Tuesday, November 19, 2013

Bigger Picture! IMPORTANT TO READ!

Background information: Currently, roughly 19% of people in America smoke cigarettes on a semi-regular basis. However, only 10% of people that smoke heavily get Lung Cancer. Lung Cancer kills the most people every year out of all cancers, mainly because it present asymptomatically until it is inoperable/untreatable. The reason that Lung Cancer occurs in a higher percent of smokers is that the inhalation of all the chemicals in the cigarettes causes many cells in the airways to die. The surviving cells then have to replicate more then they are supposed to, which leaves them at a higher risk for random mutations to occur in the DNA. Often these mutations are corrected by DNA repair enzymes, outside Macrophages who realize the cell is aberrant, or the death of the cell as a result of a mutation in a vital pathway. But since the amount of replications in the air way has been exponentially increased, the random mutations are more likely to add up to the point where a cell becomes cancerous. Thus, Lung Cancer is a fairly large problem in the smoking community, but not limited to just them.

The government allocates nearly $5 Billion a year for CT scans of smokers so that they can hopefully catch the disease in its incipient stages. Doctor Willey, a researcher of both lungs and cancer, sought a way to proactively test people for Lung Cancer. One of the major papers that Dr. Willey's lab produced in the last few years talked about a pattern seen with the levels of expression with certain antioxidant and DNA repair genes in airway epithelial cells (click here to read the paper). They found that there was a  "safe" zone in the amount of mRNA that would be transcribed from the cDNA that had been harvested from air way epithelial cells.
They concluded that for each of the 14 genes that the person does not fall into the "low prevalence" zone, the risk increases. 

Generally in the above graph the higher the number of genes that are out of the safe zone in the test (RTV) means a much higher chance of cancer. Most of the people with above 8 will develop cancer at sometime as they age.


Knowing the risk can allow for the people who haven't developed cancers to go through pre cancer therapy so that the cancer does not proliferate and kill them. This test was recently approved for usage across the country, and it will likely be used commonly by primary care physicians in the next year or so. Doctor Willey told me if they can cut the amount of CT scans they need for diagnosing cancer by just 20 percent, they've already saved the government $1 billion. This is because the biomarker tests are much cheaper and much more effective than the CT scans, saving lives and money.

In addition, another thing that is being looked at in the Willey Lab is a potentially easier method of extracting cells to test. Currently, they use cells that are harvested from Bronchoscopies, a process that takes a fair amount of time and effort to do. They're trying to find a way to get the same Lung Cancer test readings from different cell types, such as cheek cells or skin cells. This would make the Lung Cancer test even more convient and save even more money. 


So now you're probably wondering why this factors into what I'm doing. Well good question! I'm glad you're interested enough in what I'm doing to ask that. If you look above in the table with the 14 genes, you will see that CEBPG is one of the important genes. It actually has one of the smallest "safe" zones of the 14 genes. Based upon a paper that Dr. Willey's Lab produced in 2005, they know that CEBPG controls main of the important genes in air way cells, including many of the Antioxidants and DNA repair genes. All of the PCR and DNA chip electrophoresis has been centered around CEBPG. I'm helping Xiaolu and Doctor Willey with is seeing how treating cells with siRNA for CEBPG affects the expression of the other important lung genes, many of which are some of the other 13 genes in the Lung Cancer test. Depending on the results, it could be a treatment option or a new mechanism to be documented/researched. Hopefully, this has helped you understand more about the bigger picture around what I am doing this Winterim.


2 comments:

  1. Thank you Thad! This helps a lot-- but you lose me at the end. Can you simplify your explanation for what your research with CEBPG shows us? Are you trying to detect the presence of these 14 genes?

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    1. Well essentially they're trying to see how does the expression of the other genes change if we silence CEBPG.

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