The ability of leucocytes

The transcription factor Nrf2 determines the ability to adapt and survive under conditions of electrophilic, oxidative, and inflammatory stress by regulating the expression of elaborate networks comprising nearly 500 genes encoding proteins with versatile cytoprotective functions. In mice, disruption of Nrf2 increases susceptibility to carcinogens and accelerates disease pathogenesis. Paradoxically, Nrf2 is upregulated in established human tumors, but whether this upregulation drives carcinogenesis is not known. Here we show that the incidence, multiplicity, and burden of solar-simulated UV radiation-mediated cutaneous tumors that form in SKH-1 hairless mice in which Nrf2 is genetically constitutively activated are lower than those that arise in their wild-type counterparts. Pharmacologic Nrf2 activation by topical biweekly applications of small (40 nmol) quantities of the potent bis(cyano enone) inducer TBE-31 has a similar protective effect against solar-simulated UV radiation in animals receiving long-term treatment with the immunosuppressive agent azathioprine. Genetic or pharmacologic Nrf2 activation lowers the expression of the pro-inflammatory factors IL6 and IL1b, and COX2 after acute exposure of mice to UV radiation. In healthy human subjects, topical applications of extracts delivering the Nrf2 activator sulforaphane reduced the degree of solar-simulated UV radiation-induced skin erythema, a quantifiable surrogate endpoint for cutaneous damage and skin cancer risk. Collectively, these data show that Nrf2 is not a driver for tumorigenesis even upon exposure to a very potent and complete carcinogen and strongly suggest that the frequent activation of Nrf2 in established human tumors is a marker of metabolic adaptation. Cancer Prev Res; 8(6); 475-86.Ó2015 AACR.

An increase in the use of light‐based technology and medical devices has created a demand for informative and accessible data showing the depth that light penetrates into skin and how this varies with wavelength. These data would be particularly beneficial in many areas of medical research and would support the use and development of disease‐targeted light‐based therapies for specific skin diseases, based on increased understanding of wavelength‐dependency of cutaneous penetration effects. We have used Monte Carlo radiative transport (MCRT) to simulate light propagation through a multi‐layered skin model for the wavelength range of 200–1000 nm. We further adapted the simulation to compare the effect of direct and diffuse light sources, varying incident angles and stratum corneum thickness. The lateral spread of light in skin was also investigated. As anticipated, we found that the penetration depth of light into skin varies with wavelength in accordance with the optical properties of skin. Penetration depth of ultraviolet radiation was also increased when the stratum corneum was thinner. These observations enhance understanding of the wavelength‐dependency and characteristics of light penetration of skin, which has potential for clinical impact regarding optimizing light‐based diagnostic and therapeutic approaches for skin disease.