Colon Cancer - Research Paper Example

Colon Cancer Colon cancer refers to the cancer of large intestine – the lower part of digestive system. Colon cancer is the fourth mostprevailing cancer in the US population after skin, prostate/breast, and lungs. Over 90% of the people in the US diagnosed with colon cancers have age 50 or above. Somehow cancer condition has a lot to do with disruption in the homeostasis of the body system. Nucleic acid damage, excessive growth factor secretion, lipid peroxidation, unnecessary immune activation or subversions are result of chronic inflammation disrupting internal homeostasis. Exogenous factors and endogenous factors both may trigger an inflammatory response and lead to tumor development. Researchers assert that inflammation and homeostasis-linked genes play a critical role in causing colon cancer. Modern eating habits such as diets rich in sodium, refined sugar, or omega-6 fatty acids as exogenous factors can greatly change human physiology and create large imbalances at molecular and cellular levels leading to inflammatory conditions that may subsequently convert into colon cancer. A high level of low-density lipoprotein (LDL) consumption could create an inflammatory effect and alter cells response to immediate environment. Colonoscopy helps detect early state of colon cancer and set treatment regime that could be either local or systemic depending upon the Stage of cancer. The disruption of sodium homeostasis is the most critical components of cellular response while employing a drug therapy to treat cancer and chemotherapy achieves precisely this objective causing shrinkage of tumor. Introduction Colon cancer refers to the cancer of large intestine – the lower part of digestive system. It is estimated that around 143,000 people are diagnosed with colorectal cancer in 2013 in the US alone. Colon cancer is the fourth most prevailing cancer in the US population after skin, prostate/breast, and lungs. Several risk factors are associated with colon cancers and age is one of them. Usually, over 90% of people in the US diagnosed with colon cancers have age 50 or above (National Cancer Institute, 2014). Usual, symptoms of colon cancer are rectal bleeding, fatigue, weight loss that cannot be explained, constipation, and abdominal discomforts such as gas, and cramps. In early stages, no symptoms are experienced; moreover, symptoms may vary depending on its location in large intestine. Cells in the human body continue to grow and divide to create new cells for needs of the body; however, at times, this process goes abnormal, wherein new cells continue to form without old cells disintegrating. These extra cells turn into a lump; growths in inner lining of colon are known as polyps. Only some polyps cause cancer and finding and removing them reduces the risk of colon cancer. Early diagnosis can mostly cure colon cancer. Some people are genetically prone to colon cancer and some develop it due to internal disturbances disrupting homeostasis at cellular levels. Homeostasis of the Body System Several parts of the human body such as liver, kidneys, hypothalamus in brain, endocrine system, the autonomic nervous system perform several highly complex tasks to maintain favorable internal environment that keeps body healthy and fit; however, over time, due to modernization, changed eating and living conditions, and sedentary lifestyle homeostasis of the body system gets disrupted resulting into the development of cancer conditions in humans; colon cancer is also a result of such molecular imbalances along the intestinal tract. The fact is that the modern lifestyle is greatly responsible for a change in human physiology; it is appropriate to state that it has threatened normal physiological functioning. Imbalances on cellular and molecular levels are responsible to cause inflammation to the body tissues making a person susceptible to conditions such as colon cancer. Nucleic acid damage, excessive growth factor secretion, lipid peroxidation, unnecessary immune activation or subversions are the result of chronic inflammation disrupting internal homeostasis. Usually, inflammation is controlled and counteracted through regular intake of essential nutrients but the sedentary lifestyle does not provide any chance to correct homeostatic imbalance. Colon Cancer and the Homeostasis of the Body System Sokolosky and Wargovich (2012) argue, "Tissues and fluids must exist within a narrow pH range in order to function properly, pH imbalances can contribute to altered homeostasis". Acidic microenvironments support growth of cancer cells. High amount of sodium and refined sugar in the diet leads to the state of body that is full of solutes but without appropriate solvent that disturbs cellular osmotic balance leading to dehydration. That is further aggravated by lack of sufficient intake of water unable to flush toxins from the body. Poor diet leads to altered microflora composition in Gut. Thus, changed internal environment conditions disrupting homeostasis of the body leads to colon cancer. A high level of low-density lipoprotein (LDL) consumption is also responsible for an inflammatory effect on cells that alters cells response to immediate environment. Altered cell signaling is induced through inflammation causing colon cancer. It is important to note that unhealthy diet habits can develop inflammatory effects in a short duration of time (Risio, 2011). Medema and Vermeulen argue, "Under physiological conditions, intestinal homeostasis is a carefully balanced and efficient interplay between stem cells, their progeny and the microenvironment. These interactions regulate the astonishingly rapid renewal of the intestinal epithelial layer, which consequently puts us at serious risk of developing cancer." In other words, the microenvironment-derived signals play a key role in regulating stem-cell fate. Simopoulos (2002) argues that diets of primitive humans were balanced in consumption of omega-6 and omega-3 unsaturated fatty acids and profusely rich in anti-inflammatory compounds such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Currently, the average US person consumes seventeen times more omega-6 compared to omega-3. That implies that intake of pro-inflammatory molecules such as arachidonic acid has increased enormously without corresponding increase of anti-inflammatory compounds such as alpha-linolenic acid (ALA) resulting into disturbances in homeostasis leading to colon cancer. Ungerback (2012) asserts that inflammation and homeostasis-linked genes play a critical role in causing colon cancer. The Notch and the Wnt signaling pathways are important to keep the proliferative crypt cells in their proliferative and undifferentiated state and any overactive signaling via these pathways may lead to the development of neoplastic epithelial cells. It is well know that genetic changes cause abnormal Wnt signaling in colon cancer; however, medical science has not understood overactive Notch signaling responsible to causing colon tumors more clearly. Overactive Notch signaling though is found to exhibit tumor suppression in some tissues but it induces cell proliferation in the colon and supposed to be oncogenic in nature. It has been found that overactive pathways and high levels of Notch 1 gene decrease colon cancer patient survival. It has been further observed that protein levels as well as Notch2 mRNA levels tend to decrease in colon cancer cases relative to its levels at nearby normal mucosa. In colon cancer, the Notch pathway is found to be unregulated but not much of the knowledge is available on the Notch receptors to understand this behavior. The Wnt and the Notch pathways do have some sort of communication linkages but available information on their interactions along the intestinal tract is not sufficient. In colon cancer, Wnt and Notch signaling function in synergy to drive stem cell proliferation; moreover, overactivation of one of the pathways also triggers overactivation in the other causing enhanced proliferation leading to tumor formation. Screening to Controlling Colon Cancer and Treatment Regime Colonoscopy is done to screen the entire colon and it is the best procedure to detect colon cancer. If cancer is detected than more tests are needed to find how much it has spread in other areas of the body. Staging of cancer is done through MRI or CT scans of the chest, abdomen, pelvic area, and brain (Risio, 2011). Treatment will depend on the location of maligned tumor in the colon and the stage of the disease. Several options such as surgery, radiation therapy, chemotherapy, or biological therapy are available to treat the disease. Doctor can employ combination of therapies for better outcomes. Depending upon the Stage of cancer, therapies can be segregated in either local or systemic therapy. Local Therapy Radiation therapy and surgery fall in this category. Doctors remove cancerous part through surgery so that cancer does not spread further. Usually, the polypectomy (removing polyps) is performed during the most elementary stage of cancer – Stage 0. When cancer has not spread beyond the colon wall or into the lymph nodes – defined as Stage 1, surgery is employed to remove the cancerous section of colon. During Stage II cancer, along with surgery, chemotherapy or radiation therapy is administered; however, when the indications are there that cancer has passed into other tissues, radiation therapy is employed to remove any remaining cancer cells. Systemic Therapy Biological therapies and Chemotherapy are known as systemic therapies. In chemotherapy, drugs are administered in the blood stream to destroy the cancerous cells anywhere in the body. Chemotherapy is administered when cancer is diagnosed to have entered into lymph nodes at Stage III. If the doctor doubts that some cancer cells may have remained after surgery, they may incorporate radiation therapy too. Moreover, if surgery is not possible for some reasons, radiation therapy or chemotherapy may be used directly. Chemotherapy The disruption of sodium homeostasis is the most critical components of cellular response while employing a drug therapy to treat cancer. Cancer cells continue to lose sodium homeostasis as chemotherapy progresses resulting to tumor shrinkages (Schepkin et al, 2013). In chemotherapies, various drugs such as capecitabine, oxaliplatin, irinotecan, and 5-fluorouracil (5FU) are employed alone or in combination to treat Stage 3 or higher Stage colon cancers. 5FU is administered along with leucovorin also known as folinic acid to make it more effective. Drugs such as irinotecan or oxaliplatin are used when cancer has spread to the lymph nodes. Certain benefits and risks are always associated with chemotherapy. Chemotherapy reduces chance of relapse; however, it also causes some side effects too. Chemotherapy is found less effective in old age people. Chemotherapy reduces symptoms and shrinks the cancer tumor to remove it surgically (Chemotherapy for Colon Cancer, 2014). Biological Therapy Biological therapies attempt to alter the processes within the cells by using anti-cancer medicines. Many of them exist to treat colon cancer. Monocional antibodies, a kind of drugs, identify specific proteins in cancer cells and lock onto it. Since they target cancer cells, they are also known as targeted therapies. At times, cancer cells are found to have proteins known as epidermal growth factor receptors (EGFRs). They grow and divide when other growth factors get attached to the EGFR receptors. Drugs such as cetuximab or panitumumab have the tendency to lock onto the EGFR preventing their growth. Panitumumab and cetuximab can be employed when cancer has spread in other parts. Drugs are usually given in combination with chemotherapy for better results and administered intravenously. It is important to note that all colon cancers do not respond to biological therapy. Bevacizumab, another drug to act as a monocional antibody, is used to treat advanced cancers that are not controlled by chemotherapy drugs. These drugs do have some side effects. Diorrhoea, breathlessness, skin rashes, sore eyes are the common side effects in this therapy (Chemotherapy for Colon Cancer, 2014). Conclusion It is absolutely certain that cancer is a complex genetic disorder causing a series of genetic alterations in the cell. There are several diagnostic tools available and numerous treatment possibilities exist yet there is no sure-fire way to cure colon cancer cases. Drugs interfering with homeostatic-tuning pathways and anti-inflammatory drugs will remain major means to cure or wage a war against cancer. Though the understanding about genetic and environmental risk factors has increased considerably in the last couple of decades, it will still take considerable time before a surefire cure is found. Individualized treatment strategies will be possible when genome-sequencing techniques will be available in the future. Further knowledge about intestinal homeostasis-mediated genes is likely to contribute significantly in the understanding the process of colon cancer in humans and finding those who are at high risks. References Chemotherapy for Colon Cancer (2014). Early Stage Colon Cancer. macmillan.org.uk. Retrieved April 7, 2014 from http://www.macmillan.org.uk/Cancerinformation/ Cancertypes/Colonandrectum/Treatingcoloncancer/Chemotherapy/Chemotherapy.aspx Medema, J. P. & Vermeulen, L. (2011). Microenvironmental regulation of stem cells in intestinal homeostasis and cancer. Nature. http://www.nature.com/nature/journal/v474/n7351/full/nature10212.html MedicinePlus (2014). Colon Cancer. Retrieved April 7, 2014 from http://www.nlm.nih.gov/medlineplus/ency/article/000262.htm National Cancer Institute (2014). Cancer of the Colon and Rectum. Retrieved April 7, 2014 from http://www.cancer.gov/cancertopics/wyntk/colon-and-rectal Risio, M. (2011). The grand challenges in GI tract cancers. Frontiers in Oncology. Retrieved April 8, 2014 from http://journal.frontiersin.org/Journal/10.3389/fonc.2011.00046/full Schepkin, V. D., Levenson, C.W., Calixto-Bejarano, F. F., Brey, W.W., Gorkov, P. L. (2013). The Loss of Sodium Homeostasis And Apoptosis during Rodent Glioma Therapy. Retrieved April 8, 2014 from http://www.magnet.fsu.edu/library/presentations/nhmfl_presentation-4786.pdf Simopoulos A. P. (2002). The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomedicine & Pharmacotherapy. 56(8). 365–379. Sokolosky, M. L. and Wargovich, M. J. (2012). Homeostatic Imbalance and Colon Cancer: The Dynamic Epigenetic Interplay of Inflammation, Environmental Toxins, and Chemopreventive Plant Compounds. Retrieved April 8, 2014 from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3365481 Ungerback, J. (2012). Inflammation and intestinal Homeostasis-associated genes in colorectal cancer. Retrieved April 8, 2014 from http://www.diva-portal.org/smash/get/diva2:464783/FULLTEXT01.pdf%E2%80%8E Read More