Non-Muscular Invasive Bladder Cancer: Re-envisioning Therapeutic Journey from Traditional to Regenerative Interventions

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Abstract

Non-muscular invasive bladder cancer (NMIBC) is one of the most common cancer and major cause of economical and health burden in developed countries. Progression of NMIBC has been characterized as low-grade (Ta) and high grade (carcinoma in situ and T1). The current surgical intervention for NMIBC includes transurethral resection of bladder tumor; however, its recurrence still remains a challenge. The BCG-based immunotherapy is much effective against low-grade NMIBC. BCG increases the influx of T cells at bladder cancer site and inhibits proliferation of bladder cancer cells. The chemotherapy is another traditional approach to address NMIBC by supplementing BCG. Notwithstanding, these current therapeutic measures possess limited efficacy in controlling NMIBC, and do not provide comprehensive long-term relief. Hence, biomaterials and scaffolds seem an effective medium to deliver therapeutic agents for restructuring bladder post-treatment. The regenerative therapies such as stem cells and PRP have also been explored for possible solution to NMIBC. Based on above-mentioned approaches, we have comprehensively analyzed therapeutic journey from traditional to regenerative interventions for the treatment of NMIBC.

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Most cited references 154

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Bladder cancer is a complex disease associated with high morbidity and mortality rates if not treated optimally. Awareness of haematuria as the major presenting symptom is paramount, and early diagnosis with individualised treatment and follow-up is the key to a successful outcome. For non-muscle-invasive bladder cancer, the mainstay of treatment is complete resection of the tumour followed by induction and maintenance immunotherapy with intravesical BCG vaccine or intravesical chemotherapy. For muscle-invasive bladder cancer, multimodal treatment involving radical cystectomy with neoadjuvant chemotherapy offers the best chance for cure. Selected patients with muscle-invasive tumours can be offered bladder-sparing trimodality treatment consisting of transurethral resection with chemoradiation. Advanced disease is best treated with systemic cisplatin-based chemotherapy; immunotherapy is emerging as a viable salvage treatment for patients in whom first-line chemotherapy cannot control the disease. Developments in the past 2 years have shed light on genetic subtypes of bladder cancer that might differ from one another in response to various treatments.

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MicroRNAs (miRNAs) are short RNAs that direct messenger RNA degradation or disrupt mRNA translation in a sequence-dependent manner. For more than a decade, attempts to study the interaction of miRNAs with their targets were confined to the 3' untranslated regions of mRNAs, fuelling an underlying assumption that these regions are the principal recipients of miRNA activity. Here we focus on the mouse Nanog, Oct4 (also known as Pou5f1) and Sox2 genes and demonstrate the existence of many naturally occurring miRNA targets in their amino acid coding sequence (CDS). Some of the mouse targets analysed do not contain the miRNA seed, whereas others span exon-exon junctions or are not conserved in the human and rhesus genomes. miR-134, miR-296 and miR-470, upregulated on retinoic-acid-induced differentiation of mouse embryonic stem cells, target the CDS of each transcription factor in various combinations, leading to transcriptional and morphological changes characteristic of differentiating mouse embryonic stem cells, and resulting in a new phenotype. Silent mutations at the predicted targets abolish miRNA activity, prevent the downregulation of the corresponding genes and delay the induced phenotype. Our findings demonstrate the abundance of CDS-located miRNA targets, some of which can be species-specific, and support an augmented model whereby animal miRNAs exercise their control on mRNAs through targets that can reside beyond the 3' untranslated region.

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Sam S Chang, Stephen A. Boorjian, Roger Chou … (2016)

Although associated with an overall favorable survival rate, the heterogeneity of non-muscle invasive bladder cancer (NMIBC) affects patients' rates of recurrence and progression. Risk stratification should influence evaluation, treatment and surveillance. This guideline attempts to provide a clinical framework for the management of NMIBC.

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Author and article information

Journal

Journal ID (nlm-ta): Aging Dis

Journal ID (iso-abbrev): Aging Dis

Title: Aging and Disease

Publisher: JKL International LLC

ISSN (Electronic): 2152-5250

Publication date Collection: June 2021

Publication date (Electronic): 1 June 2021

Volume: 12

Issue: 3

Pages: 868-885

Affiliations

[1-ad-12-3-868] ¹Department of Urology, Taipei Medical University Hospital, Taipei 11031, Taiwan.

[2-ad-12-3-868] ²Graduate Institute of Clinical Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.

[3-ad-12-3-868] ³TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei 11031, Taiwan.

[4-ad-12-3-868] ⁴Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 11031, Taiwan.

[5-ad-12-3-868] ⁵Department of Education, Taipei Medical University Hospital, Taipei 11031, Taiwan.

[6-ad-12-3-868] ⁶Department of Urology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.

[7-ad-12-3-868] ⁷Clinical Research Center, Taipei Medical University Hospital, Taipei 11031, Taiwan.

[8-ad-12-3-868] ⁸Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei,11221, Taiwan.

[9-ad-12-3-868] ⁹Department of Urology, Department of Surgery, Taipei City Hospital Ren-Ai Branch, Taipei 10629, Taiwan.

[10-ad-12-3-868] ¹⁰School of Dental Technology, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.

Author notes

[* ]Correspondence should be addressed to: Dr. Ming-Che Liu, Graduate Institute of Clinical Medicine, school of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Email: d204097002@ 123456tmu.edu.tw.

[#]

these authors contributed equally to this work.

Article

Publisher ID: ad-12-3-868

DOI: 10.14336/AD.2020.1109

PMC ID: 8139208

PubMed ID: 34094648

SO-VID: 3d7916b2-aac2-45c1-8877-f96255ff9845

License:

this is an open access article distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

History

Date received : 19 July 2020

Date revision requested : 8 November 2020

Date accepted : 9 November 2020

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