Occupational exposure to certain polychlorinated aromatic hydrocarbons such as dioxins has been suggested to cause chloracne which is a kind of skin disease. The molecular mechanisms of dioxin-mediated chloracne have not been clarified. It is possible that dioxins contribute to the pathogenesis through activation of aryl-hydrocarbon receptor (AhR)-mediated transcription and downstream genes such as CYP1A1, GSTA1 and TGF-α. The study on genes was through chloracne lesional skin, which has rarely been reported on previously. The expression levels of key genes, such as AhR, CYP1A1, GSTA1, c-fos and TGF-α in human epidermal tissue of chloracne cases and controls were detected by real-time PCR. Compared with controls, AhR, CYP1A1, GSTA1 and c-fos transactivations were significantly induced in the skins of chloracne patients who had long-term exposure to dioxins and dibenzofuranes. The TGF-␣ mRNA content of epidermal tissue was increased, but not significantly compared with controls. The study demonstrates that constitutive activation of the AhR pathway is probably a prerequisite of chloracne pathogenesis. The changes of genes expression may disturb normal proliferation and differentiation of human epidermis cells, and then lead to chloracne.
The incidences of upper third gastric cancer (UTGC) have been increasing. However, the prognostic factors for UTGC following radical surgical treatment remains largely unknown. This study was to investigate prognostic factors for overall survival (OS), lymph node metastasis and recurrence of UTGC.Clinicopathologic data of 126 UTGC patients who underwent radical surgical treatment were retrospectively analyzed. OS and univariate analysis were determined by Kaplan–Meier analysis and the significance of the difference between curves was calculated with the log-rank test. The Cox proportional hazards regression model was applied to perform multivariate analysis. Receiver operating characteristic (ROC) curve analysis was used to determine the prognostic accuracy.The 1-, 3-, and 5-year OS for patients with UTGC were 81%, 47.6%, and 38.6% respectively. Univariate analysis showed that tumor size (P = .019), tumor invasion depth (P < .001), and lymph node metastasis (P < .001) were the risk factors for 5-year OS. Multivariate analysis identified tumor invasion depth (P < .001) and lymph node metastasis (P < .001) as independent prognostic factors for the 5-year OS in patients with UTGC. In addition, ROC curve analysis showed that tumor invasion depth (P = .017) or lymph node metastasis (P = .001) alone showed significantly effective prognosis for the 5-year OS in patients with UTGC. For UTGC patients with lymph node metastasis, tumor size (P = .023), lym embolism (P = .003), tumor invasion depth (P = .002), and invasion of tunica serosa (P = .004) were the risk factors for the 5-year OS. Multivariate analysis identified tumor size (P = .048), lym embolism (P = .032), tumor invasion depth (P = .004), and invasion of tunica serosa (P = .031) as independent prognostic factors for the 5-year OS. For UTGC patients with distant metastasis or tumor recurrence, univariate and multivariate analyses demonstrated that tumor invasion depth and lymph node metastasis were independent prognostic factors for the 5-year OS.The results suggested that for UPGC patients undergoing the radical surgical treatment, tumor invasion depth and/or lymph node metastasis are the independent prognostic factors for the 5-year OS, lymph node metastasis, distant metastasis and tumor recurrence.
Gastric cancer (GC) is the fourth most common cancer in the world and the second most common cancer in China. The aim of this study was to investigate the clinicopathologic profiles and prognosis of GC in the upper third (UT), middle third (MT) and low third (LT) of the stomach. Five hundred and forty-two patients with GC resected between January 2010 and January 2014 were retrospectively studied and divided in 3 groups according to cancer location: upper third gastric cancer (UTGC) (n = 62); MTGC (n = 131) and LTGC (n = 349). Clinical and pathological parameters including gender, age, tumor size, macroscopic types, histological types, depth of invasion, lymph node metastasis, venous infiltration and lymph embolism were compared among groups. Overall survival (OS) was calculated based on the aforementioned parameters. Univariate and multivariate survival was analyzed and Cox regression was conducted for each location. The prognostic accuracy was determined using receiver operating characteristic curve analysis. Patients with UTGC was similar to those with MTGC and both were distinct from those with LTGC based on the tumor size, macroscopic types, depth of invasion and 5-year OS. Patients with MTGC were similar to those with LTGC and distinct from UTGC patients based on gender. 5-year OS were lower for patients with UTGC than those with LTGC ( P = .001) and were comparable between MTGC and LTGC. No significant differences in 5-year OS were observed between UTGC and MTGC. Cox regression revealed that macroscopic types, depth of invasion and lymph node metastasis were the independent prognostic factors for GC patients regardless of locations. Receiver operating characteristic curve analysis revealed that macroscopic types, depth of invasion and lymph node metastasis were the significantly effective prognosis for the 5-year OS in GC patients regardless of locations. Our results showed that UTGC is distinct from LTGC whereas MTGC shares some characteristics from both UTGC and LTGC.
a b s t r a c tObjective: Chloracne is one of the most sensitive and specific hallmark of dioxin intoxication. Although its clinical features are clearly described, poor understanding of the molecular pathways of dioxin-induced chloracne hampers a rational approach to therapy. The aim of the present study was to investigate the role of EGFR, MAPK, CK17, and TGk in the pathogenesis of chloracne related to dioxin exposures. Methods: Epidermal tissues of twelve chloracne patients exposed to dioxins were compared with tissues from 12 healthy controls. These skin tissues were obtained by punch biopsies. p-EGFR and p-MAPK were examined by immunofluorescence. The mRNA and protein levels of CK17 and TGk were examined by fluorescence in situ hybridization and immunohistochemistry, respectively. Results: p-EGFR and p-MAPK were found in all chloracne tissues, whereas no expression was found in the controls. CK17 mRNA and protein were also found in all chloracne lesions, but none in controls (P = 0.000). TGk mRNA and protein were detected in both groups, but the distribution was distinct. The positive signals in the controls were mainly in the stratum granulosum, while in the chloracne tissues, the positive signals were found more significantly in the stratum granulosum and stratum spinosum. Conclusions:The results demonstrate that in the human skin the activation of mitogen-activated protein kinase pathway and up-regulation of CK17 and TGK may play roles in the pathogenesis of chloracne related to dioxin exposures.
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