Treatments for Hormone Sensitive Breast Cancer

Treatments for Hormone Sensitive Breast Cancer Rae Broz Oestrogen inhibiting Tamoxifen Citrate; an Antineoplastic Agent used to Treat Hormone Sensitive Breast Cancer The Hormone Oestrogen (E) fuels female breast growth production at puberty. Within the breast of mature women, there are milk ducts called lobes which branch out to form lobules or acinus. Together, these are called the terminal lobular unit (TDLU) (Bullock, 2013, pp. 917-918). Due to the various hormonal cycles that happen during a woman’s lifetime including, but not limited to child birth, Oestrogen and Progesterone levels are continuously fluctuating causing constant remodelling of the breast tissue. For example, menstruation causes the breast tissue to become increasingly vascular and encourages acinar tissue and ductal growth. Ancinar tissue converts to secretory glands through the release of progesterone at the luteal stage of the menstrual cycle. At this stage the terminal ducts are also dilated. (Craft. J, 2011, p. 951) Mitotic stem cell division is increased within the TDLU during these stages leading to the development and renewal of the epithelial lining, increasing the chance of cell mutations in the TDLU an area where the majority of breast cancer (BC) occur (Craft. J, 2011, p. 983). Studies show a positive sign of hormone sensitive BC is the increased amount of Oestrogen receptors (ERÃŽ ±). The more ErÃŽ ±s in the affected cells, the greater affinity with E, therefore cell reproduction rises, leading to faster BC cell replication (Patani, 2014). A benign tumor within the breast will remain localized and closely resembles normal epithelium cells within the tissue. Growth is at a slow rate within the TDLU, unlike a malignant (cancerous) tumor. The malignant tumor grows rapidly differentiating from the normal epithelial cell. It invades other tissue space and nearby blood and lymph vessels explaining why BCs easily spread into the lymphatic system and other areas of the reproductive system. Risk factors affecting hormone sensitive breast cancer development in women are Post-menopausal obesity and the woman’s age at the birth of her first child, as connections between older mothers and obese post-menopausal women to ERÃŽ ± positive BC have been discovered (Yager Davidson, 2006). Tamoxifen Citrate (Trans-1-[4- (2-dimethylaminoethoxy) phenyl] 1, 2 -diphenyl-1 –butene) is a non-steroidal drug and an antineoplastic agent called a selective estrogen receptor modulator (SERM) (Marrero-Alonso et al., 2013). It is recommended as part of the treatment of hormone sensitive breast cancer due to its affinity with ERÃŽ ± acting as an antagonist to E, slowing cell division within the breast consequently stopping the progression of the BC (Bryant, 2011, p. 822). Tamoxifen is given orally, absorbed in the gastro intestinal tract and metabolized in the liver by the enzymes CYP-450, 2D6 and 2C9. (Mandlekar, 2000 #20) Metabolites, produced are the ERÃŽ ± receptor binding 4-hydroxytamoxifen (OHT) and N-desmethyltamoxifen (DMT). Both have anti Oestrogen affects very close to their parent drug and cause apoptosis of BC cells. After dosing, various serum levels of Tamoxifen and metabolites were found within the lungs, liver ovaries and the endometrium and corpes luteum of the uterus, also in metastases within the brain and pancreas (Health Communication, 2004). Levels peak in about 3-6hours post a 10mg dose and reach a steady state around 4 weeks of therapy. They bind to albumin and are excreted mainly in the faeces so have a long half-life 5-7 days for Tamoxifen and 10-14 days for DMT (Health Communication, 2004). Due to the metabolism of Tamoxifen and its metabolites, there is a risk of serum accumulation in prolonged treatment and or patients with poor hepatic function dosing regimens major need intermittent adjustment according to serum level findings. (Health Communication, 2004). Phenytoin lowers Tamoxifen metabolism and should therefore not be used concurrently with Tamoxifen for extended periods of time unless a therapeutic drug (Endoxifen) monitoring strategy is utilized as Tamoxifen will lose effectiveness. (Gryn, Teft, Kim, 2014). It has been found that Tamoxifen treatment in postmenopausal women is beneficial in reducing calcium loss by reducing apoptosis of osteoclasts thus sustaining bone density (Nakamura et al., 2007). This unfortunately is not the case in premenopausal women; in these cases osteoporosis is often increased with the use of Tamoxifen, dependent on whether chemotherapy had caused amenorrhea or not (Vehmanen, Elomaa, Blomqvist, Saarto, 2006). Tamoxifen use has been linked to increased episodes of deep vein thrombosis (VTE) in women using the drug in breast cancer prevention treatment (Decensi et al., 2005). Finally patients receiving Tamoxifen treatment for breast cancer long term ( > five years) are at greater risk of mortality from endometrial cancer than those who did not receive Tamoxifen (Jones et al., 2012). Word count: 687 Reflection I hope I have created a better assignment this time round. I found the tutorial held on the 29/4/2014 very helpful as was the typed feedback sheet. I printed the latter out and sat it beside me while I typed out my assignment, along with the rubric and learning outcomes from the subject outline, referring to them often. The handwritten feedback was a little harder to decipher but I managed ok. My suggestion would be to type in an alternate colour e.g. Red for the feedback remarks on the actual assignment. I have learnt a lot from this assignment both about the subject and myself. I have incorporated more information into this assignment and have not included any quotes or paraphrasing from any of the texts I have used. The only similarities shown in turnitin were from my previous assignment. I have to say even with the setback I have enjoyed it. Word count: 151 References Bryant, B. a. K., K. (2011). Pharmacology for health professionals. Chatswood, NSW, Australia: Elsevier. Bullock, S. a. H., Majella. (2013). Principles of Pathophysiology. Frechs Forest, NSW, Australia: Pearson. Craft. J, G. C. a. t. A. (2011). Understanding Pathophysiology. Chatswood, NSW, Australia: Elsevier. Decensi, A., Maisonneuve, P., Rotmensz, N., Bettega, D., Costa, A., Sacchini, V., . . . Veronesi, U. (2005). Effect of tamoxifen on venous thromboembolic events in a breast cancer prevention trial. Circulation, 111(5), 650-656. doi: 10.1161/01.cir.0000154545.84124.ac Gryn, S. E., Teft, W. A., Kim, R. B. (2014). Profound reduction in the tamoxifen active metabolite endoxifen in a patient on phenytoin for epilepsy compared with a CYP2D6 genotype matched cohort. Pharmacogenetics and Genomics, Publish Ahead of Print, 10.1097/FPC.0000000000000051. Health Communication, N. (2004). MIMS Online. from Health Communication Network Jones, M., van Leeuwen, F., Hoogendoorn, W., Mourits, M., Hollema, H., van Boven, H., . . . Swerdlow, A. (2012). Endometrial cancer survival after breast cancer in relation to tamoxifen treatment: Pooled results from three countries. Breast Cancer Research, 14(3), R91. Marrero-Alonso, J., Morales, A., Garcà ­a Marrero, B., Boto, A., Marà ­n, R., Cury, D., . . . Dà ­az, M. (2013). Unique SERM-like properties of the novel fluorescent tamoxifen derivative FLTX1. European Journal of Pharmaceutics and Biopharmaceutics, 85(3, Part B), 898-910. doi: http://dx.doi.org/10.1016/j.ejpb.2013.04.024 Nakamura, T., Imai, Y., Matsumoto, T., Sato, S., Takeuchi, K., Igarashi, K., . . . Kato, S. (2007). Estrogen prevents bone loss via estrogen receptor alpha and induction of Fas ligand in osteoclasts. Cell, 130(5), 811-823. doi: 10.1016/j.cell.2007.07.025 Patani, N. a. M. L. A. (2014). Understanding response and resistance to oestrogen deprivation. Molecular and Cellular Endocrinology, Volume 382(1), 683-894. Vehmanen, L., Elomaa, I., Blomqvist, C., Saarto, T. (2006). Tamoxifen treatment after adjuvant chemotherapy has opposite effects on bone mineral density in premenopausal patients depending on menstrual status. J Clin Oncol, 24(4), 675-680. doi: 10.1200/jco.2005.02.3515 Yager, J. D., Davidson, N. E. (2006). Estrogen Carcinogenesis in Breast Cancer. New England Journal of Medicine, 354(3), 270-282. doi: doi:10.1056/NEJMra050776

Does Increased Carbon Dioxide Emissions Cause Global Warming? Essay

The warming of the Earth’s atmosphere is one of the most important environmental issues in the world today. The volatile climate and changes of heat in the atmosphere are connected with an increase of large amounts of greenhouse gases in the atmosphere. It is often talked about that the primary reason why the global warming situation is increasing is due to the increase of the amount of greenhouse gases present in the Earth’s atmosphere, primarily the amount of carbon dioxide emissions. The increased carbon dioxide amount in the atmosphere that causes global warming is a cause of concern for many people because of its potential dangerous effects to the Earth and the environment. However, there are opposing arguments against this claim, and they refute that it is not accurate to mainly attribute the problem of global warming to the increasing carbon dioxide emission caused by the activities of humans. Audience My audience will be the one’s opposing the claim that carbon dioxide emissions cause global warming. The one’s opposing this claim believes that global warming is natural and the greenhouse gases do not cause global warming. That is true to some extent; however, if we did not build all of the industrial plants after the Industrial Revolution, which produces all of the carbon dioxide emissions global warming would not be as bad. To many scientists global warming refers to the observation that the Earth is warming, without any indication of what might be causing the warming of the atmosphere. This definition indicates that global warming can be due to various factors, and one of these reasons includes the greenhouse effect. The greenhouse effect, meanwhile, is a warming near the surface of the Earth that results whe... ...make our planet the only planet known to be habitable. I was able to use this book to better improve my reader’s knowledge of global warming and the effects of global warming. "What is Global Warming? - National Wildlife Federation." Home - National Wildlife Federation. National Wildlife Federation, n.d. Web. 18 Nov. 2011. . This article defines global warming and talks about how it is happening now. The article also goes in depth of how global warming is caused by humans and the effects that global warming are causing. Another thing the article talks about is what we can do to solve the problem of global warming. This article helped me by explaining the reasons of global warming and also by telling me ways that the global warming issue can be fixed. Another reason the article helped was by explaining the different causes of global warming.

Short History of Myanmar

Derived from BAMAR * ‘Burma’ – spoken form * ‘Myanmar’ – literary form 2. BASIC FACTS * Official Name – Republic of the Union of Myanmar * Capital – Naypyidaw * Form of Government – Unitary Presidential Constitutional Republic * President – Thein Sein * Vice-President – Nyan Thun (Navy Chief) * 2nd Vice-President – Sai Mauk Kham World Organizations – UN (1948), ASEAN (June 23, 1997) * Ethnic Group – Burmans 68%, Shan 9%, Karen 7%, Rakhine 4%, Chinese 3%, Indian 2%, Mon 2%, Others 5% * Language – Burmese (Sino-Tibetan) * Currency – Kyat (K) * Religion – Theravada Buddhism 89%, Christianity 4%, Islam 4%, Others 2%, Hinduism 1% * Foreign Rulers – Chinese, Muslims, Indians, BRITISH, Japanese * Date of Independence – (from British) January 4, 1948 *Geography – largest country in the mainland SEA Bordered on the NW by India and Bangladesh, NE by Tibet an d China, SE by Laos and Thailand, S by the Bay of Bengal and Andaman Sea * Highest point is Hkakabo Razi in Kachin / highest mountain in SEA, along the borders of Myanmar, India and China / along the foothills of the Himalayas * Lowest point is Andaman Sea/Burma Sea, southeast of Bay of Bengal * Major rivers are Irrawaddy, Thanlwin, Sittang * Climate – Hot season is from March to May, rainy season is from June to October and cold season is from November to February 3. EARLY HISTORY Pyu (1st century BC) – entered the Irrawaddy Valley / established city states * Mon (6th century BC) – southern part of Myanmar / had cultural and economic links with India > Buddhism * Mranma/Bamar/Burmans (9th century BC) – settled in the Irrawaddy basin / dominant ethnic group / started the Pagan empire 4. 1044-1077 *Founded by King Anawrahta * Flourished in the upper Irrawaddy Valley * Laid the foundation of the Burmese language and culture, the spread of Burman ethnicit y, and the growth of Theravada Buddhism in Burma and in the mainland * Fall: attacks of the Mongol empire . WARRING STATES PERIOD * Ava Kingdom (1364-1555) – Led by  Burmanized Shan kings who claimed descent from Pagan kings – Founded by  Thadominbya * Hanthawaddy Kingdom/Hanthawaddy Pegu – Dominant kingdom in southern Burma – Founded by King  Wareru 6. FORTY YEARS WAR * Military conflict between Ava and Pegu * 1st half – Ava invaded Pegu and was defeated; Ava signed a truce * 2nd half – Pegu attacked Ava to stop its expansion; Ava signed another truce and broke it * After the war, Hanthawaddy Pegu reached its golden age through profits and commercializing . TOUNGOO DYNASTY * King  Mingyinyo founded the  First Taungoo Dynasty * Tabinshwehti unified most of Burma and was crowned king of all Burma in 1544 *Burma became an important trading center with the coming of European traders * Bayinnaung succeeded the throne in 1551 and reigne d for 30 years, launching a campaign of conquest invading several states 8. KONBAUNG DYNASTY * Last dynasty in Burma * Founded by a village-chief  Alaungpaya Reunited all of Burma, extinguished the Hanthawaddy dynasty and drove out the European powers who provided arms to Hanthawaddy * 1760-1855 – series of wars with Siam until the two countries exchanged Tenasserim (to Burma) and Lan Na (to Siam) 9. FIRST ANGLO-BURMESE WAR * King Bodawpaya – expanded westward which happened to include areas near the borders of the British India * British won – full control over Assam, Manipur, Cachar, Arakan, Jaintia, and Tenasserim * Burmese – forced to pay 1M pound sterling and sign a commercial treaty * Longest and most expensive war in British Indian history 10.SECOND ANGLO-BURMESE WAR * Commodore George Lambert – sent to Burma to resolve some minor issues regarding the Treaty of Yandabo * George Lambert blocked the port of Rangoon, seizing the King’s royal ship * Britain also wanted the teak forests in the southern parts of Burma and the port between Calcutta and Singapore * The British succeeded – annexed Pegu and renaming it Lower Burma 11. THIRD ANGLO-BURMESE WAR King Mindon tried to modernize the Burmese state and economy to resist British encroachments * The British claimed that Mindon’s son, Thibaw Min, was a tyrant intending to side with the French * The British won for the last time, making Burma a province of the British Raj 12. BRITISH RULE * Capital at Rangoon *Traditional Burmese society was changed by the end of monarchy * Demand for Burmese rice grew and lands were opened for cultivation * Farmers were forced to borrow money from Indian moneylenders called ‘chettiars’ * Burmese economy grew but all the power and wealth remained in the British firms 3. NATIONALIST MOVEMENT * Dominated by Ethnic Burmese * Strongly anti-Chinese and anti-Indians * Domination of Myanmar economy by foreign cap ital stimulated the dev’t of socialist ideology * The stress on Buddhism as being the core of cultural, religious and personal identity alienated the non-Burmese 14. JAPANESE RULE * Nominally declared Burma independent as the ‘State of Burma’ on August 1, 1943 * Asia for the Asians Co-Prosperity Sphere (self-sufficient bloc of Asian nations led by the Japanese and free of Western powers) * 1944: Aung San established the Anti-Fascist People’s Freedom League *1945: British troops had regained control 15. INDEPENDENCE * Britain – move Myanmar towards full self-governance (under the British Commonwealth) * January 1947: Aung San led the AFPFL to London – election for a constitution * Won the elections, but Aung San was assassinated U Nu led Myanmar to independence from the British on January 4, 1948 * Union of Burma – federal state composed of large Burmese are and four upland states * General Ne Win – led a military coup to overthr ow U Nu’s elected government * Many people supported the coup = end to the corruption, instability, inflation and social unrest * Military-based political party: Burma Socialist Program Party *1974: new Constitution – Socialist Republic of the Union Of Burma * 1987: UN – Myanmar as the least developed nation, one of the world’s 10 poorest countries * Two economies: the legal state-controlled economy & the black market economy * State Law and Order Restoration Council – General Saw Maung * Aung San Suu Kyi, daughter of Aung San, won the elections but was placed under house arrest * March 27, 2006 – the capital was officially named  Naypyidaw Myodaw (Royal City of the Seat of Kings) * 2005 – capital from  Yangon to  Naypyidaw * May 10, 2008 – from the  Union of Myanmar  to the  Republic of the Union of Myanmar

How American Manifest Destiny Effects Modern Foreign Policy

The term Manifest Destiny, which American writer John L. OSullivan coined in 1845, describes what most 19th-Century Americans believed was their God-given mission to expand westward, occupy a continental nation, and extend U.S. constitutional government to unenlightened peoples. While the term sounds like it is strictly historical, it also more subtly applies to the tendency of U.S. foreign policy to push democratic nation-building around the globe. Historical Background OSullivan first used the term to support the expansionist agenda of President James K. Polk, who took office in March 1845. Polk ran on only one platform -- westward expansion. He wanted to officially claim the southern part of Oregon Territory; annex the whole of the American Southwest from Mexico; and annex Texas. (Texas had declared independence from Mexico in 1836, but Mexico did not acknowledge it. Since then, Texas had survived -- barely -- as an independent nation; only U.S. congressional arguments over slavery had prevented it from becoming a state.) Polks policies would undoubtedly cause war with Mexico. OSullivans Manifest Destiny thesis helped drum up support for that war. Basic Elements of Manifest Destiny Historian Albert K. Weinberg, in his 1935 book Manifest Destiny first codified the elements of American Manifest Destiny. While others have debated and reinterpreted those elements, they remain a good foundation for explaining the idea. They include: Security: Simply, the first generations of Americans saw their unique position on the eastern edge of a new continent as an opportunity to create a nation without of the Balkanization of European countries. That is, they wanted a continental-sized nation, not many small nations on a continent. That obviously would give the United States few borders to worry about and enable it to conduct a cohesive foreign policy.Virtuous Government: Americans saw their Constitution as the ultimate, virtuous expression of enlightened governmental thought. Using the writings of Thomas Hobbes, John Locke, and others, Americans had created a new government without the hobbles of European monarchies -- one based on the will of the governed, not the government.National Mission/Divine Ordination: Americans believed that God, by geographically separating the U.S. from Europe, had given them the chance to create the ultimate government. It stood to reason, then, that He also wanted them to spread that govern ment to unenlightened people. Immediately, that applied to Native Americans. Modern Foreign Policy Implications The term Manifest Destiny fell out of use after the U.S. Civil War, in part to racist overtones of the concept, but it returned again in the 1890s to justify American intervention in the Cuban rebellion against Spain. That intervention resulted in the Spanish-American War, 1898. That war added more modern implications to the concept of Manifest Destiny. While the U.S. did not fight the war for true expansion, it did fight it to develop a rudimentary empire. After quickly beating Spain, the U.S. found itself in control of both Cuba and the Philippines. American officials, including President William McKinley, were hesitant to let nationals in either place run their own affairs, for fear that they would fail and allow other foreign nations to step into a power vacuum. Simply, many Americans believed that they need to take Manifest Destiny beyond American shores, not for land acquisition but to spread American democracy. The arrogance in that belief was racist itself. Wilson and Democracy Woodrow Wilson, president from 1913-1921, became a leading practitioner of modern Manifest Destiny. Wanting to rid Mexico of its dictator president Victoriano Huerta in 1914, Wilson commented that he would teach them to elect good men. His comment was fraught with the notion that only Americans could provide such governmental education, which was a hallmark of Manifest Destiny. Wilson ordered the U.S. Navy to conduct sabre-rattling exercises along the Mexican coastline, which in turn resulted in a minor battle in the town of Veracruz. In 1917, trying to justify Americas entry into World War I, Wilson remarked that the U.S. would make the world safe for democracy. Few statements have so clearly typified the modern implications of Manifest Destiny. The Bush Era It would be hard to classify American involvement in World War II as an extension of Manifest Destiny. You could make a greater case for its policies during the Cold War. The policies of George W. Bush toward Iraq, however, fit modern Manifest Destiny almost exactly. Bush, who said in a 2000 debate against Al Gore that he had no interest in nation-building, proceeded to do exactly that in Iraq. When Bush began the war in March 2003, his overt reason was to find weapons of mass destruction. In reality, he was bent on deposing Iraqi dictator Saddam Hussein and installing in his place a system of American democracy. The ensuing insurrection against American occupiers proved how difficult it would be for the United States to continue pushing its brand of Manifest Destiny.