A Case of Cystic Basal Cell Carcinoma Which Shows a Homogenous Blue/Black Area under Dermatoscopy

Basal cell carcinoma (BCC) is the most common skin tumor and contains several different histopathological types. Here, we report a case of cystic basal cell carcinoma, which is relatively rare and might be clinically misdiagnosed. A dermatoscopic examination of the case revealed a homogenous blue/black area usually not seen in BCC. We reviewed 102 BCC cases resected and diagnosed at Sapporo Medical University Hospital between April 2005 and March 2010. Among them, only three were the cystic type

Melanoma-Targeted Chemothermotherapy and In Situ Peptide Immunotherapy through HSP Production by Using Melanogenesis Substrate, NPrCAP, and Magnetite Nanoparticles

Exploitation of biological properties unique to cancer cells may provide a novel approach to overcome difficult challenges to the treatment of advanced melanoma. In order to develop melanoma-targeted chemothermoimmunotherapy, a melanogenesis substrate, N-propionyl-4-S-cysteaminylphenol (NPrCAP), sulfur-amine analogue of tyrosine, was conjugated with magnetite nanoparticles. NPrCAP was exploited from melanogenesis substrates, which are expected to be selectively incorporated into melanoma cells and produce highly reactive free radicals through reacting with tyrosinase, resulting in chemotherapeutic and immunotherapeutic effects by oxidative stress and apoptotic cell death. Magnetite nanoparticles were conjugated with NPrCAP to introduce thermotherapeutic and immunotherapeutic effects through nonapoptotic cell death and generation of heat shock protein (HSP) upon exposure to alternating magnetic field (AMF). During these therapeutic processes, NPrCAP was also expected to provide melanoma-targeted drug delivery system

ΔNp63 Controls a TLR3-Mediated Mechanism That Abundantly Provides Thymic Stromal Lymphopoietin in Atopic Dermatitis

<div><p>In the skin lesions of atopic dermatitis (AD), keratinocytes release large quantities of thymic stromal lymphopoietin (TSLP), causing unfavorable inflammation along with skin damage. Nevertheless, how TSLP influences keratinocytes themselves is still unknown. In this study, we showed that ΔNp63, a p53-homologue, predominantly expressed in keratinocytes regulated the receptor complex of TSLP, which determines susceptibility to self-derived TSLP. Expression of TSLP receptors in skin tissues and keratinocytes was assessed by immunohistochemistry and quantitative RT-PCR, and <i>in vitro</i> studies were also performed to examine the functional relevance of ΔNp63 in the expression of TSLP receptors and the constituting autocrine and/or paracrine pathway of TSLP under the condition of stimuli to innate receptors sensing cell damage. The results showed that normal keratinocytes in the upper epidermis preferentially expressed TSLP receptors and conversely lacked ΔNp63, which has an inhibitory effect on the expression of TSLP receptors. Interestingly, the epidermis of AD lesions was found to abundantly contain keratinocytes with low or undetectable levels of ΔNp63 (ΔNp63^lo/-). Moreover, in the absence of ΔNp63, keratinocytes readily presented TSLP and other cytokines by stimuli through Toll-like receptor 3 (TLR3). Together with the evidence that extrinsic TSLP itself augments TSLP production by keratinocytes without ΔNp63, the results indicate that ΔNp63^lo/- keratinocytes generate TSLP through a putative autocrine and/or paracrine pathway upon TLR3 stimulation within AD lesions, since moieties of damaged cells and pathogens stimulate TLR3.</p></div

TSLP induces signal transduction in ΔNp63-deficient HaCaT keratinocytes.

<p>Immunoblot analysis demonstrating phosphorylation of the p65 subunit of NF-κB at 24 hr after treatment with 10 µg/ml poly I:C and exogenous TSLP (10 ng/ml). The histogram shows the relative phospho- NF-κB expression normalized to NF-κB as determined by densitometric analysis. β-actin was used as a loading control. Data are representative of three independent experiments.</p

TSLP enhances inflammatory responses in ΔNp63-deficient keratinocytes.

<p>(<b>a, b</b>) Quantitative RT-PCR (<b>a</b>) and ELISA (<b>b</b>) demonstrate the level of endogenous TSLP at 24 hr (<b>a</b>) or 72 hr (<b>b</b>) after treatment with exogenous TSLP (1 or 10 ng/ml) under the condition of TLR3 stimulation (5 µg/ml poly I:C) in primary keratinocytes. (<b>c, d</b>) Quantitative RT-PCR (<b>c</b>) and ELISA (<b>d</b>) show the level of endogenous TSLP at 24 hr (<b>c</b>) or 72 hr (<b>d</b>) after stimulation with 10 µg/ml poly I:C and 10 ng/ml TSLP in siControl and sip63 HaCaT keratinocytes. (<b>e</b>) Quantitative RT-PCR confirming whether neutralization of TSLP inhibits the generation of TSLP under the condition of TLR3 stimulation (5 µg/ml poly I:C) in primary keratinocytes. One-way ANOVA followed by Tukey's multiple-comparison test. *<i>P</i><0.05, ***<i>P</i><0.005 and N.S., not significant. Data are representative of at least three independent experiments.</p

Unique expression profiles of ΔNp63 in AD epidermal lesions.

<p>(<b>a</b>) Immunohistochemical staining of ΔNp63 in normal skin and skin lesions of AD and SLE. Consecutive sections of each condition were stained with hematoxylin and eosin (HE). Bar  = 50 µm. (<b>b</b>) Level of ΔNp63 was classified into three categories depending on staining intensity, as indicated by ΔNp63^hi, ΔNp63^lo and ΔNp63⁻. The dot plot represents ratios of ΔNp63^lo/- keratinocytes in normal skin (n = 3) and AD lesions (n = 10). (<b>c</b>) Quantitative RT-PCR demonstrating the levels of TSLP and ΔNp63 mRNAs in normal skin and AD lesions. Student's <i>t</i> test. *<i>P</i><0.05 and ****<i>P</i><0.001. Data are representative of at least three independent experiments.</p