Predictive Value of Urinary Interleukin-8 Cutoff Point for Recurrences After Transurethral Resection Plus Induction Bacillus Calmette-Guérin Treatment in Non–Muscle-Invasive Bladder Tumors

Sağnak, Levent; Ersoy, Hamit; Özok, Uğur; Senturk, Bugra; Erçil, Hakan; Bahar, Gül; Öztürk, Evrim

doi:10.3816/cgc.2009.n.016

Cited by 30 publications

(22 citation statements)

References 30 publications

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“…Two patients experienced a peak of IL-8 at 4 weeks, including 1 patient receiving 10 mg MMC and1/2 dose BCG and 1 patient receiving 40 mg MMC and full dose BCG (Figure 1). However, 9 (75%) patients experienced the highest IL-8 measurement at the 6th week dose, which is consistent with previous observations in BCG monotherapy (17). …”

Section: Resultssupporting

confidence: 92%

Sequential Intravesical Mitomycin plus Bacillus Calmette–Guérin for Non–Muscle-Invasive Urothelial Bladder Carcinoma: Translational and Phase I Clinical Trial

Svatek

Zhao

Morales

et al. 2015

Clinical Cancer Research

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Purpose To determine the safety and toxicities of sequential MMC + BCG in patients with non-muscle invasive bladder cancer (NMIBC) and explore evidence for potentiation of BCG activity by MMC. Experimental Design A 3+3 phase I dose-escalation trial of six weekly treatments was conducted in patients with NMIBC. MMC (10, 20 or 40 mg) was instilled intravesically for 30 minutes, followed by a 10-minute washout with gentle saline irrigation and then instillation of BCG (half or full strength) for 2 hours. Urine cytokines were monitored and compared to levels in a control cohort receiving BCG only. Murine experiments were carried out as described previously. Results Twelve patients completed therapy including 3 patients receiving full doses. The regimen was well tolerated with no treatment-related dose limiting toxicities. Urinary frequency and urgency, and fatigue were common. Eleven (91.7%) patients were free of disease at a mean (range) follow-up of 21.4 (8.4-27.0) months. Median post-treatment urine concentrations of IL-2, IL-8, IL-10 and TNF-α increased over the 6-week treatment period. A greater increase in post-treatment urinary IL-8 during the 6-week period was observed in patients receiving MMC + BCG compared to patients receiving BCG monotherapy. In mice, intravesical MMC + BCG skewed tumor-associated macrophages (TAMs) towards a beneficial M1 phenotype. Conclusions Instillation of sequential MMC + BCG is safe and tolerable up to 40 mg MMC plus full strength BCG. This approach could provide improved antitumor activity over BCG monotherapy by augmenting beneficial M1 TAMs.

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Section: Resultssupporting

confidence: 92%

Sequential Intravesical Mitomycin plus Bacillus Calmette–Guérin for Non–Muscle-Invasive Urothelial Bladder Carcinoma: Translational and Phase I Clinical Trial

Svatek

Zhao

Morales

et al. 2015

Clinical Cancer Research

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“…Increased urine IL-8 levels are associated with increased disease stage 22 and recurrence. 23 The other 2 biomarkers in our 3-biomarker signature (PAI-1 and MMP-9) were reported in BCa. Hudson and McReynolds noted that noninvasive and invasive human BCa cell lines produce PAI-1, 24 while increased PAI-1 gene and protein expression in tissue and plasma was observed in patients with BCa and a poor prognosis.…”

Section: Discussionmentioning

confidence: 82%

Multiplex Protein Signature for the Detection of Bladder Cancer in Voided Urine Samples

Rosser

Ross²,

Chang

et al. 2013

Journal of Urology

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Purpose Accurate urine assays for bladder cancer detection would benefit patients and health care systems. Through extensive genomic and proteomic profiling of urine components we previously identified a panel of 8 biomarkers that can facilitate the detection of bladder cancer in voided urine samples. In this study we confirmed this diagnostic molecular signature in a diverse multicenter cohort. Materials and Methods We performed a case-control, phase II study in which we analyzed voided urine from 102 subjects with bladder cancer and 206 with varying urological disorders. The urine concentration of 8 biomarkers (IL-8, MMP and 10, PAI-1, VEGF, ANG, CA9 and APOE) was assessed by enzyme-linked immunosorbent assay. Diagnostic performance of the panel of tested biomarkers was evaluated using ROCs and descriptive statistical values, eg sensitivity and specificity. Results Seven of the 8 urine biomarkers were increased in subjects with bladder cancer relative to those without bladder cancer. The 7 biomarkers were assessed in a new model, which had an AUROC of 0.88 (95% CI 0.84–0.93), and 74% sensitivity and 90% specificity. In contrast, the sensitivity of voided urine cytology and the UroVysion® cytogenetic test in this cohort was 39% and 54%, respectively. Study limitations include analysis performed on banked urine samples and the lack of voided urine cytology and cytogenetic test data on controls. Conclusions The study provides further evidence that the reported panel of diagnostic biomarkers can reliably achieve the noninvasive detection of bladder cancer with higher sensitivity than currently available urine based assays.

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“…Urinary levels of immunological mediators during treatment indicated that cytokines such as IL-8 and IL-2 could be predictors of BCG outcome [21][22][23][24][25][26] .…”

mentioning

confidence: 99%

IL-4 and TNF-α Polymorphisms Are Associated with Risk of Multiple Superficial Tumors or Carcinoma in situ Development

Lima

Silva

Amaro³

et al. 2011

Urol Int

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Introduction: This study evaluates the influence of clinicopathological characteristics, bacillus Calmette-Guérin (BCG) therapeutic schedule [maintenance (mBCG) or induction (iBCG)], and TNF-α and IL-4 polymorphisms on the outcome of non-muscle-invasive bladder cancer patients treated with BCG. Material and Methods: DNA was extracted from 125 bladder cancer patients treated with BCG; TNF-308G/A and IL4-590C/T polymorphisms were genotyped. Results: The TNF-308A allele carriers had an increased risk of developing multiple tumors (OR: 2.80, p = 0.031). However, IL4-590 T carriers also had an increased risk of developing multiple and carcinoma in situ tumors (OR: 2.52, p = 0.033). For these polymorphisms, no association was found with BCG treatment outcome. When treated with iBCG, patients with multiple tumors had shorter recurrence-free survival (RFS) compared with those with a single tumor (p = 0.004); nevertheless, patients with multifocal tumors have improved RFS when treated with mBCG. Conclusions: Overall, the results suggest that multiple tumors and/or carcinoma in situ development are associated with the IL4-590C/T and TNF-308G/A polymorphisms, and emphasize the effectiveness of the mBCG schedule.

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Predictive Value of Urinary Interleukin-8 Cutoff Point for Recurrences After Transurethral Resection Plus Induction Bacillus Calmette-Guérin Treatment in Non–Muscle-Invasive Bladder Tumors

Cited by 30 publications

References 30 publications

Sequential Intravesical Mitomycin plus Bacillus Calmette–Guérin for Non–Muscle-Invasive Urothelial Bladder Carcinoma: Translational and Phase I Clinical Trial

Sequential Intravesical Mitomycin plus Bacillus Calmette–Guérin for Non–Muscle-Invasive Urothelial Bladder Carcinoma: Translational and Phase I Clinical Trial

Multiplex Protein Signature for the Detection of Bladder Cancer in Voided Urine Samples

IL-4 and TNF-α Polymorphisms Are Associated with Risk of Multiple Superficial Tumors or Carcinoma in situ Development

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