Effect of Mitomycin, Bevacizumab, and 5-Fluorouracil to Inhibit Urethral Fibrosis in a Rabbit Model

Üyetürk, Uğur; Gücük, Adnan; Fırat, Tülin; Kemahlı, Eray; Kükner, Aysel; Özyalvaçlı, Mehmet Emin

doi:10.1089/end.2014.0420

Cited by 9 publications

(5 citation statements)

References 27 publications

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“…A score of zero indicated no fibrosis, one indicated mild fibrosis (less than 25 %), two indicated moderate fibrosis (25-50 %) and three indicated severe fibrosis (more than 50 %). 25 The histological examination was performed without knowing the group to which the sample belonged.…”

Section: Histologymentioning

confidence: 99%

Comparison of Poly(l-lactide-co-ɛ-caprolactone) and Poly(trimethylene carbonate) Membranes for Urethral Regeneration: AnIn VitroandIn VivoStudy

Sartoneva

Nordback

Haimi

et al. 2018

Tissue Engineering Part A

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Urethral defects are normally reconstructed using a patient's own genital tissue; however, in severe cases, additional grafts are needed. We studied the suitability of poly(l-lactide-co-ɛ-caprolactone) (PLCL) and poly(trimethylene carbonate) (PTMC) membranes for urethral reconstruction in vivo. Further, the compatibility of the materials was evaluated in vitro with human urothelial cells (hUCs). The attachment and viability of hUCs and the expression of different urothelial cell markers (cytokeratin 7, 8, 19, and uroplakin Ia, Ib, and III) were studied after in vitro cell culture on PLCL and PTMC. For the in vivo study, 32 rabbits were divided into the PLCL (n = 15), PTMC (n = 15), and control or sham surgery (n = 2) groups. An oval urethral defect 1 × 2 cm in size was surgically excised and replaced with a PLCL or a PTMC membrane or urethral mucosa in sham surgery group. The rabbits were followed for 2, 4, and 16 weeks. After the follow-up, urethrography was performed to check the patency of the urethra. The defect area was excised for histological examination, where the epithelial integrity and structure, inflammation, and fibrosis were observed. There was no notable difference on hUCs attachment on PLCL and PTMC membranes after 1 day of cell seeding, further, the majority of hUCs were viable and maintained their urothelial phenotype on both biomaterials. Postoperatively, animals recovered well, and no severe strictures were discovered by urethrography. In histological examination, the urothelial integrity and structure developed toward a normal urothelium with only mild signs of fibrosis or inflammation. According to these results, PLCL and PTMC are both suitable for reconstructing urethral defects. There were no explicit differences between the PLCL and PTMC membranes. However, PTMC membranes were more flexible, easier to suture and shape, and developed significant epithelial integrity.

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Section: Histologymentioning

confidence: 99%

Comparison of Poly(l-lactide-co-ɛ-caprolactone) and Poly(trimethylene carbonate) Membranes for Urethral Regeneration: AnIn VitroandIn VivoStudy

Sartoneva

Nordback

Haimi

et al. 2018

Tissue Engineering Part A

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“…Bevacizumab is a VEGF inhibitor and antiangiogenic agent that is clinically used to treat some malignant tumors and chronic inflammatory diseases [22,23]. VEGF inhibition has also shown anti-fibrotic effects in experimental models of urethral, hepatic, articular and spinal epidural fibrosis [24][25][26][27]. In this context, we hypothesized that the inhibition of VEGF using bevacizumab could help to alleviate chagasic cardiomyopathy.…”

Section: Introductionmentioning

confidence: 99%

Vascular Growth Factor Inhibition with Bevacizumab Improves Cardiac Electrical Alterations and Fibrosis in Experimental Acute Chagas Disease

Nisimura,

Ferreira,

Coelho

et al. 2023

Biology

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Chagas disease (CD) caused by Trypanosoma cruzi is a neglected illness and a major reason for cardiomyopathy in endemic areas. The existing therapy generally involves trypanocidal agents and therapies that control cardiac alterations. However, there is no treatment for the progressive cardiac remodeling that is characterized by inflammation, microvasculopathy and extensive fibrosis. Thus, the search for new therapeutic strategies aiming to inhibit the progression of cardiac injury and failure is necessary. Vascular Endothelial Growth Factor A (VEGF-A) is the most potent regulator of vasculogenesis and angiogenesis and has been implicated in inducing exacerbated angiogenesis and fibrosis in chronic inflammatory diseases. Since cardiac microvasculopathy in CD is also characterized by exacerbated angiogenesis, we investigated the effect of inhibition of the VEGF signaling pathway using a monoclonal antibody (bevacizumab) on cardiac remodeling and function. Swiss Webster mice were infected with Y strain, and cardiac morphological and molecular analyses were performed. We found that bevacizumab significantly increased survival, reduced inflammation, improved cardiac electrical function, diminished angiogenesis, decreased myofibroblasts in cardiac tissue and restored collagen levels. This work shows that VEGF is involved in cardiac microvasculopathy and fibrosis in CD and the inhibition of this factor could be a potential therapeutic strategy for CD.

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“…Therefore, there is still a lot of ongoing research on the prevention and treatment of US worldwide. Some adjunctive treatments that have been investigated include wool soaked with bevacizumab, mitomycin C, and 5-fluorouracil; intralesional administration of mitomycin C, steroids, captopril, hyaluronidase, and platelet-rich plasma; drug-coated (paclitaxel) balloon dilatation; drug-coated (e.g., steroids) catheter insertion; brachytherapy; nasogastric administration of tadalafil; oral steroids; and tamoxifen (16,(21)(22)(23). These studies were mostly conducted on animal models, but to date, there is no standard animal model of US.…”

Section: Discussionmentioning

confidence: 99%

Three new experimental models of anterior urethral stricture in rabbits

Yao¹,

Wei²,

Wan³

et al. 2022

Transl Androl Urol

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Background: This study describes and compares three surgical procedures for the construction of urethral stricture (US) models in rabbits.Methods: Forty adult male rabbits were allocated to four groups: 36 rabbits were randomly assigned to three experimental groups, while the remaining 4 were assigned to a sham group. The penis was separated from the rectum. Then along the ventral midline, a longitudinal penile skin incision was made while ensuring that the urethral mucosa was intact and the muscular layer was not completely incised. In group 1 (n=12), ventral semi-circumferential mucosa electrocoagulation of a 1-cm length of the anterior urethra was performed until ulceration occurred. In group 2 (n=12), the ventral urethral mucosa was incised, and electrocoagulation of the dorsal semi-circumferential mucosa was performed. In group 3 (n=12), wholecircumferential mucosa electrocoagulation was performed. In group 4 (n=4), no special treatment was performed. Four weeks later, urethrography, urethroscopy, and histological evaluation were carried out. Results:The weights of the rabbits in the four groups were comparable. There was no significant difference between groups 2 and 3 with regard to operative time, but the operative time in these groups was significantly longer than that in group 1 (group 2 vs. group 1: P<0.05, group 3 vs. group 1: P<0.001).After the surgery, urinary fistula with infection occurred in one rabbit in group 1, and one rabbit died due to urethral atresia in group 3. According to the urethrography and urethroscopy findings, 9 out of 12 rabbits in group 1, 5 out of 12 rabbits in group 2, and 11 out of 11 rabbits in group 3 developed US, while no rabbits in the sham group developed US. Histopathological examination revealed injury to the urothelium, inflammatory infiltration, a decrease in the amount of blood vessels and smooth muscle fibers, and a decrease in the amount of collagen fibers.Conclusions: Compared with the semi-circumferential procedures, the whole-circumferential procedure had a higher success rate. Therefore, this procedure seems to have potential for the construction of longsegment rabbit US models.

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Effect of Mitomycin, Bevacizumab, and 5-Fluorouracil to Inhibit Urethral Fibrosis in a Rabbit Model

Abstract: MMC, bevacizumab, and 5-FU may inhibit UF. There were no statistically significant differences in the effectiveness among the three agents.

Cited by 9 publications

References 27 publications

Comparison of Poly(l-lactide-co-ɛ-caprolactone) and Poly(trimethylene carbonate) Membranes for Urethral Regeneration: AnIn VitroandIn VivoStudy

Comparison of Poly(l-lactide-co-ɛ-caprolactone) and Poly(trimethylene carbonate) Membranes for Urethral Regeneration: AnIn VitroandIn VivoStudy

Vascular Growth Factor Inhibition with Bevacizumab Improves Cardiac Electrical Alterations and Fibrosis in Experimental Acute Chagas Disease

Three new experimental models of anterior urethral stricture in rabbits

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