Decreased expression of alpha3 and beta1 integrin subunits is responsible for differentiation-associated changes in cells behavior in terminally differentiated human oral keratinocytes.

Primary normal human oral keratinocytes (NHOKs) terminally differentiate in serial subculture. To investigate whether this subculture-induced differentiation of NHOKs affects integrin expression and cell-matrix interaction, we studied the expression levels of integrin subunits and cellular response to the extracellular matrix (ECM) proteins in NHOKs at different population doublings. The phosphorylation statuses of focal adhesion kinase (FAK), extracellular signal regulated kinase (ERK), p38, and c-Jun amino-terminal kinase (JNK) were also determined in NHOK cells cultured on ECM proteins, to evaluate the functions of integrins with respect to cellular responses to ECM proteins. The expression levels of ®3 and ¯1 integrin subunits progressively decreased in NHOKs undergoing terminal differentiation. The ability of NHOKs to spread upon laminin and type I collagen significantly decreased in terminally differentiated oral keratinocytes. Keratinocyte migration was significantly increased on type I collagen for terminally differentiated NHOKs. Similar results were seen following preincubation of rapidly proliferating NHOKs with function-blocking antibodies to ®3 or ¯1 integrin subunit. In contrast, fibronectin had no effect on cellular responses in NHOKs, which were almost negligible in the expression levels of ®5 integrin subunits. The extent of FAK phosphorylation in terminally differentiated NHOKs was notably lower than that of rapidly proliferating cells, but was enhanced in terminally differentiated cells that were cultured on type I collagen. Our results indicate that decreased expression of ®3 and ¯1 integrin subunits is responsible for differentiation-associated changes in cells behavior in terminally differentiated oral keratinocytes. Our data also show that the abrogation of the ®5¯1 integrin function caused by omitting ®5 subunit is linked to the loss of a cell-fibronectin interaction in human oral keratinocytes.This study was supported by the Korean Science and Engineering Foundation (KOSEF) through the Intellectual Biointerface Engineering Center (IBEC) at the Seoul National University

Electrospinning of chitin nanofibers: Degradation behavior and cellular response to normal human keratinocytes and fibroblasts

An electrospinning method was used to fabricate chitin nanofibrous matrices for biodegradability and cell behavior tests. The morphology of as-spun chitin nanofibers (Chi-N) and commercial chitin microfibers (Beschitin W®; Chi-M) was investigated by scanning electron microscopy. From the image analysis, the average diameters of Chi-N and Chi-M were 163 nm and 8.77 μm, respectively. During in vitro degradation for 15 days, the degradation rate of Chi-N was faster than that of Chi-M, likely due to higher surface area of Chi-N. Chi-N that was grafted into rat subcutaneous tissue had almost degraded within 28 days, and no inflammation could be seen on the nanofiber surfaces or in the surrounding tissues (except in the early stage wound). To assay and compare the cytocompatibility and cell behavior with Chi-N and Chi-M, cell attachment and spreading of normal human keratinocytes and fibroblasts seeded on chitin matrices and the interaction between cells and chitin fibers were studied. Relatively high cell attachment and spreading of all the cells tested were observed on Chi-N in comparison to Chi-M, and Chi-N treated with type I collagen significantly promoted the cellular response. Our results indicate that the Chi-N, alone or with extracellular matrix proteins (particularly type I collagen), could be potential candidates for the cell attachment and spreading of normal human keratinocytes and fibroblasts. This property of Chi-N might be particularly useful for wound healing and regeneration of oral mucosa and skin

Periodic Endoscopies Might Not Increase the Detection of Early Gastric Cancer in a Young Population.

Screening endoscopies in individuals 40 years or older in regions where gastric cancer is prevalent increase the diagnosis of gastric cancer at an early stage. However, the benefits of screening endoscopies in a young population (<40 years) have not been evaluated.We reviewed data from patients less than 40 years old who underwent endoscopic submucosal dissection or surgery for initial-onset gastric cancer. We also administered a questionnaire to gather information concerning periodic endoscopic inspections and the period from the penultimate endoscopy to diagnosis.Of the 564 patients in this study, 101 (17.9%) patients underwent screening endoscopy within 24 months of their gastric cancer diagnosis. Lesion size was significantly smaller in the ≤24 months group than in the >24 month group (23.8 mm [standard deviation, 22.2 mm] vs. 30.5 mm [standard deviation, 23.1 mm], P = 0.008). However, the proportion of patients with early gastric cancer did not differ between the two groups (≤24 months vs. >24 months group; 67.6% vs. 65.7%, P = 0.712). On multivariable analysis, periodic endoscopies did not influence the early diagnosis of gastric cancer (with >24 months as the reference group: ≤24 months, odds ratio = 0.939, 95% confidence interval = 0.583-1.513).Although periodic endoscopies aided in the detection of gastric cancer when lesions were smaller in size, they seemed not to increase the proportion of patients with early gastric cancer in young patients diagnosed with resectable gastric cancer