CXCL-8, a chemokine secreted by melanoma and stromal cells, serves as a growth and angiogenic factor for melanoma progression. This study evaluated how modulation of CXCL-8 levels in melanoma cell lines with different tumorigenic and metastatic potentials affected multiple tumor phenotypes. A375P cells (CXCL-8 low expressor) were stably transfected with a CXCL-8 mammalian expression vector to overexpress CXCL-8, whereas A375SM cells (CXCL-8 high expressor) were transfected with a CXCL-8 antisense expression vector to suppress CXCL-8 expression. Subsequent cell proliferation, migration, invasion, and soft-agar colony formation were analyzed, and in vivo tumor growth and metastasis were evaluated using mouse xenograft models. Our data demonstrate that overexpression of CXCL-8 significantly enhanced primary tumor growth and lung metastasis, accompanied by increased microvessel density in vivo, as compared with vector control-transfected cells. We also observed increased clonogenic ability, growth, and invasive potential of CXCL-8 overexpressing cells in vitro. Knockdown of CXCL-8 using an antisense vector resulted in increased cell death and reduced tumor growth relative to control. Taken together, these data confirm that CXCL-8 expression plays a critical role in regulating multiple cellular phenotypes associated with melanoma growth and metastasis.
Topical antimicrobial treatment is indicated for mild to moderate acne vulgaris. Our literature review includes searches of Ovid, MEDLINE, EMBASE, and the databases of the Cochrane Library. A detailed search strategy is included. All searches were limited to controlled trials and systematic reviews. No year limits were applied to the searches, but we focused on trials, guidelines, and reviews published since 2004, the year that the last review of topical antimicrobials was published in this journal. Several controlled trials demonstrate that benzoyl peroxide, topical antibiotics, and topical retinoids used in combination provide the greatest efficacy and safety profile for the treatment of mild to moderate acne, but there are few trials directly comparing different combinations of these topical therapies with one another. Additionally, robust studies comparing cost and efficacy of generic combinations of the above agents with proprietary fixed-dose combination therapies that may increase compliance are also lacking. Although they have not been extensively studied, alternative agents including dapsone, salicylic acid, azelaic acid, and zinc are safe and efficacious when combined with traditional therapies.
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