Interferon-a2b Reduces Neo-Microvascular Density in the ‘Normal’ Urothelium Adjacent to the Tumor after Transurethral Resection of Superficial Bladder Carcinoma

Abstract

Backround: As angiogenesis represents one of the hallmarks of cancer we investigated whether intravesicaly administered interferon-a (IFN-a2b) reduces neo-angiogenesis in the ‘normal’ urothelium adjacent to the tumor in patients with superficial bladder carcinoma after complete transurethral resection (TUR) of the tumor. Patients and Methods: In the present study 47 patients after TUR of the tumor were examined. 10 patients (group A) received no further treatment (control group); 37 patients (group B) received intravesical treatment with IFN-a2b. The instillations started within 7 days after TUR, were performed weekly for 2 months, twice a month for the next 4 months, and thereafter monthly for 6 more months. Cold cup biopsies were taken before TUR of the transitional cell carcinoma (TCC): from the tumor (T), near tumor (NT) and from normal epithelium (N). Cold cup biopsies ‘near tumor’, were also taken during follow-up cystoscopy (C1, C2, and C3) 2, 6, and 12 months after TUR, respectively. Angiogenesis was estimated by counting the microvessels detected with CD31 immunostaining. Results: Significant differences of microvascular density (MVD) between patients of group A and B appear after TUR (p < 0.005, Kruskal-Wallis and Wilcoxon test). The MVD difference was maximal 6 months after TUR (C2_A-C2_B, second cystoscopy) and measured at 12.17 microvessels/ mm² (26.2%). Conclusion: Our results show that the intravesical administration of IFN-a2b after TUR significantly decreases the angiogenic potential of the ‘healthy’ urothelium adjacent to the tumor in patients with TCC. This observation could possibly explain, to a certain extent, the mechanism by which IFN-a2b reduces the recurrence rate of primary TCC.

Detection of Interleukin-33 in Serum and Carcinoma Tissue from Patients with Hepatocellular Carcinoma and its Clinical Implications

“…11 IFN-α can also effectively inhibit vascular endothelial cell proliferation and migration. 12 These results suggest that antiangiogenesis is the main target of IFN-α therapy in HCC.…”

Bladder Cancer Immunotherapy: BCG and Beyond

“…Interestingly, it has also been demonstrated that an optimal biologic dose with higher frequency, rather than maximal tolerated dose, produced the most significant decreases in angiogenesis. Significantly decreased angiogenesis has also been documented in human urothelium during and after IFN- α 2b treatment following transurethral resection of superficial bladder tumors [28]. …”

Perivascular epithelioid cell tumor (PEComa) of the ascending colon: the implication of IFN-α2b treatment

“…IFN-α2b was also used for other solid tumors. It reduced neomicrovascular density in the normal urothelium adjacent to the tumor after transurethral resection of superficial bladder carcinoma19). Outpatient treatment with subcutaneous IFN-α2b plus interleukin-2 treatment for metastatic renal cell cancer was also reported.…”