Background-Recent studies have shown that bone marrow-derived stem cells differentiate into the phenotype of cardiomyocytes in vivo and in vitro. We tried to regenerate infarcted myocardium by implanting ex vivo transforming growth factor (TGF)-␤-preprogrammed CD117 (c-kit)-positive (CD117 ϩ ) stem cells intramyocardially. Methods and Results-CD117ϩ cells were isolated from the bone marrow mononuclear cells of GFP-transgenic or normal C57/BL6 mice. The myogenic differentiation of CD117 ϩ cells was achieved by cultivation with TGF-␤. Using an acute myocardial infarction model, we also tried to regenerate infarcted myocardium by implanting untreated (newly isolated) or preprogrammed (24 hours of cultivation with 5 ng/mL TGF-␤ 1 ) CD117 ϩ cells intramyocardially. TGF-␤ increased the cellular expression of myosin, troponins, connexin-43, GATA-4, and NKx-2.5, which suggested that it induced the myogenic differentiation of CD117 ϩ cells. Compared with the effects of PBS injection only, the microvessel density in the infarcted myocardium was increased significantly 3 months after the implantation of either TGF-␤-preprogrammed or untreated CD117 ϩ cells. Moreover, many of the TGF-␤-preprogrammed CD117 ϩ cells were stained positively for myosin, whereas few of the untreated CD117 ϩ cells were. Histological analysis revealed newly regenerated myocardium in the left ventricular anterior wall after the implantation of TGF-␤-preprogrammed cells but not untreated cells. Furthermore, the left ventricular percent fraction shortening was significantly higher after the implantation of TGF-␤-preprogrammed cells than after the implantation of untreated CD117 ϩ cells. Conclusions-TGF-␤ conducted the myogenic differentiation of CD117ϩ stem cells by upregulating GATA-4 and NKx-2.5 expression. Therefore, the intramyocardial implantation of TGF-␤-preprogrammed CD117 ϩ cells effectively assisted the myocardial regeneration and induced therapeutic angiogenesis, contributing to functional cardiac regeneration. (Circulation. 2005;111:2438-2445.)

When pediatric, adolescent, and young adult patients present with a bone sarcoma, treatment decisions, especially after relapse, are complex and require a multidisciplinary approach. This review presents scenarios commonly encountered in the therapy of bone sarcomas with the goal of objectively presenting a consensus, multidisciplinary management approach. Little variation was found in the authors' group with respect to local control or systemic therapy. Clinical trials were universally prioritized in all settings. Decisions regarding relapse therapies in the absence of a clinical trial had very minor variations initially, but a consensus was reached after a literature review and discussion. This review presents a concise document and figures as a starting point for evidence‐based care for patients with these rare diseases. This framework allows prospective decision making and prioritization of clinical trials. It is hoped that this framework will inspire and focus future clinical research and thus lead to new trials to improve efficacy and reduce toxicity. Cancer 2017;123:2206–2218. © 2017 American Cancer Society.

Maize (Zea mays L. cv Golden Cross Bantam T51) seedlings were grown under full sunlight or 50% sunlight in a temperature-controlled glasshouse at the temperatures of near optimum (30/25°C) and suboptimum (17/13°C) with seven levels of nitrate-N (0.4 to 12 millimolars). The contents of phosphoenolpyruvate carboxylase (PEPC), pyruvate orthophosphate dikinase (PPD), and ribulose-1,5-P2 carboxylase/oxygenase (RuBisCO) were immunochemically determined for each treatment with rabbit antibodies raised against the respective maize leaf proteins (anti-PEPC and anti-PPD) or spinach leaf protein (anti-RuBisCO). The content of each enzymic protein increased with increasing N and raised under reduced temperature. The positive effect of light intensity on their contents was evident only at near optimal temperature. The relative increase in PEPC and PPD content with increasing N was significantly greater than that of RuBisCO irrespective of growth conditions. These enzymic proteins comprised about 8, 6, and 35% of total soluble protein, respectively, at near optimal growth condition. In contrast to significant increase in the proportion of soluble protein allocated to PEPC and PPD seen under certain conditions, the proportion allocated to RuBisCO decreased reciprocally with an increased biomass yield by N supply.These results indicated that the levels of PEPC and PPD parallel to maize biomass more tightly than that of RuBisCO at least under near optimal growth condition.One of the characteristic differences between C3 and C4 species is their N use efficiency, defined as biomass production per unit of N in the plants. Brown (3) has put forward the hypothesis and supporting data that C4 species utilize N more efficiently than C3 species; this hypothesis also has been supported by Schmitt and Edwards (13) with maize (C4) and wheat and rice (C3) plants.The main difference in the N use efficiency of these species appears to be based on partitioning of N among leaf proteins and the related carbon assimilation pathway (3). In C3 species the proportion of protein allocated to RuBisCO,2 a major leaf 'Supported by funds from the Japanese Ministry of Education, Science, and Culture (5860058), the Japanese Ministry of Agriculture, Forestry, and Fishery (GEP 58 II-1-28), and the Ishida Foundation (56-228).2Abbreviations: RuBisCO, ribulose-l1,5-bisphosphate carboxylase/ox-

Basic helix-loop-helix (bHLH) transcription factors are known as key regulators for mesenchymal differentiation. The present study showed that overexpression of Twist-1, a bHLH transcription factor, suppresses bone morphogenetic protein (BMP)-induced osteoblast differentiation, and downregulation of endogenous Twist-1 enhances BMP signaling. Maximal inhibition of BMP signaling was observed when Twist-1 was bound to E47, which markedly enhanced the stability of Twist-1. Co-immunoprecipitation assays revealed that Twist-1 formed a complex with Smad4 and histone deacetylase (HDAC) 1 in MC3T3-E1 cells stably expressing Twist-1. With trichostatin, an HDAC inhibitor, osteogenic factors such as alkaline phosphatase, Runx2 and osteopontin increased. Those results suggested that Twist-1 inhibited BMP signaling by recruiting HDAC1 to Smad4. Furthermore, the inhibitory effects of Twist-1 on BMP signaling were overcome by Id1 through induction of Twist-1 degradation. These findings suggest that Twist-1 can act as an inhibitor of BMP signaling, and Id1 can regulate BMP signaling through a positive feedback loop repressing Twist-1 function. These two molecules may therefore regulate differentiation of mesenchymal cells into progeny such as osteoblasts by controlling BMP signaling.