Questions

Questions – p53 and Cancer

1.The p53 gene is one of the most widely mutated genes in human cancers resulting in a protein with a sufficient function as a transcription factor resulting in a cancer cell with an enhanced survival potential when mutated. The transcription function of p53 is stress activated resulting in is an inducible activity that responds to the evolving microenvironment of the cancer cell. They are also regulatory genes whose products do control the expression of other genes. It is so that changes in p53 and its related transcription factors can lead to cascading consequences because they can induce mutations. These mutations can lead to transformation of normal cells to cancerous cells. According to the article, p53 also functions as a tumor suppressor as well as play a vital role in neoplastic development. To sum up, with p53 playing such a significant role any mutation could and or would result it a chain of consequences.

2. It is quite informative to study cancer and its implications in mice because the p53 gene and its isoforms are apparent in mice as well as humans. P53 is important because it is thought to play a role in neoplastic development. The mutation of the p53 germ line can be seen in Li-Fraumeni human patients. Mice are transgenic for p53 and have short generations, which aids in research development for humans.

3. The p53 gene family members express multiple mRNA variants due to multiple splicing and alternative promoters. This gene family is paralogous, meaning that they are from the same family of genes. The isoforms of p53, p63 and p73, gained different functions from expressing different p53 proteins, which require a different domain of protein. The different domain accounts for the different function of the isoform.

4. Protein folding and mis-folding are important to study because they help in determining relationships of different folding mechanisms and their results. Different folding sequences can lead to a deeper understanding of the way a disease, such as cancer, work and can ultimately provide a pathway to treatment or a cure. The shape of the folded protein can also be used to understand its function and design drugs to influence the processes that it is involved in. Nevertheless, proper protein folding is essential to function; mis-folding or failure to fold is essential in research of diseases as well as the genes that are involved.

5. Typically, p53 is a “tumor-suppressor gene” which indicates that if it loses function, tumors will result. However, expression of some of the isoforms of p53 can actually contribute to tumor formation. Nevertheless, not all mutations in p53 result in a loss of function. Consequently, making it incredibly difficult to understand the clinical role of p53. Considering our interviewee Norma, it is significant to determine the status of p53 because it assists in being able to keep the cancer in remission and maintain no sudden mutations and or spread of the pancreatic cancer. Being that the p53 has so many functions, keeping in mind of it experimentally and biologically assessing gene expression in relation to p53 status may provide prognostic and biologically relevant consequences.


Expression of p53 in Pancreatic Cancer Cells



Overexpression of Pancreatic Cancer in pancreas due to mutations of p53 gene

Interview

Intro . . .
Norma Tibbetts is a pancreatic cancer survivor who battled this treacherous cancer for eighteen years. When first diagnosed in 1990, her doctor gave her three months to live. Determine to not let it conquer her, she did everything in her power to conquer it and won her battle with cancer in 2008. Being the first to receive the Whipple surgery at the Shawnee Mission Medical Center, her pancreatic cancer was treated. Today Norma is helping to change the view of pancreatic cancer and raise awareness to the public. It is currently the lowest funded type of cancer research but has the second highest mortality rate. Norma Tibbetts helps to do her part by working in affiliation with the Bloch Cancer Society, where she takes calls and talks to people have been diagnosed with the condition that she once battled.

When were you diagnosed?
In 1990.

How were you diagnosed?
By a doctor who did a CT scan. Usually there are no tale-tell signs of pancreatic cancer until large amounts of pain are experienced due to the cancer infested pancreas.

What are the distinct symptoms that caught your attention?
Very specific stomach area pains. Not very many tests for pancreatic cancer, usually not caught until the cancer spreads to other parts of the body causing problems to be noticed in these regions of body.

How long did you battle cancer?
Battled cancer from 1990-2008

Which form of therapy did you use and why?
Whipple surgery. Whipple surgery is a radical surgery in which as much as 95% of the pancreas is removed to cease cancer production in the organ. In addition 75% of stomach is removed, constituting 14-16 inches of small intestine as well as the entire spleen being taken from the body. Because her pancreatic cancer involved islet cells, the cancer was very slow growing and the lymph nodes were not involved. Therefore, chemotherapy was not necessary. She had surgical therapy every three months for first 3 years, then every six months for the next 5 years. Now she is being evaluated once yearly and free of pancreatic cancer.

Before treatment what obstacles did doctors say would cause much difficulty?
Due to slow growing nature there would be no option for chemotherapy. Once the digestive system would be removed she would be limited in food consumption and become diabetic due to removal of majority of pancreas. She cannot consume foods high in fat content or that are difficult to digest such as fresh fruits and vegetables as well as whole wheat.

How did your body respond to treatment?
Took much recovery time. Trail-and-error when it came to fine tuning what could and could not be eaten when trying to establish a new diet. This is due to the fact that digestive enzymes are not being produced due to removal of the pancreas. Specific pills help to balance the problem. General feelings of nausea, discomfort and flashing were all side affects of the surgery.

Did physiological changes cause you to stop responding to treatments that you initially responded to?
No, continued response throughout treatment.

Have you heard of immunotherapy (body gets rid of cancer cells by ingesting them)?
Yes

Was immunotherapy offered as a treatments source?
No available or developed enough in pancreatic cancer field at time.

Were you offered any experimental drugs, such as recently diagnosed actor Patrick Swayze was?
No. Only some experimental drugs to help with general side affects of surgical therapy.

Why is pancreatic cancer often thought of as one of the most terminal forms of cancer?
People who suffer from pancreatic cancer are most often diagnosed late because there are no real tests for this type of cancer as well as not many symptoms. By the common time of diagnosis the cancer has already spread throughout the body causing even more damage. For thus reason many people don’t get treated and unfortunately leads to the second highest mortality rate. Pancreatic cancer is also the lowest funded type of cancer research.