A double-blind, randomized, placebo- and positive-controlled phase III trial of 1% benvitimod cream in mild-to-moderate plaque psoriasis / 中华医学杂志(英文版)

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.

Expressions of oncogenes c-fos and c-myc in skin lesion of cutaneous squamous cell carcinoma

OBJECTIVES@#To explore the expressions of c-fos and c-myc in skin lesion of cutaneous squamous cell carcinoma (CSCC).@*METHODS@#Using retrospective analysis, 73 cases of CSCC were selected from Department of Dermatology, the Second Affiliated Hospital of Xi'an Jiaotong University, which were removed between January 2000 and January 2012. It was considered as experimental group. Meanwhile, 11 cases of normal skin specimens of non tumor patients were selected as control group. The expression level of c-fos and c-myc was compared in the two groups.@*RESULTS@#The expressions of c-fos [72.60% (53/73)] and c-myc [83.56% (61/73)] in experimental group were statistically significant (P≤0.05) compared with control group (0%). Expression of c-myc protein was negatively related to differentiation of CSCC. The difference was statistically significant (χ(2)=7.26, P=0.001<0.05). While expression of c-fos protein was positively related to differentiation of CSCC, which was statistically significant (χ(2)=7.47, P=0.001 2<0.025).@*CONCLUSIONS@#The expression level of c-fos and c-myc can be used as an important indicator of CSCC differentiation, and it has closely connection with the differentiated degree, which can guide clinical prognosis.

Infliximab monotherapy for Chinese patients with moderate to severe plaque psoriasis: a randomized, double-blind, placebo-controlled multicenter trial / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Expression of integrin beta1 in squamous cell carcinoma / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the expression of integrin beta1 in squamous cell carcinoma (SCC) and explore the relationship between stem cell marker and SCC.</p><p><b>METHODS</b>The expressions of integrin beta1 in SCC tissues and SCC cell strain A431 were detected with immunohistochemical methods and cell staining method. The differentiation of SCC cells were induced with all-trans-retinoic acid (ATRA). The changes of integrin beta1 levels before and after induction were detected with RT-PCR.</p><p><b>RESULTS</b>In highly differentiated SCC tissues, integrin beta1 was constantly expressed in the basal-like cells in the edge of tumor; some cells inside arranged as island also showed positive integrin beta1 expression. In poorly differentiated SCC tissues, island-like integrin beta1-positive cells remarkably increased and distributed in a diffuse way. In SCC A431 cells, integrin beta1 was expressed unevenly in tumor cells. After treatment by ATRA, level of integrin beta1 mRNA in A431 cells significantly decreased compared with untreated control (P < 0.05), and the ratios between the intensity values of integrin beta1 to beta-actin were 0.071 +/- 0.025 and 0.029 +/- 0.018 at 24 h and 48 h, respectively, whereas in controls were 0.148 +/- 0.027 and 0.136 +/- 0.011 (P < 0.05).</p><p><b>CONCLUSIONS</b>Integrin beta1 is heterogeneously expressed in both SCC tissues and SCC A431 cells. The expression of Integrin beta1 decreases when the differentiation level of tumor cells increase, indicating that integrin beta1 is closely related with the initiation of SCC and potential cancer stem cells in SCC.</p>

A novel retinoid CD437 induces apoptosis of human epidermoid carcinoma A431 cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of a novel retinoid CD437 and all-trans retinoic acid (ATRA) in inducing cell apoptosis and inhibiting the proliferation of human epidermoid carcinoma A431 cells and normal human epidermal keratinocytes.</p><p><b>METHODS</b>MTT assay was used to determine the inhibitory effects of CD437 and ATRA on the growth of A431 cells and normal human epidermal keratinocytes, and the cell morphological changes were observed microscopically. Flow cytometry was used to investigate the effect of CD437 and ATRA on the cell cycle and apoptosis.</p><p><b>RESULTS</b>CD437 was more effective than ATRA in inhibiting the proliferation of A431 cells and normal human epidermal keratinocytes. CD437 increased the percentage of sub-G1 populations in A431 cells and induced G1 arrest in normal human epidermal keratinocytes. ATRA appeared to be relatively ineffective for inducing apoptosis in A431 cells as compared to CD437. CD437 did not duce obvious apoptosis in normal human epidermal keratinocytes.</p><p><b>CONCLUSION</b>CD437 is more effective than ATRA in inhibiting the proliferation and inducing apoptosis in A431 cells and shows selective apoptosis-inducing effect against malignant keratinocytes, suggesting its potential in the prevention or treatment of cutaneous carcinoma.</p>

Mutation detection of ATP2C1 gene in Chinese patients with Hailey-Hailey disease / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the mutations of ATP2C1 gene in Chinese patients with Hailey-Hailey disease (HHD).</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral blood leukocytes. PCR and direct DNA sequencing were used to detect the mutations in all 27 exons of ATP2C1 gene in patients of two Chinese families and a sporadic patient with HHD.</p><p><b>RESULTS</b>Three mutations in ATP2C1 gene were found, including 1 nonsense mutation, 1 deletion/frameshift mutation and 1 missense mutation. All of them were novel mutations.</p><p><b>CONCLUSION</b>All the three mutations could affect the transcription and translation, and further the function of protein encoded by ATP2C1 gene.</p>