Treatment of Superficial Bladder Tumors: Achievements and Needs

Kurth, K. H.; Bouffioux, C; Sylvester, Richard; Meijden, A.P.M. van der; Oosterlinck, Willem; Brausi, Maurizio

doi:10.1159/000052386

Cited by 108 publications

(58 citation statements)

References 63 publications

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“…Among them, intravesical administration of BCG is highly effective in reducing the recurrence rate and altering the progression rate of the disease with an increased survival rate [4]. In fact, adjuvant intravesical BCG therapy after surgical resection has become established therapy for superficial bladder cancers, resulting in ≈ 40% reduction in cancer recurrence [4,5]. However, its benefits are sometimes outweighed by its severe sideeffects: cystitis occurs in 90% of patients and other potential adverse effects (fever, allergic reactions, sepsis, etc.)…”

Section: Introductionmentioning

confidence: 99%

Synergistic potentiation of interferon activity with maitake mushroom d‐fraction on bladder cancer cells

et al. 2010

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OBJECTIVETo examine whether the combination of interferon (IFN)‐α and maitake mushroom D‐fraction (PDF), a bioactive mushroom extract, might potentiate the anticancer activity of IFN‐α in bladder cancer T24 cells in vitro.MATERIALS AND METHODSEffects of recombinant IFN‐α2b (0–50 000 IU/mL), PDF (0–700 µg/mL), or their combinations were assessed on T24 cell growth at 72 h. Cell cycle analysis and assays for double‐stranded DNA‐dependent protein kinase (DNA‐PK) were performed to explore possible antiproliferative mechanism of these agents.RESULTSIFN‐α2b was able to induce a significant (≈50%) growth reduction at 20 000 IU/mL, which further declined to ≈66% at 50 000 IU/mL. PDF had no effects up to 200 µg/mL, but there was an ≈20% and ≈53% growth reduction at 400 and 700 µg/mL, respectively. When the varying concentrations of IFN‐α2b and PDF were combined, 10 000 IU/mL of IFN‐α2b combined with 200 µg/mL of PDF resulted in an ≈75% growth reduction. This was accompanied by a G1 cell cycle arrest, shown by cell cycle analysis. Concurrently, DNA‐PK activity in IFN‐α2b/PDF‐treated cells was almost three‐fold higher than controls.CONCLUSIONSThe combination of IFN‐α2b (10 000 IU/mL) and PDF (200 µg/mL) reduced growth by ≈75% in T24 cells. This appears to be due to a synergistic potentiation of these two agents, inducing a G1 arrest with DNA‐PK activation. Therefore, the IFN‐α2b/PDF combination could trigger DNA‐PK activation that may act on the cell cycle to cease cancer cell growth.

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Section: Introductionmentioning

confidence: 99%

Synergistic potentiation of interferon activity with maitake mushroom d‐fraction on bladder cancer cells

et al. 2010

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“…Bladder cancer, clinically diagnosed as a superficial tumor, is generally treated with a transurethral resection due to its relatively indolent nature and low malignant potential. However, this superficial carcinoma often recurs and invades the muscle after the initial treatment; such progression is associated with a high risk of subsequent metastasis and poor survival (7,8). Various growth factors and molecules have been reported to be associated with tumor growth, progression, and survival in bladder cancer (9,10 thought to be one of the most useful prognostic markers for disease development, grade, recurrence-free survival, and overall survival (11 -13).…”

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confidence: 99%

Lymphangiogenesis and Angiogenesis in Bladder Cancer: Prognostic Implications and Regulation by Vascular Endothelial Growth Factors-A, -C, and -D

Miyata

Kanda

Ohba

et al. 2006

Clinical Cancer Research

113

119

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Purpose: Lymph vessel density (LVD) and microvessel density (MVD) correlate with the malignant potential of tumors and patient survival. Vascular endothelial growth factors (VEGF)-A, VEGF-C, and VEGF-D could modulate LVD and MVD. We investigated the clinical and prognostic significance of LVD and MVD on lymphangiogenic and angiogenic function of VEGF-A,VEGF-C, and VEGF-D in human bladder cancer. Experimental Design: We reviewed tissue samples from patients with nonmetastatic bladder cancer who had undergone transurethral resections (n = 126). The densities of D2-40-positive vessels (LVD) and CD34-positive vessels (MVD) were measured by a computer-aided image analysis system. Expression of VEGF-A, VEGF-C, and VEGF-D was examined by immunohistochemistry; survival analyses and their independent roles were investigated using multivariate analysis models. Results: LVD was associated with tumor grade but not with pTstage. LVD was associated with metastasis-free survival (log rank P = 0.039), but was not an independent prognostic factor. Although MVD affected survival, the combination of high LVD and high MVD in tumors was an independent predictor of metastasis-free survival. Although VEGF-C expression was positively associated with both LVD and MVD,VEGF-D was associated only with LVD.VEGF-A expression was associated with MVD in univariate analysis, however, it was not an independent factor. Conclusions: Lymphangiogenesis and angiogenesis influence metastasis-free survival, and are regulated by VEGF-C and/or VEGF-D. Our results suggest that LVD and MVD are useful tools for the selection of postoperative management and treatment strategies in patients with bladder cancer.Metastatic dissemination of the primary tumor is an important factor that negatively affects the prognosis in most malignancies and neovascularization (angiogenesis) plays a critical role in tumor growth and systemic dissemination of cancer cells (1). As such, much attention has been focused on the pathologic significance and detailed mechanism of the vascular system and angiogenesis in cancers. In addition to dissemination of cancer cells via the bloodstream, the lymphatic system is also thought to play an important role in tumor cell dissemination.Indeed, metastatic spread to regional lymph nodes is an early step in the systemic dissemination of tumors, and lymph node metastasis is generally associated with poor survival (2, 3). However, the clinical significance of the de novo formation of lymphatic capillaries (lymphangiogenesis) and its regulation in cancer remains unclear, largely because specific endothelial markers for lymphatic vessels are unknown and lymphatic vessels cannot be detected in human cancer tissues (4). In recent years, several new specific antibodies for lymphatic endothelial cells have been developed and used to investigate the clinical and pathologic significance of lymphangiogenesis in various cancers (5).Bladder cancer is the second most common malignant tumor of the urogenital region. This tumor is associated with fr...

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“…In these patients, the benefits of treatment outweigh the burden of side effects. Moreover, BCG seems to exert a better antitumour effect in CIS and high-grade cancer (Melekos et al, 1993;Kurth et al, 2000).…”

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confidence: 99%

Role of urothelial cells in BCG immunotherapy for superficial bladder cancer

2004

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Intravesical instillation of Bacillus Calmette-Guérin (BCG) is used for the treatment of superficial bladder cancer, both to reduce the recurrence rate of bladder tumour and to diminish the risk of progression. Since its first therapeutic application in 1976, major research efforts have been directed to decipher the exact mechanism of action of the BCG-associated antitumour effect. Bacillus Calmette-Guérin causes an extensive local inflammatory reaction in the bladder wall. Of this, the massive appearance of cytokines in the urine of BCG-treated patients stands out. Activated lymphocytes and macrophages are the most likely sources of these cytokines, but at present other cellular sources such as urothelial tumour cells cannot be ruled out. Bacillus Calmette-Guérin is internalised and processed both by professional antigen-presenting cells and urothelial tumour cells, resulting in an altered gene expression of these cells that accumulates in the presentation of BCG antigens and secretion of particular cytokines.

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Treatment of Superficial Bladder Tumors: Achievements and Needs

Cited by 108 publications

References 63 publications

Synergistic potentiation of interferon activity with maitake mushroom d‐fraction on bladder cancer cells

Synergistic potentiation of interferon activity with maitake mushroom d‐fraction on bladder cancer cells

Lymphangiogenesis and Angiogenesis in Bladder Cancer: Prognostic Implications and Regulation by Vascular Endothelial Growth Factors-A, -C, and -D

Role of urothelial cells in BCG immunotherapy for superficial bladder cancer

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