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Montag, September 30th, 2013 | Author:

Since the publication in 2000 of a report titled “To Err is Human” by the Institute of Medicine which called for a reduction in preventable medical errors, there has been an increasing demand for making improvements in the quality and measurement of health care outcomes…

Montag, September 30th, 2013 | Author:

A new urine test for prostate cancer that measures minute fragments of RNA is now commercially available to men nationwide through the University of Michigan MLabs…

Montag, September 30th, 2013 | Author:

IntroductionThe Rho GTPase Cdc42 is overexpressed and hyperactivated in breast tumors compared to normal breast tissue. Cdc42 regulates key processes that are critical for mammary gland morphogenesis and become disrupted during the development, progression, and metastasis of breast cancer. However, the contribution of Cdc42 to normal and neoplastic mammary gland development in vivo remains poorly understood. We were therefore interested in investigating the effects of Cdc42 overexpression on mammary gland morphogenesis as a first step towards understanding how its overexpression may contribute to mammary tumorigenesis.
Methods:
We developed a tetracycline-regulatable Cdc42 overexpression mouse model in which Cdc42 can be inducibly overexpressed in the developing mammary gland. The effects of Cdc42 overexpression during postnatal mammary gland development were investigated using in vivo and in vitro approaches, including morphometric analysis of wholemounted mammary glands, quantification of histological markers, and primary mammary epithelial cell (MEC) functional and biochemical assays.
Results:
Analysis of Cdc42 overexpressing mammary glands revealed abnormal terminal end bud (TEB) morphologies, characterized by hyperbudding and trifurcation, and increased side branching within the ductal tree. Quantification of markers of proliferation and apoptosis suggested that these phenotypes were not due to increased cell proliferation or survival. Rather, Cdc42 overexpressing MECs were more migratory and contractile and formed dysmorphic, invasive acini in three-dimensional cultures. Cdc42 and RhoA activities, phosphorylated myosin light chain, and MAPK signaling, which contribute to migration and invasion, were markedly elevated in Cdc42 overexpressing MECs. Interestingly, Cdc42 overexpressing mammary glands displayed several features associated with altered epithelial-stromal interactions, which are known to regulate branching morphogenesis. These included increased stromal thickness and collagen deposition, and stromal cells isolated from Cdc42 overexpressing mammary glands exhibited elevated mRNA expression of extracellular matrix proteins and remodeling enzymes.
Conclusions:
These data suggest that Cdc42 overexpression disrupts mammary gland branching morphogenesis by altering Rho GTPase and MAPK signaling, leading to increased MEC contractility and migration in association with stromal alterations. Our studies provide insight into how aberrant Cdc42 expression may contribute to mammary tumorigenesis.

Montag, September 30th, 2013 | Author:
As much as seventy percent of the human race will become obsolete within just three generations. Why? Because robotics technology is advancing at such a rapid pace that highly-capable humanoid robots with advanced vision recognition and motor coordination systems are…
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Montag, September 30th, 2013 | Author:
A Colombian man recently experienced the ultimate strike to his manhood following an overdose with the popular erectile dysfunction drug Viagra (sildenafil citrate). According to Colombia’s La Nacion newspaper, 66-year-old Gentil Ramirez Polania had to have his entire…
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Montag, September 30th, 2013 | Author:
The U.S. Department of Agriculture (USDA) is currently in the process of trying to ram through passage of a new “modernization” rule for conventional poultry production that would eliminate a large percentage of USDA inspectors and speed up the factory production process…
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Montag, September 30th, 2013 | Author:
Wading through all the information out there about vaccines and vaccine safety can be tiresome, as getting the honest truth from non-industry-backed sources is sometimes hard to come by and takes considerable and dedicated effort. But if you know where to look, the truth…
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Montag, September 30th, 2013 | Author:
Natural herbs are said to work well for the purpose of detoxification. This means that people can derive benefits from these herbs when it comes to detoxifying their body and restoring the good health and condition of their liver. Natural herbs are also preferred by…
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Montag, September 30th, 2013 | Author:
A devious breed of wealthy parents have been taking their families to Disney World and deliberately cutting in lines reserved for the disabled, exploiting handicapped children in the process. Disney World goes out of its way to help disabled children enjoy attractions…
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Montag, September 30th, 2013 | Author:
Cancer is one of the deadliest and most feared diseases of people all over the world these days. Twelve million individuals living in America alone were diagnosed with this disease in 2008. Five years later, more than 1.6 million new cases were diagnosed. A few of the…
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