagnosis of these two tumor types. Fluorescence in situ hybridization (FISH can also provide important data in cases in which the malignant nature of an inverted urothelial neoplasm is unclear. LGNUC with an inverted growth pattern that is negative for both Ki-67 and CK20 can be positively detected using FISH.

  2. ARID1A alterations are associated with FGFR3-wild type, poor-prognosis, urothelial bladder tumors.

    Directory of Open Access Journals (Sweden)

    Cristina Balbás-Martínez

    Full Text Available Urothelial bladder cancer (UBC is heterogeneous at the clinical, pathological, genetic, and epigenetic levels. Exome sequencing has identified ARID1A as a novel tumor suppressor gene coding for a chromatin remodeling protein that is mutated in UBC. Here, we assess ARID1A alterations in two series of patients with UBC. In the first tumor series, we analyze exons 2-20 in 52 primary UBC and find that all mutant tumors belong to the aggressive UBC phenotype (high grade non-muscle invasive and muscle invasive tumors (P = 0.05. In a second series (n = 84, we assess ARID1A expression using immunohistochemistry, a surrogate for mutation analysis, and find that loss of expression increases with higher stage/grade, it is inversely associated with FGFR3 overexpression (P = 0.03 but it is not correlated with p53 overexpression (P = 0.30. We also analyzed the expression of cytokeratins in the same set of tumor and find, using unsupervised clustering, that tumors with ARID1A loss of expression are generally KRT5/6-low. In this patient series, loss of ARID1A expression is also associated with worse prognosis, likely reflecting the higher prevalence of losses found in tumors of higher stage and grade. The independent findings in these two sets of patients strongly support the notion that ARID1A inactivation is a key player in bladder carcinogenesis occurring predominantly in FGFR3 wild type tumors.

  3. Detection of serum CYFRA21-1 in patients with urothelial bladder carci-noma%膀胱尿路上皮细胞癌患者血清 CYFRA21-1水平的测定

    Institute of Scientific and Technical Information of China (English)

    孔朝辉; 朱晓博; 范小玲

    2014-01-01

    目的:检测膀胱尿路上皮细胞癌患者血清中CYFRA21-1水平并探讨其临床意义。方法:采用电化学发光免疫分析技术检测57例膀胱尿路上皮细胞癌患者和52例泌尿系统良性疾病患者以及49例健康个体血清CY-FRA21-1水平。结果:膀胱尿路上皮细胞癌患者血清CYFRA21-1水平和阳性率均高于泌尿系统良性疾病患者与健康人群( F/χ2=28.949、15.221,P均<0.05)。膀胱尿路上皮细胞癌病理分级与血清CYFRA21-1水平及阳性率均无关(P均>0.05)。 T3及T3M+期肿瘤较Ta、T1、T2期肿瘤患者血清CYFRA21-1水平及阳性率均升高(F/χ2=2.096、34.232,P均<0.05);与初发肿瘤相比,复发膀胱尿路上皮细胞癌患者血清CYFRA21-1水平及阳性率均升高(t/χ2=3.968、9.541,P均<0.05)。结论:血清CYFRA21-1可以作为膀胱尿路上皮细胞癌的一个可靠的肿瘤标志物,特别是在监测膀胱尿路上皮癌转移或复发时更具优势。%Aim:To study value of serum CYFRA21-1 in urothelial bladder carcinoma and its clinical significance . Methods:Electrochemiluminescence method was used to detect serum CYFRA 21-1 level of 158 patients, including 57 ca-ses with urothelial bladder carcinoma (group 1), 52 cases with benign diseases of the urinary system (group 2), and 49 healthy individuals(group 3).Results: Compared with group 2 and group 3, serum CYFRA21-1 level and positive rate were significantly higher in group 1 (F/χ2 =28.949,15.221,P0.05).The CYFRA21-1 level and positive rate increased significantly in T 3 and T3M+stage compared to Ta, T1 and T2 stage(F/χ2 =2.096,34.232,P<0.05).Compared with primary tumor, serum CYFRA21-1 level and positive rate were significantly increased in recurrent urothelial bladder carcinoma ( t/χ2 =3.968, 9.541,P<0.05).Conclusion:Serum CYFRA21-1 seems to be a marker of urothelial bladder carcinoma .It is useful for monitoring this disease

  4. Molecular targets in urothelial cancer: detection, treatment, and animal models of bladder cancer

    Science.gov (United States)

    Smolensky, Dmitriy; Rathore, Kusum; Cekanova, Maria

    2016-01-01

    Bladder cancer remains one of the most expensive cancers to treat in the United States due to the length of required treatment and degree of recurrence. In order to treat bladder cancer more effectively, targeted therapies are being investigated. In order to use targeted therapy in a patient, it is important to provide a genetic background of the patient. Recent advances in genome sequencing, as well as transcriptome analysis, have identified major pathway components altered in bladder cancer. The purpose of this review is to provide a broad background on bladder cancer, including its causes, diagnosis, stages, treatments, animal models, as well as signaling pathways in bladder cancer. The major focus is given to the PI3K/AKT pathway, p53/pRb signaling pathways, and the histone modification machinery. Because several promising immunological therapies are also emerging in the treatment of bladder cancer, focus is also given on general activation of the immune system for the treatment of bladder cancer. PMID:27784990

  5. Risk stratification for kidney sparing procedure in upper tract urothelial carcinoma

    Science.gov (United States)

    Khene, Zine-Eddine; Mathieu, Romain; Kammerer-Jacquet, Solène-Florence; Seisen, Thomas; Roupret, Morgan; Shariat, Shahrokh F.; Peyronnet, Benoit

    2016-01-01

    Risk stratification for kidney sparing procedures (KSP) to treat upper tract urothelial carcinoma (UTUC) is a major issue. A non-systematic Medline/PubMed literature search was performed using the terms “upper tract urothelial carcinoma” with different combinations of keywords to review the current knowledge on this topic. Original articles, reviews and editorials in English language were selected based on their clinical relevance. Available techniques for KSP include segmental ureterectomy and endoscopic resection through a percutaneous or flexible ureteroscopic access. These approaches were traditionally restricted to patients with imperative indications. Current recommendations suggest that selected patients with normal contralateral kidney should also be candidates for such treatments. Modern imaging and endoscopy have improved to accurately stage and grade the tumor while various prognostic clinical factors and biomarkers have been proposed to identify tumor with aggressive features and worse outcomes. Several predictive models using different combinations of such baseline characteristics may help clinicians in clinical decision making. However, risk-adapted based approach that has been proposed in recent guidelines to identify patients who are more likely to benefit from KSP only relies on few clinical and pathological factors. Despite growing understanding of the disease, treatment of UTUC remains challenging. Further efforts and collaborative multicenter studies are mandatory to improve risk stratification to decide and promote optimal KSP in UTUC. These efforts should focus on the integration of promising biomarkers and predictive tools in clinical decision making.

  6. [Specific types of bladder cancer].

    Science.gov (United States)

    Bertz, S; Hartmann, A; Knüchel-Clarke, R; Gaisa, N T

    2016-02-01

    Bladder cancer shows rare variants and special subtypes with diverse prognostic importance and therefore may necessitate different therapeutic approaches. For pathologists it is important to histologically diagnose and specify such variants. Nested variants of urothelial carcinoma with inconspicuous, well-formed tumor cell nests present with an aggressive course. The plasmacytoid variant, which morphologically resembles plasma cells is associated with a shorter survival time and a high frequency of peritoneal metastasis. Micropapillary urothelial carcinoma with small papillary tumor cell islands within artificial tissue retraction spaces and frequent lymphovascular invasion also has a poor prognosis. Other important rare differential variants listed in the World Health Organization (WHO) classification are microcystic, lymphoepithelioma-like, sarcomatoid, giant cell and undifferentiated urothelial carcinomas. Additionally, there are three special types of bladder cancer: squamous cell carcinoma, adenocarcinoma and small cell neuroendocrine carcinoma of the bladder. These tumors are characterized by pure squamous cell or glandular differentiation and are sometimes less responsive to adjuvant (chemo)therapy. Small cell carcinoma of the bladder mimics the neuroendocrine features of its pulmonary counterpart, shows an aggressive course but is sensitive to (neo-)adjuvant chemotherapy. The morphology and histology of the most important variants and special types are discussed in this review. PMID:26782034

  7. A Giant Pedunculated Urothelial Polyp Mimicking Bladder Mass in a Child: A Rare Case

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    Mehmet Kaba

    2014-01-01

    Full Text Available Ureteral fibroepithelial polyps are rarely seen benign tumors with mesodermal origin. These polyps can involve kidney, pelvis, ureter, bladder, and urethra. The most common symptoms are hematuria and flank pain. The choice of treatment is either endoscopic or surgical resection of polyp by sparing kidney. Here, we presented a pediatric case with giant, fibroepithelial polyp that mimics bladder tumor, originating from middle segment of the ureter.

  8. Multifactorial, site-specific recurrence models after radical cystectomy for urothelial carcinoma: external validation in a cohort of Korean patients.

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    Hyung Suk Kim

    Full Text Available The aim of this study was to evaluate the accuracy of site-specific recurrence models after radical cystectomy in the Korean population.We conducted a review of an electronic medical record of 572 patients who underwent radical cystectomy for urothelial carcinoma of the bladder. Primary end point was the site-specific recurrence after radical cystectomy.The median follow-up in the validation cohort was 42.3 months (interquartile range: 23.0-89.3 months. During the follow-up period, there were 165 patients (28.8%, 85 (14.9%, 31 (5.4%, and 78 (13.6% who recurred in abdomen/pelvis, thoracic region, upper urinary tract, and bone, respectively. The c-indices of abdomen/pelvis, thoracic region, upper urinary tract, and bone models 3 years after radical cystectomy were 0.69 (95% confidence interval [CI], 0.65-0.73, 0.69 (95% CI, 0.64-0.75, 0.61 (95% CI, 0.52-0.69, and 0.65 (95% CI, 0.59-0.71, respectively. Kaplan-Meier curves demonstrated that models discriminated well and log-rank test were all highly significant (all p<0.001, except upper urinary tract model (p = 0.366. Decision curve analysis revealed that the use of prediction models for abdomen/pelvis, thoracic region, and bone recurrence was associated with net benefit gains relative to the treat-all strategy, but not the model for upper urinary tract recurrence.Abdomen/pelvis, thoracic region, and bone models demonstrate moderate discrimination, adequate calibration, and meaningful net benefit gains, whereas upper urinary tract model does not seem applicable to patients from Asia because it has suboptimal accuracy.

  9. Calcaneal acrometastasis from urothelial carcinoma of the ureter: a case report and literature review

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    Ryder JH

    2013-04-01

    Full Text Available Jonathan H Ryder,1 Sean V McGarry,2 Jue Wang1  1Division of Oncology/Hematology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA; 2Department of Orthopaedic Surgery and Rehabilitation, University of Nebraska Medical Center, Omaha, Nebraska, USA Purpose: Ureteral cancer is a rare entity. Typical symptoms are painless hematuria as well as flank pain. Bone metastasis of ureteral cancer can occur in nearby bone structures, such as the spine, pelvis, and hip bone. Distal bone metastasis, such as that in the calcaneus bone, however, is rare. Case report: An 82-year-old woman presented to the orthopedic clinic at the university hospital with a 3-month history of left heel pain. A magnetic resonance imaging (MRI of her foot demonstrated a calcaneal lytic lesion. A biopsy of the lytic lesion showed urothelial carcinoma with squamous differentiation. A computed tomography (CT scan of the abdomen and pelvis showed left hydronephrosis and an obstructive mass in the left ureter, at the iliac crossing. The patient received combined therapy that included local radiation, bisphosphonate, and chemotherapy, with complete resolution of her cancer-related symptoms. However, she eventually died from the progressive disease, 20 months after the initial diagnosis. Conclusion: This case highlights the rare presentation of ureter cancer with an initial presentation of foot pain, secondary to calcaneal metastasis. Multimodality therapy provides effective palliation of symptoms and improved quality of life. We also reviewed the literature and discuss the clinical benefits of multidisciplinary cancer care in elderly patients. Keywords: urothelial carcinoma, elderly, calcaneal acrometastasis, multimodality therapy, chemotherapy, radiation

  10. Rapamycin instead of mycophenolate mofetil or azathioprine in treatment of post-renal transplantation urothelial carcinoma

    Institute of Scientific and Technical Information of China (English)

    HU Xiao-peng; MA Lin-lin; WANG Yong; YIN Hang; WANG Wei; YANG Xiao-yong; ZHANG Xiao-dong

    2009-01-01

    Background Malignant tumor is the most common complication occurred in transplant recipients. It is widely recognized that immunosuppressive treatments increase the risk of cancer in transplant recipients. The efficacy and safety of rapamycin (RPM) in combination with low-dose calcineurin inhibitor (CNI) in treating 15 renal allograft recipients which developed urothelial carcinoma were observed. Methods Immunosuppressive regimen in all recipients was altered with rapamycin to replace mycophenolate mofetil (MMF) or azathioprine (Aza). The initial loading dosage was 2 mg/d, and the next dosage was 1 mg/d. The dosage of rapamycin was carefully adjusted according to the blood drug level and concentration of the drug was maintained at 4-6 ug/L. In all the 15 patients, the calcineurin inhibitor was reduced down to one third of the original dosage after the rapamycin blood concentration became stable. Surgical treatment and intravesical instillation chemotherapy were carried out in all patients. Recurrence of the tumor was monitored throughout the study. Post-transplant renal function and side effects were also closely monitored. Results Among the 15 patients, 9 had no tumor recurrence in 2 years, 2 had tumor recurrences twice, and 4 had once. There was no acute rejection observed during RPM treatment. Post-transplant renal function in 11 patients was improved, with a decreased creatinine level. Hyperlipoidemia and thrombocytopenia were the most frequent adverse events which responded well to corresponding treatments. Conclusion Among the renal allograft recipients with urothelial carcinoma, combination of rapamycin and low dose calcineurin inhibitor treatment is effective and safe.

  11. Skeletal muscle metastasis from transitional cell carcinoma of the urinary bladder: Clinicoradiological features

    Energy Technology Data Exchange (ETDEWEB)

    Nabi, G. E-mail: nabeegholam@hotmail.com; Gupta, N.P.; Gandhi, D

    2003-11-01

    AIM: To define the clinicoradiological characteristics of skeletal muscle metastasis from transitional cell carcinoma of the urinary bladder. MATERIALS AND METHODS: A retrospective review of all patients with skeletal muscle metastasis was undertaken between January 1999 to December 2001. Patients suspected of having a metastasis on radiological examinations, and subsequently proven to have metastatic disease on histological examination were included in study. The clinical presentation and radiological features of five patients with skeletal muscle metastasis from bladder tumours were reviewed from hospital records. RESULTS: Twenty-four patients had skeletal muscle metastasis from various primaries. Of these five patients had previous or concurrent primary tumours in the bladder. Patients were aged between 27-70 years (mean 52 years), and all had persistent, localized pain with or without accompanying swelling. The muscles involved were psoas in three patients, adductor muscles of thigh in one and rectus abdominis in one. Four patients had radical cystectomy with urinary diversion (two ileal conduit and two orthotopic sigmoid neobladder). One patient presented with bladder tumour and concomitant muscular metastasis. All patients underwent helical computed tomography (CT) before confirmation of diagnosis by fine-needle aspiration (FNA) or biopsy. The typical appearance of low-density enhancing lesions on CT was mistaken for abscess in two patients and failure to respond to conservative treatment led to suspicion of metastasis. Diagnosis was proven histologically in all patients (FNA in three and biopsy in two). All patients had palliative chemotherapy (Mitomycin, Vincristine, Adriamycin and Cyclophosphamide). Two patients had local palliative 3500 rad radiotherapy for persistent pain. Mean survival was 8 months (range 6-12 months). CONCLUSION: Muscular metastasis from urothelial tumours typically presents with persistent localized pain with or without swelling. The

  12. CLINICO-PATHOLOGICAL STUDY OF CARCINOMA GALL BLADDER

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    Ravindra

    2015-12-01

    Full Text Available INTRODUCTION Gall bladder cancer is 5th most common cancer of GIT. It is associated with cholelithiasis in significant number of patients. Cholelithiasis is cause or effect of gall bladder cancer is still uncertain. There are many risk factors which are common to both gall stones and cancer. Preoperative diagnosis of gall bladder cancer is increased with better and new investigation facilities. AIM The study was aimed to assess clinicopathological behaviour, sociodemography, diagnostic modalities and treatment of cancer gall bladder. MATERIAL AND METHODS It was a type of prospective study which included 75 patients with clinical features suggestive of biliary disease. Various diagnostic modalities and treatment options were assessed along with sociodemography and clinical picture. RESULT Common clinical features were pain abdomen, obstructive jaundice and lump. Nearly one third of the patients were having anaemia and abnormal liver function tests. Majority had gall bladder fossa mass with liver extension and gall stones. The most common histopathological variety of carcinoma Gallbladder was Adenocarcinoma. CONCLUSION Carcinoma Gallbladder was found to affect predominantly the older female patients after the age of 40 years. Cholelithiasis was found in 69.3% patients of carcinoma Gallbladder. The most common clinical presentation was pain abdomen (90.7%. The most common histopathological variety of carcinoma Gallbladder was Adenocarcinoma. Majority of patients were treated with palliative measures.

  13. N-Acetylation of p-aminobenzoic acid and p-phenylenediamine in primary porcine urinary bladder epithelial cells and in the human urothelial cell line 5637.

    Science.gov (United States)

    Föllmann, Wolfram; Blaszkewicz, Meinolf; Behm, Claudia; Degen, Gisela H; Golka, Klaus

    2012-01-01

    N-Acetyltransferases (NAT) are important enzymes in the metabolism of certain carcinogenic arylamines, as N-acetylation decreases or prevents their bioactivation via N-hydroxylation. To study such processes in the bladder, cell culture models may be used, but metabolic competence needs to be characterized. This study focused on the N-acetylation capacity of two urothelial cell systems, using p-aminobenzoic acid (PABA) and the hair dye precursor p-phenylenediamine (PPD), two well-known substrates of the enzyme NAT1. The constitutive NAT1 activity was investigated using primary cultures of porcine urinary bladder epithelial cells (PUBEC) and in the human urothelial cell line 5637 to assess their suitability for further in vitro studies on PABA and PPD-induced toxicity. N-Acetylation of PABA and PPD was determined by high-performance liquid chromatography (HPLC) analysis in cytosols of the two cell systems upon incubation with various substrate levels for up to 60 min. The primary PUBEC revealed higher N-acetylation rates (2.5-fold for PABA, 5-fold for PPD) compared to the 5637 cell line, based on both PABA conversion to its acetylated metabolite and formation of mono- and diacetylated PPD. The urothelial cell systems may thus be useful as a tool for further studies on the N-acetylation of aromatic amines via NAT1.

  14. SOX4 expression in bladder carcinoma

    DEFF Research Database (Denmark)

    Aaboe, Mads; Birkenkamp-Demtroder, Karin; Wiuf, Carsten;

    2006-01-01

    The human transcription factor SOX4 was 5-fold up-regulated in bladder tumors compared with normal tissue based on whole-genome expression profiling of 166 clinical bladder tumor samples and 27 normal urothelium samples. Using a SOX4-specific antibody, we found that the cancer cells expressed the...

  15. Unique Case Report of Pineal Gland Metastasis From Bladder Carcinoma

    OpenAIRE

    Li, Jun; Wang, Ping; Wang, Bin

    2016-01-01

    Abstract 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 wi...

  16. Enterovesical Fistula Secondary to Squamous Cell Carcinoma of the Bladder.

    Science.gov (United States)

    Sellers, William; Fiorelli, Robert

    2015-11-01

    Enterovesical fistulas are a well-known complication of inflammatory and malignant bowel disease. Bladder carcinoma, however, is an extremely rare etiology. We describe a case of squamous cell carcinoma of the bladder with an enterovesical fistula. This rare phenomenon has never been previously reported in western literature. We review the diagnosis, work up and treatment of enterovesical fistulas. Unfortunately, the prognosis for these highly invasive tumors is very poor and the treatment is often palliative. The high morbidity and mortality makes management of these patients exceptionally challenging.

  17. Loss of MTUS1/ATIP expression is associated with adverse outcome in advanced bladder carcinomas: data from a retrospective study

    International Nuclear Information System (INIS)

    Seventy percent of all bladder tumours tend to recur and need intensive surveillance, and a subset of tumours progress to muscle-invasive and metastatic disease. However, it is still difficult to find the adequate treatment for every individual patient as it is a very heterogeneous disease and reliable biomarkers are still missing. In our study we searched for new target genes in the critical chromosomal region 8p and investigated the potential tumour suppressor gene candidate MTUS1/ATIP in bladder cancer. MTUS1 was identified to be the most promising deleted target gene at 8p in aCGH analysis with 19 papillary bladder tumours. A correlation with bladder cancer was further validated using immunohistochemistry of 85 papillary and 236 advanced bladder tumours and in functional experiments. Kaplan-Meier analysis and multivariate Cox-regression addressed overall survival (OS) and disease-specific survival (DSS) as a function of MTUS1/ATIP expression. Bivariate correlations investigated associations between MTUS1/ATIP expression, patient characteristics and histopathology. MTUS1 expression was analysed in cell lines and overexpressed in RT112, where impact on viability, proliferation and migration was measured. MTUS1 protein expression was lost in almost 50% of all papillary and advanced bladder cancers. Survival, however, was only influenced in advanced carcinomas, where loss of MTUS1 was associated with adverse OS and DSS. In this cohort, there was also a significant correlation of MTUS1 expression and histological subtype: positive expression was detected in all micropapillary tumours and aberrant nuclear staining was detected in a subset of plasmocytoid urothelial carcinomas. MTUS1 was expressed in all investigated bladder cell lines and overexpression in RT112 led to significantly decreased viability. MTUS1 is a tumour suppressor gene in cultured bladder cancer cells and in advanced bladder tumours. It might represent one new target gene at chromosome 8p and can be

  18. Exosomal protein interactors as emerging therapeutic targets in urothelial bladder cancer

    International Nuclear Information System (INIS)

    Background: Exosomes are rich sources of biological material (proteins and nucleic acids) secreted by both tumor and normal cells, and found in urine of urinary bladder cancer patients. Objective: The objective of the study was to identify interacting exosomal proteins in bladder cancer for future use in targeted therapy. Methods: The Exocarta database (www.exocarta.org) was mined for urinary bladder cancer specific exosomal proteins. The urinary bladder cancer specific exosomal proteins (n = 248) were analyzed to identify enriched pathways by Onto-tool Pathway Express (http://vortex.cs.wayne.edu/ ontoexpress). Results: Enriched pathways included cellular architecture, motility, cell to cell adhesion, tumorigenesis and metastasis. Proteins in the 9 top-ranked pathways included CTNNA1 (alpha-catenin), CTNNB1 (beta-catenin), VSAP, ITGA4, PAK1, DDR1, CDC42, RHOA, NRAS, RHO, PIK3AR1, MLC1, MMRN1, and CTTNBP2 and network analysis revealed 10 important hub proteins and identified inferred interactor NF2. Conclusions: The importance of identifying interactors is that that they can be used as targets for therapy, for example, using Bevacizumab (avastin - an angiogenesis inhibitor) against NF2 to inhibit protein-protein interactions will inhibit tumor growth and progression by hindering the exosome biogenesis

  19. Polyoma (BK) virus associated urothelial carcinoma originating within a renal allograft five years following resolution of polyoma virus nephropathy.

    Science.gov (United States)

    Salvatore, Steven P; Myers-Gurevitch, Patricia M; Chu, Stacy; Robinson, Brian D; Dadhania, Darshana; Seshan, Surya V

    2016-03-01

    A direct role for BK polyomavirus infection in malignant tumors of renal allografts and urinary tract is emerging. Case reports suggest a link between BK virus (BKV) reactivation and development of malignancy in renal allograft recipients. Herein we describe the first case of BKV positive invasive urothelial carcinoma within the renal allograft, presenting with chronic diarrhea and weight loss 5 years following resolution of BK viremia/nephropathy (BKVN). Unique to our case was the remote history of BK viremia/BKVN, rising titer of anti-HLA antibody and presence of renal limited urothelial carcinoma with microinvasion of malignant cells staining positive for SV40 large T antigen (T-Ag). These findings suggest that persistence of subclinical BKV infection within the renal allograft may play a role in the malignant transformation of epithelial cells. Patients with history of BKVN may be at risk for kidney and urinary tract malignancy despite resolution of BK viremia/BKVN.

  20. Expression of programmed cell death protein 4 (PDCD4) and miR-21 in urothelial carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, Nicolas, E-mail: simplissimus@gmx.de [Department of Urology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn (Germany); Goeke, Friederike, E-mail: Friederike.goeke@ukb.uni-bonn.de [Department of Pathology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn (Germany); Splittstoesser, Vera, E-mail: Veri.sp@web.de [Department of Urology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn (Germany); Lankat-Buttgereit, Brigitte, E-mail: Lankatbu@staff.uni-marburg.de [Department of Internal Medicine, Philipps-University of Marburg, Baldingerstrasse, 35043 Marburg (Germany); Mueller, Stefan C., E-mail: Stefan.mueller@ukb.uni-bonn.de [Department of Urology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn (Germany); Ellinger, Joerg, E-mail: Joerg.ellinger@ukb.uni-bonn.de [Department of Urology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn (Germany)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer The tumor suppressor gene PDCD4 is down-regulated in many tumorous entities. Black-Right-Pointing-Pointer We investigate the impact of PDCD4 and its regulating factor miR-21 in urothelial carcinoma. Black-Right-Pointing-Pointer We confirm PDCD4 as a tumor suppressor gene and it could be a diagnostic marker for this tumor. -- Abstract: Background: We investigated the role of the programmed cell death 4 (PDCD4) tumor suppressor gene in specimens of transitional cell carcinoma and of healthy individuals. Methods: PDCD4 immunohistochemical expression was investigated in 294 cases in histologically proven transitional cell carcinoma in different tumorous stages (28 controls, 122 non-muscle invasive urothelial carcinoma, stages Tis-T1, 119 invasive transitional cell carcinoma stages T2-T4 and 25 metastases). MiR-21 expression, an important PDCD4 regulator, was assessed with real-time PCR analysis and showed inverse correlation to tissue PDCD4 expression. Results: Nuclear and cytoplasmatic PDCD4 immunostaining decreased significantly with histopathological progression of the tumor (p < 0001). Controls showed strong nuclear and cytoplasmatic immunohistochemical staining. MiR-21 up regulation in tissue corresponded to PDCD4 suppression. Conclusions: These data support a decisive role for PDCD4 down regulation in transitional cell carcinoma and confirm miR-21 as a negative regulator for PDCD4. Additionally, PDCD4 immunohistochemical staining turns out to be a possible diagnostic marker for transitional cell carcinoma.

  1. Expression of programmed cell death protein 4 (PDCD4) and miR-21 in urothelial carcinoma

    International Nuclear Information System (INIS)

    Highlights: ► The tumor suppressor gene PDCD4 is down-regulated in many tumorous entities. ► We investigate the impact of PDCD4 and its regulating factor miR-21 in urothelial carcinoma. ► We confirm PDCD4 as a tumor suppressor gene and it could be a diagnostic marker for this tumor. -- Abstract: Background: We investigated the role of the programmed cell death 4 (PDCD4) tumor suppressor gene in specimens of transitional cell carcinoma and of healthy individuals. Methods: PDCD4 immunohistochemical expression was investigated in 294 cases in histologically proven transitional cell carcinoma in different tumorous stages (28 controls, 122 non-muscle invasive urothelial carcinoma, stages Tis-T1, 119 invasive transitional cell carcinoma stages T2–T4 and 25 metastases). MiR-21 expression, an important PDCD4 regulator, was assessed with real-time PCR analysis and showed inverse correlation to tissue PDCD4 expression. Results: Nuclear and cytoplasmatic PDCD4 immunostaining decreased significantly with histopathological progression of the tumor (p < 0001). Controls showed strong nuclear and cytoplasmatic immunohistochemical staining. MiR-21 up regulation in tissue corresponded to PDCD4 suppression. Conclusions: These data support a decisive role for PDCD4 down regulation in transitional cell carcinoma and confirm miR-21 as a negative regulator for PDCD4. Additionally, PDCD4 immunohistochemical staining turns out to be a possible diagnostic marker for transitional cell carcinoma.

  2. External validation of an online nomogram in patients undergoing radical nephroureterectomy for upper urinary tract urothelial carcinoma

    OpenAIRE

    Ku, J H; Moon, K C; Jung, J H; Jeong, S H; Kwak, C; H.H. Kim

    2013-01-01

    Background: The objective was to validate an online nomogram developed based on the French collaborative national database on upper urinary tract urothelial carcinoma (UUT-UC) using a different cohort. Methods: The study comprised 328 patients with UUT-UC who underwent radical nephroureterectomy. The discrimination of models was quantified using Harrell's concordance index. The relationship between the model-derived and actuarial cancer-specific mortality was graphically explored within calib...

  3. Hydronephrotic urine in the obstructed kidney promotes urothelial carcinoma cell proliferation, migration, invasion through the activation of mTORC2-AKT and ERK signaling pathways.

    Directory of Open Access Journals (Sweden)

    Chi-Hao Chang

    Full Text Available Obstructive nephropathy is the most common presentation of urothelial carcinoma. The role of the urine in the obstructed kidney namely "hydronephrotic urine" in urothelial carcinoma has not been extensively explored. This study aims to evaluate whether hydronephrotic urine in the obstructed kidney could promote urothelial carcinoma. The hydronephrotic urine was collected from the obstructed kidneys of Sprague-Dawley rats induced by different periods of unilateral ureteral obstruction (UUO. By the inhibition of LY294002 and PD184352, we confirm that hydronephrotic urine promotes urothelial carcinoma cell (T24 and immortalized normal urothelial cells (E6 proliferation, migration and invasion in a dose-dependent manner through the activation of the mTORC2-AKT and ERK signaling pathways. Hydronephrotic urine also increases the expression of cyclin-D2, cyclin-B and CDK2. It also decreases the expression of p27 and p21 in both urothelial carcinoma cells and normal urothelial cells. By the protein array study, we demonstrate that many growth factors which promote tumor cell survival and metastasis are over-expressed in a time-dependent manner in the hydronephrotic urine, including beta-FGF, IFN-γ, PDGF-BB, PIGF, TGF-β, VEGF-A, VEGF-D and EGF. These results suggest that hydronephrotic urine promotes normal and malignant urothelial cells proliferation, migration and invasion, through the activation of the mTORC2-AKT and ERK signaling pathways. Further investigation using live animal models of tumor growth may be needed to clarify aspects of these statements.

  4. Impacts of CA9 gene polymorphisms on urothelial cell carcinoma susceptibility and clinicopathologic characteristics in Taiwan.

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    Shian-Shiang Wang

    Full Text Available BACKGROUND: Carbonic anhydrase 9 (CA9 is reportedly overexpressed in several types of carcinomas and is generally considered a marker of malignancy. The current study explored the effect of CA9 gene polymorphisms on the susceptibility of developing urothelial cell carcinoma (UCC and the clinicopathological status. METHODOLOGY AND PRINCIPAL FINDINGS: A total of 442 participants, including 221 healthy people and 221 patients with UCC, were recruited for this study. Four single-nucleotide polymorphisms (SNPs of the CA9 gene were assessed by a real-time PCR with the TaqMan assay. After adjusting for other co-variants, the individuals carrying at least one A allele at CA9 rs1048638 had a 2.303-fold risk of developing UCC than did wild-type (CC carriers. Furthermore, UCC patients who carried at least one A allele at rs1048638 had a higher invasive stage risk (p< 0.05 than did patients carrying the wild-type allele. Moreover, among the UCC patients with smoker, people with at least one A allele of CA9 polymorphisms (rs1048638 had a 4.75-fold (95% CI = 1.204-18.746 increased risk of invasive cancer. CONCLUSION: The rs1048638 polymorphic genotypes of CA9 might contribute to the prediction of susceptibility to and pathological development of UCC. This is the first study to provide insight into risk factors associated with CA9 variants in carcinogenesis of UCC in Taiwan.

  5. Bladder tumours in children: An interesting case report of TCC with a partial inverted growth pattern.

    Science.gov (United States)

    El Rahman, Davide Abed; Salvo, Giuseppe; Palumbo, Carlotta; Rocco, Bernardo; Rocco, Francesco

    2014-09-30

    Bladder urothelial carcinoma is typically a disease of older individuals and rarely occurs below the age of 40 years. There is debate and uncertainty in the literature regarding the clinicopathologic and prognostic characteristics of bladder urothelial neoplasms in younger patients compared with older patients, although no consistent age criteria have been used to define "younger" age group categories. We report on a 16 years old girl with transitional cell carcinoma of the bladder with a partial inverted growth pattern who presented with gross hematuria. Ultrasonography revealed a papillary lesion in the bladder; cystoscopic evaluation showed a 15 mm papillary lesion with a thick stalk located in the left bladder wall. Pathologic evaluation of the specimen was reported as "low grade transitional cell carcinoma of the bladder with a partial inverted growth pattern".

  6. Unusual presentation of high-grade neuroendocrine carcinoma of the Urinary bladder with small-cell and large-cell features

    Directory of Open Access Journals (Sweden)

    Vitor Fiorin de Vasconcellos

    2013-10-01

    Full Text Available High-grade neuroendocrine carcinoma of the urinary bladder comprehends small-cell and large-cell variants. It is a rare and aggressive neoplasm, mostly diagnosed in advanced stages. It is more frequently encountered among Caucasian men in the sixth decade of life. Urinary symptoms are the most common clinical presentation. Diagnosis is generally not troublesome once the lesions are easily detectable by imaging exams and cystoscopy. This neoplasia is associated with tobacco smoking, and is frequently associated with other carcinomatous components such as urothelial carcinoma, adenocarcinoma, and sarcomatoid carcinoma. The authors report a case of an apparently healthy female patient who presented cervical lymph node enlargement not accompanied by systemic symptoms. The supraclavicular lymph node biopsy revealed metastatic small cell carcinoma. The computed tomography scan showed a bladder wall nodular thickening, enlarged lymph nodes along the iliac, periaortic, mediastinal, cervical and supraclavicular chains, as well as an insufflating lytic bone lesion in the right iliac wing. The positron emission tomography-fluorodeoxyglucose (PET-FDG added to these findings, the presence of a paraesophageal lymph node, lymphadenomegaly in the gluteal region and a vertebral lytic lesion in T10. Resected specimen of the bladder tumor revealed a high-grade neuroendocrine carcinoma with small-cell and large-cell features.

  7. Deficiency of pRb family proteins and p53 in invasive urothelial tumorigenesis.

    Science.gov (United States)

    He, Feng; Mo, Lan; Zheng, Xiao-Yong; Hu, Changkun; Lepor, Herbert; Lee, Eva Y-H P; Sun, Tung-Tien; Wu, Xue-Ru

    2009-12-15

    Defects in pRb tumor suppressor pathway occur in approximately 50% of the deadly muscle-invasive urothelial carcinomas in humans and urothelial carcinoma is the most prevalent epithelial cancer in long-term survivors of hereditary retinoblastomas caused by loss-of-function RB1 mutations. Here, we show that conditional inactivation of both RB1 alleles in mouse urothelium failed to accelerate urothelial proliferation. Instead, it profoundly activated the p53 pathway, leading to extensive apoptosis, and selectively induced pRb family member p107. Thus, pRb loss triggered multiple fail-safe mechanisms whereby urothelial cells evade tumorigenesis. Additional loss of p53 in pRb-deficient urothelial cells removed these p53-dependent tumor barriers, resulting in late-onset hyperplasia, umbrella cell nuclear atypia, and rare-occurring low-grade, superficial papillary bladder tumors, without eliciting invasive carcinomas. Importantly, mice deficient in both pRb and p53, but not those deficient in either protein alone, were highly susceptible to subthreshold carcinogen exposure and developed invasive urothelial carcinomas that strongly resembled the human counterparts. The invasive lesions had a marked reduction of p107 but not p130 of the pRb family. Our data provide compelling evidence, indicating that urothelium, one of the slowest cycling epithelia, is remarkably resistant to transformation by pRb or p53 deficiency; that concurrent loss of these two tumor suppressors is necessary but insufficient to initiate urothelial tumorigenesis along the invasive pathway; that p107 may play a critical role in suppressing invasive urothelial tumor formation; and that replacing/restoring the function of pRb, p107, or p53 could be explored as a potential therapeutic strategy to block urothelial tumor progression.

  8. Parafibromin Staining Characteristics in Urothelial Carcinomas and Relationship with Prognostic Parameters

    Science.gov (United States)

    Karaarslan, Serap; Yaman, Banu; Ozturk, Hakan; Kumbaraci, Banu Sarsik

    2015-01-01

    Background: Parafibromin is a recently defined tumor suppressor gene. The aim of our study was to determine the relationships of parafibromin expression in urothelial carcinomas (UCs) with prognostic parameters and to evaluate the use of parafibromin as a potential marker of UC. Methods: Parafibromin expression was assessed in 49 UC specimens using immunohistochemistry. The correlations between parafibromin expression and clinical and pathologic parameters were investigated. Results: Of the patients, 42 (85.7%) were male, and the mean age was 69.6 ± 8.2 years (range, 54 to 88 years). Morphologically, the UCs were divided into two groups: papillary (n = 27) and non-papillary (n = 22). There were seven low-grade (14.3%) and 42 high-grade (85.7%) tumors. Parafibromin was negative in 13 tumors (26.5%), partially positive in 19 tumors (38.8%), and positive in 17 tumors (34.7%). Parafibromin expression was more negative in UCs from upper urinary locations (n=17) and with muscularis propria invasion (n=28), which was statistically significant (p = .009 and p = .007, respectively). There was no statistically significant relationship between parafibromin expression and gender, age, tumor grade, survival, or disease-free survival. Conclusions: We found that UC cases with parafibromin positivity had less of a tendency to show muscularis propria invasion and were more commonly located in the lower urinary system. These results need to be confirmed with studies based on larger case series. PMID:26395176

  9. XRCC1 Arg194Trp and Arg399Gln polymorphisms and arsenic methylation capacity are associated with urothelial carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Chiang, Chien-I [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Huang, Ya-Li [Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Chen, Wei-Jen [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Shiue, Horng-Sheng [Department of Chinese Medicine, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan (China); Huang, Chao-Yuan; Pu, Yeong-Shiau [Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan (China); Lin, Ying-Chin [Department of Family Medicine, Shung Ho Hospital, Taipei Medical University, New Taipei, Taiwan (China); Department of Health Examination, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan (China); Division of Family Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan (China); Hsueh, Yu-Mei, E-mail: ymhsueh@tmu.edu.tw [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China)

    2014-09-15

    The association between DNA repair gene polymorphisms and bladder cancer has been widely studied. However, few studies have examined the correlation between urothelial carcinoma (UC) and arsenic or its metabolites. The aim of this study was to examine the association between polymorphisms of the DNA repair genes, XRCC1 Arg194Trp, XRCC1 Arg399Gln, XRCC3 Thr241Met, and XPD Lys751Gln, with urinary arsenic profiles and UC. To this end, we conducted a hospital-based case–control study with 324 UC patients and 647 age- and gender-matched non-cancer controls. Genomic DNA was used to examine the genotype of XRCC1 Arg194Trp, XRCC1 Arg399Gln, XRCC3 Thr241Met, and XPD Lys751Gln by PCR-restriction fragment length polymorphism analysis (PCR-RFLP). Urinary arsenic profiles were measured by high performance liquid chromatography (HPLC) linked with hydride generator and atomic absorption spectrometry. The XRCC1 399 Gln/Gln and 194 Arg/Trp and Trp/Trp genotypes were significantly related to UC, and the odds ratio (OR) and 95% confidence interval (95%CI) were 1.68 (1.03–2.75) and 0.66 (0.48–0.90), respectively. Participants with higher total urinary arsenic levels, a higher percentage of inorganic arsenic (InAs%) and a lower percentage of dimethylarsinic acid (DMA%) had a higher OR of UC. Participants carrying XRCC1 risk diplotypes G-C/G-C, A-C/A-C, and A-T/G-T, and who had higher total arsenic levels, higher InAs%, or lower DMA% compared to those with other XRCC1 diplotypes had a higher OR of UC. Our results suggest that the XRCC1 399 Gln/Gln and 194 Arg/Arg DNA repair genes play an important role in poor arsenic methylation capacity, thereby increasing the risk of UC in non-obvious arsenic exposure areas. - Highlights: • The XRCC1 399Gln/Gln genotype was significantly associated with increased OR of UC. • The XRCC1 194 Arg/Trp and Trp/Trp genotype had a significantly decreased OR of UC. • Combined effect of the XRCC1 genotypes and poor arsenic methylation capacity on

  10. XRCC1 Arg194Trp and Arg399Gln polymorphisms and arsenic methylation capacity are associated with urothelial carcinoma

    International Nuclear Information System (INIS)

    The association between DNA repair gene polymorphisms and bladder cancer has been widely studied. However, few studies have examined the correlation between urothelial carcinoma (UC) and arsenic or its metabolites. The aim of this study was to examine the association between polymorphisms of the DNA repair genes, XRCC1 Arg194Trp, XRCC1 Arg399Gln, XRCC3 Thr241Met, and XPD Lys751Gln, with urinary arsenic profiles and UC. To this end, we conducted a hospital-based case–control study with 324 UC patients and 647 age- and gender-matched non-cancer controls. Genomic DNA was used to examine the genotype of XRCC1 Arg194Trp, XRCC1 Arg399Gln, XRCC3 Thr241Met, and XPD Lys751Gln by PCR-restriction fragment length polymorphism analysis (PCR-RFLP). Urinary arsenic profiles were measured by high performance liquid chromatography (HPLC) linked with hydride generator and atomic absorption spectrometry. The XRCC1 399 Gln/Gln and 194 Arg/Trp and Trp/Trp genotypes were significantly related to UC, and the odds ratio (OR) and 95% confidence interval (95%CI) were 1.68 (1.03–2.75) and 0.66 (0.48–0.90), respectively. Participants with higher total urinary arsenic levels, a higher percentage of inorganic arsenic (InAs%) and a lower percentage of dimethylarsinic acid (DMA%) had a higher OR of UC. Participants carrying XRCC1 risk diplotypes G-C/G-C, A-C/A-C, and A-T/G-T, and who had higher total arsenic levels, higher InAs%, or lower DMA% compared to those with other XRCC1 diplotypes had a higher OR of UC. Our results suggest that the XRCC1 399 Gln/Gln and 194 Arg/Arg DNA repair genes play an important role in poor arsenic methylation capacity, thereby increasing the risk of UC in non-obvious arsenic exposure areas. - Highlights: • The XRCC1 399Gln/Gln genotype was significantly associated with increased OR of UC. • The XRCC1 194 Arg/Trp and Trp/Trp genotype had a significantly decreased OR of UC. • Combined effect of the XRCC1 genotypes and poor arsenic methylation capacity on

  11. A rare bladder cancer - small cell carcinoma: review and update

    Directory of Open Access Journals (Sweden)

    Ismaili Nabil

    2011-11-01

    Full Text Available Abstract Small cell carcinoma of the bladder (SCCB is rare, highly aggressive and diagnosed mainly at advanced stages. Hematuria is the main symptom of this malignancy. The origin of the disease is unknown; however the multipotent stem cell theory applies best to this case. Histology and immunohistochemistry shows a tumour which is indistinguishable from small cell lung carcinoma (SCLC. Coexistence of SCCB with other types of carcinoma is common. The staging system used is the TNM-staging of bladder transitional cell carcinoma. The treatment is extrapolated from that of SCLC. However, many patients with SCCB undergo radical resection which is rarely performed in SCLC. Patients with surgically resectable disease ( or = cT4bN+M+ should be managed with palliative chemotherapy based on neuroendocrine type regimens comprising a platinum drug (cisplatin in fit patients. The prognosis of the disease is poor mainly in the case of pure small cell carcinoma. Other research programs are needed to improve the outcome of SCCB.

  12. A panel of tumor markers, calreticulin, annexin A2, and annexin A3 in upper tract urothelial carcinoma identified by proteomic and immunological analysis

    International Nuclear Information System (INIS)

    Upper tract urothelial carcinoma (UTUC) is a tumor with sizable metastases and local recurrence. It has a worse prognosis than bladder cancer. This study was designed to investigate the urinary potential tumor markers of UTUC. Between January 2008 and January 2009, urine was sampled from 13 patients with UTUC and 20 healthy adults. The current study identified biomarkers for UTUC using non-fixed volume stepwise weak anion exchange chromatography for fractionation of urine protein prior to two-dimensional gel electrophoresis. Fifty five differential proteins have been determined by comparing with the 2-DE maps of the urine of UTUC patients and those of healthy people. Western blotting analysis and immunohistochemistry of tumor tissues and normal tissues from patients with UTUC were carried out to further verify five possible UTUC biomarkers, including zinc-alpha-2-glycoprotein, calreticulin, annexin A2, annexin A3 and haptoglobin. The data of western blot and immunohistochemical analysis are consistent with the 2-DE data. Combined the experimental data in the urine and in tumor tissues collected from patients with UTUC, the crucial over-expressed proteins are calreticulin, annexin A2, and annexin A3. Calreticulin, annexin A2, and annexin A3 are very likely a panel of biomarkers with potential value for UTUC diagnosis

  13. Expression and Clinicopathologic Significance of EpCAM and E-Cadherin in Urothelial Carcinoma of Renal Pelvis%肾盂癌中EpCAM和E-Cadherin的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    单立平; 卜仁戈; 张墨; 李波; 吴斌; 宋永胜

    2012-01-01

    Objective To investigate the pmgnostic value of EpCAM and E-Cadherin in urothelial carcinoma of rpnal pelvis. Methods Ep-CAM and E-Cadherin were analyzed by immunohistochemistry using monoclonal antiliodies in 50 cases of normal mucosa and 76 cases of urothelial carcinoma of renal pelvis. Results The positive rate of EpCAM in urothelial carcinoma of renal pelvis was 60.5% .which was significantly higher than in para-cancerous mucosa of 27.6%. The expression of EpCAM was significantly related with the differential clinical stage,pathological degree,distant metastasis and bladder tumor recurrence (all P< 0.05). The expression of E-Cadherin was significantly re-lated with the differential clinical stage,pathological degree and distant metastasis (all P < 0.05). There was negative correlation between the expression of EpCAM and E-Cadherin in urothelial carcinoma of renal pelvis ( r =-0.425,P < 0.01). Conclusion The expression EpCAM and E-Cadherin are highly related to occurrence,development,infiltration and metastasis of urothelial carcinoma of renal pelvis,and evaluation of the two proteins could be a very applicable guidance for the diagnosis of metastasis and invasion of urothelial carcinoma of renal pelvis.%目的 探讨EpCAM和E-Cadherin的表达与肾盂癌病理分级和临床分期的关系.方法 应用免疫组织化学SP法检测76例不同级别肾盂癌和50例癌旁正常组织中EpCAM和E-Cadherin的表达.结果 EpCAM在肾盂癌阳性表达率为60.5%(46/76),明显高于癌旁组织27.6%(21/76),差异具有统计学意义(P<0.05);EpCAM的表达与肾盂癌不同临床分期、病理分级、远处转移及继发膀胱肿瘤相关(P<0.05);EpCAM与E-Cadherin在肾盂癌中表达呈负相关(r=-0.425,P< 0.01).结论 EpCAM及E-Cadherin的表达变化与肾盂癌的发生发展、浸润转移有良好的相关性,同步检测二者在肾盂癌组织中的表达并综合分析两者之间的关系对评价肾盂癌的侵袭转移能力判断具有一定价值.

  14. Contemporary Evaluation and Management of Upper Tract Urothelial Cancer.

    Science.gov (United States)

    Mandalapu, Rao S; Matin, Surena F

    2016-08-01

    Radical nephroureterectomy with en bloc bladder cuff excision and regional lymphadenectomy is the gold standard for the management of high-grade and high-risk upper tract urothelial carcinomas. There are a few prospective randomized controlled studies in this uncommon and often aggressive disease to support level-1 management guidelines. However, recent developments in imaging, minimally invasive techniques, lymphatic dissemination, and bladder cancer prevention raise the hope for improved risk stratification and treatments without compromising, and hopefully improving, oncological outcomes. Multimodality approaches in terms of neoadjuvant, adjuvant topical, and systemic chemotherapeutic regimens are promising, with 2 prospective trials either open or in development.

  15. A retrospective study of post-operative gall bladder pathology with special reference to incidental carcinoma of the gall bladder

    OpenAIRE

    Jagannath Dev Sharma; Indrajit Kalita; Tonmoy Das; Papari Goswami; Manigreeva Krishnatreya

    2014-01-01

    Background: Surgical removal of gall bladder for its diseases is common. However, not much is known about the incidence of incidental carcinoma in such patients in our population. Objective of current study was to analyze the different pathological entities of post-operative gall bladder specimen with particular emphasis on incidental carcinoma. Methods: This retrospective study was carried out at a multi-specialty hospital in eastern India from the pathology records for the period from Au...

  16. [Analgesics and laxatives as risk factors for cancer in the efferent urinary tract--results of the Berlin Urothelial Carcinoma Study].

    Science.gov (United States)

    Bronder, E; Klimpel, A; Helmert, U; Greiser, E; Molzahn, M; Pommer, W

    1999-01-01

    A retrospective case-control study (1990-1995), the Berlin Urothelial Cancer Study (BUS), examined analgesics and laxatives as risks for the induction of urothelial cancer in renal pelvis, ureter and bladder. Especially for renal pelvis cancer could observe substance and dose specific risk of compound analgesics. The analgesic substances Phenacetin, Paracetamol, Acetylsalicylic acid (ASA) and Pyrazolones were assessed. Besides a risk of contact laxatives (chemical or anthranoide ingredients) for urothelial cancer was found, not yet described. The highest risk shows the anthranoide plant Senna. Thus this study confirms the risk of specific analgesic ingredients and found an evidence for a new risk of contact laxatives. As both, analgesics and contact laxatives, are typical OTC--("Over the counter") products, a severe controlling is demanded and for laxatives further studies are needed. PMID:10436491

  17. Regional differences in practice patterns and associated outcomes for upper tract urothelial carcinoma in Canada

    Science.gov (United States)

    Metcalfe, Michael; Kassouf, Wassim; Rendon, Ricardo; Bell, David; Izawa, Jonathan; Chin, Joseph; Kapoor, Anil; Matsumoto, Edward; Lattouf, Jean-Baptiste; Saad, Fred; Lacombe, Louis; Fradet, Yves; Fairey, Adrian; Jacobson, Niels-Eric; Drachenberg, Darryl; Cagiannos, Ilias; So, Alan; Black, Peter

    2012-01-01

    Introduction: We delineated Canadian regional differences in practice patterns in the management of upper tract urothelial carcinoma (UTUC) after nephroureterectomy and relate these to patient outcomes. Methods: A database was created with 1029 patients undergoing radical nephroureterectomy for UTUC between 1994 and 2009 at 10 Canadian centres. Demographic, clinical and pathological variables were collected from chart review. Practice pattern variables were defined as: open versus laparoscopic nephroureterectomy, management strategy for the distal ureter, performance of lymphadenectomy and administration of chemotherapy and/or radiation therapy. The outcome measures were overall (OS), disease-specific (DSS) and recurrence-free survival (RFS). The centres were divided into three regions (West, Central, East). Cox proportional multivariable linear regression analysis was used to determine the association between regional differences in practice patterns and clinical outcomes. Results: There was a significant difference in practice patterns between regions within Canada for: time from diagnosis to surgery (p = 0.001), type of surgery (open vs. laparoscopic, p < 0.01) and method of management of the distal ureter (p = 0.001). As well, there were significant differences in survival between regions across Canada: 5-year OS (West 70%, Central 81% and East 62%, p < 0.0001) and DSS (West=79%, Central=85%, East=75%, p = 0.007) were significantly different, but there was no difference in RFS (West 47%, Central 48%, East 46%, p = 0.88). Multivariable linear regression analysis demonstrated that the differences in survival were independent of region OS (p = 0.78), DSS (p = 0.30) or RFS (p = 0.43). Conclusion: There is significant disparity in practice patterns between regions within Canada, but these do not appear to have an effect on survival. We believe that the variability in practice is a reflection of the lack of standardized treatments for UTUC and underlines the need for

  18. Association between selected dietary scores and the risk of urothelial cell carcinoma: A prospective cohort study.

    Science.gov (United States)

    Dugué, Pierre-Antoine; Hodge, Allison M; Brinkman, Maree T; Bassett, Julie K; Shivappa, Nitin; Hebert, James R; Hopper, John L; English, Dallas R; Milne, Roger L; Giles, Graham G

    2016-09-15

    Studies investigating the association of food and nutrient consumption with the risk of urothelial cell carcinoma (UCC) have produced mixed results. We used three common dietary scores, the Mediterranean Diet Score (MDS), the Alternate Healthy Eating Index 2010 (AHEI-2010) and the Dietary Inflammatory Index (DII) to assess the evidence of an association between diet and the risk of UCC. Over a median follow-up time of 21.3 years, 379 incident UCC cases were diagnosed. Dietary scores were calculated using data from a 121-item food frequency questionnaire administered at baseline. We used Cox models to compute hazard ratios (HR) for the association between dietary scores (per one standard deviation) and UCC risk. In order to reflect overall adherence to a healthy diet, a metascore was constructed by summing the quintiles of each of the three scores. None of the dietary scores was associated with the risk of UCC overall. A healthier diet was found to be inversely associated with the risk of invasive (MDS: HR = 0.86, 95% CI: 0.74-1.00, metascore: HR = 0.84, 95% CI: 0.71-0.98), but not superficial disease (heterogeneity between subtypes p = 0.04 and p = 0.03, respectively). Results were consistent but weaker for the DII and the AHEI-2010. We found some evidence of effect modification by smoking, in particular for the metascore (Current: HR = 0.77, 95% CI: 0.58-1.01, Former: HR = 0.77, 95% CI: 0.64-0.92, Never: HR = 1.01, 95% CI: 0.81-1.26, p for heterogeneity = 0.05). A healthy diet may be protective against the risk of invasive, but not superficial, UCC. Promoting healthy dietary habits may help lower the risk of invasive UCC, especially for current and former smokers. PMID:27149545

  19. Urinary 8-hydroxydeoxyguanosine and urothelial carcinoma risk in low arsenic exposure area

    International Nuclear Information System (INIS)

    Arsenic is a well-documented human carcinogen and is known to cause oxidative stress in cultured cells and animals. A hospital-based case-control study was conducted to evaluate the relationship among the levels of urinary 8-hydroxydeoxyguanosine (8-OHdG), the arsenic profile, and urothelial carcinoma (UC). Urinary 8-OHdG was measured by using high-sensitivity enzyme-linked immunosorbent assay (ELISA) kits. The urinary species of inorganic arsenic and their metabolites were analyzed by high-performance liquid chromatography (HPLC) and hydride generator-atomic absorption spectrometry (HG-AAS). This study showed that the mean urinary concentration of total arsenics was significantly higher, at 37.67 ± 2.98 μg/g creatinine, for UC patients than for healthy controls of 21.10 ± 0.79 μg/g creatinine (p < 0.01). Urinary 8-OHdG levels correlated with urinary total arsenic concentrations (r = 0.19, p < 0.01). There were significantly higher 8-OHdG levels, of 7.48 ± 0.97 ng/mg creatinine in UC patients, compared to healthy controls of 5.95 ± 0.21 ng/mg creatinine. Furthermore, female UC patients had higher 8-OHdG levels of 9.22 ± 0.75 than those of males at 5.76 ± 0.25 ng/mg creatinine (p < 0.01). Multiple linear regression analyses revealed that high urinary 8-OHdG levels were associated with increased total arsenic concentrations, inorganic arsenite, monomethylarsonic acid (MMA), and dimethylarsenate (DMA) as well as the primary methylation index (PMI) even after adjusting for age, gender, and UC status. The results suggest that oxidative DNA damage was associated with arsenic exposure, even at low urinary level of arsenic

  20. Polymorphisms in cell cycle regulatory genes, urinary arsenic profile and urothelial carcinoma

    International Nuclear Information System (INIS)

    Introduction: Polymorphisms in p53, p21 and CCND1 could regulate the progression of the cell cycle and might increase the susceptibility to inorganic arsenic-related cancer risk. The goal of our study was to evaluate the roles of cell cycle regulatory gene polymorphisms in the carcinogenesis of arsenic-related urothelial carcinoma (UC). Methods: A hospital-based case-controlled study was conducted to explore the relationships among the urinary arsenic profile, 8-hydroxydeoxyguanosine (8-OHdG) levels, p53 codon 72, p21 codon 31 and CCND1 G870A polymorphisms and UC risk. The urinary arsenic profile was determined using high-performance liquid chromatography (HPLC) and hydride generator-atomic absorption spectrometry (HG-AAS). 8-OHdG levels were measured by high-sensitivity enzyme-linked immunosorbent assay (ELISA) kits. Genotyping was conducted using polymerase chain reaction-restriction fragment length polymerase (PCR-RFLP). Results: Subjects carrying the p21 Arg/Arg genotype had an increased UC risk (age and gender adjusted OR = 1.53; 95% CI, 1.02-2.29). However, there was no association of p53 or CCND1 polymorphisms with UC risk. Significant effects were observed in terms of a combination of the three gene polymorphisms and a cumulative exposure of cigarette smoking, along with the urinary arsenic profile on the UC risk. The higher total arsenic concentration, monomethylarsonic acid percentage (MMA%) and lower dimethylarsinic acid percentage (DMA%), possessed greater gene variant numbers, had a higher UC risk and revealed significant dose-response relationships. However, effects of urinary 8-OHdG levels combined with three gene polymorphisms did not seem to be important for UC risk. Conclusions: The results showed that the variant genotype of p21 might be a predictor of inorganic arsenic-related UC risk

  1. Loss of prostasin (PRSS8 in human bladder transitional cell carcinoma cell lines is associated with epithelial-mesenchymal transition (EMT

    Directory of Open Access Journals (Sweden)

    Chai Karl X

    2009-10-01

    Full Text Available Abstract Background The glycosylphosphatidylinositol (GPI-anchored epithelial extracellular membrane serine protease prostasin (PRSS8 is expressed abundantly in normal epithelia and essential for terminal epithelial differentiation, but down-regulated in human prostate, breast, and gastric cancers and invasive cancer cell lines. Prostasin is involved in the extracellular proteolytic modulation of the epidermal growth factor receptor (EGFR and is an invasion suppressor. The aim of this study was to evaluate prostasin expression states in the transitional cell carcinomas (TCC of the human bladder and in human TCC cell lines. Methods Normal human bladder tissues and TCC on a bladder cancer tissue microarray (TMA were evaluated for prostasin expression by means of immunohistochemistry. A panel of 16 urothelial and TCC cell lines were evaluated for prostasin and E-cadherin expression by western blot and quantitative PCR, and for prostasin gene promoter region CpG methylation by methylation-specific PCR (MSP. Results Prostasin is expressed in the normal human urothelium and in a normal human urothelial cell line, but is significantly down-regulated in high-grade TCC and lost in 9 (of 15 TCC cell lines. Loss of prostasin expression in the TCC cell lines correlated with loss of or reduced E-cadherin expression, loss of epithelial morphology, and promoter DNA hypermethylation. Prostasin expression could be reactivated by demethylation or inhibition of histone deacetylase. Re-expression of prostasin or a serine protease-inactive variant resulted in transcriptional up-regulation of E-cadherin. Conclusion Loss of prostasin expression in bladder transitional cell carcinomas is associated with epithelial-mesenchymal transition (EMT, and may have functional implications in tumor invasion and resistance to chemotherapy.

  2. Productive infection of bovine papillomavirus type 2 in the urothelial cells of naturally occurring urinary bladder tumors in cattle and water buffaloes.

    Directory of Open Access Journals (Sweden)

    Sante Roperto

    Full Text Available BACKGROUND: Papillomaviruses (PVs are highly epitheliotropic as they usually establish productive infections within squamous epithelia of the skin, the anogenital tract and the oral cavity. In this study, early (E and late (L protein expression of bovine papillomavirus type 2 (BPV-2 in the urothelium of the urinary bladder is described in cows and water buffaloes suffering from naturally occurring papillomavirus-associated urothelial bladder tumors. METHODS AND FINDINGS: E5 protein, the major oncoprotein of the BPV-2, was detected in all tumors. L1 DNA was amplified by PCR, cloned and sequenced and confirmed to be L1 DNA. The major capsid protein, L1, believed to be only expressed in productive papillomavirus infection was detected by Western blot analysis. Immunohistochemical investigations confirmed the presence of L1 protein both in the cytoplasm and nuclei of cells of the neoplastic urothelium. Finally, the early protein E2, required for viral DNA replication and known to be a pivotal factor for both productive and persistent infection, was detected by Western blot and immunohistochemically. Electron microscopic investigations detected electron dense particles, the shape and size of which are consistent with submicroscopic features of viral particles, in nuclei of neoplastic urothelium. CONCLUSION: This study shows that both active and productive infections by BPV-2 in the urothelium of the bovine and bubaline urinary bladder can occur in vivo.

  3. Genome-wide methylation profiling and the PI3K-AKT pathway analysis associated with smoking in urothelial cell carcinoma

    NARCIS (Netherlands)

    Brait, Mariana; Munari, Enrico; LeBron, Cynthia; Noordhuis, Maartje G.; Begum, Shahnaz; Michailidi, Christina; Gonzalez-Roibon, Nilda; Maldonado, Leonel; Sen, Tanusree; Guerrero-Preston, Rafael; Cope, Leslie; Parrella, Paola; Fazio, VitoMichele; Ha, Patrick K.; Netto, George J.; Sidransky, David; Hoque, Mohammad O.

    2013-01-01

    Urothelial cell carcinoma (UCC) is the second most common genitourinary malignant disease in the USA, and tobacco smoking is the major known risk factor for UCC development. Exposure to carcinogens, such as those contained in tobacco smoke, is known to directly or indirectly damage DNA, causing muta

  4. Recurrence patterns of bladder transitional cell carcinoma after radical cystectomy

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Bohyun; Choi, Hyuck Jae; Kim, Mi-hyun; Cho, Kyung-Sik [Dept. of Radiology, Asan Medical Center, Univ. of Ulsan, Seoul (Korea, Republic of); E-mail: choihj@amc.seoul.kr

    2012-10-15

    Background Multidetector computed tomography (MDCT) is widely accepted as an effective imaging modality in monitoring for bladder cancer recurrence after radical cystectomy. Elucidating the pattern of bladder cancer recurrence on CT can increase the diagnostic accuracy. Purpose To evaluate the recurrence patterns of transitional cell carcinoma of the bladder and the factors associated with cancer recurrence. Material and Methods One hundred and forty-nine consecutive patients (mean age, 66.55 years; range, 32-86 years) who underwent preoperative contrast-enhanced CT and radical cystectomy were included in this study. The presence, site, and time of tumor recurrence were recorded retrospectively by two radiologists in a consensus fashion. The association of tumor recurrence and tumor factors (T stage, lymph node metastasis, nuclear grade, and tumor diameter) were also evaluated using multiple logistic regression analysis and Kaplan-Meier statistics. Results Tumor recurrence occurred in 60 patients (40.3%) with a mean time of 14 months (range, 1-64 months). The sites of recurrence included the operation site (n = 20), lymph node (n = 20), bone (n = 11), liver (n = 6), lung (n = 5), upper urinary tract (n = 4), colon (n = 3), adrenal gland (n = 2), peritoneum (n = 1), abdominal wall (n = 1), psoas muscle (n = 1), and penile skin (n = 1). Tumor recurrence was found to be associated with advanced T stage (P = 0.002) and lymph node metastasis (P < 0.001). Conclusion Transitional cell carcinomas of the bladder recur more frequently at the operation site and lymph node, and T-stage and lymph node metastasis are closely associated with tumor recurrence.

  5. Utility of a triple antibody cocktail intraurothelial neoplasm-3 (IUN-3-CK20/CD44s/p53) and α-methylacyl-CoA racemase (AMACR) in the distinction of urothelial carcinoma in situ (CIS) and reactive urothelial atypia.

    Science.gov (United States)

    Aron, Manju; Luthringer, Daniel J; McKenney, Jesse K; Hansel, Donna E; Westfall, Danielle E; Parakh, Rugvedita; Mohanty, Sambit K; Balzer, Bonnie; Amin, Mahul B

    2013-12-01

    Urothelial carcinoma in situ (CIS) is a prognostically and therapeutically significant lesion with considerable morphologic overlap with reactive conditions especially in the setting of prior therapy. Various markers including CK20, CD44s, and p53 have been used as an adjunct in making this distinction; however, the utility of these markers in the posttreatment scenario is not fully established. α-Methylacyl-CoA racemase (AMACR) is a tumor-associated marker that is expressed in a subset of high-grade urothelial carcinomas but has not been studied in CIS. This study was undertaken to evaluate the immunoreactivity of CK20, CD44s, and p53 as a triple antibody cocktail intraurothelial neoplasm-3 (IUN-3) in distinguishing CIS from its mimics and to compare its utility with AMACR in the diagnosis of CIS. A total of 135 specimens (7 benign ureters and 128 bladder biopsies-28 reactive, 33 posttherapy reactive, 43 CIS, 24 CIS posttherapy) were included in this study. Immunostaining for p53 (brown, nuclear), CD44s (brown, membranous), and CK20 (red, cytoplasmic and membranous) was performed as a cocktail, and the staining pattern was further classified as: malignant (full-thickness CK20 and/or full-thickness p53 with CD44s negativity), reactive/benign (CK20 limited to the umbrella cell layer, p53 negative, and CD44s positivity ranging from basal to full thickness), and indeterminate (CK20 and p53 positive but not full thickness and/or CD44s positive). AMACR staining was performed in 50 cases. Cytoplasmic staining for AMACR was graded as negative (absent to weak focal staining [<5% cells]) and positive (≥5%). The "IUN-3 malignant" pattern was observed in 84% of cases of CIS without a history of prior therapy and in 71% of the cases of CIS with a history of prior therapy. Cases with posttherapy reactive atypia showed an "IUN-3 reactive" pattern in 84% cases and "IUN-3 indeterminate" pattern in 16% of the cases; the IUN-3 malignant pattern was not identified in any of the

  6. Nonmuscle invasive bladder cancer:a primer on immunotherapy

    Institute of Scientific and Technical Information of China (English)

    Mahir Maruf; Sam J. Brancato; Piyush K. Agarwal

    2016-01-01

    Intravesical Bacillus Calmette-Guérin (BCG) has long been the gold standard treatment of nonmuscle invasive bladder cancer. Recently, there has been an emergence of novel immunotherapeutic agents, which have shown promise in the treatment of urothelial cell carcinoma. These agents aim to augment, modify, or enhance the immune response. Such strategies include recombinant BCG, monoclonal antibodies, vaccines, gene therapy, and adoptive T-cell therapy. Here, we review the emerging immunotherapeutics in the treatment of nonmuscle invasive bladder cancer.

  7. Nonmuscle invasive bladder cancer: a primer on immunotherapy

    Science.gov (United States)

    Maruf, Mahir; Brancato, Sam J.; Agarwal, Piyush K.

    2016-01-01

    Intravesical Bacillus Calmette-Guérin (BCG) has long been the gold standard treatment of nonmuscle invasive bladder cancer. Recently, there has been an emergence of novel immunotherapeutic agents, which have shown promise in the treatment of urothelial cell carcinoma. These agents aim to augment, modify, or enhance the immune response. Such strategies include recombinant BCG, monoclonal antibodies, vaccines, gene therapy, and adoptive T-cell therapy. Here, we review the emerging immunotherapeutics in the treatment of nonmuscle invasive bladder cancer.

  8. Identification and Validation of Protein Biomarkers of Response to Neoadjuvant Platinum Chemotherapy in Muscle Invasive Urothelial Carcinoma.

    Directory of Open Access Journals (Sweden)

    Alexander S Baras

    Full Text Available The 5-year cancer specific survival (CSS for patients with muscle invasive urothelial carcinoma of the bladder (MIBC treated with cystectomy alone is approximately 50%. Platinum based neoadjuvant chemotherapy (NAC plus cystectomy results in a marginal 5-10% increase in 5-year CSS in MIBC. Interestingly, responders to NAC (

  9. HuR cytoplasmic expression is associated with increased cyclin A expression and poor outcome with upper urinary tract urothelial carcinoma

    International Nuclear Information System (INIS)

    HuR is an RNA-binding protein that post-transcriptionally modulates the expressions of various target genes implicated in carcinogenesis, such as CCNA2 encoding cyclin A. No prior study attempted to evaluate the significance of HuR expression in a large cohort with upper urinary tract urothelial carcinomas (UTUCs). In total, 340 cases of primary localized UTUC without previous or concordant bladder carcinoma were selected. All of these patients received ureterectomy or radical nephroureterectomy with curative intents. Pathological slides were reviewed, and clinical findings were collected. Immunostaining for HuR and cyclin A was performed and evaluated by using H-score. The results of cytoplasmic HuR and nuclear cyclin A expressions were correlated with disease-specific survival (DSS), metastasis-free survival (MeFS), urinary bladder recurrence-free survival (UBRFS), and various clinicopathological factors. HuR cytoplasmic expression was significantly related to the pT status, lymph node metastasis, a higher histological grade, the pattern of invasion, vascular and perineurial invasion, and cyclin A expression (p = 0.005). Importantly, HuR cytoplasmic expression was strongly associated with a worse DSS (p < 0.0001), MeFS (p < 0.0001), and UBRFS (p = 0.0370) in the univariate analysis, and the first two results remained independently predictive of adverse outcomes (p = 0.038, relative risk [RR] = 1.996 for DSS; p = 0.027, RR = 1.880 for MeFS). Cyclin A nuclear expression was associated with a poor DSS (p = 0.0035) and MeFS (p = 0.0015) in the univariate analysis but was not prognosticatory in the multivariate analyses. High-risk patients (pT3 or pT4 with/without nodal metastasis) with high HuR cytoplasmic expression had better DSS if adjuvant chemotherapy was performed (p = 0.015). HuR cytoplasmic expression was correlated with adverse phenotypes and cyclin A overexpression and also independently predictive of worse DSS and MeFS, suggesting its roles in

  10. OPIUM USE IN TRANSITIONAL CELL CARCINOMA OF THE URINARY BLADDER

    Directory of Open Access Journals (Sweden)

    A. Nourbakhsh

    2006-08-01

    Full Text Available Opium use is one of the most common forms of substance abuse in Iran and there are some evidence indicating it is a risk factor of transitional cell carcinoma (TCC of the urinary bladder. The majority of opium users are also cigarette smokers, so consideration of the high prevalence of smoking which is the most important risk factor of TCC of the urinary bladder among opium users is essential to assess the role of opium use as a possible risk factor of TCC. This study was done to evaluate the role of opium as a risk factor of TCC. A case-control study was performed on 255 individuals diagnosed with TCC of the urinary bladder by pathologic light microscopic examination of the tumor biopsies. Control population was chosen from individuals who had no history or presenting signs or symptoms of urinary problems. Case and control groups were matched by sex and age and also by cigarette smoking habits. Forty-one (18.1% of the cases and 12 (5% of controls were recognized to be opium users. Mantel-Haenszel analysis showed an odds ratio of 3.88, with 95% confidence interval of 1.99-7.57 and P value of < 0.001. Results indicate that opium use is a risk factor for TCC. The majority of opium users are also cigarette smokers, which is another important risk factor for TCC. Routine urine cytology and early evaluation in the patients presenting with any of the symptoms of urinary bladder malignancy by means of cystoscopy and urine cytology are highly recommended.

  11. Expression of pRb, p53, p16 and cyclin D1 and their clinical implications in urothelial carcinoma.

    Science.gov (United States)

    Lee, Kyungji; Jung, Eun Sun; Choi, Young-Jin; Lee, Kyo Young; Lee, Ahwon

    2010-10-01

    The aim of this study was to assess immunohistochemical expression of p53, pRb, p16, and cyclin D1, alone or in combination, as prognostic indicators and to investigate their correlation with clinocopathologic features of urothelial carcinoma. Immunohistochemical staining for p53, pRb, p16, and cyclin D1 was performed on a tissue microarray from 103 patients with urothelial carcinoma who underwent radical cystectomy. Of the patient samples analyzed, 36 (35%), 61 (59%), 47 (46%) and 30 (29%) had altered expression of p53, pRb, p16, and cyclin D1, respectively. Abnormal expression of p53 and pRb correlated with depth of invasion (P=0.040 and P=0.044, respectively). Cyclin D1 expression was associated with tumor stage and recurrence (P=0.017 and P=0.036, respectively). Altered pRb was significantly correlated with overall survival (P=0.040). According to the expression pattern of pRb and p53, p53/pRb (altered/normal) had worse survival than p53/pRb (normal/altered) (P=0.022). Alteration of all markers had worse survival than all normal (P=0.029). As determined by multivariate analysis, tumor stage, lymph node metastasis and the combined expression of p53 and pRb are independent prognostic factors. In conclusion, immunohistochemical evaluation of cell cycle regulators, especially the p53/pRb combination, might be useful in planning appropriate treatment strategies.

  12. Surgical management of bladder transitional cell carcinoma in a vesicular diverticulum: case report.

    LENUS (Irish Health Repository)

    Raheem, Omer A

    2011-08-01

    We report a case of primary transitional cell carcinoma (TCC) of a bladder diverticum along with a literature review. A 55-year-old male presented with painless gross hematuria. A histological diagnosis of TCC within a bladder diverticulum was made following cystoscopical examination. Initially transurethral resection of bladder tumour with subsequent intravesical chemotherapy followed. As a result of recurrence and in view of bladder-sparing therapy, a distal partial cystectomy was performed. This report demonstrates that conservative bladder-sparing treatment can be achieved and subsequently followed by vigilant cystoscopy.

  13. Surgical management of bladder transitional cell carcinoma in a vesicular diverticulum: case report.

    LENUS (Irish Health Repository)

    Raheem, Omer A

    2012-02-01

    We report a case of primary transitional cell carcinoma (TCC) of a bladder diverticum along with a literature review. A 55-year-old male presented with painless gross hematuria. A histological diagnosis of TCC within a bladder diverticulum was made following cystoscopical examination. Initially transurethral resection of bladder tumour with subsequent intravesical chemotherapy followed. As a result of recurrence and in view of bladder-sparing therapy, a distal partial cystectomy was performed. This report demonstrates that conservative bladder-sparing treatment can be achieved and subsequently followed by vigilant cystoscopy.

  14. 完全腹腔镜下上尿路尿路上皮癌根治术12例分析%12 cases of reports on totally laparoscopic radical nephroureterectomy for upper urinary tract urothelial carcinoma

    Institute of Scientific and Technical Information of China (English)

    陈志军; 李庆文; 汪盛; 张家俊; 杨小淮; 韩锋; 杨帅; 伍宏亮; 代昌远

    2015-01-01

    目的:探讨完全腹腔镜肾、输尿管全长切除+膀胱部分切除术治疗上尿路尿路上皮癌的疗效及临床价值。方法12例上尿路尿路上皮癌患者在我院接受完全腹腔镜下肾盂、输尿管癌根治术,肾盂癌8例,输尿管癌4例,其中2例输尿管癌突入膀胱内。术中采用70°健侧卧位,建立人工气腹,置5枚套管,首先在肾周筋膜外行患侧肾切除,再游离输尿管至膀胱,其中肾盂癌或输尿管癌未侵入膀胱病例切开部分逼尿肌,将输尿管开口及部分膀胱黏膜拉出膀胱壁外,Hem-o-lock夹毕切断;输尿管癌侵入膀胱病例术前膀胱内保留灌注100 mL稀释后的50 mg羟基喜树碱,切开膀胱前将灌注液自导尿管放出,沿输尿管膀胱入口处周围2 cm环形切除膀胱壁及输尿管开口处肿瘤,2-0可吸收线缝合膀胱。结果该组病例均成功完成手术,无中转开放手术。手术时间150~200 min,平均170 min;术中出血80~150 mL,平均95 mL;无严重围手术期并发症。术后住院时间6~9 d,平均7 d,术后病理均为尿路上皮癌。8例患者术后辅以4次GC方案全身化疗。术后随访2~30个月,1例术后7个月因膀胱内肿瘤复发行经尿道膀胱肿瘤电切术,其余患者未见肿瘤复发、转移。结论完全腹腔镜下上尿路尿路上皮癌根治术临床疗效满意,同时具有创伤小、不需要术中更换体位、术后恢复快等优点,值得临床推广应用。%Objective To explore the efficacy and clinical value of totally laparoscopic radical resection of the kidney and ureter and partial resection of the bladder in the treatment of upper urinary tract urothelial carcinoma. Methods A total of 12 patients underwent totally laparoscopic radical resection of the renal pelvis and ureter in our hospital, including eight cases of renal pelvis cancer and four cases of ureter cancer, in which two cases of ureteral cancer were immersed into the bladder. The patients were in the

  15. Cellular origin of bladder neoplasia and tissue dynamics of its progression to invasive carcinoma

    OpenAIRE

    Shin, Kunyoo; Lim, Agnes; Odegaard, Justin I.; Honeycutt, Jared D.; Kawano, Sally; Hsieh, Michael H.; Beachy, Philip A.

    2014-01-01

    Understanding how malignancies arise within normal tissues requires identification of the cancer cell of origin and knowledge of the cellular and tissue dynamics of tumor progression. Here we examine bladder cancer in a chemical carcinogenesis model that mimics muscle-invasive human bladder cancer. With no prior bias regarding genetic pathways or cell types, we prospectively mark or ablate cells to show that muscle-invasive bladder carcinomas arise exclusively from Sonic hedgehog ( Shh )-expr...

  16. A systematic analysis on DNA methylation and the expression of both mRNA and microRNA in bladder cancer.

    Directory of Open Access Journals (Sweden)

    Jialou Zhu

    Full Text Available BACKGROUND: DNA methylation aberration and microRNA (miRNA deregulation have been observed in many types of cancers. A systematic study of methylome and transcriptome in bladder urothelial carcinoma has never been reported. METHODOLOGY/PRINCIPAL FINDINGS: The DNA methylation was profiled by modified methylation-specific digital karyotyping (MMSDK and the expression of mRNAs and miRNAs was analyzed by digital gene expression (DGE sequencing in tumors and matched normal adjacent tissues obtained from 9 bladder urothelial carcinoma patients. We found that a set of significantly enriched pathways disrupted in bladder urothelial carcinoma primarily related to "neurogenesis" and "cell differentiation" by integrated analysis of -omics data. Furthermore, we identified an intriguing collection of cancer-related genes that were deregulated at the levels of DNA methylation and mRNA expression, and we validated several of these genes (HIC1, SLIT2, RASAL1, and KRT17 by Bisulfite Sequencing PCR and Reverse Transcription qPCR in a panel of 33 bladder cancer samples. CONCLUSIONS/SIGNIFICANCE: We characterized the profiles between methylome and transcriptome in bladder urothelial carcinoma, identified a set of significantly enriched key pathways, and screened four aberrantly methylated and expressed genes. Conclusively, our findings shed light on a new avenue for basic bladder cancer research.

  17. The bladder carcinoma secondary to schistosoma mansoni infection: A case report with review of the literature

    Directory of Open Access Journals (Sweden)

    Murat Can Kiremit

    2015-01-01

    Conclusion: Regarding the increasing travels all around the world, clinicians should remember that Schistosoma infection is certainly a part of the differential diagnosis of bladder carcinoma, even if the patients are not from endemic regions.

  18. Small cell carcinoma of the urinary bladder: Virtual CT cystoscopic findings

    Directory of Open Access Journals (Sweden)

    Tsili A

    2009-01-01

    Full Text Available A 74-year-old man underwent multidetector CT virtual cystoscopy due to macroscopic hematuria. A large, irregularly-surfaced, solid bladder mass was detected, infiltrating the perivesical fat, the seminal vesicles and the prostate. CT examination of the chest and abdomen showed no distant metastases. Radical cystectomy was performed and pathology reported pure small cell carcinoma of the urinary bladder.

  19. Development of a nomogram incorporating serum C-reactive protein level to predict overall survival of patients with advanced urothelial carcinoma and its evaluation by decision curve analysis

    OpenAIRE

    Ishioka, J.; Saito, K.; Sakura, M; Yokoyama, M.; Matsuoka, Y.; Numao, N; Koga, F; Masuda, H.; Fujii, Y.; S. Kawakami; Kihara, K.

    2012-01-01

    Background: The purpose of this study is to investigate the prognostic impact of C-reactive protein (CRP) on patients with advanced urothelial carcinoma and to develop a novel nomogram predicting survival. Methods: A total of 223 consecutive patients were treated at Tokyo Medical and Dental Hospital. A nomogram incorporating V was developed based on the result of a Cox proportional hazards model. Its efficacy and clinical usefulness was evaluated by concordance index (c-index) and decision cu...

  20. Chemotherapy for bladder cancer: treatment guidelines for neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and metastatic cancer

    DEFF Research Database (Denmark)

    Sternberg, Cora N; Donat, S Machele; Bellmunt, Joaquim;

    2007-01-01

    To determine the optimal use of chemotherapy in the neoadjuvant, adjuvant, and metastatic setting in patients with advanced urothelial cell carcinoma, a consensus conference was convened by the World Health Organization (WHO) and the Société Internationale d'Urologie (SIU) to critically review...... the published literature on chemotherapy for patients with locally advanced bladder cancer. This article reports the development of international guidelines for the treatment of patients with locally advanced bladder cancer with neoadjuvant and adjuvant chemotherapy. Bladder preservation is also discussed......, as is chemotherapy for patients with metastatic urothelial cancer. The conference panel consisted of 10 medical oncologists and urologists from 3 continents who are experts in this field and who reviewed the English-language literature through October 2004. Relevant English-language literature was identified...

  1. Expression of Hpa and CD222 in bladder carcinoma and analysis of clinico-pathologic correlation

    Institute of Scientific and Technical Information of China (English)

    Shuhong Shi; Hui Zhang

    2014-01-01

    Objective:Our study aimed to investigate the relationships between the clinico-pathologic features and the hepa-ranase (Hpa) and CD222 expressions in bladder carcinoma. Methods:The expressions of Hpa and CD222 in 95 bladder carcinoma specimens and 20 paraneoplastic bladder tissues (controls) were assessed using the immunohistochemical stain-ing method. Results:The positive expression rates of Hpa and CD222 in bladder carcinoma were 68.42%and 61.05%, respectively. The positive rate of Hpa was significantly higher in the carcinoma specimens than in the control specimens (P<0.01). Similarly, the Hpa expression in the invasive bladder carcinoma was significantly higher than that in the non-invasive bladder carcinoma (P<0.01). A positive correlation was observed between the expressions of Hpa and CD222 (P<0.05). The expressions of Hpa and CD222 were significantly correlated with lymphatic invasion and TNM staging (P<0.05). The 5-year survival rate was significantly higher in negative expression of the Hpa group than that in the positive expression group (P<0.05). Compared with the non-co-positive expression group, the 5-year survival rate in the co-positive expression of Hpa and CD222 group was significantly lower (P<0.05). Conclusion:High Hpa and CD222 expressions in tumor tissues were associated with the occurrence and development of bladder carcinoma. Our results provide helpful information for the further diagnosis and therapy of bladder carcinoma.

  2. Reduced 5-Methylcytosine Level as a Potential Progression Predictor in Patients with T1 or Non-Invasive Urothelial Carcinoma

    Directory of Open Access Journals (Sweden)

    Chi-Jung Chung

    2014-12-01

    Full Text Available This study aims to elucidate the level of DNA methylation in urothelial carcinomas (UCs using 5-methylcytosine (5-MeC immunohistochemistry (IHC. We examined the relationship among 5-MeC levels, DNA (cytosine-5-methyltransferase 1 (DNMT1 immunostaining levels, and clinicopathologic features. Tissue samples included 23 normal urothelia and 150 urothelial neoplasia, which comprised 40 non-invasive and 110 invasive UCs. The levels of 5-MeC and DNMT1 were assessed based on their immunoreactivities and then divided into low and high levels. In addition, we collected information on clinical variables, pathologic features, and recurrent status from patient questionnaires and medical records. Chi-square test and multivariate logistic regression model were used for analyses. Results showed that 5-MeC levels were positively associated with DNMT1 levels in UC (p = 0.0288. Both 5-MeC and DNMT1 were low in approximately 50% (76/150 of UC. The percentage of low 5-MeC levels was higher in invasive UC (65/110; 59% than in normal urothelia (2/23; 13% and non-invasive UC (18/40; 45%. Clinical factors were independently associated with low 5-MeC levels after adjusting for age and sex, including cancer stages II–IV, presence of UC in situ, and marked inflammation. Low 5-MeC levels in stage I invasive UC were not significantly different from those of non-invasive tumors (p = 0.8478. Low DNMT1 levels were only associated with UC with squamous differentiation (p = 0.0365. Neither 5-MeC nor DNMT1 levels were associated with UC recurrence. In conclusion, a low 5-MeC level could predict the progression of UC invasion into muscle.

  3. Pathologic Response Rates of Gemcitabine/Cisplatin versus Methotrexate/Vinblastine/Adriamycin/Cisplatin Neoadjuvant Chemotherapy for Muscle Invasive Urothelial Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Franklin C. Lee

    2013-01-01

    Full Text Available Objectives. To compare pathologic outcomes after treatment with gemcitabine and cisplatin (GC versus methotrexate, vinblastine, adriamycin, and cisplatin (MVAC in the neoadjuvant setting. Methods. Data was retrospectively collected on 178 patients with T2-T4 bladder cancer who underwent radical cystectomy between 2003 and 2011. Outcomes of interest included those with complete response (pT0 and any response (≤pT1. Odds ratios were calculated using multivariate logistic regression. Results. Compared to those who did not receive neoadjuvant chemotherapy, there were more patients with complete response (28% versus 9%, OR 3.11 (95% CI: 1.45–6.64, P=0.03 and any response (52% versus 25%, OR 3.23 (95% CI: 1.21–8.64, P=0.01. Seventy-two patients received GC (n=41 or MVAC (n=31. CR was achieved in 29% and 22% of GC and MVAC patients, respectively (multivariate OR 0.39, 95% CI 0.10–1.58. Any response (≤pT1 was achieved in 56% of GC and 45% of MVAC patients (multivariate OR 0.45, 95% CI 0.12–1.71. Conclusions. We observed similar pathologic response rates for GC and MVAC neoadjuvant chemotherapy in this cohort of patients with muscle invasive urothelial cancer (MIBC. Our findings support the use of GC as an alternative regimen in the neoadjuvant setting.

  4. Patients with a negative cystoscopy and negative Nmp22® Bladderchek® test are at low risk of missed transitional cell carcinoma of the bladder: a prospective evaluation

    Directory of Open Access Journals (Sweden)

    John D. Terrell

    2011-12-01

    Full Text Available OBJECTIVES: Urine based tumor markers have uncertain utility in diagnosis or surveillance of patients with bladder cancer while cytology is commonly used. We evaluated whether cytology provides additional diagnostic information in patients with a negative NMP22® BladderChek® test (BladderChek and negative cystoscopy. MATERIALS AND METHODS: We performed subset analyses of 2 large prospective multi-center databases evaluating BladderChek for UCB detection and surveillance. These cohorts were analyzed for presence of cancer and result of urine cytology in setting of a negative cystoscopy and negative BladderChek. Subsequently, we prospectively performed cystoscopy, cytology and BladderChek on 434 patients at our institution being evaluated for UCB. RESULTS: In the detection database (n = 1331, 1065 patients had a negative cystoscopy and BladderChek. There were 3 cancers (stages Ta, Tis and T1 and cytology was atypical in one and reactive in two. In the surveillance cohort (n = 668 patients, 437 patients had negative cystoscopy and BladderChek. Cancer was found in 2 patients (stages Tis and Ta. The patient with Tis has dysplastic cytology and Ta tumor had reactive cytology. In our cohort of 434 patients, 288 pts had negative cystoscopy and BladderChek. One cancer was missed, a Ta ureteral urothelial carcinoma with a reactive cytology. CONCLUSIONS: In patients with negative cystoscopy and BladderChek, very few cancers are missed and cytology was not effective in detection. Use of a point-of-care test in conjunction with cystoscopy in lieu of cytology could decrease cost, provide immediate results, improve negative predictive value and reduce the uncertainty that results from inconclusive cytologic results.

  5. Role of VEGF in the growth and metastasis of a murine bladder carcinoma

    Institute of Scientific and Technical Information of China (English)

    WANG Feng; WU Jihong; TIAN Yuhua; CHEN Xiafang; HU Honghui; WU Wensen; LI Chuanyuan; HUANG Qian

    2003-01-01

    Bladder transitional cell carcinoma is the most common form of carcinoma in the urinary system. Although overexpression of VEGF has been identified in tissue, serum, and urine of patients with bladder cancer, the role of VEGF in transitional cell carcinoma of the bladder has not been clearly elucidated. Here, we dissected the effect of VEGF during bladder tumor growth and progression by modifying a BBN (N-butyl-N-(4-hydroxybutyl) nitrosamine) induced mouse bladder transitional cell carcinoma cell line BTT-T739 by stable transfection of antisense VEGF121 cDNA. The transfection resulted in more than 80% reduction in VEGF production. The growth of the transduced tumor cells in vitro was not affected, however, these cells formed small or no tumors in vivo. Even in the tumors formed, there were mini- mal vascularization, extensive necrosis and longer latency compared to those formed by parental cells. The permeability of tumor vasculature and metastatic tumor growth were also significantly suppressed in antisense VEGF cDNA trans- fected cells. In addition, the transfer of anti-angiogenic gene in a combination of sFlk-1 and ExTek with electroporation can suppress the tumor growth efficiently. Taken together, these results demonstrated that VEGF plays an important role in bladder tumor angiogenesis and angiogenesis plays an important role in bladder tumor growth and metastasis.

  6. A rare case of pure small cell carcinoma of urinary bladder

    Directory of Open Access Journals (Sweden)

    Sunita Singh

    2014-09-01

    Full Text Available Bladder cancer is the second most common urologic malignancy. Up to 95% of the urinary bladder tumors are of epithelial origin, from which 90% are transitional neoplasms. However, small cell carcinoma of the urinary bladder is rare tumor accounting for<0.7% of bladder cancer, of which the pure form is extremely rare. A 53‑year‑old female presented to urosurgery outpatient department complaining of hematuria and burning micturition since 3 months. Ultrsonography showed a large heteroechoic mass filling whole of the bladder. Histopathological examination of the transurethral debulked tumor mass revealed small cell carcinoma, which was confirmed on immunohistochemistry. We report this case due to its rarity and to add on to literature

  7. External Validation of Models for Prediction of Lymph Node Metastasis in Urothelial Carcinoma of the Bladder.

    Directory of Open Access Journals (Sweden)

    Ja Hyeon Ku

    Full Text Available To externally validate models to predict LN metastsis; Karakiewicz nomogram, clinical nodal staging score (cNSS, and pathologic nodal staging score (pNSS using a different cohort.Clinicopathologic data from 500 patients who underwent radical cystectomy and pelvic lymphadenectomy were analyzed. The overall predictive values of models were compared with the criteria of overall performance, discrimination, calibration, and clinical usefulness.Presence of pN+ stages was recorded in 117 patients (23.4%. Agreement between clinical and pathologic stage was noted in 174 (34.8%. Based on Nagelkerke's peudo-R2 and brier score, pNSS demonstrated best overall performance. Area under the receiver operating characteristics curve, showed that pNSS had the best discriminatory ability. In all models, calibration was on average correct (calibration-in-the-large coefficient = zero. On decision curve analysis, pNSS performed better than other models across a wide range of threshold probabilities.When compared to pNSS, current precystectomy models such as the Karakiewicz nomogram and cNSS cannot predict the probability of LN metastases accurately. The findings suggest that the application of pNSS to Asian patients is feasible.

  8. Superficial Urothelial Cancer in the Prostatic Urethra

    Directory of Open Access Journals (Sweden)

    Ziya Kirkali

    2006-01-01

    Full Text Available Transitional cell carcinoma (TCC is a multifocal disease of the urinary tract that can also involve the prostatic urethra (PU. The exact incidence of superficial involvement of the PU in patients with bladder TCC is not well known. Bladder TCC may involve the prostate in 12—40% of the patients and the degree of involvement can include urethral mucosa, ducts, acini, and stroma of the gland, which has been shown to affect the outcome. Risk factors for superficial urothelial cancer in the PU are high-grade, multifocal bladder TCC and presence of carcinoma in situ (CIS in the bladder. While visible tumors are easy to detect and resect, controversy still exists regarding the optimal technique to identify prostatic involvement by TCC. Prostatic urethral sampling by a transurethral resection biopsy or a cold-cup biopsy, particularly in the high-risk group of bladder cancer patients, has been recommended for detecting prostatic urethral involvement. Management of superficial prostatic involvement by TCC is also unclear. Currently, there is increasing recognition of the value of conservative treatment options with intravesical agents when there is superficial involvement of the PU. Particularly, intravesical bacillus Calmette-Guèrin (BCG seems to be an effective treatment alternative in the management of superficial involvement of the PU by TCC. Close follow-up by cystoscopy and PU biopsy at 3-month intervals, particularly in intermediate and high-risk patients who respond to intravesical therapy and in whom cystectomy is appropriate, is recommended in order to detect persistent tumor, recurrences, or progression.

  9. Types of HLA in the bladder transitional cell carcinoma (TCC).

    Science.gov (United States)

    Yılmaz, Erkan; Uğur Özalp, Ali; Cekmen, Arman; Eren, Bülent; Onal, Bülent; Akkuş, Emre; Erdoğan, Ergun

    2013-02-01

    HLA plays a complementary role in the interaction between tumor and body immunology. The aim of this study was to determine the existence of the association between the HLA system and transitional cell carcinoma (TCC). Using standard micro-lymphocytotoxic method of Terasaki, HLA-A, B, DR and DQ antigen types of 30 patients with TCC of the bladder were compared with the control group (30 healthy people). In the TCC patient group, HLA -DQ6(1) and HLA -DQ7(3) antigens were detected with a significantly higher frequency than in the control group (p=0.018 and p=0.038, respectively), whereas HLA-A10, B4, DR53 and DQ1 antigens were detected with significantly higher frequency in the control group (p less 0.05 in all). It suggests that patients who had the antigens detected were at higher risk of TCC, and the ones who had the antigens displaying protective features as were detected in the control group, were at lesser risk.

  10. Utility of GATA3 immunohistochemistry in differentiating urothelial carcinoma from prostate adenocarcinoma and squamous cell carcinomas of the uterine cervix, anus, and lung.

    Science.gov (United States)

    Chang, Alex; Amin, Ali; Gabrielson, Edward; Illei, Peter; Roden, Richard B; Sharma, Rajni; Epstein, Jonathan I

    2012-10-01

    Distinguishing invasive high-grade urothelial carcinoma (UC) from other carcinomas occurring in the genitourinary tract may be difficult. The differential diagnosis includes high-grade prostatic adenocarcinoma, spread from an anal squamous cell carcinoma (SCC), or spread from a uterine cervical SCC. In terms of metastatic UC, the most common problem is differentiating spread of UC to the lung from a primary pulmonary SCC. Immunohistochemical analysis (IHC) for GATA binding protein 3 (GATA3), thrombomodulin (THROMBO), and uroplakin III was performed on a tissue microarray (TMA) containing 35 cases of invasive high-grade UC. GATA3 IHC was also performed on TMAs containing 38 high-grade (Gleason score ≥8) prostatic adenocarcinomas, representative tissue sections from 15 invasive anal SCCs, representative tissue sections from 19 invasive cervical SCCs, and TMAs with 12 invasive cervical carcinomas of the cervix [SCC (n=10), SCC with neuroendocrine features (n=1), and adenosquamous carcinoma (n=1)]. In addition, GATA3 IHC was performed on representative tissue sections from 15 pulmonary UC metastases and a TMA with 25 SCCs of the lung and 5 pulmonary non-small cell carcinomas with squamous features. GATA3, THROMBO, and uroplakin III were positive in 28 (80%), 22 (63%), and 21 (60%) cases of high-grade UC, respectively. All cases of GATA3-positive staining were nonfocal; 25 (89%) cases demonstrated moderate to strong staining, and 3 (11%) demonstrated weak staining. Of the 7 cases that failed to express GATA3, 5 were positive for THROMBO and/or uroplakin III, whereas 2 were negative for all 3 markers. None of the 38 high-grade prostatic adenocarcinomas was positive for GATA3. Weak GATA3 staining was present in occasional basal cells of benign prostate glands, in a few benign atrophic glands, and in urothelial metaplasia. Of the 15 cases of anal SCCs, 2 (7%) cases showed focal weak staining, and 1 (3%) showed focal moderate staining. Weak staining was also rarely

  11. Loss of aquaporin 3 protein expression constitutes an independent prognostic factor for progression-free survival: an immunohistochemical study on stage pT1 urothelial bladder cancer

    International Nuclear Information System (INIS)

    Treatment of patients with stage pT1 urothelial bladder cancer (UBC) continues to be a challenge due to its unpredictable clinical course. Reliable molecular markers that help to determine appropriate individual treatment are still lacking. Loss of aquaporin (AQP) 3 protein expression has previously been shown in muscle-invasive UBC. The aim of the present study was to investigate the prognostic value of AQP3 protein expression with regard to the prognosis of stage pT1 UBC. AQP 3 protein expression was investigated by immunohistochemistry in specimens of 87 stage T1 UBC patients, who were diagnosed by transurethral resection of the bladder (TURB) and subsequent second resection at a high-volume urological centre between 2002 and 2009. Patients underwent adjuvant instillation therapy with Bacillus Calmette-Guérin (BCG). Loss of AQP3 protein expression was defined as complete absence of the protein within the whole tumour. Expression status was correlated retrospectively with clinicopathological and follow-up data (median: 31 months). Multivariate Cox regression analysis was used to assess the value of AQP3 tumour expression with regard to recurrence-free (RFS), progression-free (PFS) and cancer-specific survival (CSS). RFS, PFS and CSS were calculated by Kaplan-Meier analysis and Log rank test. 59% of patients were shown to exhibit AQP3-positive tumours, whereas 41% of tumours did not express the marker. Loss of AQP3 protein expression was associated with a statistically significantly worse PFS (20% vs. 72%, p=0.020). This finding was confirmed by multivariate Cox regression analysis (HR 7.58, CI 1.29 – 44.68; p=0.025). Loss of AQP3 protein expression in pT1 UBC appears to play a key role in disease progression and is associated with worse PFS. Considering its potential prognostic value, assessment of AQP3 protein expression could be used to help stratify the behavior of patients with pT1 UBC

  12. Metastatic transitional cell carcinoma of the urinary bladder presenting as a mandibular gingival swelling.

    Science.gov (United States)

    de Courten, A; Irle, C; Samson, J; Lombardi, T

    2001-05-01

    Oral cavity metastases mostly originate from the breasts, lungs, or kidneys. Transitional cell carcinoma (TCC), the most frequent malignant tumor of the urinary bladder, rarely metastasizes to the jaws. To the best of our knowledge, only 8 cases of bladder carcinoma have been reported in the English literature to metastasize to the jawbones. A new case of mandibular metastasis of urinary bladder TCC with extension to the gingiva is presented in a 64-year-old white man. The patient was referred for a periodontal infection of the upper right first molar. The clinical examination also showed a gingival swelling located in the lower left premolar region with a hypoasthesia of the left side of the lower lip. The gingival mass was biopsied, and the microscopy showed a mandibular metastatic TCC of the urinary bladder extending to the gingiva. Periodontists should be aware that, although gingival metastases are rare, when they occur they may mimic other local benign pathological conditions. PMID:11394406

  13. Primary enteric-type adenocarcinomas of the urinary bladder are histogenetically analogous to colorectal carcinomas: Immunohistochemical evaluation of 109 cases

    Directory of Open Access Journals (Sweden)

    Saad S. Eissa

    2010-04-01

    In conclusion, primary non-urachal enteric-type adenocarcinoma of the urinary bladder is morphologically and immunophenotypically similar – if not identical – to colonic adenocarcinoma. The frequent association of enteric carcinomas of the urinary bladder with intestinal metaplasia and/or colonic-type adenomas with dysplasia suggests possible carcinogenetic pathways similar to that observed in colorectal carcinomas.

  14. Identification of differentially expressed genes in two new human bladder carcinoma cell lines

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To screen and identify differentially expressed genes in two new human urothelial carcinoma cell lines, BLS-211 and BLX. Methods Suppression subtractive hybridization (SSH) was used to createa subtracted library, and clones were sequenced. Results Totally 13 over-expressed genes in BLX and 9 in BLS-211 cells were obtained, respectively. Among them, 18 were known genes and 4 were new ESTs (Expressed Sequence Tag), and were collected by GenBank dbEST database (The access number was EB390424-7). Conc...

  15. Nomograms for Prediction of Disease Recurrence in Patients with Primary Ta, T1 Transitional Cell Carcinoma of the Bladder

    OpenAIRE

    Hong, Sung Joon; Cho, Kang Su; Han, Mooyoung; Rhew, Hyun Yul; Kim, Choung-Soo; Ryu, Soo Bang; Sul, Chong Koo; Chung, Moon Kee; Park, Tong Choon; Kim, Hyung Jin; ,

    2008-01-01

    We developed nomograms to predict disease recurrence in patients with Ta, T1 transitional cell carcinoma of the bladder. Thirty-eight training hospitals participated in this retrospective multicenter study. Between 1998 and 2002, a total of 1,587 patients with newly diagnosed non-muscle invasive bladder cancer were enrolled in this study. Patients with prior histories of bladder cancer, non-transitional cell carcinoma, or a follow-up duration of less than 12 months were excluded. With univari...

  16. Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder

    DEFF Research Database (Denmark)

    Gui, Yaoting; Guo, Guangwu; Huang, Yi;

    2011-01-01

    Transitional cell carcinoma (TCC) is the most common type of bladder cancer. Here we sequenced the exomes of nine individuals with TCC and screened all the somatically mutated genes in a prevalence set of 88 additional individuals with TCC with different tumor stages and grades. In our study, we...... frequently in tumors of low stages and grades, highlighting its potential role in the classification and diagnosis of bladder cancer. Our results provide an overview of the genetic basis of TCC and suggest that aberration of chromatin regulation might be a hallmark of bladder cancer....

  17. Cancer-specific survival after radical nephroureterectomy for upper urinary tract urothelial carcinoma: proposal and multi-institutional validation of a post-operative nomogram

    OpenAIRE

    Yates, D R; Hupertan, V.; Colin, P.; Ouzzane, A; Descazeaud, A; Long, J. A.; Pignot, G; Crouzet, S; Rozet, F; Neuzillet, Y; Soulie, M.; Bodin, T; Valeri, A.; Cussenot, O; Rouprêt, M

    2012-01-01

    Background: Owing to the scarcity of upper urinary tract urothelial carcinoma (UUT-UC) it is often necessary for investigators to pool data. A patient-specific survival nomogram based on such data is needed to predict cancer-specific survival (CSS) post nephroureterectomy (NU). Herein, we propose and validate a nomogram to predict CSS post NU. Patients and methods: Twenty-one French institutions contributed data on 1120 patients treated with NU for UUT-UC. A total of 667 had full data for nom...

  18. Urothelial Cancer Stem Cells

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    Irena Dimov

    2010-01-01

    Full Text Available There is mounting evidence supporting the idea that tumors, similar to normal adult tissues, arise from a specific stem-like cell population, the cancer stem cells (CSCs, which are considered as the real driving force behind tumor growth, the ability to metastasize, as well as resistance to conventional antitumor therapy. The concept that cancer growth recapitulates normal proliferative and/or regenerative processes, even though in very dysfunctional ways, has tremendous implications for cancer therapy. The rapid development of the CSC field, shoulder to shoulder with powerful genome-wide screening techniques, has provided cause for optimism for the development of more reliable therapies in the future. However, several important issues still lie ahead. Recent identification of a highly tumorigenic stem-like compartment and existence of urothelial differentiation programs in urothelial cell carcinomas (UCCs raised important questions about UCC initiation and development. This review examines the present knowledge on CSCs in UCCs regarding the similarities between CSCs and the adult urothelial stem cells, potential origin of urothelial CSCs, main regulatory pathways, surface markers expression, and the current state of CSC-targeting therapeutic strategies.

  19. Primary Intramural Vesical Endometriosis Mimicking Urothelial Carcinoma in a Middle Aged Female

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    Shirazi N

    2015-10-01

    Full Text Available Endometriosis is the presence of ectopic endometrial tissue outside the uterus. Presence of endometrial glands and/or stroma may interfere with the normal physiological process by their infiltrative nature or by forming adhesions. Endometriosis occurs in 15-20% of women of child bearing age and commonly involves the ovaries, utero-sacral ligaments, fallopian tubes, rectum, scar sites and cervico-vaginal regions. Incidence of urinary tract involvement is estimated to be 1%. We report a case of a 38 year female presenting with low back pain, single episode of haematuria and burning during micturition. Urine culture was negative. There was no past history of pelvic surgery. On cystoscopy, a growth was visualised in the posterior urinary bladder wall suspicious of neoplastic origin. Tansurethral resection of bladder nodule was done and sent for histopathology, on which it was diagnosed as endometriosis. The case merits interest due to its atypical clinical presentation and the rarity of the lesion at this site.

  20. Plasmacytoid Transitional Cell Carcinoma of Bladder: A Clinico-pathological Study and Review of Literatures

    Institute of Scientific and Technical Information of China (English)

    FENG Xiaoli; ZHANG Hongtu; SUN Yuntian; LIU Xiuyun

    2006-01-01

    Objective: To study the pathologic features of plasmacytoid transitional cell carcinoma of the bladder, and to analyze the diagnostic features, criteria for differential diagnosis and the clinical significance of the tumor. Methods: Two cases of bladder plasmacytoid transitional cell carcinoma were studied. Routine paraffin sections with HE staining, Pap smear and immunohistochemistry by S-P method were observed under a light microscope. Pathological and clinical data were analyzed by comparison with early reported cases in literatures. Results: A characteristic feature of this tumor was of deep invasion in the lamina propria and/or muscularis propria, in addition to the component of carcinoma in situ in the mucosa, when tumors were diagnosed. The histological pattern and cytological features showed similarity to a plasmacytoid tumor. The tumor cells were strongly positive for AE1/AE3, CEA and CK18. The prognosis appeared to be worse than ordinary transitional cell carcinoma. Conclusion: The plasmacytoid transitional cell carcinoma of bladder is rare but has typical pathological, immunohistological and clinical features. Pathologists should be aware of this kind of primary tumor of bladder.

  1. Protective effects of plasma alpha-tocopherols on the risk of inorganic arsenic-related urothelial carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Chi-Jung [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Pu, Yeong-Shiau [Department of Urology, National Taiwan University Hospital, Taipei, Taiwan (China); Chen, Ying-Ting [Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Su, Chien-Tien [Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan (China); Wu, Chia-Chang [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Department of Urology, Taipei Medical Universtiy-Shuang Ho Hospital, Taipei, Taiwan (China); Shiue, Horng-Sheng [Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan (China); Huang, Chao-Yuan [Department of Urology, National Taiwan University Hospital, Taipei, Taiwan (China); Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Hsueh, Yu-Mei, E-mail: ymhsueh@tmu.edu.tw [Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China)

    2011-02-15

    Arsenic plays an important role in producing oxidative stress in cultured cells. To investigate the interaction between high oxidative stress and low arsenic methylation capacity on arsenic carcinogenesis, a case-control study was conducted to evaluate the relationship among the indices of oxidative stress, such as urinary 8-hydroxydeoxyquanine (8-OHdG), as well as plasma micronutrients and urinary arsenic profiles on urothelial carcinoma (UC) risk. Urinary 8-OHdG was measured using high-sensitivity enzyme-linked immunosorbent assay kits. The urinary arsenic species were analyzed using high-performance liquid chromatography and hydride generator-atomic absorption spectrometry. Plasma micronutrient levels were analyzed using reversed-phase high-performance liquid chromatography. The present study showed a significant protective effect of plasma alpha-tocopherol on UC risk. Plasma alpha-tocopherol levels were significantly inversely related to urinary total arsenic concentrations and inorganic arsenic percentage (InAs%), and significantly positively related to dimethylarsinic acid percentage (DMA%). There were no correlations between plasma micronutrients and urinary 8-OHdG. Study participants with lower alpha-tocopherol and higher urinary total arsenic, higher InAs%, higher MMA%, and lower DMA% had a higher UC risk than those with higher alpha-tocopherol and lower urinary total arsenic, lower InAs%, lower MMA%, and higher DMA%. These results suggest that plasma alpha-tocopherol might modify the risk of inorganic arsenic-related UC. - Research Highlights: {yields} Plasma alpha-tocopherol levels were significantly inversely related to UC risk. {yields} There were no correlations between plasma micronutrients and urinary 8-OHdG. {yields} People with lower alpha-tocopherol and higher total arsenic had increased UC risk.

  2. Protective effects of plasma alpha-tocopherols on the risk of inorganic arsenic-related urothelial carcinoma

    International Nuclear Information System (INIS)

    Arsenic plays an important role in producing oxidative stress in cultured cells. To investigate the interaction between high oxidative stress and low arsenic methylation capacity on arsenic carcinogenesis, a case-control study was conducted to evaluate the relationship among the indices of oxidative stress, such as urinary 8-hydroxydeoxyquanine (8-OHdG), as well as plasma micronutrients and urinary arsenic profiles on urothelial carcinoma (UC) risk. Urinary 8-OHdG was measured using high-sensitivity enzyme-linked immunosorbent assay kits. The urinary arsenic species were analyzed using high-performance liquid chromatography and hydride generator-atomic absorption spectrometry. Plasma micronutrient levels were analyzed using reversed-phase high-performance liquid chromatography. The present study showed a significant protective effect of plasma alpha-tocopherol on UC risk. Plasma alpha-tocopherol levels were significantly inversely related to urinary total arsenic concentrations and inorganic arsenic percentage (InAs%), and significantly positively related to dimethylarsinic acid percentage (DMA%). There were no correlations between plasma micronutrients and urinary 8-OHdG. Study participants with lower alpha-tocopherol and higher urinary total arsenic, higher InAs%, higher MMA%, and lower DMA% had a higher UC risk than those with higher alpha-tocopherol and lower urinary total arsenic, lower InAs%, lower MMA%, and higher DMA%. These results suggest that plasma alpha-tocopherol might modify the risk of inorganic arsenic-related UC. - Research Highlights: → Plasma alpha-tocopherol levels were significantly inversely related to UC risk. → There were no correlations between plasma micronutrients and urinary 8-OHdG. → People with lower alpha-tocopherol and higher total arsenic had increased UC risk.

  3. Correlation of Apobec Mrna Expression with overall Survival and pd-l1 Expression in Urothelial Carcinoma

    Science.gov (United States)

    Mullane, Stephanie A.; Werner, Lillian; Rosenberg, Jonathan; Signoretti, Sabina; Callea, Marcella; Choueiri, Toni K.; Freeman, Gordon J.; Bellmunt, Joaquim

    2016-01-01

    Metastatic urothelial carcinoma (mUC) has a very high mutational rate and is associated with an APOBEC mutation signature. We examined the correlation of APOBEC expression with overall survival (OS) and PD-L1 expression in a cohort of 73 mUC patients. mRNA expression of APOBEC3 family of genes (A3A, A3B, A3C, A3F_a, A3F_b, A3G, A3H) was measured using Nanostring. PD-L1 expression, evaluated by immunohistochemistry, on tumor infiltrating mononuclear cells (TIMCs) and tumor cells was scored from 0 to 4, with 2–4 being positive. Wilcoxon’s non-parametric tests assessed the association of APOBEC and PD-L1. The Cox regression model assessed the association of APOBEC with OS. All APOBEC genes were expressed in mUC. Increased A3A, A3D, and A3H expression associates with PD-L1 positive TIMCs (p = 0.0009, 0.009, 0.06). Decreased A3B expression was marginally associated with PD-L1 positive TIMCs expression (p = 0.05). Increased A3F_a and A3F_b expression was associated with increased expression of PD-L1 on tumor cells (p = 0.05). Increased expression of A3D and A3H was associated with longer OS (p = 0.0009). Specific APOBEC genes have different effects on mUC in terms of survival and PD-L1 expression. A3D and A3H may have the most important role in mUC as they are associated with OS and PD-L1 TIMC expression. PMID:27283319

  4. Effects of curcumin in an orthotopic murine bladder tumor model

    Directory of Open Access Journals (Sweden)

    Katia R. M. Leite

    2009-10-01

    Full Text Available Cigarette smoking (CS is the main risk factor for bladder cancer development. There are more than 100 carcinogens present in cigarette smoke. Among the potential mediators of CS-induced alterations is nuclear factor-kappa (NF-κB, which is responsible for the transcription of genes related to cell transformation, tumor promotion, angiogenesis, invasion and metastasis. Curcumin is a polyphenol compound derived from Curcuma longa that suppress cellular transformation, proliferation, invasion, angiogenesis, and metastasis by down regulating NF-κB and its regulated genes. The aim of our study was to assess the effects of curcumin in bladder urothelial carcinoma. We studied the effects of curcumin in vitro and in vivo using the orthotropic syngeneic bladder tumor animal model MB49. Curcumin promotes apoptosis of bladder tumor cells in vitro. In vivo tumors of animals treated with curcumin were significantly smaller as compared to controls. Using immunohistochemistry, we demonstrated a decrease in the expression of Cox-2 by 8% and Cyclin D1 by 13% in the animals treated with curcumin; both genes regulated by NF-κB and related to cell proliferation. In this study, we showed that curcumin acts in bladder urothelial cancer, possibly dowregulating NF-κB-related genes, and could be an option in the treatment of urothelial neoplasms. The results of our study suggest that further research is warranted to confirm our findings.

  5. Methylation of a CpG Island within the Uroplakin Ib Promoter: A Possible Mechanism for Loss of Uroplakin lb Expression in Bladder Carcinoma

    Directory of Open Access Journals (Sweden)

    Andrea E. Varga

    2004-03-01

    Full Text Available Uroplakin Ib is a structural protein on the surface of urothelial cells. Expression of uroplakin Ib mRNA is reduced or absent in many transitional cell carcinomas (TCCs but molecular mechanisms underlying loss of expression remain to be determined. Analysis of the uroplakin Ib promoter identified a weak CpG island spanning the proximal promoter, exon 1, and the beginning of intron 1. This study examined the hypothesis that methylation of this CpG island regulates uroplakin Ib expression. Uroplakin Ib mRNA levels were determined by reverse transcription polymerase chain reaction and CpG methylation was assessed by bisulfite modification of DNA, PCR, and sequencing. A correlation was demonstrated in 15 TCC lines between uroplakin Ib mRNA expression and lack of CpG methylation. In support of a regulatory role for methylation, incubating uroplakin Ib-negative lines with 5-aza-2′ -deoxycytidine reactivated uroplakin Ib mRNA expression. A trend between uroplakin Ib mRNA expression and CpG methylation was also observed in normal urothelium and bladder carcinomas. In particular, loss of uroplakin Ib expression correlated with methylation of a putative Spi/NFκB binding motif. The data are consistent with the hypothesis that methylation of specific sites within the uroplakin Ib promoter may be an important factor in the loss of uroplakin Ib expression in TCCs.

  6. 膀胱癌组织中MICA、NF-κB和p53的表达和意义%Expression and significance of MICA, NF-κB and P53 in carcinoma of the urinary bladder

    Institute of Scientific and Technical Information of China (English)

    邓汪东; 卢善明; 杨峰涛

    2012-01-01

    Objective To investigate the mechanism of the expression of MHC class Ⅰ chain-related A (MICA) in carcinoma of the urinary bladder,the relationship between MICA,nuclear factor-κB ( NF-κB) and p53 expression in bladder cancer was studied.Methods The expression of MICA,NF-κB and p53 in a total of 75 cases of urothelial carcinoma tissues and 15 normal mucous membrane tissues of the bladder was evaluated by immunohistochemistry.Results The expression rates of MICA,NF-κB and p53 protein in urothelial carcinoma were 4.08%,85.3% and 49.3%,respectively.Up-regulation of their expression was found in urothelial carcinoma compared with normal mucous membrane tissues ( P < 0.05 ).MICA expression was positively correlated with NF-κB expression( r =0.256,P =0.027),but negatively correlated with p53 expression( r =- 0.23,P =0.047 ).Conclusions Up-regulation of MICA expression was detected in bladder cancer.MICA protein may be a new tumor-associated antigen of bladder cancer.MICA expression may be regulated by NF-κB pathway,while p53 pathway may not play a part in MICA up-expression during the urothelial malignant transformation.%目的 探讨膀胱尿路上皮癌中MHC Ⅰ类链相关蛋白A(MHC classⅠ chain-related A,MICA)的表达,以及与核因子-κB(nuclear factor-κB,NF-κB)和p53的相互关系,为研究膀胱癌组织中MICA蛋白的表达机制提供组织学依据.方法 用免疫组化方法检测75例膀胱尿路上皮癌及15例正常膀胱黏膜中MICA、NF-κB和p53蛋白表达,对MICA、NF-κB和p53在正常膀胱黏膜、浸润和非浸润膀胱癌中的表达进行统计学分析.结果 (1)MICA、NF-κB和p53蛋白在膀胱癌的表达率分别为48.0%、85.3%和49.3%,均显著高于正常膀胱黏膜(P<0.05).MICA蛋白在浸润性膀胱癌的表达低于非浸润性膀胱癌(P<0.05).(2)膀胱癌组织中MICA与NF-κB蛋白表达呈正相关(r=0.256,P=0.027),而MICA和p53蛋白的表达呈负相关(r=-0.23,P=0.047).结论 膀胱癌

  7. Clinico-pathological features of bladder carcinoma in women in Pakistan and smokeless tobacco as a possible risk factor

    Directory of Open Access Journals (Sweden)

    Rafique Muhammad

    2005-08-01

    Full Text Available Abstract Background Bladder carcinoma is one of the common urological malignancies occurring worldwide in both sexes. Use of smokeless tobacco by women is common in rural areas of Pakistan. The clinico-pathological features of bladder carcinoma in women and association of smokeless tobacco as a possible risk factor for bladder carcinoma has not been well described in the literature. The objective of the study was to determine the clinico-pathological features of histologically confirmed bladder carcinoma in women and to investigate the role of smokeless tobacco use as a possible risk factor for its development. Patients and methods Of the 204 patients (160 male and 44 female M:F ratio 3.6:1 of newly diagnosed bladder carcinoma treated at Nishtar Medical College Hospital Multan from January 1998 to December 2004, the 44 female patients were evaluated with respect to age, clinical presentation, cystoscopic findings, histopathological reports and possible etiological factors. Data were collected and prospectively updated at the time of discharge from hospital and during follow-up in urology out-patient clinic. Results Transitional cell carcinoma accounted for all of the bladder carcinoma in women. Median age of the patients was 55 years and 68% patients were under 60 years of age. Majority of patients (88% presented with hematuria. Eleven (25% patients had superficial (pTa/pT1 while 33 (75% patients had muscle invasive (T2–T4 bladder carcinoma. Most (81% superficial tumors were papillary while muscle invasive tumors had solid configuration at cystoscopy. Of these, 21 (47% patients had long history of smokeless tobacco use (chewable or moist snuff. Conclusion Transitional cell carcinoma is the most common bladder malignancy in women in Pakistan. Many women with bladder carcinoma had long history of use of smokeless tobacco. Majority of patients presented with hematuria and were under 60 years of age. At the time of diagnosis 75% women had muscle

  8. [Squamous cell carcinoma of the bladder in a patient with HIV and paraplegia].

    Science.gov (United States)

    Bartel, P; Göcking, K; Janzen, J; Pannek, J

    2013-09-01

    In patients with spinal cord injury (SCI) the rate of squamous cell carcinomas (SCC) among bladder tumors is increased compared to the general population. An increased life expectancy is achieved by modern HIV treatment so that more AIDS-unrelated malignomas, e.g. bladder tumors, occur in these patients. Therefore, the risk for SCC in this group of patients is increased in patients with SCI and HIV but the combination of these two diseases is rare. We report the first case of SCC in a patient with SCI and HIV. Initial symptoms of bladder tumors in patients with SCI are often unspecific; therefore, in cases with new onset hematuria, recurrent urinary tract infections and changes in bladder function, cystoscopy and computed tomography (CT) scanning should be considered. PMID:23949540

  9. Squamous Cell Carcinoma of the Bladder Mimicking Interstitial Cystitis and Voiding Dysfunction

    Directory of Open Access Journals (Sweden)

    Colton Prudnick

    2013-01-01

    Full Text Available Squamous cell carcinoma (SCC of the bladder is a relatively uncommon cause of bladder cancer accounting for <5% of bladder tumors in the western countries. SCC has a slight male predominance and tends to occur in the seventh decade of life. The main presenting symptom of SCC is hematuria, and development of this tumor in the western world is associated most closely with chronic indwelling catheters and spinal cord injuries. A 39-year-old Caucasian female presented with bladder and lower abdominal pain, urinary frequency, and nocturia which was originally believed to be interstitial cystitis (IC but was later diagnosed as SCC of the bladder. Presentation of SCC without hematuria is an uncommon presentation, but the absence of this symptom should not lead a practitioner to exclude the diagnosis of SCC. This case is being reported in an attempt to explain the delay and difficulty of diagnosis. Background on the risk factors for SCC of the bladder and the typical presenting symptoms of bladder SCC and IC are also reviewed.

  10. Sperm associated antigen 9 plays an important role in bladder transitional cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Deepika Kanojia

    Full Text Available BACKGROUND: Majority of bladder cancer deaths are caused due to transitional cell carcinoma (TCC which is the most prevalent and chemoresistant malignancy of urinary bladder. Therefore, we analyzed the role of Sperm associated antigen 9 (SPAG9 in bladder TCC. METHODOLOGY AND FINDINGS: We examined SPAG9 expression and humoral response in 125 bladder TCC patients. Four bladder cancer cell lines were assessed for SPAG9 expression. In addition, we investigated the effect of SPAG9 ablation on cellular proliferation, cell cycle, migration and invasion in UM-UC-3 bladder cancer cells by employing gene silencing approach. Our SPAG9 gene and protein expression analysis revealed SPAG9 expression in 81% of bladder TCC tissue specimens. High SPAG9 expression (>60% SPAG9 positive cells was found to be significantly associated with superficial non-muscle invasive stage (P = 0.042 and low grade tumors (P = 0.002 suggesting SPAG9 putative role in early spread and tumorigenesis. Humoral response against SPAG9 was observed in 95% of patients found positive for SPAG9 expression. All four bladder cancer cell lines revealed SPAG9 expression. In addition, SPAG9 gene silencing in UM-UC-3 cells resulted in induction of G0-G1 arrest characterized by up-regulation of p16 and p21 and consequent down-regulation of cyclin E, cyclin D and cyclin B, CDK4 and CDK1. Further, SPAG9 gene silencing also resulted in reduction in cellular growth, and migration and invasion ability of cancer cells in vitro. CONCLUSIONS: Collectively, our data in clinical specimens indicated that SPAG9 is potential biomarker and therapeutic target for bladder TCC.

  11. Prognostic factors for primary superficial transitional cell carcinoma of the bladder: a retrospective cohort study

    Institute of Scientific and Technical Information of China (English)

    YANG Tu-bao; ZENG Fu-hua; SUN Zhen-qiu

    2006-01-01

    Background Previous studies showed that the prognostic factors for superficial transitional cell carcinoma of the bladder varied with the findings of different cohorts. Few multivariate analyses of prognostic factors for superficial bladder tumors have been reported in China and bladder preservation as a prognostic index of superficial bladder tumors is limited and scarce in Chinese patients. This study was conducted to analyze a group of risk factors for prognostic outcomes for patients with primary superficial transitional cell carcinoma of the bladder.Methods Between January 1980 to December 2000, 198 patients [172 men and 26 women; mean age (52.98±11.28) years] with primary superficial transitional cell carcinoma who were pathologically classified as Ta or T1 in Hunan Provincial Tumor Hospital (Changsha, China) were enrolled in this study. Surgical methods included local resection and electric coagulation of bladder tumors, transurethral resection of bladder tumors and partial cystectomy. After initial surgical treatment, patients were followed through a cystoscopy every three months during the first two years and every six months thereafter in the design of retrospective cohort. Survival analysis was performed to analyze risk factors of the prognostic outcomes for transitional cell carcinoma of the bladder.Canonical correlation analysis was conducted to present and interpret synthetically the multi-correlation between all kinds of prognostic outcomes and risk factor in multiply dimensions.Results The average follow-up period was (6.65±4.74) years. Assessments at three, five, and 10 years showed recurrence rates, respectively, of (28.32 ± 3.45)%, (35.31 ± 3.83)%, and (42.48 ± 4.40)%; progression rates of (8.89±2.14)%, (15.16±2.94)%, and (23.88±4.19)%; bladder-preservation rates of (94.68± 1.74)%, (93.87±1.91)%, and (91.51±2.49)%; metastasis rates of (8.25±2.05)%, (11.24±2.47)%, and (28.94±4.93)%; and cancer-related survival rates of (95.02 ±1

  12. Bladder Carcinoma Data with Clinical Risk Factors and Molecular Markers: A Cluster Analysis

    Directory of Open Access Journals (Sweden)

    Enrique Redondo-Gonzalez

    2015-01-01

    Full Text Available Bladder cancer occurs in the epithelial lining of the urinary bladder and is amongst the most common types of cancer in humans, killing thousands of people a year. This paper is based on the hypothesis that the use of clinical and histopathological data together with information about the concentration of various molecular markers in patients is useful for the prediction of outcomes and the design of treatments of nonmuscle invasive bladder carcinoma (NMIBC. A population of 45 patients with a new diagnosis of NMIBC was selected. Patients with benign prostatic hyperplasia (BPH, muscle invasive bladder carcinoma (MIBC, carcinoma in situ (CIS, and NMIBC recurrent tumors were not included due to their different clinical behavior. Clinical history was obtained by means of anamnesis and physical examination, and preoperative imaging and urine cytology were carried out for all patients. Then, patients underwent conventional transurethral resection (TURBT and some proteomic analyses quantified the biomarkers (p53, neu, and EGFR. A postoperative follow-up was performed to detect relapse and progression. Clusterings were performed to find groups with clinical, molecular markers, histopathological prognostic factors, and statistics about recurrence, progression, and overall survival of patients with NMIBC. Four groups were found according to tumor sizes, risk of relapse or progression, and biological behavior. Outlier patients were also detected and categorized according to their clinical characters and biological behavior.

  13. Animal model of naturally occurring bladder cancer: Characterization of four new canine transitional cell carcinoma cell lines

    OpenAIRE

    Rathore, Kusum; Cekanova, Maria

    2014-01-01

    Background Development and further characterization of animal models for human cancers is important for the improvement of cancer detection and therapy. Canine bladder cancer closely resembles human bladder cancer in many aspects. In this study, we isolated and characterized four primary transitional cell carcinoma (K9TCC) cell lines to be used for future in vitro validation of novel therapeutic agents for bladder cancer. Methods Four K9TCC cell lines were established from naturally-occurring...

  14. Selective arterial embolization for control of haematuria secondary to advanced or recurrent transitional cell carcinoma of the bladder.

    LENUS (Irish Health Repository)

    Halpenny, D

    2014-05-02

    Haematuria is a common symptom in patients with advanced transitional cell carcinoma of the bladder. We report our experience of selective pelvic embolization using gelfoam as an embolic agent to treat intractable haematuria in these patients.

  15. NS-398, a selective cyclooxygenase-2 inhibitor, reduces experimental bladder carcinoma outgrowth by inhibiting tumor cell proliferation.

    NARCIS (Netherlands)

    Smakman, N.; Schaap, N.P.M.; Snijckers, C.M.; Rinkes, M.J.; Kranenburg, O.

    2005-01-01

    OBJECTIVES: To evaluate the efficacy of the selective cyclooxygenase-2 (COX-2) inhibitor NS-398 in treating experimental T24 bladder carcinoma, and to assess its effect on tumor cell proliferation and survival and tumor vascularization. COX-2 overexpression is frequently observed in bladder carcinom

  16. Detection of chromosomal aberrations of bladder carcinoma by fluorescence in situ hybridization%荧光原位杂交技术检测膀胱癌染色体畸变的研究

    Institute of Scientific and Technical Information of China (English)

    李晓娟; 符生苗; 刘元晓; 邓立群

    2012-01-01

    Objective To detect the common chromosomal aberrations from (he bladder transitional cell carcinoma by using M-FISH. Methods 50 urine samples were detected by FISH with centromeric probes of chromosome 17,7,3 and band probe of 9p2 l,and then the results were analyzed. Results There were four chromosomes showing a high distortion in 50 cases of bladder carcinoma group,showing significant association between chromosome 17,7,3,9p2 1 aberrations and pathological stage,grade (P<0.01). Conclusion Fluorescence in situ hybridization is an effective way for detection of chromosomal aberrations of urothelial tumors, as well as the early diagnosis of urothelial cancer.%目的 用多色荧光原位杂交(M-FISH)检测膀胱移行细胞癌中常见的染色体畸变. 方法 50例尿液标本采用FISH技术检测9p21区带及17、7、3号染色体的畸变情况,并对结果进行相应的统计学分析. 结果 50例膀胱癌病人组中,4个染色体均显示较高的畸变率.9p21以及17、7和3号染色体畸变率与病理分期、分级均有显著相关性(P<0.01).结论 用荧光原位杂交技术是检测尿路上皮肿瘤染色体畸变的有效方法,可作为早期诊断尿路上皮肿瘤的重要途径.

  17. Fire fighters, combustion products, and urothelial cancer.

    Science.gov (United States)

    Golka, Klaus; Weistenhöfer, Wobbeke

    2008-01-01

    Urothelial cancer may be induced by different workplace chemicals, including carcinogenic aromatic amines, coke oven fumes, and cigarette smoking. The general impact of combustion products on urothelial cancer risk of exposed persons is still controversial. This raises the question whether fire fighters may have an increased risk for urothelial cancer. The present review compiles the literature on combustion products, possibly relevant for fire fighters, and the available studies on urinary bladder cancer risk in fire fighters. Chemical analyses of smoke from experimental fires as well as from fires in cities, wildlands, and industry do not indicate a generally elevated risk of bladder cancer in fire fighters. This is supported by studies on bladder cancer in fire fighters. Based on mortality studies, studies on exposures, and cancer incidence, we conclude that an elevated risk of urothelial cancer in fire fighters, in general, is not confirmed. Only in professional fire fighters more severely exposed for decades, having started their career some decades before, occupational exposure might be discussed as causative for urothelial cancer.

  18. Treatment Trends and Outcomes of Small-Cell Carcinoma of the Bladder

    Energy Technology Data Exchange (ETDEWEB)

    Koay, Eugene J. [Baylor College of Medicine, Houston, Texas (United States); MD Anderson Cancer Center, Houston, Texas (United States); Teh, Bin S., E-mail: bteh@tmh.org [Methodist Hospital, Houston, Texas (United States); Methodist Hospital Research Institute, Houston, Texas (United States); Paulino, Arnold C.; Butler, E. Brian [Methodist Hospital, Houston, Texas (United States); Methodist Hospital Research Institute, Houston, Texas (United States)

    2012-05-01

    Purpose: Treatment for small-cell carcinoma of the bladder is largely guided by case reports, retrospective reviews, and small prospective trials. This study aimed to study outcomes using a large population-based database. Methods: The Surveillance, Epidemiology, and End Results-Medicare database (1991-2005) was used to analyze how different treatment combinations of specific bladder surgeries, chemotherapy, and radiation affected patient outcomes. Trends in the use of these combinations over time were also analyzed. Results: A total of 533 patients were retrieved from the database. A bladder-sparing approach involving transurethral resection of the bladder tumor (TURBT) combined with chemotherapy and radiation yielded no significant difference in overall survival compared with patients undergoing at least a cystectomy (of whom over 90% received radical cystectomy) with chemotherapy (p > 0.05). The analysis of treatment trends indicated that these two general strategies for cure combined to account for fewer than 20% of patients. A majority of patients (54%) received TURBT as their only surgical treatment, and a subset analysis of these patients indicated that chemotherapy played a role in all stages of disease (p < 0.05) whereas radiation improved overall survival in regional-stage disease (p < 0.05). Conclusion: Relatively few patients with small-cell carcinoma of the bladder receive potentially curative therapies. Chemotherapy should be a major component of treatment. Cystectomy and bladder-sparing approaches represent two viable strategies and deserve further investigation to identify the patients who may benefit from organ preservation or not. In addition, the role of radiation in regional-stage disease should be investigated further, because it positively affects survival after TURBT.

  19. Cost-effectiveness and budget impact analysis of vinflunine used in the treatment of patients with urothelial transitional cell carcinoma resistant to platinum-based regimens

    Directory of Open Access Journals (Sweden)

    A. Yu. Kulikov

    2015-01-01

    Full Text Available As of now, vinflunine is the only second-line chemotherapy drug showing an advantage over the best maintenance therapy in a Phase IIIrandomized study treating patients with urothelial transitional cell carcinoma. Due to the advent of this drug, it was relevant to make a pharmacoeconomic analysis comparing therapy with vinflunine in combination with the best maintenance therapy and the latter only. A budget impact analysis showed that the use of the new drug required additional expenditures. The ICER reflecting the cost of one additional year of life and estimating vinflunine therapy as cost-effective was determined by the results of a cost-effectiveness analysis.

  20. Simultaneous Penile and Signet Ring Cell Bladder Carcinoma in Renal Transplant Recipient: A First Case

    Directory of Open Access Journals (Sweden)

    Francesca Manassero

    2009-01-01

    Full Text Available The incidence and prevalence of cancer increase with time after transplantation. Therefore, a risk-adapted screening process is very important in order to identify low-grade malignancies early in their development. This provides the opportunity to initiate appropriate immunosuppressive regimens depending on the tumor type and stage of development. The first case presented is one of a 65-year-old patient with a double genitourinary carcinoma (penis and bladder. The patient received kidney transplantation 7 years prior to this event. After adequate surgical treatment (partial amputation of the penis for squamous cell carcinoma and complete transurethral resection of bladder adenocarcinoma, the patient was noted to be free of tumor recurrence and had functioning renal graft with a 2-year follow-up.

  1. Long-term oncologic outcomes of laparoscopic nephroureterectomy versus open nephroureterectomy for upper tract urothelial carcinoma: a systematic review and meta-analysis.

    Science.gov (United States)

    Zhang, Su; Luo, You; Wang, Cheng; Fu, Sheng-Jun; Yang, Li

    2016-01-01

    Background. Several factors have been validated as predictors of disease recurrence in upper tract urothelial carcinoma. However, the oncological outcomes between different surgical approaches (open nephroureterectomy versus laparoscopic nephroureterectomy, ONU vs LNU) remain controversial. Therefore, we performed a meta-analysis to evaluate the oncological outcomes associated with different surgical approaches. Methods. We conducted an electronic search of the PubMed, Embase, ISI Web of Knowledge and Cochrane Library electronic databases through November 2015, screened the retrieved references, collected and evaluated the relevant information. We extracted and synthesized the corresponding hazard ratios (HRs) and 95% confidence intervals (95% CI) using Stata 13. Results. Twenty-one observational studies were eligible for inclusion in the meta-analysis. The results of the meta-analysis showed no differences in the intravesical recurrence-free survival (IRFS), unspecified recurrence-free survival (UnRFS) and overall survival (OS) between LNUandONU. However, improvements in the extravesical recurrence free survival (ExRFS) and cancer specific survival (CSS) were observed inLNU. The pooled hazard ratios were 1.05 (95% CI [0.92-1.18]) for IRFS, 0.80 (95% CI [0.64-0.96]) for ExRFS, 1.10 (95% CI [0.93-1.28]) for UnRFS, 0.91 (95% CI [0.66-1.17]) for OS and 0.79 (95% CI [0.68-0.91]) for CSS. Conclusion. Based on current evidence, LNU could provide equivalent prognostic effects for upper tract urothelial carcinoma, and had better oncological control of ExRFS and CSS compared to ONU. However, considering all eligible studies with the intrinsic bias of retrospective study design, the results should be interpreted with caution. Prospective randomized trials are needed to verify these results.

  2. Bladder squamous cell carcinomas express psoriasin and externalize it to the urine

    DEFF Research Database (Denmark)

    Celis, J E; Rasmussen, H H; Vorum, H;

    1996-01-01

    PURPOSE: To report a single biomarker, psoriasin (Mr 11.0 kd, pI 6.2), a calcium binding protein which is expressed largely by stratified squamous epithelia and is externalized to the urine of bladder squamous cell carcinoma (SCC) bearing patients. MATERIALS AND METHODS: Protein expression profiles...... identified from 100 samples of patients with suspected transitional cell carcinoma (TCC). The protein profiles of the 4 SCCs (56-1, grade III, T4; 181-1, grade I, T3; 219-1, grade III, T3 and 239-1, grade not determined, T2-4) resembled that of keratinocytes, suggesting that these cells express an early...

  3. Changes produced in the urothelium by traditional and newer therapeutic procedures for bladder cancer

    OpenAIRE

    Lopez-Beltran, A.; Luque, R J; Mazzucchelli, R; Scarpelli, M; Montironi, R

    2002-01-01

    A handful of traditional and newer therapeutic procedures, such as chemotherapy, immunotherapy, radiotherapy, photodynamic and laser treatment, and gene therapy, are used to treat epithelial malignancies of bladder origin. These treatment modalities, used either intravesically or systemically, produce morphological changes in the urothelial mucosa that can be mistaken for carcinoma. The pathologist must be able to separate toxic and drug related alterations from tumour related changes. The cl...

  4. Distinct microRNA alterations characterize high- and low-grade bladder cancer.

    OpenAIRE

    Catto, J W F; Miah, S; Owen, H C; Bryant, H.; Myers, K.; Dudziec, E.; Larre, S.; Milo, M.; Rehman, I; Rosario, D. J.; Di Martino, E; Knowles, M. A.; Meuth, M; Harris, A.L.; Hamdy, F C

    2009-01-01

    Urothelial carcinoma of the bladder (UCC) is a common disease that arises by at least two different molecular pathways. The biology of UCC is incompletely understood, making the management of this disease difficult. Recent evidence implicates a regulatory role for microRNA in cancer. We hypothesized that altered microRNA expression contributes to UCC carcinogenesis. To test this hypothesis, we examined the expression of 322 microRNAs and their processing machinery in 78 normal and malignant u...

  5. Small cell carcinoma of the urinary bladder: KIT and PDGFRA gene mutations

    Directory of Open Access Journals (Sweden)

    Nuket Eliyakin

    2015-12-01

    Full Text Available Primary small cell carcinoma of the urinary bladder is very rare. A 72-year-old was admitted to our hospital because of hematuria and dysuria. Cystoscopy revealed a bladder full of multiple, solid and papillary tumors. Biopsies from the deep and papillary tumors were taken. Histologically, tumor was pure small cell carcinoma. Immunohistochemically, the tumor cells were positive for cytokeratin, chromogranin, synaptophysin, neuron-specific enolase, CD56, CD117 and Ki67 (labeling 70%. The tumor cells were negative for CK7, CK20, CD3, CD20, LCA, CDX2, uroplakin, thyroid transcription factor 1, PSA and p63. Metastatic workup was performed an no primary or metastatic lung lesions were noted. Due to the clinical, radiologic and immunohistochemical findings, the patient was diagnosed as primary small cell carcinoma of bladder. A molecular genetic analysis for KIT (exons 9, 11, 13 and 17 and PDGFRA (exons 12 and 18 genes was performed, in paraffin micro dissection specimens, by the PCR-direct sequencing method. According to the sequencing analyses, two mutations were found at positions 558 (p.K558N and 562 (p.E562D in KIT gene exon 11 in our case. The another hand the same case presented two mutations in PDGFRA gene exon 14 at position 631 (p.P631A and 638 (p.638Q_639AinsC. The disease process was fulminant and the patient was lost due to several complications prior to any chemotherapy.

  6. THE INHIBITORY EFFECT OF MELATONIN ON THE GROWTH OF HUMAN BLADDER CARCINOMA T24 CELL LINE

    Institute of Scientific and Technical Information of China (English)

    白艳红; 慕慧; 赵晏; 蔡晓宏; 王中秋; 郭瑗

    2004-01-01

    Objective To study the inhibitory effects of melatonin and its inhibitory mechanism on the growth of human bladder carcinoma T24. Methods The inhibitory effects of melatonin with various concentrations on the human bladder carcinoma T24 lines in vitro were determined by MTT assay. The mechanism of the inhibition was observed by flow cytometry (FCM) and transmission electron microscopy (TEM). Results The 30% inhibition concentration (IC30) value was 0.71mmol·L-1 and the 50% inhibition concentration (IC50) value was 1.20mmol·L-1. The population doubling time of T24 cells treated with melatonin at 0.71mmol·L-1 was 43.2 hours, which was significant different from that of 34.6 hours of the control group. Using FCM, we found that the cell percentage increased during the G1 phase, but decreased during the S stage. The degenerated ultra-structure of the cell treated with melatonin was also observed by TEM. Conclusion The results suggest that melatonin can inhibit the growth of human bladder carcinoma T24. The inhibitory effects of melatonin might be the prolonging of the staging from G1 to S in the cell cycle.

  7. Prostate-derived ets factor represses tumorigenesis and modulates epithelial-to-mesenchymal transition in bladder carcinoma cells.

    Science.gov (United States)

    Tsui, Ke-Hung; Lin, Yu-Hsiang; Chung, Li-Chuan; Chuang, Sung-Ting; Feng, Tsui-Hsia; Chiang, Kun-Chun; Chang, Phei-Lang; Yeh, Chi-Ju; Juang, Horng-Heng

    2016-05-28

    Prostate-derived Ets (E-twenty six) factor (PDEF), an epithelium-specific member of the Ets family of transcription factors, has been shown to play a role in suppressing the development of many epithelium-derived cancers such as prostate and breast cancer. It is not clear, however, whether PDEF is involved in the development or progression of bladder cancer. In a comparison between normal urothelium and bladder tumor tissue, we identified significant decreases of PDEF in the tumor tissue. Further, the immunohistochemistry assays indicated a significantly higher immunostaining of PDEF in low-grade bladder tumors. Additionally, the highly differentiated transitional-cell bladder carcinoma RT-4 cells expressed significantly more PDEF levels than the bladder carcinoma HT1376 and the T24 cells. Ectopic overexpression of PDEF attenuated proliferation, invasion, and tumorigenesis of bladder carcinoma cells in vitro and in vivo. PDEF enhanced the expression levels of mammary serine protease inhibitor (MASPIN), N-myc downstream regulated gene 1 (NDRG1), KAI1, and B-cell translocation gene 2 (BTG2). PDEF modulated epithelial-mesenchymal-transition (EMT) by upregulating E-cadherin expression and downregulating the expression of N-cadherin, SNAIL, SLUG, and vimentin, leading to lower migration and invasion abilities of bladder carcinoma cells. Filamentous actin (F-actin) polarization and remodeling were observed in PDEF-knockdown RT-4 cells. Our results suggest that PDEF gene expression is associated with the extent of bladder neoplasia and PDEF modulated the expressions of EMT-related genes. The induction of BTG2, NDRG1, MASPIN, and KAI1 gene expressions by PDEF may explain the inhibitory functions of PDEF on the proliferation, invasion, and tumorigenesis in bladder carcinoma cells.

  8. Clinical experience of MRI in two dogs with muscle-invasive transitional cell carcinoma of the urinary bladder.

    Science.gov (United States)

    Lee, Kija; Choi, Sooyoung; Choi, Hojung; Lee, Youngwon

    2016-09-01

    This study described high-field magnetic resonance imaging (MRI) and computed tomography (CT) characteristics of muscle-invasive bladder transitional cell carcinoma (TCC) in two dogs. Ultrasonography revealed a urinary bladder mass with ambiguous result about invasion to the muscular layer. Contrast-enhanced CT showed that the bladder wall in which the mass was attached was more intensely enhanced than the normal bladder walls, supporting invasion to the muscular layer. The mass revealed an intermediate signal intensity with interruption of the hypointense muscular layer on T2-weighted MRI and showed greater enhancement compared with the normal bladder wall on postcontrast T1-weighted images. T2-weighted MRI, postcontrast T1-weighted MRI and contrast-enhanced dual-phasic CT were useful for evaluating muscle-invasive bladder TCC in dogs. PMID:27149892

  9. In the absence of overt urothelial damage, chondroitinase ABC digestion of the GAG layer increases bladder permeability in ovariectomized female rats.

    Science.gov (United States)

    Hurst, Robert E; Van Gordon, Samuel; Tyler, Karl; Kropp, Bradley; Towner, Rheal; Lin, HsuehKung; Marentette, John O; McHowat, Jane; Mohammedi, Ehsan; Greenwood-Van Meerveld, Beverley

    2016-05-01

    Loss of integrity of the protective impermeability barrier in the urothelium has been identified as significant in bladder dysfunction. In this study, we tested the theory that the luminal layer of glycosaminoglycans (GAG) serves as an important component of barrier function. The peptide polycation protamine sulfate (PS), 1 mg/ml, was instilled intravesically for 10 min into rat bladders. Chondroitinase ABC (ChABC), 63 IU/ml, was instilled into an additional six rats for 30 min to digest the GAG layer. Unmanipulated controls and sham-injected controls were also performed. After 24 h, the rats were euthanized, the bladders were removed, and permeability was assessed in the Ussing chamber and by diffusion of FITC-labeled dextran (4 kDa) to measure macromolecular permeability. The status of tight junctions was assessed by immunofluorescence and electron microscopy. In control and sham treated rat bladders, the transepithelial electrical resistance were means of 2.5 ± 1.1 vs. 2.6 ± 1.1 vs 1.2 ± 0.5 and 1.01 ± 0.7 kΩ·cm(2) in the PS-treated and ChABC-treated rat bladders (P = 0.0016 and P = 0.0039, respectively). Similar differences were seen in dextran permeability. Histopathology showed a mild inflammation following PS treatment, but the ChABC-treated bladders were indistinguishable from controls. Tight junctions generally remained intact. ChABC digestion alone induced bladder permeability, confirming the importance of the GAG layer to bladder barrier function and supports that loss of the GAG layer seen in bladder biopsies of interstitial cystitis patients could be a significant factor producing symptoms for at least some interstitial cystitis/painful bladder syndrome patients. PMID:26911855

  10. Evaluation of {sup 11}C-choline PET/CT for primary diagnosis and staging of urothelial carcinoma of the upper urinary tract: a pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Sassa, Naoto; Yamamoto, Tokunori; Gotoh, Momokazu [Nagoya University Graduate School of Medicine, Department of Urology, Nagoya (Japan); Kato, Katsuhiko; Ikeda, Mitsuru; Shimamoto, Kazuhiro; Yamamoto, Seiichi [Nagoya University Graduate School of Medicine, Department of Radiological and Medical Laboratory Sciences, Nagoya (Japan); Abe, Shinji [Nagoya University Hospital, Department of Radiological Technology, Nagoya (Japan); Iwano, Shingo; Ito, Shinji; Naganawa, Shinji [Nagoya University Graduate School of Medicine, Department of Radiology, Nagoya (Japan)

    2014-12-15

    We conducted a pilot study to prospectively evaluate the efficacy of PET/CT with {sup 11}C-choline (choline PET/CT) for primary diagnosis and staging of urothelial carcinoma of the upper urinary tract (UUT-UC). Enrolled in this study were 16 patients (9 men, 7 women; age range 51 - 83 years, mean ± SD 69 ± 10.8 years) with suspected UUT-UC. The patients were examined by choline PET/CT, and 13 underwent laparoscopic nephroureterectomy and partial cystectomy. Lymphadenectomy and chemotherapy were also performed as necessary in some of the patients. Of the 16 patients, 12 were confirmed to have UUT-UC (7 renal pelvis carcinoma and 5 ureteral carcinoma), 1 had malignant lymphoma (ureter), 1 had IgG4-related disease (ureter), and 2 had other benign diseases (ureter). Of the 16 study patients, 13 showed definite choline uptake in urothelial lesions, and of these, 11 had UUT-UC, 1 had malignant lymphoma, and 1 had IgG4-related disease. Three patients without choline uptake comprised one with UUT-UC and two with benign diseases. Of the 12 patients with UUT-UC, 3 had distant metastases, 2 had metastases only in the regional lymph nodes, and 7 had no metastases. Distant metastases and metastases in the regional lymph nodes showed definite choline uptake. The outcome in patients with UUT-UC, which was evaluated 592 - 1,530 days after surgery, corresponded to the patient classification based on the presence or absence of metastases and locoregional or distant metastases. Choline uptake determined as SUVmax 10 min after administration was significantly higher than at 20 min in metastatic tumours of UUT-UC (p < 0.05), whereas there was no statistically significant difference between the SUVmax values at 10 and those at 20 min in primary tumours of UUT-UC. This study suggests that choline PET/CT is a promising tool for the primary diagnosis and staging of UUT-UC. (orig.)

  11. Differential expression of microRNA clusters in bladder transitional cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Feng Xu; Zhifeng Wei; Zhengyu Zhang; Jingping Ge; Peng Xie; Hongqing Ma; Jianping Gao; Wen Cheng

    2013-01-01

    Objective: The aim of the study was to investigate the differential expression of microRNAs (miRNAs) in bladder transitional cell carcinoma (BTC). Methods: Fresh tissues were obtained from patients with BTC (9 cases; 3 cases with grade I, 3 cases with grade II, 3 cases with grade III) and those with normal bladder mucosa (3 cases) and stored in liquid nitrogen. Total RNA was extracted using TRizol reagent and RNA was quantified and quality control was performed. miRNA probes were labeled with Hy3TM fluorescence, then hybridized with a miRCURYTM array labeling kit. miRNA arrays were scanned and analyzed and the scanned result was validated using reverse transcription-polymerase chain reaction (RT-PCR). Results: In four groups of differentially expressed genes obtained from grade I, grade II, grade III, and grade I + grade II + grade III BTC tissues compared with normal bladder mucosa, hsa-miR-29b-1* was upregulated, and hsa-miR-923 and hsa-miR-300 were downregulated. The hsa-miR-29b-1*, hsa-miR-300, and hsa-miR-923 findings were confirmed by real-time RT-PCR. Conclusion: Genes that were differentially expressed between BTC and normal bladder mucosa may be involved in the pathogenesis and development of BTC, and may be useful for further studies of BTC-related genes.

  12. Targeting of Alpha-V Integrins Reduces Malignancy of Bladder Carcinoma

    Science.gov (United States)

    van der Horst, Geertje; Bos, Lieke; van der Mark, Maaike; Cheung, Henry; Heckmann, Bertrand; Clément-Lacroix, Philippe; Lorenzon, Giocondo; Pelger, Rob C. M.; Bevers, Rob F. M.; van der Pluijm, Gabri

    2014-01-01

    Low survival rates of metastatic cancers emphasize the need for a drug that can prevent and/or treat metastatic cancer. αv integrins are involved in essential processes for tumor growth and metastasis and targeting of αv integrins has been shown to decrease angiogenesis, tumor growth and metastasis. In this study, the role of αv integrin and its potential as a drug target in bladder cancer was investigated. Treatment with an αv integrin antagonist as well as knockdown of αv integrin in the bladder carcinoma cell lines, resulted in reduced malignancy invitro, as illustrated by decreased proliferative, migratory and clonogenic capacity. The CDH1/CDH2 ratio increased, indicating a shift towards a more epithelial phenotype. This shift appeared to be associated with downregulation of EMT-inducing transcription factors including SNAI2. The expression levels of the self-renewal genes NANOG and BMI1 decreased as well as the number of cells with high Aldehyde Dehydrogenase activity. In addition, self-renewal ability decreased as measured with the urosphere assay. In line with these observations, knockdown or treatment of αv integrins resulted in decreased metastatic growth in preclinical invivo models as assessed by bioluminescence imaging. In conclusion, we show that αv integrins are involved in migration, EMT and maintenance of Aldehyde Dehydrogenase activity in bladder cancer cells. Targeting of αv integrins might be a promising approach for treatment and/or prevention of metastatic bladder cancer. PMID:25247809

  13. Urinary bladder radiotherapy-related chondroblastic osteosarcoma: Rare case report and review of literature

    Directory of Open Access Journals (Sweden)

    Noorah Almadani

    2014-01-01

    Full Text Available Radiation-related osteosarcomas are well described malignant mesenchymal neoplasms, yet their pathogenesis is not fully understood. They are generally classified into either skeletal osteosarcomas, or their and rare soft tissue counterpart. The occurrence of osteosarcoma in the urinary bladder (UB following radiotherapy is exceedingly rare. To the best of our knowledge, only two cases of radiation-related urinary bladder osteosarcoma have been published; we herein describe another case of an 85-year-old man who developed post radiotherapy chondroblastic osteosarcoma of the urinary bladder four years following initial surgical resection and radiotherapy for bladder urothelial carcinoma. We believe that this is the first case of radiation-related chondroblastic osteosarcoma arising in the urinary bladder. In addition, we review the literature and explore the possible histogenesis of this rare neoplasm.

  14. Bladder preservation by internal iliac arterial infusion chemotherapy and irradiation in T3 bladder carcinoma patients over the age of 70 years

    Energy Technology Data Exchange (ETDEWEB)

    Hoshi, Senji; Shintaku, Ichiro; Suzuki, Ken-ichi; Takahashi, Toshiko; Kaihou, Yasuhiro; Ishidoya, Shigeto; Namima, Takashige; Ohyama, Chikara; Orikasa, Seiichi [Tohoku Univ., Sendai (Japan). School of Medicine

    2000-12-01

    Treatment by internal iliac arterial infusion chemotherapy (IA) combined with pelvic irradiation has proved to be effective for locally invasive bladder. Eight male patients, median age of 78 years (range 73-81) were enrolled. Pretreatment CT and whole layer core biopsy revealed T3a or T3b. Pelvic CT or fine needle aspiration biopsy following bipedal lymphography revealed N0 in 4 cases, N2 in 2 and N3 in 2, respectively. Three to 7 cycles of cisplatin (CDDP) 30-50 mg/m{sup 2}, methotrexate 20 mg/m{sup 2} and tetrahydropymnyl-adriamycin 20 mg/m{sup 2} every 3 week was administered combined with 40-50 Gy of whole pelvis irradiation. In 4 renal function impaired patients, 100 mg/m{sup 2} of carboplatin was administered instead of CDDP. All patients obtained complete response and the bladders were preserved. Observation periods were from 9 to 75 months (median 37 months). One N2 patient died with metastatic disease and two died without carcinoma. Two patients developed invasive bladder cancer on the side opposite to the primary tumors. Both were successfully treated by IA and irradiation. Bladders of all except one patient functioned for a long period. Side effects of IA and irradiation were not significant. IA combined with pelvic irradiation is effective and safe for elderly patients with bladder carcinoma. (author)

  15. [Neuroendocrine carcinoma of the urinary bladder. A case report].

    Science.gov (United States)

    Aragón-Tovar, Anel Rogelio; Pineda-Rodríguez, Marco Elí; Puente-Gallegos, Francisco Edgardo; Zavala-Pompa, Angel

    2014-01-01

    Antecedentes: el carcinoma neuroendocrino de células pequeñas primario de vejiga es una lesión maligna muy poco frecuente. Caso clínico: paciente masculino de 68 años de edad, que tuvo hematuria macroscópica de 24 horas de evolución. Estudios de imagen mostraron tumoración vesical de 218 cc, que en 20 días alcanzó un volumen de 426 cc. A la tinción con hematoxilina-eosina, histológicamente se apreció: placa sólida infiltrante de bordes irregulares, compuesta por células neoplásicas con claro predominio de núcleo y escaso citoplasma (células pequeñas). A la tinción inmunohistoquímica con cromogranina parecía difusamente positivo en células neoplásicas, en un patrón granular citoplasmático. A la tinción con citoqueratina de alto peso molecular se observó patrón negativo en células neoplásicas con control interno positivo en el urotelio acompañante en espécimen. De igual manera, la tumoración fue positiva para sinaptofisina y CD-56 y negativa para CK-7 y CK-20. El paciente recibió tratamiento a base de radioterapia y quimioterapia. Conclusión: el carcinoma neuroendocrino de células pequeñas primario de vejiga representa de 0.35 a 0.70% de los tumores vesicales primarios. Su diagnóstico se basa en el reconocimiento histológico e inmunohistoquímico. El tratamiento se fundamenta en quimioterapia con cisplatino más cistectomía radical, excepto cuando existe enfermedad metastásica.

  16. Rare Association of Anti-Hu Antibody Positive Paraneoplastic Neurological Syndrome and Transitional Cell Bladder Carcinoma

    Directory of Open Access Journals (Sweden)

    S. Lukacs

    2012-01-01

    Full Text Available Introduction. Paraneoplastic encephalomyelitis (PEM and subacute sensory neuronopathy (SSN are remote effects of cancer, usually associated with small-cell lung carcinoma and positive anti-Hu antibody. We describe the rare association of bladder transitional cell carcinoma (TCC with anti-Hu antibody positivity resulting in this paraneoplastic neurological syndrome. Patient. A 76-year-old female presented with bilateral muscle weakness and paraesthesia of the upper and lower limbs in a length-dependent “glove and stocking” distribution. Central nervous system symptoms included cognitive problems, personality change, and truncal ataxia. Case notes and the literature were reviewed. Result. Autoantibody screening was positive for anti-Hu antibody (recently renamed antineuronal nuclear antibody 1, ANNA-1. The diagnosis of PEM and SSN was supported by MRI and lumbar puncture results. A superficial bladder TCC was demonstrated on CT and subsequently confirmed on histology. No other primary neoplasm was found on full-body imaging. The neurological symptoms were considered to be an antibody-mediated paraneoplastic neurological syndrome and improved after resection of the tumour. Discussion. The association of anti-Hu positive paraneoplastic neurological syndrome and TCC has not been described in the literature previously. We emphasize the need for detailed clinical examination and the importance of a multidisciplinary thought process and encourage further awareness of this rare association.

  17. Staphylococcus saprophyticus ATCC 15305 is internalized into human urinary bladder carcinoma cell line 5637.

    Science.gov (United States)

    Szabados, Florian; Kleine, Britta; Anders, Agnes; Kaase, Martin; Sakinç, Türkân; Schmitz, Inge; Gatermann, Sören

    2008-08-01

    Invasion of bacteria into nonphagocytic host cells is an important pathogenicity factor for escaping the host defence system. Gram-positive organisms, for example Staphylococcus aureus and Listeria monocytogenes, are invasive in nonphagocytic cells, and this mechanism is discussed as an important part of the infection process. Uropathogenic Escherichia coli and Staphylococcus saprophyticus can cause acute and recurrent urinary tract infections as well as bloodstream infections. Staphylococcus saprophyticus shows strong adhesion to human urinary bladder carcinoma and Hep2 cells and expresses the 'Microbial Surface Components Recognizing Adhesive Matrix molecule' (MSCRAMM)-protein SdrI with collagen-binding activity. MSCRAMMs are responsible for adhesion and collagen binding in S. aureus and are discussed as an important pathogenicity factor for invasion. To investigate internalization in S. aureus, several fluorescence activated cell sorting (FACS) assays have been described recently. We used a previously described FACS assay, with slight modifications, in addition to an antibiotic protection assay and transmission electron microscopy to show that S. saprophyticus ATCC 15305 and the wild-type strain 7108 were internalized into the human urinary bladder carcinoma cell line 5637. The discovery of the internalization of S. saprophyticus may be an important step for understanding the pathogenicity of recurrent infections caused by this organism.

  18. [A Case Report of Suspected Tuberculous Granuloma in the Kidney after BCG Perfusion Therapy for Urothelial Carcinoma of the Renal Pelvis].

    Science.gov (United States)

    Kobayashi, Shin; Hori, Junichi; Okazaki, Satoshi; Hashizume, Kazumi; Watanabe, Masaki; Wada, Naoki; Kita, Masafumi; Azumi, Makoto; Iwata, Tatsuya; Matsumoto, Seiji; Kakizaki, Hidehiro

    2016-01-01

    A 66-year-old male patient was referred to our hospital for bilateral renal pelvic tumors. Ureteroscopic biopsy revealed urothelial carcinoma (UC) of low grade (G1) of the renal pelvis. Renal sparing treatment with systemic chemotherapy and percutaneous tumor resection was performed. However, during subsequent follow up, a recurrent tumor was found on the left ureter. After ureteroscopic laser ablation of the tumor, Bacillus Calmette-Guerin (BCG) perfusion therapy (once a week, total 6 weeks) was performed via a single J ureteral catheter with no adverse events. Later, another recurrent recurrence was found on the right ureter, and was managed by ureteroscopic laser ablation followed by BCG perfusion therapy via a single J ureteral catheter. However, the patient developed high fever with chill from the day after initial BCG perfusion therapy on the right side. Although we started antibiotics, high fever continued. Then antituberculous drugs were administered and his condition was improved. Computed tomographic scan revealed a right renal mass 57 mm in diameter, which was consistent with tuberculous granuloma. The tuberculous granuloma persisted despite the continuation of anti-tuberculous drugs. In exceptional cases of upper tract UC such as single kidney and bilateral tumor, BCG perfusion therapy has been used as adjunctive treatment to cure or prevent UC. However, dosages and administration methods of BCG perfusion therapy for upper tract UC still remain to be standardized. Serious adverse events after BCG perfusion therapy require prompt and proper management including the use of anti-tuberculous drugs. PMID:26932332

  19. A phase II trial of R115777, an oral farnesyl transferase inhibitor, in      patients with advanced urothelial tract transitional cell carcinoma

    DEFF Research Database (Denmark)

    Rosenberg, Jonathan E.; Maase, Hans von der; Seigne, John D.;

    2005-01-01

    BACKGROUND: R115777 is a potent farnesyl transferase inhibitor and has       significant antitumor effects in vitro and in vivo. METHODS: The objective       of the current study was to determine the objective response proportion in       patients with metastatic transitional cell carcinoma (TCC......) of the       urothelial tract who received treatment with R115777 at a dose of 300 mg       orally given twice daily for 21 days followed by 7 days of rest for every       4-week cycle. Thirty-four patients with TCC were enrolled in this Phase II       study. Patients were allowed to have received a maximum of one prior......       observed. CONCLUSIONS: The objective response rate of R115777 was not       sufficient to warrant future investigation in TCC as a single agent.       Preliminary evidence of the activity of R115777 in 2 chemotherapy-naive       patients may warrant further investigation in combination with first...

  20. Immunohistochemical Expression of Cyclooxygenase-2 in Urinary Bladder Transitional Cell Carcinomas

    Directory of Open Access Journals (Sweden)

    F Niki

    2012-07-01

    Full Text Available Background: Transitional Cell Carcinoma (TCC is the most common type of urinary bladder cancer. Cyclooxygenase-2 (COX-2, a key enzyme in prostaglandins biosynthesis, has been introduced as a new candidate for targeted therapy in this cancer. In this study, we investigated the expression of COX-2 in urinary bladder TCCs and its relationship with clinicopathological parameters such as tumor grade and stage. Methods: This cross-sectional study was performed in the Pathology department of Sina Hospital in Tehran, Iran during 2006-2011. Pathology reports of patients with definite diagnosis of urinary bladder TCCs who had undergone Transurethral Resection (TUR were reviewed and 40 cases were selected. Subsequently, COX-2 expression was assessed immunohistochemically by the examination of paraffin embedded tissue blocks. Staining in more than 5% of tumor cells was considered as positive expression. Results: COX-2 was expressed in 52.5% of the patients. High-grade tumors revealed a higher (87.5% COX-2 expression versus other grades of the lesions and there was a statistically significant difference in COX-2 expression between them (P<0.001. Patients age was also related to the expression of this marker (P=0.03. In contrast, this marker did not correlate with other characteristics including gender, lymphatic invasion or tumor stage. In addition, perineurial or vascular invasions were not detected in any of the patients. Conclusion: COX-2 expression was seen in more than half of our patients and it had a marked relation to tumor differentiation. Accordingly, this molecule may be a useful tumor marker in the assessment of urinary bladder cancers.

  1. Targeting of alpha-v integrins reduces malignancy of bladder carcinoma.

    Directory of Open Access Journals (Sweden)

    Geertje van der Horst

    Full Text Available Low survival rates of metastatic cancers emphasize the need for a drug that can prevent and/or treat metastatic cancer. αv integrins are involved in essential processes for tumor growth and metastasis and targeting of αv integrins has been shown to decrease angiogenesis, tumor growth and metastasis. In this study, the role of αv integrin and its potential as a drug target in bladder cancer was investigated. Treatment with an αv integrin antagonist as well as knockdown of αv integrin in the bladder carcinoma cell lines, resulted in reduced malignancy in vitro, as illustrated by decreased proliferative, migratory and clonogenic capacity. The CDH1/CDH2 ratio increased, indicating a shift towards a more epithelial phenotype. This shift appeared to be associated with downregulation of EMT-inducing transcription factors including SNAI2. The expression levels of the self-renewal genes NANOG and BMI1 decreased as well as the number of cells with high Aldehyde Dehydrogenase activity. In addition, self-renewal ability decreased as measured with the urosphere assay. In line with these observations, knockdown or treatment of αv integrins resulted in decreased metastatic growth in preclinical in vivo models as assessed by bioluminescence imaging. In conclusion, we show that αv integrins are involved in migration, EMT and maintenance of Aldehyde Dehydrogenase activity in bladder cancer cells. Targeting of αv integrins might be a promising approach for treatment and/or prevention of metastatic bladder cancer.

  2. Chemotherapeutic potential of quercetin on human bladder cancer cells.

    Science.gov (United States)

    Oršolić, Nada; Karač, Ivo; Sirovina, Damir; Kukolj, Marina; Kunštić, Martina; Gajski, Goran; Garaj-Vrhovac, Vera; Štajcar, Damir

    2016-07-28

    In an effort to improve local bladder cancer control, we investigated the cytotoxic and genotoxic effects of quercetin on human bladder cancer T24 cells. The cytotoxic effect of quercetin against T24 cells was examined by MTT test, clonogenic assay as well as DNA damaging effect by comet assay. In addition, the cytotoxic effect of quercetin on the primary culture of papillary urothelial carcinoma (PUC), histopathological stage T1 of low- or high-grade tumours, was investigated. Our analysis demonstrated a high correlation between reduced number of colony and cell viability and an increase in DNA damage of T24 cells incubated with quercetin at doses of 1 and 50 µM during short term incubation (2 h). At all exposure times (24, 48 and 72 h), the efficacy of quercetin, administered at a 10× higher dose compared to T24 cells, was statistically significant (P < 0.05) for the primary culture of PUC. In conclusion, our study suggests that quercetin could inhibit cell proliferation and colony formation of human bladder cancer cells by inducing DNA damage and that quercetin may be an effective chemopreventive and chemotherapeutic agent for papillary urothelial bladder cancer after transurethral resection. PMID:27149655

  3. Contrast-enhanced computed tomography of the primary tumor in muscle invasive carcinoma of the urinary bladder

    International Nuclear Information System (INIS)

    Patients with muscle invasive carcinoma of the urinary bladder were examined with contrast-enhanced CT of the primary tumor. A specially designed technique was developed to increase the diagnostic potential of CT. The most important points about the technique were controlled filling of the bladder, the use of thin slices, series of scans before and after intravenous injection of contrast medium, and long scanning times in the precontrast series. The absorbed dose to the patient resulting from the new technique was found to be within the range of the dose from urography or barium enema. This dose was considered to be acceptable given the diagnostic gain of the procedure. Features of irradiated bladder tumors were analysed to find which parameter correlated with persistent malignancy. High contrast enhancement of a tumor relative to the bladder wall was found to be the best indicator of a malignant tumour after irradiation. 127 refs

  4. Ct2 Bladder Cancer.

    Science.gov (United States)

    Soloway, Mark S

    2016-09-01

    The patient is an 80-year-old man who presented with gross hematuria. His past medical history indicates he was a cigarette smoker with 50 pack/years. He was successfully treated for carcinoma of the lung 7 years ago. He received chemotherapy, radiation, and surgery. He has mild COPD but has a good performance status. His laboratory studies do not indicate any abnormalities in terms of renal function. He does not have any significant cardiac disease. He has a medium build. He had prostate cancer and underwent a successful radical prostatectomy 10 years ago. His PSA is undetectable. He has some urinary incontinence and wears two pads/day. He underwent the appropriate investigations for gross hematuria. A CT scan of the abdomen and pelvis was normal with the exception of a 4-cm posterior mass in the bladder. There was no hydronephrosis and no enlarged lymph nodes. He underwent a transurethral resection of a solitary bladder tumor performed by another urologist. The tumor was described as large and sessile. It was located on the posterior wall and was approximately 4 cm. The bimanual examination did not reveal a mass. The pathology report stated that the tumor was a high-grade urothelial carcinoma with invasion into the muscularis propria. There was no lymphovascular invasion. I performed a reTURBT, and at that procedure, I did not identify any obvious tumor but the prior resection site was evident. I resected the prior tumor site quite extensively both in depth and width. The pathology revealed only focal carcinoma in situ. There was ample muscle in the specimen and there was some fat as well. As stated, they were free of any cancer. The patient is receptive to any treatment approach. PMID:27457483

  5. Bilateral ureteral complete obstruction with huge spontaneous urinoma formation in a patient with advanced bladder cancer.

    Science.gov (United States)

    Jou, Yeong-Chin; Shen, Cheng-Huang; Cheng, Ming-Chin; Lin, Chang-Te; Chen, Pi-Che

    2012-02-01

    Spontaneous rupture of the collecting system with extravasation of urine and urinoma formation is usually associated with urinary tract obstruction by a ureteral calculus. Tumor growth is an extremely rare cause of urinary extravasation. Here we report a case of bilateral obstructive uropathy with a huge spontaneous left retroperitoneal urinoma caused by advanced infiltrative transitional cell carcinoma of the urinary bladder. The point of leakage was located in the left renal pelvis. The urinary leakage ceased after percutaneous nephrostomy drainage, and the patient subsequently underwent radical cystoprostatectomy. Histopathology revealed a high-grade urothelial carcinoma of the urinary bladder with pelvic lymph node metastasis. The patient refused any adjuvant treatment and expired 6 months after the operation from disseminated metastasis from bladder cancer.

  6. Prostatic Adenocarcinoma Coexist with Transitional Cell Carcinoma of the Bladder and Prostate-A Case Report and Review of the Literature

    Institute of Scientific and Technical Information of China (English)

    TongZhang; YongXu; ShuminZhang

    2004-01-01

    Prostatic adenocarcinoma(PAC) with transitional cell carcinoma(TCC) of the bladder and prostate is a rare clinicopathological entity, presentation is usually late. We report a case with obstructive voiding symptoms and lumbago. Prostatic and cystic biopsy revealed PAC and TCC of bladder. Bone scan showed multiple bone metastases. He underwent transurethral resection of the prostate and bladder tumor and was found to have PAC with TCC of the bladder and prostate. We discuss the cases of PAC with TCC of the bladder and prostate.

  7. The role of radiotherapy for carcinomas of the gall bladder and extrahepatic biliary duct : retrospective analysis

    International Nuclear Information System (INIS)

    Carcinomas arising in the gall bladder(GB) or extrahepatic biliary ducts are uncommon and generally have a poor prognosis. The overall 5-year survival rates are less than 10%. Early experiences with the external radiation therapy demonstrated a good palliation with occasional long-term survival. The present report describes our experience over the past decade with irradiation of primary carcinomas of the gallbladder and extrahepatic biliary duct. From Feb. 1984 to Nov. 1995, thirty-three patients with carcinoma of the GB and extrahepatic biliary duct were treated with external beam radiotherapy with curative intent at our institution. All patients were treated with 4-MV linear accelerator and radiation dose ranged from 31.44Gy to 54.87Gy(median 44.25Gy), and three patients received additional intraluminal brachytherapy(range, 25Gy to 30Gy). Twenty-seven patients received postoperative radiation. Among 27 patients, Sixteen patients underwent radical operation with curative aim and the rest of the patients either had bypass surgery or biopsy alone. In seventeen patients, adjuvant chemotherapy was used and eleven patients were treated with 5-FU, mitomycin and leucovorin. Median follow up period was 8.5 months(range 2-97 months). The overall 2-year and 5-year survival rates in all patients were 29.9% and 13.3% respectively. In patients with GB and extrahepatic biliary duct carcinomas, the 2-year survival rates were 34.5% and 27.8% respectively. Patients who underwent radical operation showed better 2-year survival rates than those who underwent palliative operation(43.8% vs. 20.7%), albeit statistically insignificant(p>0.05). The 2-year survival rates in Stage I and II were higher than in Stage III and IV with statistical significance(p0.05). The survival of patients with relatively lower stage and/or initial good performance was significantly superior to that of others. We found an statistically insignificant trend toward better survival in patients with radical

  8. Luminal DMSO: Effects on Detrusor and Urothelial/Lamina Propria Function

    OpenAIRE

    Smith, Katrina J.; Russ Chess-Williams; Catherine McDermott

    2014-01-01

    DMSO is used as a treatment for interstitial cystitis and this study examined the effects of luminal DMSO treatment on bladder function and histology. Porcine bladder was incubated without (controls) or with DMSO (50%) applied to the luminal surface and the release of ATP, acetylcholine, and LDH assessed during incubation and in tissues strips after DMSO incubation. Luminally applied DMSO caused ATP, Ach, and LDH release from the urothelial surface during treatment, with loss of urothelial la...

  9. Quantitative histopathology in the prognostic evaluation of patients with transitional cell carcinoma of the urinary bladder

    DEFF Research Database (Denmark)

    Sasaki, M; Sørensen, Flemming Brandt; Fukuzawa, S;

    1993-01-01

    BACKGROUND: Morphologic grading of malignancy is considered to be of prognostic value in patients with transitional cell carcinomas of the urinary bladder (TCC). This qualitative approach is, however, associated with low reproducibility. Grading of malignancy can be carried out on a reproducible......, quantitative scale. METHODS: A retrospective, prognostic study of 110 patients treated for TCC in clinical Stages Ta-T4 (median follow-up time, 6 years) was performed, evaluating various grading techniques. Unbiased estimates of the volume-weighted mean nuclear volume (nuclear vV), nuclear volume fraction...... of nuclear vV are prognostically superior to morphologic grading of malignancy in noninvasive TCC, whereas both morphologically and quantitatively based malignancy grading are without prognostic value in invasive TCC....

  10. RECURRENCE RISK FACTORS IN PATIENTS WITH TRANSITIONAL CELL CARCINOMA OF BLADDER

    Institute of Scientific and Technical Information of China (English)

    YUE Xiang-hui; YANG Xiao-hong; ZHENG Fu-qing

    2005-01-01

    Objective: To study recurrence factors and set up a model to evaluate the prognosis of patients with bladder cancer.Methods: An analysis on recurrence-related factors was made by Cox's proportional hazards model analysis and logistic multiple linear regression model analysis in 212 patients with transitional cell carcinoma treated surgically from 1995~2001.These factors included clinical and pathologic figures. Results: The most important factor is metastasis to the regional lymph nodes, the Hazards ratio is 6.6 (P=0.0004), followed by multiple tumors (Hr=2.255, P<0.0001), tumor in trigone and bladder neck (Hr=2.053, P<0.0001), stage (Hr=2.057, P<0.0001), grade (Hr=1.569, P=0.0081), intravesical chemotherapeutic instillations (Hr-0.559, P=0.0011) and hematuria (Hr=0.762, P=0.0076). A predicting equation was established, and the predicting values were calculated according to the individual features of patients. The predicting and actual values were compared, and the sensitivity, specificity and overall concordance were 83.5%, 67.6% and 80.1% respectively. Conclusion:The evaluation of prognosis could be made quite accurately based on these factors.

  11. The effect of cigarette smoke and arsenic exposure on urothelial carcinoma risk is modified by glutathione S-transferase M1 gene null genotype

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Chi-Jung [Department of Health Risk Management, College of Public Health, China Medical University, Taichung, Taiwan (China); Department of Medical Research, China Medical University Hospital, Taichung, Taiwan (China); Huang, Chao-Yuan; Pu, Yeong-Shiau [Department of Urology, National Taiwan University Hospital, Taipei, Taiwan (China); Shiue, Horng-Sheng [Department of Chinese Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan (China); Su, Chien-Tien [Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan (China); Hsueh, Yu-Mei, E-mail: ymhsueh@tmu.edu.tw [Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China)

    2013-01-15

    Inter-individual variation in the metabolism of xenobiotics, caused by factors such as cigarette smoking or inorganic arsenic exposure, is hypothesized to be a susceptibility factor for urothelial carcinoma (UC). Therefore, our study aimed to evaluate the role of gene–environment interaction in the carcinogenesis of UC. A hospital-based case–control study was conducted. Urinary arsenic profiles were measured using high-performance liquid chromatography–hydride generator-atomic absorption spectrometry. Genotyping was performed using a polymerase chain reaction-restriction fragment length polymorphism technique. Information about cigarette smoking exposure was acquired from a lifestyle questionnaire. Multivariate logistic regression was applied to estimate the UC risk associated with certain risk factors. We found that UC patients had higher urinary levels of total arsenic, higher percentages of inorganic arsenic (InAs%) and monomethylarsonic acid (MMA%) and lower percentages of dimethylarsinic acid (DMA%) compared to controls. Subjects carrying the GSTM1 null genotype had significantly increased UC risk. However, no association was observed between gene polymorphisms of CYP1A1, EPHX1, SULT1A1 and GSTT1 and UC risk after adjustment for age and sex. Significant gene–environment interactions among urinary arsenic profile, cigarette smoking, and GSTM1 wild/null polymorphism and UC risk were observed after adjustment for potential risk factors. Overall, gene–environment interactions simultaneously played an important role in UC carcinogenesis. In the future, large-scale studies should be conducted using tag-SNPs of xenobiotic-metabolism-related enzymes for gene determination. -- Highlights: ► Subjects with GSTM1 null genotype had significantly increased UC risk. ► UC patients had poor arsenic metabolic ability compared to controls. ► GSTM1 null genotype may modify arsenic related UC risk.

  12. The effect of cigarette smoke and arsenic exposure on urothelial carcinoma risk is modified by glutathione S-transferase M1 gene null genotype

    International Nuclear Information System (INIS)

    Inter-individual variation in the metabolism of xenobiotics, caused by factors such as cigarette smoking or inorganic arsenic exposure, is hypothesized to be a susceptibility factor for urothelial carcinoma (UC). Therefore, our study aimed to evaluate the role of gene–environment interaction in the carcinogenesis of UC. A hospital-based case–control study was conducted. Urinary arsenic profiles were measured using high-performance liquid chromatography–hydride generator-atomic absorption spectrometry. Genotyping was performed using a polymerase chain reaction-restriction fragment length polymorphism technique. Information about cigarette smoking exposure was acquired from a lifestyle questionnaire. Multivariate logistic regression was applied to estimate the UC risk associated with certain risk factors. We found that UC patients had higher urinary levels of total arsenic, higher percentages of inorganic arsenic (InAs%) and monomethylarsonic acid (MMA%) and lower percentages of dimethylarsinic acid (DMA%) compared to controls. Subjects carrying the GSTM1 null genotype had significantly increased UC risk. However, no association was observed between gene polymorphisms of CYP1A1, EPHX1, SULT1A1 and GSTT1 and UC risk after adjustment for age and sex. Significant gene–environment interactions among urinary arsenic profile, cigarette smoking, and GSTM1 wild/null polymorphism and UC risk were observed after adjustment for potential risk factors. Overall, gene–environment interactions simultaneously played an important role in UC carcinogenesis. In the future, large-scale studies should be conducted using tag-SNPs of xenobiotic-metabolism-related enzymes for gene determination. -- Highlights: ► Subjects with GSTM1 null genotype had significantly increased UC risk. ► UC patients had poor arsenic metabolic ability compared to controls. ► GSTM1 null genotype may modify arsenic related UC risk.

  13. Concomitant Urothelial Cancer and Renal Tuberculosis

    Directory of Open Access Journals (Sweden)

    Sheray N. Chin

    2014-01-01

    Full Text Available We report a case of coexisting urothelial cancer and renal tuberculosis in the same kidney. The patient is a 72-year-old female with a remote history of treated pulmonary tuberculosis who presented with haematuria, initial investigation of which elucidated no definitive cause. Almost 1 year later, a diagnosis of metastatic urinary tract cancer was made. The patient received chemotherapy for advanced collecting duct type renal cell carcinoma, based on histological features of renal biopsy. Subsequent confirmatory immunostains however led to a revised diagnosis of urothelial cancer, necessitating a change in chemotherapy regimen. A diagnosis of ipsilateral renal tuberculosis was made based on TB-PCR testing of renal biopsy tissue and anti-TB therapy was coadministered with chemotherapy. The patient died 9 months after diagnosis of metastatic urothelial cancer.

  14. Carcinoma In Situ Is Significantly Underdetected by Prenephroureterectomy Ureteroscopy in the Management of Upper Tract Urothelial Cancers

    Directory of Open Access Journals (Sweden)

    Angela Gillan

    2015-01-01

    Full Text Available Objective. Diagnostic reliability of prenephroureterectomy ureteroscopy (PNU for the detection of upper tract carcinoma in situ (CIS remains unproven in particular and underreported in general. Methods. Patients who underwent radical nephroureterectomy (RNU in a large multicentre retrospective study for upper tract transitional cell carcinoma (UT-TCC between January 2002 and December 2013 were identified from our hospitals databases. PNU appearances, stage, and grade of ureteroscopic biopsy were compared with final histology results of RNU to assess the diagnostic reliability of PNU for carcinoma in situ (CIS. Results. Three hundred patients underwent RNU for UT-TCC. 106 (106/300; 35.3% of the cohort had PNU using white light with biopsies taken in most (92/106; 86.7%. Postnephroureterectomy histology of the cohort showed CIS in 65 (65/300; 21.6% patients. Thirty nine of patients with CIS (39/65; 60% had prenephroureterectomy ureteroscopy biopsies. Out of ten patients with CIS on ureteroscopic biopsies, six did not show CIS on final histopathology (6/10; 60%. Moreover, grading and staging on PNU biopsies of obvious tumours showed a significant nonconcordance with final histopathology of RNU specimen (P=0.02. Overall survival was also shorter in patients with CIS compared with those without; this showed strong statistical significance (P=0.004. Conclusions. There is a high incidence of CIS in upper tract with significant underdetection and discordance rate between the histopathology of biopsy samples obtained by white light PNU and resected specimen of radical nephroureterectomy. The presence of concomitant CIS and high stage disease in the upper tract TCC carried a poor prognosis following radical nephroureterectomy.

  15. Expression of MAGE-A3, NY-ESO-1, LAGE-1 and PRAME in urothelial carcinoma

    DEFF Research Database (Denmark)

    Andersen, Lars Dyrskjøt; Zieger, K; Kissow Lildal, T;

    2012-01-01

    Background: The potential for cancer-testis (CT) antigens as targets for immunotherapy in cancer patients has been heavily investigated, and currently cancer vaccine trials based on the CT antigens, MAGE-A3 and NY-ESO-1, are being carried out. Methods: We used specific q-RT-PCR assays to analyse...... the expression of the CT genes MAGE-A3, NY-ESO-1 (CTAG1B), LAGE-1 (CTAG2) and PRAME in a panel of bladder tumours from 350 patients with long-term follow-up and detailed treatment information. Results: Overall, 43% of the tumours expressed MAGE-A3, 35% expressed NY-ESO-1, 27% expressed LAGE-1 and 20% expressed...... PRAME. In all, 56% of the tumours expressed at least one of the CT genes analysed. Univariate Cox regression analysis of CT gene expression in non-muscle-invasive tumours showed that expression of MAGE-A3 (P=0.026), LAGE-1 (P=0.001) and NY-ESO-1 (P=0.040) was significantly associated with a shorter...

  16. Gene expression in the urinary bladder: a common carcinoma in situ gene expression signature exists disregarding histopathological classification

    DEFF Research Database (Denmark)

    Andersen, Lars Dyrskjøt; Kruhøffer, Mogens; Andersen, Thomas Thykjær;

    2004-01-01

    The presence of carcinoma in situ (CIS) lesions in the urinary bladder is associated with a high risk of disease progression to a muscle invasive stage. In this study, we used microarray expression profiling to examine the gene expression patterns in superficial transitional cell carcinoma (sTCC......) with surrounding CIS (13 patients), without surrounding CIS lesions (15 patients), and in muscle invasive carcinomas (mTCC; 13 patients). Hierarchical cluster analysis separated the sTCC samples according to the presence or absence of CIS in the surrounding urothelium. We identified a few gene clusters...... that contained genes with similar expression levels in transitional cell carcinoma (TCC) with surrounding CIS and invasive TCC. However, no close relationship between TCC with adjacent CIS and invasive TCC was observed using hierarchical cluster analysis. Expression profiling of a series of biopsies from normal...

  17. A Large Bladder Tumor Covered With a Thick “Shell” of Necrotic Material

    Science.gov (United States)

    Wang, Lei; Zhou, Zhe; Gong, Miao-zi; Pan, Dong-liang; Zhang, Xiang-hua; Li, Ning-chen; Na, Yan-qun

    2016-01-01

    Abstract Bladder tumor arising in a spina bifida patient is rare and may be clinically latent. We report the case of a 61-year-old female patient with spina bifida, neurogenic bladder, and a history of recurrent urinary tract infections. A B-ultrasound and non-contrast computed tomography scan did not reveal any bladder mass, but an unexplained “well-filled” bladder was observed, which was confusing as the catheter was present and open. However, a subsequent cystoscopic evaluation revealed a large bladder mass measuring 9.5 × 9.0 × 6.5 cm3, which almost filled the entire bladder. The mass had coarse and flocculent surface and seemed to be free from each observed wall of the urinary bladder. It was diagnosed as an infectious necrotic mass based on its appearance. During transurethral resection of the mass, a bladder tumor was suspected as small blood vessels and bleeding appeared within the inner layer of the mass. Pathological examination revealed necrotic material, inflammatory cells, and urothelial carcinoma cells. Then, a radical cystectomy was performed, and the pathological results indicated stage pT3bN0M0 transitional cell carcinoma. In the gross specimen, the base of the tumor measured 3 × 3 cm2 on the top of the back wall of the bladder. Bladder tumors may have atypical presentations in patients with spina bifida. Regular screening is helpful for earlier detection and improving outcomes of bladder tumors in such patients. PMID:27100442

  18. SPARING CYSTECTOMY IN PATIENTS WITH TRANSITIONAL-CELL CARCINOMA OF THE URINARY BLADDER

    Directory of Open Access Journals (Sweden)

    V. B. Matveyev

    2014-07-01

    Full Text Available Objective: to study the results of sparing cystectomy in patients with urinary bladder cancer (UBC.Subjects and methods. The study has covered 82 patients with transitional-cell UBC (T1-4aN0M0 who received radiotherapy (RT and thenunderwent radical cystectomy at the N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, in 1980 to2007. Among them there were 76 (92.7% males and 6 (7.3% females. The median age was 55.2±10.8 years. Superficial (T1 and inva-sive (Т2—4а carcinomas were detected in 33 (40.2% and 49 (59.8% patients, respectively. Category N+ was identified in 3 (3.7% patients.All the patients received RT to the bladder area (median total focal dose (TFD 56±12.3 Gy and regional metastatic zones (median TFD40.0±0.0 Gy. A full effect of irradiation was achieved in 44 (53.7% patients, of whom 41 (93.2% developed local relapses. All the 82patients underwent radical cystectomy: that with ureterostomy in 28 (34.1% cases, Bricker’s operation in 45 (54.4%, Studer’s operationin 4 (4.9%, and rectal urinary bladder in 5 (6.1%. The median follow-up was 32.7±31.9 months.Results. The median interval between RT and cystectomy was 12.5±5.1 months; the median time of surgery was 360 (60—480 min; themedian blood loss was 1515.2±1227.8 ml. Intraoperative and postoperative complications developed in 10 (12.2% and 40 (48.6%patients, respectively. Repeated operations were performed in 7 (8.4% cases. Mortality was 4.9%. A urinary derivation technique failed toaffect the incidence of complications and the rates of mortality (p > 0.05. Histological studies revealed transitional-cell carcinoma in thedistant specimens in 80 (97.6% cases. Recurrences developed in 40 (48.8% of the 82 patients following an average of 32.9 (1—150months of cystectomy: local relapses in 5 (6.1% cases; distant metastases in 29 (35.4%; a local relapse and distant metastases in 5 (6.1%;urethral recurrence in 1 (1.2% patient. Five-year overall

  19. SPARING CYSTECTOMY IN PATIENTS WITH TRANSITIONAL-CELL CARCINOMA OF THE URINARY BLADDER

    Directory of Open Access Journals (Sweden)

    V. B. Matveyev

    2009-01-01

    Full Text Available Objective: to study the results of sparing cystectomy in patients with urinary bladder cancer (UBC.Subjects and methods. The study has covered 82 patients with transitional-cell UBC (T1-4aN0M0 who received radiotherapy (RT and thenunderwent radical cystectomy at the N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, in 1980 to2007. Among them there were 76 (92.7% males and 6 (7.3% females. The median age was 55.2±10.8 years. Superficial (T1 and inva-sive (Т2—4а carcinomas were detected in 33 (40.2% and 49 (59.8% patients, respectively. Category N+ was identified in 3 (3.7% patients.All the patients received RT to the bladder area (median total focal dose (TFD 56±12.3 Gy and regional metastatic zones (median TFD40.0±0.0 Gy. A full effect of irradiation was achieved in 44 (53.7% patients, of whom 41 (93.2% developed local relapses. All the 82patients underwent radical cystectomy: that with ureterostomy in 28 (34.1% cases, Bricker’s operation in 45 (54.4%, Studer’s operationin 4 (4.9%, and rectal urinary bladder in 5 (6.1%. The median follow-up was 32.7±31.9 months.Results. The median interval between RT and cystectomy was 12.5±5.1 months; the median time of surgery was 360 (60—480 min; themedian blood loss was 1515.2±1227.8 ml. Intraoperative and postoperative complications developed in 10 (12.2% and 40 (48.6%patients, respectively. Repeated operations were performed in 7 (8.4% cases. Mortality was 4.9%. A urinary derivation technique failed toaffect the incidence of complications and the rates of mortality (p > 0.05. Histological studies revealed transitional-cell carcinoma in thedistant specimens in 80 (97.6% cases. Recurrences developed in 40 (48.8% of the 82 patients following an average of 32.9 (1—150months of cystectomy: local relapses in 5 (6.1% cases; distant metastases in 29 (35.4%; a local relapse and distant metastases in 5 (6.1%;urethral recurrence in 1 (1.2% patient. Five-year overall

  20. Co-localization of GSTP1 and JNK in transitional cell carcinoma of urinary bladder

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    Marija Pljesa-Ercegovac

    2010-01-01

    Full Text Available Transitional cell carcinoma (TCC of urinary bladder belongs to glutathione S-transferase P1 (GSTP1 overexpressing tumors. Upregulated GSTP1 in TCC is related to apoptosis inhibition. This antiapoptotic effects of GSTP1 might be mediated through protein:protein interaction with c-Jun NH2-terminal kinase (JNK. Herein, we analyzed whether a direct link between GSTP1 and JNK exists in TCC. The presence of GSTP1/JNK complexes was analyzed by immunoprecipitation and Western blotting in 20 TCC specimens, obtained after surgery. Co-localization of GSTP1 and JNK was also investigated in the 5637 TCC cell line by immunofluorescence confocal microscopy. By means of immunoprecipitation we show for the first time the presence of GSTP1/JNK complexes in all TCC samples studied. A co-localization of GSTP1 and JNK was also demonstrated in the 5637 TCC cell line by means of confocal microscopy. Protein-protein interactions, together with co-localization between GSTP1 and JNK provide evidence that GSTP1 most probably inhibits apoptosis in TCC cells by non-covalent binding to JNK.

  1. The Implicaiton of the Expression of Three Cytokines in Carcinoma of Bladder

    Institute of Scientific and Technical Information of China (English)

    YANGWeimin

    2002-01-01

    Objective To explore the expression of CK19,CK20 and bFGF in transitional cell carcinoma of the bladder(TCC) and their biological implication. Methods Samples from 54 patients with TCC were examined for expression of CK19, CK20 and Bfgf. Results There was a significant difference in CK19 expression between relapse and non-relapse groups(P0.05).There were significant differences in CD20 expression among groups with different pathological grades (P<0.05) and clinical stages (P<0.01) and between the relapse and non-relapse groups (P<0.0001).The expression of bFGF was significantly different among groups with different pathological grades and clini-cal stages and between the relapse and non-relapse groups(P<0.05).Conclusion The expression of CK19 ,CK20 and bFGF is closely associated with their biological behavior and among them bFGF is pri-marily secreted by TCC tumor tissues.

  2. Recurrent and multiple bladder tumors show conserved expression profiles

    Directory of Open Access Journals (Sweden)

    Knuutila Sakari

    2008-06-01

    Full Text Available Abstract Background Urothelial carcinomas originate from the epithelial cells of the inner lining of the bladder and may appear as single or as multiple synchronous tumors. Patients with urothelial carcinomas frequently show recurrences after treatment making follow-up necessary. The leading hypothesis explaining the origin of meta- and synchronous tumors assumes a monoclonal origin. However, the genetic relationship among consecutive tumors has been shown to be complex in as much as the genetic evolution does not adhere to the chronological appearance of the metachronous tumors. Consequently, genetically less evolved tumors may appear chronologically later than genetically related but more evolved tumors. Methods Forty-nine meta- or synchronous urothelial tumors from 22 patients were analyzed using expression profiling, conventional CGH, LOH, and mutation analyses. Results We show by CGH that partial chromosomal losses in the initial tumors may not be present in the recurring tumors, by LOH that different haplotypes may be lost and that detected regions of LOH may be smaller in recurring tumors, and that mutations present in the initial tumor may not be present in the recurring ones. In contrast we show that despite apparent genomic differences, the recurrent and multiple bladder tumors from the same patients display remarkably similar expression profiles. Conclusion Our findings show that even though the vast majority of the analyzed meta- and synchronous tumors from the same patients are not likely to have originated directly from the preceding tumor they still show remarkably similar expressions profiles. The presented data suggests that an expression profile is established early in tumor development and that this profile is stable and maintained in recurring tumors.

  3. Plasmacytoid variant of bladder cancer defines patients with poor prognosis if treated with cystectomy and adjuvant cisplatin-based chemotherapy

    Directory of Open Access Journals (Sweden)

    Keck Bastian

    2013-02-01

    Full Text Available Abstract Background Since the definition of different histologic subtypes of urothelial carcinomas by the World Health Organization (WHO 2004 classification, description of molecular features and clinical behavior of these variants has gained more attention. Methods We reviewed 205 tumor samples of patients with locally advanced bladder cancer mainly treated within the randomized AUO-AB05/95 trial with radical cystectomy and adjuvant cisplatin-based chemotherapy for histologic subtypes. 178 UC, 18 plasmacytoid (PUC and 9 micropapillary (MPC carcinomas of the bladder were identified. Kaplan Meier analysis and backward multivariate Cox’s proportional hazards regression analysis were performed to compare overall survival between the three histologic subtypes. Results Patients suffering from PUC have the worst clinical outcome regarding overall survival compared to conventional UC and MPC of the bladder that in turn seem have to best clinical outcome (27.4 months, 62.6 months, and 64.2 months, respectively; p=0.013 by Kaplan Meier analysis. Backward multivariate Cox´s proportional hazards regression analysis (adjusted to relevant clinicopathological parameters showed a hazard ratio of 3.2 (p=0.045 for PUC in contrast to patients suffering from MPC. Conclusions Histopathological diagnosis of rare variants of urothelial carcinoma can identify patients with poor prognosis.

  4. Plasmacytoid variant of bladder cancer defines patients with poor prognosis if treated with cystectomy and adjuvant cisplatin-based chemotherapy

    International Nuclear Information System (INIS)

    Since the definition of different histologic subtypes of urothelial carcinomas by the World Health Organization (WHO) 2004 classification, description of molecular features and clinical behavior of these variants has gained more attention. We reviewed 205 tumor samples of patients with locally advanced bladder cancer mainly treated within the randomized AUO-AB05/95 trial with radical cystectomy and adjuvant cisplatin-based chemotherapy for histologic subtypes. 178 UC, 18 plasmacytoid (PUC) and 9 micropapillary (MPC) carcinomas of the bladder were identified. Kaplan Meier analysis and backward multivariate Cox’s proportional hazards regression analysis were performed to compare overall survival between the three histologic subtypes. Patients suffering from PUC have the worst clinical outcome regarding overall survival compared to conventional UC and MPC of the bladder that in turn seem have to best clinical outcome (27.4 months, 62.6 months, and 64.2 months, respectively; p=0.013 by Kaplan Meier analysis). Backward multivariate Cox´s proportional hazards regression analysis (adjusted to relevant clinicopathological parameters) showed a hazard ratio of 3.2 (p=0.045) for PUC in contrast to patients suffering from MPC. Histopathological diagnosis of rare variants of urothelial carcinoma can identify patients with poor prognosis

  5. Can Bcl-XL expression predict the radio sensitivity of Bilharzial-related squamous bladder carcinoma? a prospective comparative study

    Directory of Open Access Journals (Sweden)

    Kamel Nermen A

    2011-01-01

    Full Text Available Abstract Background Local pelvic recurrence after radical cystectomy for muscle invasive bilharzial related squamous cell carcinoma accounts for 75% of treatment failures even in organ confined tumors. Despite the proven value of lymphadenectomy, up to 60% of patients undergoing cystectomy do not have it. These factors are in favor of adjuvant radiotherapy reevaluation. objectives: to evaluate the effect of adjuvant radiotherapy on disease free survival in muscle invasive bilharzial related squamous cell carcinoma of the urinary bladder and to test the predictability of radio-sensitivity using the anti apoptotic protein Bcl-XL. Methods The study prospectively included 71 patients, (47 males, 24 females with muscle invasive bilharzial related squamous cell carcinoma of the bladder (Stage pT2a-T3N0-N3M0 who underwent radical cystectomy in Assiut university hospitals between January 2005 and December 2006. Thirty eight patients received adjuvant radiotherapy to the pelvis in the dose of 50Gy/25 fractions/5 weeks (Group 1, while 33 patients did not receive adjuvant radiotherapy (group 2. Immunohistochemical characterization for bcl-xL expression was done. Follow up was done every 3 months for 12 to 36 months with a mean of 16 ± 10 months. All data were analyzed using SPSS version 16. Three years cumulative disease free survival was calculated and adjusted to Bcl-XL expression and side effects of the treatment were recorded. Results The disease free cumulative survival was 48% for group 1 and 29% for group 2 (log rank p value 0.03. The multivariate predictors of tumor recurrence were the positive Bcl-XL expression (odd ratio 41.1, 95% CI 8.4 - 102.3, p Conclusions Adjuvant radiotherapy for muscle invasive bilharzial related squamous cell carcinoma of the urinary bladder has potential effectiveness and minor side effects. Moreover, Bcl-XL expression is a valuable tool for predicting those who might not respond to this adjuvant treatment.

  6. Inhibiting Invasion into Human Bladder Carcinoma 5637 Cells with Diallyl Trisulfide by Inhibiting Matrix Metalloproteinase Activities and Tightening Tight Junctions

    Directory of Open Access Journals (Sweden)

    Yung Hyun Choi

    2013-10-01

    Full Text Available Diallyl trisulfide (DATS, an organosulfur compound in garlic, possesses pronounced anti-cancer potential. However, the anti-invasive mechanism of this compound in human bladder carcinoma is not fully understood. In this study, we evaluated the anti-invasive effects of DATS on a human bladder carcinoma (5637 cell line and investigated the underlying mechanism. The results indicated that DATS suppressed migration and invasion of 5637 cells by reducing the activities and expression of matrix metalloproteinase (MMP-2 and MMP-9 at both the protein and mRNA levels. DATS treatment up-regulated expression of tissue inhibitor of metalloproteinase (TIMP-1 and TIMP-2 in 5637 cells. The inhibitory effects of DATS on invasiveness were associated with an increase in transepithelial electrical resistance and repression of the levels of claudin family members. Although further studies are needed, our data demonstrate that DATS exhibits anti-invasive effects in 5637 cells by down-regulating the activity of tight junctions and MMPs. DATS may have future utility in clinical applications for treating bladder cancer.

  7. Mechanical characterization of benign and malignant urothelial cells from voided urine

    Science.gov (United States)

    Shojaei-Baghini, Ehsan; Zheng, Yi; Jewett, Michael A. S.; Geddie, William B.; Sun, Yu

    2013-03-01

    This study investigates whether mechanical differences exist between benign and malignant urothelial cells in voided urine. The Young's modulus of individual cells was measured using the micropipette aspiration technique. Malignant urothelial cells showed significantly lower Young's modulus values compared to benign urothelial cells. The results indicate that Young's modulus as a biomechanical marker could possibly provide additional information to conventional urinary cytology. We hope that these preliminary results could evoke attention to mechanical characterization of urine cells and spark interest in the development of biomechanical approaches to enhance non-invasive urothelial carcinoma detection.

  8. Keystone Symposia "ncRNAs in Development and Cancer", Vancouver, Canada: Increased release of exosomes and export of invasion-modulating miRNAs miR921, -23b, -and -224 from metastatic urothelial carcinoma cells

    DEFF Research Database (Denmark)

    Ostenfeld, Marie Stampe; Jeppesen, Dennis Kjølhede; Laurberg, Jens Reumert;

    2013-01-01

    Cancer cells secrete soluble factors and various extracellular vesicles, including exosomes, into their tissue microenvironment. The secretion of exosomes is speculated to facilitate local invasion and increase the propensity of tumors to form distant metastases. Here we present a characterization...... of exosome vesicles from isogenic urothelial carcinoma cell lines, with different metastatic propensity by western blotting, electron microscopy, nanoparticle tracking analysis, dynamic light scattering, and profiling of 671 miRNAs by qRT-PCR. An increase in the number of multivesicular bodies and exosomes...... was observed for metastatic FL3 cells compared to isogenic non-metastatic T24 cells. The release was significantly inhibited by knockdown of Rab27b and pharmacological inhibition of nsmase2 by GW4869. miRNA profiling was conducted on parental cells and their secreted exosomes. Here, selective export of miR921...

  9. Incidental Diagnosis of Carcinoma of the Bladder Due to Uptake of {sup 99m}Tc-MDP

    Energy Technology Data Exchange (ETDEWEB)

    Damle, Nishikant A; Pandey, Dinesh Chand; Gautam, Awadhesh Kumar; Subbarao, Kiran; Singh, Prabhjot [All India Institute of Medical Sciences, New Delhi (India); Mishra, Rohini; Das, Nitendra Lal; Pandey, Dinesh Chand; Gautam, Awadhesh Kumar [B. L. Kapur Memorial Hospital, New Delhi (India)

    2012-06-15

    A bone scan was per-formed using 740 MBq (29 mCi) {sup 99}mTc-MDP. Whole-body planar images were acquired 3 h after injection (Fig. 1). Soft tissue uptake of {sup 99}mTc-MDP is described in various benign and malignant conditions. It is known to accumulate in adenocarcinoma of lung, primary breast cancer, and colonic carcinoma among others. The postulated causes of {sup 99}mTc-MDP uptake in extraosseous neoplasms are numerous and include tumor vascularity, inflammation, local pH factors, altered calcium metabolism, hormonal influences and cell wall damage. Our case shows that TCC of the bladder was incidentally diagnosed due to MDP uptake in multiple bladder polyps detected on a bone scan done for low backache in an 80-year-old man.

  10. Survivin mRNA expression in urine as a biomarker for patients with transitional cell carcinoma of bladder

    Institute of Scientific and Technical Information of China (English)

    HOU Jian-quan; HE Jun; WEN Duan-gai; CHEN Zi-xing; ZENG Jian

    2006-01-01

    @@ Transitional cell carcinoma (TCC) of bladder is the most common malignant tumor in uropoiesis system. Up to date, there is still lack of an ideal marker for the diagnosis of TCC except CT and MRI imaging and cystoscopy. Cystoscopy is an invasive examination, which increases the possibility of urinary tract infection. Urine cytology has low sensitivity (21%-40%) in diagnosis of bladder cancer, especially for those with medium or high differentiation. The specificity is often affected by factors such as specimen collection, urinary tract infection, etc. Detecting the expression of survivin mRNA in urine by real time-PCR is simple in specimen collection and is sensitive and relatively specific, which provides a simple and noninvasive diagnostic method for TCC. Moreover it allows comparing the gene expression levels at different stages and grades of TCC, which can help define malignancy degree of TCC.

  11. A Large Bladder Tumor Covered With a Thick "Shell" of Necrotic Material: Misdiagnosis of a Patient With Spina Bifida.

    Science.gov (United States)

    Wang, Lei; Zhou, Zhe; Gong, Miao-Zi; Pan, Dong-Liang; Zhang, Xiang-Hua; Li, Ning-Chen; Na, Yan-Qun

    2016-04-01

    Bladder tumor arising in a spina bifida patient is rare and may be clinically latent.We report the case of a 61-year-old female patient with spina bifida, neurogenic bladder, and a history of recurrent urinary tract infections. A B-ultrasound and non-contrast computed tomography scan did not reveal any bladder mass, but an unexplained "well-filled" bladder was observed, which was confusing as the catheter was present and open. However, a subsequent cystoscopic evaluation revealed a large bladder mass measuring 9.5 × 9.0 × 6.5 cm, which almost filled the entire bladder. The mass had coarse and flocculent surface and seemed to be free from each observed wall of the urinary bladder. It was diagnosed as an infectious necrotic mass based on its appearance.During transurethral resection of the mass, a bladder tumor was suspected as small blood vessels and bleeding appeared within the inner layer of the mass. Pathological examination revealed necrotic material, inflammatory cells, and urothelial carcinoma cells. Then, a radical cystectomy was performed, and the pathological results indicated stage pT3bN0M0 transitional cell carcinoma. In the gross specimen, the base of the tumor measured 3 × 3 cm on the top of the back wall of the bladder.Bladder tumors may have atypical presentations in patients with spina bifida. Regular screening is helpful for earlier detection and improving outcomes of bladder tumors in such patients. PMID:27100442

  12. [Evaluation of the complementary drug Factor AF2 as a supportive agent in management of advanced urothelial carcinoma. Prospective randomized multicenter study].

    Science.gov (United States)

    Krege, S; Hinke, A; Otto, T; Rübben, H

    2002-03-01

    This is a prospective randomized multicenter trial for evaluation of the biological response modifier Factor AF2 in advanced urothelial cancer treated with chemotherapy. Main aim of the study was the analysis of supportive effects. Additionally patients were examined with regard to tumor response, time to progression and survival. 106 patients with advanced urothelial cancer received chemotherapy with cisplatin and methotrexate. They were randomized for additional Factor AF2 (500 mg i.v., given at days 0-3, 7-10 and 11-14). Myelotoxicity was more common and severe in the group without Factor AF2 reaching statistical significance. Gastrointestinal side effects occurred in both groups, though grade III to IV toxicity was more common without Factor AF2. Overall remission rate was 38%, median survival 33 weeks, mean time to progression 20 weeks. There was no significant difference between the two groups with or without Factor AF2. PMID:11993095

  13. Hexavalent chromium induces chromosome instability in human urothelial cells.

    Science.gov (United States)

    Wise, Sandra S; Holmes, Amie L; Liou, Louis; Adam, Rosalyn M; Wise, John Pierce

    2016-04-01

    Numerous metals are well-known human bladder carcinogens. Despite the significant occupational and public health concern of metals and bladder cancer, the carcinogenic mechanisms remain largely unknown. Chromium, in particular, is a metal of concern as incidences of bladder cancer have been found elevated in chromate workers, and there is an increasing concern for patients with metal hip implants. However, the impact of hexavalent chromium (Cr(VI)) on bladder cells has not been studied. We compared chromate toxicity in two bladder cell lines; primary human urothelial cells and hTERT-immortalized human urothelial cells. Cr(VI) induced a concentration- and time-dependent increase in chromosome damage in both cell lines, with the hTERT-immortalized cells exhibiting more chromosome damage than the primary cells. Chronic exposure to Cr(VI) also induced a concentration-dependent increase in aneuploid metaphases in both cell lines which was not observed after a 24h exposure. Aneuploidy induction was higher in the hTERT-immortalized cells. When we correct for uptake, Cr(VI) induces a similar amount of chromosome damage and aneuploidy suggesting that the differences in Cr(VI) sensitivity between the two cells lines were due to differences in uptake. The increase in chromosome instability after chronic chromate treatment suggests this may be a mechanism for chromate-induced bladder cancer, specifically, and may be a mechanism for metal-induced bladder cancer, in general. PMID:26908176

  14. Screening differentially expressed genes of urine exfoliated urothelial cells in transitional cell carcinoma by SSH%膀胱癌患者尿脱落细胞抑制消减文库的构建及差异基因的初步筛选

    Institute of Scientific and Technical Information of China (English)

    张冲; 郭柏鸿; 张志华; 吏葆光; 车团结; 陈一戎

    2009-01-01

    目的 应用抑制性消减杂交方法 筛选膀胱移行细胞癌患者与正常人尿脱落细胞差异表达基因.方法 分离膀胱移行细胞癌患者与正常人尿液中总mRNA,用SMART技术反转录成cDNA,经过酶切、接头连接、两轮消减杂交及两轮抑制性PCR,使得差异表达的DNA片段得以富集.PCR产物与T/A载体连接并转化大肠杆菌XL-blue构建差异表达基因的cDNA消减文库.文库扩增后随机挑取克隆进行酶切、测序及同源性分析.结果 PCR鉴定有317个克隆载有主要在200~900bp之间呈随机分布的插入片段,片段插入率达93.2%,证实建库成功.对20个质粒测序结果 经同源性比对分析,其中20个片段源于17个已知基因,1个克隆在GenBank中未检索到与其有相似性的基因序列,表明它们可能为BTCC差异表达的新基因.结论 该消减杂交文库质量町靠,它的成功构建为进一步筛选、克隆膀胱肿瘤差异表达基因提供了依据.也为膀胱肿瘤诊断基因芯片的研究与开发奠定了基础.%Objectives To Screening transitional" differentially suppression subtractive eDNA library in transitional cell carcinoma of bladder (BTCC) and normal urine exfoliated urothelial cells. Methods Total mRNA was isolated from BTCC and normal exfoliatod urothelial calls in urine, respectively. Then double-strand eDNA was synthesized and restricted by Hae Ⅲ. eDNA of BTCC was divided into two groups and ligated with either adaptor Ⅰ or adaptor 2. After hybridized twice normal exfoliated urothelial cells eDNA underwent nested PCR, the PCR products were cloned into PGM-T vector and transformed to E. Eoli JM109. Some pesitive clones were randomly picked up, digested, sequenced and homologous analyzed. Results The SSH library contained about 400 positive clones. Random analysis of 384 clones with enzyme restriction showed that 317clones contained cDNA fragments which were mainly between 200~900bp. The inserted rate reached to 82

  15. G9a Inhibition Induces Autophagic Cell Death via AMPK/mTOR Pathway in Bladder Transitional Cell Carcinoma

    OpenAIRE

    Feng Li; Jin Zeng; Yang Gao; Zhenfeng Guan; Zhenkun Ma; Qi Shi; Chong Du; Jing Jia; Shan Xu; Xinyang Wang; Luke Chang; Dalin He; Peng Guo

    2015-01-01

    G9a has been reported to highly express in bladder transitional cell carcinoma (TCC) and G9a inhibition significantly attenuates cell proliferation, but the underlying mechanism is not fully understood. The present study aimed at examining the potential role of autophagy in the anti-proliferation effect of G9a inhibition on TCC T24 and UMUC-3 cell lines in vitro. We found that both pharmaceutical and genetical G9a inhibition significantly attenuated cell proliferation by MTT assay, Brdu incor...

  16. Holmium laser versus conventional transurethral resection of the bladder tumor

    Institute of Scientific and Technical Information of China (English)

    TENG Jing-fei; WANG Kai; YIN Le; QU Fa-jun; ZHANG Dong-xu; CUI Xin-gang; XU Dan-feng

    2013-01-01

    Background Transurethral resection of the bladder tumor (TURBT) remains the gold standard for non-muscle-invasive bladder cancer (NMIBC).Laser techniques have been widely used in urology.This analysis aimed to assess the safety and efficacy of holmium resection of the bladder tumor (HoLRBT) vs.TURBT.Methods A systemic search of MEDLINE,Embase,Web of Science,and The Cochrane Library as well as manual bibliography searches were performed to identify the relevant studies.The pooled estimates of operation time,obturator nerve reflex rate,bladder perforation rate,bladder irrigation rate,catheterization time,hospital stay,and one-and two-year recurrence free survivals were calculated.Results Five studies were enrolled into our meta-analysis.No significant difference was observed in the operation time between groups (weighted mean difference (WMD) 1.01,95% confidential interval (95% CI)-3.52-5.54,P=0.66).The significant difference in the obturator nerve reflex (OR 0.05,95% CI 0.01-0.04,P=0.004),bladder perforation (OR 0.14,95% CI 0.03-0.61,P=0.009),bladder irrigation (OR 0.13,95% CI 0.04-0.45,P=0.001),catheterization time (WMD -0.96,95% CI-1.11 to-0.82,P <0.00001),and hospital stay (WMD-1.46,95% C1-1.65 to-1.27,P <0.00001) showed advantages of HoLRBT over TURBT.The 2-year recurrence free survival rate favors the HoLRBT group (OR 1.46,95%CI 1.02-2.11,P=0.04).Conclusions As a promising technique,HoLRBT is safe and efficient,and showed several advantages over TURBT.HoLRBT can be used as an alternative procedure for TURBT in terms of low-grade papillary urothelial carcinoma or Iow-orade early TNM-staoe urothelial carcinoma.

  17. A retrospective study of post-operative gall bladder pathology with special reference to incidental carcinoma of the gall bladder

    Directory of Open Access Journals (Sweden)

    Jagannath Dev Sharma

    2014-06-01

    Methods: This retrospective study was carried out at a multi-specialty hospital in eastern India from the pathology records for the period from August 2005 to July 2008. The records were analyzed for gender, age group distribution, and pathological types with different histology. Results: Out of 863 records, chronic cholecystitis 51.2% was the most common histology and malignancy was seen in 2.7% (23/863 both pre-operative and post-operative diagnosis. In the neoplastic group incidental carcinoma was diagnosed in 1.9% (17/23 of cases Conclusion: Histopathological examination of gallbladder specimen helps to identify non-neoplastic conditions with its complications and also, for the detection of incidental carcinoma. Thorough sampling of all gallbladder specimens is a must to detect focal neoplastic changes. [Int J Res Med Sci 2014; 2(3.000: 1050-1053

  18. Optimization of porcine urothelial cell cultures: Best practices, recommendations, and threats.

    Science.gov (United States)

    Pokrywczynska, Marta; Czapiewska, Monika; Jundzill, Arkadiusz; Bodnar, Magdalena; Balcerczyk, Daria; Kloskowski, Tomasz; Nowacki, Maciej; Marszalek, Andrzej; Drewa, Tomasz

    2016-07-01

    Many experimental approaches have been conducted in order to isolate urothelial cells from bladder tissue biopsies, but each method described has utilized different protocols and sources of bladder tissue. In this study, we compared the different methods of urothelial cell isolation available in literature together with standardized methods in order to obtain more unified results. Five methods for primary porcine urothelial culture establishment were compared: tissue explants and four enzymatic methods utilizing collagenase II, dispase II, combination of dispase II and trypsin, and trypsin alone. The average number of isolated cells, cell morphology, success of established culture, average number of cells from the first passage, expression of p63 and pancytokeratin and the characterization of urothelial cell growth, and aging were analyzed during the in vitro culture. The method utilizing dispase II was the most efficient and reproducible method for the isolation and culture of porcine urothelial cells when compared to the other tested methods. Urothelial cells obtained by this method grew considerably well and the cultures were established with high efficiency, which enabled us in obtaining a large quantity of cells with normal morphology. Contamination with fibroblasts in this method was the lowest. The utilization of a proper method for urothelial cell isolation is a critical step in the urinary tract regeneration when using tissue engineering techniques. In summary, this study demonstrated that by utilizing the described method with dispase II, a suitable number of cells was achieved, proving the method useful for tissue regeneration. PMID:27079486

  19. Clonal, self-renewing and differentiating human and porcine urothelial cells, a novel stem cell population.

    Directory of Open Access Journals (Sweden)

    Hans M Larsson

    Full Text Available Although urothelial progenitor-like cells have been described in the human urinary tract, the existence of stem cells remains to be proven. Using a culture system that favors clonogenic epithelial cell growth, we evaluated and characterized clonal human urothelial cells. We isolated human urothelial cells that were clonogenic, capable of self-renewal and could develop into fully differentiated urothelium once re-implanted into the subcapsular space of nude mice. In addition to final urothelial cell differentiation, spontaneous formation of bladder-like microstructures was observed. By examining an epithelial stem cell signature marker, we found p63 to correlate with the self-renewal capacity of the isolated human urothelial clonal populations. Since a clinically relevant, long-term model for functional reconstitution of human cells does not exist, we sought to establish a culture method for porcine urothelial cells in a clinically relevant porcine model. We isolated cells from porcine ureter, urethra and bladder that were clonogenic and capable of self-renewal and differentiation into fully mature urothelium. In conclusion, we could isolate human and porcine cell populations, behaving as urothelial stem cells and showing clonogenicity, self-renewal and, once re-implanted, morphological differentiation.

  20. Laparoscopic bilateral nephroureterectomy and bladder cuff excision for native renal pelvic and ureteral transitional cell carcinoma after renal transplantation.

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    Chen C

    2003-01-01

    Full Text Available A 37-years-old female who was suffering from end-stage renal disease for about 6 years received allograft renal transplantation 4 years ago. She has been receiving 50mg of Cyclosporin A orally daily for immuno-suppression since then. Gross haematuria was noted and computerised tomography showed native left renal pelvic and ureteral multi-focal transitional cell carcinoma with severe hydronephrosis. Laparoscopic bilateral nephroureterectomy and bladder cuff excision were performed. In the past, history of previous operation was considered a relative contraindication for laparoscopic surgery. To our knowledge, we present the first case of laparoscopic treatment for native renal pelvic and ureteral transitional cell carcinoma after renal allograft transplantation without a hand-assisted device. This case shows the feasibility of laparoscopic bilateral nephroureterectomy in patients with transplanted kidneys.

  1. Expression of VEGF in urinary bladder transitional cell carcinoma in an Iraqi population subjected to depleted uranium: an immunohistochemical study.

    Science.gov (United States)

    Al-Abbasi, Dhafer S; Al-Janabi, As'ad A; Al-Toriahi, Kaswer M; Jabor, Thekra A; Yasseen, Akeel A

    2009-07-01

    The present study aimed to assess the correlation between vascular endothelial growth factor (VEGF) overexpression and the grade, size, and recurrence of transitional cell carcinoma (TCC) in the south of Iraq, which includes regions that have been exposed to high levels of depleted uranium. The study also sought to evaluate whether there is any biomarker in the expression that could be correlated with the increased incidence of this type of cancer in the exposed areas. Samples of formalin-fixed and paraffin-embedded tissue from 54 patients (41 males and 13 females) with TCC and from 32 patients with benign bladder lesions (cystitis) used as controls were included in this study. The avidin-biotin complex method was used for immunohistochemical detection of VEGF. VEGF immunoexpression was positive in 77.77% of TCC but was not found in benign bladder lesions (cystitis) (P0.05). These findings support the role of VEGF in the carcinogenesis of TCC regarding evolution, behavior, and aggressiveness. Hence, VEGF could be considered as a poor prognostic parameter in bladder cancer. No positive correlation between immunohistochemical expression and the high incidence of TCC was detected (R=depleted uranium. PMID:19151604

  2. Expression of monocyte chemoattractant protein and MCP-1 gene in urothelial carcinoma of renal pelvis and its clinical significance%单核细胞趋化蛋白在肾盂尿路上皮癌中的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    白鑫; 高健刚; 侯四川; 孙小庆; 朱磊一

    2011-01-01

    Objective To investigate the monocyte chemoattractant protein (MCP-1) gene expression of urothelial carcinoma of renal pelvis and adjacent normal tissues and the correlation of the incidence and pathological grading of urothelial carcinoma of renal pelvis.Methods Twenty cases of patients with urothelial carcinoma of renal pelvis( 12 cases of male, 8 cases of female) were taken the blood, carcinoma tissues and adjacent normal tissues.Thirty cases of non-cancer patients( 18 cases of male, 12 cases of female) as control group were taken blood samples.Expression of MCP-1 in plasma were detected by ELISA method quantitative determination,and the expression of MCP-1 in urothelial carcinoma of renal pelvis and adjacent normal tissues were investigated by immunohistochemical method.Real-time quantitative PCR was used to detect the expression of MCP-1 RNA.Results MCP-1 in plasma of urothelial carcinoma patients of renal pelvis was(173.4 ±82.1)pg/ml, higher than that of non-tumor group (91.8 ±34.6) pg/ml (P <0.05).Expression of MCP-1 in high-grade urothelial carcinoma of renal pelvis was(254.1 ± 125.8)pg/ml,while in low-grade urothelial carcinoma of renal pelvis was( 151.3 ± 79.5 ) pg/ml.Immunohistochemistry showed that MCP-1 positive rate in urothelial carcinoma of renal pelvis was 90.0% ( 18/20), and in adjacent normal tissues was 65.0% ( 13/20), with significant differences ( P < 0.01 ).Positive expression rate of MCP-1 in high-grade urothelial carcinoma of renal pelvis was 100.0% (4/4) , while in low-grade urothelial carcinoma of renal pelvis was 87.5% ( 14/16 ).Total RNA and mRNA levels of MCP-1 in the urothelial carcinoma of renal pelvis were statistically significant different compared with adjacent normal tissues group (P < 0.05).Conclusion The upregulation of MCP-1 gene expression is likely to play an important role in the incidence and metastasis of the urothelial carcinoma of renal pelvis.%目的 探讨肾盂尿路上皮癌组

  3. TGF-β1 promotes the migration and invasion of bladder carcinoma cells by increasing fascin1 expression.

    Science.gov (United States)

    Zhang, Naiwen; Bi, Xiaojun; Zeng, Yu; Zhu, Yuyan; Zhang, Zhe; Liu, Yang; Wang, Jianfeng; Li, Xuejie; Bi, Jianbin; Kong, Chuize

    2016-08-01

    Transforming growth factor-β1 (TGF-β1) is a multifunctional cytokine that is reported to regulate cellular motility and invasive capability during tumor progression. Fascin1, an actin-bundling protein, increases cell motility, migration and adhesion. To investigate the function of TGF-β1 and test whether fascin1 is an important mediator of the tumor response to TGF-β1 in bladder carcinoma cells, real-time RT-PCR and western blot analysis were used to test changes in fascin1 expression after TGF-β1 (10 ng/ml) treatment in T24 and BIU87 cells. Small interfering RNA (siRNA) technique was performed to silence fascin1. Cell viability and biological behavior changes were evaluated by cell growth (MTT), wound-healing and Matrigel invasion assays. In the present study, we found that the mRNA and protein levels of fascin1 in the T24 and BIU87 cells were significantly increased after 10 ng/ml TGF-β1 treatment (pTGF-β1. The findings suggested that TGF-β1 can promote invasion and migration of T24 and BIU87 bladder carcinoma cells, and the increase in fascin1 expression may be the key point of this impact of TGF-β1.

  4. Levels of tissue inhibitor of metalloproteinases 1 in plasma and urine frompatients with bladder cancer

    DEFF Research Database (Denmark)

    Holten Andersen, MN; Brunner, N; Nielsen, HJ;

    2006-01-01

    Aim: To assess the potential use of plasma and urine levels of tissue inhibitor of metalloproteinases 1 (TIMP-1) in urothelial cancer. Methods: TIMP-1 levels were determined in urine and plasma from healthy donors (n=26), patients with bacterial bladder infection (n=24), urothelial bladder adenoma....... No correlation between plasma and urine TIMP-1 was found. Measurement of TIMP-1 in plasma and/or urine is apparently not useful for the identification of bladder cancer....

  5. Antiproliferative factor decreases Akt phosphorylation and alters gene expression via CKAP4 in T24 bladder carcinoma cells

    Directory of Open Access Journals (Sweden)

    Zhang Chen-Ou

    2010-12-01

    β-catenin changed in response to APF in these cells. In addition, the changes in cell proliferation, MMP2/p53 mRNA and protein expression, and Akt/GSK3β/β-catenin phosphorylation in response to APF treatment were all specifically abrogated following CKAP4 siRNA knockdown. Conclusions Synthetic as-APF inhibits cell proliferation in T24 bladder carcinoma cells via the CKAP4 receptor. The mechanism for this inhibition involves regulating phosphorylation of specific cell signaling molecules (Akt, GSK3β, and β-catenin plus mRNA and protein expression of p53 and MMP2.

  6. Identification of Apo-A1 as a biomarker for early diagnosis of bladder transitional cell carcinoma

    Directory of Open Access Journals (Sweden)

    Wang Shixin

    2011-04-01

    Full Text Available Abstract Background Bladder transitional cell carcinoma (BTCC is the fourth most frequent neoplasia in men, clinically characterized by high recurrent rates and poor prognosis. Availability of urinary tumor biomarkers represents a convenient alternative for early detection and disease surveillance because of its direct contact with the tumor and sample accessibility. Results We tested urine samples from healthy volunteers and patients with low malignant or aggressive BTCC to identify potential biomarkers for early detection of BTCC by two-dimensional electrophoresis (2-DE coupled with mass spectrometry (MS and bioinformatics analysis. We observed increased expression of five proteins, including fibrinogen (Fb, lactate dehydrogenase B (LDHB, apolipoprotein-A1 (Apo-A1, clusterin (CLU and haptoglobin (Hp, which were increased in urine samples of patients with low malignant or aggressive bladder cancer. Further analysis of urine samples of aggressive BTCC showed significant increase in Apo-A1 expression compared to low malignant BTCC. Apo-A1 level was measured quantitatively using enzyme-linked immunosorbent assay (ELISA and was suggested to provide diagnostic utility to distinguish patients with bladder cancer from controls at 18.22 ng/ml, and distinguish patients with low malignant BTCC from patients with aggressive BTCC in two-tie grading system at 29.86 ng/ml respectively. Further validation assay showed that Apo-A1 could be used as a biomarker to diagnosis BTCC with a sensitivity and specificity of 91.6% and 85.7% respectively, and classify BTCC in two-tie grading system with a sensitivity and specificity of 83.7% and 89.7% respectively. Conclusion Taken together, our findings suggest Apo-A1 could be a potential biomarker related with early diagnosis and classification in two-tie grading system for bladder cancer.

  7. Can Bcl-XL expression predict the radio sensitivity of Bilharzial-related squamous bladder carcinoma? a prospective comparative study

    International Nuclear Information System (INIS)

    Local pelvic recurrence after radical cystectomy for muscle invasive bilharzial related squamous cell carcinoma accounts for 75% of treatment failures even in organ confined tumors. Despite the proven value of lymphadenectomy, up to 60% of patients undergoing cystectomy do not have it. These factors are in favor of adjuvant radiotherapy reevaluation. objectives: to evaluate the effect of adjuvant radiotherapy on disease free survival in muscle invasive bilharzial related squamous cell carcinoma of the urinary bladder and to test the predictability of radio-sensitivity using the anti apoptotic protein Bcl-XL. The study prospectively included 71 patients, (47 males, 24 females) with muscle invasive bilharzial related squamous cell carcinoma of the bladder (Stage pT2a-T3N0-N3M0) who underwent radical cystectomy in Assiut university hospitals between January 2005 and December 2006. Thirty eight patients received adjuvant radiotherapy to the pelvis in the dose of 50Gy/25 fractions/5 weeks (Group 1), while 33 patients did not receive adjuvant radiotherapy (group 2). Immunohistochemical characterization for bcl-xL expression was done. Follow up was done every 3 months for 12 to 36 months with a mean of 16 ± 10 months. All data were analyzed using SPSS version 16. Three years cumulative disease free survival was calculated and adjusted to Bcl-XL expression and side effects of the treatment were recorded. The disease free cumulative survival was 48% for group 1 and 29% for group 2 (log rank p value 0.03). The multivariate predictors of tumor recurrence were the positive Bcl-XL expression (odd ratio 41.1, 95% CI 8.4 - 102.3, p < 0.0001) and radiotherapy (odd ratio 0.19, 95% CI 0.05 - 0.78, p < 0.02). With Cox regression, the only independent multivariate predictor of radio-sensitivity was the Bcl-XL expression with odd ratio 4.6 and a p value < 0.0001. All patients tolerated the treatment with no life threatening or late complications during the period of follow up

  8. Strong association between long and heterogeneous telomere length in blood lymphocytes and bladder cancer risk in Egyptian.

    Science.gov (United States)

    Wang, Hongkun; Wang, Ying; Kota, Krishna K; Kallakury, Bhaskar; Mikhail, Nabiel N; Sayed, Douaa; Mokhtar, Ahmed; Maximous, Doaa; Yassin, Etemad H; Gouda, Iman; Sobitan, Adebiyi; Sun, Bing; Loffredo, Christopher A; Zheng, Yun-Ling

    2015-11-01

    Although it is widely recognized that telomere dysfunction plays an important role in cancer, the relationship between telomere function and bladder cancer risk is not well defined. In a case-control study of bladder cancer in Egypt, we examined relationships between two telomere features and bladder cancer risk. Telomere fluorescent in situ hybridization was used to measure telomere features using short-term cultured blood lymphocytes. Logistic regression was used to estimate the strength of association between telomere features and the risk of urothelial carcinoma of the bladder. High telomere length variation (TLV) across all chromosomal ends was significantly associated with an increased risk of bladder cancer [adjusted odds ratios (OR) = 2.22, 95% confidence interval (CI) = 1.48-3.35], as was long average telomere length (OR = 3.19, 95% CI = 2.07, 4.91). Further, TLV and average telomere length jointly affected bladder cancer risk: when comparing individuals with long telomere length and high TLV to those with short telomere length and low TLV, the adjusted OR was 14.68 (95% CI: 6.74-31.98). These associations were stronger among individuals who are 60 years of age or younger. In summary, long and heterogeneous telomere length in blood lymphocytes was strongly associated with an increased bladder cancer risk in Egyptian and the association was modulated by age.

  9. Therapeutic effect of nephron-sparing management for low-grade upper tract urothelial carcinomas:a meta analysis%保肾手术对低级别上尿路上皮癌预后的Meta分析

    Institute of Scientific and Technical Information of China (English)

    王亮; 李延江; 荆涛; 俞亮; 马清昌; 刘松林; 仝义锐

    2015-01-01

    Objectives To compare the therapeutic effects of nephron-sparing management versus radical nephroureterectomy management for low-grade upper tract urothelial carcinomas.Methods Literatures on the therapy of low-grade upper tract urothelial carcinoma by nephron-sparing management or radical nephroureterectomy management were collected from Pubmed,Springer,ScienceDirect,WANFANG,CNKI and CBM.Meta analysis was conducted for the date about the 5-year survival rate and disease-specific survival rate,according to Cochrane Collaboration.Results A total of 6 studies including 436 patients were identified and analyzed.The results showed no significant differences in the 5-year survival rate(RR =0.95,95 % CI =0.61 ~ 1.48,P > 0.05) and 5 -year disease-specific survival rate(RR =0.83,95%CI =0.42 ~ 1.64,P >0.05).Conclusions A comparison between nephron-sparing management and radical nephroureterectomy management for low-grade upper tract urothelial carcinomas shows no significant differences in terms of 5-year survival rate and 5-year disease-specific survival rate,and has the same therapeutic effect; But the injury of the former is lower,so the clinicians could selectively use nephron-sparing management according to the individual differences of patients.%目的 比较低级别上尿路上皮癌保肾手术与肾输尿管根治术治疗的临床效果.方法 检索Pubmed、Springer、ScieneeDirect、万方数据库、中国期刊全文数据库、中国生物医学文献数据库及配合手工检索全面收集关于保肾手术与肾输尿管根治术治疗低级别上尿路上皮癌的临床对照研究文献,并按有关Cochrane协作网推荐的方法对术后5年生存率及5年肿瘤特异性生存率进行Meta分析.结果 按照纳入标准共纳入6篇文献,436例患者,其中保肾手术组共计177例,肾输尿管根治术组共计259例,分析显示,两组术后5年生存率差异无统计学意义,合并RR值为0.95(95%CI=0.61~1.48,P>0.05);

  10. [A case of Mullerian duct cyst torsion combined with bladder cancer].

    Science.gov (United States)

    Zhu, Fangpei; Ren, Qingling

    2016-06-28

    The diagnosis and treatment of a patient with Mullerian duct cyst torsion combined with bladder cancer were retrospectively analyzed. The patient received an open abdominal operation with right accessory resection plus pelvic adhesion release, and conducted microscopic examination for the bladder under general anesthesia. The results of histopathological examination confirmed the diagnosis of Mullerian duct cyst and papillary urothelial carcinoma at low level. After surgery, the patient received chemotherapy and follow-up observation, and all the indices for the patient were normal and no obvious discomfort. Although the final diagnosis of Mullerian duct cysts is based on histopathological examination, ultrasonography, CT scan and MRI can also detect it. Most of the Mullerian duct cysts are benign, and surgical excision is safe and effective. PMID:27374452

  11. Viable tumor volume: Volume of interest within segmented metastatic lesions, a pilot study of proposed computed tomography response criteria for urothelial cancer

    Energy Technology Data Exchange (ETDEWEB)

    Folio, Les Roger, E-mail: Les.folio@nih.gov [Lead Radiologist for CT, NIH Radiology and Imaging Sciences, 10 Center Drive, Bethesda, MD 20892 (United States); Turkbey, Evrim B., E-mail: evrimbengi@yahoo.com [Johns Hopkins University, Baltimore, MD 21218 (United States); Steinberg, Seth M., E-mail: steinbes@mail.nih.gov [Head, Biostatistics and Data Management Section, Office of the Clinical Director, Center for Cancer Research, National Cancer Institute, 9609 Medical Center Drive, Room 2W334, MSC 9716, Bethesda, MD 20892 (United States); Apolo, Andrea B. [Genitourinary Malignancies Branch, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892 (United States)

    2015-09-15

    Highlights: • It is clear that 2D axial measurements are incomplete assessments in metastatic disease; especially in light of evolving antiangiogenic therapies that can result in tumor necrosis. • Our pilot study demonstrates that taking volumetric density into account can better predict overall survival when compared to RECIST, volumetric size, MASS and Choi. • Although volumetric segmentation and further density analysis may not yet be feasible within routine workflows, the authors believe that technology advances may soon make this possible. - Abstract: Objectives: To evaluate the ability of new computed tomography (CT) response criteria for solid tumors such as urothelial cancer (VTV; viable tumor volume) to predict overall survival (OS) in patients with metastatic bladder cancer treated with cabozantinib. Materials and methods: We compared the relative capabilities of VTV, RECIST, MASS (morphology, attenuation, size, and structure), and Choi criteria, as well as volume measurements, to predict OS using serial follow-up contrast-enhanced CT exams in patients with metastatic urothelial carcinoma. Kaplan–Meier curves and 2-tailed log-rank tests compared OS based on early RECIST 1.1 response against each of the other criteria. A Cox proportional hazards model assessed response at follow-up exams as a time-varying covariate for OS. Results: We assessed 141 lesions in 55CT scans from 17 patients with urothelial metastasis, comparing VTV, RECIST, MASS, and Choi criteria, and volumetric measurements, for response assessment. Median follow-up was 4.5 months, range was 2–14 months. Only the VTV criteria demonstrated a statistical association with OS (p = 0.019; median OS 9.7 vs. 3.5 months). Conclusion: This pilot study suggests that VTV is a promising tool for assessing tumor response and predicting OS, using criteria that incorporate tumor volume and density in patients receiving antiangiogenic therapy for urothelial cancer. Larger studies are warranted to

  12. Stereological estimates of nuclear volume in the prognostic evaluation of primary flat carcinoma in situ of the urinary bladder

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Jacobsen, F

    1991-01-01

    Primary, flat carcinoma in situ of the urinary bladder is rare and its behaviour is unpredictable. The aim of this retrospective study was to obtain base-line data and investigate the prognostic value of unbiased, stereological estimates of the volume-weighted mean nuclear volume, nuclear vv, in 78...... and long duration of invasion-free period (2P greater than 0.20). Nuclear vv in the first biopsy did not differ between patients who survived and those who died from their primary flat carcinoma in situ (2P = 0.07). Dividing the patients on the basis of the group median of the first biopsy showing flat...... carcinoma in situ (nuclear vv = 261 microns 3), the survival was the same in patients with nuclear vv above and below the cut-off point (2P = 0.16). However, the survival curves showed a tendency to differ in the first 2-8 years of observation. Stereological estimates of nuclear vv provide objective...

  13. The response of variant histology bladder cancer to intravesical immunotherapy compared to conventional cancer

    Directory of Open Access Journals (Sweden)

    Ofer Nathan Gofrit

    2016-03-01

    Full Text Available Background: High-grade urothelial carcinomas (UC often show foci of variant differentiation. There is limited information in the literature about the response of these variant urothelial tumors to immunotherapy with Bacillus Calmette Guerin (BCG. We compared the response to treatment with BCG of UC containing glandular, squamous, nested and micropapillary types of differentiation to response of conventional non-muscle invasive high-grade urothelial carcinoma. Methods: A total of 100 patients were diagnosed with variant histology urothelial cancer between June 1995 and December 2013. 41 patients with Ta or T1, confirmed by 2nd look biopsies, received immunotherapy with BCG. Fourteen patients in this group were diagnosed with micropapillary differentiation 13 patients with squamous differentiation, in 9 patients glandular differentiation was seen and in 7 patients nested variant. The control group included 140 patients with conventional high-grade UC. Both groups have been treated and followed similarly. Findings: Patients with variant tumors had similar clinical features to patients with conventional disease including: age, males to female ratio, stage, presence of Tis and median follow-up. Patients with variant tumors had a significantly worse prognosis compared to patients with conventional high-grade UC including: 5-year recurrence-free survival (63.5% Vs. 71.5%, p=0.05, 5-year progression to≥T2 -free survival (60% Vs. 82.5%, p=0.002, 5-year disease-specific survival (73% Vs. 92.5%, p=0.0004 and overall survival (66% Vs. 89.5%, 0.05. Interpretation: A patient with variant bladder cancer treated with intra-vesical immunotherapy has a 27% chance of dying from this disease within 5-years compared to 7.5% for a patient with conventional high-grade UC.

  14. Schistosomiasis-induced squamous cell bladder carcinoma in an HIV-infected patient

    DEFF Research Database (Denmark)

    Marbjerg, Lis Høy; Øvrehus, Anne Lindebo Holm; Johansen, Isik Somuncu

    2015-01-01

    The burden of Schistosoma haematobium-associated bladder cancer is very high in Africa; nevertheless the disease can pose considerable diagnostic challenges in low prevalence countries. We present the case of a 40-year-old HIV co-infected woman, originally from Mozambique, who had persisting...... haematuria for more than a year. Investigations revealed invasive S. haematobium-associated squamous cell bladder cancer. If her origin had been taken into account, the diagnosis might have been made earlier. Awareness of the disease prevalence among HIV co-infected patients from endemic areas and timely...... screening of such patients is important for the early diagnosis of schistosomiasis and related complications, such as S. haematobium-associated squamous cell bladder cancer....

  15. SOX4 expression in bladder carcinoma: clinical aspects and in vitro functional characterization

    DEFF Research Database (Denmark)

    Jensen, Mads Aaboe; Birkenkamp-Demtröder, Karin; Wiuf, Carsten;

    2006-01-01

    The human transcription factor SOX4 was 5-fold up-regulated in bladder tumors compared with normal tissue based on whole-genome expression profiling of 166 clinical bladder tumor samples and 27 normal urothelium samples. Using a SOX4-specific antibody, we found that the cancer cells expressed the...... strongly impaired cell viability and promoted apoptosis. To characterize downstream target genes and SOX4-induced pathways, we used a time-course global expression study of the overexpressed SOX4. Analysis of the microarray data showed 130 novel SOX4-related genes, some involved in signal transduction (MAP...

  16. The time from diagnosis of bladder cancer to radical cystectomy in Polish urological centres – results of CysTiming Poland study

    Science.gov (United States)

    Poletajew, Sławomir; Lisiński, Janusz; Moskal, Karol; Ornat, Jacek; Renk, Kacper; Szlaga, Michał; Tworkiewicz, Jakub; Wojtkowiak, Dominik; Wołyniec, Paweł; Woźniak, Krzysztof; Radziszewski, Piotr

    2014-01-01

    Introduction The aim of the study was to assess the waiting time, from establishing the indications for radical cystectomy to surgery, in patients with urothelial carcinoma of the bladder at different Polish urological centres and to determine its influencing factors. Material and methods Retrospective analysis of data was performed on all consecutive radical cystectomies, performed in 2008–2012, at 10 Polish urological centres. The waiting time of patients from establishing the indications for radical cystectomy to surgery, as well as factors potentially influencing this time, were assessed. University (3), provincial (3) and regional (4) hospitals were defined as the 3rd, 2nd and 1st level referral hospitals, respectively. Results A total of 575 patients qualified for radical cystectomy due to muscle invasive urothelial carcinoma of the bladder (MIBC, 68% of cases) or failure of previous treatment of non–muscle invasive urothelial carcinoma of the bladder (NMIBC, 32%) were included in the analysis. The average time after the establishment of indications to surgery was 73.4 days, with a median of 56 days. In the case of 121 patients (22.1%), the waiting time exceeded 90 days. Significant differences in waiting time were found when the hospital referral levels were taken into consideration. In the 3rd level referral hospitals the median time for cystectomy was 61.5 days (p = 0.035), in the 2nd level referral hospitals – 45 days (p = 0.000) and, in the 1st level referral hospitals – 58 days (p = 0.051). Conclusions The waiting time from establishing the indications for radical cystectomy to surgery for most cases in Poland does not exceed 90 days. PMID:25667748

  17. 30. Knockdown of IGF-IR by Antisense Oligodeoxynucleotide auguments the sensitivity of bladder cancer cells to MMC

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    AND AIM: Transitional cell carcinoma (TCC) of the bladder represents the fifth most prevalent malignancy in Western population, with peak incidence found in males of the 50-to 70- year-old age group. A major problem in the management of bladder cancer is the low sensitivity of a large proportion (approximately 40%) among bladder tumors to chemotherapy and the high risk for recurrence of bladder tumors after transurethral resection. So drug resistance, especially in its multiple type forms, remains a major and difficult problem to resolve in bladder cancer therapy. This phenomenon has often been ascribed to strictly pharmacolo-gic factors, such as the overexpression of multidrug transporters P-glycoprotein, multidrug resistance related protein (MRP), and other variables closely implicated DNA repair and induction/modulation of apoptosis, such as P53 and the Bcl-protein family. Furthermore, it has been recently shown that certain growth factors(IGFs etc) may be involved in the mechanism of drug resistance. Clearly, these findings suggest the design of new strategies that might improve bladder tumor response to chemotherapy. Results have previously shown that human bladder tumor cell lines may be adapted to grow in the complete absence of serum or any other growth supplement and that this can be explained on the basis of autocrine stimulation. The acquirement of autonomous growth capacity was likely to be an important element in the oncogenesis of bladder tumors. Furthermore, criss-cross experiments showed that supernatants stimulated not only proliferation of the autologous cell line of bladder cancer, but also growth of the other bladder cancer cell lines, suggesting the production of common autocrine factors in bladder tumor cells. Some factors or their receptors involved in autocrine loop mechanism of bladder tumor cells have been confirmed, such as IL-6, the epidermal growth factor receptor, IFN-beta, transferrins-like substance etc. But certain factors which may

  18. Qualitative and quantitative histopathology in transitional cell carcinomas of the urinary bladder. An international investigation of intra- and interobserver reproducibility

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Sasaki, M; Fukuzawa, S;

    1994-01-01

    BACKGROUND: Histopathologic, prognosis-related grading of malignancy by means of morphologic examination in transitional cell carcinomas of the urinary bladder (TCC) may be subject to observer variation, resulting in a reduced level of reproducibility. This may confound comparisons of treatment...... agreement on the Bergkvist scheme was poor (kappa = 0.43). On the other hand was the interobserver agreement on invasion high (kappa = 0.75). The intraobserver reproducibility of the quantitative histopathologic variables was excellent in both Japan and Denmark for estimates of nuclear mean volume (r = 0...... density index also showed acceptable intraobserver reproducibility (Kendall's tau > 0.53). CONCLUSIONS: The international, interobserver reproducibility of the quantitative estimators yielded similar results for all histopathologic variables investigated, except for nuclear volume fraction (r = 0...

  19. Porcelain gall bladder in a case of papillary renal cell carcinoma: A rare occurrence and its impact on treatment verdict

    Directory of Open Access Journals (Sweden)

    Raghavan V. Sugi Subramaniam

    2012-01-01

    Full Text Available Multiple primary malignant neoplasms (MPMN is a rare clinical entity in which two primary malignancies are encountered in the same individual which can be synchronous (second primary within 6 months or metachronous (beyond 6 months. We present a case of a 41-year-old male who underwent left partial nephrectomy for suspected renal cell carcinoma and it was confirmed based on histopathology. The gallbladder was normal on contrast-enhanced computed tomogram (CECT abdomen. Follow-up CECT done 1 year later showed no enhancing masses in both kidneys, but incidentally porcelain gallbladder was detected. An elective open cholecystectomy was done for acalculous porcelain gall bladder owing to its premalignant nature. We report this case to highlight the relative risk of second primaries in patients treated for primary malignancies and that relevant premalignant conditions should be managed as possible second malignancies to avoid potential complications.

  20. CLINICAL SIGNIFICANCE OF TELOMERASE ACTIVITY AND PERIPHERAL VENOUS BLOOD CK-20 EXPRESSION IN BLADDER TRANSITIONAL CELL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    钟惟德; 曾广翘; 蔡岳斌; 胡建波; 魏鸿蔼

    2003-01-01

    Objective: The relationship between peripheral blood CK-20 Mrna expression and tissue telomerase activity in bladder transitional cell carcinoma (TCCB) was investigated to evaluate the feasibility of their combined detection in early-stage diagnosis and prognosis estimation of TCCB. Methods: the blood CK-20 was detected by semi-nested RT-PCR and telomerase activity in tumor tissue was examined with silver-stained TRAP reaction. Results: the blood CK-20 expression and tissue telomerase activity in TCCB were 41% and 93% respectively. No statistical significance was detected among pathological grading and clinical staging (P>0.05). Positive correlation was shown between CK-20 expression and telomerase activity with the pathologic grade or clinical stage. Conclusion: combined use of blood CK-20 and tissue telomerase activity detections might be of great importance for clinical diagnosis, treatment and prognosis evaluation.

  1. Survival after primary and deferred cystectomy for stage T1 transitional cell carcinoma of the bladder

    Directory of Open Access Journals (Sweden)

    Bedeir Ali-El-Dein

    2011-01-01

    Conclusions: Cancer-specific survival is statistically comparable for primary and deferred cystectomy in T1 bladder cancer, although there is a non-significant difference in favor of primary cystectomy. In the deferred cystectomy group, the number of TURBTs beyond three is associated with lower survival. Conservative treatment should be adopted for most cases in this category.

  2. Roles of ERβ and GPR30 in Proliferative Response of Human Bladder Cancer Cell to Estrogen

    Directory of Open Access Journals (Sweden)

    Weiren Huang

    2015-01-01

    Full Text Available Bladder cancer belongs to one of the most common cancers and is a leading cause of deaths in our society. Urothelial carcinoma of the bladder (UCB is the main type of this cancer, and the estrogen receptors in UCB remain to be studied. Our experiment aimed to investigate the possible biological effect of 17β-estradiol on human bladder-derived T24 carcinoma cells and to indicate its related mechanisms. T24 cells were treated with various doses of 17β-estradiol, and cell proliferation was detected using MTT assays. 17β-estradiol promoted T24 cell proliferation independent of ERβ/GPR30-regulated EGFR-MAPK pathway, while it inhibited cell growth via GPR30. Furthermore, the expression levels of downstream genes (c-FOS, BCL-2, and CYCLIN D1 were increased by 17β-estradiol and this effect was independently associated with activity of the EGFR-MAPK pathway. The two estrogen receptors might be potential therapeutic targets for the treatment of bladder cancer.

  3. Steroid Hormone Receptor Signals as Prognosticators for Urothelial Tumor

    Directory of Open Access Journals (Sweden)

    Hiroki Ide

    2015-01-01

    Full Text Available There is a substantial amount of preclinical or clinical evidence suggesting that steroid hormone receptor-mediated signals play a critical role in urothelial tumorigenesis and tumor progression. These receptors include androgen receptor, estrogen receptors, glucocorticoid receptor, progesterone receptor, vitamin D receptor, retinoid receptors, peroxisome proliferator-activated receptors, and others including orphan receptors. In particular, studies using urothelial cancer tissue specimens have demonstrated that elevated or reduced expression of these receptors as well as alterations of their upstream or downstream pathways correlates with patient outcomes. This review summarizes and discusses available data suggesting that steroid hormone receptors and related signals serve as biomarkers for urothelial carcinoma and are able to predict tumor recurrence or progression.

  4. Comparison between whole mount tissue preparations and virtual tissue microarray samples for measuring Ki-67 and apoptosis indices in human bladder cancer: A cross-sectional study.

    Science.gov (United States)

    Oshiro, Hisashi; Czerniak, Bogdan A; Sakamaki, Kentaro; Tsuta, Koji; Bondaruk, Jolanta; Keyhani, Afsaneh; Dinney, Colin P; Nagai, Takeshi; Kamat, Ashish M

    2016-08-01

    Recent tissue microarray (TMA)-based studies have shown that cell proliferation- and apoptosis-related biomarkers are associated with clinical outcomes in patients with bladder urothelial carcinoma. However, little is known about the differences in these biomarker measurements between whole mount tissue preparations and TMAs. This study aimed to elucidate the discrepancy in the measurements of Ki-67 indices (KIs) and apoptosis indices (AIs) between whole mount tissue preparations and TMAs of bladder urothelial carcinoma samples.Whole mount tissue preparations for Ki-67 immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick end labeling were made from 30 patients who underwent transurethral resection of bladder urothelial carcinoma. Digital microscopy-assisted virtual TMAs, consisting of 3 small round areas (1 or 0.6 mm in diameter), were generated from the same whole mount tissue preparations. The measurement results in highly reactive areas of biomarkers were compared between the whole mount tissue preparation- and the TMA-based methods. Bland-Altman plot analysis, regression analysis, and Kendall τ were performed to investigate differences in the measurement results, systematic biases, and correlations between biomarkers.Although the Bland-Altman plot analysis demonstrated that almost all the plots were within the limits of agreement, fixed biases were detected in the 1- and 0.6-mm TMAs for the KI (0.181 and 0.222, respectively) and the AI (0.055 and 0.063, respectively). Proportional biases were also detected in the 1- and 0.6-mm TMAs for the AI (P KIs and AIs were observed in whole mount tissue preparations (r = 0.260, P = 0.044) and in the 1 mm TMAs (r = 0.375, P = 0.004); however, no such correlation was observed in the 0.6 mm TMAs.Our study suggests that the measurement results for certain biomarkers of bladder urothelial carcinoma obtained from TMA-based samples can be susceptible to systematic bias, and the lack

  5. Comparison between whole mount tissue preparations and virtual tissue microarray samples for measuring Ki-67 and apoptosis indices in human bladder cancer

    Science.gov (United States)

    Oshiro, Hisashi; Czerniak, Bogdan A.; Sakamaki, Kentaro; Tsuta, Koji; Bondaruk, Jolanta; Keyhani, Afsaneh; Dinney, Colin P.; Nagai, Takeshi; Kamat, Ashish M.

    2016-01-01

    Abstract Recent tissue microarray (TMA)-based studies have shown that cell proliferation- and apoptosis-related biomarkers are associated with clinical outcomes in patients with bladder urothelial carcinoma. However, little is known about the differences in these biomarker measurements between whole mount tissue preparations and TMAs. This study aimed to elucidate the discrepancy in the measurements of Ki-67 indices (KIs) and apoptosis indices (AIs) between whole mount tissue preparations and TMAs of bladder urothelial carcinoma samples. Whole mount tissue preparations for Ki-67 immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick end labeling were made from 30 patients who underwent transurethral resection of bladder urothelial carcinoma. Digital microscopy-assisted virtual TMAs, consisting of 3 small round areas (1 or 0.6 mm in diameter), were generated from the same whole mount tissue preparations. The measurement results in highly reactive areas of biomarkers were compared between the whole mount tissue preparation- and the TMA-based methods. Bland–Altman plot analysis, regression analysis, and Kendall τ were performed to investigate differences in the measurement results, systematic biases, and correlations between biomarkers. Although the Bland–Altman plot analysis demonstrated that almost all the plots were within the limits of agreement, fixed biases were detected in the 1- and 0.6-mm TMAs for the KI (0.181 and 0.222, respectively) and the AI (0.055 and 0.063, respectively). Proportional biases were also detected in the 1- and 0.6-mm TMAs for the AI (P < 0.001 and P < 0.001, respectively). Furthermore, positive correlations between KIs and AIs were observed in whole mount tissue preparations (r = 0.260, P = 0.044) and in the 1 mm TMAs (r = 0.375, P = 0.004); however, no such correlation was observed in the 0.6 mm TMAs. Our study suggests that the measurement results for certain biomarkers of bladder

  6. Image-Guided Radiation Therapy for Muscle-Invasive Carcinoma of the Urinary Bladder with Cone Beam CT Scan: Use of Individualized Internal Target Volumes for a Single Patient

    OpenAIRE

    Saini, Gagan; Aggarwal, Anchal; Srivastava, Roopam; Sharma, Pramod K.; Garg, Madhur; Nangia, Sapna; Chomal, Manish

    2012-01-01

    Introduction While planning radiation therapy (RT) for a carcinoma of the urinary bladder (CaUB), the intra-fractional variation of the urinary bladder (UB) volume due to filling-up needs to be accounted for. This internal target volume (ITV) is obtained by adding internal margins (IM) to the contoured bladder. This study was planned to propose a method of acquiring individualized ITVs for each patient and to verify their reproducibility. Methods One patient with CaUB underwent simulation wit...

  7. Gemicitabine combined with cisplatin for urothelial carcinoma in renal transplant recipients%吉西他滨联合顺铂治疗肾移植术后并发尿路上皮癌的初步探讨

    Institute of Scientific and Technical Information of China (English)

    田野; 肖荆; 朱一辰; 张建; 侯海军; 王志鹏; 郭宇文; 杨培谦

    2014-01-01

    Objective To evaluate the clinical efficacy and side effects of intravenous chemotherapy in renal transplant recipients with urothelial carcinoma .Methods A total of 7 female renal transplant recipients aged 32-67 years with concur‐rent urothelial carcinoma receiving gemcitabine combined cisplatin (GC) scheme .Of all patients ,one received neoadjuvant chemotherapy and others chemotherapy after resection of tumors . The chemotherapy was:gemcitabine 700 -800 mg/m2 , ivgtt ,d1 ,d8 ,d15 ,cisplatine 50‐60 mg/m2 ivgtt ,d2 .Patients received the next chemotherapy cycle after 2 weeks of interval and a total of 2 to 4 cycles ,and altogether 14 cycles of chemotherapy were finished .Results The short‐term toxicity includ‐ed hematology toxicity 100% (7/7) ,digestive discomfort 71% (5/7) ,hair loss 28% (2/7) ,and proteinuria 14% (1/7) .The function of transplant kidney was impaired in one patient after one cycle of chemotherapy .During the follow‐up of 2 to 11 months ,new urothelial carcinoma appeared in one case in the off side of the renal pelvis and one patient died of metastasis in the psoas major .No obvious abnormalities were found in the other 5 patients . Conclusions Renal transplant recipients with muscle invasive urothelial carcinoma can choose GC scheme of intravenous chemotherapy ,but the effect of chemothera‐peutic drugs and the immune inhibitors often leads to severe myelosuppression .The dosage of the chemotherapeutic drugs and immune inhibitors should be reduced and decrease of white blood and platelets should be controlled in time .With careful man‐agement ,patients can tolerate side effects ,but the long‐term effect still needs further observation .%目的:观察肾移植术后并发尿路上皮癌患者行静脉化疗的副作用和临床疗效。方法回顾分析7例肾移植受者并发尿路上皮癌的患者接受吉西他滨联合顺铂方案(GC )静脉化疗的临床资料,患者均为女性,年龄范围32~67岁。肾盂

  8. Pannexin 1 channels play essential roles in urothelial mechanotransduction and intercellular signaling.

    Directory of Open Access Journals (Sweden)

    Hiromitsu Negoro

    Full Text Available Urothelial cells respond to bladder distension with ATP release, and ATP signaling within the bladder and from the bladder to the CNS is essential for proper bladder function. In other cell types, pannexin 1 (Panx1 channels provide a pathway for mechanically-induced ATP efflux and for ATP-induced ATP release through interaction with P2X7 receptors (P2X7Rs. We report that Panx1 and P2X7R are functionally expressed in the bladder mucosa and in immortalized human urothelial cells (TRT-HU1, and participate in urothelial ATP release and signaling. ATP release from isolated rat bladders induced by distention was reduced by the Panx1 channel blocker mefloquine (MFQ and was blunted in mice lacking Panx1 or P2X7R expression. Hypoosmotic shock induced YoPro dye uptake was inhibited by MFQ and the P2X7R blocker A438079 in TRT-HU1 cells, and was also blunted in primary urothelial cells derived from mice lacking Panx1 or P2X7R expression. Rinsing-induced mechanical stimulation of TRT-HU1 cells triggered ATP release, which was reduced by MFQ and potentiated in low divalent cation solution (LDPBS, a condition known to enhance P2X7R activation. ATP signaling evaluated as intercellular Ca2+ wave radius was significantly larger in LDPBS, reduced by MFQ and by apyrase (ATP scavenger. These findings indicate that Panx1 participates in urothelial mechanotransduction and signaling by providing a direct pathway for mechanically-induced ATP release and by functionally interacting with P2X7Rs.

  9. Polarized ATP distribution in urothelial mucosal and serosal space is differentially regulated by stretch and ectonucleotidases.

    Science.gov (United States)

    Yu, Weiqun

    2015-11-15

    Purinergic signaling is a major pathway in regulating bladder function, and mechanical force stimulates urothelial ATP release, which plays an important role in bladder mechanotransduction. Although urothelial ATP release was first reported almost 20 years ago, the way in which release is regulated by mechanical force, and the presence of ATP-converting enzymes in regulating the availability of released ATP is still not well understood. Using a set of custom-designed Ussing chambers with the ability to manipulate mechanical forces applied on the urothelial tissue, we have demonstrated that it is stretch and not hydrostatic pressure that induces urothelial ATP release. The experiments reveal that urothelial ATP release is tightly controlled by stretch speed, magnitude, and direction. We have further shown that stretch-induced urothelial ATP release is insensitive to temperature (4°C). Interestingly, stretch-induced ATP release shows polarized distribution, with the ATP concentration in mucosal chamber (nanomolar level) about 10 times higher than the ATP concentration in serosal chamber (subnanomolar level). Furthermore, we have consistently observed differential ATP lifetime kinetics in the mucosal and serosal chambers, which is consistent with our immunofluorescent localization data, showing that ATP-converting enzymes ENTPD3 and alkaline phosphatase are expressed on urothelial basal surface, but not on the apical membrane. In summary, our data indicate that urothelial ATP release is finely regulated by stretch speed, magnitude, and direction, and extracellular ATP signaling is likely to be differentially regulated by ectonucleotidase, which results in temporally and spatially distinct ATP kinetics in response to mechanical stretch. PMID:26336160

  10. Analysis of prognostic factors in patients with transitional cell carcinoma of the bladder treated with radical cystectomy

    Directory of Open Access Journals (Sweden)

    Antunes Alberto A.

    2006-01-01

    Full Text Available OBJECTIVE: To analyze the results of the treatment of transitional cell carcinoma (TCC of the bladder with radical cystectomy and determine which prognostic factors can be utilized as disease-free survival and cancer-specific survival independent variables. MATERIALS AND METHODS: Medical records of 113 patients submitted to radical cystectomy and bilateral iliac lymphadenectomy between 1993 and 2005 were reviewed. The risk factors analyzed were age, sex, pathological stage, tumor grade, presence of carcinoma in situ and the presence of lymph nodes involvement. RESULTS: After a mean follow-up of 31.7 ? 28.5 months, 46 patients (40.7% presented recurrence and 24 patients (21.2% died due to cancer. Only pathological stage and the lymph nodes involvement became independent variables for recurrence and survival. Patients with T4 stage presented 9.6 times the risk of recurrence of the disease when compared with stage T0 patients (p = 0.010 and the patients with lymph node involvement presented 2.5 times the risk of recurrence (p = 0.047 and 3.1 times the risk of death (p = 0.022 when compared to patients without lymph nodes involvement. CONCLUSIONS: Pathological stage and the involvement of lymph nodes represented more important prognostic variables, and in the presence of advanced stage tumors (T3/T4 and involvement of lymph nodes, the institution of adjuvant treatment should be considered.

  11. Gold Nanotheranostics: Photothermal Therapy and Imaging of Mucin 7 Conjugated Antibody Nanoparticles for Urothelial Cancer

    OpenAIRE

    Chieh Hsiao Chen; Yi-Jhen Wu; Jia-Jin Chen

    2015-01-01

    Objective. To kill urothelial cancer cells while preserving healthy cells, this study used photothermal therapy (PTT). PTT techniques target urothelial cancer cells using gold nanoparticles (GNPs) and a green light laser. Materials and Methods. The GNPs were conjugated with anti-Mucin 7 antibodies, which acted as a probe for targeting tumor cells. Conjugated GNPs were exposed to a green light laser (532 nm) with sufficient thermal energy to kill the transitional cell carcinomas (TCCs). Result...

  12. Management of Bladder Cancer following Solid Organ Transplantation

    Directory of Open Access Journals (Sweden)

    Jeffrey J. Tomaszewski

    2011-01-01

    Full Text Available Objective. Present our experience managing bladder cancer following liver and renal transplantation. Methods. Single institution retrospective review of patients diagnosed with bladder urothelial carcinoma (BUC following solid organ transplantation between January 1992 and December 2007. Results. Of the 2,925 renal and 2,761 liver transplant recipients reviewed, we identified eleven patients (0.2% following transplant diagnosed with BUC. Two patients with low grade T1 TCC were managed by TURBT. Three patients with CIS and one patient with T1 low grade BUC were treated by TURBT and adjuvant BCG. All four are alive and free of recurrence at a mean follow-up of 51 ± 22 months. One patient with T1 high grade BUC underwent radical cystectomy and remains disease free with a follow-up of 98 months. Muscle invasive TCC was diagnosed in four patients at a median of 3.6 years following transplantation. Two patients are recurrence free at 24 and 36 months following radical cystectomy. Urinary diversion and palliative XRT were performed in one patient with un-resectable disease. Conclusions. Bladder cancer is uncommon following renal and liver transplantation, but it can be managed successfully with local and/or extirpative therapy. The use of intravesical BCG is possible in select immunosuppressed patients.

  13. From Clinical Trials to the Front Line: Vinflunine for Treatment of Urothelial Cell Carcinoma at the National Cancer Institute of Naples

    Science.gov (United States)

    Facchini, Gaetano; Della Pepa, Chiara; Cavaliere, Carla; Cecere, Sabrina C.; Di Napoli, Marilena; D'Aniello, Carmine; Crispo, Anna; Iovane, Gelsomina; Maiolino, Piera; Tramontano, Teresa; Piscitelli, Raffaele; Pisconti, Salvatore; Montella, Maurizio; Berretta, Massimiliano; Sorrentino, Domenico; Perdonà, Sisto; Pignata, Sandro

    2016-01-01

    Background: The efficacy of Vinflunine, after failure of platinum-based chemotherapy in patients with metastatic or recurrent Transitional Cell Cancer of the Urothelial Tract, TCCU, has been demonstrated in an international, randomized, phase III trial comparing Vinflunine plus Best Supportive Care, BSC, with BSC alone. On the basis of that study vinflunine has been approved by the European Medicine Association, EMA, for treatment of TCCU patients after failure of a platinum treatment. However, since data in clinical trials often differ from routine clinical practice due to unselected population and less strict monitoring, “real life” experiences are very helpful to verify the efficacy of a new therapy. Methods: This was a spontaneous, observational, retrospective study involving 43 patients with metastatic TCCU treated with vinflunine at our cancer center, data about demographics, disease characteristics, and previous treatments were collected and outcome and toxicities of vinflunine were analyzed. Results: 41 of 43 patients were eligible for RR analysis, the Overall RR was 12%, the Disease Control Rate was 29%; when including only patients treated in II line the DCR rose to 33%; the median PFS and the median OS were 2.2 and 6.9 months, respectively. Conclusion: Our findings were consistent with the outcome data emerged in the phase III randomized trial and in the other observational studies conducted all around Europe in the last 2–3 years. This experience supports the use of vinflunine in patients with advanced TTCU as effective and manageable antineoplastic drug. PMID:27199753

  14. Transitional cell carcinoma of urinary bladder with metastasis in lumbar vertebrae and spinal cord compression in an ocelot(Leopardus pardalis)

    OpenAIRE

    Karen Y.R. Nakagaki; Pâmela A. Lima; Kiyoko U. Utiumi; Marco A.M. Pires; Rosana Zanatta; Fabiana M Boabaid; Edson M. Colodel; Djeison L. Raymundo

    2015-01-01

    This paper reports a case of nonpapillary and infiltrative transitional cell carcinoma (TCC) of the urinary bladder with metastasis of lumbar vertebrae and spinal cord compression in an adult female ocelot (Leopardus pardalis), from the Mato Grosso state, Brazil. The ocelot had pelvic limb paralysis and skin ulcers in the posterior region of the body and was submitted to euthanasia procedure. At necropsy was observed a multilobulated and irregular shaped, yellowish to white nodule in the urin...

  15. Urokinase-type plasminogen activator receptor (uPAR) expression is associated with T-stage and survival in urothelial carcinoma of the bladder

    DEFF Research Database (Denmark)

    Dohn, Line Hammer; Illemann, Martin; Høyer-Hansen, Gunilla;

    2015-01-01

    myofibroblasts at the invasive front and tumor core, respectively. Statistical analyses were performed to evaluate the association of uPAR localization and score with clinicopathologic covariates and survival. RESULTS: uPAR positivity was seen in 122/137 (89%) and 118/149 (74%) of the neoplasias at the invasive...... invasive tumors that could benefit from additional chemotherapy or more intensive follow-up after cystectomy....

  16. G9a Inhibition Induces Autophagic Cell Death via AMPK/mTOR Pathway in Bladder Transitional Cell Carcinoma.

    Directory of Open Access Journals (Sweden)

    Feng Li

    Full Text Available G9a has been reported to highly express in bladder transitional cell carcinoma (TCC and G9a inhibition significantly attenuates cell proliferation, but the underlying mechanism is not fully understood. The present study aimed at examining the potential role of autophagy in the anti-proliferation effect of G9a inhibition on TCC T24 and UMUC-3 cell lines in vitro. We found that both pharmaceutical and genetical G9a inhibition significantly attenuated cell proliferation by MTT assay, Brdu incorporation assay and colony formation assay. G9a inhibition induced autophagy like morphology as determined by transmission electron microscope and LC-3 fluorescence assay. In addition, autophagy flux was induced by G9a inhibition in TCC cells, as determined by p62 turnover assay and LC-3 turnover assay. The autophagy induced positively contributed to the inhibition of cell proliferation because the growth attenuation capacity of G9a inhibition was reversed by autophagy inhibitors 3-MA. Mechanically, AMPK/mTOR pathway was identified to be involved in the regulation of G9a inhibition induced autophagy. Intensively activating mTOR by Rheb overexpression attenuated autophagy and autophagic cell death induced by G9a inhibition. In addition, pre-inhibiting AMPK by Compound C attenuated autophagy together with the anti-proliferation effect induced by G9a inhibition while pre-activating AMPK by AICAR enhanced them. In conclusion, our results indicate that G9a inhibition induces autophagy through activating AMPK/mTOR pathway and the autophagy induced positively contributes to the inhibition of cell proliferation in TCC cells. These findings shed some light on the functional role of G9a in cell metabolism and suggest that G9a might be a therapeutic target in bladder TCC in the future.

  17. VALIDATION OF NEUROTENSIN TETRA-BRANCHED PEPTIDES AS TUMOR TARGETING AGENTS IN PANCREAS, COLON AND BLADDER CARCINOMA

    Directory of Open Access Journals (Sweden)

    N. Ravenni

    2012-05-01

    Full Text Available The identification of new tumor targeting agents, which might allow either cancer cell tracing or ther- apy, is a crucial issue in cancer research. Membrane receptors for endogenous peptides such as neu- rotensin, somatostatin, bombesin and many others are over-expressed in different human cancers and could therefore be targeted as tumor-specific antigens. In the meantime the extremely short half-life of pep- tides impeded their development for effective pep- tide-based tumor targeting strategies. We synthesized tetra-branched neurotensin peptides (NT4, which ensure extremely long half-life main- taining peptide specificity and increasing avidity through multimeric binding. Moreover this bio-syn- thetical strategy allows a considerable modularity of peptides through the conjugation of different func- tional unit, such as fluorophore, radioactive moieties or chemotherapeutic drugs. Aim of our studies is to validate NT4 for cancer cell tracing in different human tumors. In this view we use fluorophore-conjugated NT4 to discriminate be- tween tumor and healthy tissue obtained by surgical samples from pancreas, colon and bladder carcinoma. Peptide binding on tumor and healthy biopsies was measured in each patient by quantitative analysis of confocal microscopy images. These results show a considerable difference in fluorescence emission be- tween healthy and tumor samples in colon, pancreas and bladder cancer, opening the way to the develop- ment of NT4 as selective diagnostic tools for these pathologies. Moreover our peptides can be conju- gated with different chemotherapeutic moieties in order to allow the selective killing of tumor cells.

  18. Transitional cell carcinoma of urinary bladder with metastasis in lumbar vertebrae and spinal cord compression in an ocelot(Leopardus pardalis

    Directory of Open Access Journals (Sweden)

    Karen Y.R. Nakagaki

    2015-01-01

    Full Text Available This paper reports a case of nonpapillary and infiltrative transitional cell carcinoma (TCC of the urinary bladder with metastasis of lumbar vertebrae and spinal cord compression in an adult female ocelot (Leopardus pardalis, from the Mato Grosso state, Brazil. The ocelot had pelvic limb paralysis and skin ulcers in the posterior region of the body and was submitted to euthanasia procedure. At necropsy was observed a multilobulated and irregular shaped, yellowish to white nodule in the urinary bladder. The nodule had a soft consistency and arised from the mucosa of the urinary bladder extending throughout the muscular layers and the serosa. Nodules of similar appearance infiltrating the vertebral column the at L6 and L7 vertebrae with corresponding spinal canal invasion were also observed. The histological evaluation showed epithelial neoplastic proliferation in the urinary bladder with characteristics of nonpapillary and infiltrative TCC, with positive immunohistochemical staining for pancytokeratin, and strong immunostaining for cytokeratin of low molecular weight, and weak or absent labeling for high molecular weight cytokeratin. This is the first report of TCC of urinary bladder in ocelot in Brazil.

  19. Small Cell Carcinoma of the Urinary Bladder: A Retrospective, Multicenter Rare Cancer Network Study of 107 Patients

    Energy Technology Data Exchange (ETDEWEB)

    Pasquier, David, E-mail: d-pasquier@o-lambret.fr [Academic Radiation Oncology Department, Centre Oscar Lambret, Lille (France); Barney, Brandon [Mayo Clinic, Rochester, Minnesota (United States); Sundar, Santhanam [Department of Oncology, Nottingham University Hospitals National Health Service Trust, Nottingham (United Kingdom); Poortmans, Philip [Department of Radiation Oncology, Radboud university medical center, Nijmegen (Netherlands); Villa, Salvador [Radiation Oncology, Catalan Institute of Oncology, H. Universitari Germans Trías, Badalona, Barcelona (Spain); Nasrallah, Haitam [Division of Oncology, Rambam Health Care Campus and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa (Israel); Boujelbene, Noureddine [Department of Radiation Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne (Switzerland); Ghadjar, Pirus [Department of Radiation Oncology, Bern University Hospital, Bern (Switzerland); Lassen-Ramshad, Yasmin [Department of Oncology, Aarhus University Hospital, Aarhus (Denmark); Senkus, Elżbieta [Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk (Poland); Oar, Andrew [Genesis Cancer Care, Southport (Australia); Roelandts, Martine [Institut Jules Bordet, Brussels (Belgium); Amichetti, Maurizio [Provincial Agency for Proton Therapy, Trento (Italy); Vees, Hansjoerg [Department of Radiation Oncology, Hopital de Sion, Sion (Switzerland); Zilli, Thomas [Department of Radiation Oncology, Geneva University Hospital, Geneva (Switzerland); Ozsahin, Mahmut [Department of Radiation Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne (Switzerland)

    2015-07-15

    Purpose: Small cell carcinomas of the bladder (SCCB) account for fewer than 1% of all urinary bladder tumors. There is no consensus regarding the optimal treatment for SCCB. Methods and Materials: Fifteen academic Rare Cancer Network medical centers contributed SCCB cases. The eligibility criteria were as follows: pure or mixed SCC; local, locoregional, and metastatic stages; and age ≥18 years. The overall survival (OS) and disease-free survival (DFS) were calculated from the date of diagnosis according to the Kaplan-Meier method. The log-rank and Wilcoxon tests were used to analyze survival as functions of clinical and therapeutic factors. Results: The study included 107 patients (mean [±standard deviation, SD] age, 69.6 [±10.6] years; mean follow-up time, 4.4 years) with primary bladder SCC, with 66% of these patients having pure SCC. Seventy-two percent and 12% of the patients presented with T2-4N0M0 and T2-4N1-3M0 stages, respectively, and 16% presented with synchronous metastases. The most frequent curative treatments were radical surgery and chemotherapy, sequential chemotherapy and radiation therapy, and radical surgery alone. The median (interquartile range, IQR) OS and DFS times were 12.9 months (IQR, 7-32 months) and 9 months (IQR, 5-23 months), respectively. The metastatic, T2-4N0M0, and T2-4N1-3M0 groups differed significantly (P=.001) in terms of median OS and DFS. In a multivariate analysis, impaired creatinine clearance (OS and DFS), clinical stage (OS and DFS), a Karnofsky performance status <80 (OS), and pure SCC histology (OS) were independent and significant adverse prognostic factors. In the patients with nonmetastatic disease, the type of treatment (ie radical surgery with or without adjuvant chemotherapy vs conservative treatment) did not significantly influence OS or DFS (P=.7). Conclusions: The prognosis for SCCB remains poor. The finding that radical cystectomy did not influence DFS or OS in the patients with nonmetastatic disease

  20. Small Cell Carcinoma of the Urinary Bladder: A Retrospective, Multicenter Rare Cancer Network Study of 107 Patients

    International Nuclear Information System (INIS)

    Purpose: Small cell carcinomas of the bladder (SCCB) account for fewer than 1% of all urinary bladder tumors. There is no consensus regarding the optimal treatment for SCCB. Methods and Materials: Fifteen academic Rare Cancer Network medical centers contributed SCCB cases. The eligibility criteria were as follows: pure or mixed SCC; local, locoregional, and metastatic stages; and age ≥18 years. The overall survival (OS) and disease-free survival (DFS) were calculated from the date of diagnosis according to the Kaplan-Meier method. The log-rank and Wilcoxon tests were used to analyze survival as functions of clinical and therapeutic factors. Results: The study included 107 patients (mean [±standard deviation, SD] age, 69.6 [±10.6] years; mean follow-up time, 4.4 years) with primary bladder SCC, with 66% of these patients having pure SCC. Seventy-two percent and 12% of the patients presented with T2-4N0M0 and T2-4N1-3M0 stages, respectively, and 16% presented with synchronous metastases. The most frequent curative treatments were radical surgery and chemotherapy, sequential chemotherapy and radiation therapy, and radical surgery alone. The median (interquartile range, IQR) OS and DFS times were 12.9 months (IQR, 7-32 months) and 9 months (IQR, 5-23 months), respectively. The metastatic, T2-4N0M0, and T2-4N1-3M0 groups differed significantly (P=.001) in terms of median OS and DFS. In a multivariate analysis, impaired creatinine clearance (OS and DFS), clinical stage (OS and DFS), a Karnofsky performance status <80 (OS), and pure SCC histology (OS) were independent and significant adverse prognostic factors. In the patients with nonmetastatic disease, the type of treatment (ie radical surgery with or without adjuvant chemotherapy vs conservative treatment) did not significantly influence OS or DFS (P=.7). Conclusions: The prognosis for SCCB remains poor. The finding that radical cystectomy did not influence DFS or OS in the patients with nonmetastatic disease

  1. Downregulation of glutathione S-transferase M1 protein in N-butyl-N-(4-hydroxybutyl)nitrosamine-induced mouse bladder carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Chuang, Jing-Jing [Department of Microbiology, Immunology and Biopharmaceuticals, College of Life Sciences, National Chiayi University, Chiayi, Taiwan (China); Dai, Yuan-Chang [Department of Pathology, Chiayi Christian Hospital, Chiayi, Taiwan (China); Lin, Yung-Lun; Chen, Yang-Yi; Lin, Wei-Han [Department of Microbiology, Immunology and Biopharmaceuticals, College of Life Sciences, National Chiayi University, Chiayi, Taiwan (China); Chan, Hong-Lin [Institute of Bioinformatics and Structural Biology and Department of Medical Sciences, National Tsing Hua University, Hsinchu, Taiwan (China); Liu, Yi-Wen, E-mail: ywlss@mail.ncyu.edu.tw [Department of Microbiology, Immunology and Biopharmaceuticals, College of Life Sciences, National Chiayi University, Chiayi, Taiwan (China)

    2014-09-15

    Bladder cancer is highly recurrent following specific transurethral resection and intravesical chemotherapy, which has prompted continuing efforts to develop novel therapeutic agents and early-stage diagnostic tools. Specific changes in protein expression can provide a diagnostic marker. In our present study, we investigated changes in protein expression during urothelial carcinogenesis. The carcinogen BBN was used to induce mouse bladder tumor formation. Mouse bladder mucosa proteins were collected and analyzed by 2D electrophoresis from 6 to 20 weeks after commencing continuous BBN treatment. By histological examination, the connective layer of the submucosa showed gradual thickening and the number of submucosal capillaries gradually increased after BBN treatment. At 12-weeks after the start of BBN treatment, the urothelia became moderately dysplastic and tumors arose after 20-weeks of treatment. These induced bladder lesions included carcinoma in situ and connective tissue invasive cancer. In protein 2D analysis, the sequentially downregulated proteins from 6 to 20 weeks included GSTM1, L-lactate dehydrogenase B chain, keratin 8, keratin 18 and major urinary proteins 2 and 11/8. In contrast, the sequentially upregulated proteins identified were GSTO1, keratin 15 and myosin light polypeptide 6. Western blotting confirmed that GSTM1 and NQO-1 were decreased, while GSTO1 and Sp1 were increased, after BBN treatment. In human bladder cancer cells, 5-aza-2′-deoxycytidine increased the GSTM1 mRNA and protein expression. These data suggest that the downregulation of GSTM1 in the urothelia is a biomarker of bladder carcinogenesis and that this may be mediated by DNA CpG methylation. - Highlights: • GSTM1 and NQO-1 proteins decreased in the mouse bladder mucosa after BBN treatment. • BBN induced GSTO1 and Sp1 protein expression in the mouse bladder mucosa. • 5-Aza-2′-deoxycytidine increased GSTM1 mRNA and protein in human bladder cancer cell. • GSTM1

  2. Gall bladder carcinoma: Aggressive malignancy with protean loco-regional and distant spread

    OpenAIRE

    Dwivedi, Amit Nandan Dhar; Jain, Shivi; Dixit, Ruhi

    2015-01-01

    The most common malignancy of biliary tract is gallbladder cancer (GBC) which is the third most common cancer in gastrointestinal tract. It is a lethal disease for most patients in spite of growing awareness and improved diagnostic techniques. GBC has a very poor prognosis and the 5 year survival rate is < 10%. Although etiology of the carcinoma of the gallbladder is still obscure, various factors have been implicated, cholelithiasis being the most frequent. The incidence of GBC worldwide is ...

  3. Quantitative interrelations of Lewis antigens in normal mucosa and transitional cell bladder carcinomas.

    OpenAIRE

    Limas, C

    1991-01-01

    The factors regulating the expression of the Lewis blood group related antigens in tissues have yet to be clarified. In an attempt to resolve some of the existing controversies the quantitative interrelationship of the Le(a), Le(b), X and Y antigens in normal urothelium and transitional cell carcinomas (TCC) was studied using biopsy specimens derived from 22 patients whose ABO and Lewis red blood cell phenotype was known. A quantitative scale was devised to encompass both the extent and inten...

  4. Expression of KAI1/CD82 and MRP-1/CD9 in Transitional Cell Carcinoma of Bladder

    Institute of Scientific and Technical Information of China (English)

    AI Xing; ZHANG Xu; WU Zhun; MA Xin; JU Zhenghua; WANG Baojun; SHI Taoping

    2007-01-01

    The expression of KAI1/CD82 and MRP-1/CD9 in transitional cell carcinoma of bladder (TCCB) and its clinical significance were investigated. Immunohistochemistry was used to detect KAI1/CD82 and MRP-1/CD9 protein expression in 52 TCCB specimens. Correlation between the expression of KAI1/CD82 and MRP-1/CD9 to clinicopathologic factors was statistically analyzed. The results showed that the positive rate of KAI1/CD82 and MRP-1/CD9 in TCCB was 50% and 61.5%, respectively. The MRP-1/CD9 and KAI1/CD82 expression was significantly associated with grade of TCCB (P<0.05), but no correlation was found between MRP-1/CD9 or KAI1/CD82 expression and clinical stage of TCCB (P>0.05). The expression level of MRP-1/CD9 and KAI1/CD82 in recurrent TCCB samples was lower than that in non-recurrent samples (P<0.05). Meanwhile, the correlation between the KAI1/CD82 expression and MRP-1/CD9 expression was statistically significant (r=0.316, P<0.05). It was concluded that KAI1/CD82 and MRP-1/CD9 expression may be important prognostic indicators and potentially useful for assessing the biological behavior of TCCB.

  5. Effect of CD44 gene polymorphisms on risk of transitional cell carcinoma of the urinary bladder in Taiwan.

    Science.gov (United States)

    Weng, Wei-Chun; Huang, Yu-Hui; Yang, Shun-Fa; Wang, Shian-Shiang; Kuo, Wu-Hsien; Hsueh, Chao-Wen; Huang, Ching-Hsuan; Chou, Ying-Erh

    2016-05-01

    The carcinogenesis of transitional cell carcinoma (TCC) of the urinary bladder involves etiological factors, such as ethnicity, the environment, genetics, and diet. Cluster of differentiation (CD44), a well-known tumor marker, plays a crucial role in regulating tumor cell differentiation and metastasis. This study investigated the effect of CD44 single nucleotide polymorphisms (SNPs) on TCC risk and clinicopathological characteristics. Five SNPs of CD44 were analyzed through real-time polymerase chain reaction in 275 patients with TCC and 275 participants without cancer. In this study, we observed that CD44 rs187115 polymorphism carriers with the genotype of at least one G were associated with TCC risk. Furthermore, TCC patients who carried at least one G allele at CD44 rs187115 had a higher stage risk than did patients carrying the wild-type allele (p TCC. In conclusion, our results suggest that CD44 SNPs influence the risk of TCC. Patients with CD44 rs187115 variant genotypes (AG + GG) exhibited a higher risk of TCC; these patients may possess chemoresistance to developing late-stage TCC compared with those with the wild-type genotype. The CD44 rs187115 SNP may predict poor prognosis in patients with TCC.

  6. Theophylline controllable RNAi-based genetic switches regulate expression of lncRNA TINCR and malignant phenotypes in bladder cancer cells

    Science.gov (United States)

    Chen, Zhicong; Liu, Yuchen; He, Anbang; Li, Jianfa; Chen, Mingwei; Zhan, Yonghao; Lin, Junhao; Zhuang, Chengle; Liu, Li; Zhao, Guoping; Huang, Weiren; Cai, Zhiming

    2016-09-01

    TINCR is a well-known lncRNA which acts as a master regulator in somatic differentiation development. However, it is still unclear whether TINCR is also involved in caner occurrence and progression. In this study, we observed that TINCR was up-regulated in bladder cancer tissues and cells and contributed to oncogenesis and cancer progression. Silencing TINCR expression inhibited cell proliferation and promoted apoptosis in vitro, indicating that TINCR may be the potential therapeutic target for treating bladder urothelial carcinoma. Thus we used the synthetic biology approach to create theophylline controllable RNAi-based genetic switches which silenced TINCR in a dosage-dependent manner. Both RNAi-OFF and ON switches can be used to quantitatively control the expression of TINCR in bladder cancer to suppress the progression of bladder cancer. These findings suggest that lncRNA-TINCR could promote bladder cancer development and progression and artificial control of its expression through inducible RNAi may represent a new kind of therapeutic strategy for treating human bladder cancer.

  7. Genomic aberrations are rare in urothelial neoplasms of patients 19 years or younger.

    Science.gov (United States)

    Wild, P J; Giedl, J; Stoehr, R; Junker, K; Boehm, S; van Oers, J M M; Zwarthoff, E C; Blaszyk, H; Fine, S W; Humphrey, P A; Dehner, L P; Amin, M B; Epstein, J I; Hartmann, A

    2007-01-01

    Urothelial neoplasms in patients 19 years of age or younger are rare, and the data regarding clinical outcome are conflicting. Molecular data are not available. Urothelial tumours from 14 patients aged 4 to 19 years were analysed, including FGFR3 and TP53 mutation screening, comparative genomic hybridization (CGH), UroVysion FISH analysis, polymerase chain reaction for human papillomavirus (HPV), microsatellite analysis using the NIH consensus panel for detection of microsatellite instability (MSI) and six markers for loss of heterozygosity on chromosome arms 9p, 9q, and 17p and immunohistochemistry for TP53, Ki-67, CK20 and the mismatch repair proteins (MRPs) hMSH2, hMLH1, and hMSH6. Based on the 2004 WHO classification, one urothelial papilloma, seven papillary urothelial neoplasms of low malignant potential (PUNLMPs), five low-grade, and one high-grade papillary urothelial carcinoma were included. No multifocal tumours were found and recurrence was seen in only one patient with a urothelial papilloma. All patients were alive with no evidence of disease at a median follow-up of 3.0 years. We found no mutations in FGFR3, deletions of chromosome arms 9p, 9q or 17p, MSI or MRP loss, or HPV positivity in any of the patients. Three cases showed chromosome alterations in CGH analyses, urothelial dedifferentiation with CK20 overexpression, or aneuploidy, and one TP53 mutation with TP53 overexpression was found. Urothelial neoplasms in people younger than 20 years are predominantly low grade and are associated with a favourable clinical outcome. Genetic alterations frequently seen in older adults are extremely rare in young patients. Urothelial neoplasms in children and young adults appear to be biologically distinct and lack genetic instability in most cases. PMID:17072825

  8. Enhancement of Urinary Bladder Carcinogenesis by the Role of Chronic Bacterial Infection-induced Inflammation (Imunnohistochemical and Biochemical studies

    Directory of Open Access Journals (Sweden)

    Gabri MS*, Ashmawy AM**, Ibrahim MA*, Hosny RM

    2012-07-01

    Full Text Available Background: Bacterial infections traditionally have not been considered major causes of cancer. Recently, however, bacteria have been linked to cancer by two mechanisms: induction of chronic inflammation and production of carcinogenic bacterial metabolites. The most specific example of the inflammatory mechanism of carcinogenesis is Escherichia coli infection. E. coli has been epidemiologically linked to urothelial carcinoma of the urinary bladder by its propensity to cause lifelong inflammation. This inflammation is in turn thought to cause cancer by inducing cell proliferation and production of mutagenic free radicals and N-nitroso compounds.Material and methods: After each 3, 6 and 9 months of daily oral administration of dibutyl amine (DBA plus sodium nitrate (nitrosamine precursors in drinking water, curcuma in grinding diet and bladder injection with E. coli, rats were sacrificed. The excited bladder were dissected, processed and stained with H&E and anti-Ki67 immunohistochemical stains. This was followed by Elisa for caspse-3 and statistical analysis.Results: The current results indicated that E. coli infection in the bladder tissues increases the carcinogenic ability of nitrosamine precursors through caused marked alteration in the form hyperplastic, dysplastic and metaplastic urothelium. Also, there was a statistically significant increase in ki67 immunoreactivity in urothelium. However, a statistically significant decrease in the concentration of caspase-3 in bladder tissue consequently caused the process of carcinogenesis. All these changes were less marked after curcuma treatment when compared with the group that not treated with curcuma. Conclusion: Bacterial infection of the urinary bladder may play a major additive and possible role in bladder carcinogenesis. Rhizome of curcuma may have a protective action during induction of urinary bladder tumors.

  9. Study of false positives in 5-ALA induced photodynamic diagnosis of bladder carcinoma

    Science.gov (United States)

    Draga, Ronald O. P.; Grimbergen, Matthijs C. M.; Kok, Esther T.; Jonges, Trudy G. N.; Bosch, J. L. H. R.

    2009-02-01

    Photodynamic diagnosis (PDD) is a technique that enhances the detection of tumors during cystoscopy using a photosensitizer which accumulates primarily in cancerous cells and will fluoresce when illuminated by violetblue light. A disadvantage of PDD is the relatively low specificity. In this retrospective study we aimed to identify predictors for false positive findings in PDD. Factors such as gender, age, recent transurethral resection of bladder tumors (TURBT), previous intravesical therapy (IVT) and urinary tract infections (UTIs) were examined for association with the false positive rates in a multivariate analysis. Data of 366 procedures and 200 patients were collected. Patients were instilled with 5-aminolevulinic acid (5-ALA) intravesically and 1253 biopsies were taken from tumors and suspicious lesions. Female gender and TURBT are independent predictors of false positives in PDD. However, previous intravesical therapy with Bacille Calmette-Guérin is also an important predictor of false positives. The false positive rate decreases during the first 9-12 weeks after the latest TURBT and the latest intravesical chemotherapy. Although shortly after IVT and TURBT false positives increase, PDD improves the diagnostic sensitivity and results in more adequate treatment strategies in a significant number of patients.

  10. Combined effect of tumor necrosis factor-alpha and ionizing radiation on the induction of apoptosis in 5637 bladder carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Baierlein, S.A.; Distel, L.; Sieber, R.; Weiss, C.; Roedel, C.; Sauer, R.; Roedel, F. [Dept. of Radiation Oncology, Friedrich Alexander Univ. Erlangen-Nuremberg (Germany)

    2006-08-15

    Background and Purpose: Apoptosis can be induced by distinct but overlapping pathways. Ionizing radiation induces apoptosis by an ''intrinsic'', mitochondria-dependent pathway. Ligation of tumor necrosis factor-(TNF-){alpha}, FAS (CD95) or TRAIL receptors are typical representatives of an extrinsic, death-receptor-mediated pathway. In this study the effect of irradiation, treatment with the cytokine TNF-{alpha}, or a combination of both on the induction of apoptosis and clonogenic survival of bladder carcinoma cells was investigated. Material and Methods: 5637 bladder carcinoma cells were treated with different concentrations of recombinant TNF-{alpha} (0-10 ng/ml), irradiated with single doses ranging from 0.5 to 10 Gy, or a combination of both modalities. Apoptotic cells were quantified by the TUNEL assay up to 96 h following treatment, clonogenic cell survival by a clonogenic assay. Synergistic effects of both modalities were evaluated using isobolographic analysis. Results: Irradiation of 5637 carcinoma cells resulted in a discontinuous dose dependence of the apoptotic fraction with a pronounced increase in the range of 0-2 Gy and a slighter increase at 2-10 Gy. The percentage of apoptotic carcinoma cells also increased continuously after treatment with lower concentrations of TNF-{alpha} reaching a plateau at concentrations of 5.0-10.0 ng/ml. Isobolographic analysis revealed a supraadditive interrelationship between irradiation and TNF-{alpha} in the range between 0.005 and 0.5 ng/ml, and an additive effect for TNF-{alpha} concentrations > 0.5 ng/ml. The additive effects were confirmed in clonogenic survival assays with reduced survival fractions following combined TNF-{alpha} administration and irradiation. Conclusion: The combination of two apoptosis-inducing modalities resulted in a synergistic effect on the induction of apoptosis in 5637 bladder carcinoma cells. Although a radiosensitizing effect still has to be proven in animal models

  11. Fatores de risco em carcinomas de células transicionais da bexiga: risk factors Transitional cell carcinoma of the bladder

    Directory of Open Access Journals (Sweden)

    Ricardo Brianezi Tiraboschi

    2002-01-01

    Full Text Available OBJETIVO: Investigar alguns dados epidemiológicos do câncer vesical bem como fatores de risco. MÉTODOS: Foram selecionados 125 pacientes atendidos no período 1980-2002, com idade média de 63,6±11,3 anos, sendo 97 (77,6% homens e 28 (22,4% mulheres. As proporções de tumores G1, G2 e G3 foram: 48%, 35,2% e 16,8%. As proporções dos estádios da lesão primária foram: pTa-1 - 85 ( 68% e pT2-4 - 40 ( 32%. Entre os pacientes com tumores superficiais houve recidiva em 41 (48,2%. RESULTADOS: O grau da lesão primária mostrou relação com o estádio T (pOBJECTIVE: To analyse some epidemiological data of patients with transitional cell carcinoma of the bladder (TCC and the predictive value of conventional risk factors. METHODS: From 1980 to 2002, 125 patients were treated at our hospital and selected retrospectively for this study. The series mean age was 63,6±11,3 years, being 77.6% males and 22.4% females. The proportions of G!, G2 and G3 TCC were: 48%, 35.2% and 16.8%. The T stage was: pTa-1 - 85 (68% and pT2-4 - 40 (32%. Superficial tumors were treated by TUR alone or plus BCG (>G1, and the invasives ones by radical cystectomy. The vesical reccurence rate of superficial TCC was 48.2%. RESULTS: TCC grade showed a positive association with T stage (p<0.0001 and patient survival (p<0.0001, but not with local bladder reccurence of superficial tumors (p=0.72. The T stage also showed a strong correlation with patient survival (p<0.0001. CONCLUSION: The TCC is more common in male than in female with mean age of 63.2 years. The tumor grading and staging exhibited as strong predictive value for disease progression and patient survival.

  12. Long-term survival after gemcitabine and cisplatin in patients with locally advanced transitional cell carcinoma of the bladder: focus on supplementary treatment strategies

    DEFF Research Database (Denmark)

    Als, Anne Birgitte; Sengelov, Lisa; von der Maase, Hans

    2007-01-01

    radiotherapy as supplementary treatment. CONCLUSIONS: In patients with locally advanced bladder cancer, NED following chemotherapy alone or chemotherapy plus supplementary cystectomy or radiotherapy is essential to achieve long-term survival. Patients with a partial response should be offered radical......OBJECTIVE: The objective was to evaluate response and survival, as well as efficacy of subsequent supplementary treatment and follow-up strategy in patients with locally advanced transitional cell carcinoma of the bladder following combination chemotherapy with gemcitabine and cisplatin (GC......: A total of 25 patients (29.8%) with complete response to chemotherapy were followed by close surveillance. This group achieved a median overall survival of 47.6 mo. Another 25 patients had partial response to chemotherapy. Of these patients, 16 had supplementary treatment, with 10 achieving "no evidence...

  13. Prima-1 induces apoptosis in bladder cancer cell lines by activating p53

    Directory of Open Access Journals (Sweden)

    Camila B. Piantino

    2013-01-01

    Full Text Available OBJECTIVES: Bladder cancer represents 3% of all carcinomas in the Brazilian population and ranks second in incidence among urological tumors, after prostate cancer. The loss of p53 function is the main genetic alteration related to the development of high-grade muscle-invasive disease. Prima-1 is a small molecule that restores tumor suppressor function to mutant p53 and induces cancer cell death in various cancer types. Our aim was to investigate the ability of Prima-1 to induce apoptosis after DNA damage in bladder cancer cell lines. METHOD: The therapeutic effect of Prima-1 was studied in two bladder cancer cell lines: T24, which is characterized by a p53 mutation, and RT4, which is the wild-type for the p53 gene. Morphological features of apoptosis induced by p53, including mitochondrial membrane potential changes and the expression of thirteen genes involved in apoptosis, were assessed by microscopic observation and quantitative real-time PCR (qRT-PCR. RESULTS: Prima-1 was able to reactivate p53 function in the T24 (p53 mt bladder cancer cell line and promote apoptosis via the induction of Bax and Puma expression, activation of the caspase cascade and disruption of the mitochondrial membrane in a BAK-independent manner. CONCLUSION: Prima-1 is able to restore the transcriptional activity of p53. Experimental studies in vivo may be conducted to test this molecule as a new therapeutic agent for urothelial carcinomas of the bladder, which characteristically harbor p53 mutations.

  14. Uropathogenic E. coli Promote a Paracellular Urothelial Barrier Defect Characterized by Altered Tight Junction Integrity, Epithelial Cell Sloughing and Cytokine Release

    OpenAIRE

    Wood, M W; Breitschwerdt, E B; Nordone, S.K.; Linder, K. E.; Gookin, J.L.

    2011-01-01

    The urinary bladder is a common site of bacterial infection with a majority of cases attributed to uropathogenic Escherichia coli. Sequels of urinary tract infections (UTIs) include the loss of urothelial barrier function and subsequent clinical morbidity secondary to the permeation of urine potassium, urea and ammonia into the subepithelium. To date there has been limited research describing the mechanism by which this urothelial permeability defect develops. The present study models acute u...

  15. Gall bladder carcinoma: Aggressive malignancy with protean loco-regional and distant spread.

    Science.gov (United States)

    Dwivedi, Amit Nandan Dhar; Jain, Shivi; Dixit, Ruhi

    2015-03-16

    The most common malignancy of biliary tract is gallbladder cancer (GBC) which is the third most common cancer in gastrointestinal tract. It is a lethal disease for most patients in spite of growing awareness and improved diagnostic techniques. GBC has a very poor prognosis and the 5 year survival rate is geography and ethnicity which suggest that both genetic and environmental factors can cause GBC. The major route of spread of gallbladder cancer (GC) is loco-regional rather than distant. It spreads by lymphatic, vascular, neural, intraperitoneal, and intraductal routes. Sonography is usually the most common imaging test to evaluate symptoms of biliary tract disease including suspected GC. With recent advances in imaging modalities like multi-detector computed tomography (CT) scanners, magnetic resonance imaging-positron emission tomography/CT diagnosis of gallbladder cancer has improved. Studies have also targeted molecular and genetic pathways. Treatment options have included extended and radical surgeries and adjuvant chemotherapy. This review article deals in detail with important aspects of carcinoma gallbladder and its manifestations and challenges. Role of various imaging modalities in characterization and accurate staging has been discussed. The loco-regional spread of this aggressive malignancy is dealt explicitly. PMID:25789296

  16. Electron tomography of fusiform vesicles and their organization in urothelial cells.

    Directory of Open Access Journals (Sweden)

    Samo Hudoklin

    Full Text Available The formation of fusiform vesicles (FVs is one of the most distinctive features in the urothelium of the urinary bladder. FVs represent compartments for intracellular transport of urothelial plaques, which modulate the surface area of the superficial urothelial (umbrella cells during the distension-contraction cycle. We have analysed the three-dimensional (3D structure of FVs and their organization in umbrella cells of mouse urinary bladders. Compared to chemical fixation, high pressure freezing gave a new insight into the ultrastructure of urothelial cells. Electron tomography on serial sections revealed that mature FVs had a shape of flattened discs, with a diameter of up to 1.2 µm. The lumen between the two opposing asymmetrically thickened membranes was very narrow, ranging from 5 nm to 10 nm. Freeze-fracturing and immunolabelling confirmed that FVs contain two opposing urothelial plaques connected by a hinge region that made an omega shaped curvature. In the central cytoplasm, 4-15 FVs were often organized into stacks. In the subapical cytoplasm, FVs were mainly organized as individual vesicles. Distension-contraction cycles did not affect the shape of mature FVs; however, their orientation changed from parallel in distended to perpendicular in contracted bladder with respect to the apical plasma membrane. In the intermediate cells, shorter and more dilated immature FVs were present. The salient outcome from this research is the first comprehensive, high resolution 3D view of the ultrastructure of FVs and how they are organized differently depending on their location in the cytoplasm of umbrella cells. The shape of mature FVs and their organization into tightly packed stacks makes them a perfect storage compartment, which transports large amounts of urothelial plaques while occupying a small volume of umbrella cell cytoplasm.

  17. Experimental bladder defect in rabbit repaired with homologous bladder extracellular matrix graft

    Institute of Scientific and Technical Information of China (English)

    YANG Si-xing; SHEN Fu-jin; HU Yun-fei; JIN Hua-min; WANG Ling-long

    2005-01-01

    @@ Approximately 400 million people worldwide suffer from bladder disease such as congenital abnormalities, cancer, trauma, infection, iatrogenic injuries or other conditions which may lead to painful bladder damage or loss, so eventual bladder augmentation or substitution should be required. Gastrointestinal segments are commonly used as tissues for bladder replacement or repair, but have been associated with multiple complications such as infection, metabolic disturbances, increased mucus production, and malignancy.1 Because of the problems encountered with the use of gastrointestinal segments, several bladder substitutes have been attempted with both organic materials (skin, dura mater, peritoneum or fascia) and synthetics (such as poly vinyl, sponge, silicone). These attempts have usually failed due to mechanical, structural or biocompatibility problems. Permanent synthetic materials succumb to mechanical failure and urinary stone formation. Degradable materials lead to fibroblast deposition, scarring, and a reduced reservoir volume.2,3 It is evident that bladder tissue cannot be replaced easily due to its elastic properties and urothelial permeability function.

  18. HSD3B and gene-gene interactions in a pathway-based analysis of genetic susceptibility to bladder cancer.

    Directory of Open Access Journals (Sweden)

    Angeline S Andrew

    Full Text Available Bladder cancer is the 4(th most common cancer among men in the U.S. We analyzed variant genotypes hypothesized to modify major biological processes involved in bladder carcinogenesis, including hormone regulation, apoptosis, DNA repair, immune surveillance, metabolism, proliferation, and telomere maintenance. Logistic regression was used to assess the relationship between genetic variation affecting these processes and susceptibility in 563 genotyped urothelial cell carcinoma cases and 863 controls enrolled in a case-control study of incident bladder cancer conducted in New Hampshire, U.S. We evaluated gene-gene interactions using Multifactor Dimensionality Reduction (MDR and Statistical Epistasis Network analysis. The 3'UTR flanking variant form of the hormone regulation gene HSD3B2 was associated with increased bladder cancer risk in the New Hampshire population (adjusted OR 1.85 95%CI 1.31-2.62. This finding was successfully replicated in the Texas Bladder Cancer Study with 957 controls, 497 cases (adjusted OR 3.66 95%CI 1.06-12.63. The effect of this prevalent SNP was stronger among males (OR 2.13 95%CI 1.40-3.25 than females (OR 1.56 95%CI 0.83-2.95, (SNP-gender interaction P = 0.048. We also identified a SNP-SNP interaction between T-cell activation related genes GATA3 and CD81 (interaction P = 0.0003. The fact that bladder cancer incidence is 3-4 times higher in males suggests the involvement of hormone levels. This biologic process-based analysis suggests candidate susceptibility markers and supports the theory that disrupted hormone regulation plays a role in bladder carcinogenesis.

  19. Growth Inhibition and Apoptosis Induced by Retinoic Acid Combined with Interferon Alpha-2a on Transitional Cell Carcinoma of Bladder

    Institute of Scientific and Technical Information of China (English)

    QIANLi-xin; LIUXun-liang; ZHOUJian-wei; MonicaLiebert; ZOUChang-chun; ZOUChang-ping

    2004-01-01

    To identify new favorable agents and develop novel approaches for the chemoprevention and treatment of superficial bladder cancer and invesligate the effects of combination of relinoids and interferon α-2a on growth inhibition and apoptosis induction in bladder cancer cell lines. Methods: Four bladder cancer cell lines, grade 1 to 3,and two retinoids, all-trans-retinoic acid(ATRA) ,9.cis retinoic acid(9cRA) ,combined with inteferon α-2a(INF),were used in the study.We compared the competence of these agents to inhibit growth, induce apoptosis, affect the exptession of nuclear retinoid receptors, and modulate STAT1 protein. Resu/ts: Most of the bladder cancer cell lines were resistant to the effect of ATRA and 9cRA on growth inhibition and apoptosis induction, even at higher concentration (10-5M).The effects of ATRA and 9c RA on cell growth and apoptosis were enhanced by INF α-2a.Combination of ATRA and IFNa-2a induced ~ and Slat 1 expression in three bladder cancer cell lines, ~: The results demonstrated that INFw2a synergize with the inhibitory effect of ATRA and 9c RA on the growth intn'bition and apoptosis of bladder cancer cells in vitro, which suggested that it has a potenlJal intexest for the trealment of transitimml cell carcinmna of bladder.

  20. Effects of increasing carbon nanofiber density in polyurethane composites for inhibiting bladder cancer cell functions.

    Science.gov (United States)

    Tsang, Melissa; Chun, Young Wook; Im, Yeon Min; Khang, Dongwoo; Webster, Thomas J

    2011-07-01

    Polyurethane (PU) is a versatile elastomer that is commonly used in biomedical applications. In turn, materials derived from nanotechnology, specifically carbon nanofibers (CNFs), have received increasing attention for their potential use in biomedical applications. Recent studies have shown that the dispersion of CNFs in PU significantly enhances composite nanoscale surface roughness, tensile properties, and thermal stability. Although there have been studies concerning normal primary cell functions on such nanocomposites, there have been few studies detailing cancer cell responses. Since many patients who require bladder transplants have suffered from bladder cancer, the ideal bladder prosthetic material should not only promote normal primary human urothelial cell (HUC) function, but also inhibit the return of bladder cancerous cell activity. This study examined the correlation between transitional (UMUC) and squamous (or SCaBER) urothelial carcinoma cells and HUC on PU:CNF nanocomposites of varying PU and CNF weight ratios (from pure PU to 4:1 [PU:CNF volume ratios], 2:1, 1:1, 1:2, and 1:4 composites to pure CNF). Composites were characterized for mechanical properties, wettability, surface roughness, and chemical composition by atomic force microscopy, scanning electron microscopy, X-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy, and goniometry. The adhesion and proliferation of UMUC and SCaBER cancer cells were assessed by MTS assays. Cellular responses were further quantified by measuring the amounts of nuclear mitotic protein 22 (NMP-22), vascular endothelial growth factor (VEGF), and tumor necrosis factor alpha. Results demonstrated that both UMUC and SCaBER cell proliferation rates decreased over time on substrates with increased CNF in PU. In addition, with the exception of VEGF from UMUC (which was the same across all materials), composites containing the most CNF activated cancer cells (UMUC and SCaBER) the least, as shown by

  1. A novel bioreactor to simulate urinary bladder mechanical properties and compliance for bladder functional tissue engineering

    Institute of Scientific and Technical Information of China (English)

    WEI Xin; LI Dao-bing; XU Feng; WANG Yan; ZHU Yu-chun; LI Hong; WANG Kun-jie

    2011-01-01

    Background Bioreactors are pivotal tools for generating mechanical stimulation in functional tissue engineering study.This study aimed to create a bioreactor that can simulate urinary bladder mechanical properties, and to investigate the effects of a mechanically stimulated culture on urothelial cells and bladder smooth muscle cells.Methods We designed a bioreactor to simulate the mechanical properties of bladder. A pressure-record system was used to evaluate the mechanical properties of the bioreactor by measuring the pressure in culture chambers. To test the biocompatibility of the bioreactor, viabilities of urothelial cells and smooth muscle cells cultured in the bioreactor under static and mechanically changed conditions were measured after 7-day culture. To evaluate the effect of mechanical stimulations on the vital cells, urethral cells and smooth muscle cells were cultured in the simulated mechanical conditions. After that, the viability and the distribution pattern of the cells were observed and compared with cells cultured in non-mechanical stimulated condition.Results The bioreactor system successfully generated waveforms similar to the intended programmed model while maintaining a cell-seeded elastic membrane between the chambers. There were no differences between viabilities of urothelial cells ((91.90±1.22)% vs. (93.14±1.78)%, P >0.05) and bladder smooth muscle cells ((93.41±1.49)% vs.(92.61±1.34)%, P >0.05). The viability of cells and tissue structure observation after cultured in simulated condition showed that mechanical stimulation was the only factor affected cells in the bioreactor and improved the arrangement of cells on silastic membrane.Conclusions This bioreactor can effectively simulate the physiological and mechanical properties of the bladder.Mechanical stimulation is the only factor that affected the viability of cells cultured in the bioreactor. The bioreactor can change the growth behavior of urothelial cells and bladder smooth

  2. Gemcitabine Hydrochloride and Cisplatin or High-Dose Methotrexate, Vinblastine, Doxorubicin Hydrochloride, and Cisplatin in Treating Patients With Urothelial Cancer

    Science.gov (United States)

    2014-01-27

    Anterior Urethral Cancer; Localized Transitional Cell Cancer of the Renal Pelvis and Ureter; Posterior Urethral Cancer; Recurrent Bladder Cancer; Recurrent Urethral Cancer; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Stage III Bladder Cancer; Transitional Cell Carcinoma of the Bladder; Ureter Cancer; Urethral Cancer Associated With Invasive Bladder Cancer

  3. Primary Signet-Ring Cell Carcinoma of Urinary Bladder: A Case Report and Review of the Literature%原发性膀胱印戒细胞癌1例报告并文献复习

    Institute of Scientific and Technical Information of China (English)

    胡善彪; 王荫槐; 易路; 廖忠厚; 蔡仁中

    2011-01-01

    Objective:To investigate the clinical features of primary signet-ring cell carcinoma of unnary bladder.Methods: A case for primary Signet-ring cell carcinoma of urinary bladder was reported.The patient complained of intermittently macroscopic hematuria.We could not find any lesions out of the urinary bladder from preoperative examinations, and cystectomy plus ureterostomy had been operated.Results:Signet-ring cell carcinoma of urinary bladder had been confirmed according to the pathological examination.The patient had been transferred to the department of Oncology for luther chemotherapy after operation and now is under follow-up.Conclusions: Signet-ring cell carcinoma of urinary bladder has a series of characteristics such as extremely rare occurrence, fast development, highly malignant, local invasive growth , the trend of early pervasion and transfer,and poor prognosis.Histopathologic examination is the main way to confirm Signet-ring cell carcinoma of urinary bladder.%目的:探讨原发性膀胱印戒细胞癌的临床特征.方法:报告1例原发性膀胱印戒细胞癌患者的临床资料.患者因间歇性肉眼血尿就诊,术前检查未找到任何膀胱外病灶,行膀胱全切除术+输尿管造瘘术.结果:术后病检报告为膀胱印戒细胞癌.患者术后转肿瘤科化疗,目前正在随访中.结论:原发性膀胱SRCC非常罕见,进展快、恶性程度高,局部浸润性生长,有早期扩散转移倾向,预后差.其确诊主要依靠病理组织学检查.

  4. Body mass index versus bladder and rectal doses using 2D planning for patients with carcinoma of the cervix undergoing HDR brachytherapy

    Directory of Open Access Journals (Sweden)

    Anil Kumar Talluri

    2016-06-01

    Full Text Available Purpose: To assess bladder and rectum doses in relation to body mass index of patients undergoing high dose rate brachytherapy for the treatment of carcinoma of the cervix.Methods: The cohort consists of fifty subjects with carcinoma of the uterine cervix presented with grade II and III. Patient’s height and weight was measured before the insertion of applicator in situ. Body mass index (BMI of the patient was calculated in accordance to World Health Organization definition (weight in Kg/ height in m2. Adequacy of position and orientation of the applicator was confirmed with the help of orthogonal X-ray images and the same were transferred to the treatment planning system (TPS to generate treatment plan. Prescription doses were optimized to Point A and to reference lines placed at 0.5 cm apart from the surface of ovoids. The following dose reference points were identified on orthogonal x-ray images for analysis using the rectal marker and Foleys bulb inflated with radio opaque dye Rectal points at the level of femoral heads (RL and pubis symphysis (RLP, Anorectum Junction (AR Jn point and Rectosigmoid (RS point and Bladder point (BL. Pearson regression analysis was used to analyze data from TPS.Results: The mean BMI was 22.7 kg/m2 and average age was 49.9 years. Analysis showed that RL point dose and BMI were inversely correlated with a coefficient -0.45 (p = 0.001. The trend continued along the rectal tube in cranio-caudal direction, as RLP and AR Jn points showed inversion co-efficiency with increase in BMI,-0.48 (p < 0.01 and -0.51 (p < 0.01 respectively. Bladder point showed weak positive correlation to BMI, 0.12 (p = 0.38.Conclusion: Significant rectal dose reduction is observed with increase in BMI. Bladder dose did not show statistically significant correlation with BMI. Based on the findings, BMI constitutes a confounding factor in the treatment of carcinoma of cervix.

  5. Problems in early diagnosis of bladder cancer in a spinal cord injury patient: Report of a case of simultaneous production of granulocyte colony stimulating factor and parathyroid hormone-related protein by squamous cell carcinoma of urinary bladder

    Directory of Open Access Journals (Sweden)

    Singh Gurpreet

    2002-08-01

    Full Text Available Abstract Background Typical symptoms and signs of a clinical condition may be absent in spinal cord injury (SCI patients. Case presentation A male with paraplegia was passing urine through penile sheath for 35 years, when he developed urinary infections. There was no history of haematuria. Intravenous urography showed bilateral hydronephrosis. The significance of abnormal outline of bladder was not appreciated. As there was large residual urine, he was advised intermittent catheterisation. Serum urea: 3.5 mmol/L; creatinine: 77 umol/L. A year later, serum urea: 36.8 mmol/l; creatinine: 632 umol/l; white cell count: 22.2; neutrophils: 18.88. Ultrasound: bilateral hydronephrosis. Bilateral nephrostomy was performed. Subsequently, blood tests showed: Urea: 14.2 mmol/l; Creatinine: 251 umol/l; Adjusted Calcium: 3.28 mmol/l; Parathyroid hormone: A repeat ultrasound scan demonstrated a tumour arising from right lateral wall; biopsy revealed squamous cell carcinoma. In view of persistently high white cell count and high calcium level, immunohistochemistry for G-CSF and PTHrP was performed. Dense staining of tumour cells for G-CSF and faintly positive staining for C-terminal PTHrP were observed. This patient expired about five months later. Conclusion This case demonstrates how delay in diagnosis of bladder cancer could occur in a SCI patient due to absence of characteristic symptoms and signs.

  6. A Case of p63 Positive Diffuse Large B Cell Lymphoma of the Bladder

    Science.gov (United States)

    Jones, Carol

    2016-01-01

    Diffuse large B cell lymphoma (DLBCL), currently the most common type of non-Hodgkin lymphoma (NHL), is an aggressive B cell neoplasm that typically presents in older adults as a rapidly enlarging mass. The enlarging mass typically represents a lymph node, although extranodal disease can occur in a significant percentage (40%) of cases. The most common extranodal sites of involvement include the gastrointestinal tract and skin; primary bladder lymphoma represents only 0.2% of extranodal non-Hodgkin lymphomas. We report a case of diffuse large B cell lymphoma occurring in the bladder of an 83-year-old gentleman with an initial presentation of hematuria. This neoplasm displayed large, atypical cells with vesicular chromatin and prominent nucleoli that involved the bladder mucosa with invasion into muscularis propria, prostate, and urethra. Positive staining for p63 initially raised suspicion for poorly differentiated urothelial carcinoma; however, lack of staining for pancytokeratin and positive staining for LCA, CD20, CD79a, and PAX-5 confirmed the diagnosis of diffuse large B cell lymphoma. Though it does not occur in all cases, p63 can be positive in a significant percentage of cases of DLBCL; therefore, a diagnosis of lymphoma remains an important entity on the differential diagnosis of aggressive and particularly poorly differentiated neoplasms. PMID:27648316

  7. Luminal DMSO: Effects on Detrusor and Urothelial/Lamina Propria Function

    Directory of Open Access Journals (Sweden)

    Katrina J. Smith

    2014-01-01

    Full Text Available DMSO is used as a treatment for interstitial cystitis and this study examined the effects of luminal DMSO treatment on bladder function and histology. Porcine bladder was incubated without (controls or with DMSO (50% applied to the luminal surface and the release of ATP, acetylcholine, and LDH assessed during incubation and in tissues strips after DMSO incubation. Luminally applied DMSO caused ATP, Ach, and LDH release from the urothelial surface during treatment, with loss of urothelial layers also evident histologically. In strips of urothelium/lamina propria from DMSO pretreated bladders the release of both ATP and Ach was depressed, while contractile responses to carbachol were enhanced. Detrusor muscle contractile responses to carbachol were not affected by DMSO pretreatment, but neurogenic responses to electrical field stimulation were enhanced. The presence of an intact urothelium/lamina propria inhibited detrusor contraction to carbachol by 53% and this inhibition was significantly reduced in DMSO pretreated tissues. Detection of LDH in the treatment medium suggests that DMSO permeabilised urothelial membranes causing leakage of cytosolic contents including ATP and Ach rather than enhancing release of these mediators. The increase in contractile response and high levels of ATP are consistent with initial flare up in IC/PBS symptoms after DMSO treatment.

  8. Expressions of S100P and Ki - 67 in urothelial carcinoma of the renal pelvis and their clinical significance%S100P 与 Ki -67在肾盂尿路上皮癌中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    李云; 李胜水; 许华; 韩晓春; 刘海霞; 王丽丽; 张凤梅; 李双标; 赵倩

    2015-01-01

    目的:观察 S100P 与 Ki -67蛋白在肾盂尿路上皮癌组织中的表达,分析其与肾盂尿路上皮癌临床病理特征的关系及探讨两者与肾盂尿路上皮癌发生、发展的相关性。方法:采用免疫组织化学 SP 法检测52例肾盂尿路上皮癌与46例正常肾盂黏膜组织中 S100P、Ki -67的表达情况。结果:S100P 在肾盂尿路上皮癌组织中的阳性表达率(86.5%45/52)明显高于正常对照组(30.4%14/46)(P ﹤0.05),同样 Ki -67在肾盂尿路上皮癌组织中的阳性表达率(80.8%42/52)明显高于正常对照组(26.1%12/46)(P ﹤0.05);S100P、Ki -67在肾盂癌组织中的阳性表达与患者的性别、年龄无关(P ﹥0.05),却与病理分级、临床分期有关(P ﹤0.05);在肾盂癌组织中,S100P 与 Ki -67表达呈正相关,具有统计学意义(P ﹤0.05)。结论:S100P 与 Ki -67过表达提示其在肾盂尿路上皮癌的发生、发展中具有重要作用,因此联合检测两者可能有助于判断肾盂尿路上皮癌生物学行为及预后评估。%Objective To Investigate the expressions of S100P protein and Ki - 67 in urothelial carcinoma of the renal pelvis,and ana-lyze their expression correlation and clinical significance in urothelial carcinoma of the renal pelvis. Method The expressions of S100P and Ki - 67 were analyze by immunohistochemical in 52 cases of urothelial carcinoma of the renal pelvis and 46 cases of normal pelvis muco-sa. Results The positive rate of S100P protein in urothelial carcinoma of the renal pelvis(86. 5% 45 / 52)was significantly higher than that in normal pelvis mucosa(30. 4% 14 / 46)(P ﹤ 0. 05),Similarly,The positive rate of Ki - 67 protein in urothelial carcinoma of the renal pel-vis(80. 8% 42 / 52)was significantly higher than that in normal pelvis mucosa(26. 1% 12 / 46)(P ﹤ 0. 05);The expression of S100P、Ki -67 was not associate with patient' gender and age(P ﹥ 0. 05),but was

  9. In vivo 31P magnetic resonance spectroscopy and 1H magnetic resonance imaging of human bladder carcinoma on nude mice: effects of tumour growth and treatment with cis-dichloro-diamine platinum

    DEFF Research Database (Denmark)

    De Certaines, J D; Albrectsen, J; Larsen, V A;

    1992-01-01

    In vivo 31P NMR spectroscopy and 1H NMR imaging were used to examine the bladder T24B carcinoma in nude mice during untreated growth and in response to chemotherapy by Cis-dichloro-diammine-platinum (CDDP) at a dose of 8 mg/kg i.p. Untreated growth was associated with an increase of inorganic pho...

  10. Loss of β1-integrin from urothelium results in overactive bladder and incontinence in mice: a mechanosensory rather than structural phenotype

    OpenAIRE

    Kanasaki, Keizo; Yu, Weiqun; von Bodungen, Maximilian; Larigakis, John D.; Kanasaki, Megumi; Ayala de la Pena, Francisco; Kalluri, Raghu; Hill, Warren G.

    2013-01-01

    Bladder urothelium senses and communicates information about bladder fullness. However, the mechanoreceptors that respond to tissue stretch are poorly defined. Integrins are mechanotransducers in other tissues. Therefore, we eliminated β1-integrin selectively in urothelium of mice using Cre-LoxP targeted gene deletion. β1-Integrin localized to basal/intermediate urothelial cells by confocal microscopy. β1-Integrin conditional-knockout (β1-cKO) mice lacking urothelial β1-integrin exhibited dow...

  11. Botulinum toxin type A normalizes alterations in urothelial ATP and NO release induced by chronic spinal cord injury

    OpenAIRE

    Smith, Christopher P.; Gangitano, David A; Munoz, Alvaro; Salas, Nilson A.; Boone, Timothy B.; Aoki, K Roger; Francis, Joseph; Somogyi, George T.

    2007-01-01

    The purpose of this paper was to simultaneously examine changes in urothelial ATP and NO release in normal and spinal cord injured animals as well as in spinal cord injured animals treated with botulinum toxin type A (BoNT-A). Furthermore we correlated changes in transmitter release with functional changes in bladder contraction frequency, and determined the effects of BoNT-A on bladder efferent nerve function. Normal and spinal cord injured rat bladders were injected on day 0 with either veh...

  12. Bladder Management

    Science.gov (United States)

    ... Catheterization • Urinary Tract Infections: Indwelling (Foley) Catheter Bladder Management [ Download this pamphlet: "Bladder Management" - (PDF, 499KB) ] The ... and medication or surgery may be helpful. Bladder Management Foley or Suprapubic Catheter A tube is inserted ...

  13. N-Acetyltransferase 2 genotype, exfoliated urothelial cells and benzidine exposure.

    Science.gov (United States)

    Ma, Qing-wen; Lin, Guo-fang; Chen, Ji-gang; Guo, Wei-Chao; Qin, Yi-qiu; Golka, Klaus; Shen, Jian-hua

    2012-01-01

    Most studies report an association of the slow N-acetyltransferase 2 (NAT2) status with elevated bladder cancer risk. In this study, NAT2 genotypes and the decades-long records of Papanicolaou's grading of exfoliated urothelial cells in a former benzidine-exposed cohort of the Shanghai dyestuff industry (29 bladder cancer patients; 307 non-cancer cohort members, some of them presenting different grades of pre-malignant alterations of exfoliated urothelial cells) were investigated. The cohort members had been enrolled in regular medical surveillance since mid-1980s. No overall increase of slow NAT2 genotypes in the former benzidine-exposed bladder cancer patients was found, compared with non-diseased members of the same cohort. A lower presentation of the homozygous wild genotype NAT2 4/4 was observed in bladder cancer patients, compared with non-diseased members with averaged Papanicolaou's grading (APG)3 II (OR=0.31, 95 percent CI 0.10-0.96, p=0.034) or with APG less than II (OR=0.36,95 percent CI 0.12-1.10, p=0.063). Nevertheless, neither a protective influence of rapid NAT2 genotypes on bladder cancer risk nor on pre-malignant cytological alterations could be confirmed by the present data.

  14. Bladder Diseases

    Science.gov (United States)

    ... frequent, urgent urination Bladder cancer Doctors diagnose bladder diseases using different tests. These include urine tests, x- ... National Institute of Diabetes and Digestive and Kidney Diseases

  15. Null mutation for Macrophage Migration Inhibitory Factor (MIF is associated with less aggressive bladder cancer in mice

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    Tsimikas John

    2007-07-01

    Full Text Available Abstract Background Inflammatory cytokines may promote tumorigenesis. Macrophage migration inhibitory factor (MIF is a proinflammatory cytokine with regulatory properties over tumor suppressor proteins involved in bladder cancer. We studied the development of bladder cancer in wild type (WT and MIF knockout (KO mice given N-butyl-N-(4-hydroxybutyl-nitrosamine (BBN, a known carcinogen, to determine the role of MIF in bladder cancer initiation and progression. Methods 5-month old male C57Bl/6 MIF WT and KO mice were treated with and without BBN. Animals were sacrificed at intervals up to 23 weeks of treatment. Bladder tumor stage and grade were evaluated by H&E. Immunohistochemical (IHC analysis was performed for MIF and platelet/endothelial cell adhesion molecule 1 (PECAM-1, a measure of vascularization. MIF mRNA was analyzed by quantitative real-time polymerase chain reaction. Results Poorly differentiated carcinoma developed in all BBN treated mice by week 20. MIF WT animals developed T2 disease, while KO animals developed only T1 disease. MIF IHC revealed predominantly urothelial cytoplasmic staining in the WT control animals and a shift toward nuclear staining in WT BBN treated animals. MIF mRNA levels were 3-fold higher in BBN treated animals relative to controls when invasive cancer was present. PECAM-1 staining revealed significantly more stromal vessels in the tumors in WT animals when compared to KOs. Conclusion Muscle invasive bladder cancer with increased stromal vascularity was associated with increased MIF mRNA levels and nuclear redistribution. Consistently lower stage tumors were seen in MIF KO compared to WT mice. These data suggest that MIF may play a role in the progression to invasive bladder cancer.

  16. Null mutation for Macrophage Migration Inhibitory Factor (MIF) is associated with less aggressive bladder cancer in mice

    International Nuclear Information System (INIS)

    Inflammatory cytokines may promote tumorigenesis. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine with regulatory properties over tumor suppressor proteins involved in bladder cancer. We studied the development of bladder cancer in wild type (WT) and MIF knockout (KO) mice given N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN), a known carcinogen, to determine the role of MIF in bladder cancer initiation and progression. 5-month old male C57Bl/6 MIF WT and KO mice were treated with and without BBN. Animals were sacrificed at intervals up to 23 weeks of treatment. Bladder tumor stage and grade were evaluated by H&E. Immunohistochemical (IHC) analysis was performed for MIF and platelet/endothelial cell adhesion molecule 1 (PECAM-1), a measure of vascularization. MIF mRNA was analyzed by quantitative real-time polymerase chain reaction. Poorly differentiated carcinoma developed in all BBN treated mice by week 20. MIF WT animals developed T2 disease, while KO animals developed only T1 disease. MIF IHC revealed predominantly urothelial cytoplasmic staining in the WT control animals and a shift toward nuclear staining in WT BBN treated animals. MIF mRNA levels were 3-fold higher in BBN treated animals relative to controls when invasive cancer was present. PECAM-1 staining revealed significantly more stromal vessels in the tumors in WT animals when compared to KOs. Muscle invasive bladder cancer with increased stromal vascularity was associated with increased MIF mRNA levels and nuclear redistribution. Consistently lower stage tumors were seen in MIF KO compared to WT mice. These data suggest that MIF may play a role in the progression to invasive bladder cancer

  17. Familial aggregation of bladder cancer

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    Ilić Milena

    2011-01-01

    Full Text Available Background. Except for smoking and certain occupational exposures, the etiology of bladder cancer is largely unknown. Several case reports have described familial aggregation of transitional cell carcinoma of the bladder. Although the majority of patients with bladder cancer do not have family history of transitional cell carcinoma of the urinary tract, the study of familial transitional cell carcinoma may lead to the knowledge on the pathogenesis of this disease. The purpose of this study was to describe three cases of urinary bladder cancer in a single three-member family, i.e. in two generations (mother and son and a family member related by marriage (the patient’s wife. Case report. Three cases of urinary bladder cancer occurred in a three-member family within the interval of 5 years. The following common characteristics were detected in our patients: old age (over 60, working as farmers for more than 50 years, negative personal medical history on relevant health disorders, place of birth - village, place of residence - village, the same water supply, similar nutrition, positive family history on urinary bladder cancer or other malignant tumors, the first sign of illness was macroscopic hematuria in all the patients and the same pathohistological type of cancer - carcinoma papillare transitiocellulare. Conclusion. The stated common characteristics in our cases indicate, above all, the impact of exposure to external surrounding factors on the occurrence of urinary bladder cancer.

  18. Kinetic profiles by topographic compartments in muscle-invasive transitional cell carcinomas of the bladder: role of TP53 and NF1 genes.

    Science.gov (United States)

    Blanes, Alfredo; Rubio, Javier; Martinez, Armando; Wolfe, Hubert J; Diaz-Cano, Salvador J

    2002-07-01

    We evaluated 71 muscle-invasive transitional cell carcinomas (TCCs) of the bladder by tumor compartments. Kinetic parameters included mitotic figure counting, Ki-67 index, proliferation rate (DNA slide cytometry), and apoptotic index (in situ end labeling [ISEL] of fragmented DNA using digoxigenin-labeled deoxyuridine triphosphate and Escherichia coli DNA polymerase [Klenow fragment]). At least 50 high-power fields per compartment were screened from the same tumor areas; results are expressed as percentage of positive neoplastic cells. Mean and SD were compared by tumor compartment. DNA was extracted from microdissected samples (superficial and deep) and used for microsatellite analysis of TP53 and NF1 by polymerase chain reaction-denaturing gradient gel electrophoresis. Significantly higher marker scores were revealed in the superficial compartment than in the deep compartment. An ISEL index of less than 1% was revealed in 63% (45/71) of superficial compartments and 86% (61/71) of deep compartments. Isolated NF1 alterations were observed mainly in superficial compartments, whereas isolated TP53 abnormalities were present in deep compartments. Lower proliferation and down-regulation of apoptosis define kinetically the deep compartment of muscle-invasive TCC of the bladder and correlate with the topographic heterogeneity, NF1-defective in superficial compartments and TP53-defective in deep compartments.

  19. Evaluation of the Efficacy of the H. pylori Protein HP-NAP as a Therapeutic Tool for Treatment of Bladder Cancer in an Orthotopic Murine Model.

    Science.gov (United States)

    Codolo, Gaia; Munari, Fabio; Fassan, Matteo; de Bernard, Marina

    2015-01-01

    Bladder cancer is one of the most common malignancies of the urogenital tract. Intravesical injection of Bacillus Calmette-Guérin (BCG) is the gold standard treatment for the high-grade non-muscle invasive bladder cancer (NMIBC). However, since the treatment-related side effects are relevant, newer biological response modifiers with a better benefit/side effects ratio are needed. The tumour microenvironment can influence both tumour development and therapy efficacy. In order to obtain a good model, it is desirable to implant tumour cells in the organ from which the cancer originates. In this protocol, we describe a method for establishing a tumour in the bladder cavity of female mice and subsequent delivery of therapeutic agents; the latter are exemplified by our use of Helicobacter pylori neutrophil activating protein (HP-NAP). A preliminary chemical burn of the mucosa, followed by the injection of mouse urothelial carcinoma cell line MB49 via urethral catheterization, enables the cells to attach to the bladder mucosa. After a period, required to allow an initial proliferation of the cells, mice are treated with HP-NAP, administrated again via catheterization. The anti-tumour activity of HP-NAP is evaluated comparing the tumour volume, the extent of necrosis and the degree of vascularization between vehicle- and HP-NAP-treated animals. PMID:26068073

  20. Gene expression signatures predict outcome in non-muscle invasive bladder carcinoma - a multi-center validation study

    DEFF Research Database (Denmark)

    Andersen, Lars Dyrskjøt; Zieger, Karsten; Real, Francisco X.;

    2007-01-01

    PURPOSE: Clinically useful molecular markers predicting the clinical course of patients diagnosed with non-muscle-invasive bladder cancer are needed to improve treatment outcome. Here, we validated four previously reported gene expression signatures for molecular diagnosis of disease stage and ca...

  1. Evaluating the Prevalence of the Epidermal Growth Factor Receptor in Transitional Cell Carcinoma of Bladder and its Relationship With Other Prognostic Factors

    Science.gov (United States)

    Parvin, Mahmoud; Sabet-Rasekh, Parto; Hajian, Parastoo; Mohammadi Torbati, Peyman; Sabet-Rasekh, Parisa; Mirzaei, Hamidreza

    2016-01-01

    Background: The most common malignancy in the urinary system has been bladder cancer and the most predominant histologic subtype has been transitional cell carcinoma (TCC). There were many molecular risk factors, related with poor prognosis. One of these factors was expression of epidermal growth factor receptor (EGFR). Objectives: The aim of this study was to evaluate the prevalence of the epidermal growth factor receptor in transitional cell carcinoma of bladder and its relationship with other prognostic factors. Patients and Methods: This analytic descriptive study has performed with 61 patients with TCC of bladder after radical cystectomy whom have been hospitalized in Labbafinejad hospital in Tehran, Iran between 2007 and 2010. We have used Chi-square and t-test to analyze our data samples. Results: Records of 61 patients have studied. Fifty three of the total samples were positive for EGFR expression (86.9%). Fifty samples of these fifty-three belonged to men and three others were women’s samples (P = 0.46). Among the group with EGFR expression the results were as follows: 25 patients (47.2%) were 60 years old or less and 28 patients (52.8%) were older than 60 (P = 0.023), 16 patients (30.2%) had invasion to lamina properia, and the rest of them had invasion to deeper layers (P = 0.56). For most patients we could not determine the invasion of tumoral cells into the lymph nodes (Nx) (P = 0.067). Thirty four patients (64.2%) had not lymphovascular invasion (P = 0.44) and in forty three of patients (81.1%), perineural invasion have not seen (P = 0.23). Finally, 36 patients (67.9%) were grade 3 (P = 0.27). Conclusions: In this study we have concluded that most patients had EGFR positive expression. Also, except for the age, there was not any significant relation between expression of EGFR and the other prognostic factors such as, gender, invasion of the tumor into the layers, involving the lymph nodes, lymphovascular or perineural invasion, and grading. PMID

  2. Intact urothelial barrier function in a mouse model of ketamine-induced voiding dysfunction.

    Science.gov (United States)

    Rajandram, Retnagowri; Ong, Teng Aik; Razack, Azad H A; MacIver, Bryce; Zeidel, Mark; Yu, Weiqun

    2016-05-01

    Ketamine is a popular choice for young drug abusers. Ketamine abuse causes lower urinary tract symptoms, with the underlying pathophysiology poorly understood. Disruption of urothelial barrier function has been hypothesized to be a major mechanism for ketamine cystitis, yet the direct evidence of impaired urothelial barrier function is still lacking. To address this question, 8-wk-old female C57BL/6J mice were injected intraperitoneally with 30 mg·kg(-1)·day(-1) ketamine for 12 wk to induce ketamine cystitis. A spontaneous voiding spot assay showed that ketamine-treated mice had increased primary voiding spot numbers and smaller primary voiding spot sizes than control mice (P Ussing chamber system with isotopic urea and water. Mouse urothelial structure was also not altered, and intact umbrella cell structure was observed by both transmission and scanning electron microscopy. Furthermore, immunostaining and confocal microscopy confirmed the presence of a well-defined distribution of zonula occuldens-1 in tight junctions and uroplakin in umbrella cells. In conclusion, these data indicate that ketamine injection induces voiding dysfunction in mice but does not necessarily disrupt mouse bladder barrier function. Disruption of urothelial barrier function may not be the major mechanism in ketamine cystitis. PMID:26911853

  3. Expression microarray meta-analysis identifies genes associated with Ras/MAPK and related pathways in progression of muscle-invasive bladder transition cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Jonathan A Ewald

    Full Text Available The effective detection and management of muscle-invasive bladder Transition Cell Carcinoma (TCC continues to be an urgent clinical challenge. While some differences of gene expression and function in papillary (Ta, superficial (T1 and muscle-invasive (≥T2 bladder cancers have been investigated, the understanding of mechanisms involved in the progression of bladder tumors remains incomplete. Statistical methods of pathway-enrichment, cluster analysis and text-mining can extract and help interpret functional information about gene expression patterns in large sets of genomic data. The public availability of patient-derived expression microarray data allows open access and analysis of large amounts of clinical data. Using these resources, we investigated gene expression differences associated with tumor progression and muscle-invasive TCC. Gene expression was calculated relative to Ta tumors to assess progression-associated differences, revealing a network of genes related to Ras/MAPK and PI3K signaling pathways with increased expression. Further, we identified genes within this network that are similarly expressed in superficial Ta and T1 stages but altered in muscle-invasive T2 tumors, finding 7 genes (COL3A1, COL5A1, COL11A1, FN1, ErbB3, MAPK10 and CDC25C whose expression patterns in muscle-invasive tumors are consistent in 5 to 7 independent outside microarray studies. Further, we found increased expression of the fibrillar collagen proteins COL3A1 and COL5A1 in muscle-invasive tumor samples and metastatic T24 cells. Our results suggest that increased expression of genes involved in mitogenic signaling may support the progression of muscle-invasive bladder tumors that generally lack activating mutations in these pathways, while expression changes of fibrillar collagens, fibronectin and specific signaling proteins are associated with muscle-invasive disease. These results identify potential biomarkers and targets for TCC treatments, and

  4. Cystitis: From Urothelial Cell Biology to Clinical Applications

    Directory of Open Access Journals (Sweden)

    Gilho Lee

    2014-01-01

    Full Text Available Cystitis is a urinary bladder disease with many causes and symptoms. The severity of cystitis ranges from mild lower abdominal discomfort to life-threatening haemorrhagic cystitis. The course of disease is often chronic or recurrent. Although cystitis represents huge economical and medical burden throughout the world and in many cases treatments are ineffective, the mechanisms of its origin and development as well as measures for effective treatment are still poorly understood. However, many studies have demonstrated that urothelial dysfunction plays a crucial role. In the present review we first discuss fundamental issues of urothelial cell biology, which is the core for comprehension of cystitis. Then we focus on many forms of cystitis, its current treatments, and advances in its research. Additionally we review haemorrhagic cystitis with one of the leading causative agents being chemotherapeutic drug cyclophosphamide and summarise its management strategies. At the end we describe an excellent and widely used animal model of cyclophosphamide induced cystitis, which gives researches the opportunity to get a better insight into the mechanisms involved and possibility to develop new therapy approaches.

  5. Image-Guided Radiation Therapy for Muscle-Invasive Carcinoma of the Urinary Bladder with Cone Beam CT Scan: Use of Individualized Internal Target Volumes for a Single Patient

    Directory of Open Access Journals (Sweden)

    Gagan Saini

    2012-09-01

    Full Text Available Introduction: While planning radiation therapy (RT for a carcinoma of the urinary bladder (CaUB, the intra-fractional variation of the urinary bladder (UB volume due to filling-up needs to be accounted for. This internal target volume (ITV is obtained by adding internal margins (IM to the contoured bladder. This study was planned to propose a method of acquiring individualized ITVs for each patient and to verify their reproducibility. Methods: One patient with CaUB underwent simulation with the proposed ‘bladder protocol’. After immobilization, a planning CT scan on empty bladder was done. He was then given 300 ml of water to drink and the time (T was noted. Planning CT scans were performed after 20 min (T+20, 30 min (T+30 and 40 min (T+40. The CT scan at T+20 was co-registered with the T+30 and T+40 scans. The bladder volumes at 20, 30 and 40 min were then contoured as CTV20, CTV30 and CTV40 to obtain an individualized ITV for our patient. For daily treatment, he was instructed to drink water as above, and the time was noted; treatment was started after 20 min. Daily pre- and post-treatment cone beam CT (CBCT scans were done. The bladder visualized on the pre-treatment CBCT scan was compared with CTV20 and on the post-treatment CBCT scan with CTV30. Results: In total, there were 65 CBCT scans (36 pre- and 29 post-treatment. Individualized ITVs were found to be reproducible in 93.85% of all instances and fell outside in 4 instances. Conclusions: The proposed bladder protocol can yield a reproducible estimation of the ITV during treatment; this can obviate the need for taking standard IMs.

  6. High-risk human papillomavirus infections and overexpression of p53 protein as prognostic indicators in transitional cell carcinoma of the urinary bladder.

    Science.gov (United States)

    Furihata, M; Inoue, K; Ohtsuki, Y; Hashimoto, H; Terao, N; Fujita, Y

    1993-10-15

    Ninety Japanese patients with transitional cell carcinoma of the urinary bladder were investigated for tumor incorporation of DNA for high-risk human papillomavirus (HPV) types 16, 18, and 33 by in situ hybridization with biotinylated DNA probes. In addition, immunohistochemical analysis of p53 protein expression was performed with an antibody to p53 protein. Twenty-eight tumors were positive for HPV DNA, and multiple HPV infection was detected in 17 cases. Positive nuclear staining of cancer cells by the antibody to p53 protein was detected in 32 cases. DNA for HPV 16, 18, and/or 33 and the overexpression of p53 protein were simultaneously observed in 6 tumors by using a mirror section method. The overexpression of p53 protein was frequently detected in invasive and nonpapillary tumors (P infection was more common in noninvasive and papillary tumors (P infection or overexpression of p53 protein may be related to tumor behavior and may indicate a relatively poor prognosis in patients with transitional cell carcinoma.

  7. Malignant fibrous histiocytoma of the urinary bladder as a post-radiation secondary cancer: a case report

    Directory of Open Access Journals (Sweden)

    Nimmanon Thirayost

    2011-11-01

    Full Text Available Abstract Introduction Malignant fibrous histiocytomas have been periodically reported as the primary tumor in various organs including the urinary bladder, and is the second most frequent sarcoma of the urinary tract in adults. This report discusses a case of the well established diagnosis of a malignant fibrous histiocytoma of the bladder occurring as a post-radiation cancer after the treatment of a cervical carcinoma. Our findings support those of many previous studies and make the view of the nature of the disease clearer. Case presentation We report the case of a 54-year-old Thai woman who had been treated with radiation therapy for cervical cancer, who presented to our facility with urinary incontinence. Initially, our patient was diagnosed as having a high-grade urothelial carcinoma. Subsequent radical surgery rendered the final pathological diagnosis, confirmed histologically and immunohistochemically as malignant fibrous histiocytoma, with clinical and pathological staging of T4b N0 M0. Adjuvant chemotherapy was provided for our patient. Conclusions This type of malignancy is very aggressive and easily misdiagnosed due to its rarity. Therefore, in a patient with a prior history of irradiation in the pelvic area, this should be considered as a differential diagnosis to ensure early correct diagnosis and treatment.

  8. Occult Pelvic Lymph Node Involvement in Bladder Cancer: Implications for Definitive Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Goldsmith, Benjamin; Baumann, Brian C.; He, Jiwei; Tucker, Kai; Bekelman, Justin; Deville, Curtiland; Vapiwala, Neha [Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Vaughn, David; Keefe, Stephen M. [Department of Medical Oncology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Guzzo, Thomas; Malkowicz, S. Bruce [Department of Urology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Christodouleas, John P., E-mail: christojo@uphs.upenn.edu [Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (United States)

    2014-03-01

    Purpose: To inform radiation treatment planning for clinically staged, node-negative bladder cancer patients by identifying clinical factors associated with the presence and location of occult pathologic pelvic lymph nodes. Methods and Materials: The records of patients with clinically staged T1-T4N0 urothelial carcinoma of the bladder undergoing radical cystectomy and pelvic lymphadenectomy at a single institution were reviewed. Logistic regression was used to evaluate associations between preoperative clinical variables and occult pathologic pelvic or common iliac lymph nodes. Percentages of patient with involved lymph node regions entirely encompassed within whole bladder (perivesicular nodal region), small pelvic (perivesicular, obturator, internal iliac, and external iliac nodal regions), and extended pelvic clinical target volume (CTV) (small pelvic CTV plus common iliac regions) were calculated. Results: Among 315 eligible patients, 81 (26%) were found to have involved pelvic lymph nodes at the time of surgery, with 38 (12%) having involved common iliac lymph nodes. Risk of occult pathologically involved lymph nodes did not vary with clinical T stage. On multivariate analysis, the presence of lymphovascular invasion (LVI) on preoperative biopsy was significantly associated with occult pelvic nodal involvement (odds ratio 3.740, 95% confidence interval 1.865-7.499, P<.001) and marginally associated with occult common iliac nodal involvement (odds ratio 2.307, 95% confidence interval 0.978-5.441, P=.056). The percentages of patients with involved lymph node regions entirely encompassed by whole bladder, small pelvic, and extended pelvic CTVs varied with clinical risk factors, ranging from 85.4%, 95.1%, and 100% in non-muscle-invasive patients to 44.7%, 71.1%, and 94.8% in patients with muscle-invasive disease and biopsy LVI. Conclusions: Occult pelvic lymph node rates are substantial for all clinical subgroups, especially patients with LVI on biopsy. Extended

  9. Occult Pelvic Lymph Node Involvement in Bladder Cancer: Implications for Definitive Radiation

    International Nuclear Information System (INIS)

    Purpose: To inform radiation treatment planning for clinically staged, node-negative bladder cancer patients by identifying clinical factors associated with the presence and location of occult pathologic pelvic lymph nodes. Methods and Materials: The records of patients with clinically staged T1-T4N0 urothelial carcinoma of the bladder undergoing radical cystectomy and pelvic lymphadenectomy at a single institution were reviewed. Logistic regression was used to evaluate associations between preoperative clinical variables and occult pathologic pelvic or common iliac lymph nodes. Percentages of patient with involved lymph node regions entirely encompassed within whole bladder (perivesicular nodal region), small pelvic (perivesicular, obturator, internal iliac, and external iliac nodal regions), and extended pelvic clinical target volume (CTV) (small pelvic CTV plus common iliac regions) were calculated. Results: Among 315 eligible patients, 81 (26%) were found to have involved pelvic lymph nodes at the time of surgery, with 38 (12%) having involved common iliac lymph nodes. Risk of occult pathologically involved lymph nodes did not vary with clinical T stage. On multivariate analysis, the presence of lymphovascular invasion (LVI) on preoperative biopsy was significantly associated with occult pelvic nodal involvement (odds ratio 3.740, 95% confidence interval 1.865-7.499, P<.001) and marginally associated with occult common iliac nodal involvement (odds ratio 2.307, 95% confidence interval 0.978-5.441, P=.056). The percentages of patients with involved lymph node regions entirely encompassed by whole bladder, small pelvic, and extended pelvic CTVs varied with clinical risk factors, ranging from 85.4%, 95.1%, and 100% in non-muscle-invasive patients to 44.7%, 71.1%, and 94.8% in patients with muscle-invasive disease and biopsy LVI. Conclusions: Occult pelvic lymph node rates are substantial for all clinical subgroups, especially patients with LVI on biopsy. Extended

  10. Photo-thermal therapy of bladder cancer with Anti-EGFR antibody conjugated gold nanoparticles.

    Science.gov (United States)

    Chen, Chieh Hsiao; Wu, Yi-Jhen; Chen, Jia-Jin

    2016-01-01

    The aim of this study was to enhance the effectiveness of photo thermal therapy (PTT) in the targeting of superficial bladder cancers using a green light laser in conjunction with gold nanoparticles (GNPs) conjugated to antibody fragments (anti-EGFR). GNPs conjugated with anti-EGFR-antibody fragments were used as probes in the targeting of tumor cells and then exposed to a green laser (532nm), resulting in the production of sufficient thermal energy to kill urothelial carcinomas both in vitro and in vivo. Nanoparticles conjugated with antibody fragments are capable of damaging cancer cells even at relatively very low energy levels, while non-conjugated nanoparticles would require an energy level of 3 times under the same conditions. The lower energy required by the nanoparticles allows this method to destroy cancerous cells while preserving normal cells when applied in vivo. Nanoparticles conjugated with antibody fragments (anti-EGFR) require less than half the energy of non-conjugated nanoparticles to kill cancer cells. In an orthotopic bladder cancer model, the group treated using PTT presented significant differences in tumor development. PMID:27100501

  11. Correlating Bladder Cancer Risk Genes with Their Targeting MicroRNAs Using MMiRNA-Tar

    Institute of Scientific and Technical Information of China (English)

    Yang Liu; Steve Baker; Hui Jiang; Gary Stuart; Yongsheng Bai

    2015-01-01

    The Cancer Genome Atlas (TCGA) (http://cancergenome.nih.gov) is a valuable data resource focused on an increasing number of well-characterized cancer genomes. In part, TCGA provides detailed information about cancer-dependent gene expression changes, including changes in the expression of transcription-regulating microRNAs. We developed a web interface tool MMiRNA-Tar (http://bioinf1.indstate.edu/MMiRNA-Tar) that can calculate and plot the correlation of expression for mRNA?microRNA pairs across samples or over a time course for a list of pairs under different prediction confidence cutoff criteria. Prediction confidence was estab-lished by requiring that the proposed mRNA?microRNA pair appears in at least one of three target prediction databases:TargetProfiler, TargetScan, or miRanda. We have tested our MMiRNA-Tar tool through analyzing 53 tumor and 11 normal samples of bladder urothelial carcinoma (BLCA) datasets obtained from TCGA and identified 204 microRNAs. These microRNAs were correlated with the mRNAs of five previously-reported bladder cancer risk genes and these selected pairs exhib-ited correlations in opposite direction between the tumor and normal samples based on the cus-tomized cutoff criterion of prediction. Furthermore, we have identified additional 496 genes (830 pairs) potentially targeted by 79 significant microRNAs out of 204 using three cutoff criteria, i.e.

  12. Bladder Health

    Science.gov (United States)

    ... life (the person’s level of health, comfort, and happiness). In fact, people with bladder problems may have a lower quality of life than people with diabetes, heart disease, or high blood pressure. Bladder problems ...

  13. Urinary Bladder

    Science.gov (United States)

    ... to the symphysis pubis, and below the parietal peritoneum . The size and shape of the urinary bladder ... outer layer of the bladder wall is parietal peritoneum. In all other regions, the outer layer is ...

  14. Bladder Retraining

    Science.gov (United States)

    ... a better voiding pattern around the clock. Do Kegel Exercises Help People with IC? Some bladder retraining programs recommend practicing Kegel exercises as part of bladder retraining. Kegel exercises ...

  15. Bladder exstrophy repair

    Science.gov (United States)

    Bladder birth defect repair; Everted bladder repair; Exposed bladder repair; Repair of bladder exstrophy ... Bladder exstrophy repair involves two surgeries. The first surgery is to repair the bladder and the second one is to attach ...

  16. Therapeutic potential of thalidomide for gemcitabine-resistant bladder cancer.

    Science.gov (United States)

    Huang, Yen Ta; Cheng, Chuan Chu; Chiu, Ted H; Lai, Pei Chun

    2015-11-01

    Controversial effects of thalidomide for solid malignancies have been reported. In the present study, we evaluate the effects of thalidomide for transitional cell carcinoma (TCC), the most common type of bladder cancer. Thalidomide precipitates were observed when its DMSO solution was added to the culture medium. No precipitation was found when thalidomide was dissolved in 45% γ-cyclodextrin, and this concentration of γ-cyclodextrin elicited slight cytotoxicity on TCC BFTC905 and primary human urothelial cells. Thalidomide-γ-cyclodextrin complex exerted a concentration-dependent cytotoxicity in TCC cells, but was relatively less cytotoxic (with IC50 of 200 µM) in BFTC905 cells than the other 3 TCC cell lines, possibly due to upregulation of Bcl-xL and HIF-1α mediated carbonic anhydrase IX, and promotion of quiescence. Gemcitabine-resistant BFTC905 cells were chosen for additional experiments. Thalidomide induced apoptosis through downregulation of survivin and securin. The secretion of VEGF and TNF-α was ameliorated by thalidomide, but they did not affect cell proliferation. Immune-modulating lenalidomide and pomalidomide did not elicit cytotoxicity. In addition, cereblon did not play a role in the thalidomide effect. Oxidative DNA damage was triggered by thalidomide, and anti-oxidants reversed the effect. Thalidomide also inhibited TNF-α induced invasion through inhibition of NF-κB, and downregulation of effectors, ICAM-1 and MMP-9. Thalidomide inhibited the growth of BFTC905 xenograft tumors in SCID mice via induction of DNA damage and suppression of angiogenesis. Higher average body weight, indicating less chachexia, was observed in thalidomide treated group. Sedative effect was observed within one-week of treatment. These pre-clinical results suggest therapeutic potential of thalidomide for gemcitabine-resistant bladder cancer.

  17. Key signaling pathways in the muscle-invasive bladder carcinoma: Clinical markers for disease modeling and optimized treatment.

    Science.gov (United States)

    Kiselyov, Alex; Bunimovich-Mendrazitsky, Svetlana; Startsev, Vladimir

    2016-06-01

    In this review, we evaluate key molecular pathways and markers of muscle-invasive bladder cancer (MIBC). Overexpression and activation of EGFR, p63, and EMT genes are suggestive of basal MIBC subtype generally responsive to chemotherapy. Alterations in PPARγ, ERBB2/3, and FGFR3 gene products and their signaling along with deregulated p53, cytokeratins KRT5/6/14 in combination with the cellular proliferation (Ki-67), and cell cycle markers (p16) indicate the need for more radical treatment protocols. Similarly, the "bell-shape" dynamics of Shh expression levels may suggest aggressive MIBC. A panel of diverse biological markers may be suitable for simulation studies of MIBC and development of an optimized treatment protocol. We conducted a critical evaluation of PubMed/Medline and SciFinder databases related to MIBC covering the period 2009-2015. The free-text search was extended by adding the following keywords and phrases: bladder cancer, metastatic, muscle-invasive, basal, luminal, epithelial-to-mesenchymal transition, cancer stem cell, mutations, immune response, signaling, biological markers, molecular markers, mathematical models, simulation, epigenetics, transmembrane, transcription factor, kinase, predictor, prognosis. The resulting selection of ca 500 abstracts was further analyzed in order to select the latest publications relevant to MIBC molecular markers of immediate clinical significance. PMID:26547270

  18. The role of c-FLIP splice variants in urothelial tumours.

    OpenAIRE

    Ewald, F.; Ueffing, N; Brockmann, L; Hader, C; Telieps, T.; Schuster, M; Schulz, W A; Schmitz, I

    2011-01-01

    Deregulation of apoptosis is common in cancer and is often caused by overexpression of anti-apoptotic proteins in tumour cells. One important regulator of apoptosis is the cellular FLICE-inhibitory protein (c-FLIP), which is overexpressed, for example, in melanoma and Hodgkin's lymphoma cells. Here, we addressed the question whether deregulated c-FLIP expression in urothelial carcinoma impinges on the ability of death ligands to induce apoptosis. In particular, we investigated the role of the...

  19. Understanding the molecular pathogenesis and prognostics of bladder cancer: an overview.

    Science.gov (United States)

    Zhao, Ming; He, Xiang-Lei; Teng, Xiao-Dong

    2016-02-01

    The knowledge of cellular mechanisms in malignances of the bladder has grown exponentially. Molecular technologies have led to the discovery of the molecular pathways distinguishing low-and high-grade urothelial neoplasms. This trend portends the future in which the classification and diagnosis of the bladder tumors through morphologic analysis will be supported by molecular information correlating with prognosis and targeted therapy. This article outlines tumor molecular pathology of bladder cancer with an emphasis on several promising candidate biomarkers that may soon make their transition to the realm of clinical management of bladder cancer.

  20. Primary combined carcinoid and adenocarcinoma of the ileum associated with transitional carcinoma of the bladder. Single case report Causa infrecuente de disfagia en el postoperatorio tardío de la cirugía de la hernia de hiato

    Directory of Open Access Journals (Sweden)

    I. D. Venizelos

    2007-03-01

    Full Text Available Composite neoplasms, carcinoid and adenocarcinoma have been reported to occur in several parts of the body, including the stomach, ampulla of Vater, large bowel, lung, and urinary bladder. Here we report a case of a 74-year-old male with a composite carcinoid-adenocarcinoma of the ileum associated with a transitional cell carcinoma of the bladder. The microscopical examination of the composite tumor showed an admixture of typical carcinoid tumor and moderately a differentiated adenocarcinoma. Immunohistochemically, the two components showed clear-cut differentiations. A review of the literature revealed that this is the first reported case of composite carcinoid-adenocarcinoma of the ileum associated with transitional cell carcinoma of the urinary bladder.Las neoplasias compuestas, el carcinoide y el adenocarcinoma se ha observado que aparecen en varias partes del organismo, como el estómago, la ampolla de Vater, el intestino grueso, el pulmón y la vejiga urinaria. Publicamos aquí el caso de un varón de 74 años con un tumor compuesto de tipo carcinoide-adenocarcinoma del íleon asociado a un carcinoma vesical de células transicionales. El examen macroscópico del tumor compuesto mostró una mezcla de tumor carcinoide típico y adenocarcinoma moderadamente diferenciado. Desde el punto de vista inmunohistoquímico, los dos componentes estaban claramente diferenciados. Una revisión de la bibliografía reveló que este es el primer caso que se publica de un tumor compuesto de tipo carcinoide-adenocarcinoma del íleon asociado a un carcinoma de células transicionales de la vejiga urinaria.

  1. Neurogenic Bladder

    Directory of Open Access Journals (Sweden)

    Peter T. Dorsher

    2012-01-01

    Full Text Available Congenital anomalies such as meningomyelocele and diseases/damage of the central, peripheral, or autonomic nervous systems may produce neurogenic bladder dysfunction, which untreated can result in progressive renal damage, adverse physical effects including decubiti and urinary tract infections, and psychological and social sequelae related to urinary incontinence. A comprehensive bladder-retraining program that incorporates appropriate education, training, medication, and surgical interventions can mitigate the adverse consequences of neurogenic bladder dysfunction and improve both quantity and quality of life. The goals of bladder retraining for neurogenic bladder dysfunction are prevention of urinary incontinence, urinary tract infections, detrusor overdistension, and progressive upper urinary tract damage due to chronic, excessive detrusor pressures. Understanding the physiology and pathophysiology of micturition is essential to select appropriate pharmacologic and surgical interventions to achieve these goals. Future perspectives on potential pharmacological, surgical, and regenerative medicine options for treating neurogenic bladder dysfunction are also presented.

  2. Pokemon蛋白在膀胱尿路上皮癌中的表达及其意义%Expression of Pokemon protein and its clinical significance in bladder transitional cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    侯列军; 虞亦鸣; 孙灵军; 虞建达

    2014-01-01

    目的:检测膀胱尿路上皮癌组织中Pokemon蛋白的表达,分析其与临床病理特征间的关系。方法收集2010年3月~2013年8月宁波大学附属医院泌尿外科27例膀胱尿路上皮癌术中切除的癌、癌旁及临近正常组织,应用免疫印迹法(Western blot)检测标本中Pokemon蛋白的表达,并对其与膀胱癌的临床病理特征进行分析。结果 Western blot检测到Pokemon蛋白在膀胱尿路上皮癌组织中表达较高、在癌旁及正常组织中表达较低,差异有统计学意义(P<0.05)。膀胱癌组织中Pokemon蛋白表达与肿瘤病理分级有关,而与患者的性别、年龄、吸烟史及TNM临床分期无明显相关。结论 Pokemon蛋白表达和膀胱尿路上皮癌的发病及恶性程度有关,可能成为膀胱尿路上皮癌治疗的有效靶点。%Objective To explore the expression of Pokemon protein in bladder transitional cell carcinoma and its cor-relation with clinical features. Methods From March 2010 to August 2013, at Department of Urinary Surgery in Affili-ated Hospital of Ningbo University, 27 resection samples of patiens with bladder transitional cell carcinoma, including carcinoma tissue, paracancerous tissue and normal tissue were selected. Western blot was applied to detect the expres-sion of Pokemon protein in tissue and clinical-pathological features was analyzed. Results The result of Westen blot showed that the expression of Pokemon protein in bladder transitional cell carcinoma tissue was significantly higher than those of paracancerous tissue and normal tissue, the differences were statistically significant (P< 0.05). The ex-pression of Pokemon was related to different tumor degree, and no related to patient's gender, age, smoking history and TNM stages. Conclusion Pokemon protein is expressed in bladder transitional cell carcinoma and it may play a key role in the genesis of transitional cell carcinoma of bladder. It may be the therapeutic target of

  3. Fatty acid binding proteins (FABPs in prostate, bladder and kidney cancer cell lines and the use of IL-FABP as survival predictor in patients with renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Jung Klaus

    2011-07-01

    Full Text Available Abstract Background Fatty acid binding proteins (FABP play an important role in carcinogenesis. Modified FABP expression patterns were described for prostate, bladder and for renal cell carcinoma. Studies on metabolic relationships and interactions in permanent cell lines allow a deeper insight into molecular processes. The aim of this study is therefore a systematic overview on mRNA and protein expressions of seven FABPs in frequently used urological cell lines. Methods Nine cell lines of renal carcinomas, seven of urinary bladder carcinomas, and five of prostate carcinomas were investigated. Quantitative RT-qPCR and western blotting were used to determine different FABPs. In addition, 46 paired cancerous and noncancerous tissue samples from nephrectomy specimen with renal cell carcinomas were investigated regarding the ileum FABP mRNA expression level and associated with survival outcome. Results General characteristics of all urological carcinoma cell lines were the expression of E-and IL-FABP on mRNA and protein level, while the expressions differed between the cell lines. The protein expression was not always congruent with the mRNA expression. Renal cell carcinoma cell lines showed expressions of L-, H- and B-FABP mRNA in addition to the general FABP expression in five out of the eight investigated cell lines. In bladder cancer cell lines, we additionally found the expression of A-FABP mRNA in six cell lines, while H-FABP was present only in three cell lines. In prostate cancer cell lines, a strong reduction of A- and E- FABP mRNA was observed. The expression of B-FABP mRNA and protein was observed only in the 22 RV-1 cells. IL-FABP mRNA was over-expressed in renal tumour tissue. The IL-FABP ratio was identified as an independent indicator of survival outcome. Conclusions Distinctly different FABP expression patterns were observed not only between the cell lines derived from the three cancer types, but also between the cell lines from the

  4. Fatty acid binding proteins (FABPs) in prostate, bladder and kidney cancer cell lines and the use of IL-FABP as survival predictor in patients with renal cell carcinoma

    International Nuclear Information System (INIS)

    Fatty acid binding proteins (FABP) play an important role in carcinogenesis. Modified FABP expression patterns were described for prostate, bladder and for renal cell carcinoma. Studies on metabolic relationships and interactions in permanent cell lines allow a deeper insight into molecular processes. The aim of this study is therefore a systematic overview on mRNA and protein expressions of seven FABPs in frequently used urological cell lines. Nine cell lines of renal carcinomas, seven of urinary bladder carcinomas, and five of prostate carcinomas were investigated. Quantitative RT-qPCR and western blotting were used to determine different FABPs. In addition, 46 paired cancerous and noncancerous tissue samples from nephrectomy specimen with renal cell carcinomas were investigated regarding the ileum FABP mRNA expression level and associated with survival outcome. General characteristics of all urological carcinoma cell lines were the expression of E-and IL-FABP on mRNA and protein level, while the expressions differed between the cell lines. The protein expression was not always congruent with the mRNA expression. Renal cell carcinoma cell lines showed expressions of L-, H- and B-FABP mRNA in addition to the general FABP expression in five out of the eight investigated cell lines. In bladder cancer cell lines, we additionally found the expression of A-FABP mRNA in six cell lines, while H-FABP was present only in three cell lines. In prostate cancer cell lines, a strong reduction of A- and E- FABP mRNA was observed. The expression of B-FABP mRNA and protein was observed only in the 22 RV-1 cells. IL-FABP mRNA was over-expressed in renal tumour tissue. The IL-FABP ratio was identified as an independent indicator of survival outcome. Distinctly different FABP expression patterns were observed not only between the cell lines derived from the three cancer types, but also between the cell lines from the same cancer. The FABP patterns in the cell lines do not always

  5. Dual ligand/receptor interactions activate urothelial defenses against uropathogenic E. coli.

    Science.gov (United States)

    Liu, Yan; Mémet, Sylvie; Saban, Ricardo; Kong, Xiangpeng; Aprikian, Pavel; Sokurenko, Evgeni; Sun, Tung-Tien; Wu, Xue-Ru

    2015-11-09

    During urinary tract infection (UTI), the second most common bacterial infection, dynamic interactions take place between uropathogenic E. coli (UPEC) and host urothelial cells. While significant strides have been made in the identification of the virulence factors of UPEC, our understanding of how the urothelial cells mobilize innate defenses against the invading UPEC remains rudimentary. Here we show that mouse urothelium responds to the adhesion of type 1-fimbriated UPEC by rapidly activating the canonical NF-κB selectively in terminally differentiated, superficial (umbrella) cells. This activation depends on a dual ligand/receptor system, one between FimH adhesin and uroplakin Ia and another between lipopolysaccharide and Toll-like receptor 4. When activated, all the nuclei (up to 11) of a multinucleated umbrella cell are affected, leading to significant amplification of proinflammatory signals. Intermediate and basal cells of the urothelium undergo NF-κB activation only if the umbrella cells are detached or if the UPEC persistently express type 1-fimbriae. Inhibition of NF-κB prevents the urothelium from clearing the intracellular bacterial communities, leading to prolonged bladder colonization by UPEC. Based on these data, we propose a model of dual ligand/receptor system in innate urothelial defenses against UPEC.

  6. Long-term survival results of a randomized phase III trial of vinflunine plus best supportive care versus best supportive care alone in advanced urothelial carcinoma patients after failure of platinum-based chemotherapy

    DEFF Research Database (Denmark)

    Bellmunt, J; Fougeray, R; Rosenberg, J E;

    2013-01-01

    To compare long-term, updated overall survival (OS) of patients with advanced transitional cell carcinoma of the urothelium (TCCU) treated with vinflunine plus best supportive care (BSC) or BSC alone, after failure of platinum-based chemotherapy.......To compare long-term, updated overall survival (OS) of patients with advanced transitional cell carcinoma of the urothelium (TCCU) treated with vinflunine plus best supportive care (BSC) or BSC alone, after failure of platinum-based chemotherapy....

  7. 阴茎转移性膀胱鳞癌的诊治:附病例报告%Diagnosis and Treatment of Penis Metastatic Squamous Carcinoma of Bladder:One Case Report

    Institute of Scientific and Technical Information of China (English)

    胡志; 谢庆祥

    2012-01-01

    Objective To improve the understanding of penis metastatic squamous carcinoma of bladder. Methods A case of penis metastatic squamous carcinoma of bladder was reported. One year after the total removal of bladder, pathology report showed level 3 transitional cell carcinoma that was partly squamous, and a lump was found at the root of the penis. The pathogenic mechanism, clinical diagnosis, treatment and prognosis were analyzed. Results Scattered degenerative carcinoma cells were found after fine - needle aspiration, and total penectomy was performed. Postoperative pathology showed differentiated squamous carcinoma of penis, which met the diagnosis criteria of bladder squamous carcinoma metastasis. There were no carcinoma cells in cavernous body of the penis and urethra. Radiotherapy was given to upper pubis and inguinal areas three weeks after operation, but was terminated due to refractory dizziness. 17 months following up showed no relapse and metastasis. Conclusion Retrograde venous and lymphatic flow in the pelvic cavity may be the mechanism for penis metastatic squamous carcinoma of bladder. Fine -needle aspiration is a safe and effective method for diagnosis, and total penectomy is the main treatment, combined with radiotherapy and chemotherapy.%目的 提高对阴茎转移性膀胱癌的认识.方法 回顾性分析1例阴茎转移性膀胱鳞癌患者的临床资料,患者膀胱根治性全切术后1年,病理报告膀胱移行细胞癌3级、部分鳞化,发现阴茎根部肿块1个月.讨论其发病机制、临床诊断、治疗及预后.结果 细针穿刺见到散在变性癌细胞,行根治性阴茎全切术,术后病理报告阴茎低-中分化鳞状细胞癌,结合病史,符合膀胱癌转移,海绵体及尿道均未见肿瘤浸润.术后3周行耻骨上区和双侧腹股沟区放疗1次,因出现顽固性头晕而终止.现随访17个月未发现复发和转移.结论 肿瘤细胞循盆腔静脉丛及淋巴途径逆流是阴茎转移性膀胱癌

  8. Emerging applications of the single cell gel electrophoresis (Comet) assay. I. Management of invasive transitional cell human bladder carcinoma. II. Fluorescent in situ hybridization Comets for the identification of damaged and repaired DNA sequences in individual cells.

    Science.gov (United States)

    McKelvey-Martin, V J; Ho, E T; McKeown, S R; Johnston, S R; McCarthy, P J; Rajab, N F; Downes, C S

    1998-01-01

    ABSTRACT I: Management of invasive transitional cell human bladder carcinoma. The two main treatment options for invasive transitional cell bladder carcinoma are radiotherapy or primary cystectomy with urinary diversion or bladder substitution. Approximately 50% of patients fail to respond to radiotherapy and such patients so treated are disadvantaged by the absence of predictive information regarding their radiosensitivity, since the tumour gains additional time for metastatic spread before cystectomy is performed. The SF2 clonogenic assay, which measures the surviving fraction of tumour cells after 2 Gy X-ray irradiation, is regarded as a good measure of radiosensitivity. However, the assay is time consuming and provides results for only approximately 70% of human tumours. In this paper three bladder transitional cell carcinoma cell lines (HT1376, UMUC-3 and RT112) were exposed to X-irradiation (0-10 Gy). We have compared the responses obtained using a clonogenic assay and a more clinically feasible alkaline single cell gel electrophoresis (Comet) assay. A very good inverse correlation was obtained between cell survival (clonogenic assay) and mean tail moment (Comet assay) for the three cell lines, indicating that the Comet assay can be used to predict the radio-responsiveness of individual cell lines. The clinical usefulness of the assay for predicting response to radiotherapy in bladder cancer patients is currently being investigated. ABSTRACT II: Fluorescent in situ hybridization (FISH) Comets for the identification of damaged and repaired DNA sequences in individual cells. In mammalian cells the extent of DNA damage is partly and the rate of DNA repair very considerably dependent on DNA position and transcription. This has been established by biochemical techniques which are labour intensive and require large numbers of cells. The Comet assay for overall DNA damage and repair is relatively simple and allows individual cells to be examined. Here we present a

  9. Study on MGMT expression in transitional cell carcinoma of bladder%MGMT在膀胱移行细胞癌中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    于江华; 史海军; 窦中岭; 刘辉; 李元; 任素娟

    2010-01-01

    目的 探讨O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)在膀胱移行细胞癌(transitional cell carcinoma of bladder,TCCB)中的表达及意义.方法 采用免疫组织化学法检测80例膀胱移行细胞癌组织,30例癌旁组织及20例正常膀胱组织中的MGMT表达,分析其与临床病理的相关性及意义.结果 MGMT在膀胱移行细胞癌组织中的阳性表达率为32.5%(26/80),显著低于癌旁组织(76.7%,23/30)和膀胱正常组织(65.0%,13/20);膀胱移行细胞癌分化Ⅰ级的阳性表达率为(48.6%,18/37),显著高于Ⅱ级(23.1%,6/26) 和Ⅲ级(11.8%,2/17);但MGMT表达与膀胱癌临床分期、患者性别、患者年龄、肿瘤数量、发病次数均无显著相关.结论 MGMT可能成为膀胱癌诊断及判断预后的标志物之一.

  10. Urothelial cultures support intracellular bacterial community formation by uropathogenic Escherichia coli.

    Science.gov (United States)

    Berry, Ruth E; Klumpp, David J; Schaeffer, Anthony J

    2009-07-01

    Uropathogenic Escherichia coli (UPEC) causes most community-acquired and nosocomial urinary tract infections (UTI). In a mouse model of UTI, UPEC invades superficial bladder cells and proliferates rapidly, forming biofilm-like structures called intracellular bacterial communities (IBCs). Using a gentamicin protection assay and fluorescence microscopy, we developed an in vitro model for studying UPEC proliferation within immortalized human urothelial cells. By pharmacologic manipulation of urothelial cells with the cholesterol-sequestering drug filipin, numbers of intracellular UPEC CFU increased 8 h and 24 h postinfection relative to untreated cultures. Enhanced UPEC intracellular proliferation required that the urothelial cells, but not the bacteria, be filipin treated prior to infection. However, neither UPEC frequency of invasion nor early intracellular trafficking events to a Lamp1-positive compartment were modulated by filipin. Upon inspection by fluorescence microscopy, cultures with enhanced UPEC intracellular proliferation exhibited large, dense bacterial aggregates within cells that resembled IBCs but were contained with Lamp1-positive vacuoles. While an isogenic fimH mutant was capable of forming these IBC-like structures, the mutant formed significantly fewer than wild-type UPEC. Similar to IBCs, expression of E. coli iron acquisition systems was upregulated by intracellular UPEC. Expression of other putative virulence factors, including hlyA, cnf1, fliC, kpsD, and the biofilm adhesin yfaL also increased, while expression of fimA decreased and that of flu did not change. These results indicate that UPEC differentially regulates virulence factors in the intracellular environment. Thus, immortalized urothelial cultures that recapitulate IBC formation in vitro represent a novel system for the molecular and biochemical characterization of the UPEC intracellular life cycle.

  11. Microsatellite instability in bladder cancer

    DEFF Research Database (Denmark)

    Gonzalez-Zulueta, M; Ruppert, J M; Tokino, K;

    1993-01-01

    Somatic instability at microsatellite repeats was detected in 6 of 200 transitional cell carcinomas of the bladder. Instabilities were apparent as changes in (GT)n repeat lengths on human chromosome 9 for four tumors and as alterations in a (CAG)n repeat in the androgen receptor gene on the X...

  12. Dose and temporal effects on gene expression profiles of urothelial cells from rats exposed to diuron

    International Nuclear Information System (INIS)

    Diuron (3-(3,4-dichlorophenyl)-1,1-dimethylurea) is a substituted urea herbicide that at high dietary levels (2500 ppm) induces rat urinary bladder hyperplasia after 20 weeks of exposure and neoplasia after 2 years. The effects on the urothelium after short-term exposure have not been described. The present 7-day study evaluated the dose-dependency of urothelial alterations in the urinary bladder using light microscopy, scanning electron microscopy, and genome-wide transcriptional profiling. Male Wistar rats were fed 0, 125, 500, 2500 ppm diuron for 7 days. The urinary bladder and isolated urothelial cells of these animals were processed for microscopic examination and gene expression profiling, respectively. No significant treatment-related morphologic effects were observed. The number of differentially expressed genes (DEGs) in the exposed groups increased with diuron levels. Diuron-altered genes involved in cell-to-cell interactions and tissue organization were identified in all treatment groups. After 7 days of diuron exposure, transcriptional responses were observed in the urothelium in the absence of clear morphologic changes. These morphological findings are different from those observed in a previous study in which 20 weeks of diuron exposure was associated with simple hyperplasia secondary to the persistent cytotoxicity and necrosis associated with continuous cellular regeneration. Comparison of the gene expression profiles of rats exposed to the 2500 ppm carcinogenic diuron dose for 7 days versus 20 weeks revealed few similarities between these two time points at the gene or pathway level. Taken together, these data provide insight into the dose- and temporal-dependent morphological and transcriptional changes associated with diuron exposure that may lead to the development of tumors in the rat urinary bladder

  13. Antrodia camphorata extract induces replicative senescence in superficial TCC, and inhibits the absolute migration capability in invasive bladder carcinoma cells.

    Science.gov (United States)

    Peng, Chiung-Chi; Chen, Kuan-Chou; Peng, Robert Y; Chyau, Charng-Cherng; Su, Ching-Hua; Hsieh-Li, Hsiu Mei

    2007-01-01

    The Antrodia camphorata crude extract (ACCE), an extract obtained from a precious traditional Chinese folkloric herbal medicine Zhan-Ku (a camphor tree mushroom) since the 18th century, has showed rather significant inhibitory effects on the growth and proliferation of the transitional cell carcinomas (TCC) cell lines RT4, TSGH-8301, and T24. On treatment with ACCE at 100 microg/mL, the p53-independent overexpression of p21 with simultaneous down alteration of pRb was observed in RT4, which was thus speculative of proceeding through a mechanism of replicative senescence. On the contrary treatment with ACCE, at 50 microg/mL, resulting in simultaneous down-regulations of Cdc2 and Cyclin B1, with suppression of the absolute migrating capability of the two cell lines TSGH-8301 and T24, and eventually the cell deaths. We conclude that ACCE can be rather effective and beneficial in suppression of both the superficial cancer cell line RT4 and the metastatic cell lines (TSGH-8301 and T24) through different mechanisms.

  14. Improvements in culturing exfoliated urothelial cells in vitro from human urine.

    Science.gov (United States)

    Belik, Rouslana; Follmann, Wolfram; Degen, Gisela H; Roos, Peter H; Blaszkewicz, Meinolf; Knopf, H Jurgen; Golka, Klaus

    2008-01-01

    Human bladder cancer is a common malignant tumor that may be produced by factors such as lifestyle, environment and occupation. The aim of this study was to evaluate parameters related to the viability of exfoliated urothelial cells. Exfoliated urothelial cells were obtained from 83 urine samples of 22 healthy participants (20-53 yr). From 67 of these samples, cells were transferred to collagen-coated 24-well plates. Parameters including sample volume, pH, osmolality and participant age and gender were examined on cell viability. In successive cultures, the numbers of cell colonies and cells per cell colony were determined. The number of viable cells in the urinary sediments of males varied from 0 to 6.5 x 10(3) cells per sample (mean 1 x 10(3)). Higher cell numbers in urine samples from females (6 x 10(3)) were due to considerable amounts of exfoliated vaginal cells. Cell numbers in males were positively related to volume, osmolality, and pH of the samples, as well as to the retention time of urine in the bladder. Cell proliferation was achieved in 25 out of 67 samples and was positively related to sample osmolality and pH. Participant age and content of urinary oxalates exerted negative effects on cell proliferation in vitro. The mean number of cell colonies per sample was 1.7. The mean cell number per colony was 11.7 x 10(3). It appears that high variability in individual excretion of urothelial cells able to proliferate is a limiting factor for routine use of these cells for in vitro toxicology.

  15. FISH技术在诊断膀胱移行上皮细胞癌中的应用%Clinical practice of fluorescence in situ hybridization in diagnosing bladder transitional cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    杨渝伟; 唐洁; 陈小红; 薛冰蓉; 刘运双; 俸家富

    2011-01-01

    目的 探讨荧光原位杂交(FISH)技术在膀胱移行上皮细胞癌诊断中的价值和意义.方法用随机引物法标记 3、7、17号染色体着丝粒及p16基因探针,对该院103例膀胱移行上皮细胞癌患者尿液或膀胱冲洗液中脱落细胞FISH进行检测,分析染色体畸变或数目异常情况及与临床分期、病理分级的关系.结果 3、7、17号染色体和p16基因的畸变率分别为41.7%(43/103)、45.6%(47/103)、31.1%(32/103)和55.3%(57/103),畸变与临床分期无相关性,除p16基因外其余染色体畸变与病理分级相关,其中17号染色体畸变与病理分级显著相关(P<0.01).4个探针组合诊断膀胱移行上皮细胞癌的总阳性率为46.6%,与临床分期无相关性(P>0.05),但与病理分级显著相关(P<0.01).结论 FISH 技术检测有助于膀胱移行上皮细胞癌的诊断,并可用于探索染色体畸变与病理分级的关系.%Objective To investigate the value and significance of fluorescence in situ hybridization(FISH)in diagnosing bladder transitional cell carcinoma. Methods The probes of chromosome 3,7,17 centromeres and p16 gene were labeled by random primer method. FISH was performed on interphase nuclei of exfoliated cells collected in urine and bladder washings in 103 samples of bladder transitional cell carcinoma,and analyzed the correlations between chromosome aberration or numerical abnormality with clinical stages and pathologic grades. Results The rate of aneuploidy was 41. 7% for chromosome 3,4 5. 6% for chromosome 7,31. 1% for chromosome 17,and 55. 3% for pl6 gene in bladder transitional cell carcinoma. All the aberrations had no correlation to clinical stages. The aberrations of chromosomes 3,7,17 were significantly correlated to pathologic grades(P<0. 01) , especially, chromosome 17. As using the 4 chromosome probes in combination,the sensitivity for diagnosing bladder transitional cell carcinoma was 46. 6% , and had no correlation to clinical stages,but were

  16. Immediate versus deferred chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcinoma of the bladder (EORTC 30994): an intergroup, open-label, randomised phase 3 trial

    DEFF Research Database (Denmark)

    Sternberg, Cora N; Skoneczna, Iwona; Kerst, J Martijn;

    2015-01-01

    143 to deferred treatment), and followed up until the data cutoff of Aug 21, 2013. After a median follow-up of 7.0 years (IQR 5.2-8.7), 66 (47%) of 141 patients in the immediate treatment group had died compared with 82 (57%) of 143 in the deferred treatment group. No significant improvement in...

  17. Sequential Therapy with Gemcitabine and Carboplatin Followed by Paclitaxel as First Line Treatment for Advanced Urothelial Cancer

    Directory of Open Access Journals (Sweden)

    Joseph G Kattan, Celine Y Boutros, Fadi S Farhat, Georges Y Chahine, Khaled M Musallam, Marwan G Ghosn

    2012-01-01

    Full Text Available Objective: Gemcitabine and platinum-based compounds represent the new standard combination therapy for bladder cancer. In this study, we evaluate the efficacy and safety of gemcitabine and carboplatin followed sequentially by paclitaxel in 27 patients with advanced transitional cell carcinoma.Methods: This phase II multicentre study was based on the doublet gemcitabine 800 mg/m2 and carboplatin area under the concentration-time curve 2 on days 1 and 8 every 21 days for 4 cycles, followed sequentially by paclitaxel 60 mg/m2/w for 12 consecutive weeks. The disease was assessed after each sequence.Results: Primary tumor was localized in the bladder and renal pelvis in 25 and 2 patients, respectively. Twenty patients completed all 4 cycles of the gemcitabine and carboplatin sequence. Mean number of cycles was 3.5 (range 1 to 4. Toxicities were mainly hematologic, including Grade 3 neutropenia and anemia in 3 patients. Objective response was noted in 11 pts (40.7%, including 1 complete response (CR and 10 partial responses (PR. Three patients had stable disease and 11 progressed. Among the 20 patients, 14 received the second sequence. Mean number of paclitaxel injections was 7 (range 2 to 12. Toxicities were limited to diarrhea and neurotoxicity in 1 patient each. Objective response was documented in 6 patients (30% (3 CR and 3 PR, including the improvement of PR into CR in 2 patients. Median duration of response was 6 months. After a median follow-up of 7 months, 21 patients died and 6 remained alive, including 2 who maintained CR and 1 PR.Sixteen patients had locally advanced disease and 11 had metastatic disease, better prognostic was noticed with patients with locally advanced disease.Conclusion: the sequential approach of treatment for advanced urothelial cancer using gemcitabine and carboplatine followed by paclitaxel seems to be a safer alternative to the combined triplet, but due to the limited number of patients this study failed to improve

  18. Multilayer spiral CT Scanning in Transitional cell Carcinoma of Bladder and Application Analysis%多层螺旋CT扫描在膀胱移行细胞癌中的应用分析

    Institute of Scientific and Technical Information of China (English)

    黄云开; 曾怡群

    2013-01-01

      目的探讨多层螺旋CT诊断膀胱移行细胞癌的应用价值。方法收集48例经手术病理证实的膀胱移行细胞癌患者的CT影像资料与临床资料,展开回顾性的研究。结果48例患者中,CT术前检测出45例,未检出3例;单发病灶25例,多发病灶20例;菜花状28例,乳头状8例,局限性膀胱壁增厚9例。结论多层螺旋CT能够准确地诊断出膀胱移行细胞癌,在病理诊断的基础上,充分结合CT影像资料,将极大提高分期诊断的准确率。%Objective Application of multislice helical CT in diagnosis of bladder transitional cel cancer value. Methods Col ection of 48cases confirmed by operation and pathology of bladder transitional cel cancer patients CT images and clinical data, launched a retrospective study. Results In 48 patients, CT preoperative detection of out of 45 cases, 3 cases of solitary lesions not detected; in 25 cases, multiple lesions in 20 cases; 28 cases of papil ary cauliflower-like, in 8 cases, limitations of the bladder wal thickening in 9 cases. Conclusion Multi slice spiral CT can accurately diagnose of bladder transitional cel carcinoma, the diagnosis based on pathology, ful y integrated CT imaging data, wil greatly improve staging accuracy rate of diagnosis.

  19. Metabolic phenotype of bladder cancer.

    Science.gov (United States)

    Massari, Francesco; Ciccarese, Chiara; Santoni, Matteo; Iacovelli, Roberto; Mazzucchelli, Roberta; Piva, Francesco; Scarpelli, Marina; Berardi, Rossana; Tortora, Giampaolo; Lopez-Beltran, Antonio; Cheng, Liang; Montironi, Rodolfo

    2016-04-01

    Metabolism of bladder cancer represents a key issue for cancer research. Several metabolic altered pathways are involved in bladder tumorigenesis, representing therefore interesting targets for therapy. Tumor cells, including urothelial cancer cells, rely on a peculiar shift to aerobic glycolysis-dependent metabolism (the Warburg-effect) as the main energy source to sustain their uncontrolled growth and proliferation. Therefore, the high glycolytic flux depends on the overexpression of glycolysis-related genes (SRC-3, glucose transporter type 1 [GLUT1], GLUT3, lactic dehydrogenase A [LDHA], LDHB, hexokinase 1 [HK1], HK2, pyruvate kinase type M [PKM], and hypoxia-inducible factor 1-alpha [HIF-1α]), resulting in an overproduction of pyruvate, alanine and lactate. Concurrently, bladder cancer metabolism displays an increased expression of genes favoring the pentose phosphate pathway (glucose-6-phosphate dehydrogenase [G6PD]) and the fatty-acid synthesis (fatty acid synthase [FASN]), along with a decrease of AMP-activated protein kinase (AMPK) and Krebs cycle activities. Moreover, the PTEN/PI3K/AKT/mTOR pathway, hyper-activated in bladder cancer, acts as central regulator of aerobic glycolysis, hence contributing to cancer metabolic switch and tumor cell proliferation. Besides glycolysis, glycogen metabolism pathway plays a robust role in bladder cancer development. In particular, the overexpression of GLUT-1, the loss of the tumor suppressor glycogen debranching enzyme amylo-α-1,6-glucosidase, 4-α-glucanotransferase (AGL), and the increased activity of the tumor promoter enzyme glycogen phosphorylase impair glycogen metabolism. An increase in glucose uptake, decrease in normal cellular glycogen storage, and overproduction of lactate are consequences of decreased oxidative phosphorylation and inability to reuse glucose into the pentose phosphate and de novo fatty acid synthesis pathways. Moreover, AGL loss determines augmented levels of the serine-to-glycine enzyme

  20. Overactive bladder – 18 years – Part II

    Science.gov (United States)

    Truzzi, Jose Carlos; Gomes, Cristiano Mendes; Bezerra, Carlos A.; Plata, Ivan Mauricio; Campos, Jose; Garrido, Gustavo Luis; Almeida, Fernando G.; Averbeck, Marcio Augusto; Fornari, Alexandre; Salazar, Anibal; Dell’Oro, Arturo; Cintra, Caio; Sacomani, Carlos Alberto Ricetto; Tapia, Juan Pablo; Brambila, Eduardo; Longo, Emilio Miguel; Rocha, Flavio Trigo; Coutinho, Francisco; Favre, Gabriel; Garcia, José Antonio; Castaño, Juan; Reyes, Miguel; Leyton, Rodrigo Eugenio; Ferreira, Ruiter Silva; Duran, Sergio; López, Vanda; Reges, Ricardo

    2016-01-01

    ABSTRACT Traditionally, the treatment of overactive bladder syndrome has been based on the use of oral medications with the purpose of reestablishing the detrusor stability. The recent better understanding of the urothelial physiology fostered conceptual changes, and the oral anticholinergics – pillars of the overactive bladder pharmacotherapy – started to be not only recognized for their properties of inhibiting the detrusor contractile activity, but also their action on the bladder afference, and therefore, on the reduction of the symptoms that constitute the syndrome. Beta-adrenergic agonists, which were recently added to the list of drugs for the treatment of overactive bladder, still wait for a definitive positioning – as either a second-line therapy or an adjuvant to oral anticholinergics. Conservative treatment failure, whether due to unsatisfactory results or the presence of adverse side effects, define it as refractory overactive bladder. In this context, the intravesical injection of botulinum toxin type A emerged as an effective option for the existing gap between the primary measures and more complex procedures such as bladder augmentation. Sacral neuromodulation, described three decades ago, had its indication reinforced in this overactive bladder era. Likewise, the electric stimulation of the tibial nerve is now a minimally invasive alternative to treat those with refractory overactive bladder. The results of the systematic literature review on the oral pharmacological treatment and the treatment of refractory overactive bladder gave rise to this second part of the review article Overactive Bladder – 18 years, prepared during the 1st Latin-American Consultation on Overactive Bladder. PMID:27176185

  1. Bladder cancer: molecular determinants of personalized therapy.

    Science.gov (United States)

    Lopez-Beltran, Antonio; Santoni, Matteo; Massari, Francesco; Ciccarese, Chiara; Tortora, Giampaolo; Cheng, Liang; Moch, Holger; Scarpelli, Marina; Reymundo, Carlos; Montironi, Rodolfo

    2015-01-01

    Several molecular and genetic studies have provided new perspectives on the histologic classification of bladder tumors. Recent developments in the field of molecular mutational pathway analyses based on next generation sequencing technology together with classic data derived from the description of mutations in the FGFR3 (fibroblast growth factor receptor 3) gene, mutations on TP53 gene, and cDNA technology profiling data gives support to a differentiated taxonomy of bladder cancer. All these changes are behind the use of non-traditional approach to therapy of bladder cancer patients and are ready to change our daily practice of uro-oncology. The observed correlation of some molecular alterations with tumor behavior and the identification of their targets at cellular level might support the use of molecular changes together with morphological data to develop new clinical and biological strategies to manage patients with urothelial cancer. The current review provides comprehensive data to support personalized therapy for bladder cancer based on an integrated approach including pathologic and clinical features and molecular biology.

  2. Ketamine-induced ulcerative cystitis and bladder apoptosis involve oxidative stress mediated by mitochondria and the endoplasmic reticulum.

    Science.gov (United States)

    Liu, Keh-Min; Chuang, Shu-Mien; Long, Cheng-Yu; Lee, Yi-Lun; Wang, Chao-Chuan; Lu, Mei-Chin; Lin, Rong-Jyh; Lu, Jian-He; Jang, Mei-Yu; Wu, Wen-Jeng; Ho, Wan-Ting; Juan, Yung-Shun

    2015-08-15

    Ketamine abusers develop severe lower urinary tract symptoms. The major aims of the present study were to elucidate ketamine-induced ulcerative cystitis and bladder apoptosis in association with oxidative stress mediated by mitochondria and the endoplasmic reticulum (ER). Sprague-Dawley rats were distributed into three different groups, which received normal saline or ketamine for a period of 14 or 28 days, respectively. Double-labeled immunofluorescence experiments were performed to investigate tight junction proteins for urothelial barrier functions. A TUNEL assay was performed to evaluate the distribution of apoptotic cells. Western blot analysis was carried out to examine the expressions of urothelial tight junction proteins, ER stress markers, and apoptosis-associated proteins. Antioxidant enzymes, including SOD and catalase, were investigated by real-time PCR and immunofluorescence experiments. Ketamine-treated rats were found to display bladder hyperactivity. This bladder dysfunction was accompanied by disruptions of epithelial cadherin- and tight junction-associated proteins as well as increases in the expressions of apoptosis-associated proteins, which displayed features of mitochondria-dependent apoptotic signals and ER stress markers. Meanwhile, expressions of mitochondria respiratory subunit enzymes were significantly increased in ketamine-treated bladders. Conversely, mRNA expressions of the antioxidant enzymes Mn-SOD (SOD2), Cu/Zn-SOD (SOD1), and catalase were decreased after 28 days of ketamine treatment. These results demonstrate that ketamine enhanced the generation of oxidative stress mediated by mitochondria- and ER-dependent pathways and consequently contributed to bladder apoptosis and urothelial lining defects. Such oxidative stress-enhanced bladder cell apoptosis and urothelial barrier defects are potential factors that may play a crucial role in bladder overactivity and ulceration. PMID:26109091

  3. Overactive Bladder.

    Science.gov (United States)

    White, Nicola; Iglesia, Cheryl B

    2016-03-01

    Overactive bladder (OAB) is a condition affecting millions of individuals in the United States. Anticholinergics are the mainstay of treatment. Bladder botulinum toxin injections have shown an improvement in symptoms of OAB equivalent to anticholinergic therapy. Percutaneous tibial nerve stimulation can decrease symptoms of urinary frequency and urge incontinence. Sacral neuromodulation for refractory patients has been approved by the Food and Drug Administration for treatment of OAB, urge incontinence, and urinary retention. Few randomized, head-to-head comparisons of the different available alternatives exist; however, patients now have increasing options to manage their symptoms and improve their quality of life.

  4. 尿液CYFRA21-1诊断膀胱癌的Meta分析%Meta analysis of urine CYFRA21-1 in diagnosis of bladder carcinoma

    Institute of Scientific and Technical Information of China (English)

    夏勇; 龙嘉杰; 郭旭光

    2014-01-01

    目的:对尿液细胞角蛋白19-片段(CYFRA21-1)诊断膀胱癌的准确性进行系统评价。方法检索1990~2013年间国外公开发表的关于CYFRA21-1诊断膀胱癌的文献,对纳入的文献进行质量评价并进行Meta分析。结果共有11篇文献纳入,纳入研究对象3395例。CYFRA21-1并发的敏感度和特异性为71%和75%,拟合CYFRA21-1的SROC曲线下面积AUC为0.9082。结论尿液CYFRA21-1在诊断膀胱癌时有较好的准确性,可以作为膀胱癌诊断的辅助检查。%Objective To evaluate the accuracy of diagnostic test of urine CYFRA 21-1 for bladder carcinoma . Methods All the published clinical studies that evaluated the diagnostic value of CYFRA 21-1 in bladder carcinoma from 1990 to 2013 were analyzed .The quality of the tudies which were included evaluated according to the require-ments of Meta-analysis .All the eligible studies will be analyzed by the Meta-analysis .Results Eleven studies were collected and the sample size was 3395 cases .The pooled sensitivity [95% confidence interval (CI)] was 71% (68%to 73% )and the pooled specificity [95% confidence interval (CI)] of CYFRA21-1 was 75% (73% to 77% ) .And the area under SROC (AUC) of CYFRA21-1 was 0 .908 2 .Conclusion CYFRA21-1 is suitiable for the diagnosis of bladder carcinoma .

  5. 浅表性膀胱癌患者应对方式及其影响因素调查分析%Coping strategies of patients with superficial bladder carcinoma and the influential factors

    Institute of Scientific and Technical Information of China (English)

    伦雪萍; 柯彩霞; 马庆欢; 黄小萍

    2013-01-01

    Objective To explore the coping strategies of patients with superficial bladder carcinoma and analyze the influential factors.Method The medical coping modes questionnaire(MCMQ)was used to do the investigation among 146 patients with superficial bladder carcinoma.Results Among the coping strategies,the scores on the factors of facing,avoidance and yielding were 2.42±0.45,2.00±0.45 and 1.52±0.50,respectively.The operative method,education level,sex and stages of chemotherapy were the main factors influencing the coping strategies.Conclusions For the postoperative patients with superficial bladder carcinoma, the coping strategies were influenced by different factors.Therefore,nursing staff should attach their highlights on patients' coping strategies and instruct the patients with active coping strategies based on the their traits.%目的:探讨浅表性膀胱癌术后患者应对方式及影响因素。方法采用一般情况调查表和医学应对问卷(medical coping modes ques-tionnaire,MCMQ)对146例浅表性膀胱癌术后患者进行调查。结果浅表性膀胱癌术后患者应对方式中,面对因子得分为(2.42±0.45)分,回避因子得分为(2.00±0.45)分,屈服因子得分为(1.52±0.50)分。手术方式,文化程度,性别和化疗阶段是影响患者应对方式的主要因素。结论浅表性膀胱癌术后患者应对方式受多种因素影响,护理人员应重视评估患者的应对方式,根据患者特点,指导并帮助患者采取积极应对方式。

  6. Clinical and pathological implications of miRNA in bladder cancer

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    Braicu C

    2015-01-01

    important practical applications, taking into account that they modulate essential biological processes such as epithelial to mesenchymal transition, which is a mechanism relevant in bladder cancer. miRNAs collected from biological specimens can furnish valuable evidence with regard to bladder cancer oncogenesis, as they also have been linked to clinical outcomes in urothelial carcinoma. Therefore, a single miRNA or a signature of multiple miRNAs may improve risk stratification of patients and may supplement the histological diagnosis of urological tumors, particularly for bladder cancer.Keywords: bladder cancer, miRNA, prognostic, diagnostic

  7. Role of liposome in treatment of overactive bladder and interstitial cystitis

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    Shih-Ya Hung

    2015-03-01

    Full Text Available Intravesical (local therapy of agents has been effective in delaying or preventing recurrence of superficial bladder cancer. This route of drug administration has also shown tremendous promise in the treatment of interstitial cystitis/painful bladder syndrome (IC/PBS and overactive bladder without systemic side effects. Liposomes are lipid vesicles composed of phospholipid bilayers surrounding an aqueous core. They can incorporate drug molecules, both hydrophilic and hydrophobic, and show greater uptake into cells via endocytosis. Intravesical liposomes have therapeutic effects on IC/PBS patients, mainly because of their ability to form a protective lipid film on the urothelial surface. Recent studies have shown the sustained efficacy and safety of intravesical instillation of botulinum toxin formulated with liposomes (lipo-BoNT for the treatment of refractory overactive bladder This review considers the current status of intravesical liposomes or liposomal mediated drug delivery for the treatment of IC/PBS and overactive bladder.

  8. GATA-3 and FOXA1 expression is useful to differentiate breast carcinoma from other carcinomas.

    Science.gov (United States)

    Davis, Drew G; Siddiqui, Momin T; Oprea-Ilies, Gabriela; Stevens, Keith; Osunkoya, Adeboye O; Cohen, Cynthia; Li, Xiaoxian Bill

    2016-01-01

    GATA-3, a member of the GATA family of zinc-finger DNA binding proteins, and FOXA1, a member of the forkhead transcription factor family, are both associated with estrogen receptor expression. Both GATA-3 and FOXA1 are useful markers for breast carcinoma, but their expression in the different breast cancer subtypes and other neoplasms has not been thoroughly evaluated. We examined the expression of GATA-3 and FOXA1 in estrogen receptor-positive, Her2/neu-positive, and triple-negative breast carcinomas as well as in 10 other common carcinomas, including hepatocellular, colonic, pancreatic, gastric, endometrial (endometrioid), lung, prostatic, renal cell, urothelial, and ovarian serous carcinomas. Primary and metastatic melanomas and mesotheliomas were also evaluated. GATA-3 and FOXA1 staining of estrogen receptor-positive breast carcinomas was seen in 96.6% and 96.2%, respectively. In triple-negative breast carcinomas, GATA-3 and FOXA1 staining was seen in 21.6% and 15.9%, respectively. Among the other tumors, GATA-3 staining was only seen in urothelial carcinoma (70.9%) and FOXA1 staining was only seen in prostatic (87.5%), urothelial (5.1%) carcinomas, and mesotheliomas (40.0%). In conclusion, GATA-3 and FOXA1 are excellent breast carcinoma markers; however, their utility is limited in the triple-negative subtype. The utility of FOXA1 in diagnosing prostatic carcinoma and mesothelioma warrants further investigation.

  9. 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].

    Science.gov (United States)

    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.

  10. Expressão nuclear do P53 em carcinoma de células transicionais da bexiga Nuclear expression of P53 protein in transitional cell carcinoma of the bladder

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    José Anastácio Dias Neto

    2002-01-01

    Full Text Available OBJETIVO: Investigar a expressão imuno-histoquímica da p53 com fator de risco em carcinoma de células transicionais da bexiga (CCT. MÉTODOS: Foram estudados restrospectivamente 90 pacientes com CCT com idade média de 71 anos: G1 - 45, G2 - 29, G3 - 16, pTa-1 - 62 e pT2-4 - 28. Entre os pacientes com tumores não invasivos houve recidiva vesical em 35 casos (55,5%. Os tumores superficiais foram tratados por ressecção trans-uretral associados ao BCG (>G1, e os invasivos por cistectomia radical. O tempo médio de seguimento dos pacientes foi de 55 meses e 25 deles faleceram da doença. A expressão imuno-histoquímica foi estudada em peças preservadas em formol 10% e blocos de parafina pelo método da avidina-biotina-imunoperoxidase. Considerou-se p53 positivo o tumor com índice de marcação nuclear superior a 10%. RESULTADOS: A expressão da p53 mostrou associação com o grau do tumor e com o estádio da lesão primária (p=0,01, mas não com o tamanho do tumor vesical (p=0,25 ou com a taxa de recidiva dos tumores superficiais (p=0,81. Houve forte correlação entre o padrão de marcação da p53 com metástases (p=0,002 e com a sobrevida dos pacientes (p=0,003. CONCLUSÃO: A expressão da p53 mostrou valor preditivo para grau tumoral, estádio, incidência de metástases e sobrevida dos pacientes, mas não para recidiva vesical dos tumores superficiais.OBJECTIVE: To investigate the immunoexpression of p53 protein as a risk factor in transitional cell carcinoma of the bladder (TCC. METHODS: We analyzed retrospectively 90 patients with TCC and mean age of 71 years: G1 - 45, G1 - 29, G3 - 16, pTa-1 - 62 and pT2-4 - 28. The superficial TCC were treated TUR plus intravesical BCG (>G1, and the invasives by radical cystectomy and urinary diversion. The mean time of followup was 55 months and 25 patients died of the disease. The rate or reccurence in superficial tumors was 55.5%. The p53 immunoexpression was determined in formalin fixed

  11. Clinical guidelines for interstitial cystitis and hypersensitive bladder updated in 2015.

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    Homma, Yukio; Ueda, Tomohiro; Tomoe, Hikaru; Lin, Alex Tl; Kuo, Hann-Chorng; Lee, Ming-Huei; Oh, Seung-June; Kim, Joon Chul; Lee, Kyu-Sung

    2016-07-01

    Clinical guidelines for interstitial cystitis and hypersensitive bladder have been updated as of 2015. The guidelines define interstitial cystitis by the presence of hypersensitive bladder symptoms (discomfort, pressure or pain in the bladder usually associated with urinary frequency and nocturia) and bladder pathology, after excluding other diseases explaining symptoms. Interstitial cystitis is further classified by bladder pathology; either Hunner type interstitial cystitis with Hunner lesions or non-Hunner type interstitial cystitis with mucosal bleeding after distension in the absence of Hunner lesions. Hypersensitive bladder refers to a condition, where hypersensitive bladder symptoms are present, but bladder pathology or other explainable diseases are unproven. Interstitial cystitis and hypersensitive bladder severely affect patients' quality of life as a result of disabling symptoms and/or comorbidities. Reported prevalence suggestive of these disorders varies greatly from 0.01% to >6%. Pathophysiology would be an interaction of multiple factors including urothelial dysfunction, inflammation, neural hyperactivity, exogenous substances and extrabladder disorders. Definite diagnosis of interstitial cystitis and hypersensitive bladder requires cystoscopy with or without hydrodistension. Most of the therapeutic options lack a high level of evidence, leaving a few as recommended therapeutic options. PMID:27218442

  12. Reducing understaging of bladder cancer with the aid of photodynamic

    OpenAIRE

    K. Sfetsas; D. Mitropoulos

    2016-01-01

    Background: The authors evaluated the role of photodynamic cystoscopy in the detection of additional urothelial lesions, mainly carcinoma in situ, that would not be detected solely with white light cystoscopy, leading to disease understaging. Methods: From 2009 to 2011, 70 patients underwent white light cystoscopy, followed by photodynamic cystoscopy (blue light system, Karl Storz, Tuttlingen, Germany). Preoperatively they were instilled intravesically with 50 ml of Hexvix (Hexaminolevulin...

  13. Uroplakin 1b is critical in urinary tract development and urothelial differentiation and homeostasis.

    Science.gov (United States)

    Carpenter, Ashley R; Becknell, M Brian; Ching, Christina B; Cuaresma, Edward J; Chen, Xi; Hains, David S; McHugh, Kirk M

    2016-03-01

    Proper development and maintenance of urothelium is critical to its function. Uroplakins are expressed in developing and mature urothelium where they establish plaques associated with the permeability barrier. Their precise functional role in development and disease is unknown. Here, we disrupted Upk1b in vivo where its loss resulted in urothelial plaque disruption in the bladder and kidney. Upk1b(RFP/RFP) bladder urothelium appeared dysplastic with expansion of the progenitor cell markers, Krt14 and Krt5, increased Shh expression, and loss of terminal differentiation markers Krt20 and uroplakins. Upk1b(RFP/RFP) renal urothelium became stratified with altered cellular composition. Upk1b(RFP/RFP) mice developed age-dependent progressive hydronephrosis. Interestingly, 16% of Upk1b(RFP/RFP) mice possessed unilateral duplex kidneys. Our study expands the role of uroplakins, mechanistically links plaque formation to urinary tract development and function, and provides a tantalizing connection between congenital anomalies of the kidney and urinary tract along with functional deficits observed in a variety of urinary tract diseases. Thus, kidney and bladder urothelium are regionally distinct and remain highly plastic, capable of expansion through tissue-specific progenitor populations. Furthermore, Upk1b plays a previously unknown role in early kidney development representing a novel genetic target for congenital anomalies of the kidney and urinary tract. PMID:26880456

  14. β-adrenergic receptor activation in immortalized human urothelial cells stimulates inflammatory responses by PKA-independent mechanisms

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    Porter James E

    2005-08-01

    Full Text Available Abstract Background Interstitial cystitis (IC is a debilitating disease characterized by chronic inflammation of the urinary bladder, yet specific cellular mechanisms of inflammation in IC are largely unknown. Multiple lines of evidence suggest that β-adrenergic receptor (AR signaling is increased in the inflamed urothelium, however the precise effects of these urothelial cell signals have not been studied. In order to better elucidate the AR signaling mechanisms of inflammation associated with IC, we have examined the effects of β-AR stimulation in an immortalized human urothelial cell line (UROtsa. For these studies, UROtsa cells were treated with effective concentrations of the selective β-AR agonist isoproterenol, in the absence or presence of selective inhibitors of protein kinase A (PKA. Cell lysates were analyzed by radioimmunoassay for generation of cAMP or by Western blotting for induction of protein products associated with inflammatory responses. Results Radioligand binding demonstrated the presence of β-ARs on human urothelial UROtsa cell membranes. Stimulating UROtsa cells with isoproterenol led to concentration-dependent increases of cAMP production that could be inhibited by pretreatment with a blocking concentration of the selective β-AR antagonist propranolol. In addition, isoproterenol activation of these same cells led to significant increases in the amount of phosphorylated extracellular signal-regulated kinase (pERK, inducible nitric oxide synthase (iNOS and the induced form of cyclooxygenase (COX-2 when compared to control. Moreover, preincubation of UROtsa cells with the selective PKA inhibitors H-89 or Rp-cAMPs did not diminish this isoproterenol mediated phosphorylation of ERK or production of iNOS and COX-2. Conclusion Functional β-ARs expressed on human urothelial UROtsa cell membranes increase the generation of cAMP and production of protein products associated with inflammation when activated by the selective

  15. Comparison of dynamic contrast-enhanced and diffusion weighted magnetic resonance image in staging and grading of carcinoma bladder with histopathological correlation

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    Neetika Gupta

    2015-01-01

    Full Text Available Background: Bladder cancer is the second most common neoplasm of the urinary tract worldwide. Dynamic contrast-enhanced and diffusion-weighted MRI has been introduced in clinical MRI protocols of bladder cancer because of its accuracy in staging and grading. Aim: To evaluate and compare accuracy of Dynamic contrast enhanced (DCE and Diffusion weighted (DW MRI for preoperative T staging of urinary bladder cancer and find correlation between apparent diffusion coefficient (ADC and maximum enhancement with histological grade. Materials and Methods: Sixty patients with bladder cancer were included in study. All patients underwent Magnetic Resonance Imaging (MRI on a 1.5-T scanner with a phased-array pelvic coil. MR images were evaluated and assigned a stage which was compared with the histolopathological staging. ADC value and maximum enhancement curve were used based on previous studies. Subsequently histological grade was compared with MR characteristics. Results: The extent of agreement between the radiologic staging and histopathological staging was relatively greater with the DW-MRI (κ=0.669 than DCE-MRI (κ=0.619. The sensitivity, specificity, and accuracy are maximum and similar for stage T4 tumors in both DCEMRI (100.0, 96.2 and 96.7 and DW-MRI (100.0, 96.2 and 96.7 while minimum for stage T2 tumors - DCEMRI (83.3, 72.2, and 76.7 and DWI-MRI (91.7, 72.2, and 80. Conclusion: MRI is an effective tool for determining T stage and histological grade of urinary bladder cancers. Stage T2a and T2b can be differentiated only by DCE-MRI. Results were more accurate when both ADC and DCE-MRI were used together and hence a combined approach is suggested.

  16. 利用体内噬菌体展示技术筛选膀胱癌特异性结合肽%Selection of peptide specifically binding to bladder carcinoma by using phage display in vivo

    Institute of Scientific and Technical Information of China (English)

    罗俊茜; 张帆; 杨晓峰; 罗芳; 刘杰昊; 庞建智; 闫三华; 张小雷

    2015-01-01

    目的:利用体内噬菌体展示技术筛选与人膀胱移行细胞癌特异性结合的小分子多肽。方法:将人膀胱移行细胞癌细胞BIU87接种于裸鼠体内,制备膀胱癌荷瘤小鼠模型,尾静脉注射噬菌体展示环七肽库,然后筛选与膀胱移行细胞癌特异性结合的含外源多肽的噬菌体,经过3轮体内筛选后,免疫组织化学法及ELISA法鉴定单克隆噬菌体对BIU87的亲和力。提取阳性单克隆噬菌体单链DNA进行测序,并推导出外源多肽氨基酸序列,化学合成多肽、制备分子探针后采用激光扫描共聚焦显微镜术及流式细胞术鉴定多肽对膀胱癌细胞和组织的特异性。结果:3轮体内筛选后,噬菌体富集率达到4.334×102倍。免疫组化结果显示,肿瘤组织中噬菌体肽的含量随着每一轮筛选呈增长趋势,且结合逐渐增强,同时由于噬菌体经肝、肾代谢,可见肝脏结合大量非特异性的噬菌体。 ELISA结果显示,随机挑选的30个单克隆噬菌体斑中,有24个阳性噬菌体,其中10个噬菌体对BIU87有较强的亲和力,对其测序并推导出3种多肽序列,重复率最高的序列CSSPIGRHC(8/10)命名为NYZL1。化学合成FITC-C6-NYZL1,通过激光扫描共聚焦显微镜术、流式细胞术均证明多肽NYZL1可以特异性结合膀胱癌细胞。结论:利用体内噬菌体展示技术筛选出了与人膀胱移行细胞癌特异性结合的小分子多肽NYZL1,为膀胱癌早期诊断和靶向治疗提供一定的理论依据。%Objective:To screen the peptide binding to human bladder carcinoma cells specifically by using phage display technology in vivo.Methods: Nude mice were inoculated with bladder carcinoma cells BIU87 for establishing tumor-bearing mice model.The Ph.D.-C7CTM Peptide Library was injected intravenously via tail vein.Then we screened Phage containing exogenous peptides binding to bladder transitional carcinoma cells

  17. Clinical observation of conversion to sirolimus in the treatment of urothelial carcinoma following renal transplantation%肾移植后发生尿路上皮肿瘤的患者转换西罗莫司治疗的临床观察

    Institute of Scientific and Technical Information of China (English)

    胡小鹏; 马麟麟; 王勇; 尹航; 王玮; 杨晓勇; 张小东

    2008-01-01

    目的 观察肾移植后发生尿路上皮肿瘤的患者使用西罗莫司(SRL)联合低剂量钙调磷酸酶抑制剂(CNI)免疫抑制方案的有效性和安全性.方法 对15例肾移植后发生尿路上皮肿瘤的患者调整免疫抑制方案,采用SRL替代霉酚酸酯(或硫唑嘌呤).SRL的初始负荷剂量为2 mg,次日剂量为1 mg,之后根据SRL血药浓度调整维持剂量,使血药浓度维持在4~6μg/L;在其血药浓度稳定后将CNI减少至原用量的1/3.全部肿瘤患者均行手术治疗并辅以局部灌注化疗.转换SRL期间观察患者肿瘤的复发情况、移植肾功能及不良反应.结果 对15例患者随访2年中,9例肿瘤无复发;6例复发,其中2例复发2次,4例复发1次.在复发的患者中,4例肿瘤病理分级较转换SRL前降低,2例与转换前相同.所有复发的患者均再次行手术治疗.所有患者在使用SRL期间均未出现急性排斥反应,且其中11例患者肾功能指标较治疗前下降,4例肾功能保持稳定.转换治疗过程中出现高脂血症12例,不明原因发热4例,血小板减少3例,关节疼痛2例,所有不良反应经对症治疗后症状均有所好转.结论 肾移植后发生尿路上皮肿瘤的患者使用SRL联合低剂量CNI的免疫抑制方案是安全和有效的.%Objective To evaluate the efficacy and safety of sirolimus combined with low dose calcineurin inhibitor to treat 15 renal allograft recipients with urothelial carcinoma. Methods The im-munosuppressive regimen was modulated in 15 recepients. MMF or Aza was replaced with sirolimus. The loading dose was 2 mg/d and the next dose was 1 mg/d. The sirolimus dosage was adjusted ac-cording to the blood level and the sustained blood level was 4~6 μg/L. In all the 15 cases the calci-neurin inhibitor was reduced to one third of the original dosage after the sirolimus blood level was sta-ble. Surgical treatment and intravesical instillation chemotherapy were carried out in all cases. During the

  18. Does polyomavirus infection interfere with bladder cancer fluorescence in situ hybridization?

    Science.gov (United States)

    Hossain, Deloar; Hull, David; Kalantarpour, Fatemeh; Maitlen, Rebecca; Qian, Junqi; Bostwick, David G

    2014-03-01

    Urine cytology is a proven and widely used screening tool for the detection of urothelial carcinoma. However, morphologic features of polyomavirus infected cells, characterized by nuclear inclusions (decoy cells) are a known source of diagnostic confusion with malignancy. Fluorescence in situ hybridization (FISH) is now routinely used to support the cytological diagnosis of urothelial carcinoma and monitor for recurrence. We sought to determine whether polyomavirus infection could result in positive FISH results (aneuploidy). This study deals with retrospective study of 100 polyomavirus-infected urine samples from patients with no history of urothelial carcinoma or organ transplantation. All cases were stained with Papanicolaou and acid hematoxylin stain. One slide from each sample was de-stained and FISH was performed using chromosome enumeration probes 3, 7, 17, and locus-specific probe 9p21. Adequate cells for FISH analysis (25 cells) were present in 81 cases; 19 cases were insufficient due to loss of cells during de-staining and FISH preparation process. All polyomavirus-infected cells (decoy cells) exhibited a normal chromosome pattern. Four cases were FISH positive, but there were no positive decoy cells. Decoy cells did not exhibit aneuploidy by FISH. The presence of decoy cells does not exclude the possibility of concurrent urothelial carcinoma. Acid hematoxylin stain appeared to supplement the Papanicolou stain in identifying and confirming the presence of polyomavirus infection. PMID:24006232

  19. Nursing of patients with superficial bladder carcinoma treated with mitomycin C hyperthermic perfusion chemotherapy%丝裂霉素C热灌注化疗治疗表浅性膀胱癌患者的护理

    Institute of Scientific and Technical Information of China (English)

    钟肖红; 郭龙斌; 王斌; 巴明臣

    2012-01-01

    Objective To explore ihe key points of nursing patients with superficial bladder carcinoma treated with milomyein C (MMC) hyperthermic perfusion chemotherapy. Methods 63 patients with superficial bladder carcinoma in the study having undergone transurelhral tumor resection, were treated with milomycin C hyperthermic perfusion chemotherapy. They were managed with perioperative nursing strategies. Results During the operation, the vital signs of all patients were stable. 11 patients had mild lower atxlominal skin flushing and mild burning sensation. 26 of them contracted with odynuria, urgency and frequent micturition, which were mitigated for symptomatic treatment. 6-37 months follow-up showed normal quality of life in them. Conclusion MMC hyperthermic perfusion chemotherapy for the prevention of postoperative recurrence of superficial bladder cancer has a good clinical efficacy. The perioperative nursing should be strengthened to lower Ihe incidences of adverse reactions and reduce the pain and discomfort so that the patients can be cooperative in treatment for the purpose of ensuring curative continuity.%目的 总结丝裂霉索C热灌注化疗治疗表浅性膀胱癌患者的护理要点.方法 对63例表浅性膀胱癌患者经尿道肿瘤电切术后,应用丝裂霉索C进行热灌注化疗,并实施相应的护理.结果 患者热灌注化疗过程中生命体征平稳,化疗过程11例患者出出现下腹部皮肤潮红和轻度灼热感,26例患者术后出现尿痛、尿急、尿频,经对症处理后症状缓解.随访6 ~ 37个月,患者均生活良好,膀胱镜检查无局部及膀胱腔内其他部位肿瘤复发,临床疗效满意.结论 丝裂霉素C膀胱热灌注治疗对预防经尿道膀胱癌切除术后肿瘤复发具有较好的临床疗效.护理方面加强患者膀胱热灌注化疗过程护理,降低不良反应的发生,从而降低患者的痛苦和不适.

  20. Upregulation of the long noncoding RNA HOTAIR predicts recurrence in stage Ta/T1 bladder cancer.

    Science.gov (United States)

    Yan, Ting-Hua; Lu, Sui-Wan; Huang, Yong-Qing; Que, Gan-Bo; Chen, Jun-Hui; Chen, Yong-Ping; Zhang, Hong-Bin; Liang, Xing-Lan; Jiang, Jin-Hua

    2014-10-01

    Stage Ta/T1 urothelial carcinoma of the bladder (Ta/T1 BC) has a marked tendency to recurrence. Long noncoding RNA HOTAIR has been reported to be expressed in some human cancers such as breast cancer, and it may be positively correlated with patient's prognosis. The aim of our study was to evaluate the prognostic value of HOTAIR in Ta/T1 BC. HOTAIR expression in Ta/T1 BC tissues and adjacent normal tissues was collected from 110 patients and measured by real-time quantitative PCR. The relationships between HOTAIR and the clinical pathological characteristics of Ta/T1 BC patients were analyzed. Immunohistochemistry was done to detect the protein of Wnt inhibitory factor 1 (WIF-1) as well. Ninety out of 110 specimens were detected in HOTAIR high expression. Histological grade and expression levels of HOTAIR were positively correlated with the recurrence rate. HOTAIR expression (hazard ratio 4.712; 95 % CI 2.894-8.714; P WIF-1 expression was demonstrated in Ta/T1 BC tissues. The expression levels of HOTAIR are an independent prognostic factor of recurrence in Ta/T1 BC patients. PMID:25030736

  1. IL1RN and KRT13 Expression in Bladder Cancer: Association with Pathologic Characteristics and Smoking Status

    Directory of Open Access Journals (Sweden)

    Thomas S. Worst

    2014-01-01

    Full Text Available Purpose. To validate microarray data on cytokeratin 13 (KRT13 and interleukin-1 receptor antagonist (IL1RN expression in urothelial carcinoma of the urinary bladder (UCB and to correlate our findings with pathologic characteristics and tobacco smoking. Methods. UCB tissue samples (n=109 and control samples (n=14 were obtained from transurethral resection and radical cystectomy specimens. Immunohistochemical staining of KRT13 and IL1RN was performed and semiquantitative expression scores were assessed. Smoking status was evaluated using a standardized questionnaire. Expression scores were correlated with pathologic characteristics (tumor stage and grade and with smoking status. Results. Loss of KRT13 and IL1RN expression was observed in UCB tissue samples when compared to controls (P=0.007, P=0.008 in which KRT13 and IL1RN expression were high. IL1RN expression was significantly reduced in muscle-invasive tumors (P=0.003. In tissue samples of current smokers, a significant downregulation of IL1RN was found when compared to never smokers (P=0.013. Conclusion. Decreased expressions of KRT13 and IL1RN are common features of UCB and are associated with aggressive disease. Tobacco smoking may enhance the loss of IL1RN, indicating an overweight of proinflammatory mediators involved in UCB progression. Further validation of the influence of smoking on IL1RN expression is warranted.

  2. Bladder Cancer Advocacy Network

    Science.gov (United States)

    ... future bladder cancer research through the Patient Survey Network. Read More... The JPB Foundation 2016 Bladder Cancer ... 2016 Young Investigator Awardees The Bladder Cancer Advocacy Network (BCAN) has announced the recipients of the 2016 ...

  3. Taurine modulates neutrophil function but potentiates uropathogenic E. coli infection in the murine bladder.

    LENUS (Irish Health Repository)

    Condron, Claire

    2010-08-01

    Eradication of a urinary tract infection (UTI) appears to be related to a number of innate host defence mechanisms and their interactions with invading bacteria. Recurrent UTIs (rUTIs) pose a difficult problem in that these bacteria use both host and bacterial factors to evade elimination. Neutrophil bactericidal function is depressed, both systemically and in urine, in patients with a history of recurrent UTI. Taurine is a semi-essential amino acid and is successful in preserving neutrophil bactericidal function in urine. Taurine may preserve neutrophil function at the urothelium and thus aid UTI resolution. Adult female (6 weeks old) C57Bl\\/6 mice were randomised into three groups: a saline gavage only control group, a saline gavage + E. coli group, and a taurine gavage + E. coli group [21 g\\/70 kg taurine in 0.9% normal saline (N\\/S) for 5 days]. Whilst taurine gavage pre-treatment resulted in increased serum neutrophils respiratory burst activity, at the urothelial-endothelial interface it caused higher colony forming units in the urine and a higher incidence of E. coli invasion in the bladder wall with no evidence of increased bladder wall neutrophils infiltration on MPO assay of histological assessment. Histologically there was also evidence of reduced bladder inflammation and urothelial cell apoptosis. In conclusion, taurine effectively increases neutrophils activity but given its anti-inflammatory properties, at the expense of decreased urothelial-endothelial activation thus preventing clearance of active E. coli infection in the bladder. Despite the negative results, this study demonstrates the importance of modulating interactions at the urothelial interface.

  4. Temporal expression of elastic fiber components in bladder development.

    Science.gov (United States)

    Koo, H P; Macarak, E J; Chang, S L; Rosenbloom, J; Howard, P S

    1998-01-01

    Fetal and postnatal bovine bladders were examined for expression of elastic fiber components by immunohistochemistry as well as by measurement of steady state mRNA levels. Expression of fibrillin-1, microfibril-associated glycoprotein (MAGP) and elastin during the fetal period were compared with that of postnatal two year old animals (heifers) and adults. Each bladder was separated into two distinct tissue samples: 1) the outer smooth muscle layer (detrusor) and 2) the inner epithelium (urothelium) lined lamina propria (urotherial-lamina propria). Each of these samples was analyzed separately. Distribution of the elastic fiber components, determined by immunohistochemistry with matrix-specific antibodies, was different depending upon the region of the bladder wall examined and its developmental stage. In particular, MAGP and fibrillin-1 were conspicuously present in the urothelium during the later fetal stages. RNA products of elastic fiber genes were detectable both in the detrusor smooth muscle and urothelial-lamina propria fractions. The highest level of expression occurred in the urothelial-lamina propria fraction during the late second-early third trimester. Elastin expression was different from that of MAGP and fibrillin-1. The highest levels of steady-state elastin mRNA occurred at the earliest developmental stages examined and then progressively decreased through term. A high level of elastin expression occurred within the inner or lamina propria layer of the bladder. Since this layer is the functional capacitance layer within the bladder, its flexibility is likely related to the structural integration of elastin and associated microfibrillar components. PMID:9643643

  5. Telomerase reverse transcriptase promoter mutations in bladder cancer

    DEFF Research Database (Denmark)

    Allory, Yves; Beukers, Willemien; Sagrera, Ana;

    2014-01-01

    for detection of recurrences in urine in patients with urothelial bladder cancer (UBC). DESIGN, SETTING, AND PARTICIPANTS: A set of 111 UBCs of different stages was used to assess TERT promoter mutations by Sanger sequencing and TERT messenger RNA (mRNA) expression by reverse transcription...... surveillance after diagnosis of non-muscle-invasive UBC (n=194), was tested using a SNaPshot assay. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Association of mutation status with age, sex, tobacco, stage, grade, fibroblast growth factor receptor 3 (FGFR3) mutation, progression-free survival, disease...

  6. Development and evaluation of a training program for therapeutic radiographers as a basis for online adaptive radiation therapy for bladder carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Foroudi, Farshad [Division of Radiation Oncology, Peter MacCallum Cancer Institute, St Andrews Place, East Melbourne, Victoria 3002 (Australia)], E-mail: farshad.foroudi@petermac.org; Wong, Jacky [Radiation Therapy Services, Peter MacCallum Cancer Center, St Andrews Place, East Melbourne, Victoria 3002 (Australia); Kron, Tomas; Roxby, Paul; Haworth, Annette [Physical Sciences, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria 3002 (Australia); Bailey, Alistair [Southern Interior Cancer Centre, 399 Royal Avenue, Kelowna, British Columbia (Canada); Rolfo, Aldo; Paneghel, Andrea; Styles, Colin; Laferlita, Marcus [Radiation Therapy Services, Peter MacCallum Cancer Center, St Andrews Place, East Melbourne, Victoria 3002 (Australia); Tai, Keen Hun; Williams, Scott; Duchesne, Gillian [Division of Radiation Oncology, Peter MacCallum Cancer Institute, St Andrews Place, East Melbourne, Victoria 3002 (Australia)

    2010-02-15

    Aims: Online adaptive radiotherapy requires a new level of soft tissue anatomy recognition and decision making by therapeutic radiographers at the linear accelerator. We have developed a therapeutic radiographer training workshop encompassing soft tissue matching for an online adaptive protocol for muscle invasive bladder cancer. Our aim is to present the training program, and its evaluation which compares pre and post training staff soft tissue matching and bladder contouring using Cone Beam Computer Tomography (CBCT). Materials and Methods: Prior to commencement of an online adaptive bladder protocol, a staff training program for 33 therapeutic radiographers, with a separate ethics approved evaluation component was developed. A multidisciplinary training program over two days was carried out with a total of 11 h of training, covering imaging technology, pelvic anatomy and protocol specific decision making in both practical and theoretical sessions. The evaluation included both pre training and post training testing of staff. Results: Pre training and post training, the standard deviations in the contoured bladder between participants in left-right direction were 0.64 vs 0.59 cm, superior-inferior 0.89 vs 0.77 cm and anterior-posterior direction was 0.88 vs 0.52 cm respectively. Similarly the standard deviation in the volume contoured decreased from 40.7 cc pre training to 24.5 cc post training. Time taken in contouring was reduced by the training program (19.8 vs 17.2 min) as was the discrepancy in choice of adaptive radiotherapy plans. The greatest reduction in variations in contouring was seen in staff whose pre training had the largest deviations from the reference radiation oncologist contours. Conclusion: A formalized staff training program is feasible, well received by staff and reduces variation in organ matching and contouring. The improvement was particularly noticed in staff who pre training had larger deviations from the reference standard.

  7. Development and evaluation of a training program for therapeutic radiographers as a basis for online adaptive radiation therapy for bladder carcinoma

    International Nuclear Information System (INIS)

    Aims: Online adaptive radiotherapy requires a new level of soft tissue anatomy recognition and decision making by therapeutic radiographers at the linear accelerator. We have developed a therapeutic radiographer training workshop encompassing soft tissue matching for an online adaptive protocol for muscle invasive bladder cancer. Our aim is to present the training program, and its evaluation which compares pre and post training staff soft tissue matching and bladder contouring using Cone Beam Computer Tomography (CBCT). Materials and Methods: Prior to commencement of an online adaptive bladder protocol, a staff training program for 33 therapeutic radiographers, with a separate ethics approved evaluation component was developed. A multidisciplinary training program over two days was carried out with a total of 11 h of training, covering imaging technology, pelvic anatomy and protocol specific decision making in both practical and theoretical sessions. The evaluation included both pre training and post training testing of staff. Results: Pre training and post training, the standard deviations in the contoured bladder between participants in left-right direction were 0.64 vs 0.59 cm, superior-inferior 0.89 vs 0.77 cm and anterior-posterior direction was 0.88 vs 0.52 cm respectively. Similarly the standard deviation in the volume contoured decreased from 40.7 cc pre training to 24.5 cc post training. Time taken in contouring was reduced by the training program (19.8 vs 17.2 min) as was the discrepancy in choice of adaptive radiotherapy plans. The greatest reduction in variations in contouring was seen in staff whose pre training had the largest deviations from the reference radiation oncologist contours. Conclusion: A formalized staff training program is feasible, well received by staff and reduces variation in organ matching and contouring. The improvement was particularly noticed in staff who pre training had larger deviations from the reference standard.

  8. The method of bladder drainage in spinal cord injury patients may influence the histological changes in the mucosa of neuropathic bladder – a hypothesis

    Directory of Open Access Journals (Sweden)

    Singh Gurpreet

    2002-04-01

    Full Text Available Abstract Background In spinal cord injury (SCI patients, no correlation was found between the number of bladder infections per year, the period since injury, the neurologic level of the spinal cord lesion and the histopathology of the urinary bladder mucosa. The use of chronic indwelling urethral and/or suprapubic catheters in SCI patients is often associated with inflammatory and proliferative pathological conditions in neuropathic bladder. Presentation of the hypothesis We propose a hypothesis that the type of bladder drainage in SCI patients influences the histological changes in the mucosa of neuropathic bladder. This hypothesis implies that SCI patients with long-term indwelling urinary catheters develop certain histological changes in bladder mucosa, which are seen less frequently in SCI patients, who do not use long-term indwelling catheters. The latter group includes patients, who perform regular intermittent catheterisation and those, who wear a penile sheath and empty their bladders satisfactorily by reflex voiding. We hypothesise that the following histological lesions are seen more frequently in the neuropathic bladder of SCI patients with long-term indwelling catheters. (1 Papillary or polypoid cystitis; (2 widespread cystitis glandularis; (3 moderate to severe, acute and chronic inflammatory changes in bladder mucosa; (4 follicular cystitis; (5 squamous metaplasia; and (6 urothelial dysplasia As per this hypothesis, it is postulated that the above pathological conditions are seen less often in SCI patients, who achieve complete, low-pressure emptying of the neuropathic bladder by regular intermittent catheterisation, and SCI patients with penile sheath drainage, who empty their bladders satisfactorily by reflex voiding. Testing the hypothesis A large prospective study of bladder biopsies in SCI patients practising different methods of bladder drainage is required to validate this hypothesis that the histological changes in bladder

  9. ERas protein is overexpressed and binds to the activated platelet-derived growth factor β receptor in bovine urothelial tumour cells associated with papillomavirus infection.

    Science.gov (United States)

    Russo, Valeria; Roperto, Franco; Esposito, Iolanda; Ceccarelli, Dora Maria; Zizzo, Nicola; Leonardi, Leonardo; Capparelli, Rosanna; Borzacchiello, Giuseppe; Roperto, Sante

    2016-06-01

    Embryonic stem cell-expressed Ras (ERas) encodes a constitutively active form of guanosine triphosphatase (GTPase) that binds to and activates phosphatidylinositol 3 kinase (PI3K), which in turn phosphorylates and activates downstream targets such as Akt. The current study evaluated ERas regulation and expression in papillomavirus-associated urothelial tumours in cattle grazing on lands rich in bracken fern. ERas was found upregulated and overexpressed by PCR, real time PCR and Western blot. Furthermore, protein overexpression was also confirmed by immunohistochemistry. ERas was found to interact physically and colocalise with the activated platelet derived growth factor β receptor (PDGFβR) by coimmunoprecipitation and laser scanning confocal investigations. Phosphorylation of Akt, a downstream effector both of ERas and PDGFβR, appeared to be increased in urothelial tumour cells. Altogether, these data indicate that ERas/PDGFβR complex could play a role in the pathogenesis of bovine papillomavirus-associated bladder neoplasia. PMID:27256024

  10. Ultrasonographic evaluation of urinary bladder neoplasias

    Directory of Open Access Journals (Sweden)

    Nipa Patidar

    2015-12-01

    Full Text Available Background: Ultrasound has been shown to be a sensitive method for evaluating patients with chronic obstruction, bladder outlet obstruction, urinary tract infection, renal failure, renal and bladder neoplasm and renal transplants. It is now recommended as the method of choice for preliminary assessment and follow-up of several of these disorders. The objective of the study was to evaluate the specificity and sensitivity of ultrasonographic features of neoplastic lesions of urinary bladder. Methods: Clinical impression about the suspected abnormality was obtained from the case papers or from referring by clinical colleagues. Data was recorded under headings like clinical history, clinical examinations, investigations like urine analysis, serum creatinine and blood urea, X-ray of chest and Kidney Urinary Bladder, pelvic and abdominal Ultrasonography, and if require CT scan and guided biopsy. Results: out of total 35 cases 29 were Transitional Cell Carcinoma, 4 were Squamous Cell Carcinoma, One leiomyoma and one was secondary from bronchogenic carcinoma. Most of tumours were irregular in shape in both TCC and SCC patients. Most of tumour showed heterogeneous echo-texture in ultrasonography. While all SCC showed heterogeneous with calcification echo-texture. Most of the cases had residual urine volume was less than 100 cc. Conclusions: The primary advantage of ultrasound over the conventional study was found to be its ability to detect focal or diffuse bladder wall abnormalities in patients who presented with commonest complaint of painless hematuria. [Int J Res Med Sci 2015; 3(12.000: 3775-3778

  11. The zinc-finger transcription factor SALL4 is frequently expressed in human cancers: association with clinical outcome in squamous cell carcinoma but not in adenocarcinoma of the esophagus.

    Science.gov (United States)

    Kilic, Ergin; Tennstedt, Pierre; Högner, Anica; Lebok, Patrick; Sauter, Guido; Bokemeyer, Carsten; Izbicki, Jakob R; Wilczak, Waldemar

    2016-04-01

    SALL4 is a transcription factor originally identified as a homeotic gene essential for organ development. Early studies suggested that SALL4 is a useful marker to identify testicular and ovarian germ cell tumors. The aim of the study was to evaluate the diagnostic potential of SALL4 immunohistochemistry. Immunohistochemical staining was performed on a tissue microarray (TMA) with 3966 samples from 94 different tumor types and on a further TMA with 492 esophagus carcinomas. SALL4 immunostaining was by far most prevalent and most intensive in testicular tumors with a positivity rate of 93.1 % in seminomas, 80 % in mixed germ cell tumors (embryonic carcinomas/yolk sac tumors), and 18.5 % in teratomas, respectively. However, SALL4 expression is not specific to germ cell tumors. We observed SALL4 positivity in non-germ cell tumors as carcinomas of the kidney (28.9 % of chromophobe, 34.4 % of clear cell carcinoma), in intestinal type adenocarcinoma of the stomach (10.9 %), in adenocarcinoma (10.5 %) and squamous cell carcinoma (7.2 %) of the esophagus, and in malignant melanoma (8.1 %) and invasive urothelial bladder carcinoma (20 %). SALL4 expression was not found in lymphomas, in soft tissue tumors or breast tumors. At analysis of esophagus carcinoma TMA, no significant association was seen between SALL4 expression and overall survival in adenocarcinoma. However, SALL4 expression was strongly associated with worse overall survival in squamous cell carcinoma. SALL4 expression can be found at relevant frequencies in various tumors of different primary sites. SALL4 expression in squamous cell carcinoma of the esophagus may constitute a sign of dedifferentiation leading to poor patient prognosis. PMID:26818834

  12. Bladder cancer arising in a spina bifida patient.

    Science.gov (United States)

    Game, X; Villers, A; Malavaud, B; Sarramon, J

    1999-11-01

    We report the case of a 52-year-old patient with spina bifida, neurologic bladder, and a history of recurrent urinary tract infections (UTIs) in whom a bladder cancer was incidentally discovered. Cytology, cystoscopy, and cystography showed nonspecific, extensive inflammatory lesions. Cystography demonstrated a complex of diverticulae and cellules. Pathologic examination of a diverticulectomy specimen revealed a grade III pT3b transitional and squamous cell carcinoma. Because of the similar disease causation (recurrent UTIs, stones, and indwelling catheterization), we suggest extension of the guidelines proposed for patients with spinal cord injuries (ie, annual serial bladder biopsies) to patients with nontraumatic neurogenic bladder. PMID:10754152

  13. miRNA-148a 在膀胱癌组织中的表达及生物信息学分析%Expression of miRNA-148a in Bladder Carcinoma Tissues and Its Bioinformatics Analysis

    Institute of Scientific and Technical Information of China (English)

    谢小娟; 朱娜; 潘晶晶; 魏力强; 陈葳

    2015-01-01

    Objective To explore the role of miRNA-148a in bladder tumorous development and progression.Methods Ex-pression of miRNA-148a was assessed in 35 bladder carcinoma tissues and 16 non-carcinoma tissues by fluorescence quanti-tative real time PCR,and correlation with clinical features was evaluated.Target genes and transcription factors of miRNA-148a were predicted using bioinformatic analysis,then TF-miRNA-148a-target genes network diagram was built and the tar-get genes was analyzed of gene ontology enrichment and KEGG pathway.Results Expression of miRNA-148a was lower in bladder carcinoma tissues than in non-carcinoma tissues(0.000 8±0.000 2 vs 0.002 1±0.000 5)(t=2.46,P 0.05).268 target genes of miRNA-148a were predicted by three softwares at the same time,60 transcription factors were predicted and the binding sites with combination scroes above 80 was 657.The target genes of miRNA-148a was enriched in many biological processes,such as neuron differentiation,generation of neurons,neuron projec-tion development,cytoplasmic mRNA processing body,cytoplasm(P <0.001).They also participated in p53 signaling path-way,proteoglycans in cancer-homo sapiens,pathways in cancer,prostate cancer,protein processing in endoplasmic reticulum, focal adhesion and so on(P <0.05).According to TF-miRNA-148a-target genes network diagram,miRNA-148a was regula-ted by SP1,ESR1,AP1,MYC and BRCA1,genes of IGF1,P27kip1 ,NCOA1,PTEN,SERPINE1 might be regulated by miR-NA-148a.Conclusion miRNA-148a which was significantly down-regulation in bladder carcinoma tissues may be participate in bladder tumorous development and progression,bioinformatics analysis provides some ideas for further research.%目的:探索 miRNA-148a 在膀胱癌发生发展中的作用。方法收集35例膀胱癌组织和16例非癌组织,采用荧光定量 PCR 方法检测 miRNA-148a 的相对表达量,并分析其与临床特征的相关性;采用生物信息学分析,预测 miRNA-148a的靶基

  14. Construction and evaluation of urinary bladder bioreactor for urologic tissue-engineering purposes.

    LENUS (Irish Health Repository)

    Davis, Niall F

    2012-01-31

    OBJECTIVE: To design and construct a urinary bladder bioreactor for urologic tissue-engineering purposes and to compare the viability and proliferative activity of cell-seeded extracellular matrix scaffolds cultured in the bioreactor with conventional static growth conditions. MATERIALS AND METHODS: A urinary bladder bioreactor was designed and constructed to replicate physiologic bladder dynamics. The bioreactor mimicked the filling pressures of the human bladder by way of a cyclical low-delivery pressure regulator. In addition, cell growth was evaluated by culturing human urothelial cells (UCs) on porcine extracellular matrix scaffolds in the bioreactor and in static growth conditions for 5 consecutive days. The attachment, viability, and proliferative potential were assessed and compared with quantitative viability indicators and by fluorescent markers for intracellular esterase activity and plasma membrane integrity. Scaffold integrity was characterized with scanning electron microscopy and 4\\

  15. 钬激光联合吡柔比星灌注治疗浅表性膀胱癌%Clinical study of holmium laser resection as well as instant intravesical Pirarubicin instillation for superficial bladder carcinoma

    Institute of Scientific and Technical Information of China (English)

    杨光天; 赵海岩; 温峰

    2012-01-01

    目的 探讨经尿道钬激光切除联合吡柔比星即刻灌注治疗浅表性膀胱癌的临床疗效.方法 51例浅表性膀胱癌患者按随机数字表法分为两组,治疗组26例行经尿道膀胱肿瘤钬激光切除,术后即刻予以膀胱内保留灌注无菌蒸馏水50 ml+吡柔比星30 mg,1次;对照组25例行经尿道膀胱肿瘤电切治疗,两组术后拔除尿管时灌注1次,以后每周1次,共8次,后改为每月1次,持续至术后1年以上,随访15~39个月.结果 治疗组手术时间20~53 min,平均(31.6 ±8.9) min,无膀胱穿孔发生,术后留置导尿管1~5d,平均(2.7±0.6)d,4例复发;对照组手术时间13 ~47 min,平均(29.8±8.3)min,1例术中膀胱穿孔,术后留置导尿管3~11d,平均(4.6±1.1)d,11例复发.两组平均手术时间、膀胱穿孔例数差异均无统计学意义(均P>0.05),治疗组术后导尿管留置时间、肿瘤复发例数均低于对照组(均P<0.05).结论 经尿道钬激光切除联合吡柔比星灌注治疗浅表性膀胱肿瘤疗效优于电切治疗,术后恢复快.%Objective To study the efficacy of transurethral holmium laser resection as well as instant intravesical Pirarubicin instillation for superficial bladder carcinoma.Methods 51 cases with superficial bladder cancer were divided into observation group(A) including 26 cases and control group(B) including 25 cases stochastically.The 26 cases of group A were received transurethral holmium laser resection as well as instant intravesical Pirarubicin instillation therapy whereas 25 cases of group B received transurethral resection therapy.All patients of both groups were treated with intravesical instillation of Pirarubicin therapy regularly at least 1 year and have been followed up for 15 to 39 months.Results Differences were not significant between the two groups in the mean operation time and bladder perforation rate(P >0.05 ),but indwelling period of urethral catheter was markedly decreased in group A than group

  16. Coincidence of HPV11-Positive Urethral Condyloma Acuminatum and HPV-Negative Multiple Bladder Papillomas in a Female

    Directory of Open Access Journals (Sweden)

    Natsuko Nakazaki

    2012-01-01

    Full Text Available Human papillomaviruses (HPVs are associated with proliferative lesions in a variety of human epithelial types. A 38-year-old female presented with a diagnosis of urethral condyloma acuminatum. She underwent transurethral resection of the urethral condyloma. At that time, multiple (five bladder tumors were simultaneously found and also removed by transurethral resection. Four of the bladder tumors were diagnosed as squamous papilloma, and the other was urothelial inverted papilloma. Postoperative course was uneventful. Genomic DNA was extracted from 10 μm thick sections of each bladder tumor as well as urethral condyloma. Then, 16 types of HPV DNA sequences were assessed with the PapiPlex method using genomic DNA samples extracted from each bladder tumor as well as urethral condyloma. HPV-11 was detected in DNA extracted from the urethral condyloma, while no HPV DNA sequences were positive in any of the genomic DNA samples extracted from the bladder tumors.

  17. Iatrogenic neonatal bladder perforation

    Directory of Open Access Journals (Sweden)

    Lilia Trigui

    2011-01-01

    Full Text Available Neonatal bladder rupture is rare as a complication of bladder obstruction due to abnormal anatomy or iatrogenic causes. The present study describes the case of a 3-day-old infant with ascites due to bladder perforation secondary probably to manual decompression of the bladder. The infant underwent successful surgical repair of the perforation.

  18. Expressions of Proliferating Cell Nuclear Antigen and Wheat Germ Agglutinin Receptor in Human Bladder Carcinoma%膀胱癌增殖细胞核抗原与麦胚凝集素受体的相关关系

    Institute of Scientific and Technical Information of China (English)

    张士文; 葛根; 金伯涛

    2001-01-01

    [Purpose]To probe the relation of proliferating cell nuclear antigen (PCNA) and wheat germ agglutinin (WGA) receptors expressed in human bladder transitional cell carcinoma (TCC).[Methods]PCNA and WGA receptors were detected by immunohistochemical method (ABC method) in 63 specimens of TCC.[Results]We found that the distributions of PCNA and WGA receptors were increased with increase of histopathological grade in TCC (P<0.01).There was a higher expression in invasive tumors than that in superficial tumors (P<0.005),and there was a positive relation between PCNA and WGA receptors also.[Conclusion]It is shown that PCNA and WGA can be used as tumor markers for bladder cancer.%[目的 ]探讨增殖细胞核抗原 (proliferating cell nuclear antigen,PCNA)和麦胚凝集素 (wheat germ agglutinin,WGA)在膀胱移行细胞癌 (TCC)中表达的相关关系。 [方法 ]采用免疫组织化学 ABC法对 63例 TCC标本进行 PCNA和 WGA受体检测。 [结果 ]PCNA与 WGA的强阳性表达随着肿瘤的病理分级升高而增高;浸润性肿瘤中的 WGA受体的强阳性表达显著高于浅表性肿瘤 (P<0.05); PCNA与 WGA受体表达一致性良好,呈显著性相关 (P<0.005)。 [结论 ]我们认为 PCNA和 WGA受体均可作为 TCC的肿瘤标记物,证明了 TCC细胞的增殖活性增强将改变其细胞膜的抗原性。

  19. Molecular networks discriminating mouse bladder responses to intravesical bacillus Calmette-Guerin (BCG, LPS, and TNF-α

    Directory of Open Access Journals (Sweden)

    Dozmorov Igor

    2008-02-01

    Full Text Available Abstract Background Despite being a mainstay for treating superficial bladder carcinoma and a promising agent for interstitial cystitis, the precise mechanism of Bacillus Calmette-Guerin (BCG remains poorly understood. It is particularly unclear whether BCG is capable of altering gene expression in the bladder target organ beyond its well-recognized pro-inflammatory effects and how this relates to its therapeutic efficacy. The objective of this study was to determine differentially expressed genes in the mouse bladder following chronic intravesical BCG therapy and to compare the results to non-specific pro inflammatory stimuli (LPS and TNF-α. For this purpose, C57BL/6 female mice received four weekly instillations of BCG, LPS, or TNF-α. Seven days after the last instillation, the urothelium along with the submucosa was removed from detrusor muscle and the RNA was extracted from both layers for cDNA array experiments. Microarray results were normalized by a robust regression analysis and only genes with an expression above a conditional threshold of 0.001 (3SD above background were selected for analysis. Next, genes presenting a 3-fold ratio in regard to the control group were entered in Ingenuity Pathway Analysis (IPA for a comparative analysis in order to determine genes specifically regulated by BCG, TNF-α, and LPS. In addition, the transcriptome was precipitated with an antibody against RNA polymerase II and real-time polymerase chain reaction assay (Q-PCR was used to confirm some of the BCG-specific transcripts. Results Molecular networks of treatment-specific genes generated several hypotheses regarding the mode of action of BCG. BCG-specific genes involved small GTPases and BCG-specific networks overlapped with the following canonical signaling pathways: axonal guidance, B cell receptor, aryl hydrocarbon receptor, IL-6, PPAR, Wnt/β-catenin, and cAMP. In addition, a specific detrusor network expressed a high degree of overlap with the

  20. Suppressions of Migration and Invasion by Cantharidin in TSGH-8301 Human Bladder Carcinoma Cells through the Inhibitions of Matrix Metalloproteinase-2/-9 Signaling

    Directory of Open Access Journals (Sweden)

    Yi-Ping Huang

    2013-01-01

    Full Text Available Cancer metastasis becomes an initial cause of cancer death in human population. In many cancers, it has been shown that the high levels of matrix metalloproteinase (MMP-2 and/or MMP-9 are associated with the invasive phenotypes of cancer cells. In this study, we investigated the effects of cantharidin, a derivative of blister beetles which is one of the traditional Chinese medicines, on the adhesion, migration, and invasion of human bladder cancer TSGH-8301 cells. Cantharidin effectively suppressed TSGH-8301 cell adhesion, migration, and invasion in a concentration-dependent manner. Results from Western blotting, RT-PCR, and gelatin zymography assays indicated that cantharidin blocked the protein levels, gene expression (mRNA, and activities of MMP-2 and -9 in TSGH-8301 cells. Cantharidin also significantly suppressed the protein expressions of p-p38 and p-JNK1/2 in TSGH-8301 cells. Taken together, cantharidin was suggested to present antimetastatic potential via suppressing the levels of MMP-2 and MMP-9 expression that might be mediated by targeting the p38 and JNK1/2 MAPKs pathway in TSGH-8301 human bladder cancer cells.

  1. 膀胱内翻性乳头状瘤治疗分析%Analysis of inverted papilloma of bladder treatment

    Institute of Scientific and Technical Information of China (English)

    杨远旺; 覃家雅

    2015-01-01

    Objective:To explore the clinical characteristics and treatment methods of inverted papilloma of bladder.Methods:23 patients with inverted papilloma of bladder were selected.The clinical treatment were retrospectively analyzed.Results:22 patients were given transurethral electrocision of bladder tumor.1 case was given open resection of the tumor because of urethral stricture deformity.After operation,patients were given intravesical chemotherapy,postoperative follow-up showed no recurrence of tumor. Conclusion:Inverted papilloma of bladder is a rare tumor in urinary system.It has the growth characteristics of benign tumor. Recurrence is less.The prognosis is good.The diagnosis relies mainly on cystoscopy and biopsy.The standard treatment is transurethral electrocision of bladder tumor.After operation,patients should be given regular intravesical instillation and cystoscope check in order to prevent the recurrence of urothelial carcinoma.%目的:探讨膀胱内翻性乳头状瘤的临床特点及治疗方法。方法:收治膀胱内翻性乳头状瘤患者23例,回顾性分析其临床治疗。结果:22例患者经尿道膀胱肿物电切术,1例因尿道狭窄畸形行开放性肿瘤切除术,术后给予膀胱灌注化疗等,术后随访均未见肿瘤复发。结论:膀胱内翻性乳头状瘤是泌尿系少见的肿瘤,呈良性肿瘤生长特点,很少复发,预后良好,确诊主要依靠膀胱镜检及活检,经尿道膀胱肿物电切术为其标准治疗方法,术后应定期进行膀胱灌注及膀胱镜复查,以防止泌尿上皮癌的复发。

  2. Oncolytic Viruses in the Treatment of Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Kyle G. Potts

    2012-01-01

    Full Text Available Bladder carcinoma is the second most common malignancy of the urinary tract. Up to 85% of patients with bladder cancer are diagnosed with a tumor that is limited to the bladder mucosa (Ta, T1, and CIS. These stages are commonly termed as non-muscle-invasive bladder cancer (NMIBC. Although the treatment of NMIBC has greatly improved in recent years, there is a need for additional therapies when patients fail bacillus Calmette-Guérin (BCG and chemotherapeutic agents. We propose that bladder cancer may be an ideal target for oncolytic viruses engineered to selectively replicate in and lyse tumor cells leaving normal cells unharmed. In support of this hypothesis, here we review current treatment strategies for bladder cancer and their shortcomings, as well as recent advancements in oncolytic viral therapy demonstrating encouraging safety profiles and antitumor activity.

  3. Cool and menthol receptor TRPM8 in human urinary bladder disorders and clinical correlations

    Directory of Open Access Journals (Sweden)

    Benham Christopher D

    2006-03-01

    Full Text Available Abstract Background The recent identification of the cold-menthol sensory receptor (TRPM8; CMR1, provides us with an opportunity to advance our understanding of its role in the pathophysiology of bladder dysfunction, and its potential mediation of the bladder cooling reflex. In this study, we report the distribution of the cool and menthol receptor TRPM8 in the urinary bladder in patients with overactive and painful bladder syndromes, and its relationship with clinical symptoms. Methods Bladder specimens obtained from patients with painful bladder syndrome (PBS, n = 16, idiopathic detrusor overactivity (IDO, n = 14, and asymptomatic microscopic hematuria (controls, n = 17, were immunostained using specific antibodies to TRPM8; nerve fibre and urothelial immunostaining were analysed using fibre counts and computerized image analysis respectively. The results of immunohistochemistry were compared between the groups and correlated with the Pain, Frequency and Urgency scores. Results TRPM8-immunoreactive staining was observed in the urothelium and nerve fibres scattered in the suburothelium. The nerve fibre staining was seen in fine-calibre axons and thick (myelinated fibres. There was marked increase of TRPM8-immunoreactive nerve fibres in IDO (P = 0.0249 and PBS (P Conclusion This study demonstrates increased TRPM8 in nerve fibres of overactive and painful bladders, and its relationship with clinical symptoms. TRPM8 may play a role in the symptomatology and pathophysiology of these disorders, and may provide an additional target for future overactive and painful bladder pharmacotherapy.

  4. Primary Intraparenchymal Squamous Cell Carcinoma of the Kidney: A Rare and Unique Entity

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    Prithwijit Ghosh

    2014-01-01

    Full Text Available Primary squamous cell carcinoma (SCC of the renal parenchyma is a very unusual entity which needs to be differentiated from primary SCC of renal pelvis, SCC from another primary site, and urothelial carcinoma with extensive squamous differentiation. We are most probably describing the second case of primary SCC of the renal parenchyma in a 51-year-old male who presented with heaviness of right upper abdomen with intermittent pain in right flank. Contrast-enhanced computed tomography (CECT revealed a mass in the right lower pole of the kidney and histopathology following nephrectomy displayed the features of well-differentiated squamous cell carcinoma without urothelial involvement.

  5. Urothelial cells in smears from cervix uteri

    Directory of Open Access Journals (Sweden)

    Luis Alberto Palaoro

    2012-01-01

    Conclusions: The umbrella cells may be mistaken for dysplastic cells originating in low grade squamous intraepithelial lesions lesions (LSILs due to their nuclear and cytoplasm sizes. Therefore, it is important to know the possibility of their appearance in the cervical smears, especially in post menopausal patients in order to avoid a false diagnosis of an intraepithelial lesion. It is unlikely that deeper cells of urothelium would be confused with high grade squamous intraepithelial lesion (HSIL cells. However, their presence might be a reason of mistake in the diagnosis. TCM is an under-recognized metaplastic phenomenon of the cervix and vagina, which is a mimicker of high-grade squamous intraepithelial lesion. The differential characteristic between umbrella cells, cells from TCM and the deeper urothelial cells, and LSIL and HSIL are detailed in the present paper.

  6. Expression of a Inhibitor of Apoptosis Protein Livin in Transitional Cell Carcinoma of Bladder%凋亡抑制蛋白livin在膀胱移行细胞癌中的表达及其临床意义

    Institute of Scientific and Technical Information of China (English)

    曾剑; 温端改; 侯建全; 何军

    2006-01-01

    目的研究一种新的凋亡抑制蛋白(Inhibitor of Apoptosis Proten,IAP)livin两种异构体livin-α和livin-β mRNA在膀胱移行细胞癌(Transitional Cell Carcinoma of Bladder,TCC)组织中的表达,及其与TCC的病理分级、临床分期的相关性.方法采用逆转录聚合酶链反应(RT-PCR)法检测30例TCC患者的肿瘤组织、3例良性前列腺增生症(Benign Prostatic Hyperplasia,BPH)和2例外伤所致的膀胱破裂患者的膀胱组织中livin-α和livin-β mRNA的表达.结果 30例TCC组织中livin mRNA表达阳性率为16.7%,其表达阳性的病例病理分级均为Ⅲ级,肿瘤均侵及深肌层.而3例BPH患者和2例膀胱破裂患者的膀胱组织livin mRNA表达均呈阴性.结论 livin可作为 TCC的分子标记物,可成为对TCC恶性程度和预后判断的参考指标.

  7. Role of fibronectin in intravesical BCG therapy for superficial bladder cancer.

    Science.gov (United States)

    Ratliff, T L; Kavoussi, L R; Catalona, W J

    1988-02-01

    Intravesical bacillus Calmette-Guerin (BCG) has been demonstrated to be effective both for prophylaxis and treatment of superficial bladder cancer. In order to identify the progression of events that result in BCG-mediated antitumor activity, studies were performed to evaluate the mechanism of binding of BCG within the bladder. Histological and quantitative studies in a mouse model revealed that BCG attached to the bladder wall only in areas of urothelial damage. Preliminary in vitro data showed that BCG attached to surfaces coated with extracellular matrix proteins. Further studies were then performed using purified extracellular matrix proteins to identify the proteins responsible for attachment. BCG were observed to attach to surfaces coated only with purified fibronectin (FN) but not to other purified proteins including laminin, collagen or fibrinogen. The attachment of BCG to purified FN in vitro was dose dependent and was inhibited by anti-FN antibodies. Moreover, BCG attachment in vivo to bladders with damaged urothelial surfaces was inhibited more than 95% by anti-FN antibodies, but binding was not affected by anti-laminin antibodies or preimmune serum. A survey of commercially available BCG vaccines (Pasteur, Tice, Glaxo, Connaught) showed that only Glaxo BCG did not attach to FN-coated surfaces. Glaxo BCG also was shown to express inferior antitumor activity suggesting that the absence of FN binding by Glaxo may have been associated with the absence of antitumor activity of the vaccine.

  8. UPEC biomimickry at the urothelial barrier: lectin-functionalized PLGA microparticles for improved intravesical chemotherapy.

    Science.gov (United States)

    Neutsch, Lukas; Wambacher, Michael; Wirth, Eva-Maria; Spijker, Sylvia; Kählig, Hanspeter; Wirth, Michael; Gabor, Franz

    2013-06-25

    The urgent demand for more potent treatment schedules in bladder cancer (BCa) therapy calls for a refinement of the intravesical administration modalities. However, progress on drug delivery systems tailored to the penetration-hostile urothelial barrier lags behind the advancements in comparable fields. This study reports on a multimodal, carrier-based delivery concept that combines biorecognitive targeting with modified release strategies for improved intravesical chemotherapy. The plant lectin wheat germ agglutinin (WGA) was immobilized on poly(lactide-co-glycolide) (PLGA) microparticles (MP) to induce stable cytoadhesion via cellular carbohydrate chains, similar to the specific attachment mechanism utilized by uropathogenic bacteria. A panel of DNA-selective chemotherapeutics with established track record in uro-oncology was screened for physicochemical compatibility with the polymeric carrier formulation. Critical limitations in encapsulation efficiency were found for mitomycin C (MMC), doxorubicin (DOX), and gemcitabine hydrochloride (GEM), despite multiparametric optimization of the preparation conditions. In contrast, the amphiphilic 4-(N)-stearoyl prodrug of gemcitabine (GEM-C18) exhibited excellent processability with PLGA. In vitro bioassays on 5637 human BCa cells showed that the enhanced cytoadhesion of WGA-GEM-C18-PGLA-MP traces back to the specific lectin/carbohydrate interaction, and is not easily disrupted by adverse environmental factors. Owing to several synergistic effects, the combined prodrug/targeting approach resulted in strong cytostatic response even when adjusting the exposure scheme to the confined temporal conditions of instillative treatment. Our results highlight the importance of fine-tuning both pharmacokinetic and pharmacologic parameters to gain adequate impact on urothelial cancer cells, and assign promising potential to glycan-targeted delivery concepts for the intravesical route.

  9. Low-grade mucinous cystic tumor mimicking urinary bladder tumor: imaging-pathologic correlation.

    Science.gov (United States)

    Dohan, Anthony; Ferlicot, Sophie; Bessède, Thomas; Soyer, Philippe; Rocher, Laurence

    2013-05-01

    Mucin-producing cystitis glandularis is a rare proliferative and metaplastic change of the bladder mucosa that produces large amounts of mucus, thus taking a pseudotumoral pattern and resulting in urinary tract obstruction. We report a case of florid mucin-producing cystitis glandularis mimicking bladder carcinoma in a 77-year-old man that was documented by computed tomography and magnetic resonance imaging. Computed tomography showed diffuse, circumferential, irregular, and lobulated thickening of the bladder wall suggestive of urinary bladder carcinoma. Magnetic resonance imaging showed findings consistent with mucinous content and suggested the correct diagnosis preoperatively. PMID:23490529

  10. High frequency of tumor cells with nuclear Egr-1 protein expression in human bladder cancer is associated with disease progression

    International Nuclear Information System (INIS)

    Egr-1 (early growth response-1 transcription factor) has been proposed to be involved in invasion and metastasis processes of human bladder cancer, but Egr-1 protein expression levels in human bladder cancer have not been investigated. In the present study we investigated the expression levels of Egr-1 protein in early stages of human bladder cancer and correlated it to later progression. Expression of Egr-1 protein in human bladder cancer was examined by immunohistochemistry, on a tissue microarray constructed from tumors from 289 patients with non-muscle invasive urothelial bladder cancer. The frequency of tumor cells with nuclear Egr-1 immunolabelling correlated to bladder cancer stage, grade and to later progression to muscle-invasive bladder cancer (T2-4). Stage T1 tumors exhibited significantly higher frequencies of tumor cells with nuclear Egr-1 immunolabelling than Ta tumors (P = 0.001). Furthermore, Kaplan-Meier survival analysis showed that a high frequency of tumor cells with nuclear Egr-1 immunolabelling was significantly associated with a higher risk of progression to stage T2-4 (log-rank test, P = 0.035). Tumor cells with nuclear Egr-1 immunolabelling were found to localize at the tumor front in some of the tumor biopsies. The results from this study support a potential involvement of Egr-1 in the progression from non-muscle invasive bladder cancers to muscle invasive bladder cancer

  11. Bladder uptake of liposomes after intravesical administration occurs by endocytosis.

    Directory of Open Access Journals (Sweden)

    Bharathi Raja Rajaganapathy

    Full Text Available Liposomes have been used therapeutically and as a local drug delivery system in the bladder. However, the exact mechanism for the uptake of liposomes by bladder cells is unclear. In the present study, we investigated the role of endocytosis in the uptake of liposomes by cultured human UROtsa cells of urothelium and rat bladder. UROtsa cells were incubated in serum-free media with liposomes containing colloidal gold particles for 2 h either at 37°C or at 4°C. Transmission Electron Microscopy (TEM images of cells incubated at 37°C found endocytic vesicles containing gold inside the cells. In contrast, only extracellular binding was noticed in cells incubated with liposomes at 4°C. Absence of liposome internalization at 4°C indicates the need of energy dependent endocytosis as the primary mechanism of entry of liposomes into the urothelium. Flow cytometry analysis revealed that the uptake of liposomes at 37°C occurs via clathrin mediated endocytosis. Based on these observations, we propose that clathrin mediated endocytosis is the main route of entry for liposomes into the urothelial layer of the bladder and the findings here support the usefulness of liposomes in intravesical drug delivery.

  12. Bladder cancer; Cancer de la Vessie

    Energy Technology Data Exchange (ETDEWEB)

    Pointreau, Y. [Service de radiotherapie, centre regional universitaire de cancerologie Henry-S.-Kaplan CHU de Tours, Hpital Bretonneau, 37 - Tours (France); Universite Francois-Rabelais de Tours, GICC, 37 - Tours (France); CNRS, UMR 6239 -Genetique, Immunotherapie, Chimie et Cancer-, 37 - Tours (France); CHRU de Tours, laboratoire de pharmacologie-toxicologie, 37 - Tours (France); Denis, F. [Centre Jean-Bernard, 72 - Le Mans (France); Klotz, S.; Durdux, C. [Service d' oncologie-radiotherapie, hopital europeen Georges-Pompidou, 75 - Paris (France); Denis, F. [Centre Jean-Bernard, 72 - Le Mans (France)

    2010-07-01

    Bladder cancer is an urologic common tumor after prostate carcinoma. Radical treatment of localized invasive tumor is based on cystectomy. Surgical mutilation could be important when Bricker's urinary derivation is performed. Moreover, delayed metastasis frequently appeared in spite of radical surgery. Thus, chemoradiotherapy is a valid alternative treatment to cystectomy for selected patients. Cisplatin or derivatives are usually concurrently administered to radiation therapy up to 60 - 65 Gy. Patients undergo control cystoscopy at mid-time of treatment in order to select responders from non responders. For majority of cases, the empty bladder should be entirely treated with added margins (about 20 mm) to build the PTV. Control assessment could be improved by echography, cone beam imaging as well as bladder fiduciaries implantation before treatment. From a case report, this review summarizes the technical aspects of radiation therapy (GTV, CTV and PTV, organs at risk, planning) and main acute and late related toxicities. (authors)

  13. Emerging concepts on drug resistance in bladder cancer: Implications for future strategies.

    Science.gov (United States)

    Massari, Francesco; Santoni, Matteo; Ciccarese, Chiara; Brunelli, Matteo; Conti, Alessandro; Santini, Daniele; Montironi, Rodolfo; Cascinu, Stefano; Tortora, Giampaolo

    2015-10-01

    The combination chemotherapies with methotrexate plus vinblastine, doxorubicin and cisplatin (MVAC or CMV regimens) or gemcitabine plus cisplatin represent the standard as first-line therapy for patients with metastatic urothelial cancer. In Europe, vinflunine is an option for second-line therapy for patients progressed during first-line or perioperative platinum-containing regimen. Alternative regimens containing taxanes and/or gemcitabine may be valuated case by case. Furthermore, carboplatin should be considered in patients unfit for cisplatin both in the first and second-line setting. Based on these findings, a better comprehension of the mechanisms underlying the development of drug resistance in patients with bladder cancer will represent a major step forward in optimizing patients' outcome. This article reviews the current knowledge of the mechanisms and emerging strategies to overcome resistance in patients with advanced urothelial cancer.

  14. Impact of diabetes mellitus on bladder uroepithelial cells.

    Science.gov (United States)

    Hanna-Mitchell, Ann T; Ruiz, Giovanni W; Daneshgari, Firouz; Liu, Guiming; Apodaca, Gerard; Birder, Lori A

    2013-01-15

    Diabetic bladder dysfunction (DBD), a prevalent complication of diabetes mellitus (DM), is characterized by a broad spectrum of symptoms including urinary urgency, frequency, and incontinence. As DBD is commonly diagnosed late, it is important to understand the chronic impact of DM on bladder tissues. While changes in bladder smooth muscle and innervation have been reported in diabetic patients, the impact of DM on the specialized epithelial lining of the urinary bladder, the urothelium (UT), is largely unknown. Quantitative polymerase chain reaction analysis and electron microscopy were used to evaluate UT gene expression and cell morphology 3, 9, and 20 wk following streptozotocin (STZ) induction of DM in female Sprague-Dawley rats compared with age-matched control tissue. Desquamation of superficial (umbrella) cells was noted at 9 wk DM, indicating a possible breach in barrier function. One causative factor may be metabolic burden due to chronic hyperglycemia, suggested by upregulation of the polyol pathway and glucose transport genes in DM UT. While superficial UT repopulation occurred by 20 wk DM, the phenotype was different, with significant upregulation of receptors associated with UT mechanosensation (transient receptor potential vanilloid subfamily member 1; TRPV1) and UT autocrine/paracrine signaling (acetylcholine receptors AChR-M2 and -M3, purinergic receptors P2X(2) and P2X(3)). Compromised barrier function and alterations in UT mechanosensitivity and cell signaling could contribute to bladder instability, hyperactivity, and altered bladder sensation by modulating activity of afferent nerve endings, which appose the urothelium. Our results show that DM impacts urothelial homeostasis and may contribute to the underlying mechanisms of DBD. PMID:23174855

  15. Superficial urinary bladder tumors treatment results: A 10-year experience

    OpenAIRE

    Stanković Jablan; Dinić Ljubomir; Pavlović Svetlana

    2007-01-01

    Background/Aim. The most common urinary bladder tumors are superficial tumors. Due to their tension to relapse and progress towards deeper layers after surgical therapy, an adequate therapy significantly contributed to the improvement of the results of urinary bladder tumors treatment. Staging and gradus of the tumor, presence of the carcinoma in situ (CIS) or relapses significantly influenced the choice of the therapy. The aim of this study was to ascertain the effectiveness of the intravesi...

  16. Nursing Interventions Affect Quality of Life of Bladder Carcinoma Patients after Radical Cystectomy and Abdominal Stoma%护理干预对膀胱全切腹壁造口患者生活质量的影响

    Institute of Scientific and Technical Information of China (English)

    熊柱凤; 陈炤; 汤利萍; 吴重阳; 罗艳萍; 傅斌; 易继群; 黄娇; 傅龙龙

    2013-01-01

    目的 研究护理干预对膀胱全切腹壁造口患者生活质量及社会支持状况的影响.方法 将膀胱全切腹壁造口术患者54例随机分为对照组和观察组各27例.对照组采用膀胱全切腹壁造口患者术后常规专业护理措施;观察组在膀胱全切腹壁造口患者术后常规专业护理措施的基础上,进行健康教育、心理干预、循证护理及出院指导等护理干预措施.结果 观察组术后6个月及12个月躯体功能指数、生理功能指数、社会功能指数均优于对照组,差异有统计学意义(P<0.05).观察组社会支持总分、客观支持总分、主观支持总分优于对照组,差异有统计学意义(P<0.01).结论 护理干预能够改善膀胱全切腹壁造口患者的生活质量,促进其生理和心理的舒适,并有效地改善患者的社会支持状况.%Objective To assess the effect of nursing interventions on quality of life ( QOL ) and social support of bladder carcinoma patients after radical cystectomy and abdominal stoma. Methods Fifty - four bladder carcinoma patients who had undergone radical cystectomy and abdominal stoma were divided into the observation group and the control group. The control group was given routine nursing care after the operation. The observation group was given routing nursing care plus health education , psychological intervention, evidence - based nursing care and hospital discharge guide. Results Six and twelve months after the operation, the somatic, physiological, and social function indices of the observation group were higher than that of the control group ( P < 0. 05 ); total scores of social support, objective support, and subjective support of the observation group were higher than that of the control group ( P < 0. 01 ) . Conclusion Nursing interventions can improve the QOL of patients after radical cystectomy and abdominal stoma, promote their physical and psychological comfort and social support.

  17. Expression of the Long Non-Coding RNA HOTAIR Correlates with Disease Progression in Bladder Cancer and Is Contained in Bladder Cancer Patient Urinary Exosomes

    OpenAIRE

    Berrondo, Claudia; Flax, Jonathan; Kucherov, Victor; Siebert, Aisha; Osinski, Thomas; Rosenberg, Alex; Fucile, Christopher; Richheimer, Samuel; Beckham, Carla J.

    2016-01-01

    Exosomes are 30-150nM membrane-bound secreted vesicles that are readily isolated from biological fluids such as urine (UEs). Exosomes contain proteins, micro RNA (miRNA), messenger RNA (mRNA), and long non-coding RNA (lncRNA) from their cells of origin. Although miRNA, protein and lncRNA have been isolated from serum as potential biomarkers for benign and