Urinary Cytokines Reflecting the Immunological Response in the Urinary Bladder to Biological Response Modifiers: Their Practical Use

Schamhart, D. H. J.; Boer, Elizabeth C. de; Reijke, T.M. De; Kurth, K. H.

doi:10.1159/000052388

Cited by 35 publications

(29 citation statements)

References 72 publications

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“…3 Despite its worldwide acceptance for the treatment of superficial bladder cancer, and many mechanistic studies performed, the antitumor effector mechanism remains incompletely defined. BCG therapy results in a massive local immune response characterized by the induced cytokine expression in the bladder tissue and urine, 4 and an influx of granulocytes and mononuclear cells into the bladder wall. 5,6 A proinflammatory, Th-1 cytokine (eg, interleukin 2 [IL-2], IL-12, interferon ␥ [IFN-␥]) response typically predominates following BCG stimulation, and the generation of a Th-1 cytokine response is often associated with a favorable response.…”

Section: Introductionmentioning

confidence: 99%

Neutrophil stimulation with Mycobacterium bovis bacillus Calmette-Guérin (BCG) results in the release of functional soluble TRAIL/Apo-2L

Kemp

Ludwig

Earel

et al. 2005

Blood

112

148

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Mycobacterium bovis bacillus CalmetteGué rin (BCG) has been used to treat bladder cancer for almost 30 years; however, the effector mechanism of the BCGinduced antitumor response remains enigmatic. Most BCG research has focused on the mononuclear-cell infiltrate, but growing evidence supports a role for neutrophils in the antitumor response. Previously, we demonstrated increased urinary tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL/ Apo-2L) levels from BCG-responsive patients compared to nonresponders. Interestingly, neutrophils isolated from the urine expressed TRAIL/Apo-2L, leading us to investigate the neutrophil response to BCG. BCG-stimulated neutrophils expressed surface-bound and released functional soluble TRAIL/Apo-2L. Whereas neither interferon ␣ (IFN-␣) nor IFN-␥ directly induced TRAIL/Apo2L expression by neutrophils, IFN-␣ did stimulate TRAIL gene transcription, and IFN-primed neutrophils contained and released more TRAIL/ Apo-2L after BCG stimulation than did unprimed neutrophils. In unstimulated neutrophils TRAIL/Apo-2L was present predominantly in the azurophilic granules and plasma-membrane-enriched/ secretory-granule fraction. Finally, we observed that killed BCG, Toll-like receptor 2 (TLR2) and TLR4 agonists, and an M tuberculosis cell-wall fraction were each capable of inducing the release of soluble TRAIL/Apo-2L from neutrophils. These results further characterize the potential role neutrophils may play in initiating the antitumor response described with BCG treatment for superficial bladder cancer. IntroductionUrothelial carcinoma of the bladder accounts for approximately 5% of all cancer deaths in humans. 1 A majority of the tumors (70%-80%) are superficial at diagnosis and, after local surgical therapy, have a high rate of local recurrence (70%) and progression (30%). Thus, patients require lifelong medical follow-up examinations with inspections of their bladders, and additional surgical resection and prophylactic treatments are typically needed in the presence of recurrence. Current treatments extend time to recurrence but do not alter disease survival. The resulting economic burden on the US health care system is enormous, reaching over $4 billion annually. Indeed, as measured on the basis of cumulative per patient cost from diagnosis until death, the cost to treat bladder cancer exceeds all other forms of human cancer.In 1921, bacillus Calmette-Guérin (BCG) was isolated from Mycobacterium bovis, a mycobacterium causing bovine tuberculosis. 2 Since 1976, BCG has been used with increasing success for the treatment of superficial bladder cancer and has become the treatment of choice for this tumor entity. 3 Despite its worldwide acceptance for the treatment of superficial bladder cancer, and many mechanistic studies performed, the antitumor effector mechanism remains incompletely defined. BCG therapy results in a massive local immune response characterized by the induced cytokine expression in the bladder tissue and urine, 4 and an influx of granulocytes and mononu...

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Section: Introductionmentioning

confidence: 99%

Neutrophil stimulation with Mycobacterium bovis bacillus Calmette-Guérin (BCG) results in the release of functional soluble TRAIL/Apo-2L

Kemp

Ludwig

Earel

et al. 2005

Blood

112

148

View full text Add to dashboard Cite

show abstract

“…Following initial diagnosis and tumor resection, as many as 70% of the noninvasive tumors recur and 5-30% of the recurrent tumors progress (Brown, 2000;Burchardt et al, 2000). As a result, patients require regular followup examinations, which are associated with a significant impact on health-care resources and the patient's quality of life (Schamhart et al, 2000). Unfortunately, the means by which TCC is detected, either initially or during routine follow-up, have not changed over the last six decades, invariably requiring invasive procedures such as cystoscopy, uretheroscopy and biopsies.…”

Section: Introductionmentioning

confidence: 99%

Molecular analysis of transitional cell carcinoma using cDNA microarray

et al. 2003

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“…La inmunoterapia con BCG estimula una reacción inmune local masiva caracterizada por la expresión inducida de citoquinas en la orina y tejido vesical y una migración de monocitos y granulocitos, así como células mononucleares a la pared vesical 10 . Se produce así la activación de distintas líneas celulares que lisan el tumor por medio de la producción de perforinas.…”

Section: Discussionunclassified

Espondilodiscitis con absceso intrarraquídeo y paraespinal causada por bacilo de Calmette-Guérin (BCG)

Lara-Oya

Ramírez-Taboada

Arenas-Miras

et al. 2015

Rev. chil. infectol.

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Urinary Cytokines Reflecting the Immunological Response in the Urinary Bladder to Biological Response Modifiers: Their Practical Use

Cited by 35 publications

References 72 publications

Neutrophil stimulation with Mycobacterium bovis bacillus Calmette-Guérin (BCG) results in the release of functional soluble TRAIL/Apo-2L

Neutrophil stimulation with Mycobacterium bovis bacillus Calmette-Guérin (BCG) results in the release of functional soluble TRAIL/Apo-2L

Molecular analysis of transitional cell carcinoma using cDNA microarray

Espondilodiscitis con absceso intrarraquídeo y paraespinal causada por bacilo de Calmette-Guérin (BCG)

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