Mucosal-associated invariant T (MAIT) cells are an antimicrobial MR1-restricted T cell subset and play an important role in immune defense response to bacteria. However, little is known about the role of MAIT cells in cancer. The aims of this study were to examine the level and function of MAIT cells in cancer patients and to evaluate the clinical relevance of MAIT cell levels. Ninety-nine patients with cancer and 20 healthy controls were included in this study. Circulating MAIT cell levels were significantly reduced in patients with mucosal-associated cancers (MACs), such as gastric, colon and lung cancers, but their capacities for IFN-γ, IL-17, or TNF-α production were preserved. This MAIT cell deficiency was significantly correlated with N staging and carcinoembryonic antigen level. Percentages of MAIT cells were significantly higher in cancer tissue than in peripheral blood and immunofluorescent labeling showed MAIT cell infiltration into colon cancer tissues. Circulating MAIT cells exhibited high levels of CCR6 and CXCR6, and their corresponding chemokines, such as CCL20 and CXCL16, were strongly expressed in colon cancer tissues. Activated MAIT cells not only had lymphokine-activated killer activity, but they also had direct cytotoxicity on K562 cells via degranulation of granzyme B and perforin. This study primarily demonstrates that circulating MAIT cells are reduced in MAC patients due to migration to mucosal cancer tissues and they have the potential to kill cancer cells. In addition, this circulating MAIT cell deficiency is related to the degree of cancer progression in mucosal tissues.

Writing with ink involves the supply of liquid from a pen onto a porous hydrophilic solid surface, paper. The resulting linewidth depends on the pen speed and the physicochemical properties of the ink and paper. Here we quantify the dynamics of this process using a combination of experiment and theory. Our experiments are carried out using a minimal pen, a long narrow tube that serves as a reservoir of liquid, which can write on a model of paper, a hydrophilic micropillar array. A minimal theory for the rate of wicking or spreading of the liquid is given by balancing the capillary force that drives the liquid flow and the resistance associated with flow through the porous substrate. This allows us to predict the shape of the front and the width of the line laid out by the pen, with results that are corroborated by our experiments.

Hemiwicking refers to the spreading of a liquid on a rough hydrophilic surface driven by capillarity. Here, we construct scaling laws to predict the velocity of hemiwicking on a rough substrate and experimentally corroborate them with various arrangements and dimensions of micropillar arrays. At the macroscopic scale, where the wetting front appears parallel to the free surface of the reservoir, the wicking distance is shown to grow diffusively, i.e. like $t^{1/2}$ with $t$ being time. We show that our model is consistent with pillar arrays of a wide range of pitch-to-height ratios, either square or skewed. At the microscopic scale, where the meniscus extension from individual pillars at the wetting front is considered, the extension distance begins to grow like $t$ but the spreading slows down to behave like $t^{1/3}$ when the meniscus is far from the pillar. Our microscopic flow modelling allows us to find pillar spacing conditions under which the assumption of densely spaced pillars is valid.

To identify candidate genes that could be used as diagnostic and therapeutic targets for hepatocellular carcinoma (HCC), we searched for the genes that are overexpressed in HCC by combining representational difference analysis and microarray. Genes such as glypican-3 (GPC3), insulin-like growth factor 2, long-chain fatty-acid-coenzyme A ligase 4, farnesyl diphosphate synthase were frequently identified in our screening. Northern blot analysis with these four genes confirmed their overexpression in HCC. Among them we found that GPC3 transcript is upregulated in six out of seven cases of HCC. Immunoblot and immunohistochemical staining using polyclonal anti-GPC3 antibodies further confirmed that GPC3 protein is indeed increased in HCC tumor samples. We also found that GPC3 is secreted into culture media from cell lines derived from HCC. We conclude that GPC3 is a good molecular marker for HCC. (Cancer Sci 2003; 94: 259-262) lypican-3 (GPC3) is a member of the glypican family of heparan-sulfate proteoglycans, which are linked to the cell surface through a glycosylphosphatidylinositol anchor.1) GPC3 loss-of-function mutation in human causes type 1 Simpson-Golabi-Behmel syndrome (SGBS1), an X-linked condition characterized by pre-and postnatal overgrowth.2) GPC3 knockout mice indeed exhibited several phenotypic features of SGBS1. [3][4][5] These findings together with cell line-specific promotion of apoptosis by OCI-5/GPC3 6) suggest that GPC3 plays a negative role in cell proliferation and an apoptosis-inducing role in specific tissues.Consistent with the above idea, GPC3 expression is frequently silenced by promoter methylation in ovarian cancer cell lines, 7) rat mesothelioma cell lines and human primary tumors, 8) and breast cancer cell lines. 9) In addition, ectopic expression of GPC3 inhibited growth in some of the above cell lines, suggesting a tumor-suppressive role of GPC3. In contrast, GPC3 is known to be overexpressed in hepatocellular carcinoma, 10,11) neuroblastoma and Wilms' tumor cells.12) The role of GPC3 in these tumors is not known. It is also not known whether GPC3 protein is indeed increased in these tumors.Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide and is one of the leading causes of death among cancer patients in Korea. Identification of genes that are overexpressed in HCC not only helps our understanding of tumorigenesis, but also helps to develop diagnostic and therapeutic targets. In this study, we combined representational difference analysis (RDA) 13) and microarray 14) to identify genes that are frequently overexpressed in HCC tumor samples. Since GPC3 was the most frequently obtained gene in our screening, we further evaluated it as a tumor marker for HCC. Materials and MethodsTumor samples and cell lines. HCC tumor tissues and corresponding normal liver tissues were obtained from patients (Table 1) undergoing surgery in Kyungpook National University Hospital (Daegu, Korea) with the approval of the human research review committee and the patients' consent. C...

Melorheostosis is a rare bone disease characterized by linear hyperostosis and associated soft tissue abnormalities. The skin overlying the involved bone lesion is often tense, shiny, erythematous, and scleodermatous. In order to look for genes differentially expressed between the normal and involved skin, we cultured skin fibroblasts from the skin lesions of several afflicted patients, and identified differentially expressed genes by reverse dot-blot hybridization. We found that the genes human TGF-beta-induced gene product (betaig-h3), osteoblast-specific factor 2, osteonectin, fibronectin, and type I collagen were all downregulated in the affected skin fibroblasts, with betaig-h3 the most significantly affected. The expression of betaig-h3 was induced by TGF-beta in both affected and normal fibroblasts. In an effort to determine the mechanism of bone and skin abnormalities in melorheostosis, we made recombinant betaig-h3. Both immobilized and soluble recombinant betaig-h3 proteins with or without an RGD motif inhibited bone nodule formation of osteoblasts in vitro. Taken together, our results suggest that altered expression of several adhesion proteins may contribute to the development of hyperostosis and concomitant soft tissue abnormalities of melorheostosis, with betaig-h3 in particular playing an important role in osteogenesis.

Keratin is an important protein used for wound healing and tissue recovery. In this study, keratin was first extracted from raw materials and chemically modified to obtain stable keratin (m-keratin). The raw and m-keratin were examined by Raman spectroscopy. The molecular weight of the m-keratin was analysed by SDS-PAGE. The m-keratin was then blended with poly(hydroxybutylate-co-hydroxyvalerate) (PHBV) and electrospun to afford nanofibrous mats. These mats were characterized by field emission scanning electron microscopy (FE-SEM), electron spectroscopy for chemical analysis (ESCA) and atomic force microscopy (AFM). From the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) data, it was found that introduction of keratin enhanced cell proliferation. From wound-healing test and histological examination results, it was shown that the composite mats accelerated wound recovery remarkably as compared to the PHBV control. It was concluded that PHBV-keratin may be a good candidate as a wound dressing.

Capillary rise of water in porous cellulose sponges is investigated considering hygroscopic shape evolutions of micropores.

When a fluid-immersed array of lamellae or filaments that is attached to a substrate is dried, evaporation leads to the formation of menisci on the tips of the plates or pillars that bring them together. Similarly, when hair dries it clumps together due to capillary forces induced by the liquid menisci between the flexible hairs. Building on prior experimental observations, we use a combination of theory and computation to understand the nature of this instability and its evolution in both the two-dimensional and three-dimensional setting of the problem. For the case of lamellae, we explicitly derive the interaction torques based on the relevant physical parameters. A Bloch-wave analysis for our periodic mechanical system captures the critical volume of the liquid and the 2-plate-collapse eigenmode at the onset of instability. We study the evolution of clusters and their arrest using numerical simulations to explain the hierarchical cluster formation and characterize the sensitive dependence of the final structures on the initial perturbations. We then generalize our analysis to treat the problem of pillar collapse in 3D, where the fluid domain is completely connected and the interface is a surface with the uniform mean curvature. Our theory and simulations capture the salient features of both previous experimental observations and our own in terms of the key parameters that can be used to control the kinetics of the process