Protease-activated receptor-2 (PAR-2) is known to be involved in epidermal permeability barrier function homeostasis. PAR-2 activation occurs after barrier disruption and further activation of PAR-2 by activating peptide significantly delays barrier recovery rate. Cockroach and house dust mite allergens, both known to be associated with the development of asthma, allergic rhinitis, and atopic dermatitis, have protease activity, which can activate PAR-2. In this study, we investigated the effects of both allergens on the epidermal barrier function as well as on the epidermal calcium gradient. Both allergens, when topically applied on the barrier-disrupted site, increased protease activities in the epidermis and delayed barrier recovery and lamellar body secretion in murine skin. The topical application of PAR-2-specific antagonist or protease inhibitors normalized the barrier recovery. Cockroach allergens induced intracellular calcium oscillations in cultured human keratinocytes through PAR-2-involved pathway, which was confirmed by desensitization protocol. Abnormal calcium ion distribution after barrier disruption was also observed in allergens-applied skin. These results suggest that allergens with protease activity can influence the epidermal permeability barrier homeostasis through PAR-2 activation and consequent modulation of the calcium ions in skin.

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MicroRNAs (miRNAs) are involved in the progression of breast cancer. Some miRNAs, especially the miR-200 family, miR-9, and miR-155 have been reported to be associated with epithelial-mesenchymal transition (EMT) and breast cancer stem cell (BCSC) phenotypes. This study was designed to evaluate the expression levels of these miRNAs in human breast cancer samples and analyzed their relationship with clinicopathologic features of the tumor including breast cancer subtype, EMT, BCSC phenotype, and prognosis. Expression levels of the miR-200 family, miR-9, and miR-155 were quantified using qRT-PCR. Breast cancer subtype, BCSC phenotype (CD44+/CD24- and ALDH1+), and expression of EMT markers (vimentin expression and E-cadherin loss) were evaluated by immunohistochemistry. miR-9 was more highly expressed in HER2+ and triple-negative subtypes than in luminal subtypes. Its expression level was significantly higher in tumors with high T stage, high histologic grade, p53 overexpression, and high proliferation index. Expression of miR-9 was also higher in tumors showing the CD44+/CD24- phenotype, vimentin expression, and E-cadherin loss. Furthermore, high level of miR-9 expression was found to be an independent prognostic factor for poor disease-free survival of the patients. Expression of miR-200a and miR-141 was highest in luminal A subtype, and miR-155 expression was highest in triple-negative subtype. Although the expression levels of some miR-200 family members and miR-155 showed difference with regard to EMT or BCSC phenotype, they were not associated with patients' prognosis. In conclusion, overexpression of miR-9 is found in tumors with aggressive phenotypes and is associated with poor prognosis in breast cancer, suggesting that it may serve as a potential biomarker for breast cancer progression and a target for treatment.

ObjectiveSolitary fibrous tumor (SFT) is a very rare tumor. The purpose of this study is to determine the MR imaging features of SFT in the intracranial and extracranial head and neck regions.Materials and MethodsWe retrospectively reviewed six MR images and two CT images of six histologically proven cases of SFT that occurred in four men and two women, and their ages ranged from 46 to 59 years. These imaging findings were correlated with the microscopic findings of their surgical specimens.ResultsSix SFTs arose in the meninges (the petrous ridge and the pituitary fossa), the parotid gland, the parapharyngeal space, the buccal space and the maxillary sinus. On the MR images, SFTs in the intracranial and extracranial head and neck regions were mostly isointense to the muscle on the T1-weighted images, they were hyperintense on the T2-weighted images and they all had intense enhancement. On the T1- and T2-weighted images, hypointense lines were observed within in five SFTs. On the CT images, the SFTs were hypodense to the muscle on the unenhanced images and they were heterogeneously enhanced on the contrast-enhanced images. An exceptional case of pituitary SFT was hypointense on the T2-weighted images and it was hyperdense on the unenhanced CT images, which correlated with the increased collagenous component and the cellular compactness.ConclusionThe imaging features of SFT are nonspecific; however, SFT should be included in the differential diagnosis of masses involving the intracranial and extracranial head and neck regions.

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The transcription factors of embryonic stem cells, such as Oct4, Sox2, Nanog, Bmi1, and Klf4, are known to be associated with stemness, epithelial–mesenchymal transition and aggressive tumor behavior. This study was designed to evaluate the clinicopathological significance of their expression in breast cancer. Immunohistochemistry for Oct4, Sox2, Nanog, Bmi1, and Klf4 was performed in 319 cases of invasive breast cancer. The relationship between the expression of these markers and clinicopathologic features of the tumors, including breast cancer stem cell phenotype and epithelial–mesenchymal transition marker expression, and their prognostic value in breast cancer, were analyzed. Expression of Oct4 and Sox2 was commonly associated with high histologic grade and high Ki-67 index in the whole group and in the hormone receptor-positive subgroup. On the other hand, expression of Nanog, Bmi1, and Klf4 was inversely correlated with aggressive features of the breast cancer. Oct4 expression was associated with ALDH1 expression but not with epithelial–mesenchymal transition marker expression. In survival analysis, Oct4 expression was independently associated with poor prognosis in the whole group and in the hormone receptor-positive subgroup, but not in hormone receptor-negative subgroup. Particularly, Oct4 expression was associated with poor clinical outcome in patients with hormone receptor-positive breast cancer treated with tamoxifen. Our results indicate that Oct4 expression is associated with aggressive features, ALDH1 expression, tamoxifen resistance and poor clinical outcomes in hormone receptor-positive breast cancer, and thus may be useful as a predictive and prognostic marker in this subgroup of breast cancer.

CD4+ TIL subset and FOXP3+/CD8+ T cell ratio have different prognostic significance in breast cancer according to hormone receptor status.

The purpose of this article is to review imaging findings and to discuss the optimal imaging methods for craniosynostosis. The discussion of imaging findings are focused on ultrasonography, plain radiography, magnetic resonance imaging and computed tomography with 3-dimensional reconstruction. We suggest a strategy for imaging work-up for the diagnosis, treatment planning and follow-up to minimize or avoid ionized radiation exposure to children by reviewing the current literature.