Working units as of Sunday night, May 4th, 2008 are 8. Although the program has been running constantly with a cable connection to the internet, the low number could be due to logging in and out of user profiles with Microsoft XP.

Question Set #2 continued...

2. What effect might inbreeding have on this disorder?

A number of extrinsic and intrinsic factors contribute to the development of cancer, a disease still far from satisfactorily controlled in most communities worldwide. Studies have shown that cancer are possibly caused by both recessive and or dominant genes. Furthermore, inbreeding leads to an increase in homozygosity of a population. It also may result in a significantly higher phenotypic expression of deleterious recessive genes. One would think that inbreeding would decrease genetic variance and positive heritability. With this, inbreeding would cause an increase of the likelihood of cancer due to the reduction of genetic diversity. It would also cause a variance of susceptibility of diseases and a weaker immune system to fight the cancer cells.

Question Set 2 Answer # 1 Ayok Monydit

1. What is the estimate of H2 for Cancer? How much influence does selection have on this?


H2 is defined as the proportion of total phenotypic variance at the populatioin level that is contributed by genetic variation. According Nature Reviews Cancer 4, 769-780 (October 2004) the h2 for this prevalent types of cancer are as follows.
Lung h2=0.26
Breast h2=0.27
Prostate=0.42
Colorectal=0.35

According to Carlo Maley, ans assistant professor at Wistar Univeristy, "the dynamics of evolution are fully in play within the environment of a tumor. A tumor cell population is constantly evolving through natural selection. Mutations that aid in the survival and reproduction of cells in a tumor are the things that drive it towards malignancy. When applying chemotrophy (cell chemistry) to a cluster of cancer cells, we are likely to find resistant mutant allele. 3 of Darwin's postulates are important when analyzing the evolution of cancer cells. These factors are genetic variation, heritabilty, and natural selection. Cancer cells are highly variable on a genetic level, no two cells will be completely identicle. Most Varation found in cancer cells is hertibale, that is, it is passed from parent to offspring. This excludes variation that is result of mutation. Last but not least, variation is acted upon by natural selection (some alleles possibly mutants become fixed or lossed). These 3 factors are the guidline for determining wheather a cancer cell will evolve or not.

References

http://www.sciencemuseum.org.uk/on-line/lifecycle/79.asp

http://www.hhmi.org/biointeractive/cancer/cancer_evolution.html

Genetic predisposition to colorectal cancer
Nature Reviews Cancer 4, 769-780 (October 2004)
doi:10.1038/nrc1453

Update on Patrick Swayze: On a side note

An update on Patrick Swayze and response against rumors.

Swayze Battling Cancer
By Joal Ryan
Wed, 5 Mar 2008 02:34:20 PM PST

Patrick Swayze is undergoing treatment for pancreatic cancer but does not have just weeks to live, the actor's reps and doctor said Wednesday.
"Patrick has a very limited amount of disease and he appears to be responding well to treatment so far," Dr. George Fisher, Swayze's personal physician, said in a statement. "All of the reports stating the timeframe of his prognosis and his physical side effects are absolutely untrue."
Fisher's remarks were in rebuttal to the National Enquirer, which broke the news of Swayze's illness on its website and said the Dirty Dancing star had recently dropped 20 pounds and been given only five weeks to live.
"Patrick is continuing his normal schedule during this time," the actor's reps said, "which includes working on upcoming projects."
Speaking to E! News, Swayze's mother, dancer and choreographer Patsy Swayze, echoed the optimism of the star's doctor.
"I don't really want to talk about it, but I know he's sick," Patsy Swayze said. "But he has great doctors and a great prognosis, and that's all I can say."
According to the Pancreatic Cancer Action Network, pancreatic cancer is the deadliest of the leading cancers. Fewer than 5 percent of patients live more than five years after diagnosis.
Swayze, 55, filmed an A&E pilot in December called The Beast, in which he stars as an unconventional, undercover FBI agent. The network said Wednesday it was still considering the show for pickup next season.
As recently as Monday, Swayze was spotted running an errand at a Simi Valley, California, dance studio. An employee there told E! News the actor "looked good" and not at all as if he'd lost a lot of weight.
Producer Bobby Schwartz, who worked with Swayze last summer on the as yet unreleased indie drama Powder Blue, likewise vouched for the star's fitness on that set.
"When we were shooting, the guy looked very young, very healthy, very energetic," Schwartz told E! News.
Swayze is best known for a string of hits in the 1980s and 1990s that included Ghost, Point Break, Road House and the career-changer, Dirty Dancing, in which he played Catskills bad boy Johnny Castle.
—Additional reporting by Whitney English
(Originally published Mar. 5, 2008 at 2:04 p.m. PT.)

Kim's Reflection: p53 genes, vital in development

The articles were interesting as well as thought provoking. I thought they were good choices for our service learning project and helped in thinking beyond just cancer, and more towards the different facets of it. Some parts of the paper were a bit difficult to read, but was doable. P53 genes function at conserving stability by preventing genome mutation. Nevertheless, it is hypothesized that the p53 play an important role in neoplastic development. Its interesting to find that a person inherits only one functional copy of this important gene from their parents and through the mutation of this gene, it may lead to life-threatening diseases. From the Lee and Bernstein article, it states that it is unclear how the p53 mutations lead to neoplastic development, however; I found it a bit trivial to study the p53 gene in mice. Would continuing to study mice help in being able to control these genes? Are the p53 gene in mice similar to humans, if so to what degree? The paper, written by Lee and Bernstein was written in 1993, are there any new studies that show any different data or promising data that is able to control this gene?

P53 Article Relection ~ Brice Austin

I found the articles interesting; although, confusing at times. The main "take-home" point, I belive, is that the transgenic p53 mutations can cause cancerous tumors. P53 is responsible for neoplastic deveopment. This means that they create many other regulatory genes. In mice the wild type p53 protein keeps the p53 gene from mutating, lessening results tumors. Is there anything similar to this protein in humans? Commonly tumors still develop because the p53 tarnsgenic form still suppreses the activity of the wild type protein. Can the protein be added to or made stronger?

Ayok: What I have learned so far

The article I found most intresting to read was Lee and Bernstein's "P53 mutations increaces resistance to ionizing radiation."

The P53 gene is thought to play an important role in neoplastic development. It is thought to function as a cell cycle marker after irradiation, suggesting that mutant forms of p53 gene significantly increaces cellular resistance to a variety of hemtapoietic cell lineages(p53-2,p53-3,pL53-2). Researchers believe that p53 acts in a dominant negative manner to suppress the activity of the wild type p53 protein. Wild type p53 has been postulated to play a role in DNA repair. In this particular article, transgenic mice expressing mutant alleles of p53 were used to measure the resistance of hematopoietic cells to radition. to assess the effects of the mutant allele, the ability of radiatioon to prevent colony formation of cancer cells in a variety of tissues were observed(spleen, liver, lung, thymus). Results showed that mice that were hemizygous or either transgene showed no abnormatlities but infactt ad high incidence of lymphiod tumors. This research depicted how radiation can effect the activiny of mutant forms of p53 which interm effects how succesful radiation is in treating cancer. After addition research, I unearthed some intersting facts about the P53 gene.

Intresting facts

1. If a person inherits only one functional copy of the p53 gene from their parents, they are predisposed to cancer and usually develop several independent tumors in a variety of tissues in early adulthood, a condition known as Li-Fraumeni syndrome.

2. How cancer starts?
When there is DNA damage, the p53 gene suspends the cell cycle until the damage can be repaired. If there is a mutation in p53, the cell cycle continues unrestrained and reproduces the damaged DNA, leading to uncontrolled cell proliferation and cancer tumors. Cancer develops as a result of the cell with damaged DNA dividing, the damaged DNA being replicated and passed to each newly produced daughter cell.

3. p53 becomes activated in response to a variety of factors which include but is not limited to DNA damage (induced by either UV, IR or chemical agents,such as hydrogen peroxide). Other inducive factors are ribonucleotide depletion and deregulated oncogene expression. This activation is marked by two major events. Firstly, the half-life of the p53 protein is increased drastically, leading to a quick accumulation of p53 in stressed cells. Secondly, a conformational change forces p53 to take on an active role as a transcription regulator.