Biology of Prostate Cancer

Biology of Prostate Cancer PDG The Biological basis of illness and therapeutics Cancer of the prostate Introduction Malignancies are currently responsible for more deaths in the UK than ischaemic heart disease (Cummings et al 1998). Half of these malignant deaths are from the â€Å"big four† – Lung, Bowel, Breast and Prostate (World Cancer Research Fund 1997). These cancers are almost unknown in developing countries but the incidence reverts to the UK norm within one or two generations of immigration, which argues strongly for the presence of environmental factors. If this is true then these malignancies should be theoretically preventable. Prostate cancer is the current most prevalent male cancer, accounting for about 30% of all new cases and also for about 14% of all malignant deaths (Montironi 2001). The incidence is increasing, this may, in part, be due to the increasing age of the male population. Increasing consumption of red meat and fats are associated with an increase in risk, and a diet of vegetables and salads (especially tomatoes) is associated with a lower risk. It appears that Vit E supplements significantly reduce the risk of developing the disease (Heinonen et al 1998) Pathophysiology of the disease The prostate is a walnut sized gland which is situated just below the male bladder. It is primarily responsible for producing the seminal fluid and it also produces some hormones. In malignancy, there are several different forms. The neuroendocrine form (small cell type) can occur but it is not as common as the focal neuroendocrine type. (Di SantAgnese 2000) Prostate cancer is thought to arise primarily from one or more (usually a series) of genetic mutations in the DNA. This can either be inherited or acquired. (Hague et al 1996) In the UK the majority of prostatic malignancies are thought to be mutations occurring at directly at the tumour site rather than being genetically inherited.(Bingham et al 1998) The genetic mechanisms can involve either the activation of an oncogene or the inhibition of a tumour supressor gene. The mechanism is not simple, and it is thought that about four to six stepwise mutations in the DNA are responsible for the genesis of prostate cancer. The actual mechanism of the acquired genetic mutation is thought to be when an oncogene is translocated and fused with the activity promoter of another gene, this mechanism is often found when specific tumour markers are detected in the blood (viz. PSA). A similar mechanism is implicated in the more aggressive forms of prostatic cancer where the oncogene combines (and thereby inhibits) a tumour supressor gene. Demonstration of abnormal amounts of proteins such as PSA are useful in detecting the presence of micro-metastases when the disease process is thought to be in remission. The original sequence of the DNA is thereby changed. The actual mechanism can be by translocation (as described above) or by insertions or inversions which are more usually due to errors of RNA translation. All of these mechanisms ultimately exert their effect by interfering with the proper regulatory controls of the protein manufacturing abilities of the cell One of the main pathological features of malignancy is the neovascularisation that almost universally occurs. It is thought to begin in Benign Prostatatic Hypertrophy (BPH), and progresses through the pre-malignant into the frank malignant state. (Bostwick et al 2000) This is thought to be a result of the increase in detectable levels of Vascular Endothelial Growth Factor (VEGF). The levels of VEGF are highest in the most malignant forms of the disease, and is amenable to external hormonal manipulation. The commonest sites of metastatic disease are in the bone and the liver. (Mazzucchelli et al 2000) There is considerable evidence to support the implication of oncogenes in the aetiology of this cancer. Oncogenes such as c-myc and c-erb-B of have been found, as have supressor genes such as p27(Kip1) and pp32R1/2. Oncogenes have also been implicated in the formation and regression of the metastatic form of the disease. (Lijovic et al 2000) There appears to be a genetic association with the cancer as 10% of sufferers have a family history of the disease (Selley et al 1997) Modern management of prostate cancer The management of prostate cancer is primarily dependent on the clinical staging. There are several different types of staging currently employed. The commonest is the Gleason staging (I-IV) with III being the clinically commonest presentation. Significant factors in the staging are: Neuroendocrine differentiation Angiogenesis Perineural invasion Proliferation markers Other factors also play a part including the PSA and other blood borne entities. The first two factors are arguably the most important. We have learned a great deal about the detection and treatment of prostate cancer in the recent past, but the mortality figures do not reflect the increase in our knowledge. The two overriding clinical factors are early detection (ideally in the pre-invasive state) and the identification of the other prognostic factors. Chemoprevention is a field that is gaining in momentum at the present, but it is still largely experimental. (Montironi et al 1999) The current mainstay of treatment at present is hormonal manipulation A recent paper by Armstrong (et al 2001) looks at the current role of cellular immunotherapy in the field of prostate cancer management. This is a field which also holds exciting practical prospects for tumour management. It involves giving the patient vaccines prepared from antigenically active tumour cells or activated lymphocytes. Specifically cytotoxic T-lymphocytes are used to identify and then destroy the tumour cells. They do this by being programmed to recognise a specific protein on the surface of the malignant prostate cell. Clinical trials have shown that this method of treatment is at its most effective when first line (hormonal) treatment has reduced the size of the tumour to a residual amount, which is at high risk of relapse. For reasons that are not yet fully understood, this method appears to suffer from a developing tolerance to the malignancy by the lymphocytes. This is currently the focus of intense research activity. ( Hwu et al.1999) A more recent development still is an offshoot of this type of treatment and that is the use of gene modified vaccines. This involves vaccines which contain genetically modified cells. The most effective found so far are those which work by making cells increase the production of cytokines in close proximity to the tumour cells. (Alvarez-Vallina et al 1996) This appears to increase the antigenic appeal of those cells and thereby render them more amenable to attack from the immune system. This avoids the difficulties with the side effects that were seen when cytokines were given systemically. (Gao et al 2000) Other mechanisms for gene therapy involve the ingenious use of viruses to transfer the altered DNA into the malignant cell. In prostate malignancies, their use has been disappointing because of problems with side effects, but the theory is also promising (Relph et al 2004) PSA and related proteins such as prostate specific membrane antigen (PSMA) are commonly helpful in monitoring the progress or relapse of the disease (Montie 1997) PSA is being experimentally exploited by being coupled to enzymes such as thymidine kinease. This can be placed in the body by a retrovirus and therefore infects all cells but is only activated in prostate cells. They are refered to as the Trojan Horse Vectors and appear to very successful in early trials. Proponents of the technique refer to it as performing a genetic prostatectomy. More modern techniques still involves the detection of prostate cells in the bloodstream using a reverse transcriptase and polymerase chain reaction. This is thought to be a particularly sensitive assay for the prediction of surgical failure (Olsson et al 2003) The downside to these treatments involving genes, is that the mechanisms of protein synthesis and regulation are unimaginably complex. Attempts to cure one malignancy may unwittingly cause another by a process called Insertional mutagenesis, where the desired effect in one cell is hindered by an unwanted malignant change in another. (Armstrong 2001) Conclusions The advances in our understanding of the molecular basis of prostate cancer have been spectacular in the last decade. Interventional genetics now are on the brink of offering a real chance of survival to patients with resistant disease. Patients with widespread disease are usually desperate to try any form of novel treatment. Although the theory and understanding of many of the oncogenic processes are already well advanced, it is vital not to give a patient false hope of cure. (Bingham et al 1998) To this end the Dept. of Health has set up a new governing body in the shape of he Genetic Therapy Advisory Committee (GTAC) to consider and oversee all new and proposed treatments. The major hurdles that remain in this field are how to effect the stable and specific transfer of genes into tumour cells, how to ensure the safety of both patients and staff and to define exactly where the best place is for gene therapy alongside the mainstream treatments today. (Montironi 2001) References Alvarez-Vallina L, Hawkins RE.2002 Antigen-specific targeting of CD28-mediated T cell co-stimulation using chimeric single-chain antibody variable fragment-CD28 receptors. Eur J Immunol; 2002 26: 2304-2309 Armstrong, David Eaton, and Joanne C Ewing 2001 Science, medicine, and the future: Cellular immunotherapy for cancer BMJ, Dec 2001; 323: 1289 1293. Bingham SA, Atkinson C, Liggins J, Bluck L, Coward A. 1998 Phytoestrogens: where are we now? Br J Nutr 1998; 79: 393-406 Bostwick DG, Grignon D, Hammond EH, Amin MB, Cohen M, Crawford D, et al. 1999 Predictive factors in prostate cancer. College of American Pathologists Consensus Statements 1999. Arch Pathol Lab Med 2000; 124: 996-1000. Cummings JH and Sheila A Bingham 1998 Fortnightly review: Diet and the prevention of cancer BMJ, Dec 1998; 317: 1636 1640. Di SantAgnese PA. 2000 Divergent neuroendocrine differentiation in prostatic carcinoma. Sem Diagn Pathol 2000; 17: 149-161 Gao L, Bellantuono I, Elsasser A, Marley SB, Gordon MY, Goldman JM, et al. 2000 Selective elimination of leukemic CD34(+) progenitor cells by cytotoxic T lymphocytes specific for WT1. Blood 2000; 95: 2198-2203 Hague A, Butt AJ, Paraskeva C. 1996 The role of butyrate in human colonic epithelial cells: an energy source or inducer of differentiation and apoptosis? Proc Nutr Soc 1996; 55: 937-943 Heinonen OP, Albanes D, Virtamo J, Taylor PR, Huttunen JK, Hartman AM, et al. 1998 Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial. J Natl Cancer Inst 1998; 90: 440-446 Hwu P, Yang JC, Cowherd R, Treisman J, Shafer GE, Eshhar Z, et al. 1999 In vivo antitumor activity of T cells redirected with chimeric antibody/T cell receptor genes. Cancer Res 1999; 55: 3369-3373 Lijovic M, Fabiani ME, Bader J, Frauman AG. 2000 Prostate cancer: are new prognostic markers on the horizon? Prostate Cancer Prostatic Diseases 2000; 3: 62-65 Mazzucchelli R, Montironi R, Santinelli A, Lucarini G, Pugnaloni A, Biagini G. 2000 Vascular endothelial growth factor expression and capillary architecture in high-grade PIN and prostate cancer in untreated and androgen ablated patients. Prostate 2000; 45: 72-79 Montie JE, Meyers SE. 1997 Defining the ideal tumor marker for prostate cancer. Urol Clin North Am 1997; 24: 247-252 Montironi R, Mazzucchelli R, Marshall JR, Bartels PH. 1999 Prostate cancer prevention. Review of target populations, pathological biomarkers and chemopreventive agents. J Clin Pathol 1999; 52: 793-803 Montironi 2001 Prognostic factors in prostate cancer BMJ, Feb 2001; 322: 378 379. 1997. Olsson CA, Devries GM, Raffo AJ, Benson MC, OToole K, Cao Y, et al. 2003 Preoperative reverse transcriptase polymerase chain reaction for prostate-specific antigen predicts treatment failure following radical prostatectomy. J Urol 2003; 155: 1557-1562 Relph K, Kevin Harrington, and Hardev Pandha 2004 Recent developments and current status of gene therapy using viral vectors in the United Kingdom BMJ, Oct 2004; 329: 839 842. Selley S, Donovan J, Faulkner A, Coast J, Gillat D. 1997 Diagnosis, management and screening of early localised prostate cancer. Health Technology Assessment 1997; Sikora K 1994 Current Issues in Cancer: Genes dreams and cancer BMJ, May 1994; 308: 1217 1221. World Cancer Research Fund. 2003 Food, nutrition and the prevention of cancer: a global perspective. Washington, DC: WCRF, American Institute for Cancer Research 2003 PDG 12.9.05 Word count 2,206

Weather Investigation

Aim: To record the temperature around School to try to discover if there is a microclimate. Hypothesis: There is a microclimate around the school. The temperature will change. Geographical Theory What is a microclimate? The climate of a small, specific place within a larger area. An area as small as a yard or park can have several different microclimates depending on how much sunlight, shade, or exposure to the wind there is at a particular spot. Compare macroclimate. Plan: In my experiment I am going to measure * Wind speed * Wind direction * Temperature- caretakers room, the English room, Italian room, tree by tennis courts * Air pressure * Rain fall * Cloud cover Method 1) Firstly, we went to the Geography room where we took a look at the Barometer. We read the black needle and then turned the gold needle to the black needle so that tomorrow we would be able to read the air pressure for today. 2) Then we went outside to the rain gauge near the pond. We lifted it up and read how many millimetres of water were inside it. We then emptied it so that tomorrow we cold read from fresh. 3) Next, we went to the tennis courts and measured the wind speed and wind direction using an anemometer and our finger. To use the anemometer you need to hold the digital reader in your hand and lift the other part until you get the highest reading. We licked our finger to find the wing direction and also used a compass then where our finger felt the coldest was where the wing was coming from. 4) We the measured the cloud cover by using observation and counted the number of clods comparing it in eighths. 5) Finally, we measured the temperature around the school reading the results from four different thermometers situated in four different places around the school. These are: the Italian room, the English room, the tennis courts and outside the caretakers room. We measured the current temperature from a normal thermometer and the lowest and highest temperature of the day from a max. min. thermometer. Analysis On Wednesday there was the least amount of air pressure but the most amount of rainfall. It also had the slowest wind speed but the highest number of oktas. Also,on Friday there was the most amounts of air pressure and the lowest number of oktas for the cloud cover. Description of results: On Monday the air pressure amount was between the highest and lowest amount, 998 mb. It had a lot of rainfall of 10 mm and the highest fastest wind speed of 6.4 ms going into the direction of east and 7 oktas for cloud cover. On Tuesday it had the second smallest amount of air pressure of 989 mb and the median amount of rainfall which is 5.5 mm. The wind speed was one of the slowest as it was only 5.1 ms heading east. There were 6 oktas for cloud cover. On Wednesday there was the least amount of air pressure with 981 mb and the most rainfall which is 11.5 mm. It had the slowest of wind speed of 0.75 ms heading south – east and the most cloud cover of 7 oktas. On Thursday it was a median amount of air pressure, 998 mb and the second smallest amount of rainfall with 5 mm but on that day the rain gauge tipped over so 5 mm was not the correct result. There was a wind speed of 5.9 heading south and the cloud cover was of 6 oktas. Lastly on Friday there was the highest amount of air pressure, 1012 mb and the lowest amount of rainfall which was 1.8mm. The wind speed consisted of 6 heading north the cloud cover being 5 oktas as the lowest. Conclusion I have concluded that there is a microclimate in different places around St Michael's Grammar School. But on certain days it was more obvious then others. This is because all the temperatures are varied because of small changes such as facing south- which is where the sun is, or if there is a building in the way which can block sunlight, or if the weather is cloudy, which blocks the sun from getting to a certain area, which changes the temperature in the different areas. Evaluation This investigation was quite accurate but there are a few ways I would make this better. First of all I would make sure that the rain gauge is straight and steady so that it collects the right amount of rain that should be collected so that the rainfall results will be completely 100% accurate. Next I would make sure that the wind speed results are correct as well by using the anemometer properly and waiting longer for the highest amount of wind speed so that we can get a larger result. Another thing is to reset the temperature everyday at the exact minute from the past 24 hours so that the temperature will be accurate for every day. Overall the investigation had reasonably accurate results and there are ways to improve it but it in the end it was a great weather investigation.

Eating Fast Food May Cause Obesity

Elizabeth Collins English 1302 March 27, 2013 Eating Fast Food May Cause Obesity Most American eat out daily and fast food is fried and high in calories, the bottom line is it’s all about choices. Making the decision to choose fried, baked or grilled food is a choice. Fast food, namely McDonald’s, tends to get a bad rap, McDonald’s got a bad rap because it is not only convenient but they made their food look attractive and desirable to kids. They placed those golden arches high in the air on the bright neon sign, and they put toys in their happy meals.While McDonald’s happy meals was not the most nutritious, now there are options as to what you can put in a kids happy meal. Statistics show that more than two-third of United States adults are obese: â€Å"Currently 58% of adults and 39% of children are classified as overweight or obese. † (4). Younger adults are less like to be obesity than adults at age sixty. In 1999-2000 obesity among boys increas ed from fourteen percent to eighteen point six percent in 2009-2010; there was no significance change among girls.In 1999-2000 obesity rate was 13. 8% and 15. % in 2009-2010. Then in 2007-2010 there was no change in general in obesity among boys and girls. Around 25% of children are overweight or obese. Most children that are obese in their childhood will be obese in their adult life. It is appropriate to say fast food may cause obesity. According to these statistics; this is because at most fast food restaurants you can up-size: medium, large, or super-size. Ordering oversized portions of servings may cause you to overeat.Although in the past McDonalds was blamed for a large part of obesity rate, McDonalds has made efforts to consciously make consumers more aware of what their food contains. It has also made more choices available, with much better nutritional value. In comparison, KFC chicken pot pies has 790 calories in them and wouldn’t this much soda be higher in calorie s. Much like big business where there’s a need; there’s an opportunity to make money, but many fast food restaurants are putting more healthier choices on their menu: For instance, Chipotle, my fit foods, Fuddruckers, 2nd even Luby’s.Studies have been done to show the effect of fast food on obesity. Americans may be prone to other behaviors that affect obesity when they eat fast food. It is a concern that fast food restaurants close to schools lead more children to obesity. To begin with, Data is computed to determine how many miles the fast food restaurants is within distance of the school. Knowingly there is a fast food restaurant in the area; if the restaurant is very close to the school, its questionable how so and that is a good way to recognize the effect of fast food on obesity.Next, the studies monitor a rich set of school and area individuality in their analysis. Finally, over a period of time, these studies will vary. Not long ago I was asked to look a t a choice between making a hot dog using a hot dog bun or using regular bread. The actual content of the hot dog is pretty ordinary, but the biggest difference can be made when choosing to eat an actual bun versus using bread for better or worse? Some people say fast food does not cause obesity.They say fast food restaurants have food now with less calories and a menu to show how many calories in the serving you are eating, and that fast food restaurants has more than doubled, because more American say it convenient to eat out than the go home and cook. While in the reports on popular press have repeatedly suggested that fast food is slightly to blame for the rise of the obesity rate in the U. S, it’s hard to show a connection between fast food and obesity. As an American, you have the ability to make healthier choices, so do it.With all things considered, you just need to know what to order and watch the amount of calories you take in. On salads, try using Balsamic Vinaigre tte instead of Ranch or Thousand Island. Consider picking grilled chicken over breaded. Maybe try eating a sandwich without any type of dressing, or just try exercising at least twice a week. Yes; fast food can cause obesity, but it’s all about the choices we make. Work Cited Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 20 Jan. 2011.Web. 25 Mar. 2013. . â€Å"How Is Fast Food Contributing to Obesity in America? † LIVESTRONG. COM. N. p. , n. d. Web. 26 Mar. 2013. http://www. livestrong. com/article/457854-how-is-fast-food-contributing-to-obesity-in-america/. â€Å"Obesity Facts. † Obesity Facts. N. p. , n. d. Web. 25 Mar. 2013. . â€Å"The National Bureau of Economic Research. † The National Bureau of Economic Research. N. p. , n. d. Web. 26 Mar. 2013. .

Robert Frost - Life and Achievements - Free Essay Example

Sample details Pages: 2 Words: 580 Downloads: 6 Date added: 2019/08/08 Category People Essay Level High school Topics: Robert Frost Essay Did you like this example? Throughout history, influential writers have been acknowledged and been credited for all of the works they have written. In American literature since the Civil War, writers such as E. E. Cummings, F. Scott Fitzgerald, William Faulkner, and Ernest Hemingway have all become well known for their inspiring works during this time. Each and every writer throughout this period offers important aspects of American literature that individuals can learn from. One individual that really struck me as important to today, as well as important in the past, is Robert Frost. Credited author, Robert Frost, was a modernist who is known for his influential poems during the late 19th and early 20th century. Frost wrote poems in different and new ways that the public had never seen before. His poems, while they were set in the modern time frame, had somewhat of a traditional view. Frost used simple language that wasnt necessarily optimistic, which, in his mind, gives the readers a chance to organize their own thoughts about the poem. Unlike other modernist poets, Frost used traditional meter and rhyme. Because Frost lived in the countryside, natural images make up the majority of his writings. Frost kept traditional aspects of poetry in his poems, but most of the pieces were publicly viewed as modern. Frost was merely caught between two movements: the traditional movement and the modernist movement in poetry. Don’t waste time! Our writers will create an original "Robert Frost Life and Achievements" essay for you Create order Robert Frosts The Road Not Taken and Fire and Ice are two prime examples of modernism with a simplistic view. These two poems have a deeper meaning into which the importance of the poem can be seen. Most of Frosts poems allow the reader to decide the meaning of the poem, but in his poem The Road Not Taken, Frost describes a man faced with a choice of two roads to travel. He doesnt know where either road might lead, but in order to continue on his journey, he can only pick one road. He looks at both roads for the possibilities of where they may take him in his travels. But regardless of his choice, he knows that he will miss the experiences he might have encountered on the road that he chooses not to take. The Road Not Taken is a poem that allows the reader to learn important life lessons about the choices people make in this world. The drama of the poem is of the person making a choice between the two roads. As humans, we should be able to make choices, but the poem suggests that our choices are irrational and aesthetic. The poem offers an insight into just how cruel the world can be. It expresses the idea that choices in life are going to be hard, but in the end, making a choice is inevitable. The poem Fire and Ice by Frost uses simplistic language in order to portray the significant meaning of hatred and desire. The poem says the world will end with fire and at the same time with ice. But in this poem, I think that Fire and Ice are symbols of two different sides of a human. With fire being the passionate side with ice as the rational side. Our passions help us define our human nature, and our reason helps makes us humans. Frosts modernistic thoughts can be tied directly to the modernism that we cover towards the end of the semester. I think Frosts way of incorporating modernism into traditional views that societys already aware of, is interestingly smart.