669 The tumour suppressor gene, AIMP3 sensitises bladder cancer to chemo/radiotherapy in vitro and is a prognostic marker for overall survival in patients treated with radiotherapy for muscle invasive disease

396 Background: Cystectomy has become one of the standard forms of therapy for patients with muscle invasive bladder cancer with long term follow-up data supporting radical surgical management. Methods: Data are collected retrospectively on patients who underwent cystectomy at the Royal Liverpool University Hospital. The aim was to document the overall survival of patients undergoing cystectomy at this centre. Results: Data were collected on 147 patients between September 2007 and June 2013. Median patient age was 66 (IQR: 61, 72) with 33 (23%) females. 107 (73%) patients had muscle invasive TCC, 13 (9%) had recurrent non-muscle invasice disease, 9 (6%) had salvage surgery following radical radiotherapy and 6 (4%) had persistent carcinoma in situ. 28 patients (20%) had hydronephrosis. 34 (23%) patients underwent neo-adjuvant chemotherapy. 2 (1%) patients had Combined synchronous urethrectomy and 5 (3%) had Combined synchronous nephroureterectomy. Post operatively positive lymph nodes were observed in 22 (19%) of surgical specimens and 83 (72%) had persistent muscle invasive disease. Survival rates at 12 and 60 months are 0.92 (0.88, 0.97) and 0.52 (0.39, 0.71) respectively. Multivariate analysis show that post operative T (HR: 3.99 (1.05, 15.18)) and N (HR: 5.40 (2.17, 13.44)) status are both independent predictors of over all survival. Conclusions: Real life data from our centre showed that the patient population and overall survival estimates for patients with muscle invasive bladder cancer treated with radical cystectomy and lymph node dissection are consistent with previous published literature. .

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Mutation and homozygous deletion of ARHGEF10 in bladder cancer; a candidate tumour suppressor gene at 8p23.3

Cancer Genetics and Cytogenetics ◽

10.1016/j.cancergencyto.2010.07.053 ◽

2010 ◽

Vol 203 (1) ◽

pp. 68

Author(s):

Sarah V. Williams ◽

Claire Taylor ◽

Fiona Platt ◽

Carolyn D. Hurst ◽

Jo Aveyard ◽

...

Keyword(s):

Bladder Cancer ◽

Suppressor Gene ◽

Homozygous Deletion ◽

Tumour Suppressor Gene ◽

Tumour Suppressor ◽

Candidate Tumour Suppressor

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Mir-20a-5p induced WTX deficiency promotes gastric cancer progressions through regulating PI3K/AKT signaling pathway

10.21203/rs.3.rs-37466/v2 ◽

2020 ◽

Author(s):

Jian Li ◽

Danli Ye ◽

Peng Shen ◽

Xiaorong Liu ◽

Peirong Zhou ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Proliferation ◽

Signaling Pathway ◽

Suppressor Gene ◽

Tumour Suppressor Gene ◽

Mtor Signaling ◽

Tumour Suppressor ◽

Mtor Signaling Pathway

Abstract Background: The X-linked gene WTX (also called AMER1) has been reported to function as a tumour suppressor gene in Wilms’ tumour. In our previous study, WTX expression was shown to be significantly reduced in gastric cancer (GC), but the function and mechanism associated with WTX loss had yet to be fully elucidated. Methods: WTX expression and clinical significance were father analyzed in GC and control normal gastric tissues, and validated in public databases. The candidate pathway which was regulated by WTX during GC progression was searched by KEGG pathway analysis. The miRNA which monitored WTX expression was screened by miRNA microarray. After verified the pathway and miRNA both in vitro and in vivo, the relationship of miRNA, WTX and the downstream pathway were analyzed by Western blot, immunohistochemistry, RT-PCR, Co-immunoprecipitation (Co-IP), and luciferase analyses.Results: The results showed that WTX serves as a tumour suppressor gene in GC. The loss of WTX which is associated with the aggressiveness of GC by promoting GC cell proliferation in vitro and high metastasis in vivo. Furthermore, WTX expression was positively correlated with the overall survival of GC patients. Microarray assays, bioinformatics analysis, and verification experiments showed that WTX loss activates the PI3K/AKT/mTOR pathway and promotes GC cell proliferation and invasion. And the aberrant miR-20a-5p upregulation contributes to WTX loss in GC, which stimulates PI3K phosphorylation to activate PI3K/AKT/mTOR signaling pathway and promoted GC progression.Conclusions: The results of the present study elucidated the mechanism of GC progression, which is at least partially caused by aberrant miR-20a-5p upregulation leading to the inhibition of WTX expression and PI3K/AKT/mTOR signaling pathway activation. These findings provide a comprehensive understanding of the action of the miR-20a-5p/WTX/PI3K/AKT/mTOR signaling pathway in the progression and metastasis of GC.

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PD-L1 promotes malignant progression by inducing EMT and enhancing stemness in muscle-invasive bladder cancer

10.21203/rs.3.rs-394619/v1 ◽

2021 ◽

Author(s):

Fujin Jiang ◽

Ying Ding ◽

Ting Chen ◽

Xianyun Zhang ◽

Song Ma ◽

...

Keyword(s):

Overall Survival ◽

Bladder Cancer ◽

Invasive Bladder Cancer ◽

In Vitro Experiments ◽

Muscle Invasive Bladder Cancer ◽

Invasion And Migration ◽

Muscle Invasive ◽

Effect Of Pd ◽

Emt Markers

Abstract Objective: Despite radical treatment for aggressive muscle-invasive bladder cancer(MIBC), the prognosis remained poor. Programmed cell death ligand 1(PD-L1) plays an important role in suppressing immune responses.We investigate if PD-L1 and EMT synergistically contribute to MIBC progression. Methods: In vitro experiments, we evaluated the effects of PD-L1 on proliferation, invasion, migration of MIBC cells and studied the relationship between PD-L1 and CSC/EMT markers by overexpressing and knocking down PD-L. The association of PD-L1 with EMT was detected in MIBC human specimens and the synergistic effect of PD-L1and EMT was assessed by analysis of overall survival (OS). Results: Our data demonstrated that PD-L1 promotes proliferation, invasion and migration of MIBC cells. The positive correlation between PD-L1 and CSC/EMT markers was verified both in vitro experiments and in 130 MIBC specimens. Moreover, patients with positive PD-L1/positive EMT exhibited poorer overall survival than patients with other combinations. Conclusion: The close relationship between PD-L1 and EMT may offer potential therapeutic strategy that co-targeting PD-L1 and EMT may improve the prognosis of MIBC patients.

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Expression of the p53 tumour suppressor gene as a prognostic marker in platinum-treated patients with ovarian cancer

European Journal of Cancer ◽

10.1016/s0959-8049(97)10169-1 ◽

1998 ◽

Vol 34 (6) ◽

pp. 845-850 ◽

Cited By ~ 27

Author(s):

D Marx ◽

H Meden ◽

T Ziemek ◽

T Lenthe ◽

W Kuhn ◽

...

Keyword(s):

Ovarian Cancer ◽

Prognostic Marker ◽

Suppressor Gene ◽

Tumour Suppressor Gene ◽

Tumour Suppressor ◽

P53 Tumour Suppressor Gene

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Mir-20a-5p induced WTX deficiency promotes gastric cancer progressions through regulating PI3K/AKT signaling pathway

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-020-01718-4 ◽

2020 ◽

Vol 39 (1) ◽

Author(s):

Jian Li ◽

Danli Ye ◽

Peng Shen ◽

Xiaorong Liu ◽

Peirong Zhou ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Proliferation ◽

Signaling Pathway ◽

Suppressor Gene ◽

Tumour Suppressor Gene ◽

Mtor Signaling ◽

Tumour Suppressor ◽

Mtor Signaling Pathway

Abstract Background The X-linked gene WTX (also called AMER1) has been reported to function as a tumour suppressor gene in Wilms’ tumour. In our previous study, WTX expression was shown to be significantly reduced in gastric cancer (GC), but the function and mechanism associated with WTX loss had yet to be fully elucidated. Methods WTX expression and clinical significance were father analyzed in GC and control normal gastric tissues, and validated in public databases. The candidate pathway which was regulated by WTX during GC progression was searched by KEGG pathway analysis. The miRNA which monitored WTX expression was screened by miRNA microarray. After verified the pathway and miRNA both in vitro and in vivo, the relationship of miRNA, WTX and the downstream pathway were analyzed by Western blot, immunohistochemistry, RT-PCR, Co-immunoprecipitation (Co-IP), and luciferase analyses. Results The results showed that WTX serves as a tumour suppressor gene in GC. The loss of WTX which is associated with the aggressiveness of GC by promoting GC cell proliferation in vitro and high metastasis in vivo. Furthermore, WTX expression was positively correlated with the overall survival of GC patients. Microarray assays, bioinformatics analysis, and verification experiments showed that WTX loss activates the PI3K/AKT/mTOR pathway and promotes GC cell proliferation and invasion. And the aberrant miR-20a-5p upregulation contributes to WTX loss in GC, which stimulates PI3K phosphorylation to activate PI3K/AKT/mTOR signaling pathway and promoted GC progression. Conclusions The results of the present study elucidated the mechanism of GC progression, which is at least partially caused by aberrant miR-20a-5p upregulation leading to the inhibition of WTX expression and PI3K/AKT/mTOR signaling pathway activation. These findings provide a comprehensive understanding of the action of the miR-20a-5p/WTX/PI3K/AKT/mTOR signaling pathway in the progression and metastasis of GC.

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