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Purpose: Recent studies have shown that Aurora-A expression is associated with bladder cancer initiation and progression. In this study, the effects of intravesical Aurora-A inhibitor Alisertib (ALS) and bacillus Calmette-Guérin (BCG) were compared on bladder carcinogenesis., Methods: Two mg N-Methyl-N-nitrosourea was administered intravesically to forty of Wistar-albino rats every other week for 8 weeks. At week 10, rats were divided into four groups (10/group): No-treatment (vehicle), ALS-alone, BCG-alone, and ALS + BCG. The intravesical treatment of ALS, BCG, and ALS plus BCG was performed once a week for 6 weeks. At week 16, bladders were collected for immunohistopathological and Western blot analysis. The cell cycle regulators p53, p21, Aurora-A, phosphorylated Aurora-A (p-Aurora-A), and apoptotic marker cleavage of poly [ADP-ribose] polymerase (c-PARP) were determined by Western blot., Results: Histopathologically relatively healthy urothelium was observed in ALS + BCG group (87.5%) compared to the ALS-alone (50%) and the BCG-alone (50%) groups. The lowest expression of p21 and p53 was detected in the BCG-alone, while the highest level of expression was evident in no-treatment group. The ALS treatment alone caused a slight decrease in Aurora-A while there was a dramatic decrease in p-Aurora-A in comparison to no-treatment group. In overall combined treatment with ALS + BCG significantly increased c-PARP compared to all mono-treatments, and decreased all cell cycle parameters compared to no-treatment group., Conclusions: Although intravesical ALS treatment has similar antiproliferative effects like BCG, ALS + BCG combined treatment led to a best histopathologic and apoptotic response. Consequently, BCG combined with Aurora-A inhibition may provide a new intravesical treatment modality in the prevention of bladder carcinogenesis.

Intravesical Bacillus Calmette-Guerin (BCG) is the best treatment modality for progression of non-muscle invasive bladder cancer. We aimed to monitor changes at the proteome level to identify putative protein biomarkers associated with the response of urothelial precancerous lesions to intravesical BCG treatment. The rats were divided into three groups (n = 10/group): control, non-treated, and BCG-treated groups. The non-treated and BCG-treated groups received N-methyl-N-nitrosourea intravesically. BCG Tice-strain was instilled into bladder in BCG-treated group. At the endpoint of experiment, all surviving rat bladders were collected and equally divided into two portions vertically from dome to neck. Half of each bladder was assessed immunohistopathologically and the other half was used for 2D-based comparative proteomic analysis. Differentially expressed proteins were validated by Western blot analysis. Precancerous lesions of bladder cancer were more common in non-treated group (77.8%) than in BCG-treated group (50%) and the control group (0%). Greater than twofold changes occurred in the expression of a number of proteins. Among them, Rab-GDIβ, aldehyde dehydrogenase 2 (ALDH2) and 14-3-3 zeta/delta were important since they were previously reported to be associated with cancer and their expression levels were found to be lower in BCG-treated group in comparison to the non-treated group. ALDH2 and 14-3-3 zeta/delta were also found to be highly expressed in the non-treated group compared to the control group. The down-regulation of these proteins and Rab-GDIβ was achieved with BCG; this result indicates that they may be used as putative biomarkers for monitoring changes in bladder carcinogenesis in response to BCG immunotherapy.

Objective: To compare the effect of subconjunctivally injected bevacizumab, etanercept and the combination of both drugs on experimental corneal neovascularization in rats., Design: Experimental study., Participants: 28 male Wistar-Albino rats., Methods: Right corneas of rats were cauterized by silver nitrate sticks. Rats were divided randomly and equally into 4 groups so that each group contained 7 subjects. Immediately after the cauterization, 0.05 ml normal saline was injected subconjunctivally in group 1 (control group); 0.05 ml (1.25 mg) bevacizumab was injected subconjunctivally in group 2; 0.05 ml (1.25 mg) etanercept was injected subconjunctivally in group 3; 0.05 ml (1.25 mg) bevacizumab and 0.05 ml (1.25 mg) etanercept was injected subconjunctivally in group 4. The rats were euthanized on the 8th day, and digital photographs were obtained before the eyes were enucleated. The area of corneal neovascularization was calculated from digital photographs. Corneal sections were analyzed by histopathologically., Results: The burn stimulus score was +1 or higher in all eyes. The difference of the neovascularization score between groups was found to be statistically significant (p = 0.001). The area of corneal neovascularization was 79.8% in group 1, 43.2% in group 2, 54.5% in group 3, and 34.8% in group 4. In group 4, corneal neovascularization was inhibited more than in the other groups. Histologic examination showed that the treatment groups had less neovascularization, inflammation, and fibroblast activity than the control group (p< 0.05)., Conclusions: Our study has shown that etanercept does have some antiangiogenic and anti-inflammatory effects in treatment of corneal neovascularization. The combination of bevacizumab and etanercept may be a promising approach in the treatment of corneal neovascularization., (Copyright © 2013 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Aim and Scope: To investigate the inhibitory effect of subconjunctival application of VEGF antibodies bevacizumab, ranibizumab, pegaptanib, and HER2 antibody trastuzumab on corneal neovascularization in a rat model of experimental corneal neovascularization., Material and Method: Thirty male Wistar albino rats were included in the study. A chemical burn was induced in central cornea of one eye of the rats by a 75% silver nitrate and 25% potassium nitrate stick. Rats were randomly divided into five groups so that each group contained 6 subjects. Right after the chemical burn, 0.1 ml serum physiologic was injected subconjuctivally in control group (group 1). 1.25 mg/0.05 ml bevacizumab was injected in group 2; 1.2 mg/0.1 ml trastuzumab was injected in group 3; 0.5 mg/0.05 ml ranibizumab was injected in group-4; and 0.3 mg/0.1 ml pegaptanib was injected in group 5. On the 8th day of the experiment, rat corneas were photographed by digital photo-camera. Later, eyes of the sacrificed rats were enucleated and corneal speciements were histopathologically analyzed. The percentages of neovascularization on corneal photographs were examined with digital image analysis., Results: The percentage of corneal neovascularization in all treatment groups was found to be significantly lower than the control group (p < 0.05). Bevacizumab was found to be more effective than all other agents (p < 0.05). While the degree of inflammation and vascularization in bevacizumab and trastuzumab groups were significantly lower than the control group (p < 0.05), the difference was not significant in ranibizumab and pegaptanib groups (p > 0.05). In all treatment groups, fibroblast intensity was significantly lower than the control group. In terms of corneal thickness, no significant difference was observed between treatment and control groups (p > 0.05)., Conclusion: Bevacizumab, ranibizumab, pegaptanib, and trastuzumab were found effective for the inhibition of corneal NV. In our study we detected that the most effective agent was bevacizumab.

Tectocerebellar dysraphism is a very rare malformation associated with encephalocele and tectal deformity. This article presents tectocerebellar dysraphism with a solely vermian content of encephalocele and tectal beaking defined by magnetic resonance imaging (MRI) in a 5-month-old girl who was successfully treated surgically and demonstrated excellent prognosis at the 4-year follow-up.

Objective: Single-dose subconjunctival platelet-rich plasma (sPRP) injections with or without antibiotic treatment were investigated for their effect on corneal epithelial wound healing in a rabbit model., Materials and Methods: A total of 24 rabbits were used in this study. After collecting intracardiac blood samples from 16 rabbits, platelet-rich plasma was obtained by centrifugation. Animals were divided into 3 groups. A mechanical corneal epithelial defect of 7-mm diameter was created on the central cornea of the right eye of each animal. Group 1 (n = 8) received only sPRP, whereas group 2 (n = 8) received sPRP with topical antibiotic throughout the study. The third group (n = 8) served as the control group. Each animal was examined daily under biomicroscope for 10 days. Epithelial defect was measured in horizontal and vertical diameter with a 1/100 sensitive micrometer, and area of the defect was calculated. One animal was sacrificed in each group on the third and seventh day, and all remaining animals were sacrificed on the 10th day. Corneal histopathology was investigated for epithelial regeneration, presence of inflammation, and structural integrity of fibroblasts. All data were statistically analyzed for difference between the study groups., Results: Group 1 had a significantly smaller size in horizontal and vertical defect diameters on each day as compared with the control group. Healing of the epithelial defect in group 1 was found to be significantly different than that in the control group (P < 0.05). No significant difference was observed between group 2 and control group except for the first day. Group 1 had a significantly better healing process after the fourth day as compared with group 2. Histopathological investigations revealed a steady fibroblast migration, quicker epithelial regeneration, and less inflammation in group 1 as compared with the other 2 groups., Discussion and Conclusions: sPRP seems to improve corneal epithelial wound healing. However, antibiotic and sPRP combination may have a retarded healing effect as compared with platelet-rich plasma alone.