Polyaromatic hydrocarbons (PAHs) are prevalent, potent carcinogens, and 7,12-dimethylbenzaanthracene (DMBA) is a model PAH widely used to study tumorigenesis. Mice lacking Langerhans cells (LCs), a ...signatory epidermal dendritic cell (DC), are protected from cutaneous chemical carcinogenesis, independent of T cell immunity. Investigation of the underlying mechanism revealed that LC-deficient skin was relatively resistant to DMBA-induced DNA damage. LCs efficiently metabolized DMBA to DMBA-trans-3,4-diol, an intermediate proximal to oncogenic Hras mutation, and DMBA-treated LC-deficient skin contained significantly fewer Hras mutations. Moreover, DMBA-trans-3,4-diol application bypassed tumor resistance in LC-deficient mice. Additionally, the genotoxic impact of DMBA on human keratinocytes was significantly increased by prior incubation with human-derived LC. Thus, tissue-associated DC can enhance chemical carcinogenesis via PAH metabolism, highlighting the complex relation between immune cells and carcinogenesis.
T-pro are tumor-infiltrating TCRαβ+CD8+ cells of reduced cytotoxic potential that promote experimental two-stage chemical cutaneous carcinogenesis. Toward understanding their mechanism of action, ...this study uses whole-genome expression analysis to compare T-pro with systemic CD8+ T cells from multiple groups of tumor-bearing mice. T-pro show an overt T helper 17–like profile (high retinoic acid–related orphan receptor-(ROR)γt, IL-17A, IL-17F; low T-bet and eomesodermin), regulatory potential (high FoxP3, IL-10, Tim-3), and transcripts encoding epithelial growth factors (amphiregulin, Gro-1, Gro-2). Tricolor flow cytometry subsequently confirmed the presence of TCRβ+ CD8+ IL-17+ T cells among tumor-infiltrating lymphocytes (TILs). Moreover, a time-course analysis of independent TIL isolates from papillomas versus carcinomas exposed a clear association of the “T-pro phenotype” with malignant progression. This molecular characterization of T-pro builds a foundation for elucidating the contributions of inflammation to cutaneous carcinogenesis, and may provide useful biomarkers for cancer immunotherapy in which the widely advocated use of tumor-specific CD8+ cytolytic T cells should perhaps accommodate the cells' potential corruption toward the T-pro phenotype. The data are also likely germane to psoriasis, in which the epidermis may be infiltrated by CD8+ IL-17-producing T cells.
Scientific developments in indoor tanning and melanoma Ratanaprasatporn, Linda, ScB; Neustadter, Jason, MD; Weinstock, Martin A., MD, PhD
Journal of the American Academy of Dermatology,
04/2011, Letnik:
64, Številka:
4
Journal Article
POZ/BTB proteins influence cellular development and in some examples act as oncoproteins. However, several POZ/BTB transcription factors have been found in terminally differentiated neurons, where ...their functions remain unknown. One example is NAC1, a constitutively-expressed protein that can regulate behaviors associated with cocaine use. The present study represents an initial attempt to understand the actions of NAC1 within neurons by using adenoviral-mediated gene transfer into differentiated PC-12 cells. Cell survival in PC-12 cells overexpressing NAC1 was greatly reduced compared with cells infected by a control Ad-GFP. The morphological appearance of the dying cells was consistent with programmed cell death. Fragmentation of genomic DNA occurred in PC-12 cells infected with adenoviruses encoding NAC1 but not control viruses. NAC1 over expression was followed by the down regulation of the anti-apoptotic proteins Bcl-2 and Bcl-2-xl. Concurrently, levels of the pro-apoptotic proteins Bax and p53 increased following NAC1 overexpression. These observations suggest that NAC1expression in PC-12 cells induces apoptosis by altering the expression of these upstream mediators of the execution phase of programmed cell death. These findings raise the possibility that aberrantly regulated NAC1 expression in the mammalian brain may contribute to programmed cell death.
Peroneal tendon subluxation is a major cause of posttraumatic lateral ankle pain. Because peroneal subluxation often occurs only when the foot is dorsiflexed and everted, findings on static imaging ...studies may appear to be normal. We therefore evaluated the effectiveness of sonography in revealing peroneal tendon subluxation in patients performing stress maneuvers.
From June 2001 to June 2003, 13 consecutive patients (10 females and three males; mean age, 30.4 years; age range, 16-66 years) in whom peroneal tendon subluxation was clinically suspected were scanned with a high-frequency linear array transducer by an experienced sonologist. The ankles in 10 asymptomatic volunteers were also scanned. Sequential axial and longitudinal sonograms of the peroneus longus and peroneus brevis tendons at rest were obtained and evaluated for tendinitis and tendon tears. Real-time axial sonograms were then obtained while the foot was dorsiflexed and everted. Of the 13 patients, 12 had sonographic findings of peroneal tendon subluxation and underwent surgical exploration. The sonographic and surgical reports of these 12 patients were compared.
All 12 patients with sonographic findings of peroneal tendon subluxation were subsequently found to have subluxation at surgery. The positive predictive value of dynamic sonography for peroneal tendon subluxation was therefore 100%. Sonography revealed peroneus brevis tendon tears in five patients and a peroneus longus tear in one; all findings were confirmed at surgery, with no false-positive sonograms. Only four of the 20 asymptomatic ankles showed subluxation, and none had any other tendon abnormalities.
Sonography is an effective technique for diagnosing peroneal tendon subluxation, as well as associated tears of the peroneal tendons.
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