The receptor tyrosine kinase ErbB-2 plays an important role in the regulation of growth factor-induced signal transduction cascades in the epithelium, and ErbB-2 is frequently overexpressed in epithelial tumors. Our previous studies on clinical prostate cancer specimens indicated that ErbB-2 expression was increased in patients undergoing hormone ablation therapy. We had also shown that the critical cell cycle regulatory gene cyclin D1 and its promoter were targets of proliferative signaling in prostate cancer cell lines, and that cyclin D1 was required for ErbB-2-induced mammary tumorigenesis. In the current studies, we found that increased ErbB-2 membrane expression correlated with increased nuclear cyclin D1 staining in clinical prostate cancer specimens, and that expression of ErbB-2 was capable of inducing cell cycle progression in human prostate cancer cell lines. We further showed that ErbB-2 induced the cyclin D1 promoter in DU145 cells, and that small interfering RNA knockdown of cyclin D1 protein levels blocked a significant proportion of the heregulin-induced cell cycle progression in LNCaP cells. Probasin promoter-targeted expression of an activated ErbB-2 isoform induced cyclin D1 expression in the mouse prostate, commensurate with prostate intraepithelial neoplasia. Together, these in vitro and in vivo studies identify cyclin D1 as a critical downstream target of ErbB-2 in the prostate epithelium, both of which are possible therapeutic targets for cancer intervention. Furthermore, our novel mouse model provides a useful platform for ongoing in vivo investigations of ErbB-2 signaling in the prostate epithelium. [Cancer Res 2007;67(9):4364-72]

Melasma is a common skin condition that is characterized by a chronic and relapsing course. It typically manifests as gray-to-brown patches on sun-exposed areas of the face and neck, which disproportionately affects those of Asian, African, and Hispanic descent. Melasma has been associated with pregnancy, changes in uterine or ovarian hormones, oral contraceptives, and excessive sun exposure. 1

BACKGROUND Ultrasound energy has been used for cutaneous rejuvenation, including treatment of fine lines and wrinkles. Ultrasound waves of high intensity can induce thermal injury in the dermis, which causes tissue coagulation and remodeling. OBJECTIVE To examine the safety and utility of a novel ultrasound device that uses high-intensity, high-frequency, parallel ultrasound beams to improve fine lines and wrinkles of the face and neck. MATERIALS AND METHODS A prospective, multicenter, clinical study investigated the utility of this novel ultrasound device to improve fine lines and wrinkles. Sixty subjects were enrolled for single treatment to the face and neck. RESULTS Fifty-eight subjects completed the study. The mean age was 58 years, and 87.9% were women. Fitzpatrick skin Types I to VI were represented. Assessments compared 12-week follow-up with baseline. Two blinded reviewers agreed in identifying pretreatment and post-treatment photographs for 78% of subjects. There was significant improvement of 1 to 3 Fitzpatrick Wrinkle and Elastosis Scale units in 86% of subjects. For investigator global improvement scores, 88% of subjects had improvement. Overall, 72% of subjects noted improvement, and the majority were satisfied. There were no device-related adverse events. CONCLUSION Treatment with a novel ultrasound device that uses high-intensity, high-frequency, parallel ultrasound beams safely improved the clinical appearance of fine lines and wrinkles of the face and neck.

The role of genetic testing in the practice of dermatology is expanding, yet obtaining coverage for genetic testing remains a challenge. We propose several solutions as to how this can be remedied.