Journal Of Clinical Investigation Online Early Table Of Contents: Jan. 19, 2009

Main Category: Pregnancy / Obstetrics
Also Included In: Prostate / Prostate Cancer;  Breast Cancer;  Cardiovascular / Cardiology
Article Date: 20 Jan 2009 - 2:00 PDT

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Fetal heath affected by mother's diet

In the United States, there has been a recent dramatic rise in the number of children classified as obese and diagnosed with obesity-related diseases, such as type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). One factor thought to contribute to this rise is obesity of the mother during pregnancy. However, a team of researchers, at Oregon Health and Science University, Beaverton, and the University of Colorado School of Medicine, Aurora, have found the offspring of both lean and obese nonhuman primate mothers chronically consuming a high-fat diet exhibited an increased risk of developing NAFLD. Importantly, if mothers fed a high-fat diet were reverted to a low-fat diet during a subsequent pregnancy, this second offspring exhibited fewer signs of NAFLD. The team, led by Kevin Grove and Jacob Friedman, therefore suggests that a developing fetus is highly susceptible to maternal consumption of excess fat, whether or not the mother is obese, and that a healthy maternal diet is most important for the obesity-related health of a developing fetus.

TITLE: Maternal high-fat diet triggers lipotoxicity in the fetal livers of nonhuman primates

AUTHOR CONTACT:
Kevin L. Grove
Oregon Health and Science University, Beaverton, Oregon, USA.

Jacob E. Friedman,
University of Colorado School of Medicine, Aurora, Colorado, USA.

View the PDF of this article at: https://www.the-jci.org/article.php?id=32661

ONCOLOGY: Antibodies targeting the protein Pim-1 inhibit cancer cell growth

In a number of human cancers, including prostate cancer, the protein Pim-1 has been found to be expressed more highly than in the corresponding noncancerous tissue. Pei Xiang Xing and colleagues, at Burnet Institute Incorporating Austin Research Institute, Australia, have now taken therapeutic advantage of this by generating an antibody that binds to Pim-1 and using it to inhibit the growth of human and mouse prostate cancer cell lines in mouse models of prostate cancer. Further in vitro analysis revealed that the antibody worked by inducing cancer cells to die and that it synergistically enhanced the antitumor effects of two chemotherapeutic drugs. The researchers therefore suggest that using antibodies that target Pim-1 might of benefit to individuals with prostate cancer.

TITLE: Pim-1-specific mAb suppresses human and mouse tumor growth by decreasing PIM-1 levels, reducing Akt phosphorylation, and activating apoptosis

AUTHOR CONTACT:
Pei Xiang Xing
Burnet Institute Incorporating Austin Research Institute, Heidelberg, Victoria, Australia.

View the PDF of this article at: http://www.the-jci.org/article.php?id=33216

ONCOLOGY: Role for the protein FAK in breast cancer

A team of researchers, led by Filippo Giancotti and Yuliya Pylayeva, at Memorial Sloan-Kettering Cancer Center, New York, has provided new insight into the initiation, maintenance, and progression to metastasis of a specific subset of human and mouse breast cancers.

A marked proportion of breast cancers are associated with excessive activation of either Ras or PI3K signaling pathways, and many therapies aimed at disrupting these signaling pathways are under development. In this study, the FAK gene was found to be amplified in a substantial number of the human breast cancer samples analyzed. Consistent with this having a role in tumor development, mice lacking the Fak gene in breast tissue were protected in a model of breast cancer caused by excessive activation of Ras and PI3K. Further, silencing the FAK gene arrested the growth of human breast cancer cells with excessive activation of either Ras or PI3K signaling pathways. The authors therefore suggest that combined inhibition of FAK and either PI3K or Ras signaling may provide an effective approach for the treatment of breast cancer.

TITLE: Ras- and PI3K-dependent breast tumorigenesis in mice and humans requires focal adhesion kinase signaling

AUTHOR CONTACT:
Filippo G. Giancotti
Memorial Sloan-Kettering Cancer Center, New York, New York, USA.

Yuliya Pylayeva
NYU School of Medicine, New York, New York, USA.

View the PDF of this article at: http://www.the-jci.org/article.php?id=37160

HEMATOLOGY: No PKC-alpha protein, no inappropriate blood clot formation

The predominant cause of a heart attack is atherothrombosis, where a blood clot (otherwise known as a thrombus) forms in a blood vessel supplying the heart at the site of a ruptured or eroded atherosclerotic plaque (the entity that causes hardening or furring of the arteries). Platelets have a key role in the development of these blood clots, and the development of antithrombotic drugs that do not impair other functions of platelets, in particular their role in stopping bleeding, is therefore of immense interest. As Alastair Poole and colleagues, at the University of Bristol, United Kingdom, have found that mice lacking the protein PKC-alpha exhibited diminished thrombus formation in vivo but showed no evidence of overt bleeding, they suggest that PKC-alpha is a potential target for antithrombotic therapy. In particular, they propose that future studies should determine whether current drugs targeting PKC-alpha (e.g., aprinocarsen) are of benefit in the setting of atherothrombosis.

TITLE: PKC-alpha regulates platelet granule secretion and thrombus formation in mice

AUTHOR CONTACT:
Alastair W. Poole
University of Bristol, Bristol, United Kingdom.

View the PDF of this article at: http://www.the-jci.org/article.php?id=34665

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Article adapted by Medical News Today from original press release.
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Source: Karen Honey
Journal of Clinical Investigation