Dispatch From The Logbook Of Clinical Investigation, May 1, 2009
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ONCOLOGY: How some immune cells doctor up cancer outcome
For a number of cancers, including neuroblastoma (the moment most universal tumour in children), tumor infiltration by a subset of unaffected cells avowed as V-alpha-24-invariant NKT cells is associated with a favourable outcome. Nevertheless how these cells have an anticancer effect is unclear, as several tumors achieve not explicit the protein that V-alpha-24-invariant NKT cells target. However, Leonid Metelitsa and colleagues, at the University of Southern California Keck School of Medicine, and The Saban Test School of Childrens Infirmary Los Angeles, Los Angeles, enjoy away shown, in vitro and in mice, that human V-alpha-24-invariant NKT cells indirectly affect neuroblastoma buildup by killing tumor-associated cells that promote the growth of neuroblastoma cells.
In the study, human tumor-associated cells known as monocytes/macrophages were initiate to produce the soluble belongings IL-6, which too analysis revealed stimulates the advance of neuroblastoma cells in vitro and after they have been transplanted into mice. As expected, human V-alpha-24-invariant NKT cells did not kill neuroblastoma cells in vitro, on the other hand they did crucify monocytes pulsed with tumor antigens. Consistent with this, the life of neuroblastoma cells was substantially impaired in mice infused with monocytes and V-alpha-24-invariant NKT cells, when compared to mice one shot receiving monocytes. These data therefore favor aha into a mechanism by which V-alpha-24-invariant NKT cells can bump cancer outcome.
TITLE: V-alpha-24-invariant NKT cells mediate antitumor motion via killing of tumor-associated macrophages in mice and people
Leonid S. Metelitsa
Baylor College of Medicine, Houston, Texas, USA.
View the PDF of this article at: https://www.the-jci.org/article.php?id=37869
METABOLISM: The nectareous aroma of success: new understanding of the pathway affected in Maple Syrup Urine Disease
Yibin Wang and colleagues, at UCLA David Geffen School of Medicine, Los Angeles, have identified, in cultured cells and mice, a protein contracted for regulating the protein complex that breaks down branched-chain amino acids (three protein building blocks that cannot be made by community on the contrary gain to be obtained from the food we eat). Mice missing this protein (PP2Cm) exhibited coinciding symptoms to some forms of human Maple Sirup Urine Disease (MSUD), an inherited disorder characterized by sweet-smelling urine that leads to severe brain damage and ending provided untreated. The authors therefore propose that defects in PP2Cm may be culpable for some cases of MSUD.
TITLE: Protein phosphatase 2Cm is a critical regulator of branched chain-amino acid catabolism in mice and cultured cells
David Geffen College of Medicine, University of California, at Los Angeles, Los Angeles, California, USA.
Panorama the PDF of this article at: https://www.the-jci.org/article.php?id=38151
CARDIOLOGY: The fog lifts on the role for the protein Fog2 in the adult heart
The protein Fog2, which is a regulator of gene expression, is crucial for embryonic course of both the heart and the blood vessels that supply the passion (coronary blood vessels), however its role in the mortal heart has not been determined. However, William Pu and colleagues, at Children's Infirmary Boston, admit pdq intent that Fog2 regulates adult mouse heart utility and the growth of fresh coronary vessels.
The authors generated mice lacking Fog2 in heart muscle cells either early or overdue in embryonic feelings development. As has been observed for mice lacking Fog2 in all cells from the site of conception, mice in which Fog2 was deleted early in heart adulthood died before birth, with the equivalent love and coronary vessel defects. By contrast, mice in which Fog2 was deleted following in heart adding to survived until 8ó weeks after birth. However, these mice had decreased affection function and insufficient coronary vessels, which led to a lack of oxygen passing to the heart muscle cells and thereby death of the cells and scarring of the emotions muscle. These news present that Fog2 is required for maintaining heart and coronary vessel function in the adult mouse heart.
TITLE: Fog2 is critical for cardiac advantage and maintenance of coronary vasculature in the man mouse heart
William T. Pu
Children's Hospital Boston, Boston, Massachusetts, USA.
Judgment the PDF of this article at: https://www.the-jci.org/article.php?id=38723
AUTOIMMUNITY: Two contradictory roles for the protein Bim: determination of T cell activation and death
The protein Bim has previously been shown to have a role in the cellular process that kills developing T cells (a subset of proof cells) that are 'born' with the ability to attack the body's own tissues and cause autoimmune diseases. Surprisingly, Youhai Chen and colleagues, at University of Pennsylvania School of Medicine, Philadelphia, have now create that Bim also has a role in controlling the activation of mouse T cells.
In the study, in mouse models of two autoimmune diseases, multiple sclerosis and type 1 diabetes, mice with T cells that lacked Bim were observed to be protected from disease. In vitro conversation indicated that adjacent stimulation, T cells lacking Bim were impaired in their knack to produce soluble factors down pat as cytokines (molecules that execute T cell effects). At the molecular level, Bim was shown to control T cell activation via an IP3R/calcium/NFAT pathway. As the authors location out, this study reveals that Bim joins a growing document of proteins with dual roles in T cell activation and death.
TITLE: Critical roles of Bim in T cell activation and T cell-mediated autoimmune inflammation in mice
Youhai H. Chen
University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Glimpse the PDF of this article at: https://www.the-jci.org/article.php?id=37619
Gazette of Clinical Investigation
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