Substance P is a peptide mainly secreted by neurons and is involved in many biological processes, including nociception and inflammation. Animal models have provided insights into the biology of this peptide and offered compelling evidence for the importance of substance P in cell-to-cell communication by either paracrine or endocrine signaling. Substance P mediates interactions between neurons and immune cells, with nerve-derived substance P modulating immune cell proliferation rates and cytokine production. Intriguingly, some immune cells have also been found to secrete substance P, which hints at an integral role of substance P in the immune response. These communications play important functional roles in immunity including mobilization, proliferation and modulation of activity of immune cells. This Review summarizes current knowledge of substance P and its receptors, as well as its physiological and pathological roles. We focus on recent developments in the immuno-biology of substance P and we discuss the clinical implications of its ability to modulate the immune response.

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.

IntroductionSignificant advances in three-dimensional (3D) imaging technology have allowed for the incorporation of 3D digital displays into medical and surgical devices. Despite initial adoption of the NGENUITY® 3D Visualization System in vitreoretinal surgery, there are limited publications regarding its use. The generally accepted main benefits include improved ergonomics, enhanced surgical team communication and education, reduced retinal phototoxicity, increased depth of field, and display image manipulation. Despite these potential benefits, many retina specialists have questioned its universal applicability to a wide variety of vitreoretinal surgeries.ObjectiveTo report on the variety of indications and surgical efficacy of the NGENUITY® 3D Visualization System in vitreoretinal surgery via a review of surgical experience at two vitreoretinal practices in both the academic and community settings.MethodsA retrospective review was conducted of consecutive surgical cases performed on the NGENUITY® 3D Visualization System at Massachusetts Eye and Ear Infirmary and Florida Retina Institute from June 1st, 2017 to November 1st, 2018. Age, presenting diagnosis, surgical procedure, and intraoperative details were recorded.Results272 vitreoretinal surgeries on the Alcon NGENUITY® 3D Visualization System were identified between June 1st, 2017 and November 1st, 2018 at the participating institutions. A detailed breakdown of the indications for surgery and related procedures is reported. During all 272 cases on the 3D digital system, there were no complications attributed to the visualization system.ConclusionThis series illustrates the diversity of vitreoretinal surgeries that can be performed on this system without compromising surgical viewing or increasing surgical complications. The Alcon NGENUITY® 3D Visualization System possesses favorable ergonomics, illumination levels, depth of field, display filters, and trainee experience.

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.