A multi center real world observation to evaluate the efficacy of cryotherapy versus local hyperthermia for the treatment of plane warts.

Most plane warts are recalcitrant to treatment. Both cryotherapy and local hyperthermia have been applied to treat plane warts. However, no direct comparative study on their respective efficacy and safety has ever been performed. To assess the efficacy and safety of local hyperthermia at 43 ± 1°C versus liquid nitrogen cryotherapy for plane warts. Sequential patients with plane warts entered the study, either receiving cryotherapy or local hyperthermia therapy at the discretion of the patients and the recommendations of consultants. Cryotherapy with liquid nitrogen was delivered in two sessions 2 weeks apart, while local hyperthermia was delivered on three consecutive days, plus two similar treatments 10 ± 3 days later. The temperature over the treated skin surface was set at 43 ± 1°C for 30 min in each session. The primary outcome was the clearance rates of the lesions 6 months after treatment. Among the 194 participants enrolled, 183 were included in the analysis at 6 months. Local hyperthermia and cryotherapy achieved clearance rates of 35.56% (48/135) and 31.25% (15/48), respectively (p = 0.724); recurrence rates of 16.67% (8/48) and 53.33% (8/15) (p = 0.01); and adverse events rates of 20.74% (28/135) and 83.33% (40/48), respectively (p < 0.001). Cryotherapy had a higher pain score (p < 0.001) and a longer healing time (p < 0.001). Local hyperthermia at 43°C and cryotherapy had similar efficacy for plane warts. Local hyperthermia had a safer profile than cryotherapy but it required more treatment visits during a treatment course. More patients preferred local hyperthermia due to its treatment friendly nature.

Local Hyperthermia Versus Cryotherapy for Treatment of Plantar Warts: A Prospective Multi-centre Non-randomized Concurrent Controlled Clinical Trial.

Cryotherapy is one of the most common treatments for warts; however, pain during treatment and relatively high recurrence rates limit its use. Local hyperthermia has also been used successfully in the treatment of plantar warts. The aim of this study was to compare the clinical effectiveness of local hyperthermia vs cryotherapy for the treatment of plantar warts. This multi- centre, open, 2-arm, non-randomized concurrent controlled trial included 1,027 patients, who received either cryotherapy or local hyperthermia treatment. Three months after treatment, local hyperthermia and cryotherapy achieved complete clearance rates of 50.9% and 54.3%, respectively. Recurrence rates were 0.8% and 12%, respectively. Pain scores during local hyperthermia were significantly lower than for cryotherapy. Both local hyperthermia and cryotherapy demonstrated similar efficacy for clearance of plantar warts; while local hyperthermia had a lower recurrence rate and lower pain sensation during treatment.

SFRP5 inhibits melanin synthesis of melanocytes in vitiligo by suppressing the Wnt/ß-catenin signaling.

Secreted frizzled-related protein 5 (SFRP5) plays a pivotal role in regulating the development of many tissues and organs, however, as an inhibitor of Wnt signaling, the role of SFRP5 in vitiligo remains unknown. Hence, we speculated that SFRP5 might be associated with melanogenesis in melanocytes by regulating Wnt signaling in vitiligo. In this study, we found that SFRP5 was overexpressed in the skin lesions of patients with vitiligo. Compared with that in normal epidermal melanocytes (PIG1), the expression of SFRP5 was increased in vitiligo melanocytes (PIG3V). To investigate the effect of SFRP5 on melanin synthesis, PIG1 cells were infected with recombinant SFRP5 adenovirus (AdSFRP5), and PIG3V cells were infected with recombinant siSFRP5 adenovirus (AdsiSFRP5). The results showed that SFRP5 overexpression inhibited melanin synthesis in PIG1 cells through downregulation of microphthalmia-associated transcription factor (MITF) and its target proteins via suppression of the Wnt/ß-catenin signaling pathway. Accordingly, SFRP5 silencing increased melanin synthesis and activated the Wnt signaling pathway in PIG3V cells. Moreover, SFRP5 overexpression also downregulated the transcriptional activity of T cell factor/lymphoid enhancer factor (TCF/LEF) in PIG1 cells. Furthermore, this inhibitory effect of SFRP5 on melanin synthesis was reversed by treatment with the ß-catenin agonist, SKL2001. The inhibitory action of SFRP5 in pigmentation was further confirmed in vivo using a nude mouse model. Hence, our results indicate that SFRP5 can inhibit melanogenesis in melanocytes. Additionally, our findings showed that SFRP5 plays a vital role in the development of vitiligo, and thus may serve as a potential therapeutic target for vitiligo.

A double-blind, randomized, placebo- and positive-controlled phase III trial of 1% benvitimod cream in mild-to-moderate plaque psoriasis.

BACKGROUND: Benvitimod cream, a novel synthetic small molecule, was effective in treating mild-to-moderate plaque psoriasis. We conducted a phase III clinical trial to assess the efficacy and safety of benvitimod cream in patients with mild-to-moderate plaque psoriasis. METHODS: We randomly assigned 686 patients (2:1:1) to receive 1% benvitimod cream, 0.005% calcipotriol ointment or placebo twice a day for 12 weeks. The primary efficacy end points were the percentage of patients with a 75% or greater reduction from baseline in the psoriasis area and severity index (PASI 75) score and with a score of 0 or 1 in static physician's global assessment (sPGA) at week 12. RESULTS: The results showed that 50.4% of patients in the benvitimod group achieved PASI 75, which was significantly higher than that in the calcipotriol (38.5%, P < 0.05) and placebo (13.9%, P < 0.05) groups. The proportion of patients achieving an sPGA score 0 or 1 was 66.3% in the benvitimod group and 63.9% in the calcipotriol group, which were both significantly higher than that in the placebo group (34%, P < 0.05). In the long-term follow-up study, 50.8% of patients experienced recurrence. After retreatment with 1% benvitimod, 73.3% of patients achieved an sPGA score of 0 or 1 again at week 52. Adverse events included application site irritation, follicular papules, and contact dermatitis. No systemic adverse reactions were reported. CONCLUSION: During this 12-week study, benvitimod cream was demonstrated with high effectiveness and safety in patients with mild-to-moderate plaque psoriasis. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR), ChiCTR-TRC-13003259; http://www.chictr.org.cn/showprojen.aspx?proj=6300.

Increased circulating Th17 cells and elevated serum levels of TGF-beta and IL-21 are correlated with human non-segmental vitiligo development.

Although non-segmental vitiligo (NSV) results from the autoimmune destruction of melanocytes, the detailed immune mechanisms have not yet been fully elucidated. Th17 cells have been identified to be implicated in human autoimmune diseases. In this study, the frequencies of peripheral blood Th17 cells and serum levels of IL-17A and Th17 cell-related cytokines were examined in 45 patients with active NSV compared to 45 race-, gender-, and age-matched healthy controls. Our results showed increased circulating Th17 cell frequencies and elevated serum IL-17A, TGF-ß1, and IL-21 levels in patients with NSV. Meanwhile, the increased Th17 cell frequencies are positively correlated with serum TGF-ß1 level, and the body surface area of lesions is positively correlated with elevated TGF-ß1 and IL-21 levels and Th17 cell frequencies. Furthermore, positive correlation was identified between Th17 and Th1 cell frequencies in patients with NSV. These results further indicate the potential involvement of Th17 cells and the collaborative contribution of Th17 and Th1 in NSV development, and suggest that the elevated serum TGF-ß1 and IL-21 levels could contribute to enhanced Th17 cell differentiation in NSV.

Two new susceptibility loci 1q24.2 and 11p11.2 confer risk to severe acne.

Severe acne is a chronic inflammatory skin disorder characterized by widespread inflammatory lesions including nodules, cysts and potential scarring. Here we perform the first genome-wide association study of severe acne in a Chinese Han population comprising 1,056 cases and 1,056 controls using the Illumina HumanOmniZhongHua-8 BeadChip. In an independent cohort of 1,860 cases and 3,660 controls of Chinese Han, we replicate 101 SNPs of which 3 showed consistent association. We identify two new susceptibility loci at 11p11.2 (DDB2, rs747650, P(combined)=4.41 × 10⁻9 and rs1060573, P(combined)=1.28 × 10⁻8) and 1q24.2 (SELL, rs7531806, P(combined)=1.20 × 10⁻8) that are involved in androgen metabolism, inflammation processes and scar formation in severe acne. These results point to new genetic susceptibility factors and suggest several new biological pathways related to severe acne.

WITHDRAWN: Comparision between 308-nm excimer laser and 308-nm excimer lamp in the treatment of vitiligo - a randomized self control study.

Ahead of Print article withdrawn by publisher.

Association analyses identify three susceptibility Loci for vitiligo in the Chinese Han population.

To identify susceptibility loci for vitiligo, we extended our previous vitiligo genome-wide association study with a two-staged replication study that included 6,857 cases and 12,025 controls from the Chinese Han population. We identified three susceptibility loci, 12q13.2 (rs10876864, P(combined)=8.07 × 10(-12), odds ratio (OR)=1.18), 11q23.3 (rs638893, P(combined)=2.47 × 10(-9), OR=1.22), and 10q22.1 (rs1417210, P(combined)=1.83 × 10(-8), OR=0.88), and confirmed three previously reported loci for vitiligo, 3q28 (rs9851967, P(combined)=8.57 × 10(-8), OR=0.88), 10p15.1 (rs3134883, P(combined)=1.01 × 10(-5), OR=1.11), and 22q12.3 (rs2051582, P(combined)=2.12 × 10(-5), OR=1.14), in the Chinese Han population. The most significant single-nucleotide polymorphism in the 12q13.2 locus is located immediately upstream of the promoter region of PMEL, which encodes a major melanocyte antigen and has expression loss in the vitiligo lesional skin. In addition, both 12q13.2 and 11q23.3 loci identified in this study are also associated with other autoimmune diseases such as type 1 diabetes and systemic lupus erythematosus. These findings provide indirect support that vitiligo pathogenesis involves a complex interplay between immune regulatory factors and melanocyte-specific factors. They also highlight similarities and differences in the genetic basis of vitiligo in Chinese and Caucasian populations.

Infliximab monotherapy for Chinese patients with moderate to severe plaque psoriasis: a randomized, double-blind, placebo-controlled multicenter trial.

BACKGROUND: Tumor necrosis factor-α is a key mediator in the pathogenesis of psoriasis. Infliximab is a monoclonal antibody that specifically binds to tumor necrosis factor-α. The purpose of this study was to validate the efficacy and safety of 5 mg/kg infliximab therapy in Chinese patients with moderate to severe plaque psoriasis. METHODS: In this multicenter, double-blind, placebo-controlled trial, 129 patients with moderate-to-severe psoriasis were randomized to the induction therapy (weeks 0, 2 and 6) with infliximab 5 mg/kg (n = 84) or placebo (n = 45), followed with infliximab 5 mg/kg scheduled at week 14 and week 22 in the infliximab group, and infliximab 5 mg/kg scheduled at weeks 10, 12 and 16 in the placebo group. The primary end point was the proportion of patients who achieved at least 75% improvement in Psoriasis Area and Severity Index (PASI 75 response rate) from baseline at week 10. RESULTS: At week 10, 81.0% of patients treated with infliximab (5 mg/kg) achieved a 75% or greater improvement compared with 2.2% of patients treated with placebo (P < 0.001). A significant improvement in PASI, Physician's Global Assessment (PGA) and Dermatology Life Quality Index (DLQI), was seen from week 6 through week 14 in the infliximab group compared with the placebo group. Through week 22, PASI, PGA, DLQI were well maintained. The incidence of adverse events for the infliximab treatment group was slightly higher in comparison to the placebo treatment group during the first 10 weeks without statistical significance. However, there were 3 cases of tuberculosis that developed during the 26 weeks treatment with infliximal. CONCLUSIONS: Infliximab treatment was effective as induction and maintenance treatments for Chinese patients with moderate to severe plaque psoriasis. Most drug-induced adverse events were mild to moderate, and well tolerated. Screening for tuberculosis is essential and prophylactic treatment should be given if necessary.

Systemic analyses of immunophenotypes of peripheral T cells in non-segmental vitiligo: implication of defective natural killer T cells.

Although it is widely believed that non-segmental vitiligo (NSV) results from the autoimmune destruction of melanocytes, a clear understanding of defects in immune tolerance, which mediate this uncontrolled self-reactivity, is still lacking. In the present study, we systemically evaluated circulating regulatory T (Treg) cells, including CD4(+) CD25(+) FoxP3(+) Treg cells and invariant natural killer T (iNKT) cells, as well as naïve and memory CD4(+) and CD8(+) T cells and their cytokine production, in a cohort of 43 progressive NSV patients with race-, gender-, and age-matched healthy controls. We found that the general immunophenotypes of CD4(+) and CD8(+) T cells and the percentage of CD4(+) CD25(+) FoxP3(+) Tregs were comparable between NSV and healthy controls. However, percentages of peripheral iNKT cells were significantly decreased in NSV patients compared to that in healthy controls. Our data confirm the previous notion that the percentage of peripheral CD4(+) CD25(+) FoxP3(+) Tregs remains unaltered in NSV and suggests the involvement of defective iNKT cells in the pathogenesis of NSV.

Treatment of psoriasis with recombinant human LFA3-antibody fusion protein: a multi-center, randomized, double-blind trial in a Chinese population.

To evaluate clinical efficacy and safety of injectable recombinant human LFA3-antibody fusion protein (rhLFA3-IgFP), a multi-center, randomized, double-blind, double-dummy, parallel-controlled clinical trial was performed in 212 cases of moderate to severe psoriasis. Intramuscular injection of rhLFA3-IgFP (15 mg/week) and oral administration of blank dummy methotrexate at the dose of 7.5 mg/week was performed in the patients in the experimental group, and control patients were orally administered with methotrexate at the dose of 7.5 mg/week and intramuscularly injected with the blank dummy rhLFA3-IgFP (15 mg/week). PASI was determined prior to and at 2, 4, 6, 8, 12, 16, 20 weeks after the treatment. The efficacy evaluation was carried out on 192 patients, and no significant differences were found in PASI50, PASI75 & PASI90 between the two groups after twelve weeks' treatment (p>0.05). After discontinuation, PASI scores continued to decrease drastically in the experiment group, whereas they increased in the control group. At 8 weeks after discontinuation, PASI scores were decreased by 62.32% (p<0.05) and 52.67% (p<0.05) in the experimental and control groups, respectively. No serious adverse reactions were observed. In conclusion, the results of our investigation demonstrated that rhLFA3-IgFP was an effective therapy for chronic plaque psoriasis with lasting action and low incidence of adverse reactions.

Pathogen characteristics and its sensitivity against antimicrobial agents in fatal bacterial granuloma after eyelid trauma in vitro.

AIM: To understand the pathogen characteristics and its sensitivity against antimicrobial agents in fatal bacterial granuloma after eyelid trauma (FBGT) in vitro, and to provide laboratory evidence for diagnosis. METHODS: The FBGT pathogens were isolaated and cultured with reformed rabbit-brain anaerobic enriched broth (RRAB), and identified by ATB/API 20A system. The minimum inhibiting concentration (MIC) was determined by anaerobic broth dilution method. RESULTS: A total of 22 strains of pathogen were separated from 21 patients with FBGT and identified as Propionibacterium acnes (PA) by ATB/API 20A system. The MIC of ciprofloxacin for 22 PA strains was 0.0625-0.5mg/L, the MIC of penicillin, ampicillin, ampicillin/sulbactam, cefoperazone, lincomycin, and imipenem/cilastatin were 0.125-0.5mg/L, the MIC of ticarcillin/clavulanic acid was 0.250-1.000 mg/L, and the MIC of metronidazole was 64-256mg/L. The pathogen of FBGT was strictly anaerobic PA, which growed slowly and better in nutritious RRAB broth. All PA were resistant to metronidazole, but susceptive to other routine antimicrobial agents, such as penicillin, ampicillin and lincomycin. CONCLUSION: [corrected] FBGT should not be treated with metronidazole. Clinicians should choose combined use of drugs or operation to treat FBGT according to patients' individual condition and the results of drug sensitivity test.

Genome-wide association study for vitiligo identifies susceptibility loci at 6q27 and the MHC.

We conducted a genome-wide association study of generalized vitiligo in the Chinese Han population by genotyping 1,117 cases and 1,429 controls. The 34 most promising SNPs were carried forward for replication in samples from individuals of the Chinese Han (5,910 cases and 9,916 controls) and Chinese Uygur (713 cases and 824 controls) populations. We identified two independent association signals within the major histocompatibility complex (MHC) region (rs11966200, Pcombined=1.48x10(-48), OR=1.90; rs9468925, Pcombined=2.21x10(-33), OR=0.74). Further analyses suggested that the strong association at rs11966200 might reflect the reported association of the HLA-A*3001, HLA-B*1302, HLA-C*0602 and HLA-DRB1*0701 alleles and that the association at rs9468925 might represent a previously unknown HLA susceptibility allele. We also identified one previously undescribed risk locus at 6q27 (rs2236313, Pcombined=9.72x10(-17), OR=1.20), which contains three genes: RNASET2, FGFR1OP and CCR6. Our study provides new insights into the genetic basis of vitiligo.

Preparation and anti-inflammatory activity of triptolide ethosomes in an erythema model.

CONTEXT: The aim of this work was to evaluate the suitability of ethosomes as carriers for the topical application of triptolide in a rat model of erythema. OBJECTIVE: We determined the optimal conditions for preparing ethosomes, and we measured their vesicle size by a laser particle-size analyzer and the efficiency of entrapment of triptolide by ultracentrifugation. METHODS: The in vitro percutaneous permeation of triptolide-loaded ethosomes was investigated by measuring diffusion across a sample of rat skin. To explore the transdermal delivery in vivo, we used a model in which erythema was induced in rats by methyl nicotinate and determined the change in erythema index caused by the anti-inflammatory activity of triptolide by a reflection spectrophotometer. RESULTS: The optimal conditions for preparing triptolide ethosomes consisted of ultrasonication of 45% (v/v) ethanol and 2% (w/v) DPPC for 5 minutes, which produced an average vesicle size of 51.4 nm and an entrapment efficiency of 98%. This ethosomal formulation of triptolide caused the greatest in vitro 24-hour accumulation of triptolide (83.7%) with no permeation time delay, and it reduced erythema in vivo more rapidly and more completely than other formulations. CONCLUSIONS: Ethosomes might be a promising carrier that would enable the beneficial properties of triptolide to be safely delivered in a topical formulation.

Increased Th17 cells are accompanied by FoxP3(+) Treg cell accumulation and correlated with psoriasis disease severity.

Both T-helper 17 cells (Th17) and CD4(+)CD25(+) regulatory T cells (Treg) play important roles in the pathogenesis of psoriasis. However, the relationship between Th17 and Treg cells and their dynamic variations in psoriasis remain unclear. In this study, we found that both Th17 and FoxP3(+) Treg cells were increased in psoriasis patients both in the peripheral circulation and skin tissue lesions and were positively correlated with disease severity. The ratio of Th17 to Treg cells in skin tissue lesions was inversely correlated with PASI scores, while it was positively correlated with PASI scores in the circulation. IL-17 secretion by CD4(+) T cells was not regulated by Treg cells, even though Treg cells exhibited significant inhibition on CD4(+) T cells proliferation and IFN-gamma production. These findings provide new information regarding the association between Th17 and Treg cells, which will further our understanding of the pathogenesis of psoriasis.

Negative regulation of endogenous protein kinase Calpha on the dynamic change of carbachol-induced intracellular calcium response in different melanoma cells.

Regulations of intracellular protein kinase C (PKC) on carbachol (CCh)-induced intracellular calcium ([Ca(2+)]i) responses were investigated in different stages of melanoma cells. We found that CCh (1 mM) significantly increased [Ca(2+)]i with 6-, 4-, 4-, and 25-folds intensities in WM793B, 451Lu, SK-MEL-5, and A2058 melanoma cells, respectively. Pretreatment of phorbol 12, 13-dibutyrate (PDBu, 2 microM), an activator of intracellular PKC, significantly suppressed CCh-induced peak reactions in WM793B, SK-MEL-5, and A2058 cells. RT-PCR data showed that mRNA levels of PKCalpha were 12-, 4-, 6-, and 0.9-folds higher in above four melanoma cells. Short interfering RNA (siRNA) targeting to PKCalpha in WM793B cells enhanced CCh-induced peak calcium reactions. Present data indicated that CCh-induced [Ca(2+)]i responses were dynamically changed in different stages of melanoma progression. Moreover, intracellular PKCalpha activated by exogenous agonist and expressed through endogenous gene transcription negatively regulated CCh-induced calcium responses. The functional analysis on the relationship between CCh-induced calcium response and endogenous PKCalpha expression might be helpful to predict the development of melanoma.

The influence of BCR density on the differentiation of natural poly-reactive B cells begins at an early stage of B cell development.

B cell antigen receptor (BCR) density plays a role in the differentiation of immature B cells to their mature compartments; however, the exact strategy of its influence on the development of natural autoreactive B cells is still unclear. In the present study, we explored the role of BCR surface density in autoreactive B cell development by studying two lines of mice containing distinct copy numbers of an IgH transgene with V(H) derived from a poly-reactive natural antibody 3B4. Surface BCR levels were found to be related to the transgene copy number in these mice. In mice with higher copy numbers of the transgene, the BCRs were found to promote the remaining of autoreactive B cells into marginal zone (MZ) and B-1a subsets; meanwhile, elevated surface BCR levels were correlated with a significant decrease of follicular (Fo) B cell numbers and a reduction in the number of multiple stages of immature B cells both in spleen and bone marrow (BM). Interestingly, no difference in the ratio of cell apoptosis and proliferation was found in all stages of B cell development between two lines, except that more severely aberrant proliferation of pro/pre-B cells in BM was found in mice with higher transgene copies. This data supports the idea that natural poly-reactive B cells can be positively selected into MZ and B-1 cells, and high BCR surface density favors this selection. More importantly, our data suggests that the influence by receptor expression on the differentiation of natural poly-reactive B cells begins at an early stage of B cell development.

Association study of NFKB1 and SUMO4 polymorphisms in Chinese patients with psoriasis vulgaris.

Nuclear factor kappa-beta (NF-kappaB) is a critical transcription factor modulating the expression of many genes involved in the pathogenesis of psoriasis. SUMO4 is a negative regulator of NF-kappaB in the cell-signaling pathway. Two functional polymorphisms of the NFKB1 and SUMO4 genes have been found to be associated with the risks of some autoimmune-related diseases, but no published study has investigated the role of these polymorphisms in the etiology of psoriasis in the Chinese population. In this hospital-based, case-control study of 519 Chinese psoriasis vulgaris patients and 541 matched controls, we genotyped the NFKB1-94 ins/delATTG and the SUMO4 rs237025 A>G polymorphisms and assessed their respective associations with psoriasis vulgaris risk. We found that the genotype distribution of NFKB1-94 ins/delATTG polymorphism was statistically different between psoriasis patients and controls (P = 0.031). But the difference was not still statistically significant after correction for multiple comparisons. The frequency of wild WW genotype in psoriasis patients was statistically higher than that in controls (35.8 vs. 29.0%, respectively, P = 0.021). The W allele frequency in cases was also significantly higher than that in controls (59.7 vs. 54.1%, P = 0.008). Compared with the DD genotype, a significantly increased psoriasis risk was associated with the NFKB1 WW genotype (adjusted OR = 1.57, 95% CI = 1.10-2.24). In addition, the WW genotype frequency was also statistically higher in the psoriatic subgroups of onset age 20, male patients and sporadic patients than that in controls. But, no associations of the SUMO4 rs237025 A>G polymorphism with the susceptibility of psoriasis were detected. In conclusion, we found a marginal association between the NFKB1-94 ins/delATTG WW genotype and the increased psoriasis vulgaris risk and the association was more evident in the subgroups of onset age 20, male patients and sporadic patients in Chinese.

Optimal frequency of treatment with the 308-nm excimer laser for vitiligo on the face and neck.

OBJECTIVES: This study was designed to determine the optimal treatment frequency with the 308-nm excimer laser for vitiligo and identify key clinical variable(s) associated with treatment efficacy at the optimal frequency. BACKGROUND DATA: Optimal clinical parameters for excimer laser treatment of vitiligo have not been fully determined. Data about the influence on treatment frequency of different clinical variables of vitiligo are needed to facilitate effective treatment regimens. METHODS: A total of 187 patients were treated with the 308-nm excimer laser for 20 sessions at different frequencies (0.5, 1.0, 2.0, and 3.0 per week). The repigmentation rate was graded on a six-point scale and was blindly evaluated by independent physicians. RESULTS: The final percentage of repigmentation for group 0.5 was statistically lower than those for group 1.0, 2.0, and 3.0, and percentages of final levels of repigmentation among these three groups were not statistically different. The clinical variables showed no statistical differences in the final repigmentation effect. Repigmentation occurred fastest with treatment frequencies of 2.0 and 3.0 and there was no statistically significant difference between them. The onset of repigmentation correlated with the area of vitiliginous patches treated, not with the other clinical variables. CONCLUSIONS: The 308-nm excimer laser is effective for therapy to treat vitiligo on the face and neck. The ultimate laser-induced repigmentation effect does not correlate with treatment frequency and repigmentation occurs faster with treatment frequencies of 2.0 and 3.0 than that of 1.0. It appears that the onset of repigmentation correlates with the total area of vitiliginous patches and the optimal treatment frequency. Monitored studies on a larger population with long-term follow-up would be needed to confirm and extend our findings.

The role of glycogen synthase kinase 3beta in the transformation of epidermal cells.

Glycogen synthase kinase 3beta (GSK3beta) is a multifunctional serine/threonine kinase. We showed that the expression of GSK3beta was drastically down-regulated in human cutaneous squamous cell carcinomas and basal cell carcinomas. Due to its negative regulation of many oncogenic proteins, we hypothesized that GSK3beta may function as a tumor suppressor during the neoplastic transformation of epidermal cells. We tested this hypothesis using an in vitro model system, JB6 mouse epidermal cells. In response to epidermal growth factor (EGF) or 12-O-tetradecanoylphorbol-13-acetate (TPA), the promotion-sensitive JB6 P+ cells initiate neoplastic transformation, whereas the promotion-resistant JB6 P- cells do not. JB6 P- cells expressed much higher levels of GSK3beta than JB6 P+ cells; JB7 cells, the transformed derivatives of JB6, had the least amount of GSK3beta. The activity of GSK3beta is negatively regulated by its phosphorylation at Ser9. EGF and TPA induced strong Ser9 phoshorylation in JB6 P+ cells, but phosphorylation was seen at a much lesser extent in JB6 P- cells. EGF and TPA-stimulated Ser9 phosphorylation was mediated by phosphoinositide-3-kinase (PI3K)/Akt and protein kinase C (PKC) pathways. Inhibition of GSK3beta activation significantly stimulated activator protein-1 (AP-1) activity. Overexpression of wild-type (WT) and S9A mutant GSK3beta in JB6 P+ cells suppressed EGF and TPA-mediated anchorage-independent growth in soft agar and tumorigenicity in nude mice. Overexpression of a kinase-deficient (K85R) GSK3beta, in contrast, potentiated anchorage-independent growth and drastically enhanced in vivo tumorigenicity. Together, these results indicate that GSK3beta plays an important role in skin tumorigenesis.