Ana M. Corbacho

Induction of stress proteins and MMP-9 by 0.8 ppm of ozone in murine skin.

Ozone (O(3)) is among the most reactive environmental oxidant pollutants to which cutaneous tissues are exposed. O(3) exposure has been shown to induce antioxidant depletion as well as the oxidation of lipids and proteins within the outermost skin layer, the stratum corneum. However, relatively little is known regarding the potential effects of O(3) on the cellular constituents of the underlying skin epidermis and dermis. In the present study, hairless mice exposed for 6 h to 0.8 ppm O(3) showed increases in lipid peroxidation, as quantitated by increases in 4-hydroxynonenal-protein adducts. O(3) exposure caused an induction of the stress proteins HSP27 and heme oxygenase-1 (HO-1), starting at 6 h and increasing up to 18 h after O(3) exposure. This was accompanied by an increase in matrix metalloproteinase-9 (MMP-9) mRNA and activity levels, indicative of possible injurious-reparative processes. Collectively, our data demonstrate that skin exposure to O(3) not only affects antioxidant levels and oxidation markers in the outermost stratum corneum layer, but also induces cellular stress responses in the deeper cellular layers of the skin.

Suppression of breast cancer growth and angiogenesis by an antisense oligodeoxynucleotide to p21Waf1/Cip1

Under some conditions, p21(Waf1/Cip1) plays an assembly factor role for the cyclins and cyclin-dependent kinases, and recent reports demonstrate that p21 can act as an anti-apoptotic protein. Thus, it is logical to exploit this function of p21 as an anti-cancer target. We have performed a pilot study showing that daily subcutaneous injection of a phosphorothioate antisense p21 oligodeoxynucleotide, which we have previously shown to attenuate p21 levels in vitro, into nude mice who have been implanted with highly metastatic breast cancer cells results in inhibition of tumor growth and angiogenesis. Inhibition of in vitro endothelial capillary formation confirms that these oligodeoxynucleotides have a direct effect upon tumor angiogenesis. The attractiveness of our novel approach to breast cancer therapy, which capitalizes on the anti-apoptotic function of p21, derives from the ease of transfection of antisense oligodeoxynucleotides as well as the observations that p21(-/-) mice do not develop spontaneous tumors, making techniques exploiting the assembly factor and anti-apoptotic role of p21 worthy of further study against breast cancer.

Cytokine induction of prolactin receptors mediates prolactin inhibition of nitric oxide synthesis in pulmonary fibroblasts.

Prolactin (PRL) has been implicated as a modulator of immune function, and some of its actions may be linked to NO synthesis. Because NO acts as a mediator of inflammation, we speculated that an inflammatory milieu could unmask pathways by which PRL could affect NO synthesis. Here, we show that pro‐inflammatory cytokines induce the expression of PRL receptors in pulmonary fibroblasts, allowing PRL to inhibit cytokine‐induced NO production and the expression of the inducible nitric oxide synthase (iNOS). Inhibition of iNOS expression by PRL correlates with the phosphorylation of STAT‐5b (signal transducer and activator of transcription 5b) and the suppression of expression of IRF‐1 (interferon regulatory factor 1), a transcription factor for iNOS. These results reveal previously unrecognized mechanisms by which PRL and PRL receptors may play significant modulatory roles during immune–inflammatory processes.

Introducing and engaging diverse high school students to biophotonics through multi-year courses

The National Science Foundation (NSF) funded Center for Biophotonics Science and Technology (CBST) has created various high school biophotonics research academies for both students and teachers from diverse socioeconomic backgrounds. These academies engage diverse students for 10 hours to over 350 hours per year for multiple years with an emphasis on learning the basics of biophotonics and then conducting original, team-based research. We have developed three versions of the academy, one focused on biology and biophotonics, one on cancer and biophotonics, and a third on plants and biophotonics. A fourth emphasis on biomedical engineering and biophotonics is planned. We have conducted one of these academies for three years and have had very good student retention and science fair winners. As part of our program we also have a summer academy for training teachers. Challenges have arisen amongst the various levels of Academies, chief among them sustainability. In the future, more extensive evaluation, curriculum consolidation, and widespread dissemination are critical.