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Epigenetics dissertation
Epigenetics dissertation
Epigenetics dissertation
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Epigenetics and Cancer Introduction: Cancer is beyond mutations. By definition, epigenetics is the change in gene translation that is caused by alterations not directly due to genetic mutations in the DNA sequence. The 2 main mechanisms are DNA methylation and covalent modification of histones. By methylation, certain molecular tags (methyl groups) bind to a specific sequence of a gene, that results in its disability hence incapable of being translated into its appropriate protein product. These changes affect the cell’s functions leaving its DNA unchanged. Epi is derived from Latin meaning above; hence an epigenetic configuration overlies our genetic predispositions. DNA methylation and Cancer: DNA methylation primarily occurs within sites in the DNA sequence known as CpG dinucleotides, which is a 2 base pair sequence involving a Cytosine bonded to a Guanine by a phosphodiester bond. DNA methylation is catalyzed by the enzyme: DNA methyl trasnferase (DNMTs). Methylation of DNA segments leads to the silencing of transposable elements. Hence this mechanism is repressive to transcription, by that enhancing genomic stability. However, there exist “CpG” islands that are associated with gene promoters that escape methylation hence stability. Hypermethylation of CpG islands at tumor suppressor genes turns them off, while hypomethylation leads to the instability and inappropriate activation of oncogenes and transposable elements. Methylation can be directly related to genetic mutations, an example of this case is methylated cytosine. Methylated cytosine mutates spontaneously in vivo through deamination to give thymine. According to Andy Bannister (n.d.), “37% of somatic p53 mutations and 58% of germ line mutations occur at methylated... ... middle of paper ... ...chl, T. (n.d.). microRNAs in Human Cancer. Retrieved July 8, 2013, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3704221/ Johnson, G. (2013, November). The Long Trail of Cancer Cues. Scientific American, 309(5), 46-49. Li, Y., Wicha, M. S., Schwartz, S. J., & Sun, D. (2011, February 4). Implications of Cancer Stem Cell Theory for Cancer Chemoprevention by Natural Dietary Compounds. Retrieved December 12, 2013, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248810/ Nikitina, E. G., Urazova, L. N., & Stegny, V. N. (2012). MicroRNAs and Human Cancer.Experimental Oncology, 34(1), 2-8. Retrieved from http://archive.nbuv.gov.ua/portal/chem_biol/eol/2012_1/002.pdf Wang, K., Wu, X., & Huang, J. (2013, February 28). Cancer stem cell theory: therapeutic implications for nanomedicine. Retrieved December 12, 2013, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3589204/
Epigenetics is the word that is used for genes that are modified in order to assist certain genome sequences that lead to diseases and disorders. Epigenetics has come a long way since the first genome sequence had its draft breakthrough in the year 2000 (NOVA 2012). From depression to cancer, epigenetics has made its way through to provide families with the appropriate knowledge and perhaps medication in order to avoid these diseases and disorders in the future.
The underlying purpose of the experiments performed in the study, Promoter Hypermethylation of KLF4 Inactivates its Tumor Suppressor Function in Cervical Carcinogenesis, is to investigate the mechanism by which the KLF4 gene is silenced in cervical carcinomas. Cervical cancer accounts for 250,000 female deaths every year. Developing therapies for cervical cancer has been limited due to the lack of genetic and epigenetic data of the mechanism causing the cancer. The KLF4 gene is a transcriptional regulator of cell growth and differentiation. It functions as a tumor suppressor in cervical cancer, but is found to be inactivated in cervical cancer. The overexpression of KLF4 protein is known to inhibit cervical cancer cell growth and tumor formation by activating a cell cycle suppressor. Promoter CpG island hypermethylation can result in transcriptional silencing of many tumor suppressing genes. Two CpG regions, BSQ1 and BSQ3, were examined in this experiment.
The cancer stem cell theory hypothesizes that tumors or cancers arise from mutations or epigenetic changes in normal stem cells. These mutated or genetically altered stem cells possess the properties of the normal stem cells such as the ability to self-renew, differentiate into any type of body cell, and resist apoptosis. Hence, the cancer stem cells (CSC) are named so. It is also suggested that because of the above-mentioned properties of the cancer stem cells, the current anti-cancer therapies are not entirely successful (Gil et al, 2008). Despite surgery and other therapies, even if very few of these cancer stem cells survive, they can continue to act as a source for more tumors, even though the therapies eliminate all visible signs of cancer.
In 2013 about 580,350 Americans were projected to die of cancer, almost 1,600 people a day. Cancer remains the second most common cause of death in the US, accounting for nearly 1 of every 4 deaths (Cancer Facts). Doctors and scientists are always trying to discover new ways to help battle cancer as well as other diseases. Doctors have tried everything from plants to radiation to try and destroy cancerous cells. Instead of destroying them Scientists and doctors are now trying to replace the old cancerous cells. In order to replace these cells they will need new cells. Stem cell research is the newest way doctors are trying to help with diseases. There are different types of stem cells. Stem cells are cells found primarily in embryos, and they have not yet taken on the characteristics of any particular type of cell, such as bone, muscle tissue or brain matter. The newest research being done is with embryotic stem cells. Embryotic Stem cells have been used in medical therapies to aid patients with many types of diseases; that being said it is imperative that we continue researching, practicing, and funding these medical advancements.
Groups of transcription factor binding sites called enhancers and silencers can turn a gene on/off in specific parts of the body.
“Stem Cells: The Future of Medicine.” Medschool.umaryland.edu. University of Maryland School of Medicine Web 14 Nov 2013
My sister, Kathy, was diagnosed with cancer in 2013. I was shocked because my sister was always the healthy one among all us girls, the type of cancer, Kathy called colon cancer, Cancer that forms in the tissues of the colon. Most oncogene mutations of indisputable normal genes designate proto-oncogenes. Proto-oncogenes determine the “excellent” genes that usually rule what cell do and the way typically it distribute. Once a factor mutates (changes) into cell, it come back a "hurtful" factor that may become usefulness on or activated once it's not believe to be. Once this occurs, the cell becomes out of management, which might pass to cancer. As scientists learn additional throughout oncogenes, they will be powerful to develop a medication that inhibits or restrain them.
Almost everyone is touched by cancer in some way and the number of people living with and beyond cancer grows greater every year. Globally 14 million people are diagnosed with cancer each year and 8 million people will die from it annually. Half of all men and one-third of all women will develop cancer during their lifetime. (13) There are many treatments for cancer, mainly: surgery, radiation and chemotherapy. These traditional treatments have many negative side effects. Therefore, increasingly, other treatments, such as hormonal therapy and targeted therapy are being used for certain cancers. Nanotechnology is a form of targeted therapy that destroys cancer tumors with minimal damage to healthy tissues and organs. Scientists are already using nanotechnology in early detection of elimination of cancer cells before they form tumors. But the real game changer will be when nanotechnology targets cancer tumors in treatment (11,13).
Panno, J. (2005). Cancer: The Role of Genes, Lifestyle, and Environment. Facts on File Science Library: The New Biology. Facts On File.
Cancer occurs when cells divide uncontrollably. Cells keep dividing even though new cells are not needed. Change from normal to cancerous cells requires gene alterations.
An ordinary human body contains approximately one trillion cells and precisely 46 chromosomes in each cell. However, the human body can be altered by a genetic mutation. Over the course of history, genetic mutations have had a large impact on the human race. They have brought harm to numerous amounts of people. Cancer, in particular, is one of the most lethal diseases. Cancer begins when a portion of DNA inside a chromosome is damaged, causing a cell to mutate. Then, the mutated cell reproduces multiple times and creates a tumor. Afterwards, cancer cells break off of the tumor, enter the bloodstream, and disperse throughout the body. If the cells break off, the tumor is considered malignant - this type of cancer is very difficult to cure. Many patients today stay optimistic for a medication to heal cancer. It is imperative to address a few of the causes and effects of cancer in order to gain a general knowledge of genetic mutations.
Epigenetics is the study of both heritable and non-heritable changes in gene translation, which do not stem from mutation. Epigenetic alterations to DNA may occur in several different ways; histone modification, DNA methylations, expression of microRNAs, and changes of the chromatin structure (Ntanasis-Stathopoulos et al). Depending on their presentation, they may be passed on to offspring. The exact mechanism of heritable epigenetic modification has not been discovered, but all of these alterations may have some impact on a wide range of disorders and have far reaching implications in the medical field. The study of epigenetics seeks to answer the age old question of whether nature or nurture is responsible for our phenotype, and it has arrived at the answer that in fact, both are. The discovery of epigenetic changes may lead us to cure many disorders, and even personality problems.
Cancer is a disease that affects human somatic cells. It causes the cells to divide uncontrollably and form masses known as tumors. There are two different types of cancer tumors. Some tumors are benign and other tumors are malignant. Benign tumors look similar to the tissues that they came from and develop slowly. The tumor remains in the same area that the tumor originated in. Malignant tumors are formed from cells that do not resemble the tissue that they came from. They vary in shape and size. This enables pieces of the tumor to break off and spread to other places in the body. Over the past few decades cancer has become a very prominent disease. There are many different types of cancer and many different causes for the the disease. Most cancers are because of a genetic mutation. The most common type occur when a cell is dividing. Proto-oncogenes, which are alleles in a normal cells, mutate to form oncogenes. These oncogenes cause cancer because they do not allow the cells to self destruct or become epistatic. There have been several research projects which have been testing epistatis.
The Phase I trial will be discussed here as it pertains to the topic at hand. The typical treatment for cervical cancer if surgery is not a viable option – like if the cancer has spread, then called locally advanced cervical cancer – is chemotherapy and radiation treatment at the same time. This phase I clinical trial is simply looking to add ipilimumab to this regimen, but once the chemo/radiation has been completed (LACC article). Chemo and radiation destroy tumor cells, which causes tumor-associated antigens to be released. Once released, these antigens are exogenous (outside the cell) and will be presented to helper T cells to initiate an immune response.
Panno, Joseph. Cancer: The Role of Genes, Lifestyle, and Environment. New York: Facts On File, 2005. Print.