Jianwen Ren

Apoptosis induced by synthetic retinoic acid CD437 on human melanoma A375 cells involves RIG-I pathway

Human malignant melanoma is notoriously resistant to currently available pharmacological modulation. Our aim was to evaluate the anti-tumor effect of a novel synthetic retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carbo-xylic acid (CD437) on melanoma cell line A375. Analysis of cell morphology showed that CD437 promoted marked apoptosis in A375 cells. To explore the mechanisms of CD437-induced apoptosis, an NF-κB-luciferase reporter assay was performed, demonstrating that apoptosis induction by CD437 required activation of transcription factor NF-κB. Importantly, based on the findings that RIG-I (retinoic acid inducible gene I) can be induced by retinotic acid and can activate NF-κB through a CARD-containing adaptor protein VISA, we proposed a hypothesis that RIG-I was involved in the signal pathway of NF-κB activation induced by CD437 through the adaptor protein VISA. By specially cleaving VISA with hepatitis C virus (HCV) non-structural (NS)3/4A, the RIG-I pathway was blocked, with subsequent simultaneous inhibition of CD437-induced NF-κB activation and cell apoptosis in A375 cells. These results support our hypothesis and suggest that RIG-I may be a useful intermediate biologic marker for retinoid chemoprevention and treatment studies.

Novel frameshift mutation of the DSRAD gene in a Chinese family with dyschromatosis symmetrica hereditaria

© 2008 The Authors 1375 JEADV 2008, 22, 1365–1401 Journal compilation

Two novel frameshift mutations of the DSRAD gene in Chinese pedigrees with dyschromatosis symmetrica hereditaria

Background  Dyschromatosis symmetrica hereditaria (DSH) is an autosomal dominant disorder characterized by a mixture of hyperpigmented and hypopigmented macules localized on the back of the extremities and caused by the mutations in the DSRAD gene.

Comparison between synthetic retinoid CD437 and acitretin inhibiting melanoma A375 cell in vitro

Objective: To investigate the effects of synthetic retinoid CD437 and acitretin on cell proliferation, apoptosis, cycle arrest and Bax/ Bcl-2 protein expression of melanoma A375 cell. Methods:MTT assay was used to determine the anti-proliferative effects of CD437 and acitretin on melanoma A375 cell. Flow cytometry was performed to investigate the influence of CD437 and acitretin on cell cycle and cell apoptosis. SABC immunocytochemistry was employed for detection of Bax/bcl-2 protein expressions. Results:10 -5 mol/L CD437 was more effective than acitretin in inhibiting proliferation and inducing apoptosis of A375 cell after 24 h treatment, growth inhibiting ratio and apoptosis ratio(58.6%vs43.25% and 28.03%vs17.13%, P < 0.05 respectively). CD437 promoted G0/G1 arrest in melanoma A375 cell, however acitretin could not. CD437 and acitretin could up-regulate the expression of Bax protein and down- regulate the expression of bcl-2 protein(P < 0.05). Conclusion:CD437 is more effective than acitretin in inhibiting proliferation and inducing apoptosis and cycle arrest on A375 cell. CD437 may have more potentialities than acitretin for subsidiary treatment of melanoma. Mitochondrial apoptosis pathway is partially involved in two drugs inducing apoptosis on A375 cell.

Apoptotic effect and mechanisms of AHPN on human skin malignant melanoma cell A375

Abstract Objective To study apoptotic effects of synthetic retinoic acid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid(AHPN) on human skin malignant melanoma A375 cells in comparison with the natural ligand all-trans-retinoic acid(ATRA) in vitro and the mechanisms related to the actions of AHPN. Methods MTT assay was used to determine the anti-proliferative effects of AHPN and ATRA on A375 cells. Flow cytometry was performed to investigate the influence of AHPN and ATRA on cell cycle and cell apoptosis. In addition, transfection and luciferase activity assays were employed to explore the mechanisms of how AHPN executes its proapoptotic function. Results Firstly, AHPN promoted apoptosis and G1 arrest in A375 cells compared with ATRA. Secondly, the activity of NF-κ B in A375 cells treated with AHPN increased 2–3 times compared with solvent DMSO treatment. Conclusion AHPN, in comparison with ATRA, is a more effective alternative for therapy of malignant melanoma. The potentially proapoptotic function of AHPN requires activation of NF-κ B.

Meta-Analysis of the Association between Vitiligo and Human Leukocyte Antigen-A

Objective. The objective of this study was to systematically evaluate the association between vitiligo and human leukocyte antigen- (HLA-) A. Methods. PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure, and reference lists were searched for relevant original articles. Results. Nineteen case-control studies comprising 3042 patients and 5614 controls were included, in which 33 HLA-A alleles were reported. Overall, three alleles (HLA-A⁎02, A⁎33, and Aw⁎31) were significantly associated with increased risk of vitiligo, two (HLA-A⁎09 and Aw⁎19) were associated with decreased risk, and the remaining 28 were unassociated. Twelve alleles, seven alleles, and 19 alleles were common to three ethnicities, both types of vitiligo, and both typing methods, respectively. In the subgroup analysis by ethnicity and typing methods, the association of six alleles and five alleles was inconsistent in three populations and both typing methods, respectively. In the subgroup analysis by clinical type, the association of all seven alleles was consistent in both types of vitiligo. Conclusion. The meta-analysis suggests that HLA-A⁎02, A⁎33, and Aw⁎31 are associated with increased risk of vitiligo, while HLA-A⁎09 and Aw⁎19 are associated with decreased risk of vitiligo. The association of some alleles varies in terms of ethnicity and typing methods.