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Bladder Cancers (bladder + cancers)
Selected AbstractsEvaluating the In Vitro and In Vivo Efficacy of Nano-Structured Polymers for Bladder Tissue Replacement ApplicationsMACROMOLECULAR BIOSCIENCE, Issue 5 2007Megan Pattison Abstract Bladder cancers requiring radical cystectomy, along with congenital and acquired disorders which result in obstruction of the bladder, necessitate surgical measures (including augmentation); such diagnoses bring a clinical need for effective bladder replacement implant designs. Many recent approaches for the design of soft tissue replacement materials have relied on the use of synthetic polymeric substances; unfortunately, the optimal soft tissue implant material is yet to be found. This may, in part, be because current polymeric formulations fail to sufficiently biomimic the neighboring bladder tissue. This study took a brand new approach in designing the next generation of tissue-engineered bladder constructs through the use of nanotechnology, or materials with nanometer (less than 100 nm) surface features. Results provided evidence that nano-structured polymeric scaffolds (specifically, PLGA and PU) created using chemical etching techniques are capable of enhancing the human bladder smooth muscle cell adhesion, proliferation, and the production of extracellular matrix (ECM) proteins. Preliminary in vivo results also speak to the usefulness of such nano-structured materials. In combination, these findings suggest that nano-dimensional PLGA and PU scaffolds are promising replacement materials for the human bladder wall. [source] Papillary and muscle invasive bladder tumors with distinct genomic stability profiles have different DNA repair fidelity and KU DNA-binding activitiesGENES, CHROMOSOMES AND CANCER, Issue 4 2009Johanne Bentley Low-grade noninvasive papillary bladder tumors are genetically stable whereas muscle invasive bladder tumors display high levels of chromosomal aberrations. As cells deficient for nonhomologous end-joining (NHEJ) pathway components display increased genomic instability, we sought to determine the NHEJ repair characteristics of bladder tumors and correlate this with tumor stage and grade. A panel of 13 human bladder tumors of defined stage and grade were investigated for chromosomal aberrations by comparative genomic hybridization and for NHEJ repair fidelity and function. Repair assays were conducted with extracts made directly from bladder tumor specimens to avoid culture-induced phenotypic alterations and selection bias as only a minority of bladder tumors grow in culture. Four noninvasive bladder tumors (pTaG2), which were genetically stable, repaired a partially incompatible double-strand break (DSB) by NHEJ-dependent annealing of termini and fill-in of overhangs with minimal loss of nucleotides. In contrast, four muscle invasive bladder cancers (pT2-3G3), which displayed gross chromosomal rearrangements, repaired DSBs in an error-prone manner involving extensive resection and microhomology association. Four minimally invasive bladder cancers (pT1G3) had characteristics of both repair types. Error-prone repair in bladder tumors correlated with reduced KU DNA-binding and loss of TP53 function. In conclusion, there were distinct differences in DSB repair between noninvasive papillary tumors and higher stage/grade invasive cancers. End-joining fidelity correlated with stage and was increasingly error-prone as tumors became more invasive and KU binding activity reduced; these changes may underlie the different genomic profiles of these tumors. © 2008 Wiley-Liss, Inc. [source] In-hospital mortality after resection of biliary tract cancer in the United StatesHPB, Issue 1 2010James E. Carroll Jr Abstract Objective:, To assess perioperative mortality following resection of biliary tract cancer within the U.S. Background:, Resection remains the only curative treatment for biliary tract cancer. However, current data on operative mortality after surgical resections for biliary tract cancer are limited to small and single-center studies. Methods:, Using the Nationwide Inpatient Sample 1998,2006, a cohort of patient-discharges was assembled with a diagnosis of biliary tract cancer, including intrahepatic bile duct, extrahepatic bile duct, and gall bladder cancers. Patients undergoing resection, including hepatic resection, bile duct resection, pancreaticoduodenectomy, and cholecystectomy, were retained. The primary outcome measure was in-hospital mortality. Categorical variables were analyzed by chi-square. Multivariable logistic regression was performed to identify independent predictors of in-hospital mortality following resection. Results:, 31 870 patient-discharges occurred for the diagnosis of biliary tract cancer, including 36.2% intrahepatic ductal, 26.7% extrahepatic ductal, and 31.1% gall bladder. Of the total, 18.6% underwent resection: mean age was 69.3 years (median 70.0); 60.8% were female; 73.7% were white. Overall inpatient surgical mortality was 5.6%. Independently predictive factors of mortality included patient age ,50 (vs. <50; age 50,59 odds ratio [OR] 5.51, 95% confidence interval [CI] 1.70,17.93; age 60,69 OR 7.25, 95% CI 2.29,22.96; age , 70 OR 9.03, 95% CI 2.86,28.56), the presence of identified comorbidities (congestive heart failure, OR 3.67, 95% CI 2.61,5.16; renal failure, OR 4.72, 95% CI 2.97,7.49), and admission designated as emergent (vs. elective; OR 1.82, 95% CI 1.39,2.37). Conclusion:, Increased in-hospital mortality for patients undergoing biliary tract cancer resection corresponded to age, comorbidity, hospital volume, and emergent admission. Further study is warranted to utilize these observations in promoting early detection, diagnosis, and elective resection. [source] Retroperitoneal lymph node dissection in patients with interaortocaval lymph node metastases of transitional cell carcinoma of the urinary tractINTERNATIONAL JOURNAL OF UROLOGY, Issue 4 2004CHUL JANG KIM Abstract Three patients suffered from renal pelvic, ureteral and bladder cancers that were treated with both standard surgical treatments and two adjuvant cycles of cisplatin-based combination chemotherapy. Metastases of interaortocaval lymph nodes were detected in all patients between 9 and 33 months from the surgery for primary lesions. All patients received three cycles of cisplatin-based combination chemotherapy and retroperitoneal lymph node dissection (RPLND). The chemotherapy achieved partial response (62,98%). Two patients with viable cancer cells died with hepatic metastases; the first 15 months and the second 25 months from the date of diagnosis of distant lymph node metastasis. The third patient, who had no viable cancer cells, remains alive and disease-free 36 months later. Therefore, RPLND after chemotherapy provides prognostic information that helps to define patients who might benefit from additional systemic chemotherapy. [source] Multiple biopsies of normal-looking urothelium in patients with superficial bladder cancer: Are they necessary?INTERNATIONAL JOURNAL OF UROLOGY, Issue 12 2003NAOHIRO FUJIMOTO Abstract Background:, The objective of the study presented here was to assess the usefulness and indications of multiple biopsies of normal-appearing urothelium in patients with superficial bladder cancer. Methods:, Between December 1996 and December 2002, multiple biopsies of normal-appearing bladder mucosa were performed in 100 patients with superficial bladder transitional cell carcinoma. Biopsy specimens were taken from seven different sites in females and nine different sites in males. Results:, In eight of 100 patients, bladder cancers were detected in the biopsy specimens. Three cases were Ta and five were Tis. All of the five patients with carcinoma in situ (CIS) in their biopsy specimens had multiple papillary broad-base tumors and positive urinary cytology. The detection ratio of CIS in patients with these findings was 17.9% (5/28). No concomitant CIS was detected in the 72 patients who had a solitary tumor, pedunculated tumor(s), or negative urinary cytology. Conclusion:, Multiple mucosal biopsies of normal-appearing urothelium are not necessary for all patients with superficial bladder cancer. They are, however, necessary for patients with multiple papillary broad-base tumors and positive urinary cytology. [source] Evaluation of cases where the right kidney is higher than the left kidneyINTERNATIONAL JOURNAL OF UROLOGY, Issue 7 2003SEIICHI SAITO Abstract Background: Finding the right kidney higher than the left kidney on excretory urography (EXU) is unusual. In the present study, the position of the kidneys was evaluated in patients, and the frequency, causes or attribution were investigated. Methods: Kidney positions were evaluated in 1625 patients. Subsequent evaluations by computed tomography scan were performed for each case where the right kidney was higher than the left. If a patient had right hydronephrosis, bladder evaluations such as ultrasonography and/or cystoscopy were also conducted. Patients with a left contracted kidney were excluded. Results: The right kidney was higher than the left in 81 (5%) of 1625 cases. In 30 cases (37%), the cause or attribution existed in the right urinary tract. Eleven of these cases were due to tumors or cysts in the right kidney, four were due to congenital anomalies, and 15 were due to hydronephrosis. In 10 (12.3%) of the cases, the cause or attribution existed in the left urinary tract. All of them were cysts or tumors of the left kidney. Of the other 13 (16.0%) cases, eight were caused by hepatatrophy and splenomegaly as a result of liver cirrhosis, two were caused by aortic aneurysm, one was caused by visceral inversion, one was caused by a right ovarian tumor, and one was caused by pneumonectomy. Malignancies, including two renal cell carcinomas and three bladder cancers at the right ureteral orifice, were found in five cases (6%). Conclusion: The above results suggest that the right kidney is higher than the left in five percent of all cases undergoing EXU. In cases where the right kidney is higher than the left, and a left contracted kidney cannot be found, further evaluation is recommend. [source] Usefulness of PSA screening in outpatients with bladder cancer: Preliminary resultsINTERNATIONAL JOURNAL OF UROLOGY, Issue 5 2002Kohei Kurokawa Abstract Background: We performed prostate-specific antigen (PSA) screening and evaluated its usefulness in outpatients with bladder cancer who may have an elevated risk for prostate cancer. Methods: Sixty-one new or followed-up outpatients with bladder cancer were examined between September 1999 and December 2000 in the Department of Urology, Gunma University Hospital, Japan. PSA was measured after informed consent was obtained, and patients in whom the PSA level was 4.1 ng/mL or higher were selected for thorough examination. In the examination, one examiner performed DRE (digital rectal examination) and, based on DRE and TRUS (transrectal ultrasonography) findings, determined whether prostate biopsy was indicated. Results: The average age of the 61 cases was 69.1 ± 8.6 years, and the average PSA level was 3.5 ± 5.8 ng/mL. The PSA level was 4.1 ng/mL or higher in 11 (18.0%) patients, nine of whom underwent six-sextant biopsy under TRUS guidance. Of these nine cases, four (6.6%) were diagnosed as having prostate cancer. The Gleason score was 7 in three cases and 9 in one case. The clinical stage was T2N0M0 in three cases and T3N0M0 in one case. Conclusions: On PSA screening in patients with bladder cancer and patients with a history of transurethral resection of the bladder tumor (TUR-BT), prostate cancer was found in 6.6%. This rate is higher than in the general population. These cancers were classified into intermediate to high-risk groups, and the prognosis of prostate cancers could be more important than those of the bladder cancers in two cases (50%). We conclude that PSA screening for inpatients with bladder cancer may be useful. [source] The T-box transcription factor Tbx2: Its role in development and possible implication in cancerIUBMB LIFE, Issue 2 2010Amaal Abrahams Abstract Tbx2 is a member of the T-box family of transcription factors that are crucial in embryonic development. Recent studies suggest that T-box factors may also play a role in controlling cell cycle progression and in the genesis of cancer. Tbx2 has been implicated in several developmental processes such as coordinating cell fate, patterning and morphogenesis of a wide range of tissues and organs including limbs, kidneys, lungs, mammary glands, heart, and craniofacial structures. Importantly, Tbx2 is overexpressed in several cancers including melanoma, small cell lung carcinoma, breast, pancreatic, liver, and bladder cancers and can suppress senescence, a cellular process, which serves as a barrier to cancer development. This review presents a state of the art overview of the role and regulation of Tbx2 in early embryonic development and in cancer. © 2009 IUBMB IUBMB Life, 62(2): 92,102, 2010 [source] Significance of the Grb2 and Son of Sevenless (Sos) Proteins in Human Bladder Cancer Cell LinesIUBMB LIFE, Issue 4 2000Takafumi Watanabe Abstract The epidermal growth factor (EGF) receptor has been suggested to have an important role in tumor initiation and progression of human bladder cancers. Grb2 protein, which is the downstream effector of the EGF receptor, acts as an adaptor protein between the EGF receptor and the Ras guanine-nucleotide exchange factor, son of sevenless (Sos) protein. Sos protein regulates the action of Ras protein by promoting the exchange of GDP for GTP . However, the significance of Grb2 and Sos proteins, which is related to EGF-triggered Ras activation, has not been elucidated in human bladder cancer. The aim of the present study is to clarify the significance of these proteins in human bladder cancer cell lines. In the present study, we used four human bladder cancer cell lines (T24, KU-7, UMUC-2, UMUC-6) and two kinds of cultured normal urothelial cells (HMKU-1, HMKU-2) isolated from patients with no malignancy. We examined the expression of EGF receptor, Grb2, and Sos proteins in these cells by Western blot analysis. Furthermore, the bladder cancer cell lines were subjected to sequence analysis to identify a point mutation in the c-H-ras gene at codon 12. There was no marked difference in the expression of the EGF receptor between human bladder cancer cell lines and cultured normal urothelial cells. On the other hand, expression of Grb2 and Sos proteins was substantially increased in all human bladder cancer cell lines examined in comparison with cultured normal urothelial cells, whether codon 12 of H-ras was mutated or not. These results suggest that the amplification of both Grb2 and SOS proteins plays an important role in the carcinogenesis of human bladder cancer. [source] siRNA-mediated Knockdown of the Heme Synthesis and Degradation Pathways: Modulation of Treatment Effect of 5-Aminolevulinic Acid-based Photodynamic Therapy in Urothelial Cancer Cell LinesPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 4 2009Makito Miyake Photodynamic therapy mediated by 5-aminolevulinic acid (ALA-PDT) has been developed as a therapeutic modality for refractory superficial bladder cancers. Here, in experiments using urothelial cancer cell lines, we investigated the effects of siRNA modulating heme-synthetic and degradation pathways for ALA-PDT. Targeted knockdown of ferrochelatase (FECH) suppressed heme synthesis and significantly increased intracellular protoporphyrin IX (PpIX) accumulation, leading to enhanced phototoxicity in four of five cell lines. Heme oxygenase-1 (HO-1) is recognized as important for cytoprotection against oxidative stress such as PDT. Targeted knockdown of HO-1 leads to decreased intracellular PpIX accumulation, resulting in a failure to enhance ALA-PDT effect in four cell lines. Knockdown of HO-1 caused marked growth inhibition in UM-UC-2 overexpressing HO-1, whereas no inhibitory effect was observed in UM-UC-3 lacking HO-1 expression. Moreover, HO-1 protein levels and (GT)n repeat polymorphism of the HO-1 gene promoter region were examined with the implication that the constitutive expressions of HO-1 protein were associated with a shorter (GT)n repeat. Our results suggested that (1) FECH siRNA improved the phototoxicity of ALA-PDT, (2) overexpression of HO-1 was associated with shorter (GT)n repeat of the promoter region, and (3) siRNA-mediated knockdown of HO-1 could suppress the growth of bladder cancer cells overexpressing HO-1. [source] Ex Vivo Fluorescence Imaging of Normal and Malignant Urothelial Cells to Enhance Early DiagnosisPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 5 2007Karine Steenkeste ABSTRACT Urinary cytology is a noninvasive and unconstraining technique for urothelial cancer diagnosis but lacks sensitivity for detecting low-grade lesions. In this study, the fluorescence properties of classical Papanicolaou-stained urothelial cytological slides from patients or from cell lines were monitored to investigate metabolic changes in normal and tumoral cells. Time- and spectrally-resolved fluorescence imaging was performed at the single cell level to assess the spectral and temporal properties as well as the spatial distribution of the fluorescence emitted by urothelial cells. The results reveal quite different fluorescence distributions between tumoral urothelial cells, characterized by a perimembrane fluorescence localization, and the normal cells which exhibit an intracellular fluorescence. This is not caused by differences in the fluorescence emission of the endogenous fluorophores NAD(P)H, flavoproteins or porphyrins but by various localization of the EA 50 Papanicolaou stain as revealed by both the spectral and time-resolved parameters. The present results demonstrate that the use of single-cell endofluorescence emission of Papanicolaou-stained urothelial cytological slides can allow an early ex vivo diagnosis of low-grade bladder cancers. [source] Search for the tumor-related proteins of transition cell carcinoma in Taiwan by proteomic analysisPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 3 2006Kun-Hung Sheng Abstract To better understand the carcinogenesis of bladder cancer in Taiwan, we utilized the proteomic approach to search for potential biomarkers of transitional cell carcinoma,(TCC). Analysis by 2-DE and MS/MS indicated that seven proteins are down-regulated and three proteins up-regulated in grade III samples as compared with those of grade,II. Of these deregulated proteins, fatty acid binding proteins, annexin,V, heat-shock protein,27, and lactate dehydrogenase have been shown to be associated with bladder cancer. Our studies also found altered expression of a group of proteins that have not been documented previously in bladder cancer, including annexin,I, 15-hydroxyprostaglandin dehydrogenase, galectin-1, lysophospholipase and mitochondrial short-chain enoyl-coenzyme,A hydratase,1 precursor. These results illustrate a pattern of differential protein expression between low- and high-grade tumors and it may be utilized as the molecular fingerprinting of a subset of bladder cancers. In addition, the present study provides a valuable resource in the study of pathological mechanisms in cancers of urothelial origin. The immunohistochemical staining of grade,II and III TCC samples with antiserum to annexin,I protein was utilized to confirm that the annexin,I protein is up-regulated in grade,III TCC. [source] A re-staging transurethral resection predicts early progression of superficial bladder cancerBJU INTERNATIONAL, Issue 6 2006HARRY W. HERR OBJECTIVE To determine whether pathology on a re-staging transurethral resection (TUR) predicts the early progression of superficial bladder cancer. PATIENTS AND METHODS In all, 710 patients presenting with multiple superficial bladder cancers were evaluated by re-staging TUR and followed for 5 years. Tumours were classified by stage as confined to mucosa (Ta) or invading submucosa (T1), and by grade (low- or high-grade). Pathology on re-staging TUR was correlated with the endpoints of tumour recurrence and stage progression. RESULTS Of the 710 patients, 490 (69%) had a recurrence and 149 (21%) progressed over 5 years. Eighty patients had high-grade invasive (T1G3) cancer on re-staging TUR and 61 (76%) progressed to muscle invasion (median time to progression 15 months), compared with 88 of 630 (14%) who had no evidence of tumour (T0) or other than T1 tumours detected on re-staging TUR. CONCLUSION A re-staging TUR identifies patients with superficial bladder cancer who are at high risk of early tumour progression. [source] A clinicopathological study of the expression of extracellular matrix components in urothelial carcinomaBJU INTERNATIONAL, Issue 4 2005Elli Ioachim OBJECTIVE To measure the immunohistochemical expression of the extracellular matrix (ECM) components tenascin, fibronectin, collagen type IV and laminin in urothelial carcinomas, and to correlate their expression with clinicopathological features to clarify the prognostic value of these molecules and their role in tumour progression. MATERIALS AND METHODS Tumour specimens obtained during transurethral resection of bladder tumour (TURBT) from 103 patients (82 men and 2 1 women, mean age 66.7 years, range 27,89) were studied retrospectively. The expression of tenascin, fibronectin, collagen type IV and laminin was correlated with clinicopathological features (tumour grade and stage, multiplicity, simultaneous in situ component, the proliferative activity as estimated by the two proliferation associated indices, Ki-67 and proliferating cell nuclear antigen, the recurrence rate, and the progression of invading tumour). Specimens investigated for tenascin expression from patients with superficial bladder cancers were categorized into 28 treated by TURBT only and 53 who had TURBT followed by intravesical instillations of interferon. RESULTS Cytoplasmic tenascin expression was detected in tumour cells in 20% of specimens. Tenascin was expressed in the tumour stroma in 76% of specimens, and was positively correlated with tumour grade and stage. Stromal tenascin expression was positively correlated with proliferative activity, and with the expression of fibronectin and collagen type IV. Fibronectin was expressed in the tumour stroma in 89% of specimens and was positively correlated with tumour stage, proliferative activity, and expression of collagen type IV and laminin. Collagen type IV was expressed in 93% of specimens, and was positively correlated with tumour grade and stage. Laminin was expressed in 78% of specimens and had no significant correlation with the clinicopathological features. Patients treated with TURBT alone and who had low levels of tenascin had a longer tumour-free interval than those with high levels of tenascin. CONCLUSION Levels of tenascin might be valuable for predicting the risk of early recurrence. The expression of tenascin, fibronectin and collagen type IV seems to be correlated with more aggressive tumour behaviour. Furthermore, their interrelationships could indicate that they are involved in the remodelling of bladder cancer tissue, probably influencing tumour progression. [source] Validation study of the prediction system for clinical response of M-VAC neoadjuvant chemotherapyCANCER SCIENCE, Issue 1 2007Ryo Takata To predict the efficacy of the M-VAC neoadjuvant chemotherapy for invasive bladder cancers, we previously established the method to calculate the prediction score on the basis of expression profiles of 14 predictive genes. This scoring system had clearly distinguished the responder group from the non-responder group. To further validate the clinical significance of the system, we applied it to 22 additional cases of bladder cancer patients and found that the scoring system correctly predicted clinical response for 19 of the 22 test cases. The group of patients with positive predictive scores had significantly longer survival than that with negative scores. When we compared our results with a previous report describing the prognosis of the patients with cystectomy alone, the results imply that patients with positive scores are likely to benefit from M-VAC neoadjuvant chemotherapy, but that the chemotherapy would shorten the lives of patients with negative scores. We are confident that our prediction system to M-VAC therapy should provide opportunities for achieving better prognosis and improving the quality of life of patients. Taken together, our data suggest that the goal of ,personalized medicine', prescribing the appropriate treatment regimen for each patient, may be achievable by selecting specific sets of genes for their predictive values according to the approach shown here. (Cancer Sci 2007; 98: 113,117) [source] | |||||||||||||||||||||||||