The Dose-Response Relationship of bacillus Calmette-Guérin and Urothelial Carcinoma Cell Biology

Shah, Gopitkumar; Zhang, Guangjian; Chen, Fanghong; Cao, Yanli; Kalyanaraman, Balaraman; See, William A.

doi:10.1016/j.juro.2015.11.073

Cited by 11 publications

(6 citation statements)

References 28 publications

(25 reference statements)

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“…Mathematical modelling indicated that increased BCG cfu can be beneficial and that reducing the number of instillations may be efficacious [ 29 ]. Shah et al demonstrated that a higher BCG Tice cfu (4 × 10 7 cfu/0.1 mL) reduced tumor growth in murine bladders after three instillations [ 30 ]. We hypothesize that reducing the number of instillations when using higher doses of BCG should reduce associated side-effects and dampening of the immune response.…”

Section: Introductionmentioning

confidence: 99%

Intravesical High Dose BCG Tokyo and Low Dose BCG Tokyo with GMCSF+IFN α Induce Systemic Immunity in a Murine Orthotopic Bladder Cancer Model

et al. 2021

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This study evaluates a short therapy schedule for bladder cancer using BCG Tokyo. BCG Tokyo was evaluated in vitro using bone marrow derived dendritic cells, neutrophils, RAW macrophages and the murine bladder cancer cell line, MB49PSA, and compared to other BCG strains. BCG Tokyo > BCG TICE at inducing cytokine production. In vivo, high dose (1 × 107 colony forming units (cfu)) and low dose (1 × 106 cfu) BCG Tokyo with and without cytokine genes (GMCSF + IFNα) were evaluated in C57BL/6J mice (n = 12–16 per group) with orthotopically implanted MB49PSA cells. Mice were treated with four instillations of cytokine gene therapy and BCG therapy. Both high dose BCG alone and low dose BCG combined with cytokine gene therapy were similarly effective. In the second part the responsive groups, mice (n = 27) were monitored by urinary PSA analysis for a further 7 weeks after therapy cessation. More mice were cured at day 84 than at day 42 confirming activation of the immune system. Cured mice resisted the re-challenge with subcutaneous tumors unlike naïve, age matched mice. Antigen specific T cells recognizing BCG, HY and PSA were identified. Thus, fewer intravesical instillations, with high dose BCG Tokyo or low dose BCG Tokyo with GMCSF + IFNα gene therapy, can induce effective systemic immunity.

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Section: Introductionmentioning

confidence: 99%

Intravesical High Dose BCG Tokyo and Low Dose BCG Tokyo with GMCSF+IFN α Induce Systemic Immunity in a Murine Orthotopic Bladder Cancer Model

et al. 2021

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“…The level of HMGB1 release significantly correlated with BCG dose and exposure time in T24 and 253J cell lines. 37 Although our study revealed some associations between HMGB1 expression and prognosis of BUC, the precise mechanisms of HMGB1 involved in oncogenic processes of BUC still requires further study in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 68%

Overexpression of high mobility group box 1 contributes to progressive clinicopathological features and poor prognosis of human bladder urothelial carcinoma

Huang

Zhao

et al. 2018

OTT

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BackgroundHigh mobility group box 1 (HMGB1), a versatile protein with intranuclear and extracellular functions, plays an important role in a variety of human cancers. However, the clinical/prognostic significance of HMGB1 expression in human bladder urothelial carcinoma (BUC) remains unclear. The aim of this study was to investigate the HMGB1 expression in human BUC with regard to its clinical and prognostic significance.Patients and methodsHMGB1 mRNA and protein expressions in tumor and paired normal bladder tissues were detected in 20 BUC cases by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. HMGB1 protein expression in 165 primary BUC tissues was evaluated by immunohistochemistry (IHC), and its correlations with clinicopathological characteristics and prognosis were also analyzed. Student’s t-test, χ2 test, Kaplan–Meier plots, and Cox proportional hazard regression model were performed to analyze the data.ResultsBy using qRT-PCR and Western blot, the upregulated expression of HMGB1 mRNA and protein was detected in BUC, compared with paired normal tissue (P<0.05). By using IHC, high HMGB1 expression was examined in 84 of 165 (51.0%) BUC cases. High HMGB1 expression was significantly correlated with poorer differentiation and higher T and N classification (all P<0.05). Univariate analysis showed that high HMGB1 expression was significantly associated with a shortened patients’ overall survival (OS) and disease-free survival (DFS; both P<0.001). In different subgroups of BUC patients, HMGB1 expression was a prognostic factor in patients with different histological grades or T classification (all P<0.05), pN− (both P<0.001) for OS and DFS, and pT1/pN− (P<0.05) for OS. HMGB1 expression, as well as pT and pN status, was an independent prognostic factor for both OS (P=0.001, hazard ratio [HR] =2.973, 95% confidence interval [CI] =1.550–5.704) and DFS (P<0.001, HR =3.019, 95% CI =1.902–4.792) in multivariate analysis.ConclusionOverexpression of HMGB1 may be a new independent molecular marker for the poor prognosis of patients with BUC.

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“…The optimal BCG dose remains a controversial subject [ 14 , 16 ]. It has been demonstrated in vitro that the BCG dose has a direct impact on cellular response and relative anti-tumor effect [ 17 ]. To this end, it may be advantageous to incorporate higher doses.…”

Section: Discussionmentioning

confidence: 99%

Vertebral Osteomyelitis Secondary to Bacillus Calmette-Guérin Instillation Therapy for Transitional Cell Carcinoma In Situ

Jaber

Samiullah

Surti

2021

Cureus

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Transitional cell carcinoma is the sixth most common cancer among men and the 17th most common cancer in women. The treatment methods for the condition range from noninvasive chemotherapy to more invasive procedures like cystectomy and complete transurethral resection of bladder tumor (TURBT) followed by intravesical Bacillus Calmette-Guérin (BCG) therapy (BCG). Intravesical BCG treatment is known to be effective as it is associated with increased survivability and long-term benefits, especially in early-stage, minimally-invasive disease. It is generally considered to be safe, even though some adverse reactions have been described. Vertebral osteomyelitis secondary to intravesical BCG therapy is a rare complication but one that has been reported in the literature. Although our patient had multiple comorbidities, including a previous vertebral compression fracture prior to treatment, complications from intravesical BCG treatment should always be considered in the differential. Further multi-center retrospective studies are needed to better ascertain its true risk given its increasing use as a treatment modality for transitional cell carcinoma.

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The Dose-Response Relationship of bacillus Calmette-Guérin and Urothelial Carcinoma Cell Biology

Abstract: Bacillus Calmette-Guérin dose has a direct impact on urothelial carcinoma cell biology. Increased dose intensity, particularly in nonresponders, may represent a strategy to increase bacillus Calmette-Guérin treatment efficacy.

Cited by 11 publications

References 28 publications

Intravesical High Dose BCG Tokyo and Low Dose BCG Tokyo with GMCSF+IFN α Induce Systemic Immunity in a Murine Orthotopic Bladder Cancer Model

Intravesical High Dose BCG Tokyo and Low Dose BCG Tokyo with GMCSF+IFN α Induce Systemic Immunity in a Murine Orthotopic Bladder Cancer Model

Overexpression of high mobility group box 1 contributes to progressive clinicopathological features and poor prognosis of human bladder urothelial carcinoma

Vertebral Osteomyelitis Secondary to Bacillus Calmette-Guérin Instillation Therapy for Transitional Cell Carcinoma In Situ

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