bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epstein–Barr virus DNA load in tumour tissues correlates with poor differentiation status in non‐muscle invasive urothelial carcinomas
Authors: Chuang Kun‐Lung , Pang See‐Tong , Liao Shuen‐Kuei , Wu Chun Te , Chang Ying Hsu , Chuang Heng‐Chang , Chuang Cheng‐Keng 
Published: August 2010

What’s known on the subject? and What does the study add? Epstein‐Barr virus (EBV) could be detected in bladder cancer. In our paper, we showed that DNA of EBV could be detected more in the high grade urothelial carcinoma. In superficial bladder cancer, although high grade tumour associated with higher EBV titers, the recurrence free survival was not compromised by high EBV DNA load.OBJECTIVETo detect the correlation between the clinical staging, grading and genomic Epstein–Barr virus (EBV) viral numbers in tumour tissues of urothelial carcinoma patients.PATIENTS AND METHODSFrom June 2004 to May 2008, 60 urothelial carcinoma patients (50 cases of bladder carcinoma and 10 of upper tract urothelial carcinoma (UTUC) were enrolled in the study. Eight patients who underwent transurethral resection of prostate for prostate hyperplasia and two patients receiving nephrectomy for non‐function kidney were used as normal controls. The EBV viral copy numbers in genomic DNA were evaluated using a real‐time PCR‐based study. The BamHI W region of the Namalwa cell line was constructed to the plasmid clone and was used as standard curve for absolute quantitative PCR (Q‐PCR).RESULTSEpstein–Barr virus DNA was detected in 56% (28/50) and 60% (6/10) of the bladder and UTUC patients, respectively. The EBV DNA could not be detected in the normal control group. By pooling the UTUC and bladder patients in stage Ta,T1, the high copy number in fixed genomic DNA amount (100 ng/20 µL) was correlated with the high grading in stage Ta,T1 urothelial carcinoma (P= 0.014). The overall grading was not statistically associated with EBV copy number (P= 0.25). Although the copy numbers between paired tumour and normal tissues were not statistically different (P= 0.169), there were more copies of EBV in the normal tissues adjacent to the tumours than in those free from urothelial carcinoma. There was no significant difference between recurrence of non‐muscle invasive bladder cancer and the presence of EBV (P > 0.05).CONCLUSIONSEpstein–Barr virus DNA could be detected in the genome of the urothelial carcinoma specimens. The poor differentiation status was correlated with the high load of the EBV genome in non‐muscle invasive urothelial carcinoma. However, recurrence‐free survival was not greater in EBV‐positive patients than in EBV‐negative patients.
Novel ZEB1 expression in bladder tumorigenesis
Authors: Kenney Patrick A. , Wszolek Matthew F. , Rieger‐Christ Kimberly M. , Neto Brasil Silva , Gould Justin J. , Harty Niall J. , Mosquera Juan Miguel , Zeheb Ron , Loda Massimo , Darling Douglas S. , Libertino John A. , Summerhayes Ian C. 
Published: August 2010

What’s known on the subject? and What does the study add? Epithelial‐mesenchymal transition (EMT) is involved in tumor progression where the underlying cellular changes associated with EMT have been identified in in vitro models and confirmed in a limited number of in vivo studies. ZEB1, which targets E‐cadherin repression, is a transcriptional regulator that has been implicated in EMT, and is associated with uterine and colorectal cancers. Regulation of ZEB1 expression has been shown to involve different microRNAs (miRNAs), identifying a potential role for miRNA in EMT.In the present study we have identified novel expression of ZEB1 in bladder tumours and shown a role for ZEB1 in enhanced migration and invasion potential in in vitro assays. Confirmation of ZEB1 expression in bladder tumours was shown in tissue microarrays (TMAs).OBJECTIVETo evaluate ZEB1 expression in bladder tumorigenesis and define a possible role for this transcription factor in urothelial carcinomas of the bladder (UCBs).MATERIALS and METHODSFive hundred and fifty‐eight samples were assembled in 10 tissue microarrays (TMAs; 263 non‐muscle‐invasive Ta/T1/Tis, 295 muscle‐invasive T2–T4). All tumours were transitional cell carcinomas (TCCs) and processed for immunohistochemistry to assess nuclear ZEB1 expression. Expression levels of ZEB1 were modulated in bladder carcinoma cell lines CUBIII or UM‐UC‐3 after forced expression or shRNA knockdown, respectively. Protein expression levels were determined using western blot analysis and transfectants were assessed for migration and invasion potential in standard in vitro assays.RESULTSNuclear ZEB1 expression was recorded in 22.8% of non‐muscle‐invasive UCBs and 21.7% of muscle‐invasive UCBs, including 24.1% grade I/II and 21.1% grade III tumours, and absent in normal bladder mucosa. No significant correlation was observed for tumour stage and grade, nodal involvement, vascular invasion, metastasis and overall or cancer‐specific survival. The introduction or knockdown of ZEB1 expression in bladder carcinoma cell lines showed enhanced or reduced migration and invasive potential, respectively. Changes in ZEB1 expression were accompanied by altered microRNA (miRNA) expression underlying events linked to epithelial–mesenchymal transition (EMT).CONCLUSIONThe results in the present study showed novel expression of ZEB1 in bladder cancer in the absence of a link to clinical variables of change, including metastasis and survival. However, in vitro assays showed enhanced or reduced migration and invasion after the introduction or reduction of ZEB1, respectively, in transfected bladder cell lines. Modulation in expression of ZEB1 was closely linked to changes in the miR‐200 family along with alternative known prognostic indicators of bladder tumour progression.
Clinical significance of runt‐related transcription factor 1 polymorphism in prostate cancer
Authors: Huang Shu‐Pin , Lan Yu‐Hsuan , Lu Te‐Ling , Pao Jiunn‐Bey , Chang Ta‐Yuan , Lee Hong‐Zin , Yang Wen‐Hui , Hsieh Chi‐Jeng , Chen Lu‐Min , Huang Li‐Chia , Ting Wen‐Chien , Bao Bo‐Ying 
Published: August 2010

What’s known on the subject? and What does the study add? Although most clinically localized prostate cancer patients who underwent radical prostatectomy have a favorable outcome, molecular markers capable of providing prognostic information are still urgently needed to identify high‐risk patients who might benefit from aggressive treatment. In this study, we found that RUNX1 rs2253319 polymorphism was significantly associated with higher risks of advanced pathological stage, lymph node metastasis, and time to disease recurrence. Our results suggest that a simple and pretreatment analysis of genetic variants might add prognostic value to the currently used indicators for outcome prediction in patients receiving radical prostatectomy.OBJECTIVETo investigate the association of RUNX1 rs2253319 with clinicopathological characteristics of prostate cancer (PCa) and disease recurrence after radical prostatectomy (RP).PATIENTS AND METHODSTaking advantage of the systematic stage and grade for each tumor in a cohort of 314 patients with localized PCa receiving RP, we evaluated the associations of RUNX1 rs2253319 with age at diagnosis, preoperative prostate‐specific antigen (PSA) level, Gleason score, surgical margin, pathologic stage, status of lymph node metastasis, and PSA recurrence after RP.RESULTSThe minor allele, T, and the minor homozygote TT genotype of RUNX1 rs2253319 were significantly associated with a 1.49‐ to 2.76‐fold higher risk for advanced pathologic stage and a 3.35‐ to 9.52‐fold higher risk for lymph node metastasis. RUNX1 rs2253319 TT genotype was also associated with poorer PSA‐free survival compared with the major homozygote CC genotype in Kaplan–Meier analysis (log‐rank test, P= 0.038) and multivariate Cox proportional hazards model adjusting for age and PSA concentration (P= 0.045).CONCLUSION RUNX1 rs2253319 is associated with adverse clinicopathological features and might be a prognostic factor for the recurrence of PSA in patients with PCa receiving RP.
Findings of fat‐suppressed T2‐weighted and diffusion‐weighted magnetic resonance imaging in the diagnosis of non‐palpable testes
Authors: Kato Toshiki , Kojima Yoshiyuki , Kamisawa Hideyuki , Takeuchi Mitsuru , Mizuno Kentaro , Sasaki Shigeru , Kohri Kenjiro , Hayashi Yutaro 
Published: August 2010

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? Both conventional magnetic resonance imaging (MRI) and ultrasonography (US) have been used for children with non‐palpable testes to facilitate a preoperative diagnosis, but the accuracy of these examinations was not satisfactory. In the present study, to improve the diagnostic accuracy of non‐palpable testes by MRI examination, we employed fat‐suppressed T2‐weighted imaging and DWI, as well as conventional MRI. Additional MRI assessments are useful methods to improve the accuracy of diagnosing non‐palpable testes.OBJECTIVETo evaluate the magnetic resonance imaging (MRI) findings, diagnostic accuracy and clinical usefulness of fat‐suppressed T2‐weighted and diffusion‐weighted imaging (DWI) in the management of non‐palpable testes.PATIENTS AND METHODSIn all, 56 children (63 non‐palpable testes) aged 8 months–11 years (mean 24.7 months) with non‐palpable testes were enrolled.T1‐ and T2‐weighted imaging, as well as fat‐suppressed T2‐weighted imaging and DWI were performed during MRI examination, and the imaging results were compared with surgical findings.RESULTSIn the 63 non‐palpable testes, MRI identified 22% (14/63) as intra‐abdominal, 20% (13/63) as intra‐canalicular, 29% (18/63) as testicular nubbins, and 29% (18/63) as unidentifiable. Although it was difficult to confirm their presence in the abdominal cavity using T1‐ and T2‐weighted imaging alone, additional assessment, including fat‐suppressed T2‐weighted imaging and DWI facilitated the detection of intra‐abdominal testes more easily because they were imaged at a markedly higher signal intensity. The sensitivity, specificity and positive and negative predictive values for the MRI vs the operative findings were 100, 97.3, 96.3, and 100%, respectively. The overall prediction accuracy was 98.4%.CONCLUSIONAdditional MRI assessments, fat‐suppressed T2‐weighted imaging and DWI are useful examinations to improve the preoperative diagnostic accuracy of non‐palpable testes.
Trends in the treatment of localized prostate cancer using supplemented cancer registry data
Authors: Hamilton Ann S. , Albertsen Peter C. , Johnson Terri Kang , Hoffman Richard , Morrell Donna , Deapen Dennis , Penson David F. 
Published: August 2010

Study Type – Therapy (cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? Variation in treatment of localized prostate cancer has been shown to exist according to demographic and clinical factors, patient and provider preference, and region of residence since there is no consensus concerning appropriate treatment.Between 1998 and 2002 the proportion of men choosing watchful waiting declined from 12.6% to 9.0% while those receiving brachytherapy (with or without external beam radiation therapy) increased from 14.9% to 17.7%. Based on Gleason score, PSA, and age at diagnosis, younger African‐American men may be receiving less aggressive therapy than indicated, while older men with low risk tumours may be receiving more aggressive therapy than necessary.OBJECTIVETo conduct an analysis of localized prostate cancer treatment in the USA between 1998 and 2002.PATIENTS AND METHODSResults from the National Cancer Institute’s Patterns of Care study from 10 regional cancer registries in 1998 and 14 registries in 2002 were compared using univariate and multivariate statistical methods.RESULTSPatients with localized prostate cancer in 2002 were younger, had lower prostate‐specific antigen values, and higher Gleason scores compared with those diagnosed in 1998. Little change occurred in age‐adjusted percentages of men who were treated with a radical prostatectomy (45–46%) or by external beam radiation (EBRT) alone (19–20%). The proportion receiving brachytherapy (BT), alone or with EBRT, increased from 14.9 to 17.7%, while the proportion receiving watchful waiting declined from 12.6 to 9.0%. Younger African‐American men with intermediate/high‐risk disease were less likely to receive any type of aggressive therapy in comparison with Non‐Hispanic White men. Over 70% of men who were ≥75 years of age, with low‐risk disease, were treated with EBRT or BT.CONCLUSIONSOlder men with low‐risk disease might be overtreated with aggressive therapy, while younger intermediate/high‐risk African‐American men appear less likely to receive indicated aggressive therapy.
Racial differences in prediction of time to prostate cancer diagnosis in a prospective screening cohort of high‐risk men: effect of TMPRSS2 Met160Val
Authors: Giri Veda N. , Ruth Karen , Hughes Lucinda , Uzzo Robert G. , Chen David Y.T. , Boorjian Stephen A. , Viterbo Rosalia , Rebbeck Timothy R. 
Published: August 2010

What’s known on the subject? and What does the study add? The TMPRSS2‐ERG fusion is a common gene fusion event in prostate tumours. Germline genetic variants that predict fusion in the tumour are under study.This study evaluates one germline genetic variant regarding predicting time to prostate cancer diagnosis among high‐risk men undergoing screening for prostate cancer. A specific genotype is associated with earlier time to prostate cancer diagnosis among Caucasian men with a family history of prostate cancer. The results suggest that such variants may be useful after further study in stratifying high‐risk men for individualized early detection approaches.INTRODUCTION

To evaluate the TMPRSS2‐ERG gene polymorphism with respect to self‐identified race or ethnicity (SIRE), time to prostate cancer (PCA) diagnosis, and screening parameters in the Prostate Cancer Risk Assessment Program, a prospective screening program for high‐risk men.

PATIENTS AND METHODS

A total of 631 men aged between 35 and 69 years were studied. ‘High‐risk’ was defined as ≥ one first degree or two second degree relatives with PCA, any African American (AA) man regardless of familial PCA, and men with BRCA1/2 mutations.
Men with elevated prostate‐specific antigen (PSA) concentrations or other indications for PCA underwent biopsy. Men were followed from time of study entry to PCA diagnosis.
Cox models were used to evaluate time to PCA diagnosis by genotype.

RESULTS

Genotype distribution differed significantly by SIRE (CT/TT vs CC, P < 0.0001). Among 183 Caucasian men with at least one follow‐up visit, PCA was more than doubled in men carrying CT/TT vs CC genotypes (hazard ratio = 2.55, 95% CI = 1.14–5.70) after controlling for age and PSA.
No association was seen among AA men by TMPRSS2 genotype.

CONCLUSIONS

The T‐allele of the Met160Val variant in TMPRSS2, which has been associated with the TMPRSS2–ERG fusion, may be informative of time to PCA diagnosis for a subset of high‐risk Caucasian men who are undergoing regular PCA screening.
This variant, along with other genetic markers, warrant further study for personalizing PCA screening.
Leukotriene D4 receptor antagonist montelukast alleviates protamine sulphate‐induced changes in rat urinary bladder
Authors: Çetinel Şule , Çanıllıoğlu Yasemin Ersoy , Çikler Esra , Şener Göksel , Ercan Feriha 
Published: August 2010

What's known on the subject? and What does the study add? The mastocytosis in detrusor muscle and the leaky epithelium in interstitial cystitis were the most studied features. In this study the leaky epithelium was shown using the ruthenium red staining in electron microscopy and uroplakin distribution in light microscopy besides the mast cell concentration in detrusor muscle using tryptase immunohistochemistry.OBJECTIVE

To study the effects of montelukast (ML), a leukotriene receptor antagonist which has been shown to be effective in inhibiting the action of cysteinyl‐containing leukotrienes, on protamine sulphate (PS)‐induced changes in rat urinary bladder.

MATERIALS AND METHODS

Wistar female rats were catheterized and intravesically infused with PBS (control group) or PS (PS group) dissolved in PBS twice in 24 h.
In the PS‐applied and ML‐treated group (PS + ML group) after the 10 mg/kg PS instillation, ML was injected i.p. twice daily for 3 days.
The urinary bladder was investigated for general morphology under a light microscope.
Tryptase immunohistochemistry was used to observe mast cell distribution and activation. Uroplakin distribution was also identified with immunohistochemistry.

RESULTS

Alterations of glycosaminoglycan (GAG) and urothelial permeability were seen with ruthenium red (RR) staining techniques under a transmission electron microscope, and topographical changes of luminal urothelial structure were seen with a scanning electron microscope.
Biochemically malondialdehyde (MDA) and gluthatione (GSH) concentrations were analysed. In the PS group, there was degenerated urothelium with irregular uroplakin distribution, increased inflammatory cell infiltration, increased number of both granulated and activated mast cells, irregularity of GAG and penetration of RR into the intercellular spaces and dilated tight junctions.
In PS + ML group, there was relatively regular uroplakin distribution, a decrease in inflammatory cell infiltration, a decreased number of both activated and granulated mast cells in the mucosa, regular GAG and no penetration of RR into the intercellular areas, and regular tight junctions in most regions.
The significant decrease in MDA and the increased GSH concentrations in the PS + ML group was in accordance with the histological findings.

CONCLUSION

Montelukast appears to have a protective function in the bladder injury model via the anti‐inflammatory effects of this leukotriene receptor antagonist.
Expression of integrin proteins in non‐muscle‐invasive bladder cancer: significance of intravesical recurrence after transurethral resection
Authors: Behnsawy Hosny M. , Miyake Hideaki , Abdalla Medhat A. , Sayed Mohamed A. , Ahmed Abd El‐Fattah I. , Fujisawa Masato 
Published: August 2010

Study Type – Aetiology (case control) Level of Evidence 3b What’s known on the subject? and What does the study add? A number of studies have reported several clinicopathological factors closely associated with intravesical recurrence of non‐muscle invasive bladder cancer (NMIBC). In addition, various types of molecular markers have been shown to be useful for predicting intravesical recurrence of NMIBC following transurethral resection (TUR).Of six subunits of integrin proteins, including α2, α3, α5, α6, β1 and β4, the expression level of the β4 subunit in NMIBC, in addition to pathological T stage and concomitant carcinoma in situ appeared to be independently related to intravesical recurrence. Therefore, consideration of the expression levels of integrins, particularly that of the β4 subunit, in TUR specimens would contribute to further accurate prediction of intravesical recurrence of NMIBC.OBJECTIVES

To evaluate the expression of integrin proteins, a family of transmembrane heterodimers, in non‐muscle‐invasive bladder cancer (NMIBC).
To assess the significance of these proteins as prognostic indicators in patients undergoing transurethral resection (TUR).

PATIENTS AND METHODS

The present study comprised 161 patients diagnosed as having NMIBC after TUR.
Expression levels of six subunits of integrin proteins, including α2, α3, α5, α6, β1 and β4, were measured in TUR specimens by immunohistochemical staining.

RESULTS

Of the six proteins, expression levels of α2‐, α3‐, α6‐ and β4‐subunits were significantly associated with the incidence of intravesical recurrence. Univariate analysis identified expression levels of α3‐, α6‐ and β4‐subunits as important predictors of intravesical recurrence, while tumour size, pathological T stage and concomitant carcinoma in situ (CIS) were also important.
Multivariate analysis showed that the expression level of the β4 subunit, pathological T stage and concomitant CIS are independently related to intravesical recurrence.
There were significant differences in intravesical recurrence‐free survival for patients who were positive for the three independent risk factors; intravesical recurrence occurred in 10 of 49 (20.4%) patients who were negative for all risk factors, 31 of 68 who were positive for one risk factor (45.6%), and 30 of 44 who were positive for two or three risk factors (68.2%).

CONCLUSIONS

Consideration of the expression levels of integrins, particularly those of the β4 subunit, in TUR specimens, in addition to conventional variables, would contribute to accurate prediction of intravesical recurrence after TUR for NMIBC patients.
Frequency of regulatory T cells in peripheral blood and in tumour‐infiltrating lymphocytes correlates with poor prognosis in renal cell carcinoma
Authors: Liotta Francesco , Gacci Mauro , Frosali Francesca , Querci Valentina , Vittori Gianni , Lapini Alberto , Santarlasci Veronica , Serni Sergio , Cosmi Lorenzo , Maggi Laura , Angeli Roberta , Mazzinghi Benedetta , Romagnani Paola , Maggi Enrico , Carini Marco , Romagnani Sergio , Annunziato Francesco 
Published: August 2010

What’s known on the subject? and What does the study add? Treg overexpression has been demonstrated in several neoplasms, including liver, breast, pancreas and melanoma, while it has not been well evaluated in renal cancer.In renal cancer patients versus controls we found an increased expression of these cells, especially in tumour‐infiltrating lymphocytes. Moreover, Treg frequency significantly correlated with pathological stage, nuclear grade and prognostic models.OBJECTIVE

To compare the frequency of T regulatory cells (Tregs) in peripheral blood of patients (pPB) affected by renal cell carcinoma (RCC) both with the frequency of Tregs found in PB of healthy donors (hPB) and that of Tregs present in tumour infiltrating lymphocytes (TILs). To verify in vitro the inhibitory activity of tumour isolated Tregs on the effector T cells and, finally, to assess the prognostic role of Treg frequency determination.

PATIENTS AND METHODS

Treg frequency in hPB, pPB and TILs was evaluated in 30 patients and 20 healthy controls by measuring both membrane‐CD25 and intracytoplasmic‐Foxp3 expression by flow cytometry.
Treg inhibitory activity was evaluated by an in vitro proliferation assay performed on total, CD25‐depleted mononuclear cells (MNC) and CD25‐depleted MNC cultured in the presence of purified CD25+ Tregs.
Finally, Treg frequency in pPB and TIL were correlated with conventional prognostic factors and scores of University of California Los Angeles and Kattan predictive models.

RESULTS

Treg frequency was higher in TILs than in pPB (P= 0.002), whereas there were no important differences between hPB and pPB. CD25+ cells isolated either from PB and tumours showed the ability to significantly suppress in vitro both proliferation and interferon‐γ production by CD25‐depleted MNC, thus demonstrating that they are active Tregs.
Treg frequency was found to significantly correlate both with pathological stage (pPB, P= 0.03; TIL, P= 0.04) and nuclear grade (TIL, P= 0.005), both for UCLA and Kattan models (all: P < 0.05 for both pPB and TIL).

CONCLUSION

Treg frequency is significantly higher in TIL than in pPB of patients with RCC. Tregs showed in vitro an inhibitory activity on effector T cells isolated from kidney tumours. The increase in both peripheral and intratumoral Tregs in subjects affected with RCC were associated with worse prognosis.