[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: 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.
No preview · Article · Jan 2012 · American Journal of Clinical Dermatology
[Show abstract][Hide abstract] ABSTRACT: Smoking methamphetamine (MA) creates a potential risk of environmental (second-hand) exposure to others. Despite the public health concerns, essentially no data are available on the health effects of smoked MA. Using a unique rodent inhalation exposure system, our laboratory has previously published that acute inhalation of relevant doses of MA vapor is associated with significant injury in the lungs of mice.
The purpose of this study was to determine if MA is directly toxic to lung epithelial cells and whether other components in the MA smoke contribute to this toxicity. We also sought to characterize MA smoke to find previously unidentified compounds in the MA smoke that may contribute to the toxic effects of MA. We hypothesized that MA smoke contains compounds that contribute to MA toxicity in lung epithelial cells.
In vitro studies were conducted utilizing mouse lung epithelial cells to determine toxicity of compounds by LDH release. Fourier Transform Infrared Spectroscopy, Aerosol Mass Spectrometry, and Ultra-high Sensitivity Aerosol Spectrometry were employed to measure trace gases, major smoke constituents, and aerosol contribution to MA emissions.
MA was not directly toxic to mouse lung epithelial cells. However, the MA pyrolysis product trans-phenylpropylene oxide dose-dependently caused cell death. When heated, MA vaporized into very small particles that likely are able to deeply penetrate the lung. In addition, we found unidentified components of MA smoke that will be characterized in future studies.
We conclude that environmental exposure to MA smoke may present a potential health concern and that further studies are warranted.