Radiotherapy plus Chemotherapy in Muscle-Invasive Bladder Cancer

Atkins, Carl D.; Wrzesinski, Stephen H.

doi:10.1056/nejmc1206002

Cited by 6 publications

(4 citation statements)

References 10 publications

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“…A total of 60,490 new diagnosed bladder cancer patients in the United States, and about 12,240 of these patients died of the disease in 2017 [ 2 ]. Besides traditional surgical treatment, targeted chemotherapy and immunotherapy have gained importance in treating bladder cancer [ 3 – 6 ]. However, 25% of bladder cancer is reported to be muscle invasive, and approximately 50% of these patients die from a life-threatening metastasis within 2 years [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Suppressed OGT expression inhibits cell proliferation while inducing cell apoptosis in bladder cancer

et al. 2018

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BackgroundThis study aimed to explore hyper-O-linked N-acetylglucosaminylation (O-GlcNAcylation) with an elevation of the expression of O-linked-β-N-acetylglucosamine transferase (OGT) in human bladder cancer.MethodsImmunohistochemical staining for OGT and O-GlcNAcylation was performed in 20 paired human bladder cancer and adjacent normal tissues, as well as in human bladder cancer tissue microarrays (N = 169). The expression level of OGT and O-GlcNAcylation in cell lines were detected using the Western blot analysis. The effects of O-GlcNAcylation on the cell proliferation of bladder cancer were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clone formation assays. Cell apoptosis and cell cycle analysis were detected using flow cytometry. The autophagy of bladder cancer cells was investigated using the Western blot analysis, and GFP–LC3 plasmid was used to detect the autophagic flux. MTT assay was performed to detect the sensitivity of bladder cancer cells to cisplatin after OGT knockdown.ResultsThe expression of OGT and the O-GlcNAcylation were upregulated in bladder cancer tissues and cell lines. O-GlcNAcylation and OGT were observed in nucleus and cytoplasm and found to be higher in muscle-invasive bladder cancer (MIBC) than in non-muscle-invasive bladder cancer (NMIBC). Reducing hyper-O-GlcNAcylation by OGT knockdown inhibited the proliferation of bladder cancer cells in vitro and xenograft tumor growth in vivo, triggered apoptosis, as well as led to cell cycle arrest. It also increased autophagy in bladder cancer cells. This study demonstrated increased autophagy pro-survival, but not pro-death. Reducing hyper-O-GlcNAcylation by OGT knockdown facilitated the chemosensitivity of bladder cancer cells to cis-platinum.ConclusionsThe data indicated that hyper-O-GlcNAcylation enhanced oncogenic phenotypes and was involved in DNA damage response in bladder cancer.

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Section: Introductionmentioning

confidence: 99%

Suppressed OGT expression inhibits cell proliferation while inducing cell apoptosis in bladder cancer

et al. 2018

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“…Despite significant advances in therapies including surgery and chemotherapy, the overall survival rate is not significantly improved. It is very important to search for the molecular mechanism and potential targets regulating bladder cancer aggressiveness and chemoresistance, which could be used for development of new therapy [ 3 - 5 ].…”

Section: Introductionmentioning

confidence: 99%

Rab27A overexpression promotes bladder cancer proliferation and chemoresistance through regulation of NF-κB signaling

et al. 2017

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Overexpression of Rab27A has been found in human cancers. However, the clinical significance and biological effects of Rab27A in bladder cancer tissues and cell lines have not been investigated. Here, we checked Rab27A protein in 87 cases of bladder cancer using immunohistochemistry. We found that Rab27A was overexpressed in 39 of 87 (44.8%) cancer cases. Significant association was found between Rab27 and invading depth (p=0.0083). We knocked down Rab27A in 5637 cell line and transfected Rab27A plasmid in BIU-87 cell line. Rab27A depletion inhibited cell growth rate and invasion while its overexpression induced cell growth and invasion. Rab27A also promoted cancer cell growth in vivo. Cell viability and Annexin V/PI staining demonstrated that Rab27A maintained cancer cell survival and reduced apoptosis rate when treated with cisplatin. JC-1 staining showed that Rab27A upregulated mitochondrial membrane potential. Western blot demonstrated that Rab27A overexpression upregulated cyclin D1, cyclin E, p-IκB, p-p65, Bcl-2, cIAP1, cIAP2 protein expression. NF-κB inhibitor BAY 11-7082 abolished the effects of Rab27 on cisplatin resistance and Bcl-2 protein. In conclusion, the present study demonstrated that Rab27A overexpression facilitates bladder cancer growth, invasion and chemoresistance in bladder cancer, possibly through regulation of NF-κB signaling pathway.

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“…Bladder cancer is one of the 10 most common cancers in China that contributes to increasing morbidity and mortality. Though treatment methods such as surgery, radiotherapy, chemotherapy, and therapeutics have significantly improved the quality of life of bladder cancer patients [ 2 ], the prognosis and the 5-year survival rate is extremely poor due to late diagnosis and aggressive metastasis [ 3 ]. Early diagnosis is key for positive prognosis and to improve the survival rate [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

MicroRNAs in biofluids are novel tools for bladder cancer screening

Liu

et al. 2017

Oncotarget

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MicroRNAs (miRNAs) are short non-coding RNAs that play important roles in basic cellular processes, including differentiation, proliferation, apoptosis and autophagy. They are also involved in various stages of tumorigenesis and play key roles in bladder cancer initiation and progression. Notably, the altered expression of miRNAs in the tumors is reflected in body fluids, including blood and urine, which opens avenues for non-invasive diagnosis and prognosis. Many studies have demonstrated that epigenetic changes extensively alter tumoral microRNA expression. The high reproducibility, specificity and sensitivity of miRNA levels in body fluids suggest their potential use as biomarkers for cancer screening and diagnosis. For example, recent technological advances have made it possible to detect miRNAs in urine for bladder cancer screening. In this review, we focus mainly on the current knowledge and future challenges for incorporating miRNAs in body fluids, like urine and blood, for making clinical diagnoses and assessing prognoses in bladder cancer.

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Radiotherapy plus Chemotherapy in Muscle-Invasive Bladder Cancer

Cited by 6 publications

References 10 publications

Suppressed OGT expression inhibits cell proliferation while inducing cell apoptosis in bladder cancer

Suppressed OGT expression inhibits cell proliferation while inducing cell apoptosis in bladder cancer

Rab27A overexpression promotes bladder cancer proliferation and chemoresistance through regulation of NF-κB signaling

MicroRNAs in biofluids are novel tools for bladder cancer screening

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