JCI online early table of contents: Dec. 19, 2011

December 19, 2011

EDITOR'S PICK: Potential concern about drugs in clinical trial

Drugs that enhance levels of small molecules derived naturally in the body from a major component of animal fats (small molecules known as epoxyeicosatrienoic acids [EETs]) are currently in clinical trials for the treatment of high blood pressure and diabetes. A team of researchers -- led by Dipak Panigrahy and Mark Kieran, at the Dana-Farber Cancer Institute, Boston; Sui Huang, at the Institute for Systems Biology, Seattle; and Darryl Zeldin, at the National Institute of Environmental Health Science, Research Triangle Park -- has now generated data in mice that raise concern about the use of these drugs in humans.

The key observation of the team was that EETs promote primary tumor growth and spread to distant sites (metastasis) in a variety of mouse models of cancer. As noted by the authors and, in an accompanying commentary, Raymond DuBois and Dingzhi Wang, at The University of Texas MD Anderson Cancer Center, Houston, the data generated suggest not only that raising levels of EETs in humans could have severe adverse effects but also that EET antagonists could provide a new approach to preventing and treating metastasis.

TITLE: Epoxyeicosanoids stimulate multiorgan metastasis and tumor dormancy escape in mice

Dipak Panigrahy
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
Phone: 617-919-2198; Fax: 617-730-0231; E-mail: dipak.panigrahy@childrens.harvard.edu.

Sui Huang
Institute for Systems Biology, Seattle, Washington, USA.
Phone: 206-354-3569; Fax: 206-732-1299; E-mail: sui.huang@systemsbiology.org.

Mark W. Kieran
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
Phone: 617-632-4907; Fax: 617-632-4897; E-mail: mark_kieran@dfci.harvard.edu.

Darryl C. Zeldin
National Institute of Environmental Health Science, NIH, Research Triangle Park, North Carolina, USA.
Phone: 919-541-1169; Fax: 919-541-4214; E-mail: zeldin@niehs.nih.gov.

View this article at: http://www.jci.org/articles/view/58128?key=0c8bd9a605072d7d0278

TITLE: Epoxyeicosatrienoic acids: a double-edged sword in cardiovascular diseases and cancer

Raymond N. DuBois
The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Phone: 713-745-4495; Fax: 713-792-6375; E-mail:

View this article at: http://www.jci.org/articles/view/61453?key=e8ce6b5c07973027cbe1

EDITOR'S PICK: Blood pressure drug limits cigarette smoke-induced lung injury in mice

Chronic obstructive pulmonary disease (COPD) is among the most common causes of death in the US. It is a smoking-related disease for which there are currently no disease-altering therapies. However, hope that one could be developed is now provided by the work of Enid Neptune and colleagues, at Johns Hopkins University, Baltimore, in a mouse model of lung disease caused by exposure to cigarette smoke.

Neptune and colleagues found that lostartan, a drug used widely in the clinic (e.g., to treat high blood pressure), reduced lung disease in mice caused by exposure to cigarette smoke. Losartan blocks the protein angiotensin receptor type 1, and its effects on cigarette smoke-induced lung injury were a result of the fact that blocking angiotensin receptor type 1 leads to a decrease in levels of the soluble molecule TGF-beta. The authors therefore suggest that other TGF-beta-targeted therapeutics might also be viable candidates for the treatment of COPD.

TITLE: Angiotensin receptor blockade attenuates cigarette smoke-induced lung injury and rescues lung architecture in mice

Enid Neptune
Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Phone: 410-955-4176; Fax: 410-955-0036; E-mail: eneptune@jhmi.edu.

View this article at: http://www.jci.org/articles/view/46215?key=1757af37800194593ae0

ONCOLOGY: A full TANC(1) needed to drive rhabdomyosarcoma

Rhabdomyosarcoma (RMS) accounts for 5% of all new pediatric cancers. In some patients, RMS is caused by a genetic event that gives rise to a fusion protein (PAX-FOXO1) that drives the development of the cancer. Rene Galindo and colleagues, at the University of Texas Southwestern Medical Center, Dallas, have now generated data in Drosophila and mammalian models that provide new insight into the molecular mechanisms by which PAX-FOXO1 drives the development of cancer. These data, which indicate a key role for the protein TANC1 in RMS driven by PAX-FOXO1, have identified new avenues of research for those seeking to develop candidates for targeted RMS therapy.

TITLE: Drosophila and mammalian models uncover a role for the myoblast fusion gene TANC1 in rhabdomyosarcoma

Rene L. Galindo
University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA.
Phone: 214-648-4116; Fax: 214-648-4070; E-mail: rene.galindo@utsouthwestern.edu.

View this article at: http://www.jci.org/articles/view/59877?key=d24a5f9b7050c9b5a16b

ONCOLOGY: Growth factor link to breast cancer

The growth factor IGF-1 has been implicated in the development of breast cancer. A team of researchers led by Robin Fuchs-Young, at The University of Texas M.D. Anderson Cancer Center, Smithville, has now demonstrated in mice that the level of expression of the protein estrogen receptor alpha (ER-alpha) on mammary gland cells influences whether IGF-1 can promote breast cancer. Fuchs-Young and colleagues therefore suggest that prepubertal and postmenopausal women are likely to be most susceptible to the potential breast cancer-promoting effects of increased levels of IGF-1, since these are the times in a woman's life when ER-alpha levels are highest.

TITLE: Developmental stage determines estrogen receptor alpha expression and nongenomic mechanisms that control IGF-1 signaling and mammary proliferation

Robin Fuchs-Young
The University of Texas M.D. Anderson Cancer Center, Smithville, Texas, USA.
Phone: 512-237-9547; Fax: 512-237-6440; E-mail: rfyoung@mdanderson.org.

View this article at: http://www.jci.org/articles/view/42204?key=7e26e09e330e04540afb

METABOLIC DISEASE: Heparan sulfate: protecting the cells destroyed in type 1 diabetes

Type 1 diabetes is a lifelong disease characterized by high levels of sugar (glucose) in the blood. It is caused by the patient's immune system attacking and destroying the cells in their pancreas that produce the hormone insulin, which regulates blood glucose levels. Surprisingly, little is known about the mechanisms regulating the sensitivity and resistance of these cells, which are known as beta-cells, to immune system attack. Now, Charmaine Simeonovic and colleagues, at The Australian National University, Australia, have determined that the molecule heparan sulfate is essential for mouse beta-cell survival. Importantly, in a mouse model of type 1 diabetes, production of an active heparan sulfate-degrading protein (heparanase) was associated with beta-cell destruction, while treatment with an inhibitor of heparanase protected the mice from disease. Simeonovic and colleagues therefore suggest that maintaining expression of heparan sulfate on beta-cells could provide a new approach to preventing the development of type 1 diabetes.

TITLE: Heparan sulfate and heparanase play key roles in mouse beta-cell survival and autoimmune diabetes

Charmaine J. Simeonovic
The John Curtin School of Medical Research, The Australian National University, Canberra, Australia.
Phone: 61-2-6125-4709; Fax: 61-2-6125-2595; E-mail: Charmaine.Simeonovic@anu.edu.au.

View this article at: http://www.jci.org/articles/view/46177?key=f37890b794c1c03854d8

GENETICS: Linking genetic variation to changes in protein function

Many common human diseases, including type 2 diabetes, are thought to arise as a result of both genetic and environmental factors. It is hoped that defining the genetic component of such diseases could provide not only insight into cause but also candidate therapeutic approaches. In this context, variants of the GCKR gene have been suggested to be clinically important, with some linked to type 2 diabetes. However, how these variants affect protein function and influence disease has not been determined. Now, a team of researchers led by Francis Collins, at the National Human Genome Research Institute, Bethesda, has characterized the function of a large number of variants of the GCKR gene. The data generated indicate that the majority of the GCKR variants tested do affect protein function and are likely to provide an important genetic component of several clinical conditions.

TITLE: Correlation of rare coding variants in the gene encoding human glucokinase regulatory protein with phenotypic, cellular, and kinetic outcomes

Francis S. Collins
National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
Phone: 301-496-2433; Fax: 301-402-2700; E-mail: collinsf@mail.nih.gov.

View this article at: http://www.jci.org/articles/view/46425?key=6490486025063609e222

ENDOCRINOLOGY: Sugar overload: refining the role of the hormone GLP-1

How does the body deal with the sudden influx of sugar that it receives after we have eaten a meal? The answers to this question not only provide insight into how the body works but can yield information that could be useful in the development of new therapeutic approaches to treating type 2 diabetes, a chronic disease characterized by high levels of sugar (glucose) in the blood. In relation to this question, Daniel Drucker and colleagues, at the University of Toronto, Toronto, have investigated in detail the function of the hormone GLP-1, which is produced by cells in the gut after food ingestion. They find that GLP-1 acts directly on cells in the pancreas to control the production of insulin, the hormone that controls blood glucose levels. These data refine our understanding of the complexity of the response to sudden sugar influx.

TITLE: Pancreatic GLP-1 receptor activation is critical for incretin control of glucose metabolism in mice

Daniel J. Drucker
Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
Phone: 416-361-2661; Fax: 416-361-2669; E-mail: d.drucker@utoronto.ca.

View this article at: http://www.jci.org/articles/view/42497?key=3ec16515fd8d7e92fe24

JCI Journals

Related Breast Cancer Articles from Brightsurf:

Oncotarget: IGF2 expression in breast cancer tumors and in breast cancer cells
The Oncotarget authors propose that methylation of DVDMR represents a novel epigenetic biomarker that determines the levels of IGF2 protein expression in breast cancer.

Breast cancer: AI predicts which pre-malignant breast lesions will progress to advanced cancer
New research at Case Western Reserve University in Cleveland, Ohio, could help better determine which patients diagnosed with the pre-malignant breast cancer commonly as stage 0 are likely to progress to invasive breast cancer and therefore might benefit from additional therapy over and above surgery alone.

Partial breast irradiation effective treatment option for low-risk breast cancer
Partial breast irradiation produces similar long-term survival rates and risk for recurrence compared with whole breast irradiation for many women with low-risk, early stage breast cancer, according to new clinical data from a national clinical trial involving researchers from The Ohio State University Comprehensive Cancer Center - Arthur G.

Breast screening linked to 60 per cent lower risk of breast cancer death in first 10 years
Women who take part in breast screening have a significantly greater benefit from treatments than those who are not screened, according to a study of more than 50,000 women.

More clues revealed in link between normal breast changes and invasive breast cancer
A research team, led by investigators from Georgetown Lombardi Comprehensive Cancer Center, details how a natural and dramatic process -- changes in mammary glands to accommodate breastfeeding -- uses a molecular process believed to contribute to survival of pre-malignant breast cells.

Breast tissue tumor suppressor PTEN: A potential Achilles heel for breast cancer cells
A highly collaborative team of researchers at the Medical University of South Carolina and Ohio State University report in Nature Communications that they have identified a novel pathway for connective tissue PTEN in breast cancer cell response to radiotherapy.

Computers equal radiologists in assessing breast density and associated breast cancer risk
Automated breast-density evaluation was just as accurate in predicting women's risk of breast cancer, found and not found by mammography, as subjective evaluation done by radiologists, in a study led by researchers at UC San Francisco and Mayo Clinic.

Blood test can effectively rule out breast cancer, regardless of breast density
A new study published in PLOS ONE demonstrates that Videssa® Breast, a multi-protein biomarker blood test for breast cancer, is unaffected by breast density and can reliably rule out breast cancer in women with both dense and non-dense breast tissue.

Study shows influence of surgeons on likelihood of removal of healthy breast after breast cancer dia
Attending surgeons can have a strong influence on whether a patient undergoes contralateral prophylactic mastectomy after a diagnosis of breast cancer, according to a study published by JAMA Surgery.

Young breast cancer patients undergoing breast conserving surgery see improved prognosis
A new analysis indicates that breast cancer prognoses have improved over time in young women treated with breast conserving surgery.

Read More: Breast Cancer News and Breast Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.