Effects of Acetylic Salicylic Acid and Pentoxifylline on the Efficacy of Intravesical BCG Therapy in Orthotopic Murine Bladder Cancer (Mb49)

GUNTHER, J-H.; Frambach, M.; Deinert, Irina; Brandau, Sven; Jocham, Dieter; Böhle, Andreas

doi:10.1097/00005392-199905000-00093

Cited by 5 publications

(5 citation statements)

References 13 publications

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“…A drug delivery system that could promote uptake into the urothelium and, thus, form a controlled release depot would be of great therapeutic benefit. Often, intravesical administration of chemotherapeutics occurs immediately after transurethral resection of the tumor for cases involving low grade noninvasive bladder cancer; however, tumor reimplatation and subsequent tumor regrowth typically occurs at these traumatized sites. , Recent and ongoing studies in our laboratory have demonstrated that paclitaxel-loaded HPGs effectively increased the drug partitioning into bladder tissue in an ex vivo model. Furthermore, it has been shown that anionic, carboxylate bearing polyamidoamine dendrimers are readily taken up by endocytosis .…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Characterization of Carboxylic Acid Conjugated, Hydrophobically Derivatized, Hyperbranched Polyglycerols as Nanoparticulate Drug Carriers for Cisplatin

Letchford

Heller

et al. 2010

Biomacromolecules

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Hyperbranched polyglycerols (HPGs) with hydrophobic cores and derivatized with methoxy poly(ethylene glycol) were synthesized and further functionalized with carboxylate groups to bind and deliver cisplatin. Low and high levels of carboxylate were conjugated to HPGs (HPG-C(8/10)-MePEG(6.5)-COOH(113) and HPG-C(8/10)-MePEG(6.5)-COOH(348)) and their structures were confirmed through NMR and FTIR spectroscopy and potentiometric titration. The hydrodynamic diameter of the HPGs ranged from 5-10 nm and the addition of COOH groups decreased the zeta potential of the polymers. HPG-C(8/10)-MePEG(6.5)-COOH(113) bound up to 10% w/w cisplatin, whereas HPG-C(8/10)-MePEG(6.5)-COOH(348) bound up to 20% w/w drug with 100% efficiency. Drug was released from HPG-C(8/10)-MePEG(6.5)-COOH(113) over 7 days at the same rate, regardless of the pH. Cisplatin release from HPG-C(8/10)-MePEG(6.5)-COOH(348) was significantly slower than HPG-C(8/10)-MePEG(6.5)-COOH(113) at pH 6 and 7.4, but similar at pH 4.5. Release of cisplatin into artificial urine was considerably faster than into buffer. Carboxylated HPGs demonstrated good biocompatibility, and drug-loaded HPGs effectively inhibited proliferation of KU-7-luc bladder cancer cells.

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Section: Resultsmentioning

confidence: 99%

Synthesis and Characterization of Carboxylic Acid Conjugated, Hydrophobically Derivatized, Hyperbranched Polyglycerols as Nanoparticulate Drug Carriers for Cisplatin

Letchford

Heller

et al. 2010

Biomacromolecules

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“…181920 In orthotopic bladder cancer models autoclaved BCG had no antitumor effect and the magnitude of the antitumor/immune response correlated with BCG viability. 21 In the clinical setting a direct correlation between therapeutic efficacy and BCG viability was observed. 4 While highlighting the relevance of BCG viability, no prior studies have provided mechanistic insight into how bacterial viability influences the tumor response.…”

Section: Discussionmentioning

confidence: 99%

587 Loss of BCG Viability Adversely Affects the Direct Response of Urothelial Carcinoma Cells to BCG Exposure

Zhang¹,

Chen²,

Cao³

et al. 2013

Journal of Urology

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INTRODUCTION-The attenuated mycobacterium Bacille Calmette Guerin (BCG) is widely utilized as intravesical "immunotherapy" for the treatment of non-muscle invasive urothelial carcinoma. Previous studies have demonstrated that in both the laboratory and clinical setting, BCG viability is a variable that correlates with anti-tumor efficacy. This study evaluated how loss of BCG viability impacted a number of molecular and phenotypic intermediate endpoints that characterize, and/or contribute to, the direct effect of BCG on Urothelial carcinoma (UC) cells.

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“…A randomized clinical trial showed that though mitomycin C improved therapeutic efficacy of BCG, it also increased toxicity among mid and high risk NMIBC patients, which mitigate its chance to be further explored as a safe intervention [91]. In a murine model, acetylic salicylic acid and pentoxifylline seem to be effective in improving BCG efficacy [92]. In a systemic meta-analysis, it was concluded that compared to BCG alone, the synergistic effect of intravesical BCG and chemotherapy improved recurrence free survival, overall survival and disease specific survival with significantly decreased rate of fever, irritative symptoms and hematuria therapy among NMIBC patients [93].…”

Section: Intravesical Immunotherapy With Bcgmentioning

confidence: 99%

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

Shih¹,

Chen²,

Chang³

et al. 2021

Aging and disease

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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 lowgrade (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 abovementioned approaches, we have comprehensively analyzed therapeutic journey from traditional to regenerative interventions for the treatment of NMIBC.

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Effects of Acetylic Salicylic Acid and Pentoxifylline on the Efficacy of Intravesical BCG Therapy in Orthotopic Murine Bladder Cancer (Mb49)

Abstract: The efficacy of BCG therapy in murine orthotopic bladder cancer is dependent on BCG viability and is not compromised by ASA or POF. Clinical trials to evaluate the efficacy of routine ASA or POF to reduce BCG side effects in patients, using self-assessment criteria, should be initiated.

Cited by 5 publications

References 13 publications

Synthesis and Characterization of Carboxylic Acid Conjugated, Hydrophobically Derivatized, Hyperbranched Polyglycerols as Nanoparticulate Drug Carriers for Cisplatin

Synthesis and Characterization of Carboxylic Acid Conjugated, Hydrophobically Derivatized, Hyperbranched Polyglycerols as Nanoparticulate Drug Carriers for Cisplatin

587 Loss of BCG Viability Adversely Affects the Direct Response of Urothelial Carcinoma Cells to BCG Exposure

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

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