Dimitrios Georgas

Expression of microRNAs in basal cell carcinoma

Background  Perturbations in the expression profiles of microRNAs (miRNAs) have been reported for a variety of different cancers. Differentially expressed miRNAs have not been systematically evaluated in basal cell carcinoma (BCC) of the skin.

Comparative microarray analysis of microRNA expression profiles in primary cutaneous malignant melanoma, cutaneous malignant melanoma metastases, and benign melanocytic nevi

Perturbations in microRNA (miRNA) expression profiles have been reported for cutaneous malignant melanoma (CMM) predominantly when examined in cell lines. Despite the rapidly growing number of newly discovered human miRNA sequences, the availability of up-to-date miRNA expression profiles for clinical samples of primary cutaneous malignant melanoma (PCMM), cutaneous malignant melanoma metastases (CMMM), and benign melanocytic nevi (BMN) is limited. Specimens excised from the center of tumors (lesional) from patients with PCMM (n=9), CMMM (n=4), or BMN (n=8) were obtained during surgery. An exploratory microarray analysis was performed by miRNA expression profiling based on Agilent platform screening for 1205 human miRNAs. The results from the microarray analysis were validated by TaqMan quantitative real-time polymerase chain reaction. In addition to several miRNAs previously known to be associated with CMM, 19 unidentified miRNA candidates were found to be dysregulated in CMM patient samples. Among the 19 novel miRNA candidates, the genes hsa-miR-22, hsa-miR-130b, hsa-miR-146b-5p, hsa-miR-223, hsa-miR-301a, hsa-miR-484, hsa-miR-663, hsa-miR-720, hsa-miR-1260, hsa-miR-1274a, hsa-miR-1274b, hsa-miR-3663-3p, hsa-miR-4281, and hsa-miR-4286 were upregulated, and the genes hsa-miR-24-1*, hsa-miR-26a, hsa-miR-4291, hsa-miR-4317, and hsa-miR-4324 were downregulated. The results of this study partially confirm previous CMM miRNA profiling studies identifying miRNAs that are dysregulated in CMM. However, we report several novel miRNA candidates in CMM tumors; these miRNA sequences require further validation and functional analysis to evaluate whether they play a role in the pathogenesis of CMM.

Expression levels of the microRNA maturing microprocessor complex component DGCR8 and the RNA-induced silencing complex (RISC) components argonaute-1, argonaute-2, PACT, TARBP1, and TARBP2 in epithelial skin cancer.

The microprocessor complex mediates intranuclear biogenesis of precursor microRNAs from the primary microRNA transcript. Extranuclear, mature microRNAs are incorporated into the RNA‐induced silencing complex (RISC) before interaction with complementary target mRNA leads to transcriptional repression or cleavage. In this study, we investigated the expression profiles of the microprocessor complex subunit DiGeorge syndrome critical region gene 8 (DGCR8) and the RISC components argonaute‐1 (AGO1), argonaute‐2 (AGO2), as well as double‐stranded RNA‐binding proteins PACT, TARBP1, and TARBP2 in epithelial skin cancer and its premalignant stage. Patients with premalignant actinic keratoses (AK, n = 6), basal cell carcinomas (BCC, n = 15), and squamous cell carcinomas (SCC, n = 7) were included in the study. Punch biopsies were harvested from the center of the tumors (lesional), from healthy skin sites (intraindividual controls), and from healthy skin sites in a healthy control group (n = 16; interindividual control). The DGCR8, AGO1, AGO2, PACT, TARBP1, and TARBP2 mRNA expression levels were detected by quantitative real‐time reverse transcriptase polymerase chain reaction. The DGCR8, AGO1, AGO2, PACT, and TARBP1 expression levels were significantly higher in the AK, BCC, and SCC groups than the healthy controls (P < 0.05). There was no significant difference in the TARBP2 expression levels between groups (P > 0.05). This study indicates that major components of the miRNA pathway, such as the microprocessor complex and RISC, are dysregulated in epithelial skin cancer.

Microarray analysis of microRNA expression in cutaneous squamous cell carcinoma

BACKGROUND MicroRNAs (miRNAs) are a novel class of short RNAs that are capable epigenetically regulating gene expression in eukaryotes. MicroRNAs have been shown to be dysregulated in a variety of cancers. The data on miRNA expression in cutaneous squamous cell carcinoma (cSCC) are very limited, and microarray-based miRNA expression profiles of cSCC have not yet been determined. OBJECTIVE To describe differentially expressed miRNAs in cSCC. METHODS Seven patients with cSCC were enrolled in the present study. Tumor biopsies (n=7) were taken from the center of each tumor. Adjacent healthy skin (n=7) was biopsied as a control (intraindividual control). miRNA expression profiles of all specimens were detected by microarray miRNA expression profiling based on miRBAse 16 scanning for 1205 potential human miRNA target sequences. The microarray results were confirmed by TaqMan quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS Non-stringent filtering with a non-adjusted p ≤ 0.05 revealed thirteen up-regulated and eighteen down-regulated miRNAs. Non-stringent filtering with a non-adjusted p ≤ 0.01 revealed three up-regulated (hsa-miR-135b, hsa-miR-424 and hsa-miR-766) and six down-regulated (hsa-miR-30a*, hsa-miR-378, hsa-miR-145, hsa-miR-140-3p, hsa-miR-30a and hsa-miR-26a) miRNAs in cSCC. CONCLUSION This study reveals differentially expressed miRNAs that may play a role in the molecular pathogenesis of cSCC and that are excellent candidates for further validation and functional analysis.

The miRNA machinery in primary cutaneous malignant melanoma, cutaneous malignant melanoma metastases and benign melanocytic nevi

Although several studies have shown a dysregulation of microRNA (miRNA) expression profiles in cutaneous melanoma, there has been little research on the miRNA machinery itself. In this study, we investigated the mRNA expression profiles of different miRNA machinery components in primary cutaneous malignant melanoma (PCMM), cutaneous malignant melanoma metastases (CMMM) and benign melanocytic nevi (BMN). Patients with PCMM (n = 7), CMMM (n = 6) and BMN (n = 7) were included in the study. Punch biopsies were harvested from the centers of tumors (lesional) and from BMN (control). In contrast to previous reports exploring specific clusters of miRNAs in PCMM, the present study investigates mRNA expression levels of Dicer, Drosha, Exp5, DGCR8 and the RISC components PACT, argonaute-1, argonaute-2, TARBP1, TARBP2, MTDH and SND1, which were detected by TaqMan real-time reverse transcription polymerase chain reaction (RT-PCR). Argonaute-1, TARBP2 and SND1 expression levels were significantly higher in BMN compared to PCMM (p < 0.05). TARBP2 expression levels were significantly higher in CMMM compared to PCMM (p < 0.05). SND1 expression levels were significantly higher in CMMM compared to PCMM and BMN (p < 0.05). Dicer, Drosha, DGCR8, Exp5, argonaute-2, PACT, TARBP1 and MTDH expression levels showed no significant differences within groups (p > 0.05). The results of this study show that the miRNA machinery components argonaute-1, TARBP2 and SND1 are dysregulated in PCMM and CMMM compared to BMN and may play a role in the process of malignant transformation.

Effects of a Long-Pulsed 800-nm Diode Laser on Axillary Hyperhidrosis: A Randomized Controlled Half-Side Comparison Study

Background Generally, axillary hyperhidrosis (AH) is treated with antiperspirant agents, botulinum toxin, or local surgery. The effect of laser treatment on sweat secretion in patients with AH has not been investigated. Objective To evaluate the effect of diode laser epilation on the sweat rate of patients with AH. Materials and Methods We performed a randomized half‐side controlled trial. Twenty‐one patients were treated with 5 cycles of an 800‐nm diode laser. Sweat rates were documented using gravimetry and a visual analogue scale. Histologic examination was performed in all patients before and after treatment. Results A significant reduction in sweat rate was observed on the laser‐treated (median 89 mg/min, range 42–208 mg/min vs 48 mg/min, range 17–119 mg/min; p < .001) and the untreated contralateral (median 78 mg/min, range 25–220 mg/min vs median 65 mg/min, range 24–399 mg/min; p = .04) sides, although no significant difference was found between the treated and untreated sides (p = .10). Conclusion Although we observed a significant decrease in sweat rate on laser‐treated sites, laser epilation was not able to reduce the sweat rate significantly more than on the untreated contralateral side. These results probably indicate a placebo effect rather than a direct therapeutic effect of laser epilation.

A randomized, half-side comparative study of aminolaevulinate photodynamic therapy vs. CO2 laser ablation in immunocompetent patients with multiple actinic keratoses

Background  Photodynamic therapy (PDT) and laser ablation (LA) are frequently used treatment options for multiple actinic keratoses (AK), yet they have not been compared head to head.

The expression of antimicrobial peptides is significantly altered in cutaneous squamous cell carcinoma and precursor lesions.

Background  Antimicrobial peptides and proteins are not only effectors of the immune system but are also attributed important roles in tumour progression or tumour suppression in several malignancies such as oral squamous cell carcinoma (SCC).

Microbial Profile and Antimicrobial Susceptibility of Bacteria Found in Inflammatory Hidradenitis Suppurativa Lesions

Background: The role of bacterial colonization in hidradenitis suppurativa (HS) lesions is poorly understood. To date, data on the related microbial profile and especially on bacterial resistance rates are scarce. Methods: The results of bacterial cultures and susceptibility patterns of the isolated microorganisms obtained from deep portions of HS lesions from patients who underwent surgery at our HS Centre between 2010 and 2015 were retrospectively evaluated. Results: Analyses of 113 bacterial samples from 113 HS patients revealed bacterial growth in 95 samples (84.1%). Polymicrobial growth was found in 51 samples (45.1%). Coagulase-negative staphylococci and Staphylococcus aureus were the most commonly isolated bacteria, followed by Proteus mirabilis and Escherichia coli. Data on susceptibility testing were available for 68 samples, which yielded 129 isolates. The isolated strains were primarily resistant to penicillin G, followed by erythromycin, clindamycin and ampicillin. The highest effectiveness against isolates was observed for fosfomycin, imipenem, fluoroquinolones (moxifloxacin, ciprofloxacin, levofloxacin), and cotrimoxazole. Conclusions: Our findings on bacterial species and their topographical distribution revealed that the microbial flora in HS lesions reflects commensal flora of the skin. Due to the susceptibility rate and immunomodulatory and anti-inflammatory properties, cotrimoxazole may represent an alternative antibiotic agent and should be considered for therapy in HS patients.

In vivo determination of epidermal thickness using high-definition optical coherence tomography

A . MOR I TA T-T . KUO H. INAGAK I 1 Department of Anatomic Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi Mizuho-cho, Mizuhoku, Nagoya 467-8601, Japan Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan Department of Pathology, Chang Gung Memorial Hospital, Taoyuan, Taiwan Correspondence: Hiroshi Inagaki. E-mail: hinagaki@med.nagoya-cu.ac.jp