Development Of Bladder Carcinoma Research Articles

Immunohistochemical expression of androgen receptors in urothelial carcinoma of urinary bladder. Is it significant? Experience from coastal India.

Bladder carcinoma (BC) ranks second among the genitourinary cancers worldwide. Influence of androgens and expression of androgen receptors in neoplasms are recent findings which were implicated in the development of BC. We aimed to study androgen receptor (AR) expression in bladder urothelial neoplasms and correlate its expression with grade and stage of the tumor. Immunohistochemistry (IHC) was done on samples collected in a tertiary care hospital over one year consisting of 71 urothelial BC and 20 non-neoplastic urothelial conditions. Two pathologists graded the IHC and nuclear staining was considered as positive expression. AR was expressed in 23.9% (17/71) of bladder urothelial neoplasms. AR was expressed in 25.7% and 22.3% of high and low-grade tumors and 25% and 22.3% of non muscle-invasive and muscle-invasive BC. AR expression had no significant correlation with gender, age (> 50 years), muscle invasion or grade. AR expression was significantly absent in non-neoplastic conditions (p = 0.018). AR has varied expression in BC and it is relatively lower in this study population.

Endogenous and exogenous hydrogen sulfide modulates urothelial bladder carcinoma development in human cell lines

The role of H2S in urothelial carcinoma (UC) is still unclear. Here we have evaluated the expression of H2S producing enzymes as well as the effect of endogenous and exogenous H2S on human bladder UC cells. In human UC cells the expression of cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST); is significantly lower as compared to healthy cells. A modulatory role for the H2S pathway is supported by the finding that, the overexpression of CSE or CBS, but not 3-MST, inhibits cell proliferation and promotes apoptosis. A similar effect is obtained by using exogenous H2S. Diallyl trisulfide (DATS), which is a fully characterized H2S donor, inhibits the proliferation of UC cells in a time and concentration-dependent manner as well as promotes apoptosis. Moreover, DATS also induces autophagy, as determined by transcriptomic and western blot analysis. Finally, DATS inhibits mRNA expression levels of canonical markers of epithelial-mesenchymal transition by limiting migration and clonogenic ability of human UC cells in vitro. In conclusion, in urothelial carcinoma, there is an impairment of H2S pathway that involves CSE and CBS- derived hydrogen sulfide. Thus, targeting H2S signaling pathway in urothelial carcinoma could represent a novel therapeutic strategy.

CircMCTP2 (has-circ-0000658) facilitates the proliferation and metastasis of bladder carcinoma through modulating the miR-498/murine double minute-2 axis

ABSTRACT CircMCTP2 is a novel circRNA, which is associated with various kinds of malignant tumors progression, such as gastric cancer. However, the function of circMCTP2 in bladder carcinoma (BC) has no idea. The purpose of this study was tantamount to functionally dissect circMCTP2 in the progression of BC. In our study, circMCTP2 expression was strongly increased in BC tissues and cell lines. High expression of circMCTP2 predicted a poor prognosis of BC patients. CircMCTP2 deficiency impaired the cell growth, migration as well as invasive ability of BC cell lines (J82 and T24). In vivo, circMCTP2 deficiency cut the tumor growth rates and the tumor weight. In BC cells, circMCTP2 deficiency enhanced the translation of E-cadherin, while diminishing the translation of N-cadherin, Vimentin, and Snail. Moreover, circMCTP2 acted as a sponge of miR-498 to regulate murine double minute-2 (MDM2) expression. In BC tissues, a negative correlation was observed between the expression levels of circMCTP2 and miR-498. Additionally, either miR-498 silencing or MDM2 over-expression augmented the carcinogenic action of circMCTP2 on BC. In conclusion, our study showed that circMCTP2 regulates the expression of MDM2 by sponging miR-498 to promote the development of BC. These findings offer a new strategy for early diagnosis of BC and its therapeutics.

Circular RNA circFLNA inhibits the development of bladder carcinoma through microRNA miR-216a-3p/BTG2 axis

ABSTRACT Recent studies have shown that circular RNA circFLNA is abnormally expressed in a variety of malignant tumors, but its role and mechanism in bladder carcinoma (BCa) are still unclear. The present paper aims to contribute to research on the effects and mechanism of circFLNA on the malignant phenotype of BCa. In this study, the expressions of circFLNA, miR-216a-3p and BTG2 in BCa and BCa cells (EJ, T24, 5637, TCC-SUP) were detected by qRT-PCR. EdU staining, colony formation, Transwell assay, wound healing assays, and sphere formation assay were used to measure the cell proliferation, viability, invasion, migration, and cell stemness of BCa cells after circFLNA overexpression. In addition, the correlation existed between miR-216a-3p and circFLNA or BTG2 was confirmed by Dual-Luciferase Reporter assay and RNA pull-down. Western blot was utilized to determine the expression of BTG2, MMP2, epithelial-mesenchymal transition (EMT)-related proteins (vimentin, E-cadherin) and stem cell-specific proteins (CD34, OCT4, SOX2). Our study confirmed that downregulated circFLNA and BTG2 expression and upregulated miR-216a-3p were found in both BCa tissues and cell lines. Meanwhile, upregulated circFLNA inhibited proliferation, invasion and migration, EMT and stemness of BCa cells. MiR-216a-3p was a target gene of circFLNA and could target BTG2. Further analysis finally demonstrated that circFLNA sponged miR-216a-3p and indirectly promoted BTG2 expression, ultimately regulating proliferation, migration, invasion and EMT of BCa cells. In conclusion, circFLNA inhibits the malignant phenotype of BCa cells and their stemness through miR-216a-3p/BTG2, thus suppressing BCa progression.

Association of BRCA1 and BRCA2 genes in arsenic-induced urinary bladder carcinoma

Objective: Study was performed to determine content of arsenic in urinary bladder tumour tissue and association of BRCA1 and BRCA2 protein expression with urinary bladder carcinoma development. Materials and methods: This study was performed in a tertiary care hospital of Eastern India. Post-operative tumour tissue was analysed for arsenic content as well as BRCA1 and BRCA2 expression. Statistical analysis was done and association between stage, grade and BRCA1 and BRCA2 expression with arsenic level in tumour tissue was done. Results: Total 50 patients were included in study. Out of which 26 were arsenic positive as well as 24 were arsenic negative. Maximum patients in arsenic positive group were from arsenic endemic zones of West Bengal, India. There was significant correlation between higher stage and grade of tumour and arsenic positivity. BRCA1 correlation was significant with arsenic positive group whereas BRCA2 correlation was not significant with arsenic positive group. Conclusion: Bladder carcinomas are more common in arsenic endemic zones of our country. This association can help in future to develop drugs which act on selected mutation of genes such as BRCA1, especially in arsenic-associated bladder cancers.

High nuclear expression of HIF1α, synergizing with inactivation of LIMD1 and VHL, portray worst prognosis among the bladder cancer patients: association with arsenic prevalence.

Our study was aimed to understand the importance of LIMD1-VHL-HIF1α pathway in development of bladder carcinoma (BlCa) in association with arsenic prevalence. At first, the mRNA expression pattern of the genes of this pathway (LIMD1, VHL and HIF1α) was checked in GEO datasets and in our samples. Next, genetic and epigenetic profiling of LIMD1 and VHL was done in our sample pool, validated in T24 BlCa cell line. The results were next correlated with various clinico-pathological parameters. Differential under-expression of LIMD1 and VHL genes was found in muscle-invasive BlCa (MIBC) in comparison to non-muscle-invasive BlCa (NMIBC). However, HIF1α protein, but mRNA, was found to be overexpressed among the MIBC samples; depicting the probability of HIF1α protein stabilization. Analysis of genetic and epigenetic profiles of LIMD1 and VHL exposed a frequent promoter methylation of LIMD1 gene in MIBC samples. Further, in-depth look into the results unveiled that the high nuclear expression of HIF1α was significantly correlated with genetic alterations of LIMD1, alone or in combination with VHL. Moreover, treating the T24 cells with a de-methylating agent (5-aza-2'-deoxycytidine) re-expressed the methylated LIMD1 and VHL genes, which in turn, reduced the HIF1α protein level significantly. Additionally, patients with high arsenic content (> 112ng/g, AsH) seemed to have recurrent promoter methylation in LIMD1, as well as co-methylation/alteration of LIMD1 and VHL gene. Lastly, high nuclear expression of HIF1α in association with co-alteration of VHL and LIMD1 showed the worst overall survival (OS) among the patients. To conclude, MIBC samples portrayed higher alterations in VHL and LIMD1, thereby, stabilizing HIF1α protein and lowering the OS of patients.

LncRNA PVT1 accelerates malignant phenotypes of bladder cancer cells by modulating miR-194-5p/BCLAF1 axis as a ceRNA.

Background: Numerous studies proved that long non-coding RNA (lncRNA) is involved in the progression of multifarious diseases, especially in some carcinomas. As a potential tumor biomarker, plasmacytoma variant translocation 1 gene (PVT1) is involved in the development and progression of multifarious cancers. Nevertheless, the intrinsic and concrete molecular mechanism of PVT1 in bladder cancer still remained unclear, which is also the dilemma faced in many non-coding RNA studies.Results: Our research revealed that PVT1 was significantly higher expression in bladder carcinoma specimens and cell lines. Further experiments indicated that knockdown or overexpression of PVT1 restrained or promoted the malignant phenotype and WNT/β-catenin signaling in bladder cancer cells. Meanwhile miR-194-5p was in contrast and miR-194-5p could partially reverse the function of PVT1 in malignant bladder tumor cells. As a microRNA sponge, PVT1 actively promotes the expression of b-cells lymphoma-2-associated transcription factor 1 (BCLAF1) to sponge miR-194-5p and subsequently increases malignant phenotypes of bladder cancer cells. Therefore, it performs a carcinogenic effect and miR-194-5p as the opposite function, and serves as an antioncogene in the bladder carcinomas pathogenesis.Conclusion: PVT1-miR-194-5p-BCLAF1 axis is involved in the malignant progression and development of bladder carcinomas. Experiments revealed that PVT1 has a significant regulatory effect on bladder cancer (BC) and can be used as a clinical diagnostic marker and a therapeutic molecular marker for patients suffering from BC.Methods: In urothelial bladder carcinoma specimens and cell lines, the relative expression levels of PVT1 and miR-194-5p were detected by quantitative reverse transcription PCR (RT-qPCR). Through experiments such as loss-function and over-expression, the biological effects of PVT1 and miR-194-5p on the proliferation, migration, apoptosis and tumorigenicity were explored in bladder cancer cells. Co-immunoprecipitation, proteomics experiments, dual luciferase reporter gene analysis, western blot and other methods were adopted to investigate the PVT1 potential mechanism in bladder carcinomas.

Immunohistochemical Expression of Fibroblast Growth Factor Receptor 3 and Cyclooxygenase-2 in Urinary Bladder Carcinomas with Correlation of Schistosomiasis in Egyptian Patients

BACKGROUND: In Egypt, schistosomal infestation is a leading cause of bladder cancer. A mutation in the fibroblast growth factor receptor 3 (FGFR-3) gene is the most common and most specific genetic abnormality in bladder cancer. Similarly, cyclooxygenase-2 (COX-2) is an inducible, pro-inflammatory enzyme with previous studies showing higher expression in schistosomal-associated bladder cancer.
 AIM OF THE STUDY: The aim of the study was to evaluate the immunohistochemical expression of FGFR3 and COX2 in bladder carcinoma and correlates their expression to the associated schistosomal infestation to implicate possible therapeutic treatments.
 MATERIALS AND METHODS: This retrospective study included a total of 90 cases of archived, formalin fixed, paraffin-embedded tissue blocks that included variable subtypes and grades of urothelial carcinomas. Immunohistochemistry for expression of FGFR-3 and COX2 was performed using a standard avidin-biotin-peroxidase system.
 RESULTS: About 73.3% of the total cases (66 cases) showed variable positive reactivity for FGFR3, of which 33.3% (22 cases) were associated with bilharzia infection. A statistically significant correlation was detected between FGFR-3 and tumor size, grade, histologic subtype, LN status, lymphovascular invasion, and stage. About 83.3% of the total cases (75 cases) showed variable positive immunoreactivity for COX-2, of which 37.3% (28 cases) were bilharzial-associated. A positive correlation was established between COX-2 and grade, concomitant in situ changes and cases associated with bilharzia infection.
 CONCLUSION: FGFR-3 can be used as a prognostic marker for low-grade urothelial tumors. Results also portray that COX-2 has an inflammatory inciting role in bladder carcinoma development, especially in patients with a history of schistosomiasis (bilharziasis). Both COX-2 and FGFR-3 should be explored further for its use alone or in combination with conventional treatment, to reduce the recurrence rate and progression of superficial (low grade) tumors.

Circular RNA MYLK as a competing endogenous RNA promotes bladder cancer progression through modulating VEGFA/VEGFR2 signaling pathway

Accumulating evidences indicate that circular RNAs (circRNAs) play a vital role in modulating gene expression. However, the mechanisms underlying circRNAs remain largely elusive. Here, we screened circRNA and mRNA expression profiles of bladder carcinoma (BC) using microarray analysis. We found that circRNA-MYLK and VEGFA were significantly up-regulated and co-expressed in BC. Importantly, circRNA-MYLK levels were related to the progression of stage and grade of BC. Mechanistically, we demonstrated that circRNA-MYLK could directly bind to miR-29a and relieve suppression for target VEGFA, which activated VEGFA/VEGFR2 signaling pathway. Functionally, we found that ectopically expressing circRNA-MYLK accelerated cell proliferation, migration, tube formation of HUVEC and rearranged cytoskeleton. Moreover, up-regulating circRNA-MYLK promoted epithelial-mesenchymal transition (EMT). Whereas circRNA-MYLK knockdown decreased cell proliferation, motility, and induced apoptosis. Finally, up-regulating circRNA-MYLK promoted the growth, angiogenesis and metastasis of BC xenografts. Taken together, this study demonstrated for the first time that circRNA-MYLK might function as competing endogenous RNA (ceRNA) for miR-29a, which could contribute to EMT and the development of BC through activating VEGFA/VEGFR2 and downstream Ras/ERK signaling pathway. Our data suggest that circRNA-MYLK would be a promising target for BC diagnosis and therapy.

Development of vascular complications and bladder carcinoma in diabetics using pioglitazone: A five-year Indian review

BackgroundPioglitazone has better cardiovascular outcomes and a questionable relationship with bladder carcinoma in diabetes mellitus, type II (DM-2). We sought to evaluate the role of pioglitazone in the Indian population. MethodsThis is a retrospective study at an academic medical center in India. All DM-2 patients in 2008 with a new prescription of pioglitazone were age- and gender-matched with non-users. We excluded patients with gestational DM or DM type I. They were followed forward for five years and demographic data, micro- and macro-vascular complications, mortality, and bladder carcinoma were recorded. Two-tailed p≤0.05 was considered statistically significant. ResultsTwo cohorts of 260 patients, with mean age of 58±11 years with 413 (79.4%) males, were followed for five years. Pioglitazone users had higher hypertension, obesity, DM-2 family history (all p<0.003), and use of insulin and oral hypoglycemics (all p<0.0001) in comparison to non-users. HbA1c was not different between groups. Over five years, pioglitazone users had lesser retinopathy and myocardial infarctions (all p<0.01). Five cases of bladder carcinoma were noted, all in the pioglitazone group, however without statistical significance. Baseline variables, including mean daily pioglitazone dose, were not statistically different between patients with and without bladder carcinoma. Nephropathy and MI were independent predictors for development of bladder carcinoma within pioglitazone users. ConclusionsPioglitazone users had significantly lesser myocardial infarctions and retinopathy despite more difficult to control DM 2. In an age- and gender-matched cohort of users and non-users, pioglitazone did not contribute to development of bladder cancer in the Indian population.

P21 and p27 Immunoexpression in Upper Urinary Tract Urothelial Carcinomas.

p21 and p27 are members of cyclin-dependent kinase family, which function as tumor suppressors and they are involved in development and progression of several malignancies. We investigated their expression in upper urinary tract urothelial carcinoma (UUTUC). Radical nephroureterectomy materials of 34 patients were assessed by immunohistochemistry to evaluate expression of p21 and p27 in UUTUC. Results were correlated with various clinicopathological variables as age, gender, tumor grade and stage, tumor architecture, multifocality, subsequent bladder carcinoma development and clinical outcome.p21 and p27 expression was observed in 52.9% (n=18) and 88.2% (n=30), respectively. A total of 21 tumors (61.7%) showed either total loss of p21 expression (n=16, 47%) or lower expression (n=5, 14.7%). No correlation was found between p21 expression and clinicopathologic variables. Cases showing total loss or lower p27 expression (11.7% and <25.6%, respectively) (n=19, 55.8%) constituted 67.6% (n=23) of the cases totally. This loss or lower p27 expression correlated with a shorter overall survival in both univariate and multivariate analysis (p=0.039 and p=0.037, respectively). None of the noninvasive tumors (papillary and nodular tumors) showed loss of p27 (p=0.016) while 33.3% of invasive ones showed p27 loss. Noninvasive tumor architecture also correlated with subsequent bladder carcinoma development (p=0.032) while invasive tumor architecture correlated with advanced stage (T3 and T4) (p=0.003). p27 is widely expressed in UUTUC, while p21 expression is observed in half of the cases. Loss of p27 expression correlated with tumor architecture and overall survival in UUTUC. However, further research is needed to assess their role in UUTUC.

ATDC/TRIM29 Drives Invasive Bladder Cancer Formation through miRNA-Mediated and Epigenetic Mechanisms

Bladder cancer is a common and deadly malignancy but its treatment has advanced little due to poor understanding of the factors and pathways that promote disease. ATDC/TRIM29 is a highly expressed gene in several lethal tumor types, including bladder tumors, but its role as a pathogenic driver has not been established. Here we show that overexpression of ATDC in vivo is sufficient to drive both noninvasive and invasive bladder carcinoma development in transgenic mice. ATDC-driven bladder tumors were indistinguishable from human bladder cancers, which displayed similar gene expression signatures. Clinically, ATDC was highly expressed in bladder tumors in a manner associated with invasive growth behaviors. Mechanistically, ATDC exerted its oncogenic effects by suppressing miR-29 and subsequent upregulation of DNMT3A, leading to DNA methylation and silencing of the tumor suppressor PTEN. Taken together, our findings established a role for ATDC as a robust pathogenic driver of bladder cancer development, identified downstream effector pathways, and implicated ATDC as a candidate biomarker and therapeutic target.

Human papillomavirus infection and pathogenesis in urothelial cells: a mini-review.

Several recent studies described that high-risk human papillomavirus (HPV) infection could have a potential role in the development of malignancies other than cervical cancer, such as laryngeal carcinoma, penile carcinoma, and anal carcinoma. However, the etiological role of HPV infection in the pathogenesis of urinary tract has not been clarified. Many epidemiological studies demonstrated that HPV infections frequently occur in the external genitalia through sexual contact; however, it was reported that HPV infection could also occur in the urinary tract, including the urethra and urinary bladder. Some morphological changes of cells associated with HPV infection and mild atypical cells, suspected to be intraneoplasia, were seen in HPV-positive samples obtained from the urinary tract. Some clinical studies and meta-analysis have indicated that HPV infection is likely to have a certain etiological correlation with the development of bladder carcinoma, although its prevalence may vary according to HPV type, study population, region, histological type, detection methods, and other variables. According to the results of previous studies, the prevalence of HPV greatly widely varies in cases of bladder carcinoma. Further research by case-control or large-scales studies is thus required to reach a more definite conclusion.

MiR-708 promotes the development of bladder carcinoma via direct repression of Caspase-2

Bladder cancer is one of the world's top ten malignant tumors. The crucial role of microRNA in carcinogenesis has been well emphasized. Considering miRNA expression was tumor stage-, tissue-, or even development-specific, more experimental evidences about the functions of miRNAs in bladder cancer should be discovered to advance applying of miRNA in the diagnosis or therapy of cancer. MiR-708 level in bladder carcinoma and adjacent noncancerous tissues was tested by real-time qPCR. Cell apoptosis was analyzed by using flow cytometry. The tumorigenicity of bladder carcinoma cells was evaluated in nude mice model. Luciferase reporter gene assays were performed to identify the interaction between miR-708 and 3'UTR of Caspase-2 mRNA. The protein level of Caspase-2 was determined by western blotting. In this study, we reported that miR-708 was frequently dysregulated in human bladder carcinoma tissues compared to normal tissues. In addition, we found that silencing of miR-708 could promote the T24 and 5637 cells to apoptosis and inhibit the bladder tumor growth in vivo. Also, Caspase-2 was proved to be one of direct targets of miR-708 in T24 and 5637 cells. Further results showed that Caspase-2 was involved in the miR-708 regulated cell apoptosis. All together, these results suggest miR-708 may act as an oncogene and induce the carcinogenicity of bladder cancer by down-regulating Caspase-2 level.

Deletion of Leucine Zipper Tumor Suppressor 2 (Lzts2) Increases Susceptibility to Tumor Development

Using an Lzts2 knock-out mouse model, we characterized the biological role of Lzts2 in tumorigenesis. Both heterozygous and homozygous deletion of the Lzts2-targeted allele in mice shows an increased incidence in spontaneous tumor development, although Lzts2 homozygous knock-out mice show significantly higher incidences than heterozygous mice. Treatment of Lzts2-deficient mice with a carcinogen, N-butyl-N-(4-hydroxybutyl) nitrosamine, increases the susceptibility to N-butyl-N-(4-hydroxybutyl) nitrosamine-induced bladder carcinoma development. Examination of human prostate cancer tissue specimens shows a reduction of LZTS2 protein expression in prostate cancer cells. Further analyses of mouse embryonic fibroblasts isolated from Lzts2 knock-out embryos show that loss of Lzts2 enhances cell growth. These data provide the first line of evidence demonstrating that deletion of Lzts2 increases susceptibility to spontaneous and carcinogen-induced tumor development.

Expression and role of miR-34a in bladder cancer

Objective To investigate the expression and biological function of microRNA-34a (miR-34a) in bladder cancer.Methods Forty-two cases of bladder cancer specimen,including 17 noninvasive carcinoma and 25 muscle invasive carcinoma classified by UICC 2002 TNM,or 18 low-grade and 24 high-grade classified by WHO 1973.Meanwhile,mucosa adjacent to the carcinoma was selected as normal control.The gene expression of miR-34a was determined using real-time quantitative polymerase chain reaction in 42 cases of bladder carcinoma samples.Mature mimics of miR-34a were chemically synthesized and transiently transfected-intoT24 bladder cancer cells.The effects of miR-34a on apoptosis and proliferation in T24 cells were evaluatedby flow cytometry and MTS respectively.Results 61.9％ of carcinoma samples showed low expression of miR-34a,which was correlated with the malignancy and tumor size of bladder carcinoma.26.5％ (11 cases) was negative and 11.6％ (5 cases) showed high expression.Furthermore,upregulation of miR-34a in T24 cells contributed to cell growth and apoptosis.The apoptosis rate of T24 cells was (9.11 ± 0.41)％,which had significant difference compared with NC mimics and blank control group respectively (P ＜ 0.01).Conclusion The relative low expression of miRNA-34a may be involved in the tumorigenesis and development of bladder carcinoma. Key words: MicroRNA-34a; Bladder neoplasm; Carcinoma; Apoptosis

A Case Study of Human Papillomavirus-associated Bladder Carcinoma Developing after Urethral Condyloma Acuminatum

We report a 35-year-old man with bladder carcinoma developing 2 months after urethral condyloma acuminatum, with an 8-year history of persistent human papilloma virus-58 infection in the urinary tract. DNA was extracted from paraffin-embedded tissue specimens. Human papilloma virus-6 and -58 were detected in the condyloma, whereas human papilloma virus-58 was detected in the carcinoma. In situ hybridization analysis also demonstrated high-risk human papilloma virus-DNA signals in the condyloma and carcinoma tissues. Immunohistochemistry showed that p16-INK4a and mcm-7, surrogate markers of oncogenic human papilloma virus E7 protein, were weakly expressed in the condyloma tissue but were strongly expressed in the carcinoma tissues, suggesting that human papilloma virus-58 was present in the episomal state in the condyloma, whereas human papilloma virus-58 DNA was integrated into the host cells and its infection may have a role in the development of bladder carcinoma. Human papilloma virus-58 was continuously detected in the urethral brushing samples 8 years after treatment for urethral condyloma, and human papilloma virus-58 infection was still persistent in the urethra.

Meta-Analysis of Studies Analyzing the Role of Human Papillomavirus in the Development of Bladder Carcinoma

PurposeWe aimed to ascertain the degree of association between bladder cancer and human papillomavirus (HPV) infection.Materials and MethodsWe performed a meta-analysis of observational studies with cases and controls with publication dates up to January 2011. The PubMed electronic database was searched by using the key words "bladder cancer and virus." Twenty-one articles were selected that met the required methodological criteria. We implemented an internal quality control system to verify the selected search method. We analyzed the pooled effect of all the studies and also analyzed the techniques used as follows: 1) studies with DNA-based techniques, among which we found studies with polymerase chain reaction (PCR)-based techniques and 2) studies with non-PCR-based techniques, and studies with non-DNA-based techniques.ResultsTaking into account the 21 studies that were included in the meta-analysis, we obtained a heterogeneity chi-squared value of Qexp=26.45 (p=0.383). The pooled odds ratio (OR) was 2.13 (95% confidence interval [CI], 1.54 to 2.95), which points to a significant effect between HPV and bladder cancer. Twenty studies assessed the presence of DNA. The overall effect showed a significant relationship between virus presence and bladder cancer, with a pooled OR of 2.19 (95% CI, 1.40 to 3.43). Of the other six studies, four examined the virus's capsid antigen and two detected antibodies in serum by Western blot. The estimated pooled OR in this group was 2.11 (95% CI, 1.27 to 3.51), which confirmed the relationship between the presence of virus and cancer.ConclusionsThe pooled OR value showed a moderate relationship between viral infection and bladder tumors.

Mesane Kanseri Gelişiminde Moleküler Mekanizmaların Rolü

Kanser türleri içinde önemli bir yer tutan mesane kanseri, Batı ülkelerinde yapılan çalışmalara göre sıklık sıralamasında erkeklerde dördüncü sırayla tüm kanserlerin %5-10'unu, kadınlardaysa sekizinci sıradaki yeriyle % 4'ünü oluşturmaktadır. Mesane kanserinin etiyolojisi, büyük oranda bilinmemekle birlikte, çevresel, demografik ve genetik faktörlerin etkili olduğu düşünülmektedir. Mesane kanserinin gelişiminde rol oynayan çevresel faktörler; sigara, mesleki karsinojenler, şistozomiyazis, kronik sistit, tedavi amaçlı siklofosfamid kullanımı ve pelvik radyoterapidir. Mesane kanserinin gelişiminde rol oynayan demografik faktörler cinsiyet, ırk ve yaştır. Mesane kanserinin gelişiminde çok sayıda onkogenlerin ve tümör süpresör genlerin çeşitli seviyelerdeki mutasyonları önemli rol oynamaktadır. Onkogenler, hücresel seviyede dominant etkiye sahip genlerdir; yani aktive edildiklerinde veya ekspresyon seviyeleri arttığında tek bir mutant allel, bir hücreyi normal fenotipten malign fenotipe dönüştürmeye yetebilir. Mesane kanseriyle ilişkili en iyi bilinen onkogenler; H-ras, erb-B2 ve c-myc'dir. Tümör baskılayıcı genlerse onkogenlerin tersine hücre çoğalmasını inhibe edici özelliktedir. Tümör baskılayıcı genlerin, kanser gelişiminde etkili olabilmesi için her iki allelinin fonksiyonunu yitirmesi gerekir ve dolayısıyla bu genler, kanser gelişimindeki etkileri bakımından resesif özelliktedirler. Kromozom 13q'daki retinoblastoma geni (Rb) ve kromozom 17p'deki p53 geni, en iyi çalışılmış tümör baskılayıcı gendir. Kanserin ilerlemesinde anjiyogenez gelişimi, hücre dışı matriks ve hücre adezyon moleküllerindeki çeşitli anormallikler etkili olmaktadır. Ayrıca mesane kanserinin gelişiminde ve ilerlemesinde, mikrosatellit kararsızlığıyla çeşitli epigenetik faktörlerin de etkili olduğu gösterilmiştir. Mesane kanserinin gelişiminde ve ilerlemesinde rol oynayan karmaşık mekanizmaların anlaşılması için yeni çalışmalara ihtiyaç vardır.

Estrogen exposure and bladder cancer risk in Egyptian women

Objective To examine associations between reproductive history and urinary bladder cancer in Egyptian women. Methods We used questionnaire data from an ongoing, multicenter case–control study in Egypt. Controls were matched on age and residence area. This analysis focused on female cases with confirmed urothelial (UC) and squamous cell (SCC) carcinoma of the bladder. Results We recruited 779 women (540 controls, 239 cases; >98.0% nonsmokers). Younger age at menopause (<45 y) and older age at first pregnancy (>18 y) were factors significantly associated with increased risk of bladder cancer, even after adjusting for schistosomiasis history and other covariates in the multivariable logistic model; adjusted odds ratio and 95% confidence intervals were 1.98 (1.41, 2.77) and 6.26 (3.46, 11.34), respectively. On the other hand, multiple pregnancies or use of oral contraceptives were associated with decreased odds of having bladder cancer. Similar associations were observed with UC and SCC when analyzed separately; however, the magnitude of association with SCC was lower than with UC. Conclusion Our data suggest that early estrogen exposure, or the relative lack of it, plays a role in urinary bladder carcinoma development among Egyptian women.