Local Immune Stimulation by Intravesical Instillation of Baculovirus to Enable Bladder Cancer Therapy

Ang, Wei Xia; Ying, Zhao; Kwang, Timothy Weixin; Wu, Chunxiao; Chen, Can; Toh, Han Chong; Mahendran, Ratha; Esuvaranathan, Kesavan; Shu, Wang

doi:10.1038/srep27455

Cited by 14 publications

(8 citation statements)

References 50 publications

(86 reference statements)

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“…cial non-invasive tumors to deep myometrial invasive cancers [2]. In China, BCa is the most common urological malignancy with the highest morbidity and cancer-related mortality, and its incidence has been consistently increased in previous years [3,4].…”

mentioning

confidence: 99%

Immune Checkpoint Human Endogenous Retrovirus-H Long Terminal Repeat-Associating Protein 2 is Upregulated and Independently Predicts Unfavorable Prognosis in Bladder Urothelial Carcinoma

Lin

Wang

et al. 2019

Nephron

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Background/Aims: human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) is highly expressed in multiple solid malignant tumors, making it a potential biomarker for tumorigenesis and invasion. However, the expression and clinical significance of HHLA2 in bladder urothelial carcinoma (BUC) have not been extensively studied. This study aimed to investigate the relationship between HHLA2 expression and clinicopathological characteristics of BUC. Methods: A total of 212 patients pathologically diagnosed with BUC were included in this study. HHLA2 expression was analyzed by immunohistochemical staining and qRT-polymerase chain reaction. Correlations of HHLA2 expression and pathological characteristics, including 5-year recurrence-free survival (RFS) and overall survival (OS) were examined, and the diagnostic value of HHLA2 was estimated by using the receiver operating characteristic (ROC) curve. Results: Immunohistochemical staining showed that the expression of HHLA2 was significantly upregulated in BUC tissues compared with normal bladder tissues. In BUC tissues, HHLA2 expression was significantly associated with tumor size, tumor stage, tumor grade, and lymph node metastasis (all p < 0.05). HHLA2 expression was an independent prognostic factor of tumor metastasis (p < 0.05). The Kaplan-Meier survival curve revealed that high HHLA2 expression was significantly correlated with the poor RFS and OS of BUC patients (both p < 0.05), and the ROC curve showed HHLA2 could be a good diagnostic marker. Conclusions: HHLA2 can independently predict unfavorable prognosis in BUC.

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mentioning

confidence: 99%

Immune Checkpoint Human Endogenous Retrovirus-H Long Terminal Repeat-Associating Protein 2 is Upregulated and Independently Predicts Unfavorable Prognosis in Bladder Urothelial Carcinoma

Lin

Wang

et al. 2019

Nephron

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“…kidney and bladder), we postulate the distribution pattern is related to vesicoureteral reflux of anti-CD47-QD from the bladder into the kidneys. While technically challenging, mouse bladder instillation is a well-established technique for testing intravesical therapies 43 , 44 , for generation of orthotopic models of bladder cancer 45 , 46 , and for treatment of bacterial infection 47 . To retain the intravesical agent and prevent efflux during incubation, a blocking strategy is usually employed.…”

Section: Discussionmentioning

confidence: 99%

“…To retain the intravesical agent and prevent efflux during incubation, a blocking strategy is usually employed. Strategies include tying the urethral opening 48 , clamping the catheter 43 or connecting an air-filled syringe to the catheter 45 as in our study. Mouse bladders only have approximately 150 µl capacity, in which we instilled 50 µl of solution.…”

Section: Discussionmentioning

confidence: 99%

In vivo biodistribution and toxicity of intravesical administration of quantum dots for optical molecular imaging of bladder cancer

Pan

Chang

Marcq

et al. 2017

Sci Rep

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Optical molecular imaging holds the potential to improve cancer diagnosis. Fluorescent nanoparticles such as quantum dots (QD) offer superior optical characteristics compared to organic dyes, but their in vivo application is limited by potential toxicity from systemic administration. Topical administration provides an attractive route for targeted nanoparticles with the possibility of minimizing exposure and reduced dose. Previously, we demonstrated successful ex vivo endoscopic imaging of human bladder cancer by topical (i.e. intravesical) administration of QD-conjugated anti-CD47. Herein we investigate in vivo biodistribution and toxicity of intravesically instilled free QD and anti-CD47-QD in mice. In vivo biodistribution of anti-CD47-QD was assessed with inductively coupled plasma mass spectrometry. Local and systemic toxicity was assessed using blood tests, organ weights, and histology. On average, there was no significant accumulation of QD outside of the bladder, although in some mice we detected extravesical biodistribution of QD suggesting a route for systemic exposure under some conditions. There were no indications of acute toxicity up to 7 days after instillation. Intravesical administration of targeted nanoparticles can reduce systemic exposure, but for clinical use, nanoparticles with established biosafety profiles should be used to decrease long-term toxicity in cases where systemic exposure occurs.

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“…This could be relief by reducing the instillation duration. 33,36,37 p53 gene therapy experiences several failed clinical trials and it is still far from 100% efficacy. There are barriers that blocked gene therapy efficacy.…”

Section: Targeting P53mentioning

confidence: 99%

Manipulation of p53 Protein in Bladder Cancer Treatment

Mansor¹

2021

imjm

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Chemotherapy and radiotherapy are gold standard treatment for bladder cancer (BC) for over 50 years. The efficacy on early stage BC patients is virtuous. However, patients with aggressive cancer growth benefited less from the therapy. Aberrant p53 was found in more than 50% of high-grade BC patients. Therefore, targeting p53 in a subset of high-grade BC patients expressing aberrant p53 is a promising strategy. In this paper, p53 role in BC carcinogenesis is discussed. Followed by p53-targeting strategies in current BC treatment. Besides, p53-targeting strategies that have been implemented in other types of cancer and their potential to be adapted in BC will be deliberated. Although targeting p53 is promising, none of the strategies studied were successfully implemented in healthcare settings. Restoration of p53 as the guardian of the genome is an exciting area for translational research. It has potential to replace the genotoxic chemotherapy and radiotherapy, thus, eliminating the notorious painful sideeffects on a subset of high-grade BC patients. Searches were performed on PubMed and Google Scholar web using the keywords “bladder cancer” or “urothelial cancer” or “urothelial cell carcinoma” and “p53”. Only full papers of research articles and review papers were included for analysis. Papers were categorized as either p53 function, current treatment using p53 and future potential treatment using p53 for details analysis.

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Local Immune Stimulation by Intravesical Instillation of Baculovirus to Enable Bladder Cancer Therapy

Cited by 14 publications

References 50 publications

Immune Checkpoint Human Endogenous Retrovirus-H Long Terminal Repeat-Associating Protein 2 is Upregulated and Independently Predicts Unfavorable Prognosis in Bladder Urothelial Carcinoma

Immune Checkpoint Human Endogenous Retrovirus-H Long Terminal Repeat-Associating Protein 2 is Upregulated and Independently Predicts Unfavorable Prognosis in Bladder Urothelial Carcinoma

In vivo biodistribution and toxicity of intravesical administration of quantum dots for optical molecular imaging of bladder cancer

Manipulation of p53 Protein in Bladder Cancer Treatment

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