1.1 General background
The definition for “tumor” has undergone several changes largely due to scientific advancement in our understanding of cancer and the ability to differentiate one form from another. Tumor originally applied to the swelling caused by inflammation, but the non-neoplastic usage of tumor has almost vanished; thus, the term is now equated with neoplasm, and sometimes interchangeably used with the term cancer. Currently, a tumor is generally defines as an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissues and persists in the same excessive manner after cessation of the stimuli which evoked the change [1]. Over the past 5 decades, cancer research has received tremendous attention from the global scientific community with frantic efforts to answer some fundamental questions about the very nature of cancer; how different is one cancer from the other?; how do cancer evade the host’s defense surveillance and at precisely what point?; how do cancer metastasize coupled with their seemingly preference for
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some specific secondary sites?; how can cancer cells be selectively eliminated with minimal or no harm to normal cells/ tissues?, etc. Several successes have been chalked up though, with more and more specific cancer antigens/ markers for diagnosis being identified [2] and improved therapy for certain cancers with corresponding enhanced quality of life for survivors. These achievements give the hope that with intensified, integrated, collaborative and rigorous basic science and translational research, the currently unanswered questions are likely to be answered. 1.1.2 Global Cancer Burden In spite of the strives in cancer research for almost a century, the global burden of the disease remains high and keep rising. According to GLOBOCAN 2012 report, an estimated 14.1 million new cancer cases and 8.2 million cancer-related mortality occurred in 2012, compared with 12.7 million and 7.6 million, respectively, in 2008. These events are projected to increase to 19.3 million new cancer cases per year by 2025, due to growth and ageing of the global population [4, 5]. The significantly emerging rise in human immunodefficiency syndrome (AIDS)- associated and non-AIDS-defining cancers add to this global challenge [Deeken et al, 2012]. Prevalence estimates for 2012 revealed that there were approximately 33 million people alive who were above the age of 15 years who had had a cancer diagnosed in the previous five years [6]. The most commonly diagnosed cancers worldwide were those of the lung (1.8 million, 13.0% of the total), breast (1.7 million, 11.9%), and colorectum (1.4 million, 9.7%). The most common causes of cancer death were cancers of the lung (1.6 million, 19.4% of the total), liver (0.8 million, 9.1%), and stomach (0.7 million, 8.8%). 1.1.4 Host’s Tumor and Antitumor Immune Machinery The basic mechanisms of cellular division and DNA replication are fundamentally prone to errors that may undermine the integrity of the genome of a cell, and renders it tumorigenic or transformed.
As such, healthy cells undergoing replication employ several intrinsic tumor-suppressor mechanisms including apoptosis, senescence, necrosis, autophagy, and mitotic catastrophe to control the transformation process and/ or eliminate such transformed cells [11]. Notwithstanding, some of the transformed cells acquire mutations that enable them to evade these intrinsic cell antitumor protocols [9]. In an immunocompetent host, however, the immune system serves as a potent extrinsic antitumor machinery. The immune system is capable to completely eliminate and/ or keep in a dormant state (equilibrium) nascent transformed cells that have evaded the intrinsic control measures during cellular development [11,
12]. 1.2 Problem Statement The 20th century has witnessed an alarming rate of cancer incidence worldwide. Much of these have been attributed to the ever changing lifestyle and environment of man. Although several achievements have been made in cancer diagnosis, treatment and prevention, the old questions of how do people develop cancer? Is cancer development a logical process? When is the host’s inherent defense mechanisms and surveillance subverted? How best do we intervene to prevent cancer development? and many fundamental questions are still under rigorous scientific investigations and remain to be comprehensively resolved. Several researches seek to address these issues using different models and techniques in a bid to provide satisfactory answers to these questions. The roles of the immune system in tumor initiation, promotion, metastasis as well as tumor arrest/ elimination have also received much attention in recent years and comprehensively reviewed [11, 39]. The trend of current data seem to point to the immune system as a very critical player at each stage of cancer development and that it can act to facilitate or hinder the transition from one state to the other during cancer initiation and progression. More importantly, there is evidence pointing to the immune system inducing a form of cell death, an immunological cell death (ICD), during chemotherapy and/ or radiotherapy [39]. Surprisingly, this phenomenon remained in the dark and largely unexplored for a long time because cell death modality was generally considered immunologically silent [40]. In addition, because the United States National Cancer Institute guidelines for anti-cancer drug screening required that human tumors be xenotransplanted into immunocompromised mice, the role of the immune system during therapy was systematically neglected [41]. Nude mice models are widely used to investigate several of the developmental stages of cancer hence the likelihood that significant, but subtle, influence of an intact immune system on primary tumor initiation and progression still remains elusive, and this needs to be investigated in vivo in immunocompetent hosts. 1.4 Research Hypothesis This study hypothesizes that in addition to the genetic and molecular aberrant characteristics of transformed cells (quality), the initial number/ density of transformed (quantity), as a physical or biophysical factor, may be critical for the establishment of clinically overt tumors, and that this factor could modulate the host’s immune and molecular responses to either arrest or promote tumor progression in an immunocompetent host. 1.5 Research Objectives This research seeks to use a murine syngeneic melanoma model to investigate in vivo the significance of and influence of cancer cell numbers (physical factor) on some molecular and immunological factors essential for the arrest or establishment and progression of primary overt tumors in immunocompetent hosts. The specific focuses are to: (a). Determine the minimum number of melanoma cells, thus a minimum threshold (MT), critical to successfully establish primary overt tumors in immunocompetent syngeneic hosts. (b). Determine both the early and late systemic and local molecular and immune responses during the tumor establishment or arrest process. (d). Evaluate and propose systemic immunological signature of diagnostic and/ or prognostic significance.
In the story “The Approximate Size of My Favorite Tumor,” by Sherman Alexie, Jimmy uses humor to cope with tragedies in his life, such as his mother-in- law passing away, harassment by the police, and his wife Norma leaving him. Humor is something that is not only used when there is a tragedy event; it is also used in at joyful events for example, at a wedding giving the best man speech. Jimmy uses humor to fulfill the gap in his life that was created by the unfortunate event of him having a tumor. Jimmy is very optimist person, who looks at life as glass half full instead glass half empty by having humor in everything. Humor is something that comes naturally to some people not everyone has this ability; having humor in life can help a person deal with unfortunate events, if the humor is tasteful and used efficiently. Humor is a great asset in a person life; it helps a person to establish a bond with friends and family, also it’s a great tool to motivate a person to face their challenges and keep their head up in the hard times.
Laughter is often said to reduce stress and produce pain reliving hormones. It is the ‘fountain of youth’, the secret ingredient to longevity. A person who laughs all the time is, more often than not, healthier and happier than a person who rarely laughs at all. Laughter is known as a natural form of medicine. However, like many other things, some people take the laughter and the jokes too far. This is the case in the story, “The Approximate Size of My Favorite Tumor,” by Sherman Alexie.
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.
..., 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?").
I have chosen to write about the constellation Cancer (The Crab). I chose Cancer because it is one of only a handful of constellations that I am actually able to identify in the night sky. Cancer is one of the twelve Zodiac constellations; people whose birthdays fall between June 21st and July 22nd have Cancer as their sign. Cancer is the Latin word for crab, and despite the fact that the constellation looks more like a lobster then a crab, it is still referred to as a crab. The constellation is visible from the northern hemisphere from late winter to early spring.
To understand how immunotherapy works it helps to know how your immune system works to fight against cancer. Cancer cells have substances on their surfaces called tumor antigens that raise an alarm in the immune system that says cancer is present. Antigen presenting cells ( APCs) roam the body seeking out and ingesting tumor antigens. The APCs then activate B cells and T cells. The B cells differentiate into plasma cells and secrete antibodies that bind to the tumor cell and mark them for elimination ( a humoral immune response). When T cells are activated they proliferate and undergo expansion, seek out, and destroy cells bearing the specific tumor antigens ( a cellular immune response). Sometimes your immune response does not destroy all of the cancer cells and this r...
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,...
According to “Medical News Today” cancer is a disease that is caused by an over growth of anomalous cells on one or more lungs. Cells often go up the air pipes which can cause difficulty to breath. Due to the over production of cells the tissue cells often begin to over produce; which results in tumors. There are two types of tumors: malignant and benign. Malignant tumors are the more dangerous of the two due to its invasive nature; which makes it cancerous. While benign is not invasive in other words non-cancerous. This is why cancer spreads to multiple areas and can be sometimes very difficult to fight. Cancer cells are abnormal not only because of their evasive nature, but also because of its irregular life cycle. Rather than expire like a regular cell, they continuously grow and duplicate which causes the disease to spread. This makes cell abnormal in shape and other qualities; known as a sickle cell. Due to the large growth and reproduction rate of the cells this makes the spreading of the cancer more rapid. Each cancer has specific symptom, for lung cancer the sympto...
Healthy cells grow and divide in a way to keep your body functioning properly. But when a cell is damaged and becomes cancerous, cells continue to divide, even when new cells aren't...
There are two types of tumors, benign tumors and malignant tumors. Benign tumors are not cancerous. These types of tumors can usually be removed and do not come back in most cases. Benign tumors do not spread to other parts of the body and the cells do not invade other tissues. Unlike b...
When a cell in our body has become infected or has become cancerous it’s surface changes. This is how the immune system can tell good cells from bad ones (the markings on the surface.) Once a bad cell has been recognized our bodies sends cells to destroy the damaged cell and prevent the spread of whatever caused the damage in the first place. The next step our body takes is to have the affected cells start to produce interferons and other helpful substances. These help to fight off unwanted organisms, and also to warn other cells of the invaders and prepare them to resist them therefore preventing the spread of disease.
Different characteristics of tumours may point to malignancy in some organs but in other locations may indicate a benign growth. For example, Thieme indicates that “an echopenic halo suggests metastasis in the liver but suggests a...
Cancer develops when cells in a part of the body begin to grow out of
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.
Our immune system protects our bodies from pathogens like bacteria and viruses very efficiently in most cases. One big question that has come up is why does the immune system not respond to cancerous cells in the same way? Why are cancer cells not eradicated like other dangerous foreign cells? This seems very strange, especially since the immune system has cells that are specific to destroying cancer cells and virus-infected cells, called natural killer cells. To begin to answer this question it is useful to examine cancer cells and their interactions with the immune system in more detail.