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National Cancer Institute®
Ultima Vez Modificado: 1 de julio del 2002
UI - 11598450
AU - Iori F; De Dominicis C; Liberti M; Frioni D; Vahedi M; Leonardo C; De
TI - Nunzio C; Laurenti C Superficial bladder tumors in patients under 40 years of age: clinical, prognostic and cytogenetic aspects.
SO - Urol Int 2001;67(3):224-7
AD - Department of Urology U. Bracci (IIIrd Division, Dir. Prof. C. Laurenti), University of Rome La Sapienza, Viale Regina Elena, I-00161 Rome, Italy.
Bladder carcinoma with transitional cells is the most frequent neoplasia in the urinary system, but it is quite rare in patients under 40 years of age (0.4-2%). An analysis of 21 patients under 40 and a review of other reports show that tumors in patients under 20 years old have little tendency to recur and to progress, while tumors in patients aged between 21 and 40 have a behavior pattern similar to older age groups regarding recurrence and disease progression. Preliminary results of a study using fluorescent in situ hybridization with probes for the centromere of chromosomes 7 and 17 showed a high incidence of aneusomy with regard to these chromosomes and a genetic difference between superficial tumors in the young and in adults. Using probes from chromosomes already described in bladder carcinogenesis, we obtained higher sensitivity and specificity in detecting aneuploid events. Copyright 2001 S. Karger AG, Basel
UI - 11598453
AU - Watters AD; Stacey MW; Going JJ; Grigor KM; Cooke TG; Sim E; Bartlett JM
TI - Genetic aberrations of NAT2 and chromosome 8: their association with progression in transitional cell carcinoma of the urinary bladder.
SO - Urol Int 2001;67(3):235-9
AD - Department of Surgery, Glasgow Royal Infirmary, University of Glasgow, Glasgow G31 2ER, UK. email@example.com
INTRODUCTION/OBJECTIVE: N-acetyltransferase 2 (NAT2), mapped to 8p22, is a polymorphic enzyme which metabolizes aromatic amines. Loss of heterozygosity of 8p22 is associated with an increased risk of bladder cancer. This study evaluated NAT2 and chromosome 8 in sequential tumours from bladder cancer patients to determine if NAT2 alterations increase the risk of progression. MATERIALS AND METHODS: Thirty-seven sequential carcinomas from 19 patients were assessed using fluorescence in situ hybridization. RESULTS: Five carcinomas showed loss of NAT2; 4 of these were from pTa/pT1 tumours. Polysomy 8 was observed in 4 of 14 (29%) primary carcinomas (pTa/pT1), in 4 of 12 (33%) pTa/pT1 recurrences, and in 90% (9/10) of the detrusor muscle invasive tumours (pT2+). 6 of 8 (75%) locally invasive tumours with polysomy 8 were from patients who subsequently developed disease progression (pT2+). In total, 13.5% (5/37) of the carcinomas were abnormal for NAT2, and 46% (17/37) were abnormal for chromosome 8 copy number. Polysomy 8 was associated with high grade (p = 0.01) and stage (p = 0.03) and disease progression (p = 0.03). CONCLUSION: Whilst there does not appear to be an association between loss of NAT2 and risk of progression in transitional cell carcinoma, the high rate of polysomy of chromosome 8 implies that other genes on this chromosome significantly influence disease progression. Copyright 2001 S. Karger AG, Basel
UI - 11695203
AU - Patriarca S; Gafa L; Ferretti S; Vitarelli S; Cesaraccio R; Crocetti E;
TI - Ferrante MC; Rollo P; Tagliabue G Coding criteria of bladder cancer: effects on estimating survival.
SO - Epidemiol Prev 2001;25(3 Suppl):42-7
AD - Registro Tumori Piemonte, Centro per l'epidemiologia e la prevenzione oncologica, CPO Piemonte, Dipartimento di oncologia, Ospedale San Giovanni antica sede, Torino. firstname.lastname@example.org
The aim of this study is to evaluate the consistency between routine methods for coding urinary bladder tumours in eight Italian cancer registries and the European Network of cancer registries (ENCR) criteria. Furthermore, it aims to evaluating the impact of the discordance on survival data. Eight cancer registries took part in the study: Ferrara, Florence, Macerata, Ragusa, Romagna, Sassari, Turin and Varese. The first 100 cases of neoplasm of the urinary bladder incident in the years 1993-1994 were identified from the files of each registry. The original pathology reports were made available. A working group considered eligible to the study 699 cases of microscopically confirmed transitional carcinoma (ICD-O morphology code 812-813). Using the ENCR criteria, each of these was classified according to morphology code (8120 vs. 8130) and behaviour (1/ uncertain, /2 non-invasive, 3/ invasive). Information of tumour behaviour was classified as follows: (i) present, when expressly stated in the original report, (ii) deducible, when not expressly stated but suggested by the pathologist's description, and (iii) absent, when impossible to determine on the basis of the original pathology report. The working group classification of tumour behaviour and the classification of the registry of origin were compared. There was a full concordance in the case of complete agreement on the morphology code, and partial concordance when only the invasive or non-invasive behaviour code was agreed upon. As much as 92.5% cases were microscopically confirmed. Tumour behaviour was expressly stated in the original report of 69.2% cases, not stated but suggested by the pathologist's description in 21.2% cases, and impossible to determine in 9.6%. Agreement between the panel and the registry of origin was complete in 71.2% cases and partial in 12.3% while there was a complete discordance in 16.5% cases. The panel interpreted as non-invasive 111 cases coded as invasive by the registry of origin. Conversely, it was estimated that 24% cases included in incidence data were non-invasive. This article discusses the impact of misclassification on survival data.
UI - 11953150
AU - Zheng S; Zhang J; Di X; Xiao Z; Wang D; Li C; He Z; Han N; Guo S; Cheng
TI - S; Gao Y [Loss of heterozygosity fine mapping of chromosome 17p13 in transitional cell carcinoma of human urinary bladder]
SO - Zhonghua Yi Xue Za Zhi 2002 Feb 10;82(3):161-3
AD - Department of Etiology and Carcinogenesis, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China.
OBJECTIVE: To determine the frequency and common deletion region of allelic losses on chromosome 17p13 in transitional cell carcinoma (TCC) of human urinary bladder so as to provide clues for isolation of candidate tumor suppressor genes associated with TCC of urinary bladder. METHODS: Loss of heterozygosity (LOH) analysis was made on 44 samples of surgically resected primary TCC by using 13 microsatellite markers to map the regions frequently deleted on chromosome 17p13. The relationship between the LOH in each locus and pathological grade and stage was analyzed. RESULTS: Out of the 44 samples, 35 (79.5%) showed allelic loss in at least one of the 17p13 loci. The highest frequency of LOH (41.4%, 12/29) was at D17S513 in 17p13.2, the second highest frequency of LOH (40.5%, 17/42) was at D17S1308 in 17p13.3, and the lowest (14.3%, 4/28) was at D17S261 in 17p13.1. The most frequent LOH loci were mainly located in three regions: D17S695-D17S1308 in 17p13.3, D17S1533-D17S831 in 17p13.2, and TP53 in 17p13.1. Among them only the LOH frequency of TP53 locus was positively correlated to the grade (chi(2) = 5.104, P < 0.05) and stage (chi(2) = 5.382, P < 0.05) of TCC of unrinary bladder. CONCLUSION: In 17p13 region, except for TP53 gene, still exist two candidate tumor suppressor genes located in D17S695-D17S1308 and D17S1533-D17S831 involved in the carcinogenesis of TCC of urinary bladder. LOH of TP53 locus may be one of the later events in TCC, and LOH in 17p13.3 and 17p13.2 may be the early events of TCC of uninary bladder.
UI - 12034625
AU - Lammle M; Beer A; Settles M; Hannig C; Schwaibold H; Drews C
TI - Reliability of MR imaging-based virtual cystoscopy in the diagnosis of cancer of the urinary bladder.
SO - AJR Am J Roentgenol 2002 Jun;178(6):1483-8
AD - Department of Radiology, Klinikum rechts der Isar der Technischen Universitat Munchen, Ismaninger Str. 22, D-81675 Munich, Germany.
OBJECTIVE: Our purpose was to evaluate MR imaging-based virtual endoscopy in patients with urinary bladder cancer compared with conventional cystoscopy as the gold standard. SUBJECTS AND METHODS: Twenty-five patients with urinary bladder cancer diagnosed on conventional cystoscopy underwent MR imaging of the pelvis. Patients were examined without external bladder filling or administration of IV contrast medium. No medications were administered. The data obtained by MR imaging were reconstructed for virtual endoscopy on a workstation. The locations and sizes of tumors were individually determined and compared with results of conventional cystoscopy. RESULTS: Twenty-four patients were evaluated; one patient's examination was excluded from analysis because of metallic artifacts. Seventeen patients were diagnosed with a single bladder tumor. Five patients had two tumors each, and two patients had three tumors. Tumor diameter ranged from 0.4 to 6.4 cm. Thirty (90.9%) of 33 tumors detected on cystoscopy were visualized with virtual endoscopy. The detection rate for 23 tumors of 1 cm or greater was 100%. Difficult conditions for conventional cystoscopy, including hematuria, anterior wall involvement, and urethral strictures, had no deleterious impact on virtual cystoscopy. Difficulties in detection on virtual endoscopy were associated with flat bladder tumors with minimal surface elevation. CONCLUSION: The results of this study suggest a high reliability in the diagnosis of urinary bladder cancer by MR imaging-based virtual cystoscopy-a noninvasive method, independent of medication or contrast enhancement, that may be of value for screening, primary diagnosis, and surveillance. Virtual MR cystoscopy may be indicated when conventional cystoscopy cannot be performed or is ineffective.
UI - 10792157
AU - Corrigan NT; Crooks J; Shand J
TI - Are dedicated bladder films necessary as part of intravenous urography for haematuria?
SO - BJU Int 2000 May;85(7):806-10
AD - Departments of Radiology and Urology, Stobhill General Hospital, Glasgow, UK.
OBJECTIVE: To determine the use and assess the value of full-bladder films during intravenous urography (IVU) which, despite the widespread availability of flexible cystoscopy, remain part of IVU in many radiology departments. Materials and methods A telephone survey of all Scottish radiology departments where IVU is regularly used showed that half routinely included a full-bladder film in the series. The reports of all IVU over 2 years in the authors' department were analysed retrospectively. The index urogram of all patients with bladder tumours confirmed during this period was reviewed independently by three observers, and together with the initial radiological reports was correlated with the cystoscopic and histological findings. RESULTS: From 2625 patients, 139 (5.2%) IVU reports commented on the bladder; 1423 patients presented with no haematuria. None of the patients without haematuria, where a comment was made about the bladder, had pathological evidence of a tumour. Overall 121 of 464 (26%) new bladder tumours were diagnosed on IVU before cystoscopy. Multiple tumours were always undetected and large tumours were often overlooked. CONCLUSIONS: Despite its continuing popularity, IVU is a poor means of identifying bladder tumours and routine views of the full bladder should be abandoned.
UI - 11287448
AU - Castelao JE; Yuan JM; Skipper PL; Tannenbaum SR; Gago-Dominguez M;
TI - Crowder JS; Ross RK; Yu MC Gender- and smoking-related bladder cancer risk.
SO - J Natl Cancer Inst 2001 Apr 4;93(7):538-45
AD - University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine of the University of Southern California, Los Angeles 90089-9181, USA. email@example.com
BACKGROUND: There is growing evidence that, when smoking habits are comparable, women incur a higher risk of lung cancer than men. Because smokers are also at risk for bladder cancer, we investigated possible sex differences in the susceptibility to bladder cancer among smokers. METHODS: A population-based, case--control study was conducted in Los Angeles, CA, involving 1514 case patients with bladder cancer and 1514 individually matched population control subjects. Information on tobacco use was collected through in-person interviews. Peripheral blood was collected from study participants to measure 3- and 4-aminobiphenyl (ABP)-hemoglobin adducts, a marker of arylamine exposure. Data were analyzed to determine whether the risk of bladder cancer differs between male and female smokers and whether female smokers exhibit higher levels of ABP-hemoglobin adducts than male smokers with comparable smoking habits. All statistical tests were two-sided. RESULTS: Cigarette smokers had a statistically significant 2.5-fold higher risk (95% confidence interval = 2.1 to 3.0) of bladder cancer than never smokers. Use of filtered versus nonfiltered cigarettes, low-tar versus higher tar cigarettes, or the pattern of inhalation did not modify the risk. The risk of bladder cancer in women who smoked was statistically significantly higher than that in men who smoked comparable numbers of cigarettes (P =.016 for sex-lifetime smoking interaction). Consistent with the sex difference in smoking-related bladder cancer risk, the slopes of the linear regression lines of the 3- and 4-ABP--hemoglobin adducts by cigarettes per day were statistically significantly steeper in women than in men (P values for sex differences <.001 and.006, respectively). CONCLUSION: The risk of bladder cancer may be higher in women than in men who smoked comparable amounts of cigarettes.
UI - 12050554
AU - van der Poel HG; Molenaar B; van Beusechem VW; Haisma HJ; Rodriguez R;
TI - Curiel DT; Gerritsen WR Epidermal growth factor receptor targeting of replication competent adenovirus enhances cytotoxicity in bladder cancer.
SO - J Urol 2002 Jul;168(1):266-72
AD - Department of Urology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
PURPOSE: We evaluated the delivery and oncolytic potential of targeted replication competent adenoviruses in bladder cancer lines. MATERIALS AND METHODS: Seven established human bladder cancer tumor lines (5637, SW800, TCCsup, J82, Scaber, T24 and 253J) were studied for the expression of integrins alpha(v)beta3, alpha(v)beta5, Coxsackievirus and adenovirus receptor, epidermal growth factor receptor (EGF-R) and epithelial cell adhesion molecule antigens using flow cytometry analysis. Bispecific single chain Fv fragments were used to target replication deficient luciferase reporter adenovirus to EGF-R (425-s11) or to epithelial cell adhesion molecule (C28-s11) antigens. Moreover, a fiber modified adenovirus targeting alpha(v)-integrins was studied. Replication competent serotype-5 adenoviruses attenuated to replicate specifically in retinoblastoma pRb (Ad5-d24) or p53 deficient (Ad5-d55K) cells were tested in vitro for oncolytic properties. RESULTS: Low to absent Coxsackievirus and adenovirus receptor expression was found in 5 of the 7 tumor lines (SW800, J82, T24, 5637 and Scaber). EGF-R expression was found in all cell lines, whereas elevated epithelial cell adhesion molecule expression was seen in 3 (5637, Scaber and TCCsup), alpha(v)beta3-integrin was found in 1 (Scaber) and alpha(v)beta5-integrin was found in 3 (TCCsup, 253J and T24). EGF-R targeting using 425-s11 improved transgene expression in all cell lines from 2.1 to 12.5 times over nontargeted viruses. Epithelial cell adhesion molecule and integrin targeting was inferior to EGF-R targeting with a maximal increase in transgene expression of 2 times for epithelial cell adhesion molecule in 5637cells and 1.6 times for integrin targeting in T24 cells. Comparison of the wild-type replication competent virus with conditionally replicating adenoviruses (Ad5-d55K and Ad5-d24) showed superior oncolytic activity for the latter 2 in all lines. Furthermore, improved cytotoxicity (29% to 33%) was obtained in 4 of the 7 lines after pre-incubation of Ad5-d24 with 425-s11. CONCLUSIONS: EGF-R directed bispecific single chain antibodies enhance adenovirus mediated transgene expression and oncolysis in bladder cancer lines.
UI - 12050493
AU - Yossepowitch O; Dalbagni G
TI - Transitional cell carcinoma of the bladder in young adults: presentation, natural history and outcome.
SO - J Urol 2002 Jul;168(1):61-6
AD - Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
PURPOSE: The natural history and prognosis of bladder cancer in young patients is not well defined. We analyzed our experience with such patients. MATERIALS AND METHODS: The medical records of 74 patients presenting with transitional cell carcinoma of the bladder at 40 years and younger were reviewed and compared with those of 75 patients diagnosed with bladder transitional cell carcinoma at 65 years old and older. RESULTS: Median followup was 28.1 months (range 1 to 155) and 34.7 (range 1 to 178) in young and old patients, respectively. Initial stage distribution was similar with 80% of patients presenting with superficial disease. No difference was observed in the disease-free progression or disease-free recurrence rate among the groups in patients initially presenting with stage Ta, Tis or T1 tumors. A significantly higher proportion of older versus younger patients underwent cystectomy (54% versus 23%). We did not observe a difference in pathological stage distribution or the rate of extravesical disease in young and old patients (47% and 45%, respectively). Younger patients who ultimately underwent radical cystectomy had significantly lower disease-free survival, mainly due to a higher rate of distant metastases than in the older group (41% versus 24%). The rate of local recurrence was similar. CONCLUSIONS: Bladder transitional cell carcinoma in young adults has a clinical stage distribution and natural history similar to that in older patients. Our study suggests that a subset of young patients who ultimately undergo radical cystectomy have particularly aggressive tumors, portending a poor outcome.
UI - 12050494
AU - Filbeck T; Pichlmeier U; Knuechel R; Wieland WF; Roessler W
TI - Clinically relevant improvement of recurrence-free survival with 5-aminolevulinic acid induced fluorescence diagnosis in patients with superficial bladder tumors.
SO - J Urol 2002 Jul;168(1):67-71
AD - Department of Urology, St. Joseph's Hospital and Institute of Pathology, University of Regensburg, Germany.
PURPOSES: Fluorescence diagnosis induced by 5-aminolevulinic acid enables more thorough transurethral resection of superficial bladder carcinoma compared with conventional white light. We performed a prospective, single institution, randomized trial to investigate whether the residual tumor rate and long-term tumor recurrence can be decreased by fluorescence diagnosis. MATERIALS AND METHODS: A total of 301 patients underwent transurethral resection of bladder tumors with white light or fluorescence diagnosis. Transurethral resection was repeated 5 to 6 weeks later to evaluate the residual tumor rate. To determine recurrence-free survival patient followup was performed every 3 months by white light cystoscopy and urine cytology. Recurrence-free survival was analyzed via Kaplan-Meier methods and multivariable Cox regression analysis. RESULTS: A total of 191 patients with superficial bladder carcinoma were available for efficacy analysis. The residual tumor rate was 25.2% in the white light arm versus 4.5% in the fluorescence diagnosis arm (p <0.0001). Median followup in the white light arm in 103 cases was 21.2 months (range 4 to 40) compared with 20.5 (range 3 to 40) in the 88 in the fluorescence diagnosis arm. Recurrence-free survival in the fluorescence diagnosis group was 89.6% after 12 and 24 months compared with 73.8% and 65.9%, respectively, in the white light group (p = 0.004). This superiority proved to be independent of risk group. The adjusted hazard ratio of fluorescence diagnosis versus white light transurethral resection was 0.33 (95% confidence interval 0.16 to 0.67). CONCLUSIONS: Fluorescence diagnosis is significantly superior to conventional white light transurethral resection with respect to the residual tumor rate and recurrence-free survival. The differences in recurrence-free survival imply that fluorescence diagnosis is a clinically relevant procedure for decreasing the number of tumor recurrences.
UI - 11482447
AU - Kontani K; Kawakami M; Nakajima T; Katsuyama T
TI - Tobacco use and occupational exposure to carcinogens, but not N-acetyltransferase 2 genotypes are major risk factors for bladder cancer in the Japanese.
SO - Urol Res 2001 Jun;29(3):199-204
AD - Department of Urology, Shinshu University School of Medicine, Matsumoto, Japan.
Our study investigated the risks of genotypes of N-acetyltransferase 2 (NAT2), tobacco use and/or occupational exposure to carcinogens in patients with bladder cancer and in age- and sex-matched controls in Japanese. NAT2 genotypes were categorized into two groups, homozygous mutant (slow acetylator genotype) and homozygous and heterozygous wild type (fast acetylator genotype). The percentage of NAT2 slow acetylator types was 6.7% in the bladder cancer patients, close to the value for controls (6.1%). There was no association between NAT2 slow acetylator genotype and the risk of bladder cancer. This association was also insignificant when subjects were restricted to those who used tobacco or those occupationally exposed to carcinogens. In contrast, tobacco use in combination with exposure to carcinogens was a significant risk factor, as based on the odds ratio and chi-square test. The combination of both factors should be an additive risk factor for bladder cancer. In this study, we demonstrated that the environmental factors of smoking habit and occupational exposure for carcinogenicity are much more important than genetic factors in bladder cancer.
UI - 11528193
AU - Sagol O; Yorukoglu K; Tuna B; Ozer E; Sis B; Guray M; Mungan U; Kirkali
TI - Z Expression of pS2 protein and its relation with the Ki-67 proliferative indices and tumor recurrence in superficial bladder carcinomas.
SO - Eur Urol 2001 Aug;40(2):163-8
AD - Department of Pathology, Dokuz Eylul University School of Medicine, Inciralti/Izmir, Turkey.
OBJECTIVE: To investigate the expression and possible role of pS2 protein as a predictor of tumor recurrence in superficial transitional cell carcinoma of the bladder and to determine its relation with tumor stage, grade, size, number, recurrence and proliferative activity. METHODS: Paraffin sections of transurethral resection material from 80 patients with superficial transitional cell bladder carcinoma were stained with pS2 and Ki-67 antibodies using the standard streptavidin biotin immunoperoxidase method. Cytoplasmic pS2 staining was scored on a scale of 1-3 and the Ki-67-labelling index was determined as a percentage of positively staining tumor cells. RESULTS: An inverse relationship was found between pS2 expression and Ki-67 index (p<0.001). pS2 expression showed no relation with any clinicopathological prognostic parameters as well as the recurrence rate. The recurrence rate was only associated with increased tumor number (p = 0.05), while the time to first recurrence was significantly related to tumor size, proliferative activity and tumor grade (p = 0.04, p<0.001, and p = 0.03, respectively). On the other hand, higher tumor grade was correlated with increased tumor number, Ki-67 index and tumor stage (p = 0.016, p = 0.006, and p<0.001, respectively). CONCLUSION: pS2 expression is associated with a low proliferative potential of superficial transitional cell carcinoma of the bladder, while it does not seem to be related to the recurrence rate of the tumor and other prognostic factors. Tumor size and proliferative activity may aid in the estimation of the time to the first recurrence.
UI - 11684850
AU - Popov I; Jelic S; Radosavljevic D; Nikolic-Tomasevic Z
TI - Amsacrine and cisplatin in poor prognosis patients with metastatic transitional cell carcinoma of the urothelium: a phase-II study.
SO - Eur Urol 2001 Sep;40(3):324-9
AD - Institute of Oncology and Radiology of Serbia, Belgrade, FR Yugoslavia. firstname.lastname@example.org
OBJECTIVES: Amsacrine, as a single agent, was reported to be effective in patients with metastatic transitional cell carcinoma of the urinary bladder. Amsacrine is also associated with a lower toxicity than cyclophosphamide, doxorubicin and cisplatin therapy and has similar activity. But amsacrine has been forgotten in clinical studies of transitional cell carcinoma of the urinary bladder. The aim of present study was to investigate the toxicity and efficacy of amsacrine and cisplatin in chemotherapy-naive patients with metastatic transitional cell carcinoma of the urinary bladder. METHODS: We have treated 54 patients (41 males/13 females) with a median age of 62 (38-72) years. Performance status was 0/2, I/27 II/17 and III/8. The treatment included: amsacrine 85 mg/ m(2), days 1-2, and cisplatin 30 mg/m(2), days 2-5. Cycles were repeated every 4 weeks. We applied 169 cycles (median 3/patient). Of 54 patients, 39 had previous surgery and 12 had previous radiotherapy. Histological tumor grade was I/7, II/27 and III/20. RESULTS: 51 patients were evaluable for response (3 patients refused further treatment during the first cycle): 2 complete remission (4%); 15 partial remission (29%); 23 stable disease (45%), and 11 progressive disease (22%). The response rate was 33% (95% CI 21-46). On an intent-to-treat basis the response was 32% (95% CI 19-44). Durations of complete and partial responses were 14 (range 12-16) and 6.5 (range 3-11) months, respectively. Median survival was 9 (range 3-21) months. All patients were evaluable for toxicity. Grades III-IV toxicity was as follows: anemia 11%; neutropenia 37%, and thrombocytopenia 20%. None of the patients was excluded from the study because of toxicity. CONCLUSION: The combination of amsacrine and cisplatin is a regimen with mild and manageable toxicity. The present regimen seems to be active. Randomized study of the present regimen versus another low-toxicity regimens are necessary, especially for poor prognosis patients including those with a low performance status.
UI - 11711760
AU - Balbi JC; Larrinaga MT; De Stefani E; Mendilaharsu M; Ronco AL; Boffetta
TI - P; Brennan P Foods and risk of bladder cancer: a case-control study in Uruguay.
SO - Eur J Cancer Prev 2001 Oct;10(5):453-8
AD - Seccion de Epidemiologia, Instituto Nacional de Oncologia, Montevideo, Uruguay.
A case-control study on 144 cases of transitional cell bladder carcinoma and 576 hospitalized controls was conducted in Montevideo, Uruguay. Barbecued meat, salted meat and fried eggs were associated with significant increased risks of bladder cancer (odds ratio (OR) for high intake of salted meat 4.04, 95% confidence interval (CI) 2.24-7.27). On the other hand, all fruits, cooked vegetables, potatoes and cheese were associated with inverse associations (OR for high consumption of potatoes 0.38, 95% CI 0.23-0.64). The associations with salted and barbecued meat suggest that the way of preserving or cooking meat play a role in bladder carcinogenesis. More precisely, N-nitroso compounds and heterocyclic amines could be involved in this process.
UI - 12036941
AU - Thompson TE; Rogan PK; Risinger JI; Taylor JA
TI - Splice variants but not mutations of DNA polymerase beta are common in bladder cancer.
SO - Cancer Res 2002 Jun 1;62(11):3251-6
AD - Molecular and Genetic Epidemiology Group, The Laboratory of Molecular Carcinogenesis, The National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
DNA polymerase beta (POLbeta) is a highly conserved protein that functions in base excision repair. Loss of the POLbeta locus on chromosome 8p is a frequent event in bladder cancer, and loss of POLbeta function could hinder DNA repair leading to a mutator phenotype. Both point mutations and large intragenic deletions of POLbeta have been reported from analysis of various tumor cDNAs but not from genomic DNA. We noticed that the breakpoints of the presumed rearrangements were delineated by exon-exon junctions, which could instead be consistent with alternative splicing of POLbeta mRNA. We tested the hypothesis that the reported intragenic deletion were splice variants by screening genomic DNA of human bladder tumors, bladder cancer cell lines, and normal bladder tissues for mutations or deletions in exons 1-14, exon alpha, and the promoter region of POLbeta. We found no evidence of somatic mutations or deletions in our sample set, although two polymorphisms were identified. Examination of cDNA from a subset of the original sample set revealed that truncated forms of POLbeta were surprisingly common. Forty-eight of 89 (54%) sequenced cDNA clones had large deletions, each beginning and/or ending exactly at exon-exon junctions. Because these deletions occur at exon-exon junctions and are seen in cDNA but not genomic DNA, they are consistent with alternative mRNA splicing. We describe 12 different splicing events occurring in 18 different combinations. Loss of exon 2 was the most frequent, being found in 42 of 49 (86%) of the variant sequenced clones. The splice variants appear to be somewhat more common and variable in bladder cancer cell lines and tumor tissues but occur at a high frequency in normal bladder tissues as well. We examine alternative splicing in terms of the information content of splice donor and acceptor site sequences, and discuss possible explanations for the predominant splicing event, the loss of exon 2.
UI - 12057106
AU - Dreicer R
TI - Locally advanced and metastatic bladder cancer.
SO - Curr Treat Options Oncol 2001 Oct;2(5):431-6
AD - Department of Hematology/Oncology, Taussig Cancer Center, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA. email@example.com
Metastatic transitional cell carcinoma of the bladder is an aggressive neoplasm characterized by rapid growth and dissemination with a median survival of typically less than 1 year. Despite the availability of a myriad of antineoplastics with moderate-significant anti-tumor activity yielding overall response rates in the 40% to 80% range, randomized trials continue to demonstrate median survival rates in the 13- to14-month range, with very limited long-term survival. Subsets of patients with advanced bladder cancer present additional management problems, including those with renal insufficiency or nontransitional-cell histology. Various observers have noted the similarity in treatment outcomes in advanced bladder cancer and extensive small cell lung cancer where chemotherapy produces relatively high response rates but with limited impact on survival. The optimal chemotherapy combination for patients with advanced bladder cancer remains undefined, however, there is increasing recognition that in order to achieve tangible improvements in complete response rates and survival in this disease will likely require a combination of chemotherapy and targeted molecular therapies and in some settings adjunctive surgery.
UI - 11828990
AU - Gontero P; Tizzani A; Muir GH; Caldarera E; Macaluso MP
TI - The genetic alterations in the oncogenic pathway of transitional cell carcinoma of the bladder and its prognostic value.
SO - Urol Res 2001 Dec;29(6):377-87
AD - Patologia Urologica, Universita' di Torino, Italy. firstname.lastname@example.org
This review focuses on the main oncogenes studied in transitional cell carcinoma (TCC) in order to describe their mechanisms of action and investigate their possible prognostic value. Each oncogene family is reported following the order through which the proliferative signal is transduced from the extracellular space via a growth factor to the nucleus where transcription factors are switched on. Oncogenic activation at any level of the pathway will cause an increased transcription of genes enhancing the cell cycle, and proliferation will therefore be amplified. The main molecular or immunohistochemical studies from the literature on the aberrant expression of these genes are examined and compared with the aid of tables. Conclusions suggest that, although some may initially appear promising, no oncogene, has thus far been found to have a definite prognostic value superior to conventional grading and staging.
UI - 11828992
AU - Toruner GA; Ucar A; Tez M; Cetinkaya M; Ozen H; Ozcelik T
TI - P53 codon 72 polymorphism in bladder cancer--no evidence of association with increased risk or invasiveness.
SO - Urol Res 2001 Dec;29(6):393-5
AD - Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey.
We studied the effect of the p53 gene Arg72Pro polymorphism on bladder cancer susceptibility in a case control study of 121 bladder cancer patients and 114 age-sex matched controls to determine whether this polymorphism is a biomarker for the risk and how aggressive the disease is. Genomic DNA was obtained from venous blood samples for genotype determination by PCR and restriction digestion. The genotype frequencies in the patient group were Arg/Arg: 0.3553, Arg/Pro: 0.4711, Pro/Pro: 0.1736, and in the control group Arg/Arg: 0.3684, Arg/Pro: 0.4825, Pro/Pro: 0.1491. The distribution of genotypes between the two groups was not statistically different (chi2 = 0.260, df: 2, P=0.878). The patient group was subdivided into two groups as superficial bladder cancer (n = 88) and invasive bladder cancer (n = 33), according to the presence of muscle invasion. The distribution of genotypes in the superficial group was Arg/Arg: 0.3409, Arg/Pro: 0.5114, Pro/Pro: 0.1477 and in the invasive group Arg/Arg: 0.3940, Arg/Pro: 0.3636, Pro/Pro: 0.2424. No association was observed with the invasiveness of the tumor (chi2 = 2.542, df 2, P = 0.281). Stratification of the data by tobacco exposure did not result in a significant difference in genotype frequencies. These data do not support an association between the p53 Arg72Pro polymorphism and bladder cancer.
UI - 11828995
AU - Tsai FJ; Lu HF; Yeh LS; Hsu CD; Chen WC
TI - Lack of evidence for the association of tumor necrosis factor-alpha gene promoter polymorphism with calcium oxalate stone and bladder cancer patients.
SO - Urol Res 2001 Dec;29(6):412-6
AD - Department of Medical Genetics, China Medical College Hospital, China Medical College, Taichung, Taiwan.
Urinary stone disease and bladder cancer are two of the most commonly seen urologic diseases in Taiwan. Tumor necrosis factor-alpha (TNF-alpha) is one of the cytokines secreted by macrophages and is related to a sequence of events in response to inflammation and cancer formation. We investigated the polymorphism of the TNF-alpha gene promoter -308 as a genetic marker in searching for the association between these two commonly seen urologic diseases. One hundred and fourteen patients with transitional cell carcinoma of the urinary bladder and 103 patients with calcium oxalate stone were compared with 150 healthy controls. The polymorphism was detected by polymerase chain reaction-based restriction analysis (Nco I endonuclease). The results revealed no significant differences between normal individuals and the patients with the two commonly seen urologic diseases (P > 0.05). We concluded that the polymorphism of the TNF-alpha promoter -308 is not a valid genetic marker for these two urologic diseases.
UI - 11961481
AU - Wax JR; Pinette MG; Blackstone J; Cartin A; McCrann DJ
TI - Nonbilharzial bladder carcinoma complicating pregnancy: review of the literature.
SO - Obstet Gynecol Surv 2002 Apr;57(4):236-44
AD - Maine Medical Center, Portland, Maine, USA. email@example.com
The purpose of this review is to evaluate tumor presentation and characteristics, and maternal-fetal outcomes of pregnancies complicated by nonbilharzial bladder carcinoma. The mean age of the patients was 29.5 years (range = 18-40). Symptoms and diagnosis occurred after the first trimester in 20 (83%) and 22 (92%) cases, respectively. Presenting complaints included painless gross hematuria [N = 12 (50%)], vaginal bleeding [N = 7 (29%)], dysuria [N = 2 (8.4%)], abdominal pain [N = 2 (8.4%)], and 1 instance each of urgency, frequency, recurrent cystitis, and no symptoms. Tumors were initially identified by ultrasound [N = 12 (50%)], cystoscopy [N = 11 (46%)], and intravenous urography [N = 1 (4.5%)]. Transitional cell carcinoma was found in 17 (74%), adenocarcinoma in 5 (22%), and squamous cell carcinoma in 1 (4.5%) patient. Tumors did not favor a specific bladder location, tended to be low grade [8 (40%) = grade 1, 7 (35%) = grade 2; 5 (21%) = grade 3], and noninvasive [N = 19 (79%)]. Treatment was typically by transurethral resection (N = 18), but 3 women required radical cystectomy, 2 received radiation, 1 received chemotherapy, and 1 underwent partial cystectomy. Three (14%) women died of their disease and 3 (14%) fetuses were lost because of complications of cancer or its treatment. Bladder carcinoma in pregnancy can mimic cystitis or obstetric hemorrhage and should be considered when evaluations for these conditions are negative. Routine ultrasound evaluation of the bladder in these patients may improve the diagnostic yield. Pregnancy is not a contraindication to treating most forms of bladder cancer. TARGET AUDIENCE: Obstetricians and Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader will be able to list the various types of bladder cancers, to describe the presenting symptoms in a patient with a bladder cancer, and to outline the work up and treatment strategies for bladder cancer.
UI - 11718635
AU - Xiaoxu L; Jianhong L; Jinfeng W; Klotz LH
TI - Bladder adenocarcinoma: 31 reported cases.
SO - Can J Urol 2001 Oct;8(5):1380-3
AD - Department of Urology, The Second Affiliated Hospital of Shanxi Medical University, Taiyuan, 030001 Shanxi, P.R. of China.
SUMMARY: retrospective review of 31 cases of bladder adenocarcinoma. METHODS: All patients diagnosed with adenocarcinoma of the bladder at the second affiliated hospital and commercial worker's hospital in Shanxi between 1985 and 1999 were reviewed. RESULTS: The cohort consisted of 31 patients, 25 with primary bladder adenocarcinoma, and 6 patients with urachal adenocarcinoma. Compared to the patients with primary adenocarcinoma, the urachal group were younger (67 versus 56 years), and more likely to be female (M:F 3:1 versus 1:2), and had a worse survival (45% versus 20% at 3 years). In the primary bladder adenocarcinoma group, the 3-year survival rate was 45% after radical cystectomy, and 33% after partial cystectomy. Local tumor recurrence after partial cystectomy was 25%. CONCLUSION: Urachal adenocarcinoma occurred in a younger age group with a female predominance compared to primary adenocarcinoma. Partial cystectomy was associated with a relatively high rate of local tumor recurrence.
UI - 12087158
AU - Gu L; Wu J; Zhu BB; Li GM
TI - Deficiency of a novel mismatch repair activity in a bladder tumor cell line.
SO - Nucleic Acids Res 2002 Jul 1;30(13):2758-63
AD - Department of Pathology and Laboratory Medicine, Suite MS 117, Markey Cancer Center, University of Kentucky Medical Center, Lexington, KY 40536, USA.
We demonstrate here that a cell line derived from a bladder cancer is defective in strand-specific mismatch repair. The mismatch repair deficiency in this cell line is associated with microsatellite instability and blocks an early step in the repair pathway. Since the addition of a known mismatch repair component hMutSalpha, hMutSbeta, hMutLalpha, replication protein A or proliferating cellular nuclear antigen could not restore mismatch repair to the mutant extract, the bladder tumor cell line is likely to be defective in an uncharacterized repair component. However, the repair in the mutant extract could be complemented by a partially purified activity derived from HeLa nuclear extracts. Therefore, in addition to revealing that a loss of mismatch repair function is associated with bladder cancer, this study provides information implicating a new mismatch repair activity.
UI - 12115522
AU - van Gils CH; Conway K; Li Y; Taylor JA
TI - HRAS1 variable number of tandem repeats polymorphism and risk of bladder cancer.
SO - Int J Cancer 2002 Aug 1;100(4):414-8
AD - Molecular and Genetic Epidemiology Section, Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
The HRAS1 variable number of tandem repeats (VNTR) polymorphism, 1 kb downstream from the HRAS1 gene, has been reported to be associated with risk of various cancers. To examine whether individuals with rare HRAS1 VNTR alleles are at increased risk of bladder cancer we carried out a case control study with 230 bladder cancer cases and 203 hospital-based controls frequency-matched on ethnicity, gender and age. For genotyping we used a PCR-based long-gel electrophoretic assay that provides precise allele size discrimination. We did not find evidence of a strong overall effect of the HRAS1 VNTR on bladder cancer risk. Genotype data for whites and blacks were analyzed separately, but the number of black subjects was too small to estimate meaningful odds ratios. Compared to white subjects with 2 common alleles, the odds ratio (OR) for white subjects with 1 rare allele was 0.9 (95% confidence interval (CI) = 0.5-1.4) and for those with 2 rare alleles OR = 1.7 (95% CI = 0.6-5.4). HRAS1 genotype may be related to the prognosis of bladder cancer, however, because incident cases, i.e., newly diagnosed cases had a higher frequency of rare alleles than did prevalent cases, i.e., cases already existing at the time of recruitment. Repeating the analyses with incident cases only (n = 53), the OR for subjects with 1 rare allele was 1.2 (95% CI = 0.6-2.4) and for those with 2 rare alleles 3.2 (95% CI = 0.8-13.7). The number of incident cases was too small to draw firm conclusions on a possible association with a subgroup of tumors with a poor prognosis. Published 2002 Wiley-Liss, Inc.
UI - 11906253
AU - Benimetskaya L; Guzzo-Pernell N; Liu ST; Lai JC; Miller P; Stein CA
TI - Protamine-fragment peptides fused to an SV40 nuclear localization signal deliver oligonucleotides that produce antisense effects in prostate and bladder carcinoma cells.
SO - Bioconjug Chem 2002 Mar-Apr;13(2):177-87
AD - Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria, 3052, Australia.
The development of antisense technology has focused on improving methods for oligonucleotide delivery into cells. In the present work, we describe a novel strategy for oligonucleotide delivery based on a bifunctional peptide composed of a C-terminal protamine-fragment that contains a DNA-binding domain and an N-terminal nuclear localization signal sequence derived from the SV40 large-T antigen (The sequences of two of the peptides are R6WGR6-PKKKRKV [s-protamine-NLS] and R4SR6FGR6VWR4-PKKKRKV [l-protamine-NLS]). We demonstrated, by intrinsic fluorescence quenching, that peptides of this class form complexes with oligodeoxynucleotides. To evaluate delivery, we used a 20-mer phosphorothioate oligomer (Isis 3521) targeted to the 3'-untranslated region of the PKC-alpha mRNA and G3139, an 18-mer phosphorothioate targeted to the first six codons of the human bcl-2 open reading frame, and complexed them with either of two peptides (s- or l-protamine-NLS). These peptides bind to and deliver antisense oligonucleotides to the nucleus of T24 bladder and PC3 prostate cancer cells, as demonstrated by confocal microscopy. Furthermore, as shown by Western and Northern blotting, the peptide-oligonucleotide complexes produced excellent downregulation of the expression of the complementary mRNAs, which in turn resulted in downregulation of protein expression. However, under certain circumstances (predominantly in PC3 cells), incubation of the cells with chloroquine was required to produce antisense activity. Using this strategy, PKC-alpha protein and mRNA expression in T24 and PC3 cells and bcl-2 expression in PC3 cells was reduced by approximately 75 +/- 10% at a minimum concentration of oligomer of 0.25 microM, in combination with 12-15 microM peptide. On the basis of our results, we conclude that arginine-rich peptides of this class may be potentially useful delivery vehicles for the cellular delivery of antisense oligonucleotides. This new strategy may have several advantages over other methods of oligonucleotide delivery and may complement already existing lipid-based technologies.
UI - 12094376
AU - Swierczynski SL; Epstein JI
TI - Prognostic significance of atypical papillary urothelial hyperplasia.
SO - Hum Pathol 2002 May;33(5):512-7
AD - Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD 21231, USA.
Typical papillary hyperplasia, a recently recognized precursor lesion to low-grade papillary urothelial neoplasms, consists of undulating folds of cytologically benign urothelium. Well-developed, branching fibrovascular cores of a papillary neoplasm are not evident. We have noted lesions with the architectural pattern of papillary hyperplasia; however, the overlying urothelium demonstrated varying degrees of cytologic atypia. We identified 15 cases of atypical papillary hyperplasia (13 males, 2 females, age 55 to 92) with overlying urothelium showing cytologic atypia. Of these cases, 8 (53%) were received in consultation. Of the 15 cases, 8 exhibited overlying flat carcinoma in situ (CIS), 4 had overlying dysplasia, and 3 were transitional between papillary hyperplasia with atypia and the earliest lesions of papillary neoplasia. Of these cases, 5 patients had multiple specimens with atypical papillary hyperplasia (range, 2 to 8) over time. Concurrent to the diagnosis of atypical papillary hyperplasia, there were 25 different urothelial lesions: CIS (n = 11), papilloma (n = 1), papillary neoplasm of low malignant potential with CIS (n = 1), high-grade papillary urothelial carcinoma (n = 10; 3 with CIS), small-cell carcinoma (n = 1), and infiltrating urothelial carcinoma (n = 1). Of 11 patients with known prior history, 2 had 12 prior urothelial neoplasms (9 low-grade papillary neoplasms, 2 papillary urothelial neoplasms of low malignant potential, and 1 high-grade papillary cancer). Of 10 patients with atypical papillary hyperplasia and a minimum of 1 year of follow-up, 9 had 19 recurrences: CIS (n = 4), papilloma (n = 1), papillary neoplasm of low malignant potential (n = 1), infiltrating urothelial carcinoma (n = 3; 1 with CIS), and high-grade pap
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