On page 182, Carroll discusses the conditions necessary for tumors: chance mutations, selection, and time. Explain how these three main components of evolution apply to tumor formation and growth. Also, explain how tumors spread through the body and proliferate in other body tissue. What are some specific examples of mutations that cause tumors? Discuss the Philadelphia chromosome and its association with chronic myelogenous leukemia as well as other examples.
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A chance mutation in the DNA that controls how cells multiply and how cells interact with one another can cause selective advantages that allow them to proliferate unchecked. Additional mutations occur that may give cells the ability to leave their original location and invade other parts of the body, called metastasis (Carroll 183). Chance mutations are selected for during natural selection and they proliferate over time due to unregulated cell growth, causing tumors and cancers. The Philadelphia chromosome associated with chronic myelogenous leukemia (CML) is the mutated chromosome where breakage and attachment of chromosomes occurs, causing different genes to fuse together. This fusion of different genes disrupts the normal control of a potent regulatory protein called the ABL kinase. This even causes these cells to become cancerous. Protein kinases, an enzyme that transfers phosphate groups from ATP to a protein, is important in a widespread cellular mechanism for regulating protein activity by phosphorylating proteins. Most proteins kinases phosphorylate their substrates on either serine or threonine. These serine/threonine kinases are widely involved in signaling pathways in animals, plants, and fungi. Protein kinases form phosphorylation cascades, each cascade of protein phosphorylation bringing a conformational change. Each shape change results from the interaction of the charged phosphate groups with charged or polar amino acids. Among these protein kinases are those that regulate cell reproduction, and abnormal activity of such a kinase frequently causes abnormal cell growth, as is the Philadelphia chromosome mutation. Scientists have found Gleevec or Imatinib effective in fighting CML tumors by latching on to a particular part of the ABL kinase protein, inhibiting its activity. The mutation of threonine in the ABL protein to isoleucine causes resistance of CML patients to Gleevec. Currently scientists have found that BMS-354825 is another ABL kinase inhibitor that is active against fourteen out of fifteen different Gleevec-resistant kinases.
ReplyDeleteAnother example of mutations causing cancer is lung cancer. Lung cancer is strongly associated with carcinogenic chemicals from cigarette smoke. These carcinogenic chemicals such as nitrosamines and polycyclic aromatic hydrocarbon causes mutations in the K-RAS gene. These K-RAS gene belongs to the RAS family of genes that mediate cell growth and development. When these genes carry mutations, uncontrolled cell growth can occur, leading to cancer. in cigarette smoke causes mutations – in a gene known as K-RAS – that are commonly associated with a number of human cancers, a new US study has found. More than 30 percent of lung cancers, 90 per cent of pancreatic cancers and 50 per cent of colon cancers are associated with mutations at a specific site in the gene K-RAS. A latest study led by Dr Eric Moon-shong Tang introduced the carcinogen benzo(a)pyrene diol expoxide, a known cancer-causing chemical in cigarette smoke, to normal human lung epithelial cells and fibroblasts. The carcinogen preferentially bound to the K-RAS gene at codon 12, an area especially vulnerable to mutation. Researchers discovered that this site was not very well able to repair itself, resulting in proliferation of unregulated tumors.
http://no-smoking.org/oct02/10-17-02-1.html
http://en.wikipedia.org/wiki/Cancer#Mutation:_chemical_carcinogens
A tumor is the name of a lesion, mass, or swelling that is formed by an abnormal growth of cells or neoplastic cells. A tumor can be either benign (non-cancerous) or malignant (cancerous).
ReplyDeleteBrain tumors are caused by the cells loss of its ability differentiate and control/regulate its growth and function. Although no one knows what exactly causes tumors (such as a brain tumor) it is clear that people who are exposed to certain risk factors have a higher chance that they will have a tumor. Some uncontrolled risk factors that increase your chance at a specific type of tumor, a brain tumor, include: being male, race (4:1 chance of getting a tumor to not getting a tumor, white: non-white), age, and family history; however, radiation exposure to chemicals such as formaldehyde, vinyl chloride, and acrylonitrile are controllable factors.
The reason that these controllable risk factors increase your chances of developing a tumor is because they increase the chances for mutation. Studies by Lloyd Morgan have shown that exposure from X-rays, Atomic bombs, and any radioactive substances are energy sufficient to break molecular bonds (DNA), which creates free ‘radicals’. These ‘radicals’ cause further DNA damage, which is thought to cause cancer. However, these mutations aren’t necessarily caused by environmental factors. Anything which replicates will suffer from mutations, and unless error correction takes place, the errors will continue to replicate. The chance that a mutation survives apoptosis, aid from helper molecules (DNA polymerases, helper T (immune)) decreases with the risk factors listed above, but the failure of these molecules indefinitely causes tumor growths and or cancer.
The mutations which cause cancer often are ‘self-amplifying’, exponentially increasing their rate over time. This scenario is an undesirable example of survival of the fittest, where evolution of the body’s design works against itself.
http://en.wikipedia.org/wiki/Cancer#Causes
http://www.medicinenet.com/brain_tumor/page4.htm
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ReplyDeleteTumors develop as a result of uncontrolled cell division, which is controlled in the body by a molecule called cyclin. In the cell cycle, cyclin is the protein that binds to the kinase (the enzyme that drives the cell cycle) in order to activate it. The involvement of several Cdk proteins and cyclins are necessary to move past the the G1 checkpoint, from where the cell will normally complete the division. However, when a cell undergoes transormation (the process that converts a normal cell to a cancerous cell), the cell no longer appears to need the growth factors, so they grow continously. In people with hepatocellular carcinoma, the immune system produces antibodies in response to the detection of cyclin B1. After detection, it invokes such a response because in cancerous cells, the cyclin behaves in a manner similar to an antigen would. It is known that cyclin B1 in fact causes this behavior of the immune system because in a test, the researchers studying cyclin and its function as a tumor antigen were not able to find any antibodies that were created in response to cyclin B1 in healthy subjects. After recognition, the immune system synthesiszed various lymphocytes to fight the tumor. In most cases, the immune system is able to fight off the cancerous cells within two years. However, if the immune system is not able to overcome the threat of the cells, the cells spread through a process called metastasis.
ReplyDeleteAs for the Philadelphia chromosome, it is a chromosomal abnormality. While it is normally associated with chronic myelogenous leukemia, it can also be linked to acute lymphoblastic leukemia (ALL), as well as acute myelogenous leukemia (AML).
According to the American Society of Hematology (ASH), more than twenty five percent of all ALL cases include Philadelphia chromosome positive (Ph+) ALL. ALL is defined as the overproduction of lymphocytes by the bone marrow, as it results in the decrease of available healthy white blood cells, red blood cells, and platelets. In its study of the clinical features of Ph+ ALL, the ASH noted that the chance at acquiring this disease increases along with age. Unfortunately, the chance at long term survival after the application of chemotherapy is at a measly 10%. For that reason, allogeneic stem cell transplantation is considered to be the top choice for treatment of adult Ph+ ALL. An allogeneic stem cell transplantation is when a person receives blood forming stem cells from a genetically similar individual (such as a brother or sister). The use of imatinib has also been tested, and the ASH recorded synergy between synergy and chemotherapy, suggesting that if there is a way to use the two in conjunction with each other efficiently in the future, there may be a greater chance for survival.
http://asheducationbook.hematologylibrary.org/cgi/content/full/2005/1/118
http://www.cancer.gov/cancertopics/pdq/treatment/adultALL/Patient
http://en.wikipedia.org/wiki/Imatinib
http://en.wikipedia.org/wiki/Philadelphia_chromosome
http://en.wikipedia.org/wiki/Acute_lymphoblastic_leukemia
http://cancerres.aacrjournals.org/cgi/content/full/66/1/6?ck=nck
http://en.wikipedia.org/wiki/Cancer