Wenbin Tan

Topical Rapamycin Suppresses the Angiogenesis Pathways Induced by Pulsed Dye Laser: Molecular Mechanisms of Inhibition of Regeneration and Revascularization of Photocoagulated Cutaneous Blood Vessels

Pulsed dye laser (PDL) is the most effective treatment for port wine stain (PWS) birthmarks. However, regeneration and revascularization of photocoagulated blood vessels may result in poor therapeutic outcome. We have recently shown that rapamycin (RPM), an angiogenesis inhibitor, can reduce the regeneration and revascularization of photocoagulated blood vessels. Herein, we attempt to further elucidate the molecular pathophysiology on the inhibition of the regeneration and revascularization of photocoagulated blood vessels by topical RPM in an animal model.

The somatic GNAQ mutation (R183Q) is primarily located within the blood vessels of port wine stains

Author(s): Tan, Wenbin; Nadora, Dawnica Mercado; Gao, Lin; Wang, Gang; Mihm, Martin C; Nelson, J Stuart

Topical Rapamycin Systematically Suppresses the Early Stages of Pulsed Dye Laser-Induced Angiogenesis Pathways

Administration of topical rapamycin (RPM) suppresses the regeneration and revascularization of photocoagulated blood vessels induced by pulsed dye laser (PDL).

Topical axitinib suppresses angiogenesis pathways induced by pulsed dye laser.

The recurrence of port‐wine stain (PWS) blood vessels by pulsed dye laser (PDL)‐induced angiogenesis is a critical barrier that must be overcome to achieve a better therapeutic outcome.

Pathological alterations involve the entire skin physiological milieu in infantile and early-childhood port-wine stain

Author(s): Tan, W; Zakka, LR; Gao, L; Wang, J; Zhou, F; Selig, MK; Anvari, R; Sukanthanag, A; Wang, G; Mihm, MC; Nelson, JS

Activation of Pkcα and Pi3k Kinases in Hypertrophic and Nodular Port Wine Stain Lesions.

Abstract: Port wine stain (PWS) is a congenital, progressive vascular malformation. Many patients with PWS develop hypertrophy and discrete nodularity during their adult life, but the mechanism(s) remain incompletely understood. In this study, we attempted to investigate activation status of PKC&agr;, PI3K, PDPK1 and PLC-&ggr; and protein levels of PP2A and DAG to explore their potential roles in the formation of hypertrophic and nodular PWS lesions. We found phosphorylated levels of PKC&agr;, PI3K, PDPK1, and PLC-&ggr; and protein levels of PP2A and DAG showed moderate increases in the endothelial cells of hypertrophic PWS as compared to the adjacent normal skin. These increases extended throughout the entire stroma of blood vessels in PWS nodules. Many proliferating cells, such as fibroblasts, also showed strong activation of PKC&agr;, PI3K, PDPK1 and PLC-&ggr; and upregulations of PP2A and DAG in nodular PWS lesions. Our data showed that there is aberrant activation of PKC&agr;, PI3K, PDPK1 and PLC-&ggr; and upregulation of PP2A and DAG mainly in endothelial cells in hypertrophic PWS areas, but presenting in the entire vasculatures and surrounding fibroblasts in PWS nodules. Our data suggest that both PKC&agr; and PI3K signaling pathways contribute to the development of hypertrophy and nodularity in adult PWS.

The Role of Laser Speckle Imaging in Port-Wine Stain Research: Recent Advances and Opportunities

Here, we review our current knowledge on the etiology and treatment of port-wine stain (PWS) birthmarks. Current treatment options have significant limitations in terms of efficacy. With the combination of 1) a suitable preclinical microvascular model, 2) laser speckle imaging (LSI) to evaluate blood-flow dynamics, and 3) a longitudinal experimental design, rapid preclinical assessment of new phototherapies can be translated from the lab to the clinic. The combination of photodynamic therapy (PDT) and pulsed-dye laser (PDL) irradiation achieves a synergistic effect that reduces the required radiant exposures of the individual phototherapies to achieve persistent vascular shutdown. PDL combined with antiangiogenic agents is a promising strategy to achieve persistent vascular shutdown by preventing reformation and reperfusion of photocoagulated blood vessels. Integration of LSI into the clinical workflow may lead to surgical image guidance that maximizes acute photocoagulation, which is expected to improve PWS therapeutic outcome. Continued integration of noninvasive optical imaging technologies and biochemical analysis collectively are expected to lead to more robust treatment strategies.

Propranolol as a potentially novel treatment of arteriovenous malformations

Author(s): Lu, Jianyun; Anvari, Radean; Wang, Jinwei; Huang, Jian; Pei, Shiyao; Xiang, Yaping; Huang, Jinhua; Yin, Zhaoqi; Chen, Jing; Nelson, J Stuart; Tan, Wenbin

Activation of RhoA, Smad2, c-Src, PKC-βII/δ and JNK in atopic dermatitis

Atopic dermatitis is a multifactorial skin disease characterised by chronic and relapsing inflammation whose pathogenesis is incompletely understood. We found that the expression of TGFβR1 and the activation of SMAD2, RhoA, JNK, PKC‐βII/δ and c‐Src were upregulated in the infiltrated inflammatory cells, fibroblasts and vasculatures in the dermis and epidermis. In addition, increases in the expression of TGFβR1 and phosphorylation levels of JNK and c‐Src were positively correlated with the inflammatory progression of atopic dermatitis severity.

Coexistence of Eph receptor B1 and ephrin B2 in port‐wine stain endothelial progenitor cells contributes to clinicopathological vasculature dilatation

Port‐wine stain (PWS) is a vascular malformation characterized by progressive dilatation of postcapillary venules, but the molecular pathogenesis remains obscure.