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Chapuis, Aude G.,Lee, Sylvia M.,Thompson, John A.,Roberts, Ilana M.,Margolin, Kim A.,Bhatia, Shailender,Sloan, Heather L.,Lai, Ivy,Wagener, Felecia,Shibuya, Kendall,Cao, Jianhong,Wolchok, Jedd D.,Gree The Rockefeller University Press 2016 The Journal of experimental medicine Vol.213 No.7
<P>Adoptive transfer of peripheral blood–derived, melanoma-reactive CD8<SUP>+</SUP> cytotoxic T lymphocytes (CTLs) alone is generally insufficient to eliminate bulky tumors. Similarly, monotherapy with anti-CTLA4 infrequently yields sustained remissions in patients with metastatic melanoma. We postulated that a bolus of enhanced IL-21–primed polyclonal antigen-specific CTL combined with CTLA4 blockade might boost antitumor efficacy. In this first-in-human case study, the combination successfully led to a durable complete remission (CR) in a patient whose disease was refractory to both monoclonal CTL and anti-CTLA4. Long-term persistence and sustained anti-tumor activity of transferred CTL, as well as responses to nontargeted antigens, confirmed mutually beneficial effects of the combined treatment. In this first-in-human study, Chapuis et al. demonstrate that the combination of adoptive cellular therapy with CTLA4 blockade induces long-term remission in a melanoma patient resistant to both modalities administered serially and individually.</P>
The spatiotemporal development of adipose tissue
Han, J.,Lee, J.-E.,Jin, J.,Lim, J. S.,Oh, N.,Kim, K.,Chang, S.-I.,Shibuya, M.,Kim, H.,Koh, G. Y. The Company of Biologists 2011 Development Vol.138 No.22
<P>Adipose tissue is a structure highly specialized in energy storage. The adipocyte is the parenchymal component of adipose tissue and is known to be mesoderm or neuroectoderm in origin; however, adipocyte development remains poorly understood. Here, we investigated the development of adipose tissue by analyzing postnatal epididymal adipose tissue (EAT) in mouse. EAT was found to be generated from non-adipose structure during the first 14 postnatal days. From postnatal day 1 (P1) to P4, EAT is composed of multipotent progenitor cells that lack adipogenic differentiation capacity in vitro, and can be regarded as being in the 'undetermined' state. However, the progenitor cells isolated from P4 EAT obtain their adipogenic differentiation capacity by physical interaction generated by cell-to-matrix and cell-to-cell contact both in vitro and in vivo. In addition, we show that impaired angiogenesis caused by either VEGFA blockade or macrophage depletion in postnatal mice interferes with adipose tissue development. We conclude that appropriate interaction between the cellular and matrix components along with proper angiogenesis are mandatory for the development of adipose tissue.</P>