scholarly journals The emerging role of the androgen receptor in bladder cancer

2015 ◽  
Vol 22 (5) ◽  
pp. R265-R277 ◽  
Author(s):  
Alan P Lombard ◽  
Maria Mudryj
Keyword(s):  
Bladder Cancer ◽  
Androgen Receptor ◽  
Therapeutic Potential ◽  
Gender Disparity ◽  
Bladder Tumors

Men are three to four times more likely to get bladder cancer than women. The gender disparity characterizing bladder cancer diagnoses has been investigated. One hypothesis is that androgen receptor (AR) signaling is involved in the etiology and progression of this disease. Although bladder cancer is not typically described as an endocrine-related malignancy, it has become increasingly clear that AR signaling plays a role in bladder tumors. This review summarizes current findings regarding the role of the AR in bladder cancer. We discuss work demonstrating AR expression in bladder cancer and its role in promoting formation and progression of tumors. Additionally, we discuss the therapeutic potential of targeting the AR in this disease.

scholarly journals Can CT Virtual Cystoscopy Replace Conventional Cystoscopy in Early Detection of Bladder Cancer?

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Sachin Abrol ◽  
Ankush Jairath ◽  
Sanika Ganpule ◽  
Arvind Ganpule ◽  
Shashikant Mishra ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Early Detection ◽  
Predictive Value ◽  
Bladder Tumor ◽  
Urothelial Cancer ◽  
Routine Clinical Practice ◽  
Bladder Tumors ◽  
Virtual Cystoscopy ◽  
Sensitivity Specificity

Aim. To correlate findings of conventional cystoscopy with CT virtual cystoscopy (CTVC) in detecting bladder tumors and to evaluate accuracy of virtual cystoscopy in early detection of bladder cancer.Material and Method. From June 2013 to June 2014, 50 patients (46 males, four females) with history and investigations suggestive of urothelial cancer, with mean age 62.76 ± 10.45 years, underwent CTVC by a radiologist as per protocol and subsequently underwent conventional cystoscopy (CPE) the same day or the next day. One urologist and one radiologist, blinded to the findings of conventional cystoscopy, independently interpreted the images, and any discrepant readings were resolved with consensus.Result. CTVC detected 23 out of 25 patients with bladder tumor(s) correctly. Two patients were falsely detected as negative while two were falsely labeled as positive in CTVC. Virtual and conventional cystoscopy were comparable in detection of tumor growth in urinary bladder. The sensitivity, specificity, positive predictive value, and negative predictive value of virtual cystoscopy were 92% each.Conclusion. CTVC correlates closely with the findings of conventional cystoscopy. Bladder should be adequately distended and devoid of urine at the time of procedure. However, more studies are required to define the role of virtual cystoscopy in routine clinical practice.

Novel oncogenic function of ATDC in bladder cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4591-4591
Author(s):  
Phillip Lee Palmbos ◽  
Lidong Wang ◽  
Huibin Yang ◽  
Taylor Detzler ◽  
Gina Ney ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bladder Cancer ◽  
Cancer Cell ◽  
Pten Expression ◽  
Cancer Tissue ◽  
Bladder Tumors ◽  
Human Bladder ◽  
Urothelial Carcinomas ◽  
Normal Bladder

4591 Background: Bladder cancer is a common and deadly disease, but the molecular events leading to its initiation and progression are incompletely understood. We recently identified Ataxia-Telangiectasia Group D Associated (ATDC) as a novel oncogene which drives tumor proliferation and invasion in pancreatic carcinoma (Cancer Cell, 2009). In this study, we describe the role of ATDC as an oncogene in bladder cancer. Methods: To further determine the oncogenic role of ATDC, we generated ATDC transgenic (tg) mice in which ATDC expression was driven by a CMV promoter and characterized the resulting tumors. Results: Interestingly, the dominant phenotype in these mice was the development of both non-invasive and invasive urothelial carcinomas (9% and 20% respectively, average age of onset 10-12 months of age). Histologically, these tumors were indistinguishable from human urothelial carcinomas. Gene expression profiling of invasive tumors derived from ATDC tg mice demonstrated a marked overlap with gene signatures of human invasive bladder cancers. ATDC was the 11th most highly up-regulated gene in bladder cancers represented in the Oncomine gene expression database. Analysis of a human bladder cancer tissue microarray (311 samples) by IHC showed elevated expression in 70% (173/252) of muscle-invasive carcinomas, 22% (5/23) of papillary tumors and little or no expression in normal bladder urothelium. ATDC tg mouse bladder tumors demonstrated loss of p53 signaling and down-regulation of PTEN expression, which correlated with ATDC induced methylation of the PTEN promoter by DNMT3A. Furthermore, ATDC knock-down in invasive cancer cell lines resulted in decreased proliferation, invasion and reactivation of p53-mediated signaling and PTEN expression. Conclusions: ATDC is a novel oncogene that is highly expressed in human bladder cancers and is sufficient to drive the development of invasive bladder tumors in tg mice. The mechanism by which ATDC drives bladder cancer formation involves alterations in p53 and PTEN pathways known to be important in bladder tumorigenesis.

ATDC as a novel oncogene in bladder cancer.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 269-269
Author(s):  
Phillip Lee Palmbos ◽  
Lidong Wang ◽  
Huibin Yang ◽  
Taylor Detzler ◽  
Gina Ney ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bladder Cancer ◽  
Cancer Cell ◽  
Pten Expression ◽  
Cancer Tissue ◽  
Bladder Tumors ◽  
Human Bladder ◽  
Urothelial Carcinomas ◽  
Normal Bladder

269 Background: Bladder cancer is a common and deadly disease, but the molecular events leading to its initiation and progression are incompletely understood. We recently identified Ataxia-Telangiectasia Group D Associated (ATDC) as a novel oncogene which drives tumor proliferation and invasion in pancreatic carcinoma (Cancer Cell, 2009). In this study, we describe the role of ATDC as an oncogene in bladder cancer. Methods: To further determine the oncogenic role of ATDC, we generated ATDC transgenic (tg) mice in which ATDC expression was driven by a CMV promoter and characterized the resulting tumors. Results: The dominant phenotype in these mice was the development of both papillary and invasive urothelial carcinomas (9% and 20% respectively, average age of onset 10-12 months of age). Histologically, these tumors were indistinguishable from human urothelial carcinomas. Gene expression profiling of invasive tumors derived from ATDC tg mice demonstrated a marked overlap with gene signatures of human invasive bladder cancers. Analysis of a human bladder cancer tissue microarray (311 samples) showed elevated expression in 70% (173/252) of muscle-invasive carcinomas, whereas normal bladder had no expression. 22% (5/23) of papillary tumors also expressed elevated levels of ATDC. ATDC was the 11th most highly up-regulated gene in bladder cancers represented in the Oncomine gene expression database. ATDC tg mouse bladder tumors demonstrated loss of p53 signaling and down-regulation of PTEN expression, which was determined to be due to ATDC abrogation of p53 function by cytoplasmic sequestration and ATDC-mediated methylation of the PTEN promoter. Furthermore, ATDC knock-down in invasive cancer cell lines resulted in decreased proliferation, invasion and reactivation of p53-mediated signaling and PTEN expression. Conclusions: ATDC is a novel oncogene that is highly expressed in human bladder cancers and is sufficient to drive the development of invasive bladder tumors in tg mice. The mechanism by which ATDC drives bladder cancer formation involves alterations in p53 and PTEN pathways known to be important in bladder tumorigenesis.

Role of diffusion weighted magnetic resonance imaging in assessment of urinary bladder cancer

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Mahmoud Mohamed S Al Thqaby ◽  
Sherif H Abu-Gamrah ◽  
Ayman M Ibrahem ◽  
Ahmed M Hussein ◽  
Mohamed Elazab
Keyword(s):  
Bladder Cancer ◽  
Urinary Bladder ◽  
Pathological Examination ◽  
Low Grade ◽  
Bladder Tumors ◽  
T Stage ◽  
Diffusion Weighted ◽  
Contrast Enhanced ◽  
The Mean

Abstract Purpose The aim of this work is to ellucidate the role of diffusion-weighted imaging in T-stage of bladder cancer, to find correlation between the apparent diffusion coefficient (ADC) and histologic grade and to detect early tumor recurrence. Materials and Methods In this retrospective study, 34 patients were gathered, 28 men and 6 women, with ages ranging from 46 to 90 years, presented with gross hematuria or suspected of urinary bladder tumors detected on U/S and/or CT examinations. The patients were referred to Radiology department at national cancer institute for MRI examination after fulfilling inclusion and exclusion criteria. The urinary bladder tumors were classified in accordance with TNM classification from the American Joint Committee on Cancer into: T1 or lower, T2 (T2a or T2b), T3 (T3a or T3b), and T4.The mean ADC value of patients with low grade tumor (G1) and patients with high grade tumor (G2 or G3) was done The results were compared with histo-pathological examination obtained by transurethral resection (TUR) or after radical cystectomy. Results The overall accuracy of T stage diagnosis was 74.29% for T2-weighted images, 88.57 % for DW images, 80 % for contrast-enhanced images, and about 88.57 % for T2 plus DWIs. The mean ADC of G3 tumors was significantly lower than that of G1 and G2 tumors. Conclusion Our results suggest that adding DWIs to T2WIs lead to marked improvement regarding the accuracy for differentiating T2 or lower tumors from T3 and higher tumors, helping to limit the usage of contrast enhanced MRI imaging as a noninvasive diagnostic tool.

scholarly journals The Role of Androgens and Androgen Receptor in Human Bladder Cancer

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 594
Author(s):  
Elizabeth Martínez-Rojo ◽  
Laura Cristina Berumen ◽  
Guadalupe García-Alcocer ◽  
Jesica Escobar-Cabrera
Keyword(s):  
Bladder Cancer ◽  
Androgen Receptor ◽  
Aromatic Amines ◽  
Human Bladder Cancer ◽  
Human Bladder ◽  
Different Types ◽  
Internal Genitalia ◽  
Sex Disparity ◽  
Aniline Dyes

Bladder cancer (urothelial carcinoma) is one of the most frequently diagnosed neoplasms, with an estimated half a million new cases and 200,000 deaths per year worldwide. This pathology mainly affects men. Men have a higher risk (4:1) of developing bladder cancer than women. Cigarette smoking and exposure to chemicals such as aromatic amines, and aniline dyes have been established as risk factors for bladder cancer and may contribute to the sex disparity. Male internal genitalia, including the urothelium and prostate, are derived from urothelial sinus endoderm; both tissues express the androgen receptor (AR). Several investigations have shown evidence that the AR plays an important role in the initiation and development of different types of cancer including bladder cancer. In this article, we summarize the available data that help to explain the role of the AR in the development and progression of bladder cancer, as well as the therapies used for its treatment.

scholarly journals Androgen Receptor Signaling Induces Cisplatin Resistance via Down-Regulating GULP1 Expression in Bladder Cancer

2021 ◽  
Vol 22 (18) ◽  
pp. 10030
Author(s):  
Yuki Teramoto ◽  
Guiyang Jiang ◽  
Takuro Goto ◽  
Taichi Mizushima ◽  
Yujiro Nagata ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Androgen Receptor ◽  
Molecular Mechanisms ◽  
Direct Interaction ◽  
Androgen Treatment ◽  
Downstream Effector ◽  
Bladder Cancer Cells ◽  
Cisplatin Sensitivity ◽  
Muscle Invasive

The underlying molecular mechanisms of resistance to cisplatin-based systemic chemotherapy in bladder cancer patients remain to be elucidated, while the link between androgen receptor (AR) activity and chemosensitivity in urothelial cancer has been implicated. Our DNA microarray analysis in control vs. AR knockdown bladder cancer lines identified GULP1 as a potential target of AR signaling. We herein determined the relationship between AR activity and GULP1 expression in bladder cancer cells and then assessed the functional role of GULP1 in cisplatin sensitivity. Androgen treatment in AR-positive cells or AR overexpression in AR-negative cells considerably reduced the levels of GULP1 expression. Chromatin immunoprecipitation further showed direct interaction of AR with the promoter region of GULP1. Meanwhile, GULP1 knockdown sublines were significantly more resistant to cisplatin treatment compared with respective controls. GULP1 knockdown also resulted in a significant decrease in apoptosis, as well as a significant increase in G2/M phases, when treated with cisplatin. In addition, GULP1 was immunoreactive in 74% of muscle-invasive bladder cancers from patients who had subsequently undergone neoadjuvant chemotherapy, including 53% of responders showing moderate (2+)/strong (3+) expression vs. 23% of non-responders showing 2+/3+ expression (P = 0.044). These findings indicate that GULP1 represents a key downstream effector of AR signaling in enhancing sensitivity to cisplatin treatment.

scholarly journals Differential protein expression profiling by iTRAQ-2DLC-MS/MS of human bladder cancer EJ138 cells transfected with the metastasis suppressor KiSS-1 gene

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16043-e16043
Author(s):  
L. Grau ◽  
I. Ruppen ◽  
M. Gil ◽  
J. M. Piulats ◽  
J. Bellmunt ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Progression ◽  
Biological Networks ◽  
Molecular Mechanisms ◽  
Reversed Phase ◽  
Metastasis Suppressor ◽  
Molecular Pathways ◽  
Bladder Tumors ◽  
Poor Overall Survival

e16043 Background: The use of isobaric tags for relative and absolute quantization (iTRAQ) followed by multidimensional liquid chromatography (LC) and tandem mass spectrometry (MS/MS) analysis is emerging as a powerful methodology for biomarker and drug target discovery. KiSS-1 is a metastasis suppressor gene reported to be involved in the progression of several solid neoplasias. The loss of KiSS-1 expression has been shown to be inversely correlated with increasing tumor stage and poor overall survival in bladder tumors. In order to identify the molecular pathways associated with the metastasis suppressor role of KiSS-1 in bladder cancer, we carried out a proteome discovery analysis using an iTRAQ approach. Methods: Bladder cancer cells (EJ138) were transiently transfected with a vector encompassing the full length KiSS-1 gene. Protein extracts collected after 24h and 48h transfection were fractionated, digested with trypsin and treated with iTRAQ reagents. The labelled peptides were separated through Strong Cation Exchange (SCX) and Reversed Phase LC and analysed by MALDI TOF/TOF MS. Several software packages were utilized for data analysis: ProteinPilot, Protein Center for gene ontology (GO) analysis and Ingenuity Pathway. Results: Comparative analysis among transfected, mock and empty vector exposed cells have identified more than 800 proteins with high confidence (>99%), showing high correlation rates among replicates (>70%). The involvement of the identified proteins in biological networks has served to characterize molecular pathways associated with KiSS-1 expression and to select critical candidates for validation analyses by Western Blot using independent transfected replicates. As part of complementary clinical validation strategies, inmunohistochemical analyses performed in metastatic bladder tumours spotted onto tissue microarrays (n = 175) have revealed the role of KiSS-1, ezrin and filamin in bladder cancer progression. Conclusions: Our proteomic study not only has served to reveal molecular mechanisms associated with the metastasis suppressor role of KiSS-1 in bladder cancer, but also to identify novel potential metastatic biomarkers for patients affected with bladder tumors. No significant financial relationships to disclose.

scholarly journals Novel Molecular Classification of Muscle-Invasive Bladder Cancer Opens New Treatment Opportunities

2018 ◽  
Author(s):  
Lucía Trilla-Fuertes ◽  
Angelo Gámez-Pozo ◽  
Guillermo Prado-Vázquez ◽  
Andrea Zapater-Moros ◽  
Mariana Díaz-Almirón ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Androgen Receptor ◽  
Invasive Bladder Cancer ◽  
Bladder Tumors ◽  
High Group ◽  
Muscle Invasive Bladder Cancer ◽  
Flux Balance ◽  
Balance Analysis ◽  
Muscle Invasive ◽  
Computational Analyses

AbstractBackgroundMuscle-invasive bladder tumors are associated with high risk of relapse and metastasis even after neoadjuvant chemotherapy and radical cystectomy. Therefore, further therapeutic options are needed and molecular characterization of the disease may help to identify new targets.ObjectiveThe aim of this work is to characterize muscle-invasive bladder tumors at molecular levels using computational analyses.Design, Settings and ParticipantsThe TCGA cohort of muscle-invasive bladder cancer patients was used to describe these tumors.Outcome Measurements and Statistical AnalysisProbabilistic graphical models, layer analyses based on sparse k-means coupled with Consensus Cluster, and Flux Balance Analysis were applied to characterize muscle-invasive bladder tumors at functional level.ResultsLuminal and Basal groups were identified, and an immune molecular layer with independent value was also described. Luminal tumors had decreased activity in the nodes of epidermis development and extracellular matrix, and increased activity in the node of steroid metabolism leading to a higher expression of androgen receptor.This fact points to androgen receptor as a therapeutic target in this group. Basal tumors were highly proliferative according to Flux Balance Analysis, which make these tumors good candidates for neoadjuvant chemotherapy. Immune-high group had higher expression of immune biomarkers, suggesting that this group may benefit from immune therapy.ConclusionsOur approach, based on layer analyses, established a Luminal group candidate for androgen receptor inhibitor therapy, a proliferative Basal group which seems to be a good candidate for chemotherapy, and an immune-high group candidate for immunotherapy.Patient SummaryMuscle-invasive bladder cancer has a poor prognosis in spite of appropriate therapy. Therefore, it is still necessary to characterize these tumors to propose new therapeutic targets. In this work we used computational analyses to characterize these tumors and propose treatments.

Abstract 3654: Prognostic role of androgen receptor in bladder cancer

2012 ◽  
Author(s):  
Arndt Hartmann ◽  
Simone Bertz ◽  
Bastian Keck ◽  
Lars Dyrskjot ◽  
Torben Orntoft ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Androgen Receptor ◽  
Prognostic Role
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