Organ transplant status, anatomic location, and age impact rates of adnexal involvement of actinic keratoses.

Actinic keratoses (AKs) are pre-malignant skin lesions that can give rise to squamous cell carcinomas. Involvement of adnexal structures by AKs has been postulated to confer resistance to therapy and facilitate malignant progression. In our study, we identified several factors associated with increased risk of adnexal involvement of AKs. We found an increased risk of follicular involvement in AKs on the head and neck, a slightly increased risk of eccrine involvement with increasing age, and an increased risk of eccrine involvement in organ transplant patients. Additionally, our data showed a higher overall rate of follicular involvement of AKs than previously reported.

Targeting the Platelet-Derived Growth Factor-beta Stimulatory Circuitry to Control Retinoblastoma Seeds.

Purpose: Vitreous seeding remains the primary reason for treatment failure in eyes with retinoblastoma (Rb). Systemic and intra-arterial chemotherapy, each with its own inherent set of complications, have improved salvage rates for eyes with advanced disease, but the location and biology of vitreous seeds present a fundamental challenge in developing treatments with minimal toxicity and risk. The aim of this study was to target the platelet-derived growth factor (PDGF)- PDGF-receptor ß (PDGFRß) signaling pathway and investigate its role in the growth of Rb seeds, apoptotic activity, and invasive potential. Methods: We performed ex vivo analyses on vitreous samples from Rb patients that underwent enucleation and from patient-derived xenografts. These samples were evaluated by quantitative PCR, immunohistochemistry, and ELISA. The effects of disruption of the PDGF-PDGFRß signaling pathway, both by pharmacologic and genomic knockdown approaches, were evaluated in vitro by cell proliferation and apoptotic assays, quantitative PCR analyses, Western blotting, flow cytometry, and imaging flow cytometry. A three-dimensional cell culture system was generated for in-depth study of Rb seeds. Results: Our results demonstrated that PDGFRß signaling is active in the vitreous of Rb patients and patient-derived xenografts, sustaining growth and survival in an AKT-, MDM2-, and NF-κB-dependent manner. The novel three-dimensional cell culture system mimics Rb seeds, as the in vitro generated spheroids have similar morphologic features to Rb seeds and mimicked their natural physiology. Conclusions: Targeting the PDGFRß pathway in vitro reduces Rb cell growth, survival, and invasiveness and could augment current therapies. This represents a novel signaling pathway for potential targeted therapy to further improve ocular survival in advanced Rb.

Drugs on the Horizon for Chronic Pruritus.

Chronic pruritus is a common condition that has a detrimental impact on quality of life. As the molecular pathogenesis of itch is elucidated, novel therapies that disrupt itch pathways are being investigated. Emerging treatments include drugs targeting the neural system, drugs targeting the immune system, antihistamines, bile acid transport inhibitors, and topical drugs that work through a variety of mechanisms such as phosphodiesterase-4 inhibition or targeting of nerve ion channels. Many of these therapies show promising results in the treatment of chronic itch of various etiologies, such as atopic dermatitis, psoriasis, uremic pruritus, and cholestatic pruritus.