RNA binding protein influences chemotherapy resistance

Genes and their level of expression is important in cells. It is what gives a particular cell its unique qualities. Different levels of different genes are expressed in cells in the liver compared with those in the lung, for example. In cancer, the amount of gene expression is frequently altered, resulting in either increased concentrations (overexpression) or not quite enough (underexpression). Such alterations could lead to aberrant growth or even to resistance to current cancer chemotherapy.

Increasing evidence has been accumulating that implicate an RNA binding protein, called HuR, in the development of chemotherapeutic resistance. Several papers in the past few years have shown that increased amounts of HuR, along with where the protein in located in the cell, can dramatically alter how a cancer cell responds to therapy. In pancreatic cancer cells, increased HuR levels in the cytoplasm of the cell significantly aids in the response to gemcitabine, the current chemotherapy for pancreatic cancer. In breast cancer, and now in glioma cells, increased HuR levels increases the resistance to currently used chemotherapy including tamoxifen, etoposide, cisplatin and topotecan.

While this data is still in the preclinical stages, and much more needs to be done before it can be used in the clinic, it still offers new insights into how resistance develops in cancer. RNA binding proteins are not particularly well studied compared with other proteins and microRNAs. It is exciting to see a slow and steady progression in this field.

Natalia Filippova et. al.
Molecular Cancer Research 9:648-659

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A significant percentage of internet addicts suffer from depression

Internet addiction is a problem for 4% of US college students, according to a recent paper by Christakis et. al., published in the BMC Medicine, June 22, 2011. Unlike previous studies that had problematic participant selection biases that inflated the percentage of those addicted to the internet, this study selected 18 - 20 year old undergraduate students from a broader audience at large public US universities.

Using facebook to select and survey these students, Christakis et. al. demonstrate that 4% of students had internet addiction and a significant proportion admitted to longer daily use of the internet than they had intended. This percentage was lower than previous reports, however it is possibly a better representation of the general population. Interestingly, they also found that 12% of participants also suffered moderate to severe depression, suggesting an overlap in these ailments. Statistical analysis of their data revealed that depressed people are 24% more likely to also have internet addiction. As internet usage continues to increase, it will be critically important to address issues of depression and loss of physical connectivity with other people.

Dimitri Christakis et. al.
BMC Medicine 2011, 9:77

http://www.biomedcentral.com/1741-7015/9/77

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deFEATing cancer

In the quest to understand how cancer develops and is spread, scientists have been searching for the gene, genes, or signaling pathways whose inappropriate expression or mutation results in disease. In a paper published in the new open access journal from Nature, Scientific Reports, Takahashi et. al. have identified a potential initiator of cancer.

They found that a protein called CGI-01 was overexpressed in many cancerous tissues, but faintly expressed, if at all, in normal tissues. This protein, which they renamed FEAT for Faintly Expressed in normal tissues, Aberrant overexpression in Tumors, appears to be turned on in early stages of pre-cancerous lesions or cancer itself. When expressed, FEAT protein inhibits cell death mechanisms, or apoptosis, leading to increased and uncontrolled cell growth. Mice expressing heaps of FEAT protein spontaneously develop either hepatocellular carcinoma (HCC), a form of liver cancer, or lymphoma, a blood cancer. More in depth analysis investigating how FEAT actually promotes cancer revealed that FEAT overexpression results in activation of cell signaling cascades, both tyrosine kinase and hedgehog signaling pathways, that have previously been implicated in cancer promotion. May this be a way to detect early stages of cancer development? If this data holds true, it could be a promising detection tool.

Atsushi Takahashi et al, Scientific Reports 1: 15.
http://www.nature.com/srep/index.html

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Gossip, Gossip, Gossip - how negative gossip influences us

Let's face it -- we gossip. Positive, neutral or negative gossip about people is spread. More often by some people than by others, but nonetheless, it exists. We even gossip about people we don't know. It turns out that our brains more readily remember unfamiliar faces when they are associated with negative gossip when compared with neutral or positive gossip. In this recent study in Science Magazine (Science 332: 1446-1448 June 17, 2011), authors, Anderson et. al., show that negative gossip actually results in longer visual focus on that face. This increases our ability to recall and remember that face.

Normally, when an emotionless and unfamiliar face is shown to us, the focus of our eyes switches back and forth between each eye. We don't perceive this switching because approximately equal amounts of time are divided between each eye and we are looking at one image. Scientists tested if this eye dominance was altered at all if the faces shown were associated with different forms of gossip. They hypothesized that gossip may increase the amount of time focused on a particular image, leading to increased memory and recall.

By showing an facial image to one eye and a separate (non-facial) to the other eye -- they used a house image -- scientists found that the dominance of the images that is seen switches back and forth between the eyes. However, when a face is associated with negative information, or gossip, more time is spent looking at that image than the non-facial image. This is not true for positive or neutral-associated faces. Does this mean that we learn better from negative information? Perhaps. But, what it does indicate is that our brains do not retain or focus on faces that associate with neutral, or non, information as readily as those that are associated with negative gossip.

Our immune systems can detect if bacteria is viable or not

Immune cells are able to recognize whether a bacteria is viable or not. This new evidence is remarkable, but why does this matter? Vaccines used to ward off disease come in two main varieties, live-attenuated (viable) or killed (dead) forms. Use of viable vaccines produces a more robust immune response. Until now, the underlying reason why has remained unknown. Sander et. al. (Nature 474: 385-389, June 10, 2011) demonstrate that an underlying reason for this is that the immune system can differentiate between viable and non-viable agents.

The presence (and detection) of prokaryotic mRNA signals to the immune system that the invading bacteria is viable and, therefore, potentially infectious. As a result, a strong immune response is initiated. It is not just presence of prokaryotic mRNA, however, but specifically, the immune cells recognize a lack of the 3’ -polyA tail on this mRNA. This means that killed virus that can retain the prokaryotic mRNA (i.e. killing with paraformaldehyde retains the mRNA) or is vaccines that are augmented with prokaryotic mRNA can produce an enhanced immune response. This could have a significant impact on vaccine design and development.

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Nicotine suppresses appetite by activation of specific neurons

Many people use smoking as a mechanism to suppresses appetite and control their body weight. Nicotine in cigarettes is the culprit, affecting peripheral energy expenditures, but also affecting the central nervous system to regulate feeding. Mineur et. al. (Science 332: 1330-1332, June 10, 2011) have now uncovered some the of the molecular steps involved in nicotine-suppressed appetite control. In mouse models, nicotine binds to its receptor (the nicotinic acetylcholine receptor or nAChR) in a specific region of the brain called the arcuate nucleus (ARC). Here nicotine activates the pro-opiomelanocortin (POMC) neurons that begin to fire more frequently. This increased neuron stimulation produces more melanocortin that is known to decrease the urge to eat. The hope is that this work can lead to the development of new therapy to treat obesity and other metabolic syndromes.

miRNAs strike again!

The ever-increasing number of articles documenting how miRNAs are key players in gene regulation, where overexpression or underexpression of a myriad of miRNAs results in disease states, continues to rise. Clearly, gene regulation is complex and control of transcription or translation is a key determinate in the development of disease. MicroRNAs are proving to be critical mediators of disease states and could potentially be therapeutic targets. Combined with other forms of regulation (epigenetic, transcriptional regulation, post-transcriptional modifications, and so on...) it will be possible to understand how cells specially fine-tune gene expression to maximize performance and prevent disease. Once a complete picture -- involving miRNAs, proteins, RNA, DNA, epigenetic mediators -- is fully realized, then real targeted therapy can be designed. But first, we must understand how each component works. Every new paper documenting how miRNAs control genes and disease is another step to understanding how to successfully target diseases with pharmacologic agents.