Background and Objectives: A novel carbon dioxide (CO 2 ) laser device employing ablative fractional resurfacing was tested on human skin in vivo for the first time. Study Design/Materials and Methods: An investigational 30 W, 10.6 mm CO 2 laser system was focused to a 1/e 2 spot size of 120 mm to generate an array of microscopic treatment zones (MTZ) in human forearm skin. A range of pulse energies between 5 and 40 mJ was tested and lesion dimensions were assessed histologically using hematoxylin & eosin. Wound healing of the MTZ's was assessed immediately-, 2-day, 7-day, 1-month, and 3-month post treatment. The role of heat shock proteins was examined by immunohistochemistry. Results: The investigational CO 2 laser system created a microscopic pattern of ablative and thermal injury in human skin. The epidermis and part of the dermis demonstrated columns of thermal coagulation that surrounded tapering ablative zones lined by a thin eschar layer. Changing the pulse energy from 5 to 30 mJ resulted in a greater than threefold increase in lesion depth and twofold increase in width. Expression of heat shock protein (hsp)72 was detected as early as 2 days post-treatment and diminished significantly by 3 months. In contrast, increased expression of hsp47 was first detected at 7 days and persisted at 3 months post-treatment. Conclusion: The thermal effects of a novel investigational ablative CO 2 laser system utilizing fractional resurfacing were characterized in human forearm skin. We confirmed our previous ex vivo findings and show for the first time invivo, that a controlled array of microscopic treatment zones of ablation and coagulation could be deposited in human skin by varying treatment pulse energy. Immunohistochemical studies of heat shock proteins revealed a persistent collagen remodeling response lasting at least 3 months. We successfully demonstrated the first in-vivo use of ablative fractional resurfacing (AFR TM ) treatment on human skin.

Background and Objectives: We introduce a novel CO 2 laser device that utilizes ablative fractional resurfacing for deep dermal tissue removal and characterize the resultant thermal effects in skin. Study Design/Materials and Methods: A prototype 30 W, 10.6 mm CO 2 laser was focused to a 1/e 2 spot size of 120 mm and pulse duration up to 0.7 milliseconds to achieve a microarray pattern in ex vivo human skin. Lesion depth and width were assessed histologically using either hematoxylin & eosin (H&E) or lactate dehyrdogenase (LDH) stain. Pulse energies were varied to determine their effect on lesion dimensions. Results: Microarrays of ablative and thermal injury were created in fresh ex vivo human skin irradiated with the prototype CO 2 laser device. Zones of tissue ablation were surrounded by areas of tissue coagulation spanning the epidermis and part of the dermis. A thin condensed lining on the interior wall of the lesion cavity was observed consistent with eschar formation. At 23.3 mJ, the lesion width was approximately 350 mm and depth 1 mm. In this configuration, the cavities were spaced approximately 500 mm apart and interlesional epidermis and dermis demonstrated viable tissue by LDH staining. Conclusion: A novel prototype ablative CO 2 laser device operating in a fractional mode was developed and its resultant thermal effects in human abdominal tissue were characterized. We discovered that controlled microarray patterns could be deposited in skin with variable depths of dermal tissue ablation depending on the treatment pulse energy. This is the first report to characterize the successful use of ablative fractional resurfacing as a potential approach to dermatological treatment. Lasers Surg. Med. 39:87-95, 2007. ß

Activation of the hedgehog pathway, through the loss of patched (PTC) or the activation of smoothened (SMO), occurs frequently in basal cell carcinoma (BCC), the most common human cancer. However, the molecular basis of this neoplastic effect is not understood. The downstream molecule Gli1 is known to mediate the biological effect of the pathway and is itself up-regulated in all BCCs. Gli1 can drive the production of BCCs in the mouse when overexpressed in the epidermis. Here we show that Gli1 can activate platelet-derived growth factor receptor ␣ (PDGFR␣) in C3H10T 1 ⁄2 cells. Functional up-regulation of PDGFR␣ by Gli1 is accompanied by activation of the ras-ERK pathway, a pathway associated with cell proliferation. The relevance of this mechanism in vivo is supported by a high level expression of PDGFR␣ in BCCs of mice and humans. In the murine BCC cell line ASZ001, in which both copies of the PTC gene are inactivated, DNA synthesis and cell proliferation can be slowed by re-expression of PTC, which downregulates PDGFR␣ expression, or by downstream inhibition of PDGFR␣ with neutralizing antibodies. Therefore, we conclude that increased expression of PDGFR␣ may be an important mechanism by which mutations in the hedgehog pathway cause BCCs.