Platelet derived growth factor receptor alpha is essential for establishing a microenvironment that supports definitive erythropoiesis

金沢大学大学院自然科学研究科大阪大学微生物病研究所 情報伝達分野The hematopoietic system undergoes a qualitative change during the embryogenesis of most vertebrates. It is designated as the shift of primitive to definitive hematopoiesis and suitable microenvironment must be established to support this shift. While studying the role of platelet derived growth factor receptor α (PDGFR α) in embryonic hematopoiesis, we found that it was expressed in a stromal cell component of liver, a major site of this shift, but not in the yolk sac, the site of primitive hematopoiesis. Thus, we considered that development of PDGFRα positive stromal cells is an essential requirement for this shift. Without PDFGRα positive cell component, erythropoiesis was suppressed in the culture of fetal liver. Moreover, injection of an antagonistic anti-PDGFRα monoclonal antibody during embryogenesis suppressed the production of definitive erythrocytes. These indicated that PDGF exerts its effect on a subset of stromal components to prepare a microenvironment that can support the definitive erythropoiesis. © 2006 The Japanese Biochemical Society

Magnetic Ordering in V-Layers of the Superconducting System of Sr2VFeAsO3

Results of transport, magnetic, thermal, and 75As-NMR measurements are presented for superconducting Sr2VFeAsO3 with an alternating stack of FeAs and perovskite-like block layers. Although apparent anomalies in magnetic and thermal properties have been observed at ~150 K, no anomaly in transport behaviors has been observed at around the same temperature. These results indicate that V ions in the Sr2VO3-block layers have localized magnetic moments and that V-electrons do not contribute to the Fermi surface. The electronic characteristics of Sr2VFeAsO3 are considered to be common to those of other superconducting systems with Fe-pnictogen layers.Comment: 4 pages, 4 figures, To appear in JPSJ 79 (2010) 12371

Study of Ni-doping Effect of Specific Heat and Transport Properties for LaFe1-yNiyAsO0.89F0.11

Specific heats and transport quantities of the LaFe1-yNiyAsO0.89F0.11 system have been measured, and the results are discussed together with those reported previously by our group mainly for LaFe1-yCoyAsO0.89F0.11 and LaFeAsO0.89-xF0.11+x systems. The y dependence of the electronic specific heat coefficient gamma can basically be understood by using the rigid-band picture, where Ni ions provide 2 electrons to the host conduction bands and behave as nonmagnetic impurities. The superconducting transition temperature Tc of LaFe1-yNiyAsO0.89F0.11 becomes zero, as the carrier density p (=2y+0.11) doped to LaFeAsO reaches its critical value p_c_ ~0.2. This p_c_ value of ~0.2 is commonly observed for LaFe1-yCoyAsO0.89F0.11 and LaFeAsO0.89-xF0.11+x systems, in which the relations p = x+0.11 and p = y+0.11 hold, respectively. As we pointed out previously, the critical value corresponds to the disappearance of the hole-Fermi surface. These results indicate that the carrier number solely determines the Tc value. We have not observed appreciable effects of pair breaking, which originates from the nonmagnetic impurity scattering of conduction electrons and strongly suppresses T_c_ values of systems with sign-reversing of the order parameter over the Fermi surface(s). On the basis of the results, the so-called s_+-_ symmetry of the order parameter with the sign-reversing is excluded.Comment: 4 pages, 7 figures, submitted to J. Phys. Soc. Jpn, (modified version

栄養素を考慮した献立管理システムを用いて作成した献立のレシピバランスの評価 : ユーザからのフィードバックを考慮した献立表推薦システムの場合

Japanese are increasingly searching for recipes online when they cook. At many recipe site, users can search for and contribute recipes. However, such recipe sites often fail to provide detailed nutritional information. In this study, registered dietitians evaluated the results of a score used by a cooking group. the score involved the number of recipes used, within one week, of grain dishes, main dishes (fish and meat), side dishes(vegetables), fruits, milk and others (juice and sweets). The score of grain dishes, main dishes, side dishes, fruits and milk was lower than the ideal score provided by the Japanese Food Guide Spinning Top. These results indicate that it is necessary to improve the selection of meals by a menu management system

Concomitant administration of radiation with eribulin improves the survival of mice harboring intracerebral glioblastoma

Glioblastoma is the most common and devastating type of malignant brain tumor. We recently found that eribulin suppresses glioma growth in vitro and in vivo and that eribulin is efficiently transferred into mouse brain tumors at a high concentration. Eribulin is a non‐taxane microtubule inhibitor approved for breast cancer and liposarcoma. Cells arrested in M‐phase by chemotherapeutic agents such as microtubule inhibitors are highly sensitive to radiation‐induced DNA damage. Several recent case reports have demonstrated the clinical benefits of eribulin combined with radiation therapy for metastatic brain tumors. In this study, we investigated the efficacy of a combined eribulin and radiation treatment on human glioblastoma cells. The glioblastoma cell lines U87MG, U251MG and U118MG, and SJ28 cells, a patient‐derived sphere culture cell line, were used to determine the radiosensitizing effect of eribulin using western blotting, flow cytometry and clonogenic assay. Subcutaneous and intracerebral glioma xenografts were generated in mice to assess the efficacy of the combined treatment. The combination of eribulin and radiation enhanced DNA damage in vitro. The clonogenic assay of U87MG demonstrated the radiosensitizing effect of eribulin. The concomitant eribulin and radiation treatment significantly prolonged the survival of mice harboring intracerebral glioma xenografts compared with eribulin or radiation alone (P < .0001). In addition, maintenance administration of eribulin after the concomitant treatment further controlled brain tumor growth. Aberrant microvasculature was decreased in these tumors. Concomitant treatment with eribulin and radiation followed by maintenance administration of eribulin may serve as a novel therapeutic strategy for glioblastomas

A randomized phase III study of short-course radiotherapy combined with Temozolomide in elderly patients with newly diagnosed glioblastoma; Japan clinical oncology group study JCOG1910 (AgedGlio-PIII)

BACKGROUND: The current standard treatment for elderly patients with newly diagnosed glioblastoma is surgery followed by short-course radiotherapy with temozolomide. In recent studies, 40 Gy in 15 fractions vs. 60 Gy in 30 fractions, 34 Gy in 10 fractions vs. 60 Gy in 30 fractions, and 40 Gy in 15 fractions vs. 25 Gy in 5 fractions have been reported as non-inferior. The addition of temozolomide increased the survival benefit of radiotherapy with 40 Gy in 15 fractions. However, the optimal regimen for radiotherapy plus concomitant temozolomide remains unresolved. METHODS: This multi-institutional randomized phase III trial was commenced to confirm the non-inferiority of radiotherapy comprising 25 Gy in 5 fractions with concomitant (150 mg/m2/day, 5 days) and adjuvant temozolomide over 40 Gy in 15 fractions with concomitant (75 mg/m2/day, every day from first to last day of radiation) and adjuvant temozolomide in terms of overall survival (OS) in elderly patients with newly diagnosed glioblastoma. A total of 270 patients will be accrued from 51 Japanese institutions in 4 years and follow-up will last 2 years. Patients 71 years of age or older, or 71-75 years old with resection of less than 90% of the contrast-enhanced region, will be registered and randomly assigned to each group with 1:1 allocation. The primary endpoint is OS, and the secondary endpoints are progression-free survival, frequency of adverse events, proportion of Karnofsky performance status preservation, and proportion of health-related quality of life preservation. The Japan Clinical Oncology Group Protocol Review Committee approved this study protocol in April 2020. Ethics approval was granted by the National Cancer Center Hospital Certified Review Board. Patient enrollment began in August 2020. DISCUSSION: If the primary endpoint is met, short-course radiotherapy comprising 25 Gy in 5 fractions with concomitant and adjuvant temozolomide will be a standard of care for elderly patients with newly diagnosed glioblastoma. TRIAL REGISTRATION: Registry number: jRCTs031200099 . Date of Registration: 27/Aug/2020. Date of First Participant Enrollment: 4/Sep/2020