Introduction
As creatures of the light, it is natural for us to fear the dark unknown of death. However, if we only knew how prevalent death is in our lives, perhaps we would not be so afraid or disgusted by it. For it is death that keeps our body running functionally, and giving the organ systems physical definition, enabling them to work properly. The building blocks of our bodies-- cells-- are alive and constantly growing, and if they continued to do so without pause, our organ systems would become enlarged and misshapen, and we as an unified organism would die. Therefore, our cells commit suicide on a regular basis via programmed cell death, more commonly referred to as apoptosis; this is done either to cull excess cells to give way to new ones, or when cells start malfunctioning and don’t want to reproduce. Apoptosis should not be confused with its foil, cell necrosis, which is is another death system that kicks in when cells and tissues are dealt trauma, and it is highly irregular, as opposed to the regulated apoptosis. Each death system has its own purposes in the body, and the interruptions of these small deaths can ultimately lead to the death of the entire organism-- life is not merely followed by death-- it is supported by it.
The apoptosis process is a fairly recent medical discovery, as intensive research had only begun in the late 1900s, leading Drs Brenner, Horvitz and Sutton to their ground-breaking discoveries in the field, earning them the Nobel Prize in Medicine (Hung and Chow, 2004). Their research began in Caenorhabditis elegans, which has more simple DNA and body processes than mammals. However, it was soon discovered that the genes which regulate apoptosis in the nematode are similar to those in large orga...
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... in glioma cells (suppression of autophagy, mentioned above, is often accompanied by activiation of apoptosis). Silencing eEF-2 kinase expression with the inhibitors (NH125) remarkably increased the TMZ-activated apoptosis in human glioma cells. One other important discovery of this experiment was that the combination of TMZ and NH125 did not cause TMZ to destroy normal human astrocytes. Essentially, co-treatment of TMZ with NH125 made TMZ more effective against glioma and produced a better survival benefit for the mice, but could not cure the mice. This may be because the amount of NH125 (eEF-2 inhibitor) used was not enough, or the dosages of TMZ and NH125 were not optimal. Nonetheless, development of better and more effective inhibitors of eEF-2 kinase may help in finding the cure for glioblastoma multiforme, the malignant and extremely aggressive brain tumor.
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.
Chemotherapy is the treatment of a tumor with chemical agents to reduce mass or eradicate a tumor completely. There are certain mechanisms by which chemotherapy inhibits cancer. The first mechanism is cell death by cytotoxicity. Some chemical agents in certain amounts are toxic to cells. The cells die due to the toxic...
An idea first brought to the attention of the world back in the 1960’s when researchers first noted that the cell could destroy its own contents by a matter of enclosure within the membrane. (1) This lead to the formation of vesicles that were efficiently transported to a recycling component called the lysosome, for degradation. The term autophagy simply means "self-eating”. Scientifically, the term accounts for “a normal physiological process that deals with the destruction of cells in the body”. (2) Due to the complexity of the phenomenon, little advances had been made until a series of experiments were conducted in the early 1990’s. Yoshinori Ohsumi; a Japanese cell biologist born in 1945, conducted an experiment using the test subject of yeast, which led him to identify the critical genes for autophagy. Through further studies, he noted the underlying correlation between autophagy mechanisms used in yeast and the machinery used in our cells. Ohsumi’s new discoveries created the path in understanding the critical importance of autophagy in many
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,...
“Since 1990, over 6 million Americans have died of cancer, more than the combined casualties from the Civil war, WWII, and the Vietnam and Korean conflicts combined” (Faguet, p. 5). According to American Cancer Society projections, there were 1,529,560 new cases of cancer in 2010. Cancer is becoming more and more common around the world. New cancers are constantly being discovered. Researchers are finding new ways to detect cancer and treat it so that the fatality rate does not rise. However, there are some cancers that researchers have not yet discovered a cure for. It is very important for Cancer Research to continue so that one day these cancers will no longer be a treat.
The beginning of apoptosis,, is the most significant anti-cancer function of p53. If DNA damage is not repairable, p53 can activate pro-apoptosis genes such as p21, DNA-damage-inducible protein 45, Bcl-2 family, and growth arrest, etc. Furthermore, p53 can interact with hundreds of proteins to maintain the cells processes and apoptosis. P53 can also keep the cell cycle in check by repressing the expression of genes like bcl-2, bcl-X, cyclin B1, MAP4 and survivin (Bai and Zhu, 2006). The physiological responsibilities of p53 are keeping the genetic stability and regulating the normal cell cycle through a regulatory network system. A mutation of Tp53 gene would cause a loss of function in the p53 protein, ultimately resulting in a cellular canceration. The function of p53 is preventing cancerization of cells by repairing genes or activating apoptosis. To achieve these functions, p53 interacts
Death is part of the circle of life and it's the end of your time on earth; the end of your time with your family and loved ones. Nobody wants to die, leaving their family and missing the good times your loved ones will have once you pass on. In the Mercury Reader, Elisabeth Kübler-Ross “On the Fear of Death” and Joan Didion “Afterlife” from The Year of Magical Thinking” both share common theses on death and grieving. Didion and Kübler-Ross both explain grieving and dealing with death. Steve Jobs commencement speech for Stanford’s graduation ceremony and through personal experience jumps further into death and how I feel about it. Your time is on earth is limited one day you will die and there are many ways of grieving at the death of a loved one. I believe that the fear of death and the death of a loved one will hold you back from living your own life and the fear of your own death is selfish.
For years people have been looking for a cure for the devastating disease of cancer. Cancer is the third highest killer in the US with over 2,500,000 victims per year. Oncologists and scientists around the country are researching all forms of cancer in an effort to understand, treat, and ultimately defeat this disease. Already there have been numerous advances in the field, such as chemotherapy and gene therapy. One advance has been the use of a cell process known as apoptosis. By harnessing this normal cell process, scientists hope to have found an effective way to combat cancer.
Ou XM, Chen K, Shih JC (2006) Monoamine oxidase A and repressor R1 are involved in apoptotic signaling pathway. Proc Natl Acad Sci U S A 103:10923?10928
What is death? What makes death such an avoided subject? According to Merriam-Webster’s Dictionary, death is defined as: the permanent cessation of vital functions; the end of life. So maybe we fear death and death’s process because the thought of life ending is unbearable or because we know little about the dying process and naturally, as humans, we fear the unknown. These all may be true and in most cases probably are. But if one was to take a look at death and the process and consider the true meaning of that very moment in one’s life, maybe we would view it differently and maybe, just maybe, see life itself in a whole new way?! Marie de Hennezel, in her book Intimate Death defines death as . . . “our life’s culmination, it’s crowning moment and what gives it both sense and worth” (xi). She sheds light on the positive side of death, the part no one thinks about or acknowledges. And she shows us that death can in fact make us see how amazing life can be. In his book, The Body Silent, Robert Murphy shares with us the changes in life and actions of society when faced with the process of death.
Average human life spans between 20 and 30 years for most of our species history. Most people today are thus living highly unnaturally long lives. Because of the high incidence of infectious disease, accidents, starvation, and violent death among our ancestors, very few of them lived much beyond 60 or 70. There was therefore little selection pressure to evolve the cellular repair mechanisms (and pay their metabolic costs). As a result of these circumstances in the distant past, we now suffer the inevitable decline of old age: damage accumulates at a faster pace than it can be repaired; tissues and organs begin to malfunction; and then we die.
One thing that we often hear is that “death is just a part of life.” So often in our day and age do we hear people utter these words. However, death is far more significant and impactful than some would allege. True death is not merely a time when we cease to exist; it is an entombment, a mindset in which we are dead to this world. Throughout our lives, it is true that we can all be dead in one way or another, but it does not have to be that way. When we have our eyes opened to what death actually is, it is far easier to grasp what the true meaning of life is, and to embrace it. Often, we will come across individuals who are enveloped in death and others who are immersed in true life. The shadow of death and entombment lies upon some, encompassing