Blocking glutamate-mediated signalling inhibits human melanoma growth and migration.

Glutamate is an excitatory neurotransmitter that has been shown to regulate the proliferation, migration and survival of neuronal progenitors in the central nervous system through its action on metabotropic and ionotropic glutamate receptors (GluRs). Antagonists of ionotropic GluRs have been shown to cause a rapid and reversible change in melanocyte dendritic morphology, which is associated with the disorganization of actin and tubulin microfilaments in the cytoskeleton. Intracellular expression of microtubule-associated protein (MAP) 2a affects the assembly, stabilization and bundling of microtubules in melanoma cells; stimulates the development of dendrites; and suppresses melanoma cell migration and invasion. In this study, we investigated the relationship between glutamate-mediated signalling and microtubules, cell dendritic morphology and melanoma cell motility. We found that metabotropic GluR1 and N-methyl-d-aspartate receptor antagonists increased dendritic branching and inhibited the motility, migration and proliferation of melanoma cells. We also demonstrated that the invasion and motility of melanoma cells are significantly inhibited by the combination of increased expression of MAP2a and either metabotropic GluR1 or N-methyl-d-aspartate receptor antagonists. Moreover, the blockade of glutamate receptors inhibited melanoma growth in vivo. Collectively, these results demonstrate the importance of glutamate signalling in human melanoma and suggest that the blockade of glutamate receptors is a promising novel therapy for treating melanoma.

Treatment of infraorbital dark circles using a low-fluence Q-switched 1,064-nm laser.

OBJECTIVE: To evaluate the efficacy and safety of the low-fluence 1,064-nm Q-switched neodymium-doped yttrium aluminium garnet (QSNY) laser in treating infraorbital dark circles. PARTICIPANTS AND METHODS: Thirty women with infraorbital dark circles (predominant color dark brown) participated in this open-label study. Participants underwent eight sessions of low-fluence QSNY laser treatment at 4.2 J/cm(2) at 3- to 4-day intervals. A spot size of 3.5 mm was used, with a pulse duration of 8 ns. The melanin deposition in the lesional skin was observed in vivo using reflectance confocal microscopy (RCM). Morphologic changes were evaluated using a global evaluation, an overall self-assessment, a narrow-band reflectance spectrophotometer, and a skin hydration measurement instrument. RESULTS: Twenty-six of 30 patients showed global improvement that they rated as excellent or good. Twenty-eight rated their overall satisfaction as excellent or good. The melanin index indicated a substantial decrease, from 225.84 at baseline to 182.65 (p < .05). RCM results showed a dramatic decrease of melanin deposition in the upper dermis. Adverse effects were minimal. CONCLUSIONS: The characteristic finding for dark-brown infraorbital dark circles is melanin deposition in the upper dermis. Treatment of infraorbital dark circles using low-fluence 1,064-nm QSNY laser is safe and effective. The authors have indicated no significant interest with commercial supporters.

Immunohistological evaluation of skin responses after treatment using a fractional ultrapulse carbon dioxide laser on back skin.

BACKGROUND AND OBJECTIVE: Fractional photothermolysis (FP) lasers have been widely used in treating photo-aged skin, acne scars, and other skin conditions. Although plenty of clinical data have demonstrated the efficacy of the FP laser, only limited histologic studies have been available to observe serial short- to long-term skin responses. METHODS: Seven healthy Chinese women received one pass of fractional carbon dioxide laser treatment on the left upper back. Biopsies were taken at the baseline and 4 hours, 1 day, 5 days, 1 month, 3 months, 6 months, and 1 year after the procedure for hematoxylin and eosin stains, immunohistochemical evaluation (for heat shock proteins and elastin), and Verhoeff-iron-hematoxylin stains (for collagen and elastic fiber). RESULTS: Remarkably greater expression of heat shock protein (HSP)70 could be observed 4 hours after the procedure, which diminished significantly by 3 months, 6 months, and 1 year after the procedure. HSP47 reached its peak expression 1 month after the procedure, especially around microscopic thermal zones, and maintained its high level of expression 3 and 6 months after the procedure. Distinct new formation and remodeling of collagen and elastic fibers could be observed 3 and 6 months after procedure. CONCLUSION: FP-induced HSP expression and new formation of collagen and elastic fibers lasted as long as 6 months, longer than the previously acknowledged 3 months.

Increased expression of MAP2 inhibits melanoma cell proliferation, invasion and tumor growth in vitro and in vivo.

Malignant melanoma (MM) is characterized by aggressive metastasis and high mortality rate. Microtubule-associated proteins 2 (MAP2) is expressed abundantly in majority of melanocytic nevi and primary melanomas, but absent in metastatic melanomas. To determine whether MAP2 correlates with tumor progression of MM, we investigated the effects of MAP2 inhibition on the biological behaviour of metastatic melanoma in vitro and in vivo. Our results demonstrated that adenovirus-mediated MAP2 induced apoptotic cell death and cell cycle arrest in metastatic human and mouse melanoma cell lines in vitro, and substantially inhibited the growth of melanomas in nude mice in vivo. In addition, intracellular expression of MAP2 was found to induce the morphologic alteration, suppress the migration and invasion and affect the assembly, stabilization and bundling of microtubules in melanoma cells. This is the first study that MAP2 expression significantly inhibits the growth of MM in vivo. Our results suggest that MAP2 may serve as a promising molecular target for therapy and chemoprevention of MM in humans.

Acitretin induces apoptosis through CD95 signalling pathway in human cutaneous squamous cell carcinoma cell line SCL-1.

Skin cancers are by far the most common human malignancies. Retinoids have shown promising preventive and therapeutic effects against a variety of human malignancies. The aim of this study was to investigate the apoptosis-inducing effect of acitretin on human skin squamous cell carcinoma (SCC) SCL-1 cells. We found that acitretin preferentially inhibited the growth of SCL-1 cells in a dose- and time-dependent manner, but not of non-malignant keratinocyte HaCaT cells. This inhibition appeared to be due to induction of apoptosis as revealed by enzyme-linked immunosorbent assay. AnnexinV/propidium iodide assay and morphological observation confirmed the pro-apoptotic effect of acitretin on SCL-1 cells. We further demonstrated that apoptosis was induced within 1-2 days and involved activation of caspases-8, -9, -3 and poly (ADP-ribose) polymerase (PARP). Caspase-8 inhibitor effectively suppressed acitretin-induced apoptosis whereas caspase-9 inhibitor did not. Acitretin increased the levels of CD95 (Fas), CD95-ligand and Fas-associated death domain. Neutralizing ZB4 anti-Fas antibody significantly inhibited the apoptosis in SCL-1 cells induced by acitretin. These results suggest that acitretin is able to induce apoptosis in skin cancer cells possibly via death receptor CD95 apoptosis pathway without affecting the viability of normal keratinocyte.

Narrow-band ultraviolet B phototherapy for early stage mycosis fungoides.

Recently there have been some reports concerned the treatment of early stage mycosis fungoides (MF) with narrow-band ultraviolet B (NB-UVB) phototherapy. In most of the previous reports, NB-UVB phototherapy was given three times a week on non-consecutive days. Our aim was to evaluate the effect of a twice weekly regimen of NB-UVB phototherapy in the treatment of early-stage MF. Eight patients with early stage MF received NB-UVB phototherapy twice weekly. Six patients (75%) had a complete response in a mean of 23.4 treatments, two (25%) had a partial response. Upon discontinuation of treatment, four patients with complete response relapsed in a mean time to relapse of 5 months. The twice weekly regimen of NB-UVB phototherapy is effective and well-tolerated in the treatment of early stage MF.

Juvenile generalized pustular psoriasis.

Generalized pustular psoriasis (GPP) is an erythrodermic, generalized form of pustular psoriasis. GPP is rare in children. The present study describes a case of juvenile GPP and reviews 12 juvenile GPP inpatients treated at our hospital in the period 1978-2005.

Sweet's syndrome associated with skin methicillin-resistant Staphylococcus epidermidis infection.

A 53-year-old Chinese man presented with fever, a painful exudative plaque around his left eye and subsequent multiple tender plaques and nodules on his bilateral face, neck and back. He had a 12-year history of refractory anemia, a subtype of myelodysplastic syndrome. Repeated bacterial cultures of exudates from the lesion of the left zygomatic area showed growth of methicillin-resistant Staphylococcus epidermidis. A biopsy of a plaque on the back showed edema of the papillary dermis and marked neutrophilic infiltrates in the upper dermis. The patient was diagnosed with Sweet's syndrome (SS), and responded well to combination therapy of amoxycilline/sulbactam and corticosteroids. To our knowledge, this is the first reported case of SS associated with skin S. epidermidis infection.

Childhood bullous pemphigoid treated by i.v. immunoglobulin.

Bullous pemphigoid is an acquired autoimmune subepidermal blistering disorder mostly seen in the elderly. Childhood bullous pemphigoid is very rare. For the first time we report a case of childhood bullous pemphigoid associated with infantile eczema. Two weeks after a routine vaccination, a 3.5-month-old boy with infantile eczema developed a generalized blistering disorder. Histopathology revealed a subepidermal blister. Direct immunofluorescence showed linear depositions of C3 along the basement membrane zone. Indirect immunofluorescence studies demonstrated the presence of circulating immunoglobulin G antibodies directed against the epidermal side of salt-split skin. Enzyme-linked immunosorbent assay demonstrated serum level of anti-BP180 antibody elevated. The patient was successfully treated by high-dose i.v. immunoglobulin.

Prevalence and risk of metabolic syndrome in patients with systemic lupus erythematosus: A meta-analysis.

PURPOSE: To conduct a systematic review and meta-analysis assessing the prevalence of metabolic syndrome (MetS) in patients with systemic lupus erythematosus (SLE) and the association between SLE and MetS. METHOD: A database search of PubMed, the Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI), Weipu database and Wanfang database updated until March 2017 was conducted. The pooled prevalence, the odds ratio (OR) and 95% confidence intervals (CI) were calculated. Publication bias was assessed with Egger's test method. RESULTS: In the study of the prevalence of MetS in patients with SLE, 47 studies containing 8367 subjects were included. These studies were published from 2006 to 2016. The pooled prevalence of MetS in patients with SLE was 0.26 (95% CI: 0.23-0.29). In the study of the relationship between SLE and MetS, 24 studies involving 2744 cases and 3028 controls were included. Comparing to control, the SLE patients had high risk of MetS (OR = 1.88, 95% CI: 1.54-2.30, P = 0.000). CONCLUSION: The systematic review and meta-analysis demonstrated the prevalence of MetS in patients with SLE was 26% and the patients with SLE were more prone to having MetS than the control population. The analysis was a basic summary of all relevant researches and provided valuable evidence for prevention and treatment.

Seven novel mutations of the ADAR gene in Chinese families and sporadic patients with dyschromatosis symmetrica hereditaria (DSH).

Dyschromatosis symmetrica hereditaria (DSH) is an autosomal dominant pigmentary genodermatosis characterized by hyperpigmented and hypopigmented macules of on the extremities and caused by the mutations in the ADAR gene(also called DSRAD) encoding for RNA-specific adenosine deaminase. Here we reported clinical and molecular findings of 6 Chinese multi-generation families and 2 sporadic patients with DSH. We found that the same mutation could lead to different phenotypes even in the same family and we did not establish a clear correlation between genotypes and phenotypes. Seven novel heterozygous mutations of ADAR were identified, which were c.2433_2434delAG (p.T811fs), c.2197G>T (p.E733X), c.3286C>T (p.R1096X), c.2897G>T (p.C966F), c.2797C>T (p.Q933X), c.2375delT (p.L792fs) and c.3203-2A>G respectively. Our data add new variants to the repertoire of ADAR mutations in DSH.

A functional SNP in the MDM2 promoter mediates E2F1 affinity to modulate cyclin D1 expression in tumor cell proliferation.

BACKGROUND: The MDM2 oncogene, a negative regulator of p53, has a functional polymorphism in the promoter region (SNP309) that is associated with multiple kinds of cancers including non-melanoma skin cancer. SNP309 has been shown to associate with accelerated tumor formation by increasing the affinity of the transcriptional activator Sp1. It remains unknown whether there are other factors involved in the regulation of MDM2 transcription through a trans-regulatory mechanism. METHODS: In this study, SNP309 was verified to be associated with overexpression of MDM2 in tumor cells. Bioinformatics predicts that the T to G substitution at SNP309 generates a stronger E2F1 binding site, which was confirmed by ChIP and luciferase assays. RESULTS: E2F1 knockdown downregulates the expression of MDM2, which confirms that E2F1 is a functional upstream regulator. Furthermore, tumor cells with the GG genotype exhibited a higher proliferation rate than TT, correlating with cyclin D1 expression. E2F1 depletion significantly inhibits the proliferation capacity and downregulates cyclin D1 expression, especially in GG genotype skin fibroblasts. Notably, E2F1 siRNA effects could be rescued by cyclin D1 overexpression. CONCLUSION: Taken together, a novel modulator E2F1 was identified as regulating MDM2 expression dependent on SNP309 and further mediates cyclin D1 expression and tumor cell proliferation. E2F1 might act as an important factor for SNP309 serving as a rate-limiting event in carcinogenesis.

Baicalein inhibits DMBA/TPA-induced skin tumorigenesis in mice by modulating proliferation, apoptosis, and inflammation.

Baicalein, one of the four major flavanoids extracted from the root of Scutellaria baicalensis, has been shown to exert chemopreventive effect against several cancers, including skin cancer. However, the precise mechanisms remain to be elucidated. In the present study, we investigated the chemopreventive activity of baicalein against 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-mediated skin tumorigenesis in C57BL/6 mice. We found that topical treatment with baicalein resulted in a significant inhibitory effect on DMBA/TPA-mediated tumor promotion. Furthermore, we observed that baicalein suppressed cell proliferation and promoted apoptosis in DMBA/TPA-mediated group. Additionally, pretreatment with baicalein inhibited the production of inflammatory cells in DMBA/TPA-induced skin/tumors. Further experiments showed that baicalein reduced TPA-induced skin hyperplasia as well as infiltration of polymorphonuclear leukocytes in the dermis. In conclusion, our data suggest that baicalein inhibits DMBA/TPA-induced skin tumorigenesis by suppressing proliferation and inflammation and promoting apoptosis.

Treatment and mortality rate of bullous pemphigoid in China: a hospital-based study.

Bullous pemphigoid (BP) has been reported to be associated with significant morbidities and a considerable mortality rate. We retrospectively studied 94 patients with BP in a Chinese tertiary medical center between 2005 and 2010 to evaluate the treatment of BP and prognostic factors for the mortality of BP. Cerebrovascular diseases (42.55%) and hypertension (39.36%) were the most common pre-existing conditions. Cardiopathy, diabetes and psoriasis pre-existed in 24.47%, 22.34% and 5.32%, respectively. Eighty of all 94 patients were treated by systemic corticosteroid at prednisone 0.3 mg/kg to 1.5 mg/kg daily. Patients were followed up for a minimum of 1 year or until the time of death. The mean duration of follow-up was 32 months. Kaplan-Meier analysis showed a 1-year survival probability of 76.6% (standard error 4.4%), with a 95% confidence interval (68.04%, 85.16%). Multivariate analysis revealed that increased age, bedridden condition, presence of cerebrovascular diseases at diagnosis, pre-existing cardiopathy and low serum albumin level were associated with the elevated 1-year mortality rate of BP.