Transactivation of PTGS2 by PAX5 signaling potentiates cisplatin resistance in muscle-invasive bladder cancer cells

2018 ◽  
Vol 503 (4) ◽  
pp. 2293-2300 ◽  
Author(s):  
Bing-wei Dong ◽  
Wei-bo Zhang ◽  
Shu-min Qi ◽  
Chang-you Yan ◽  
Juan Gao
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Cisplatin Resistance ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Bladder Cancer Cells ◽  
Muscle Invasive

Role of heat shock protein 90 inhibition with 17-(allylamino)-17 (demethoxygeldenamycin) in muscle-invasive bladder cancer cells.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 273-273
Author(s):  
H. Williams
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Intracellular Signaling ◽  
Heat Shock Protein 90 ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Bladder Cancer Cells ◽  
Muscle Invasive

273 Background: Muscle invasive bladder cancer portends a poor long term prognosis. Platinum based therapy is the mainstay of treatment but more effective agents are needed for management of this disease. Heat shock protein 90 (Hsp90) is a ubiquitous protein that has been shown to be overexpressed in tumor cells. It functions as a molecular chaperone responsible for the stability and function of a number of proteins critical to the oncogenic process. 17-(allylamino)-17 demethoxygeldanamycin (17 AAG) is a Hsp90 inhibitor that is currently in phase III trials in several tumor models. The purpose of this study was to evaluate the role of 17 AAG treatment for bladder cancer in vitro. Methods: Seven bladder cancer cell lines representing muscle invasive bladder cancer were treated in the presence and absence of 17 AAG. Both short term and long term treatments were evaluated for their effects on growth, motility and invasion of the cancer cells. Expression of proteins involved in cell growth, survival and metastasis were evaluated with Western blotting. Results: Our data demonstrated that 17 AAG treatment resulted in induction of apoptosis, inhibition of cell cycle progression through inhibition of MAP kinase pathway and cyclin D1 expression. Decreased tumor cell motility and invasion was observed with 17 AAG treatment. Several intracellular signaling pathways involved in cell proliferation, invasion and metastasis were inhibited. Conclusions: Hsp90 inhibition in muscle invasive bladder cancer cells impacts growth, motility and invasiveness by inhibiting numerous intracellular signaling pathways. Taken together, these findings suggest a possible role for Hsp90 inhibitors in bladder cancer tumorigenesis. No significant financial relationships to disclose.

scholarly journals Prognostic Value of BUB1 for Predicting Non-Muscle-Invasive Bladder Cancer Progression

2021 ◽  
Vol 22 (23) ◽  
pp. 12756
Author(s):  
Xuan-Mei Piao ◽  
Chaelin You ◽  
Young Joon Byun ◽  
Ho Won Kang ◽  
Junho Noh ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bladder Cancer ◽  
Cancer Cells ◽  
Mitotic Checkpoint ◽  
Invasive Bladder Cancer ◽  
Common Disease ◽  
Muscle Invasive Bladder Cancer ◽  
Bladder Cancer Cells ◽  
Muscle Invasive ◽  
Normal Controls

Non-muscle-invasive bladder cancer (NMIBC) is a common disease with a high recurrence rate requiring lifetime surveillance. Although NMIBC is not life-threatening, it can progress to muscle-invasive bladder cancer (MIBC), a lethal form of the disease. The management of the two diseases differs, and patients with MIBC require aggressive treatments such as chemotherapy and radical cystectomy. NMIBC patients at a high risk of progression benefit from early immediate cystectomy. Thus, identifying concordant markers for accurate risk stratification is critical to predict the prognosis of NMIBC. Candidate genetic biomarkers associated with NMIBC prognosis were screened by RNA-sequencing of 24 tissue samples, including 16 NMIBC and eight normal controls, and by microarray analysis (GSE13507). Lastly, we selected and investigated a mitotic checkpoint serine/threonine kinase, BUB1, that regulates chromosome segregation during the cell cycle. BUB1 gene expression was tested in 86 NMIBC samples and 15 controls by real-time qPCR. The performance of BUB1 as a prognostic biomarker for NMIBC was validated in the internal Chungbuk cohort (GSE13507) and the external UROMOL cohort (E-MTAB-4321). BUB1 expression was higher in NMIBC patients than in normal controls (p < 0.05), and the overexpression of BUB1 was correlated with NMIBC progression (log-rank test, p = 0.007). In in vitro analyses, BUB1 promoted the proliferation of bladder cancer cells by accelerating the G2/M transition of the cell cycle. Conclusively, BUB1 modulates the G2/M transition to promote the proliferation of bladder cancer cells, suggesting that it could serve as a prognostic marker in NMIBC.

scholarly journals SLC35F2, a Transporter Sporadically Mutated in the Untranslated Region, Promotes Growth, Migration, and Invasion of Bladder Cancer Cells

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 80
Author(s):  
Roland Kotolloshi ◽  
Martin Hölzer ◽  
Mieczyslaw Gajda ◽  
Marc-Oliver Grimm ◽  
Daniel Steinbach
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Untranslated Region ◽  
Tumour Cells ◽  
Invasive Bladder Cancer ◽  
Migration And Invasion ◽  
Sequencing Analysis ◽  
Muscle Invasive Bladder Cancer ◽  
Bladder Cancer Cells ◽  
Muscle Invasive

Bladder cancer is a very heterogeneous disease and the molecular mechanisms of carcinogenesis and progression are insufficiently investigated. From the DNA sequencing analysis of matched non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) samples from eight patients, we identified the tumour-associated gene SLC35F2 to be mutated in the 5′ and 3′ untranslated region (UTR). One mutation in 3′UTR increased the luciferase activity reporter, suggesting its influence on the protein expression of SLC35F2. The mRNA level of SLC35F2 was increased in MIBC compared with NMIBC. Furthermore, in immunohistochemical staining, we observed a strong intensity of SLC35F2 in single tumour cells and in the border cells of solid tumour areas with an atypical accumulation around the nucleus, especially in the MIBC. This suggests that SLC35F2 might be highly expressed in aggressive and invasive tumour cells. Moreover, knockdown of SLC35F2 repressed the growth of bladder cancer cells in the monolayer and spheroid model and suppressed migration and invasion of bladder cancer cells. In conclusion, we suggest that SLC35F2 is involved in bladder cancer progression and might provide a new therapeutic approach, for example, by the anti-cancer drug YM155, a cargo of the SLC35F2 transporter.

scholarly journals Nuclear Factor-κB Overexpression is Correlated with Poor Outcomes after Multimodality Bladder-Preserving Therapy in Patients with Muscle-Invasive Bladder Cancer

2019 ◽  
Vol 8 (11) ◽  
pp. 1954
Author(s):  
Yun Chiang ◽  
Chung-Chieh Wang ◽  
Yu-Chieh Tsai ◽  
Chao-Yuan Huang ◽  
Yeong-Shiau Pu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Invasive Bladder Cancer ◽  
Nuclear Factor ◽  
Muscle Invasive Bladder Cancer ◽  
Free Survival ◽  
Bladder Cancer Cells ◽  
Epidermal Growth ◽  
Muscle Invasive

The aim of this study was to investigate prognostic molecular targets for selecting patients with muscle-invasive bladder cancer undergoing bladder-preserving therapy. Pretreatment biopsy samples from patients with muscle-invasive bladder cancer receiving trimodality bladder-preserving therapy were analyzed for expression levels of p53, p16, human epidermal growth factor receptor-2 (Her-2), epidermal growth factor receptor (EGFR), nuclear factor-kappa B (NFκB; p65), E-cadherin, matrix metalloproteinase-9 (MMP9), meiotic recombination 11 homolog (MRE11), programmed death-1 ligand (PD-L1), and mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6) by immunohistochemical (IHC) staining. The correlations between these molecular markers with local progression-free survival (LPFS), distant metastasis-free survival (DMFS), and overall survival (OS) were explored. Biopsy samples from 41 out of 60 patients were evaluated using IHC. Univariate analysis revealed that the high expression of NFκB is associated with significantly worse LPFS, DMFS, and OS, and low expression of p16 is associated with significantly lower LPFS. Upon further multivariate analysis including sex, age, stage, and selected unfavorable factors in the model, NFκB and p16 independently remained significant. The investigational in vitro study demonstrated that irradiation induces up-regulation of NFκB signaling. Irradiated bladder cancer cells showed increased invasion capability and clonogenic survival; inhibition of NFκB signaling by an NFκB inhibitor, SC75741, or RNA interference reversed the observed increases. NFκB expression (p65) is associated with prognostic significance for both LPFS and DMFS in patients treated with bladder-preserving therapy, with consistent impact on cell viability of bladder cancer cells. NFκB may be a putative molecular target to help with outcome stratification.

scholarly journals The Antitumor Effects of Plasma-Activated Saline on Muscle-Invasive Bladder Cancer Cells In Vitro and In Vivo Demonstrate Its Feasibility as a Potential Therapeutic Approach

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1042
Author(s):  
Hao Zhang ◽  
Jishen Zhang ◽  
Bo Guo ◽  
Hailan Chen ◽  
Dehui Xu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Culture Media ◽  
Invasive Bladder Cancer ◽  
Antitumor Effects ◽  
Muscle Invasive Bladder Cancer ◽  
Plasma Irradiation ◽  
Muscle Invasive

Muscle-invasive bladder cancer (MIBC) is a fast-growing and aggressive malignant tumor in urinary system. Since chemotherapy and immunotherapy are only useable with a few MIBC patients, the clinical treatment of MIBC still faces challenges. Here, we examined the feasibility of plasma-activated saline (PAS) as a fledgling therapeutic strategy for MIBC treatment. Our data showed that plasma irradiation could generate a variety of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in saline. In vivo tests revealed that pericarcinomatous tissue injection with PAS was effective at preventing subcutaneous bladder tumor growth, with no side effects to the visceral organs after long-term administration, as well as having no obvious influence on the various biochemistry indices of the blood in mice. The in vitro studies indicated that adding 30% PAS in cell culture media causes oxidative damage to the bladder transitional cells T24 and J82 through enhancing the intracellular ROS level, and eventually induces cancer cells’ apoptosis by activating the ROS-mediated Fas/CD95 pathway. Therefore, for an intracavity tumor, these initial observations suggest that the soaking of the tumor tissue with PAS by intravesical perfusion may be a novel treatment option for bladder cancer.

scholarly journals 901 Bacillus Calmette-Guerin can subvert patients antitumor immune response by downregulating HLA-I expression on cancer cells

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A945-A945
Author(s):  
Mathieu Rouanne ◽  
Julien Adam ◽  
Camelia Radulescu ◽  
Diane Letourneur ◽  
Severine Mouraud ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Treatment Strategies ◽  
Invasive Bladder Cancer ◽  
Patient Treatment ◽  
Routine Practice ◽  
Bladder Cancer Patient ◽  
Muscle Invasive Bladder Cancer ◽  
Bcg Therapy ◽  
Muscle Invasive

BackgroundPatients with high-risk non muscle-invasive bladder cancer (NMIBC) frequently relapse after standard BCG immunotherapy and have a dismal outcome after progression to muscle-invasive bladder cancer (MIBC).1 2 The mechanisms of tumor resistance to such immunotherapy remain elusive.MethodsWe performed functional assays of fresh human bladder tumors mixed with BCG, reinforced with in vitro experiments and in situ transcriptomics analyses together with immune profiling by immunohistochemistry (IHC) in a cohort of T1 NMIBC pre- and post BCG therapy.ResultsWe found two distinct patterns of BCG-induced immune subversion. In the first pattern, intracellular infection by live BCG was associated with HLA-I loss and epithelial-to-mesenchymal transition characteristics. Mechanistically, LC3-GFP reporter cell line showed a significant induction of autophagy upon BCG exposure. HLA-I deficient tumors displayed a myeloid immunosuppressive microenvironment together with an upregulation of autophagy-related genes, and dismal outcome. Conversely, HLA-I+ BCG-treated tumors generated a Th1 type of immune response associated with an upregulation of exhaustion markers. Such patients had a very favorable outcome upon radical surgery.ConclusionsWe surmise that HLA-I expression in bladder cancers does not result from immunoediting but rather from HLA-I molecules endocytosis related to autophagy induction in infected cancer cells. Cancer cells HLA-I scoring by immunohistochemistry staining can be easily implemented by pathologists in routine practice to stratify future bladder cancer patient treatment strategies.ReferencesPietzak EJ, Zabor EC, Bagrodia A, et al. Genomic differences between “primary” and “secondary” muscle-invasive bladder cancer as a basis for disparate outcomes to cisplatin-based neoadjuvant chemotherapy. Eur Urol 2019;75(2):231–239.. Patrick J Hensley, Kelly K Bree, Matthew T Campbell, et al. Progression of disease after BCG therapy: refining patient selection for neoadjuvant chemotherapy before radical cystectomy. J Urol 2021 June 29;101097JU0000000000001943.Ethics ApprovalOur study obtained ethics approval from the Foch Hospital Ethics Committee (IRB00012437). All the participants gave informed consent before taking part.ConsentWe surmise that HLA-I expression in bladder cancers does not result from immunoediting but rather from HLA-I molecules endocytosis related to autophagy induction in infected cancer cells. Cancer cells HLA-I scoring by immunohistochemistry staining can be easily implemented by pathologists in routine practice to stratify future bladder cancer patient treatment strategies.

Sex and Racial Disparities in the Treatment and Outcomes of Muscle-invasive Bladder Cancer

Urology ◽  
2020 ◽  
Author(s):  
Jessica Marinaro ◽  
Alexander Zeymo ◽  
Jillian Egan ◽  
Filipe Carvalho ◽  
Ross Krasnow ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Racial Disparities ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive
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