scholarly journals Fibroblasts from pBOO promote tumorigenesis by secreting TGFbeta1 to induce EMT in bladder urothelial carcinoma cells

2018 ◽  
Author(s):  
Xiongbing Lu ◽  
Lingxing Duan ◽  
Jian Zhang ◽  
Zhihua Zeng ◽  
Renrui Kuang
Keyword(s):  
Bladder Cancer ◽  
Cell Invasion ◽  
Outlet Obstruction ◽  
Neutralizing Antibody ◽  
Urinary Bladder Cancer ◽  
High Propensity ◽  
Muscle Invasive ◽  
Activated Fibroblasts ◽  
Carcinoma Associated Fibroblasts ◽  
Tgf Β1

Abstract Urinary bladder cancer (UBC) is one of the most common malignancies worldwide. UBC patients at muscle invasive stage have poor clinical outcome, due to high propensity for metastasis. Non-tumor activated fibroblasts, named α-SMA+Fs, is similar to carcinoma-associated fibroblasts (CAFs) which could express α-SMA. However, whether α-SMA+Fs patients could induce UBC cell invasion is unclear. Herein, we found that characterization of primary α-SMA+Fs separated from PBOO (partial bladder outlet obstruction) rats was fell in between normal fibroblasts (α-SMA-Fs) and CAFs. Additionally, the conditional medium from α-SMA+Fs enhanced the NBT-II cell invasion through inducing EMT, and the oncogenic function of mixed supernatant of α-SMA+Fs/CAFs was stronger than that of CAFs. Inhibition of TGF-β1 by TGF-β1 neutralizing antibody decreased the EMT-associated gene expression and NBT-II cell invasion, suggesting that α-SMA+Fs can induce tumor EMT through TGF-β1. Xenograft experiments showed that the tumorigenic effect of α-SMA+Fs in mice was also between CAFs and α-SMA-Fs, and α-SMA+Fs/CAFs also had a strong tumorigenic effect. We preformed rats with PBOO and found that the incidence of invasive bladder cancer in PBOO+BBN group was higher than in BBN group, suggesting the PBOO treatment contributed to tumorigenesis. Thus, α-SMA+Fs promoted tumorigenesis by secreting TGF-β1 to induce EMT.

scholarly journals Overexpressed miR-200a promotes bladder cancer invasion through direct regulating Dicer/miR-16/JNK2/MMP-2 axis

Oncogene ◽  
2019 ◽  
Vol 39 (9) ◽  
pp. 1983-1996 ◽  
Author(s):  
Rui Yang ◽  
Jiheng Xu ◽  
Xiaohui Hua ◽  
Zhongxian Tian ◽  
Qipeng Xie ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cell Invasion ◽  
Biological Significance ◽  
Protein Translation ◽  
Mechanistic Studies ◽  
Mrna Transcription ◽  
Ongoing Development ◽  
Muscle Invasive ◽  
Dicer Expression ◽  
New Strategies

AbstractInvasive bladder cancer (BC) is one of the most lethal malignant urological tumors. Although miR-200a has been reported as an onco-miRNA that targets the PTEN gene in endometrioid carcinoma, its biological significance in BC invasion has been poorly explored. In the current study, we found that miR-200a was markedly overexpressed in both human BC tissues and BBN-induced muscle-invasive BC tissues. We further showed that miR-200a overexpression specifically promoted human BC cell invasion, but not migration, via transcriptional upregulation of matrix metalloproteinase (MMP)-2. Mechanistic studies indicated that the increased phosphorylation of c-Jun mediated the increasing levels of MMP-2 mRNA transcription. Further investigation revealed that Dicer was decreased in miR-200a overexpressed BC cells; this resulted in inhibition of miR-16 maturation and consequently led to increased JNK2 protein translation and c-Jun activation. Taken together, the studies here showed that miR-200a overexpression inhibited Dicer expression, in turn, resulted in inhibition of miR-16 maturation, leading to upregulation of JNK2 expression, c-Jun phosphorylation, MMP-2 transcription and, ultimately, BC invasion. Collectively, these results demonstrate that miR-200a is an onco-miRNA that is a positive regulator for BC invasion. This finding could be very useful in the ongoing development of new strategies to treat invasive BC patients.

scholarly journals Revisiting Histone Deacetylases in Human Tumorigenesis: The Paradigm of Urothelial Bladder Cancer

2019 ◽  
Vol 20 (6) ◽  
pp. 1291 ◽  
Author(s):  
Aikaterini Giannopoulou ◽  
Athanassios Velentzas ◽  
Eumorphia Konstantakou ◽  
Margaritis Avgeris ◽  
Stamatia Katarachia ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Urinary Bladder ◽  
Histone Deacetylases ◽  
Strong Association ◽  
Hdac Inhibitors ◽  
Urinary Bladder Cancer ◽  
Molecular Heterogeneity ◽  
Urothelial Bladder Cancer ◽  
Urothelial Bladder ◽  
Muscle Invasive

Urinary bladder cancer is a common malignancy, being characterized by substantial patient mortality and management cost. Its high somatic-mutation frequency and molecular heterogeneity usually renders tumors refractory to the applied regimens. Hitherto, methotrexate-vinblastine-adriamycin-cisplatin and gemcitabine-cisplatin represent the backbone of systemic chemotherapy. However, despite the initial chemosensitivity, the majority of treated patients will eventually develop chemoresistance, which severely reduces their survival expectancy. Since chromatin regulation genes are more frequently mutated in muscle-invasive bladder cancer, as compared to other epithelial tumors, targeted therapies against chromatin aberrations in chemoresistant clones may prove beneficial for the disease. “Acetyl-chromatin” homeostasis is regulated by the opposing functions of histone acetyltransferases (HATs) and histone deacetylases (HDACs). The HDAC/SIRT (super-)family contains 18 members, which are divided in five classes, with each family member being differentially expressed in normal urinary bladder tissues. Since a strong association between irregular HDAC expression/activity and tumorigenesis has been previously demonstrated, we herein attempt to review the accumulated published evidences that implicate HDACs/SIRTs as critical regulators in urothelial bladder cancer. Moreover, the most extensively investigated HDAC inhibitors (HDACis) are also analyzed, and the respective clinical trials are also described. Interestingly, it seems that HDACis should be preferably used in drug-combination therapeutic schemes, including radiation.

scholarly journals The increased risk for thromboembolism pre-cystectomy in patients undergoing neoadjuvant chemotherapy for muscle-invasive urinary bladder cancer is mainly due to central venous access: a multicenter evaluation

2019 ◽  
Vol 52 (4) ◽  
pp. 661-669 ◽  
Author(s):  
Kristoffer Ottosson ◽  
Sofia Pelander ◽  
Markus Johansson ◽  
Ylva Huge ◽  
Firas Aljabery ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Central Venous Access ◽  
Urinary Bladder Cancer ◽  
Venous Access ◽  
Central Venous ◽  
Chemotherapy Administration ◽  
Increased Risk ◽  
Chi Squared ◽  
Muscle Invasive

Abstract Purpose To investigate if patients receiving neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) had an increased risk of thromboembolic events (TEE) and to evaluate when these events occur on a timeline starting from 6 months pre-cystectomy, during NAC-administration and 60 months post-cystectomy. Methods Two hundred and fifty five patients undergoing radical cystectomy during 2009–2014 at three Swedish cystectomy centers (Umeå, Linköping and Sundsvall) were in-detail reviewed retrospectively, using individual medical records. One hundred and twenty nine patients were ineligible for analysis. NAC patients (n = 67) were compared to NAC-naïve NAC-eligible patients (n = 59). The occurrence of TEE was divided into different periods pre-cystectomy and post-cystectomy. Statistical analyses included Chi-squared and logistical regression tests. Results Significant associations were found between receiving NAC and acquiring a TEE during NAC therapy pre-cystectomy. All but one pre-cystectomy event was venous and all but one of the patients received NAC. 31% (14/45) of TEEs occurred pre-cystectomy. The incidence of TEEs pre-cystectomy in NAC-naive NAC-eligible patients was only 10% (2/20), whereas the incidence of TEEs in NAC patients occurred pre-cystectomy in 48% (12/25) and 11/12 incidents were detected during NAC therapy—this including 7/11 (64%) incidents affecting veins in anatomical conjunction with the placement of central venous access for chemotherapy administration. Conclusions There is a significantly increased risk for TEE pre-cystectomy during chemotherapy administration in MIBC patients receiving NAC, compared to the risk in NAC-naïve NAC-eligible MIBC patients. In 64% of the pre-RC TEEs in NAC patients, there was a clinical connection to placement of central venous access.

scholarly journals Lysophosphatidic Acid Upregulates Recepteur D’origine Nantais Expression and Cell Invasion via Egr-1, AP-1, and NF-κB Signaling in Bladder Carcinoma Cells

2020 ◽  
Vol 21 (1) ◽  
pp. 304
Author(s):  
Pham Ngoc Khoi ◽  
Shinan Li ◽  
Ung Trong Thuan ◽  
Dhiraj Kumar Sah ◽  
Taek Won Kang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Lysophosphatidic Acid ◽  
Cell Invasion ◽  
Bladder Carcinoma ◽  
Carcinoma Cells ◽  
Lpa Receptor ◽  
Carcinoma Metastasis ◽  
Muscle Invasive ◽  
G Protein Coupled ◽  
Bladder Carcinoma Cells

Muscle invasive bladder carcinoma is a highly malignant cancer with a high mortality rate, due to its tendency to metastasize. The tyrosine kinase recepteur d’origine nantais (RON) promotes bladder carcinoma metastasis. Lysophosphatidic acid (LPA) is a phospholipid derivative, which acts as a signaling molecule to activate three high affinity G-protein coupled receptors, LPA1, LPA2, and LPA3. This in turn leads to cell proliferation and contributes to oncogenesis. However, little is known about the effects of LPA on invasive bladder cancer (IBC). In this study, we discovered that LPA upregulated RON expression, which in turn promoted cell invasion in bladder cancer T24 cells. As expected, we found that the LPA receptor was essential for the LPA induced increase in RON expression. More interestingly, we discovered that LPA induced RON expression via the MAPK (ERK1/2, JNK1/2), Egr-1, AP-1, and NF-κB signaling axes. These results provide experimental evidence and novel insights regarding bladder malignancy metastasis, which could be helpful for developing new therapeutic strategies for IBC treatment.

scholarly journals Pre-operative pyuria predicts tumor recurrence in patients undergoing transurethral resection of bladder tumor with post-operative instillation of BCG

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Syed Atif Hussain ◽  
Majed Saeed ◽  
Atta Ur Rehman Rana ◽  
Khizar Hayat Gondala ◽  
Ali Shandar Durrani ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Transurethral Resection ◽  
Tumor Recurrence ◽  
Bladder Tumor ◽  
White Blood Cells ◽  
Urinary Bladder Cancer ◽  
Early Morning ◽  
Outcome Variable ◽  
Urine Specimen ◽  
Muscle Invasive

BACKGROUND & OBJECTIVE: In Pakistan, urinary bladder cancer is one of the top ten malignancies. The most important concern after its treatment is tumor recurrence. Recent literature claimed that pre-operative pyuria in patients undergoing transurethral resection of bladder tumor was associated with significantly higher frequency of recurrence. However, there was controversy in existing literature and no such local published material was available which necessitated the present study. To determine the frequency of pre-operative pyuria in patients undergoing transurethral resection of bladder tumor for non-muscle invasive bladder cancer (NMIBC) with post-operative instillation of Bacillus Calmette Guerin (BCG) and to compare the frequency of tumor recurrence in patients with and without pre-operative pyuria. METHODOLOGY: It was a comparative study. This study involved 280 patients of both genders aged between 20-80 years. Pre-operative pyuria was diagnosed if early morning midstream urine specimen showed ≥10 white blood cells/HPF. Outcome variable was frequency of recurrence after 12 weeks of treatment on check cystoscopy. RESULTS: The mean age of the patients was 57.1±8.5 years. There were 236 (84.3%) male and 44 (15.7%) female patients in the study. 155 (55.4%) patients were tobacco smoker. Pre-operative pyuria was diagnosed in 127 (45.4%) patients while tumor recurrence was observed in 183 (65.4%) patients. The frequency of tumor recurrence was significantly higher in patients with pre-operative pyuria (85.8% vs. 48.4%; p<0.001). CONCLUSION: Pre-operative pyuria was a frequent finding in patients with non-muscle invasive bladder tumor and was associated with higher frequency of tumor recurrence which warrants routine screening of such patients for pyuria and increased frequency of tumor recurrence.

scholarly journals Squamous Cell Carcinoma of the Urinary Bladder: Clinicopathological and Molecular Update

2021 ◽  
Author(s):  
Sunil Vitthalrao Jagtap ◽  
Swati S Jagtap ◽  
Parneet Kaur ◽  
Snigdha Vartak
Keyword(s):  
Squamous Cell Carcinoma ◽  
Bladder Cancer ◽  
Urinary Bladder ◽  
Urothelial Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Urinary Bladder Cancer ◽  
Cell Phenotype ◽  
Molecular Features ◽  
Muscle Invasive

Urinary bladder cancer is one of the most prevalent cancers worldwide.Squamous Cell Carcinoma (SCC) is an uncommon subtype of urinary bladder carcinoma.It is a malignant epithelial neoplasm arising in the urinary bladder demonstrating a pure squamous cell phenotype. On histopathology it is considered when tumor is showing pure squamous morphology without any component of conventional urothelial carcinoma. The SCC is a histologically distinct form of cancer. It arises from the uncontrolled multiplication of cells showing particular cytological or tissue architectural characteristics of squamous cell differentiation, such as the presence of keratin, tonofilament bundles or desmosomes. Majority of bladder SCC are high grade, high stage tumors with most cancers having muscle invasion at the time of diagnosis while overall about 80% of bladder cancers are non-muscle invasive bladder cancer at diagnosis.COX-2 is markedly expressed in all SCCs. An increased COX-2 level induces the development of SCC of the bladder affecting many biological features of this tissue including apoptosis, cell adhesion, angiogenesis and invasiveness.TERT promoter mutations, commonly found in conventional urothelial carcinoma, are also highly prevalent in urinary bladder squamous cell carcinoma suggesting a common tumorgenesis and potential utility as a molecular urine-based-screening assay.This review summarizes the current features related to clinical , pathological, and molecular features of SCC of urinary bladder.

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