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4.
JAMA Dermatol ; 158(5): 542-546, 2022 05 01.
Article in English | MEDLINE | ID: mdl-35319719

ABSTRACT

Importance: Ultraviolet radiation exposure is an important modifiable risk factor for keratinocyte carcinoma (KC) in fair-skinned non-Hispanic White populations; however, the evidence for this relationship in darker-skinned populations is less certain. Objective: To assess and synthesize the published data concerning the association between UV exposure and the risk of KC in individuals with skin of color. Evidence Review: PubMed, Cochrane, and Web of Science databases were searched from database origin through January 2022. Studies deemed eligible included UV exposure as a risk factor for KC in individuals with skin of color, defined as any race other than non-Hispanic White, Fitzpatrick skin types IV to VI, or tanning ability of rarely or never burns. The UV index, irradiance, latitude, history of phototherapy, history of sunburn, or occupational exposure were used as measures of exposure. The Oxford Centre for Evidence-Based Medicine guidelines were used to assess evidence quality. Findings: A total of 72 716 articles appeared in the search. After duplicate removal, 29 393 database records were screened, 454 full-text articles were assessed, a forward and reverse citation search was performed, and 12 articles, with clinical data spanning the years 1990 to 2019, met inclusion criteria. More than 32 970 KCs in individuals with skin of color were included. Eight studies found no association between UV exposure and KC, while 4 studies showed a positive association. Study types included 1 ecological study, 9 cohort studies, and 2 case-control studies. The quality of the studies was rated from moderate to low (2b to 4). Conclusions and Relevance: Results of this systematic review show that the evidence assessing the association of UV exposure with KC is of moderate to low quality. The studies that found no association were among patients receiving phototherapy. Studies assessing nonphototherapy-related UV exposure, such as geographic location or occupation, found small positive associations in primarily East Asian individuals. There were no studies performed in the US, no studies among Black individuals, and only 1 study among a Hispanic population. Further research is required to better assess whether these associations exist across populations of patients with darker skin types.


Subject(s)
Carcinoma , Sunburn , Humans , Keratinocytes , Skin Pigmentation , Sunburn/complications , Sunburn/epidemiology , Ultraviolet Rays/adverse effects
5.
Pediatr Dermatol ; 38(1): e7-e9, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33630374

Subject(s)
Hand , Ulcer , Humans
6.
J Clin Med ; 5(4)2016 Mar 23.
Article in English | MEDLINE | ID: mdl-27023622

ABSTRACT

Osteopontin (OPN) plays an important functional role in both physiologic and pathologic states. OPN is implicated in the progression of fibrosis, cancer, and metastatic disease in several organ systems. The epithelial-mesenchymal transition (EMT), first described in embryology, is increasingly being recognized as a significant contributor to fibrotic phenotypes and tumor progression. Several well-established transcription factors regulate EMT and are conserved across tissue types and organ systems, including TWIST, zinc finger E-box-binding homeobox (ZEB), and SNAIL-family members. Recent literature points to an important relationship between OPN and EMT, implicating OPN as a key regulatory component of EMT programs. In this review, OPN's interplay with traditional EMT activators, both directly and indirectly, will be discussed. Also, OPN's ability to restructure the tissue and tumor microenvironment to indirectly modify EMT will be reviewed. Together, these diverse pathways demonstrate that OPN is able to modulate EMT and provide new targets for directing therapeutics.

7.
Surgery ; 158(4): 1039-47; discussion 1047-8, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26189955

ABSTRACT

INTRODUCTION: Osteopontin (OPN) mediates metastasis and invasion of hepatocellular carcinoma (HCC). Epigallocatechin-3-gallate (EGCG), found in green tea, suppresses HCC tumor growth in vitro. We sought to investigate the role of EGCG in modulating OPN in cell lines of metastatic HCC. METHODS: Experimental HCC cell lines included HepG2 and MHCC-97H HCC cells, which express high levels of OPN, and the Hep3B cells, which express lesser levels of OPN. Cells were treated with EGCG (0.02-20 µg/mL) before measurement of OPN with enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain reaction. Scratch assay measured cell migration. Binding of the OPN promoter to RNA pol II was evaluated by the use of Chromatin-IP assay after EGCG treatment. Transcriptional regulation of OPN was investigated with luciferase reporter plasmids containing various deletion fragments of the human OPN promoter. Measurement of the half-life of OPN mRNA was conducted using actinomycin D. RESULTS: Treatment of MHCC-97H and HepG2 cells with 2 µg/mL and 20 µg/mL EGCG caused a ∼6-fold and ∼90-fold decrease in secreted protein levels of OPN (All P < .001). OPN mRNA was decreased with EGCG concentrations of 0.2-20 µg/ml (All P < .001). The 3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (ie, MTT) assay revealed that differences in OPN expression were not due to viability of the HCC cell lines. Promoter assay and chromatin immunoprecipitation analysis revealed no effect of EGCG on the transcriptional regulation of OPN. Posttranscriptionally, EGCG decreased the half-life of OPN mRNA from 16.8 hours (95% confidence interval 9.0-125.1) to 2.5 hours (95% confidence interval 2.1-3.2) (P < .001). Migration was decreased in EGCG treated cells at 24 hours (8.0 ± 2.4% vs 21.2 ± 10.8%, P < .01) and at 48 hours (13.2 ± 3.6% vs 53.5 ± 19.8%, P < .001). CONCLUSION: We provide evidence that EGCG decreases OPN mRNA and secreted OPN protein levels by decreasing the half-life of OPN mRNA in MHCC-97H cells. The translatability of EGCG for patients with HCC is promising, because EGCG is an inexpensive, easily accessible chemical with an extensive history of safety.


Subject(s)
Antineoplastic Agents/pharmacology , Biomarkers, Tumor/metabolism , Carcinoma, Hepatocellular/drug therapy , Catechin/analogs & derivatives , Liver Neoplasms/drug therapy , Osteopontin/metabolism , RNA, Messenger/metabolism , Antineoplastic Agents/therapeutic use , Biomarkers, Tumor/genetics , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Catechin/pharmacology , Catechin/therapeutic use , Cell Line, Tumor , Cell Movement/drug effects , Enzyme-Linked Immunosorbent Assay , Half-Life , Humans , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Neoplasm Metastasis , Osteopontin/genetics , Reverse Transcriptase Polymerase Chain Reaction
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