Navigation Links
JCI online early table of contents: Nov. 14, 2011

EDITOR'S PICK: Glioblastoma multiforme in the Dock

Glioblastoma multiforme (GBM) is the most common malignant brain cancer in humans. Patients with GBM have a poor prognosis because it is a highly aggressive form of cancer that is commonly resistant to current therapies. A team of researchers led by Bo Hu and Shi-Yuan Cheng, at the University of Pittsburgh Cancer Institute, Pittsburgh has now identified a molecular pathway that drives the aggressive cancerous nature of a substantial proportion of glioblastomas; specifically, those that overexpress the protein PDGFR-alpha. This pathway could represent a new therapeutic target for treating individuals with glioblastomas that overexpress PDGFR-alpha.

PDGFR-alpha is overexpressed in a substantial proportion of GBMs, and overexpression of this protein is associated with a poor prognosis and shorter survival time. Hu, Cheng, and colleagues found that PDGFR-alpha signaling in human glioblastoma cells triggered a signaling cascade that involved phosphorylation of the protein Dock180 at tyrosine residue 1811 (Dock180Y1811) and downstream activation of the protein Rac1, which led to tumor cell growth and invasion. In human glioblastoma cells, if Dock180 was manipulated so that it could not be phosphorylated at tyrosine residue 1811 PDGFR-alpha failed to promote tumor growth, survival, and invasion. Thus, these data define a signaling pathway of importance in driving the aggressive cancerous nature of glioblastomas that overexpress PDGFR-alpha.

TITLE: Activation of Rac1 by Src-dependent phosphorylation of Dock180Y1811 mediates PDGFR-alphastimulated glioma tumorigenesis in mice and humans

Bo Hu
University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA.
Phone: 412-623-7791; Fax: 412-623-4840; E-mail:

Shi-Yuan Cheng
University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA.
Phone: 412-623-3261; Fax: 412-623-4840; E-mail:

View this article at:

CARDIOLOGY: Grown up function for the protein Tbx20

Mutations in the gene TBX20 are associated with both congenital heart disease and a heart disease in adults known as cardiomyopathy, which puts people at risk of an irregular heart beat and/or sudden death. Consistent with the association with congenital heart disease in humans, the protein Tbx20 has a role in heart development in mice. However, the role of Tbx20 in the adult mouse heart has not been determined so there are no clues as to whether the association of TBX20 mutations with cardiomyopathy in adult humans is a result of defects in TBX20 function during development or adulthood. A team of researchers led by Marcelo A. Nobrega, at the University of Chicago, Chicago; and Sylvia M. Evans, at the University of California San Diego, La Jolla has now investigated this issue and determined that Tbx20 functions in adult mouse heart muscle cells to control the expression of genes involved in controlling the beating of the heart. If TBX20 has a similar function in adult human heart muscle cells, these data suggest that defects in TBX20 function during adulthood underlie the association of TBX20 mutations with cardiomyopathy in adult humans.

TITLE: Tbx20 regulates a genetic program essential to adult mouse cardiomyocyte function

Marcelo A. Nobrega
University of Chicago, Chicago, Illinois, USA.
Phone: 773-834-7919; Fax: 773-83-.8470; E-mail:

Sylvia M. Evans
University of California San Diego, La Jolla, California, USA.
Phone: 858-822-2452; Fax: 858-822-3027; E-mail:

View this article at:

AUTOIMMUNITY: Linking genetic variants to autoimmune disease

Genetic studies have linked numerous genetic variations to susceptibility to developing an autoimmune disease. However, the functional consequences of most of these genetic variations remain unknown. Among the genes with variations linked to autoimmune diseases, including type 1 diabetes, rheumatoid arthritis, and Crohn's disease, is PTPN2, which templates a protein known as TCPTP. A team of researchers led by Tony Tiganis, at Monash University, Australia, has now identified a new immune function for TCPTP that might explain the link between PTPN2 genetic variations and autoimmune diseases.

In an accompanying commentary, Arthur Weiss and Julie Zikherman, at the University of California San Francisco, discuss how important it is to unravel the functional implications of genetic analyses so as to further understanding of the mechanisms underlying human autoimmune diseases.

TITLE: T cell protein tyrosine phosphatase attenuates T cell signaling to maintain tolerance in mice

Tony Tiganis
Monash University, Clayton, Victoria, Australia.
Phone: 61-3-9902-9332; Fax: 61-3-9902-9500; E-mail:

View this article at:


TITLE: Unraveling the functional implications of GWAS: how T cell protein tyrosine phosphatase drives autoimmune disease

Arthur Weiss
University of California San Francisco, San Francisco, California, USA.
Phone: 415-476-1291; Fax: 415-502-5081; E-mail address:

View this article at:

HEMATOLOGY: A stimulus package for cutaneous T cell lymphomas: mutations in the protein proIL-16

There are many types of non-Hodgkin lymphoma (NHL); together they account for approximately 4% of all cancer diagnoses. Cutaneous T cell lymphomas (CTCLs) are a diverse group of NHLs that affect the skin. The mechanisms underlying the development of these conditions are not well understood. A team of researchers led by William Cruikshank, at Boston University School of Medicine, Boston, has now shed some light on these mechanisms, generating data using cells from patients with CTCL that suggest that the growth of advanced CTCLs is facilitated, at least in part, by mutations in the protein proIL-16.

TITLE: Loss of nuclear proIL-16 facilitates cell cycle progression in human cutaneous T cell lymphoma

William W. Cruikshank
Boston University School of Medicine, Boston, Massachusetts, USA.
Phone: 617-638-5295; Fax: 617-638-5227; E-mail:

View this article at:

HEMATOLOGY: Role for the protein HVEM in red blood cell production

The production of red blood cells (a process known as erythropoiesis) is tightly controlled. This is to ensure that there are sufficient red blood cells to deliver adequate amounts of oxygen to the tissues but not too many such that unwanted blood clots form in the blood vessels, an event that can cause heart attack and stroke. Therapeutics that stimulate erythropoiesis (e.g., recombinant EPO) are used to treat some patients with anemia. However, these therapeutics, which are known as erythropoiesis-stimulating agents (ESAs), can have severe adverse side effects and there is a need for new and improved drugs. A team of researchers led by Koji Tamada, at the University of Maryland, Baltimore, has now identified a new signaling pathway that promotes erythropoiesis in mice. Stimulation of the protein HVEM initiates this pathway. Thus, Tamada and colleagues suggest that stimulation of HVEM signaling could provide a new therapeutic approach to treating individuals with conditions currently treated with ESAs such as recombinant EPO.

TITLE: Herpesvirus entry mediator regulates hypoxia-inducible factor𔂿a and erythropoiesis in mice

Koji Tamada
University of Maryland, Baltimore, Maryland, USA.
Phone: 410-328-5114; Fax: 410-328-6559; E-mail:

View this article at:

METABOLIC DISEASE: AMP(K)ed up protection from insulin resistance

The number of people who are obese is increasing dramatically. Being obese puts an individual at increased risk of developing type 2 diabetes and its associated adverse health conditions. This is in part because inflammatory cells known as macrophages accumulate in the fat tissue and produce inflammatory factors that contribute to the development of insulin resistance, a condition in which cells in the body fail to respond normally to the hormone insulin and that precedes diabetes. A team of researchers led by Gregory Steinberg, at McMaster University, Hamilton, has now determined that in mice, expression of the protein AMPK-beta-1 in bone marrowderived cells such as macrophages helps reduce fat tissue macrophage inflammation and liver insulin resistance. The team therefore suggests that activation of AMPK-beta-1 could provide a new therapeutic approach to treating insulin resistance.

TITLE: Hematopoietic AMPK-beta-1 reduces mouse adipose tissue macrophage inflammation and insulin resistance in obesity

Gregory R. Steinberg
McMaster University, Hamilton, Ontario, Canada.
Phone: 905-521-2100, ext. 21691; Fax: 905-777-7856; E-mail:

View this article at:

Contact: Karen Honey
Journal of Clinical Investigation

Related medicine news :

1. JCI online early table of contents: Nov. 7, 2011
2. Online Forums Can Help Women Cope With Pregnancy Loss
3. Parents who go online for pediatric health information are open to doctors website recommendations
4. Survey reveals reasons doctors avoid online error-reporting tools
5. Penn-developed online informed consent tool could boost number of patients in cancer clinical trials
6. New online learning module gives children of domestic violence a voice
7. JCI online early table of contents: September 26, 2011
8. JCI online early table of contents: Sept. 19, 2011
9. JCI online early table of contents: Sept. 12, 2011
10. 2011 European Muldisciplinary Cancer Congress abstracts online Sept. 12
11. JCI online early table of contents: Sept. 1, 2011
Post Your Comments:
(Date:10/13/2015)... Boulder, Colorado (PRWEB) , ... October 13, 2015 ... ... launched the first high-tech foam roller with 11 hours of vibrating power. Tested ... to reduce recovery time and increase athletic performance. , Mark's background in sporting ...
(Date:10/13/2015)... , ... October 13, 2015 , ... The American Institutes ... college campus health staff caring for students who have experienced sexual assault and other ... the White House during the Violence Against Women Act's 21st anniversary. ...
(Date:10/13/2015)... M.A. (PRWEB) , ... October 13, 2015 , ... Sir ... service to the local Boston chapter of Ronald McDonald House Charities® (RMHC®). This ... that has supported Sir Grout of Greater Boston since its inception. , “We believe ...
(Date:10/13/2015)... ... ... "My friend's son suffers from eczema, and he had a horrible habit ... Platteville, Colo. "I came up with this kit as a way to prevent children ... child from rubbing or scratching his or her face. This protects sensitive skin from ...
(Date:10/13/2015)... , ... October 13, 2015 , ... ... anesthesia and pain management services, today announced its partnership with WPC Healthcare ... data from disparate systems and organizes the data into an aggregated data repository ...
Breaking Medicine News(10 mins):
(Date:10/13/2015)... Oct. 13, 2015 Attracting mid- to large-sized medical ... to growing Baltimore into a major ... by the Maryland Technology Enterprise Institute (Mtech) . ... pieces in place to support innovation hubs and a thriving ... Mtech Baltimore. "This study is important because we believe ...
(Date:10/13/2015)... , Oct. 13, 2015  Graduate students ... care and medical research, will soon have the ... patient care – the drug discovery and development ... ) has collaborated with 10 leaders from academic ... "Making Medicines: The Process of Drug Development."  Lilly ...
(Date:10/13/2015)... SAN FRANCISCO , October 13, 2015 ... expected to reach USD 26.8 billion by 2022, according ... Anesthesia and respiratory devices, owing to their capability to ... expected to witness a substantial growth. --> ... reach USD 26.8 billion by 2022, according to a ...
Breaking Medicine Technology: