The article begins by stating that the tumor suppressor p53 has great importance in the prevention of cancer growth and expansion. Although cancer is the most spoken about topic and p53’s significance against it, p53 also has a hand in ischemia, neurodegeneration, and ageing. While this tumor suppressor seems to be very busy it also regulates the repair of DNA and death of the cell, just to name a few. The activity of p53 can be seen when binding to the DNA at target sequences for transcription. It was pointed out that the doings of p53 are not designated to the nucleus such as other transcription factors as determined over time. Further mentioned in the introduction is a statement that lists this as the most studied mechanism while also related to the material covered in class is apoptosis. P53 inducts apoptosis in the by intrinsic mitochondria-mediated pathway, also transcriptionally through pro-apoptotic parts of the pathway, and in a transcription–independent way which has been recently been looked further into. As if the roles above were not plentiful enough cytoplasmic p53 is also thought to influence autophagy, movement of vesicles, signal transduction, cell metabolism and possibly stem cell expansion, but all are truly determined. Towards the end of the introductory section the authors state that there are still many mechanisms of cytoplasmic p53’s activation leading to apoptosis that are uncertain as well as some p53 missense mutants that lead to oncogenesis. The authors express that the article mainly will speak about the proper or improper activities performed by p53 on the mechanism in the cytoplasm while also looking for areas where beneficial treatments may be used.
While much is unknown regarding the cytoplasmic lo...
... middle of paper ...
...eve that this would be the area I would spend ample time, continually testing.
A portion of this paper caught my curiosity found in the section relating cytoplasmic p53 and pathophysiology in which they brought up material that was covered in the class room. This related to the activation of caspase-3 that was dependent upon p53. Although also found in the article is the relation of caspase-3 with being activated from cytochrome-c attachment to Apaf-1 forming an apoptosome leading to apoptosis, which was displayed on a diagram from class. It is also remarkable that a review summary still contains so much complexity from many sources when previously examining primary source articles that only contain material coming from one study alone. Overall the article was very interesting to review and gives a better understanding of the many studies that are being conducted.
Mitochondria synthesises its own protein which are released in response to various apoptotic stimuli. These proteins promote apoptosis by activating caspases and nucleases or by neutralizing cytosolic inhibitors of this process.[3]
Specifically “TP53, p16INK4A, and SMAD4. The p53 nuclear protein activates transcription of a cyclin kinase inhibitor p21WAF1/CIP1. Following genomic stress, inappropriate growth factor stimulation or expression of oncogenic ras increased expression of p53, and thus p21WAF1/CIP1 resulted in inactivation of specific CDK/cyclin complexes” (MedScape). If this transformed cell can escape internal and external fail-safe mechanisms, receive nutrients, and activate its proliferative program, it can form a mass of cancerous cells. Tumor growth can cause the loss of pancreatic functions. Another characteristic of pancreatic cancer is metastasis happens early in tumor growth, which is most likely responsible for pancreatic cancer’s aggressive
Thought to be an oncogene, a gene that has potential in transforming normal cells into tumor cells, p53 was regarded as the most prominent tumor suppressor gene [1]. P53 is a gene which signals apoptosis (programmed cell death) if a cell cannot be repaired due to an extensive amount of damage. As stated in the textbook, p53 regulation occurs by an E3 ubiquitin-protein ligase known as MDM2 [1]. "Controlling the controller" is a statement that describes the molecular interaction where the presence of MDM2 targets the p53 for proteosome via degradation. With three main checkpoints in cell cycle, the literature states p53 functioning from G1 into S phase in a chaotic cell [2]. The normal state of cells is to keep p53 levels low in order to prevent uncontrolled apoptosis and random cell cycle arrest from occurring. In a further note, although p53 promotes apoptosis and cell cycle arrest, cancer may result from p53 unable to recognize the problematic site. In turn, a mutation in p53 may result engaging in new activities. These activities include cellular transformation, tumor metastasis,...
Studies have shown that the transduction of cisplatin-DNA adduct recognition signal occurs through pathways other than p53, including the following: AKT pathway, c-ABL, MAPK/JNK/ERK, and MKP1/CL10011. These other pathways are not covered in this paper due to page limits.
“The word 'leukemia' is a very frightening word. In many instances, it's a killer and it's something that you have to deal with in a very serious and determined way if you're going to beat it” - Kareem Abdul-Jabbar. Many people, including tons of children, fight leukemia every day trying to beat this vicious cancer. Without knowing how leukemia is exactly caused, it puts a damper on how to avoid it.
The body is composed of cells. Normally, these cells divide at a composed and calculated manner. If cells die or are destroyed, the body creates more cells through the division of existing cells. However, occasionally, problems with some cells in the body may occur.
The cell cycle is the process by which cells progress and divide. In normal cells, the cell cycle is controlled by a complex series of signaling pathways by which a cell grows, replicates it’s DNA and divides, these are called proto-oncogenes. A proto-oncogene is a normal gene that could become an oncogene due to mutations. This process has mechanisms to ensure that errors are corrected, if they are not, the cells commit suicide (apoptosis). This process is tightly regulated by the genes within a cell’s nucleus. In cancer, as a result of genetic mutations, this process malfunctions, resulting in uncontrolled cell proliferation. Mutations in proto-oncogene or in a tumour suppressor gene allow a cancerous cell to grow and divide without the normal control imposed by the cell cycle. A change in the DNA sequence of the proto-oncogene gives rise to an oncogene, which
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 ...
The Hallmarks of Cancer written by Doughlas Hanahan and Robert A. Weinberg proposed the underlying principles and the essential characteristics of the development of human tumors. This article distilled all the existing research to depict the fundamental characteristics of cancer. Hanahan and Weinberge proposed six hallmarks shared among all cancers mentioned in this article includes supporting proliferative signaling, evading growth suppressor, resisting cell death, enabling replicative immortality, sustaining angiogenesis, and tissue invasion and metastasis. Four emerging hallmarks are also introduced in this article, depicting the current 10 underlying principles shared by cancerous cells. Hanahan and Weinberg also provided specific examples of potential mechanisms for the hallmarks. All of the mechanisms of hallmarks of cancer must be fulfilled in the development of cancerous cells.
Throughout the years, apoptosis has been thoroughly studied and investigated by millions of scientists around the world. Throughout people’s knowledge of cells, the cell cycle, mitosis and meiosis, and viruses, there are still questions that we ask. These questions can range from why doesn’t a human continue to grow when we produce millions of cells, what happens to cells that fail the mitosis and meiosis checkpoints, and what happens to the cells that are infected by viruses. The answer to these common and educational questions is all in the process known as apoptosis. Apoptosis is the death of cells that occurs as a normal and controlled part of an organism's growth or development. The common questions that people ask about the cell process
Leukemia is a cancer of the white blood cells. It begins in the bone marrow, the soft tissue inside the bones. Within the bone marrow is where white blood cells are created, that help fight off bacteria, viruses, and other microorganisms within the body that cause infections. The disease develops to when the white blood cells are being produced out of control. The cells that are being produced do not work properly as they should, they grow faster than a normal cell would and don’t know when to stop growing. Overtime, if not treated properly, the white blood cells will over crowd blood cells, creating a serious problem such as anemia, bleeding and infection. Leukemia cells can spread to the lymph nodes and other organs in the body causing swelling and pain.
The emphasis on health and fitness has become paramount in our society today in an effort to prevent and combat diseases such as Cancers. Cancers are a group of over 100 diseases that affects every aspect of the human system from skin, to bones, to muscles, to blood. One of the most common blood disorders is Leukemia. As defined by the U.S. National Library of Medicine, Leukemia is a type of blood cancer that begins in the bone marrow. The bone marrow is the soft tissue in the center of the bone that is responsible for the production of blood cells. The term leukemia means white blood. The term leukocytes refer to white blood cells, which are body’s defense against infections and other foreign substances. When Leukemia occurs there is an uncontrolled increase in the number of white blood cells. When this occurs, these cancerous cells inhibit the production of healthy red blood cells, platelets, and mature white blood cells. Over time the cancerous cells can spread to the bloodstream and lymph nodes. They can also travel to the Central Nervous System and the rest of the body.
Acute Myeloid Leukemia (AML) is the most common type of acute leukemia in adults. AML is a heterogeneous disease which results from genetic alterations in normal hematopoietic stem cells. These alterations induce differentiation arrest and/or excessive proliferation of abnormal leukemic cells or blasts [1]. Recent genomic studies have identified that recurrent somatic mutations in patients with AML blocks differentiation and/or enhance self-renewal by altered transcription factors [2,3]. The genetic or the epigenetic changes acquired by AML cells disrupt the key growth regulatory pathways and changes will make the normal cells to attain certain malignant characteristics which include inappropriate proliferation in the absence of normal growth signals, indefinite self-renewal in a manner analogous to a stem cell, escape from programmed cell death, inhibition of differentiation, aberrant cell cycle checkpoint control and genomic instability [4].
If the levels of p53 are decreased, then the DNA is not being fixed or disposed of. In damaged radiation or chemotherapy cancer cells the gene p53 assists in their cell death (Porth, Carol, Kathryn J. Gaspard, 138). Therefore, if there is a deficiency in this p53 protein then DNA is not being fixed or disposed of and certain cancer treatments are not going to be as effective. With the lack of p53 protein there are many dangers. There is going to be an accumulation of bad DNA in many cells. With the lack of cell death not only is the DNA bad but there will form a mass from these cells not being disposed of in the way they were meant
Growth and differentiation of cells in the body normally are precise and regulated. When cells grow uncontrollably, mutations can occur and cancers can form. As a mechanism of introducing the biological basis of cancer, this tasks has been developed to help students gain a conceptual understanding of how the process of mitosis not only provides a complete set of genes to each somatic cell, it can result in cells that divide abnormally resulting in cancer.