Verteporfin (VP), a benzoporphyrin derivative, is clinically used in photodynamic therapy for neovascular macular degeneration. Recent studies indicate that VP may inhibit growth of hepatoma cells without photoactivation hrough inhibition of YAP-TEAD complex. In this study, we examined the effects of VP without light activation on human retinoblastoma cell lines. Verteporfin but not vehicle control inhibited the growth, proliferation and viability of human retinoblastoma cell lines (Y79 and WERI) in a dose-dependent manner and was associated with downregulation of YAP-TEAD associated downstream proto-oncogenes such as c-myc, axl, and surviving. In addition VP affected signals involved in cell migration and angiogenesis such as CTGF, cyr61, and VEGF-A but was not associated with significant effect on the mTOR/autophagy pathway. Of interest the pluripotency marker Oct4 were downregulated by Verteporfin treatment. Our results indicate that the clinically used photosensitizer VP is a potent inhibitor of cell growth in retinoblastoma cells, disrupting YAPTEAD signaling and pluripotential marker OCT4. This study highlights for the first time the role of the YAP-TEAD pathway in Retinoblastoma and suggests that VP may be a useful adjuvant therapeutic tool in treating Rb patients.

Verteporfin (VP), a light-activated drug used in photodynamic therapy for the treatment of choroidal neovascular membranes, has also been shown to be an effective inhibitor of malignant cells. Recently, studies have demonstrated that, even without photo-activation, VP may still inhibit certain tumor cell lines, including ovarian cancer, hepatocarcinoma and retinoblastoma, through the inhibition of the YAP-TEAD complex. In this study, we examined the effects of VP without light activation on human glioma cell lines (LN229 and SNB19). Through western blot analysis, we identified that human glioma cells that were exposed to VP without light activation demonstrated a downregulation of YAP-TEAD-associated downstream signaling molecules, including c-myc, axl, CTGF, cyr61 and survivin and upregulation of the tumor growth inhibitor molecule p38 MAPK. In addition, we observed that expression of VEGFA and the pluripotent marker Oct-4 were also decreased. Verteporfin did not alter the Akt survival pathway or the mTor pathway but there was a modest increase in LC3-IIB, a marker of autophagosome biogenesis. This study suggests that verteporfin should be further explored as an adjuvant therapy for the treatment of glioblastoma.

Introduction:Research is crucial for health-care delivery. However, medical students may not participate in research during their training, which might negatively affect their understanding of the importance of research and their future ability to conduct research projects. This is more prominent in developing countries. We aim to assess the attitudes of a sample of Syrian medical students toward research and suggest plausible solutions to reduce their self-reported barriers.Methods:A cross-sectional study was conducted using a self-administered, pretested questionnaire.Results:Three hundred and twenty-three responses were included. Most students demonstrated positive attitudes toward research. However, most of the responses indicated that they did not receive any training in academic writing or research and therefore did not have the opportunity to participate in formal research projects or scholarly writing. Students reported various types of barriers that challenged their progress in the field of research. Students who reported being encouraged by their professors to participate in research and writing/publishing scientific papers or reported receiving training about these activities were more likely to participate in research projects or writing scientific articles.Conclusion:Students have positive attitudes toward research and publication while they reported poor education, limited participation, and presence of many barriers that impede their participation in such activities.

Mullerian Inhibiting Substance (MIS) has been shown to inhibit ovarian cancer cells both in-vitro and in-vivo. Furthermore, recent evidence suggests that MIS may effectively target a putative ovarian cancer progenitor cell population enriched by a panel of CD44+, CD24+, Ep-CAM+, and E-cadherin-cell surface markers. In order to accommodate clinical testing of MIS in ovarian cancer patients, the production of recombinant human MIS must be optimized to increase yield and purity. Here we show that, compared to wild type, the substitution of the MIS leader sequence to that of human serum albumin, combined with a modification of the endogenous cleavage site from RAQR/S to a furin/kex2 RARR/S consensus site results in high expression, increased C-terminus cleavage and a reduction in unwanted cryptic internal cleavage products when produced in CHO cells. Purified MIS containing these alterations retains its capacity to induce regression of the Mullerian duct in fetal rat embryonic urogenital ridge assays.

Fasting Ramadan, in which Muslims abstain from specific habits and behaviors from dawn to sunset, is one of the five Pillars of Islam. While there are several exemptions from fasting, many Muslim patients with acute or chronic medical conditions still choose to fast, which may adversely affect their health if not addressed properly. Some patients may not be well educated about the effects of some medical treatments and procedures on the validity of their fast, which can unnecessarily lead to suboptimal management of their conditions or treatment nonadherence. Since spirituality, religiosity, and personal beliefs affect patients' health behaviors and adherence to treatments, health-care providers need to learn how fasting Ramadan can affect the health of their Muslim patients, especially those with chronic medical conditions, and how to help them achieve safe fasting. This article aims to provide an overview of the main topics that primary care physicians may need to know in order to improve their cultural competence when caring for their fasting Muslim patients.

Verteporfin (VP) was first used in Photodynamic therapy, where a non-thermal laser light (689 nm) in the presence of oxygen activates the drug to produce highly reactive oxygen radicals, resulting in local cell and tissue damage. However, it has also been shown that Verteporfin can have non-photoactivated effects such as interference with the YAP-TEAD complex of the HIPPO pathway, resulting in growth inhibition of several neoplasias. More recently, it was proposed that, another non-light mediated effect of VP is the formation of cross-linked oligomers and high molecular weight protein complexes (HMWC) that are hypothesized to interfere with autophagy and cell growth. Here, in a series of experiments, using human uveal melanoma cells (MEL 270), human embryonic kidney cells (HEK) and breast cancer cells (MCF7) we showed that Verteporfin-induced HMWC require the presence of light. Furthermore, we showed that the mechanism of this cross-linking, which involves both singlet oxygen and radical generation, can occur very efficiently even after lysis of the cells, if the lysate is not protected from ambient light. This work offers a better understanding regarding VP’s mechanisms of action and suggests caution when one studies the non-light mediated actions of this drug.

PURPOSE To compare effectiveness of fornix- and limbal-based conjunctival flaps in trabeculectomy surgery. DESIGN Systematic review. METHODS Setting CENTRAL, MEDLINE, LILACS, ISRCTN registry, ClinicalTrials.gov, WHO, and ICTRP were searched to identify eligible randomized controlled trials (RCTs). Study Population RCTs in which benefits and complications of fornix- vs limbal-based trabeculectomy for glaucoma were compared in adult glaucoma patients. Observation Procedure We followed Cochrane methodology for data extraction. Main Outcome Measures Proportion of failed trabeculectomies at 24 months, defined as the need for repeat surgery or uncontrolled intraocular pressure (IOP) > 22 mm Hg, despite topical/systemic medications. RESULTS The review included 6 trials with a total of 361 participants, showing no difference in effectiveness between fornix-based vs limbal-based trabeculectomy surgery, although with a high level of uncertainty owing to low event rates. In the fornix-based and limbal-based surgery, mean IOP at 12 months was similar, with ranges of 12.5–15.5 mm Hg and 11.7–15.1 mm Hg, respectively. Mean difference was 0.44 mm Hg (95% CI −0.45 to 1.33) and 0.86 mm Hg (95% CI −0.52 to 2.24) at 12 and 24 months of follow-up, respectively. Mean number of postoperative glaucoma medications was similar between the 2 groups. Mean difference was 0.02 (95% CI −0.15 to 0.19) at 12 months. As far as postoperative complications, an increased risk of shallow anterior chamber was observed in the limbal-based group. CONCLUSION Similar efficacy of trabeculectomy surgery with respect to bleb failure or IOP control was observed in both types of conjunctival flap incisions. A significant difference was detected in the risk of postoperative shallow anterior chamber, which was increased in the limbal-based group.

No abstract