Additional file 1: Figure S1. of Anti-proliferative effects of T cells expressing a ligand-based chimeric antigen receptor against CD116 on CD34+ cells of juvenile myelomonocytic leukemia

Effects of GMR CAR T cells on GM or erythroid colony growth of CB and BM CD34+ cells. Either GMR CAR T cells or mock T cells were incubated with normal CB CD34+ cells (n = 3) or normal BM CD34+ cells (n = 3) at E:T ratios of 1:1 and 1:4, in the presence of SCF + TPO + IL-3 for 2 days. Cells were then cultured on methylcellulose in media supplemented with GM-CSF, SCF, IL-3, and erythropoietin. After 14 days, the numbers of GM colonies and erythroid colonies were calculated for each. Values are expressed as percentages of the total colony numbers obtained by culture in the absence of T cells. The numbers of GM colonies grown by 500 CB CD34+ cells and BM CD34+ cells in the absence of T cells were 38.6 ± 4.6 and 24.5 ± 2.9, respectively. The numbers of erythroid colonies grown by 500 CB CD34+ cells and BM CD34+ cells in the absence of T cells were 42.7 ± 15.5 and 19.1 ± 2.6, respectively. (EPS 439 kb

Quantitative high-throughput analysis of tumor infiltrating lymphocytes in breast cancer

In breast cancer (BC), the development of cancer immunotherapy including immune checkpoint inhibitors has progressed. Tumor infiltrating lymphocytes (TILs) is one of the important factors for an immune response between tumor cells and immune cells in the tumor microenvironment, and the presence of TILs has been identified as predictors of response to chemotherapy. However, because complex mechanisms underlies the crosstalk between immune cells and cancer cells, the relationship between immune profiles in the tumor microenvironment and the efficacy of the immune checkpoint blocked has been unclear. Moreover, in many cases of breast cancer, the quantitative analysis of TILs and immuno-modification markers in a single tissue section are not studied. Therefore, we quantified detailed subsets of tumor infiltrating lymphocytes (TILs) from BC tissues and compared among BC subtypes. The TILs of BC tissues from 86 patients were classified using multiplex immunohistochemistry and an artificial intelligence-based analysis system based on T-cell subset markers, immunomodification markers, and the localization of TILs. The levels of CD4/PD1 and CD8/PD1 double-positive stromal TILs were significantly lower in the HER2- BC subtype (p <0.01 and p <0.05, respectively). In triple-negative breast cancer (TNBC), single marker-positive intratumoral TILs did not affect prognosis, however CD4/PDL1, CD8/PD1, and CD8/PDL1 double-positive TILs were significantly associated with TNBC recurrence (p<0.05, p<0.01, and p<0.001, respectively). TIL profiles differed among different BC subtypes, suggesting that the localization of TILs and their tumor-specific subsets influence the BC microenvironment

Spatial and Quantitative Analysis of Tumor-Associated Macrophages : Intratumoral CD163-/PD-L1+TAMs as a Marker of Favorable Clinical Outcomes in Triple-Negative Breast Cancer

Tumor-associated macrophages (TAMs) and abnormalities in cancer cells affect cancer progression and response to therapy. TAMs are a major component of the tumor microenvironment (TME) in breast cancer, with their invasion affecting clinical outcomes. Programmed death-ligand 1 (PD-L1), a target of immune checkpoint inhibitors, acts as a suppressive signal for the surrounding immune system; however, its expression and effect on TAMs and the clinical outcome in breast cancer are unknown. In this study, we used high-throughput multiple immunohistochemistry to spatially and quantitatively analyze TAMs. We subjected 81 breast cancer specimens to immunostaining for CD68, CD163, PD-1, PD-L1, CD20, and pan-CK. In both stromal and intratumoral areas, the triple-negative subtype had significantly more CD68/CD163, CD68/PD-L1, and CD163/PD-L1 double-positive cells than the estrogen receptor (ER)/progesterone receptor (PR) subtype. Interestingly, a higher number of CD68+/PD-L1+/CK-/CD163- TAMs in the intratumoral area was correlated with a favorable recurrence rate (p = 0.048). These findings indicated that the specific subpopulation and localization of TAMs in the TME affect clinical outcomes in breast cancer

インスリン依存型糖尿病をもつ児童・生徒の学校生活の実態とニーズ調査

In order to improve factual understanding of school life of children with insulin dependent diabetes mellitus (commonly known as IDDM or Type 1 diabetes), questionnaire research was carried out, after obtaining prior approval, with 67 applicants and their parent/guardian of the 2000 Diabetes Summer Camp. The results clearly indicate inadequate consideration for IDDM sufferers in schools, such as causation of hypoglycemia and insufficient provision of suitable areas for insulin injection, and suggest a necessity for higher cooperation levels between the school and the patients\u27 families. On a separate note, they also call for higher awareness, in children of development phase, of the importance of self-control and monitoring in living with IDDM, and the need to provide adequate psychological support to such children during the long-term treatment process

大学院生による三重大学大学院教育学研究科に関する意識調査 : これでええんか 大学院生

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Mitochondrial Genome Variation in Eastern Asia and the Peopling of Japan

To construct an East Asia mitochondrial DNA (mtDNA) phylogeny, we sequenced the complete mitochondrial genomes of 672 Japanese individuals (http://www.giib.or.jp/mtsnp/index_e.html). This allowed us to perform a phylogenetic analysis with a pool of 942 Asiatic sequences. New clades and subclades emerged from the Japanese data. On the basis of this unequivocal phylogeny, we classified 4713 Asian partial mitochondrial sequences, with <10% ambiguity. Applying population and phylogeographic methods, we used these sequences to shed light on the controversial issue of the peopling of Japan. Population-based comparisons confirmed that present-day Japanese have their closest genetic affinity to northern Asian populations, especially to Koreans, which finding is congruent with the proposed Continental gene flow to Japan after the Yayoi period. This phylogeographic approach unraveled a high degree of differentiation in Paleolithic Japanese. Ancient southern and northern migrations were detected based on the existence of basic M and N lineages in Ryukyuans and Ainu. Direct connections with Tibet, parallel to those found for the Y-chromosome, were also apparent. Furthermore, the highest diversity found in Japan for some derived clades suggests that Japan could be included in an area of migratory expansion to Continental Asia. All the theories that have been proposed up to now to explain the peopling of Japan seem insufficient to accommodate fully this complex picture