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.
The acquisition of an immortalized proliferative potential is very important for human tumors because, otherwise, the tumors will not grow in number nor will they metastasize. Mutations in progenitor cells would not be transmitted too far as they have limited replication and proliferation ability. Thus, the growth of the tumors will be limited. Hence, if there is even a very small population of cells with the ability to proliferate continuously, there will be a source for productions of more cells for the tumor. Clonogenic assays have shown that, though most cells in a tumor have a limited ability to proliferate, a subset of cancer cells exist in these tumors that continuously proliferate and give rise to new tumors on transplantation.
Strategy to target cancer stem cells: The identification of CSC is essential for development of better and effective therapeutic strategies. The drugs used in the current therapies and treatments target not only the tumor cells, but also, the norm...
... middle of paper ...
...plicates the identification of the loss of tumor suppressor gene (TSG) is epigenetic changes in the gene promoter. Hypomethylation of DNA and hyperacetylation of histones in the promoter region leads to successful transcription of the DNA. Therefore, any alteration in either of the two will disrupt the gene transcription.
Hypermethylation of the CpG island in the promoter of TSG leading to gene inactivation has been well established. Inactivation of TSGs due to promoter methylation is relatively lesser compared to LOH due to chromosomal recombination or gene conversion and hence difficult to detect.
The other epigenetic change that may contribute to TSG inactivation is alterations in histone modification such as reduced acetylation of the histone.
Histone modification may or may not be dependent on DNA methylation and is difficult to detect compared to LOH.
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.
Background and objective. Tumor heterogeneity is shown to be related to clinical outcome in cancer patients. The concept of a small subset of cancer stem cells being responsible for tumor relapse and metastasis comes out as a promising strategy for targeted cancer therapy. However, cancer stem cells are not easy to identify and isolate. The aim of this study was to determine the putative colon cancer stem cell subsets in human colon cancer cell lines HCT116 and HT29, which differ in their aggressiveness and differentiation capacity. Material and methods. Flow cytometry was used to asses HCT116 and HT29 cell lines for the expression of stemness-associated surface markers CD24, CD44, CD117, CD133, ESA, ABCB1. Both cell lines were treated with 5-fluoruracil and the phenotype of chemoresistant cells was investigated. Side population was visualized via Rhodamine 123 staining. Relative expression of ABCG2, c-Myc and Oct4 genes was quantified using qPCR analysis. Results and conclusions. It was shown that HCT116 and HT29 cell lines differ in their stemness-related properties. We imply that putative CSC subset for HCT116 cell line is CD44+/CD24-/CD133- (4,1% of all cells) and for HT29 cells – CD24+/CD44-/CD133- (4,9% of all cells).
LJI308 is a potent and selective inhibitor of RSK. The p90 ribosomal S6 kinase (RSK) comprises a family of serine/threonine kinase which is expressed in various human cancers. RSK is the cytosolic substrate for the ERK (extracellular sianal-regulated kinase), involved in direct regulation of cell survival, proliferation, and cell polarity. Previous studies have demonstrated that RSK pathway is important for the growth and proliferation of cancer stem cells [1,2].
When one thinks of fatal diseases, what comes to mind? Cancer? Organ failure? Brain damage? All of those things and more could be a thing of the past with the incredible potential of stem cell research. Stem cells are like blank cells that can take the form of other kinds of cells. This gives them the ability to heal damaged areas, or grow replacement tissue for tissue that has been diseased. Stem cells can come from several different places, some of which cause lots of controversy and ethical debate. Because of this, stem cell research is not federally funded by the United States government. But, stem cell research has tons of potential and should get more attention for the greater good of our 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.
Stem Cells: What, How and Why? Stem cells are infinitely valuable when considering their potential applications in the medical profession. While current legislative restrictions have halted the development of new ?stem cell lines? to any agency or company that receives any form of governmental grants, there is no question that the medical profession is standing at the brink of a new era of technological advancements in healthcare and research.
..., while a cell undergoes cell cycle, when a cell comes in contact with another cell, it stops reproducing. However, cancer cells continue to duplicate repeatedly until there is a mass of cells or a tumor to form (see figure 9). Lastly, in cell division when there is a mutation or abnormality in the DNA, a normal cell stops dividing. However, a cancerous cell will continue to duplicate and form mutations (“Cell Biology and Cancer”). Also, cancer cells are harmful because they grow and duplicate with complete disregard to the functions and limitations of the body (see figure 10). Also, cancerous cells have the ability to spread through metastasis throughout parts of the body through the bloodstream. In terms of similar behavior to that of normal cells, cancerous cells also duplicate, but at a very different rate ("Cancer Cells vs. Normal Cells: What's Different?").
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...
Groups of transcription factor binding sites called enhancers and silencers can turn a gene on/off in specific parts of the body.
What if there was a cure for cancer or a treatment for spinal injuries? Would you support the research? What if there was a way that you could repair damaged nerves. Some believe that stem cells may hold the answers to some of these questions. What are stem cells and why should you or I even care about them? Some believe that they are a miracle treatment waiting to happen while others believe that stem cells are highly immoral. Why does so much controversy surround the issue? Why is the conversation of stem cells feared by some and praised by others? To some stem cells are the medical hopes for the future, something for us to hang on to as we do battle with major diseases that include cancer, Parkston’s disease and spinal injuries. To others stem cell researchers are murderers who are trying to play God’s hand. A many have pledged their support to stem cell research including a few well known celebrities. Reeves’, who was best known for his role in the early Superman movies, and J. Fox two well-known celebrities, have pledged to stem cell research, both have created a private fund for the research of stem cells. This celebrity however has not swayed everyone to support stem cell researches cause. Just as there are supporters of stem cells there are those who believe that the use of stem cells is immoral. Since the first stem cells were separated there have been doctors, religious groups and even some political figure head have shown their opposition for stem cell research. Even with the knowledge and promise that stem cells show many of those who truly oppose stem cells have not changed their mind. The question is are their reasons good enough to halt the research of stem cell or are they just holding back what will soon be inevi...
... T., Sheikhattar, R., & Shilatifard, A. (2009). An operational definition of epigenetics. Genes and Development, 781-783. Retrieved from http://genesdev.cshlp.org/content/23/7/781.long
Another easily identifiable factor in increasing the onset of DM are the epigenetic risk factors. The genetic susceptibility, caused by the missing genomic information, can be accounted by additional variants like histone posttranslational modifications, which remove or rearrange the histones bound with the DNA. DNA methylation alters the methylation levels of INS gene promoters and has been discovered in patients with TD1 that altered methylation of histones upstream of HLA-DRB1 and HLA-DQB1. Noncoding RNAs give rise to altered expression of miRNAs in regulatory T cells of T1D.
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.
Tumors are formed by the alteration of the body’s own cells. This can be caused by environmental factors such as radiation, like UV exposure, chemicals or viruses 1. These can disrupt genes that control growth and cause an increase in cell division and proliferation. Proto-oncogenes are those genes that control normal but essential cell processes that keep cell growth and death in check. Two important categories are apoptosis genes, which regulate cell death, and tumor suppressor genes, which decrease cell propagation 1 . If these genes were mutated to the point where they cannot produce a functioning protein, cell division would continue far past what it was supposed to and unhealthy cells would be allowed to live and continue to multiply. This is what creates a malignant tumor. Certain conditions in the body can also promote the growth of cancer cells. One of these is a deficiency of natural killer (NK) cells, which are able to kill cancer cells by creating a pore in the cell membrane with perforin and releasing granzymes into the cell. Low levels of perforin allow for tumor growth 1. Chronic inflammation can also ...