Rooting out recurrent breast cancer
Due to chemotherapy resistance and a high rate of relapse, triple negative cancers are among the most difficult breast cancers to treat. In this issue of the Journal of Clinical Investigation, researchers led by Carlos Arteaga at Vanderbilt University identified a protein, TGF-β, that is highly expressed in triple negative breast cancer cells after chemotherapy. In a mouse model of breast cancer, TGF-β both diverted cells down a path to becoming cancerous and allowed for cancer to come back after treatment. Importantly, loss of TGF-β prevented tumor recurrence in mice. These studies identify a mechanism by which cancer cells elude standard chemotherapy and provide a rationale for testing the therapeutic potential of agents that block TGF-β.
TITLE:
TGFβ inhibition enhances chemotherapy action against triple negative breast cancer
AUTHOR CONTACT:
Carlos Arteaga
Vanderbilt University, Nashville, TN, USA
Phone: 615-936-3524; Fax: 615-936-1790; E-mail: carlos.arteaga@vanderbilt.edu
View this article at: http://www.jci.org/articles/view/65416?key=201b874c7a54cc627c43
Targeting T cells in rheumatoid arthritis
Rheumatoid arthritis (RA) is an autoimmune disorder in which immune cells attack the joints, causing inflammation, swelling, and erosion. Specific sets of immune cells, known as T cells, are responsible for inducing disease. In this issue of the Journal of Clinical Investigation, researchers led by Harvey Cantor at Harvard University analyzed the contributions of different subsets of T cells to an RA-like condition in mice. Cantor and colleagues identified a subset of regulatory T cells (CD8+ Tregs) that can remove pathogenic T cell subsets and inhibit disease progression. Additionally, they identified small proteins that induced more CD8+ Tregs. These findings suggest that enhancing specific T cell subsets may be useful in combating RA and other autoimmune diseases.
TITLE:
Amelioration of arthritis through mobilization of peptide-specific CD8+ regulatory T-cells
AUTHOR CONTACT:
Harvey Cantor
Dana Farber Cancer Institute, Boston, MA, USA
Phone: 617-632-3348; Fax: 617-632-4630; E-mail: harvey_cantor@dfci.harvard.edu
View this article at: http://www.jci.org/articles/view/66938?key=921590f51ca9f29cbc53
New insight into RASopathy-associated lymphatic defects
The RAS pathway is a cellular signaling pathway that regulates growth and development in humans. RASopathies are a group of diseases characterized by defects in RAS signaling. Many patients with RASopathies present with defects in the lymphatic system, which removes excess fluid from tissues, absorbs fats from the digestive system, and transports immune cells. To determine how alterations in the RAS pathway affect development of the lymphatic system, researchers at Yale University generated transgenic mice that expressed mutations associated with a RASopathy known as Noonan syndrome. In this issue of the Journal of Clinical Investigation, Michael Simon and colleagues report that excess RAS pathway activation triggers increased activity of a protein known as ERK. Mice with RASopathy-associated mutations exhibited lymphatic defects similar to those seen in humans, but the defects could be reversed by treatment with an ERK inhibitor. These findings demonstrate that excessive ERK activation underlies lymphatic defects in RASopathies and suggest that ERK inhibition could be a useful therapeutic strategy.
TITLE:
Endothelial ERK signaling controls lymphatic fate specification
AUTHOR CONTACT:
Michael Simons
Yale University School of Medicine, New Haven, CT, USA
Phone: 203-785-7000; Fax: 203-785-7144; E-mail: michael.simons@yale.edu
View this article at: http://www.jci.org/articles/view/63034?key=d664ce492ed2f61c7592
ALSO IN THIS ISSUE
TITLE:
Modified Foxp3 mRNA protects against asthma through an IL-10-dependent mechanism
AUTHOR CONTACT:
Michael Kormann
University of Tübingen, Tübingen, DEU
Phone: 49-707-129-84305; Fax: 49-70-712-94717; E-mail: kormann.michael@gmail.com
View this article at: http://www.jci.org/articles/view/65351?key=1acddb3759378c79fb19
TITLE:
CXCL5 limits macrophage foam cell formation in atherosclerosis
AUTHOR CONTACT:
Johan Duchene
Max Delbrück Center for Molecular Medicine, Berlin, DEU
Phone: +49 (0)30 9406-3592; E-mail: johan.duchene@mdc-berlin.de
View this article at: http://www.jci.org/articles/view/66580?key=23f5fa3db75c3616de65
TITLE:
SHP-1 phosphatase activity counteracts increased T cell receptor affinity
AUTHOR CONTACT:
Nathalie Rufer
University of Lausanne, Lausanne, UNK, CHE
Phone: +41 21 314 01 99; Fax: +41 21 314 74 77; E-mail: nathalie.rufer@unil.ch
View this article at: http://www.jci.org/articles/view/65325?key=462a82b5364e445f6d07
TITLE:
PAR-1 contributes to the innate immune response during viral infection
AUTHOR CONTACT:
Nigel Mackman
University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Phone: 919 843 3961; Fax: 919 843 4896; E-mail: nmackman@med.unc.edu
View this article at: http://www.jci.org/articles/view/66125?key=6861131db424291005b5
TITLE:
Muscle lipogenesis balances insulin sensitivity and strength through calcium signaling
AUTHOR CONTACT:
Clay F. Semenkovich
Washington University, St. Louis, MO, USA
Phone: 314-362-4454; E-mail: csemenko@dom.wustl.edu
View this article at: http://www.jci.org/articles/view/65726?key=115fd524a9c30f654cbe
Journal
Journal of Clinical Investigation