Recent advances in biomedical engineering require the development of new types of blood-compatible polymers that also allow non-blood cell attachment for the isolation of stem cells and circulating tumor cells (CTCs) from blood and for the development of artificial organs for use under blood-contact conditions. Poly(2-methoxyethyl acrylate) (PMEA) and poly(tetrafurfuryl acrylate) (PTHFA) were previously identified as blood-compatible polymers. Here, it is demonstrated that cancer cells can attach to the PMEA and PTHFA substrates, and the differences in the attachment mechanisms to the PMEA and PTHFA substrates between cancer cells and platelets are investigated. It is also found that the adsorption-induced deformation of fibrinogen, which is required for the attachment and activation of platelets, does not occur on the PMEA and PTHFA substrates. In contrast, fibronectin is deformed on the PMEA and PTHFA substrates. Therefore, it is concluded that cancer cells and not platelets can attach to the PMEA and PTHFA substrates based on this protein-deformation difference between these substrates. Moreover, it is observed that cancer cells attach to the PMEA substrate via both integrin-dependent and -independent mechanisms and attach to the PTHFA substrate only through an integrin-dependent mechanism. It is expected that PMEA and PTHFA will prove useful for blood-contact biomedical applications.

Loss-of-function mutations in the Ca release-activated Ca channel genes ORAI1 and STIM1 abolish store-operated Ca entry (SOCE) and result in ectodermal dysplasia with amelogenesis imperfecta. However, because of the limited availability of patient tissue, analyses of enamel mineralization or possible changes in ameloblast function or morphology have not been possible. Here, we generated mice with ectodermal tissue-specific deletion of Stim1 ( Stim1 cKO [conditional knockout]), Stim2 ( Stim2 cKO), and Stim1 and Stim2 ( Stim1/2 cKO) and analyzed their enamel phenotypes as compared with those of control ( Stim1/2) animals. Ablation of Stim1 and Stim1/2 but not Stim2 expression resulted in chalky enamel and severe attrition at the incisor tips and molar cusps. Stim1 and Stim1/2 cKO, but not Stim2 cKO, demonstrated inferior enamel mineralization with impaired structural integrity, whereas the shape of the teeth and enamel thickness appeared to be normal in all animals. The gene expression levels of the enamel matrix proteins Amelx and Ambn and the enamel matrix proteases Mmp20 and Klk4 were not altered by the abrogation of SOCE in Stim1/2 cKO mice. The morphology of ameloblasts during the secretory and maturation stages was not significantly altered in either the incisors or molars of the cKO animals. However, in Stim1 and Stim1/2 cKO incisors, the alternating modulation of maturation-stage ameloblasts between the smooth- and ruffle-ended cell types continued beyond the regular cycle and extended to the areas corresponding to the zone of postmodulation ameloblasts in the teeth of control animals. These results indicate that SOCE is essential for proper enamel mineralization, in which Stim1 plays a critical role during the maturation process.

Circulating tumor cells have received attention for their role in cancer diagnosis and the decision on which chemotherapeutic course to take. For these purposes, the isolation of circulating tumor cells has been important. Previously, we reported that non-blood cells can adhere on blood-compatible polymer substrates, such as poly(2-methoxyethyl acrylate) and poly(tetrahydrofurfuryl acrylate). In this study, we examined whether blood-compatible poly(2-methoxyethyl acrylate) and poly(tetrahydrofurfuryl acrylate) allow the adhesion and growth of A549 lung cancer cells for isolating circulating tumor cells by adhesion-mediated manner to diagnose metastatic cancer and to decide on the chemotherapeutic course. A549 cells can adhere on poly(2-methoxyethyl acrylate) and poly(tetrahydrofurfuryl acrylate) substrates via an integrin-dependent mechanism after 1 h of incubation, suggesting that blood-compatible poly(2-methoxyethyl acrylate) and poly(tetrahydrofurfuryl acrylate) substrates possess the ability to capture circulating tumor cells selectively from peripheral blood. After 1 day of culture, A549 cells started to spread on poly(2-methoxyethyl acrylate) and poly(tetrahydrofurfuryl acrylate) substrates. A549 can also grow on poly(2-methoxyethyl acrylate) and poly(tetrahydrofurfuryl acrylate) substrates. Additionally, the chemoresistance of A549 cells against 5-fluorouracil on poly(2-methoxyethyl acrylate) and poly(tetrahydrofurfuryl acrylate) substrates was similar to that on the conventional cell culture substrate, tissue culture polystyrene. These results indicate that circulating tumor cells can be cultured on poly(2-methoxyethyl acrylate) and poly(tetrahydrofurfuryl acrylate) substrates after they are isolated from peripheral blood, and poly(2-methoxyethyl acrylate) and poly(tetrahydrofurfuryl acrylate) substrates can be used as circulating tumor cell culture substrates for screening anti-cancer drugs. Therefore, poly(2-methoxyethyl acrylate) and poly(tetrahydrofurfuryl acrylate) substrates might be able to be applied to the development of a new device for a circulating tumor cell–based diagnosis of metastatic cancer and a personalized medicine approach regarding the decision of which chemotherapeutic course should be taken.

Immune checkpoint inhibitors blocking the interaction between PD-1 and PD-L1 are revolutionizing the cancer immunotherapies with durable clinical responses. Although high expression of PD-L1 in tumor tissues has been implicated to correlate with the better response to the anti-PD-1 therapies, this association has been still controversial. In this study, to characterize immune microenvironment in tumors, we examined mRNA levels of immunerelated genes and characterized T cell repertoire in the tumors of 13 melanoma patients before and after nivolumab treatment. We found that, in addition to the PD-L1 (P ¼ 0.03), expression levels of PD-1 ligand-2 (PD-L2), granzyme A (GZMA) and human leukocyte antigen-A (HLA-A) in the pre-treatment tumors were significantly higher (P ¼ 0.04, P ¼ 0.01 and P ¼ 0.006, respectively) in responders than in non-responders. With nivolumab treatment, tumors in responders exhibited a substantial increase of CD8, GZMA and perforin 1 (PRF1) expression levels as well as increased ratio of TBX21/GATA3, suggesting dominancy of Th1 response. The scoring system using three possible biomarkers