Irresponsiveness of two retinoblastoma cases to conservative therapy correlates with up- regulation of hERG1 channels and of the VEGF-A pathway

<p>Abstract</p> <p>Background</p> <p>Treatment strategies for Retinoblastoma (RB), the most common primary intraocular tumor in children, have evolved over the past few decades and chemoreduction is currently the most popular treatment strategy. Despite success, systemic chemotherapeutic treatment has relevant toxicity, especially in the pediatric population. Antiangiogenic therapy has thus been proposed as a valuable alternative for pediatric malignancies, in particolar RB. Indeed, it has been shown that vessel density correlates with both local invasive growth and presence of metastases in RB, suggesting that angiogenesis could play a pivotal role for both local and systemic invasive growth in RB. We present here two cases of sporadic, bilateral RB that did not benefit from the conservative treatment and we provide evidence that the VEGF-A pathway is significantly up-regulated in both RB cases along with an over expression of hERG1 K⁺channels.</p> <p>Case presentation</p> <p>Two patients showed a sporadic, bilateral RB, classified at Stage II of the Reese-Elsworth Classification. Neither of them got benefits from conservative treatment, and the two eyes were enucleated. In samples from both RB cases we studied the VEGF-A pathway: VEGF-A showed high levels in the vitreous, the <it>vegf-a, flt-1, kdr</it>, and <it>hif1-α </it>transcripts were over-expressed. Moreover, both the transcripts and proteins of the hERG1 K⁺channels turned out to be up-regulated in the two RB cases compared to the non cancerous retinal tissue.</p> <p>Conclusions</p> <p>We provide evidence that the VEGF-A pathway is up-regulated in two particular aggressive cases of bilateral RB, which did not experience any benefit from conservative treatment, showing the overexpression of the <it>vegf-a</it>, <it>flt-1</it>, <it>kdr </it>and <it>hif1-α </it>transcripts and the high secretion of VEGF-A. Moreover we also show for the first time that the <it>herg1 </it>gene transcripts and protein are over expressed in RB, as occurs in several aggressive tumors. These results further stress the relevance of the VEGF-A pathway in RB and the correlation with hERG1, making aggressive and recurrent RB cases good candidates for antiangiogenesis therapies based on the targeting of VEGF-A.</p

Effects of intraoperative sponge mitomycin C and 5-fluorouracil on scar formation following strabismus surgery in rabbits.

PURPOSE: To investigate the influence of 5-fluorouracil (5-FU) and mitomycin C (MMC) on the postoperative adhesions following strabismus surgery in rabbits. METHODS: Twenty-one New Zealand white rabbits were used in this prospective, masked, controlled trial. Both eyes of 20 animals underwent 3-mm recession of the superior rectus muscle (SRM). In group I (io animals), one eye of each animal received topical application of MMC (0.2 mg/ml) for 5 minutes and the other eye (control eye) was treated with balanced salt solution (BSS) using an intraoperative sponge. In group II (10 animals), a randomly chosen eye of each animal was treated with 5-FU soaked sponges (50 mg/ml) for 5 minutes and the fellow eye (control eye) with BSS. Two eyes of a rabbit were included as unoperated controls. Four weeks after the surgery, conjunctival vascularity and postoperative adhesions between the SRM Tenon's capsule (TC) and SRM sclera (scl) were assessed. Additionally, eyes were enucleated and evaluated histopathologically for evidence of scarring, granuloma formation, and muscle tissue changes under a light microscope. RESULTS: MMC-treated eyes had a higher rate of avascular conjunctiva compared to both controls and 5-FU-treated eyes. Mean adhesion scores, particularly between the SRM-scl, were lower in eyes treated with antiproliferative agents compared to controls. The difference was statistically significant in MMC-treated eyes for the adhesions between SRM-scl (p = 0.03). Histopathological examination revealed less scarring and granuloma formation in MMC- and 5-FU-treated eyes compared to their control eyes. CONCLUSIONS: MMC, and to a lesser extent 5-FU, are shown to be effective in reducing postoperative scarring following strabismus surgery in rabbits. It seems reasonable to suggest that antimetabolites should be used for cases having an increased risk of postoperative adhesions

Comparative study of 0.1% olopatadine hydrochloride and 0.5% ketorolac tromethamine in the treatment of seasonal allergic conjunctivitis.

PURPOSE: To compare the therapeutic effects of two ophthalmic solutions (0.1% olopatadine hydrochloride and 0.5% ketorolac tromethamine) with different pharmacological mechanisms on the clinical signs and Symptoms of seasonal allergic conjunctivitis (SAC). METHODS: Forty patients with the signs and symptoms of SAC (i.e. hyperaemia, itching, mucus discharge, tearing) were included in this placebo-controlled, randomized, parallel group, single centre study. In group 1 (20 patients) one eye of each patient was treated with olopatadine and the other with placebo. In group 2 (20 patients) one eye of each patient was treated with ketorolac solution and the other with placebo. The principal signs and symptoms of SAC (hyperaemia and itching) were evaluated at 30 mins and at 2, 7 and 15 days. RESULTS: In group 1, both parameters improved significantly in eyes treated with olopatadine compared with those receiving placebo at all control examinations (all p 0.05). However, the itching score was significantly lower in the olopatadine group from the second day through to the end of the study (p < 0.05). CONCLUSIONS: Both olopatadine and ketorolac ophthalmic solutions were found to be effective in alleviating the clinical signs and symptoms of SAC compared to placebo. However, olopatadine reduces ocular itching significantly more than ketorolac

tromethamine in the treatment of seasonal allergic conjunctivitis

Purpose: To compare the therapeutic effects of two ophthalmic solutions (0.1% olopatadine hydrochloride and 0.5% ketorolac tromethamine) with different pharmacological mechanisms on the clinical signs and Symptoms of seasonal allergic conjunctivitis (SAC).Methods: Forty patients with the signs and symptoms of SAC (i.e. hyperaemia, itching, mucus discharge, tearing) were included in this placebo-controlled, randomized, parallel group, single centre study. In group 1 (20 patients) one eye of each patient was treated with olopatadine and the other with placebo. In group 2 (20 patients) one eye of each patient was treated with ketorolac solution and the other with placebo. The principal signs and symptoms of SAC (hyperaemia and itching) were evaluated at 30 mins and at 2, 7 and 15 days.Results: In group 1, both parameters improved significantly in eyes treated with olopatadine compared with those receiving placebo at all control examinations (all p 0.05). However, the itching score was significantly lower in the olopatadine group from the second day through to the end of the study (p < 0.05).Conclusions: Both olopatadine and ketorolac ophthalmic solutions were found to be effective in alleviating the clinical signs and symptoms of SAC compared to placebo. However, olopatadine reduces ocular itching significantly more than ketorolac

HLA-B51 gene and its expression in association with Behçet's Disease in Denizli Province of Turkey.

Behçet's Disease (BD) is a multisystemic inflammatory disorder as a triad of symptoms including recurrent oral and genital aphthous ulceration, and uveitis with unknown pathogenesis. Many researchers have tried to investigate the association of HLA-B51 gene with the BD. We aimed to investigate the association of the HLA-B51 gene and its expression, also polymorphic structure by PCR, RT-PCR and sequence specific oligonucleotide primers and probes in BD patients (n: 35) and control group (n: 50). According to our results, we did not observe any association in between HLA-B51 gene, its polymorphism, expression and BD patients