Thursday, November 28, 2019
Marketing Effectiveness The Most Pressing Problem in Business Marketing Today
Introduction Marketing effectiveness can be defined as the ââ¬Å"quality of marketers to optimize their efforts and achieve the best short-term and long-term resultsâ⬠. (Buyline Research 1, pp. 5) This concept is directly related to Return on Marketing Investment (ROMI) and ROI which are often utilized in the description of the relationship between costs and the returns gained mainly in the form of profits (Buyline Research 2).Advertising We will write a custom research paper sample on Marketing Effectiveness: The Most Pressing Problem in Business Marketing Today specifically for you for only $16.05 $11/page Learn More Itââ¬â¢s sometimes very difficult to measure the effectiveness of marketing activities either in advance or after they have been executed. The situation may be further complicated if a company uses different marketing strategies. This paper seeks to report on the difficulties that are frequently faced while measuring marketing eff ectiveness. It further describes how best the issue can be tackled by describing the strategies that can be employed to measure the effect of individual marketing activities. Difficulties in measuring marketing activities The current business environment is characterized by intense competition. Therefore firms cannot do without marketing activities such as advertising to promote their survival (King, pp. 2). Many companies usually face a dilemma in establishing whether their investment in marketing truly yields a competitive advantage for them or not. Companies can be disappointed after investing heavily in unsuccessful campaigns. However, even when good returns are realized, one should say it is not easy to determine the exact contribution of each marketing activity to that success. Research conducted indicates that most firms cannot hold their marketing departments accountable for the vast resources they use to carry out marketing activities. Few companies that have developed meas urement tools, are measuring the wrong things. The majority of them are not in a position to measure anything at all. The research indicates that about 54% of companies usually set their marketing budgets basing on historical data ââ¬â clearly showing that they do not have any idea on the effectiveness (King, pp. 3). It is further noted that only about 20% of marketing executives are able to accurately estimate the impact that follows budget cuts. Itââ¬â¢s further identified that firms that cannot accurately report on the progress of a marketing ROI usually do not have individuals that have been specifically assigned to that task (Powell 5).Advertising Looking for research paper on business economics? Let's see if we can help you! Get your first paper with 15% OFF Learn More Because of the difficulty that is associated with measuring the impact of advertising, existence of external impacts, and the difficulty in establishing controls; several firms cannot measu re the value of advertisement. In one particular study carried out in the year 2008, it was established that 100 biggest U.S retail banks use up to USD 2 billion on advertising annually. This implies that banks in todayââ¬â¢s society must rely on advertisement for survival (Stern 17). Strategies for effective measurement of marketing Marketers should be in a position to collect all the data that are required to measure their marketing activities. They should be able to know the specific aspects as well as the priorities that should be measured. They should understand what should be measured in the future and most important why they are carrying out the measurements. A well planned measurement will give the firm the confidence to undertake innovations that bring a positive impact. Firms need to determine whether there are gaps in coverage, put measures in place to ensure that measurement is managed automatically rather than manually, and lastly the measurement should be integrated into the larger marketing portfolio rather be left on its own (Powell 27). Figure1: A chart showing marketing metrics continuum Identification of key performance indicators for marketing Research has revealed that marketing performance indicators usually vary depending on the specific areas of responsibility. Metrics for different areas of responsibility that are needed for effective monitoring of marketing activities include: The brand managers are required to monitor changes in statistics of aspects such as brandy equity, brand awareness, brand preference, brand image and brand loyalty (Buyline Research 12). Itââ¬â¢s important to note that internal tools within the organization are used to collect data as an ongoing process.Advertising We will write a custom research paper sample on Marketing Effectiveness: The Most Pressing Problem in Business Marketing Today specifically for you for only $16.05 $11/page Learn More However, the best information for gauging the success of a brand is usually derived from the outside environment. Usually, the data should be collected by hand and kept in form of reports or spreadsheet. Using such data, the brand manager can monitor the increase or decrease in a productââ¬â¢s market performance over time. Usually, the product marketing managers often spend most of their time in the manufacturing rather than the marketing side. Research indicates there are elaborate systems that have been developed to inform the product marketing manager about the manufacturing process but very few to reveal progress on the marketing side (King, pp. 5). Similar to the brand manager, the product marketing manager is often centered on the opinions of the customer. He or she takes a kin interest in factors such as addition of new features, lowering or raising of the prices. Product managers therefore keep an eye on the brand of related evaluations (Powell 34). In most cases they take action following reports of market share, customer satisfaction, sales and price sensitivity. Public relations managers work in departments that are preoccupied with identifying how the public perceives the company, using indicators such as exposures on TV or leading newspapers (Lenskold 14). It is important to note that companies receive both positive and negative exposures and both should be used in measuring the success of the PR department. The different responsibilities carried out by the above mentioned positions are crucial in the measurement of marketing effectiveness. They are vital for the identification of the three essential things in a marketing campaign; the cost, the revenue or leadsââ¬â¢ generates and the life time value of customers (King, pp. 4). The advertising manager is concerned with the number of viewers the company reached and how those can be increased. There are specialized software applications that allow advertisers to catalogue and track these numbers (King, pp. 6). Sales manage rs always think about the sales figures of the various commodities offered by the company. They carry out comparative studies to determine sales figures across different regions. This individuals form part of the company accounting systems, they ensure that orders are booked, invoices are sent and commissions are always paid.Advertising Looking for research paper on business economics? Let's see if we can help you! Get your first paper with 15% OFF Learn More Focus on performance measurement through automation It is important to note that performance measurement and marketing automation work hand in hand. For effective evaluation of marketing performance, the data capture process should be automated (Buyline Research 9). The automation should ensure that data are not only captured and organized but also measured in the most effective way. Savvy marketing automation investment decisions include greater ââ¬Å"control of the measuring capabilities that is offered by different solutions, the capture process, the different available option and instant analysisâ⬠(King 35, pp. 3). There are several automation solutions but most are not effective as they require much more effort to access data before shaping for relevant analysis. A study has been carried out to identify the marketing performance monitoring activities that are under automated portfolios in a number of firms (Powell 9). When marketers were asked about what they desired mos t in the coverage areas, they felt underserved, and gave interesting responses. Most of them stated that better measurement capabilities would increase their loyalty by 51% with the likelihood of increasing their investment by 44% (Lenskold 12). This implies that marketers are in constant search for performance measurement solutions to determine the effectiveness of their marketing activities (Stern 24). They hope that there will be a rapid development in the automation tools which will in turn help them to foster internal and external success (Buyline Research 6). Economic Modeling Studies have established that in order to successfully measure the effectiveness of advertising and other marketing activities, it is imperative to carry out econometric analysis. This is important for establishing the impact of each element in the marketing mix, the effectiveness and ROI (King, pp. 6). Advanced data mining techniques should be employed in the determination of the strengths and weaknesse s of the marketing program implemented by a given firm (Lenskold 8). The identified challenges can be corrected by carrying out changes in the pricing, advertising and promotion. The econometric analysis examines influences from the external environment in the form of competition, changes in the market environment due to seasonality and changes of other economic conditions in order to have a better understanding of how they impact sales performance. If the results are accurately determined then planning can be carried out for future advertising, promotion, pricing, and other marketing activities to improve sales performance and distribute marketing resources for increased ROI (Stern 7). Studies have shown that econometric models provide a standard measurement technique across different portfolios of a business, marketing lines and markets; an accurate measurement of the historical performance; forecasting of the future performance and the optimization of the business operations thro ugh the media mix or channel (Buyline Research 11). Econometric modeling often requires input from a variety of key factors that include external data such as consumer data, economic performance data, competitive advertisement and internal data such as product specifications and process changes. Channel data should incorporate TV, radio, branch, magazines, point of sale and direct mail information (Buyline Research 11). Product data can include deposits, lending and other products that can be attained from the banking sector. Historical data should be collected from modeling inputs and arranged in the order of time series fashion so as to allow for adjustments to be made in the future regarding the seasonality, competitiveness, market mix, distribution changes and interaction effects (Powell 56). All the dynamics in the marketing arena are put into consideration so that a model is developed to allow pinpointing variations in any specific component. In spite of the fact that economet ric modeling provides a valuable tool for evaluating difficult actions such as spending on media, there is no single measurement method that can provide the necessary insights into marketing effectiveness across the different channels (Buyline Research 13). Therefore, it is better to combined with other control methodologies to provide an overall effective means of measuring the effectiveness of marketing activities of a given company (Buyline Research 14). Test/Control methodologies The dynamic nature of marketing activities makes it difficult for a firm to evaluate the impact of individual marketing portfolios on subsequent customer numbers. This occurs because the potential customers are informed through many different channels in the marketing arena. Due to this observation, itââ¬â¢s common for the effect of specific marketing activities on consumer behavior to be overstated or understated because the impact of other is not properly evaluated resulting into a biased measureme nt (Lenskold 5). Well designed experimental tests are usually multivariate which can be effectively used to measure the impact of an individual marketing activity. Matching is commonly employed in the measurement of the effectiveness of advertising. The method relies on the contrasting outcomes of participating markets with outcomes of comparable non participants (Buyline Research14). Conclusion This paper sought to report on the difficulties that are frequently faced while measuring marketing effectiveness. It further describes how best the issue can be tackled by describing the strategies that can be employed to measure the effect of individual marketing activities. Indeed, it has been established that it is very difficult to carry out an effective measurement of the impact of marketing activities. There are a lot of companies worldwide that are often misled and may not be able to know what marketing activity contributes. This paper has provided some of the most effective ways thr ough which firms can effectively measure their marketing activities. They include automation and economic modeling as well as the use of test controls. Works Cited Buyline Research. Marketing Perfomance Measurement: Target Areas Whereà Marketers Want to Improve How The Measure Up. Massachusetts: Buyline Research LLC, 2008. King, William. ââ¬Å"Measuring Marketing Effectiveness in Comparison With Sales.â⬠2011. Web. Lenskold, James. The Path To campaign, Customer, and Corporate profitability. New York: McGraw Hill Professional, 2003. Powell, Guy. Marketing Calculator: Measuring and Managing return on marketingà investiment. New York: John Wiley and Sons, 2008. Stern, Jim. Best Practice: Measuring Marketing Effectiveness. CA: Synergex International Corporation, 2003. This research paper on Marketing Effectiveness: The Most Pressing Problem in Business Marketing Today was written and submitted by user Mauricio U. to help you with your own studies. You are free to use it for research and reference purposes in order to write your own paper; however, you must cite it accordingly. You can donate your paper here.
Monday, November 25, 2019
An Era of Punk essays
An Era of Punk essays Sex, drugs, and rock and roll was the rallying cry for a movement that changed American culture forever. Rock and roll first startled the American scene in the mid-1950s, but no one then could have predicted the remarkable vitality and staying power of this new music. The early tradition of rock has gone through many transitions. Provocative and outlandish stage attire and behavior have been an important resource since the birth of rock and roll. Decades following the birth of rock and roll, many have witnessed a steady ever changing parade of hair styles, costumes, gestures and props. As the level of tolerance and acceptance grew, rock stars adopted more bizarre and shocking images. It is in this context that punk rock, seen by some as a startling new direction in the late 1970s must be considered. Rock music achieved a new respectability and power at the same time (Ward, Stokes, Tucker, Rock of Ages, 547). Punk was rocks most notable attempt in the late 1970s to inject angry, rebellious, risk taking notations into the music. The musical style called punk rock developed in the United States out of raw and energetic music played by the garage bands of the mid-sixties. These bands were mainly teenagers playing basic guitar chords, and failing away at drums and cymbals in their own garages. This resulted in sounds that were rough, raw, and musically undisciplined, which expressed their interests and brought music to their level (Charlton, Rock Music, 204). Given that the greatest garage bands could barley play, we may assume not only that virtuosity has nothing to do the form, but also that the Utopian dream of every man and artist can come true right here, in our suburban land of opportunity the ultimate proof that rock and roll is the most democratic and all-American of art forms (Miller, History of Rock While teenage gara...
Thursday, November 21, 2019
Electric Vehicles and Zero-Emission Cars Essay Example | Topics and Well Written Essays - 1250 words
Electric Vehicles and Zero-Emission Cars - Essay Example Introduction The 21st century has ushered in a new host of problems. To a large extent one recognizes that the increasing move towards globalization has created many of these challenges. One of the most predominant difficulties is energy consumption. Energy consumption is a notable concern both for the difficulties associated with attaining overseas petroleum, as well as environmental concerns over gas emissions. While petroleum use, most scientists agree, threatens the environment, society still has maintained a strong reliance on this energy source. In recent years, however, electric vehicles and zero-emission cars have emerged that have posed a slight challenge to the petroleum hegemony. This essay considers various elements related to these vehicles and cars. Electric Vehicles and Zero-Emission Cars While most people are aware of electric and hybrid vehicles, few understand their history or cursory issues. The electric vehicle is a vehicle that implements an electric motor for it s primary power source. Within this context of recognition there are a number of different types of vehicles that implement electric power. One sort of electric vehicle uses energy that is located at an outside power source. Another form of electric vehicle operates from electric energy that was originally produced by an outside power source; one recognizes that hybrid vehicles would fall within this category as they gain their energy from an external electrical supply. The final type of electric vehicle is one that produces electric energy from an internal source (Mitchell 2010, p. 7). While most people associate electric vehicles with cars, in actuality electricity has been used to power a wide range of transportation devices. In these regards, everything from boats to planes to trains has been powered using electric energy. Electric vehicles have a long history. Indeed, one considers that by the early 18th century engineers and scientists had been experimenting with electric prop ulsion. Still, it wasnââ¬â¢t until the 20th century that electric vehicles were popularized within the United States. While electric vehicles were among the first types of cars produced, to a large extent electric propulsion remained marginalized to petroleum devices throughout the 20th century. Towards the end of the 20th century electric cars gained a slight resurgence. In 1990 the California Air Resources Board mandated that major automobile manufacturers produce electric vehicles for sale. Through the decade then automobile manufacturers increased production of these vehicles. Towards the end of the 1990s, however, consumers increasingly began to move towards sports utility vehicles. One of the main recognitions in these regards is that the lower-gas prices that were experienced during this period and the robust economy created a situation where electric vehicles were increasingly untenable. Still, with the on-set of the 21st century the hybrid car emerged as a trend. The 200 1 the Toyota Prius became the first mass-produced hybrid electric car. A number of other hybrid vehicles would follow. Hybrid vehicles held a number of benefits over vehicles that entirely relied on electric power.
Wednesday, November 20, 2019
Operation Management Assignment Example | Topics and Well Written Essays - 1000 words
Operation Management - Assignment Example The tools include the following; This approach is aimed at eliminating defects through minimising the number of errors that a products or service has. I shall be extensively utilising this tool within my job to perform assessment of the processes involved in my daily work activities in order to detect areas which have weaknesses and make essential corrections for improvement of the outcomes. Observations of the business processes within the various jobs which I undertake will be key to the effective application of this tool in enhancing my performance while working for the various companies and running my own business as well. The application of this tool within the various working stations will enhance my analytical skills as the utilisation of this tool requires analysis of statistics which are related to the business process. Evaluation of the processes will be based on the targets which I shall have set at the beginning of the business processes which will include the desired profits and other financial targets as well. This tool seeks to assess the various processes which are used within the business environment in order to determine the kind of improvements which can be undertaken. This tool will be critical in assessment of the activities which are involved in the different jobs which I will be undertaking. Assessment of the activities will ensure that I understand the job in detail in order to be able to improve my performance on every job that I shall undertake. Within the management positions which I will hold, this tool will be critical to the understanding of the operations in order to enhance the performance of the firms which I shall be working for, I relation to the kind of work I shall be doing. By understanding the job requirements from the process flow chart, I shall be able to manage the operations better as they will be clear to me. This is one of the most effective tools that can be utilised in the business
Monday, November 18, 2019
Education Research Paper Example | Topics and Well Written Essays - 1000 words - 2
Education - Research Paper Example There are a variety of post reading strategies that will heighten, enrich and refine interest in a specific topic, but the primary objective of post reading strategies is to further clarify and develop interpretations of readings and text, and to aid students recall whatever they have individually developed in their minds after reading a particular text. There are generally four main types of post reading strategies or activities. These are: a) Those provide students with the opportunity to ask questions with regards to assignments or readings. b) Those that concentrate on text structure c) Those that involve peer and classroom review d) Those that extend learning This paper will be based on the following paragraph from the book Tangerine by Edward Bloor: Antoine studied my face. He said, ââ¬Å"Youââ¬â¢re Erik Fisherââ¬â¢s little brother?â⬠I tightened up at the sound of Erikââ¬â¢s name. I mumbled, ââ¬Å"Yes.â⬠Antoine said quietly, ââ¬Å"Itââ¬â¢s time to sta rt telling the truth, little brother. Do you understand what Iââ¬â¢m saying?â⬠I nodded like I understood. But, I didnââ¬â¢t. Not really. Not until he added, ââ¬Å"Donââ¬â¢t spend your life under the bleachers, little brother. The truth shall set you free.â⬠I nodded with real conviction now. ... Activity 1: Web The discussion web is a graphic illustration that helps students prepare for discussions in the classroom (Kinsella & Widener, 2001). In this case, the students will be required to develop a discussion centered on the paragraph drawn from the book that has been mentioned earlier and to primarily focus on the content. The discussion web is geared towards helping the students examine all sides of an issue and understand all perspectives emanating from that particular issue. Your role (the teacher) in this activity will be that of a moderator and an encourager (Behrens & Rosen, 2008). As a moderator, you will help the students to create a topic and stay focused on it. As an encourager, you will help the students engage participants and ensure that they are free to voice their opinions and points of view. Prepare students for listening or reading by establishing a purpose for reading, activating previous knowledge and introducing important vocabulary. After students have read the paragraph, introduce the web by way of a provocative question. For instance, ââ¬Å"was Paul a dishonest person?â⬠1. Students will be required (in pairs) to discuss the pros and cons of the question and then complete the web as a unit or team. They will take turns filling in as many NO and YES statements as they can generate. 2. Pairs are rearranged into units of four students, who then compare their webs and come up with one answer to the question. 3. The group chooses and records the most appropriate and strongest argument and gives its reasons for that choice. 4. Each group selects a spokesperson to report (in three minutes) the results, and then students with
Friday, November 15, 2019
Cytochrome P450 and Breast Cancer
Cytochrome P450 and Breast Cancer Cytochrome P450 The cytochrome P450 (CYP) enzymes are a superfamily of haem-containing mono-oxygenases involved in the oxidative metabolism of a wide range of xenobiotics and endogenous compounds including steroids in the body.(40, 41) These membrane-bound enzymes are found primarily in the liver, sited in the smooth endoplasmic reticulum (SER) of hepatocytes.(42) CYPs are also found, to a lower extent, in extra-hepatic tissues such as the small intestine, kidney and lung where they carry out enzymatic biotransformation of foreign chemicals.(43) In human liver, three main CYP families (CYP1, CYP2 and CYP3) are heavily involved in drug metabolism.(44) Phase 1 metabolism reactions such as oxidation, reduction and hydrolysis of substrates introduce functional groups into drug molecules. The intermediate metabolites then enter Phase 2 reaction which involves conjugation to produce inactive polar metabolites for elimination from the body.(30) Most P450 metabolisms deactivate substrates to form inactive intermediates for elimination; paradoxically, CYPs can convert substrates into active intermediates which contribute to cellular toxicity or carcinogenicity.(30, 43) + Figure 11: The microsomal monooxygenase P450 system. Cytochrome P450 incorporates one atom of oxygen to the substrate (RH), forming a hydroxylated product (ROH); and incorporates another atom of oxygen to form a water molecule. NADPH serves as a coenzyme in the system. The hydroxylated product can then undergo Phase 2 reactions to produce conjugates which are catalysed by a variety of enzymes such as gluthathione transferases.(43) Cytochrome P450 and Breast Cancer CYPs are involved in the metabolism of a wide range of substrates including carcinogens and anticancer drugs.(43) CYPs can convert anticancer drugs into inactive metabolites; or activate mitogenic compounds such as the oestradiol metabolite 4-hydroxyestradiol.(45) It was established that metabolism of the carcinogen benzopyrene by CYPs may generate products which can cause specific mutation in the p53 gene and initiate cancer.(46) The microsomal monooxygenase P450 system (MMO) generates ROS which, at high levels, can induce cellular oxidative stress which affects cancer cell proliferation.(47, 48) Expression of individual CYPs were observed in different types of human cancers including breast cancer.(43) However the knowledge on the role of CYPs in cancer cells is limited. This has attracted increasing interest of experimentalists in the investigation of the effect of CYP-mediated metabolism in cancer cells. Over the years, overexpression of CYP1A1 and CYP1B1 are the most profound findings in the field of pharmaco-oncology.(44) CYP1A1 catalyses the metabolism of oestradiol to inactive 2-hydroxyestradiol for excretion from the body.(41, 49) In contrast, CYP1B1 mediates conversion of oestradiol to 4-hydroxyestradiol which is capable of producing ROS and contributes to breast carcinogenesis.(41, 49) Previous study has reported that oestradiol can regulate CYP1B1 expression in MCF-7 cells through ER-mediated pathway.(41) Another study treated MCF-7 cells with aryl hydrocarbon receptor agonist which induces P450 enzymes to catalyse 4-hydroxylation of 17à ²-estradiol.(50) Higher CYP1B1 mRNA levels and increased hydroxylation activity of 17à ²-estradiol were observed in breast tumours. (50) This correlates with another study which had shown that CYP1B1 protein was absent in normal breast tissue.(51) Murray et al. had identified the presence of CYP1A and CYP3A in 40% and 22% of the breast tumours respectively.(52) Another P450 subfamily CYP2C was also reported to be present in both normal and breast tumour tissues at similar levels.(53) These evidences further support the hypothesis that expression of individual CYPs in breast cancer cells might play a role in breast tumourigenesis. If the hypothesis is confirmed to be true, the levels of individual CYPs in breast tumour can become a good marker in providing diagnostic and therapeutic strategies in breast cancer treatment. CYP2C8 Figure 12: The structure of CYP2C8, a haemoprotein from the cytochrome P450 superfamily. Figure adapted from reference (54). CYP2C8 is a member of the CYP2C subfamily which accounts for 7% of the total microsomal CYP content.(55) CYP2C8 mediates Phase 1 oxidative metabolism of about 5% of drugs in the liver.(55) Sited mainly in the endoplasmic reticulum of hepatocytes, CYP2C8 mRNA was also detected in extra-hepatic sites such as the kidney, brain, uterus and mammary gland.(56) In a study, 10 breast cancer tissue samples were analysed using specific primers for RT- PCR for the expression of CYP2C8.(57) Interestingly, CYP2C8 mRNA was detected in all the samples analysed.(57) Another study has detected CYP2C8 mRNA in breast cancer cells and CYP2C8 knockdown suppressed the growth of breast cancer cell lines MCF-7, T47D and MDA-MB-231.(58) Anti-cancer drug Paclitaxel and carcinogen benzopyrene are the main substrates of CYP2C8 in enzymatic metabolisms.(43) CYP2C8 primarily catalyses 6à ±-hydroxylation of Paclitaxel, a mitotic inhibitor used in malignant tumour, into inactive metabolite for elimination.(59, 60) Results from several studies had shown that single-nucleotide polymorphisms (SNPs) in CYP2C8 gene, especially the CYP2C8*3 variant allele which is more common in Caucasians, results in alteration in CYP2C8 enzymatic activity.(61, 62) Dai et al. had reported that subjects homozygous for CYP2C8*3 had decreased 6à ±-hydroxylation Paclitaxel metabolism compared to subjects with wild-type CYP2C8 gene.(62) As a result, although more likely to achieve therapeutic response from Paclitaxel treatment, breast cancer patients who are CYP2C8*3 carriers have a significant increased risk of neuropathy due to the narrow therapeutic window of Paclitaxel.(60, 61, 63) Besides, it was also reported that CYP2C8*3 variant caused defective metabolism of an endogenous CYP2C8 substrate, arachidonic acid, into epoxyeicosatrienoic acids which promote invasion in vitro and angiogenesis in vivo.(62, 64) In mice, overexpression of CYP epoxygenase in the metabolism of arachidonic acid had resulted in metastasis of MDA-MB-231 human breast cancer cells to the lungs associated with angiogenesis.(65) In another study involving 652 breast cancer patients in Southern Sweden, CYP2C8 polymorphism was studied against early breast cancer-related events to investigate the impact of polymorphism on breast cancer-free survival after diagnosis. (64)The result had shown that CYP2C8*3 variant resulted in shorter disease free survival in 297 ER-positive patients with invasive tumours treated with Tamoxifen, probably due to the role of CYP2C8 in drug metabolism.(64) In addition, researchers also found out that CYP2C8*3 carriers with breast tumour larger than 20mm had more than twofold higher risk of lymph node involvement.(64) Despite studies had detected the expression of CYP2C8 in breast cancer cells, its role in breast cancer is still not widely known. It has been hypothesised that overexpression of CYP2C8 may influence proliferation of breast cancer cells due to its role to generate reactive oxygen species (ROS) as a by-product of the process of breast cancer drugsââ¬â¢ metabolism. Furthermore, CYP2C8 polymorphism might result in inter-individual variation in tumour progression and therapeutic response to anticancer treatments. The expression levels of CYP2C8 in breast tumours might therefore be a good target in designing new anticancer drugs. Quercetin: The CYP2C8 Inhibitor Figure 13: The chemical structure of the CYP2C8 inhibitor Quercetin and its derivatives. Figure adapted from (66). Quercetin is a flavonoid found in a variety of polyphenols such as fruits, vegetables and plants.(67) As a competitive inhibitor of CYP2C8, Quercetin inhibits the 6à ±-hydroxylation of taxol catalysed by CYP2C8.(68) Quercetin was reported to inhibit cell proliferation of several human cancers such as leukaemia, gastric carcinoma and breast carcinoma.(68) Currently Quercetin is under Phase 1 clinical trial for anticancer treatment. (68) Quercetin showed a dose-dependent inhibition on cell growth of ER-positive MCF-7 breast carcinoma which could be reversed by removal of Quercetin from culture medium or by addition of 17à ²-estradiol to the cells treated with Quercetin.(69) In another recent study, researchers had shown that Quercetin induces cell cycle arrest and apoptosis in a time and concentration-dependent manner in cell line MCF-7 (refer Figure 15).(67) The results had suggested that Quercetin might be a promising anticancer drug although its exact mechanism on inhibiting cell proliferation is not fully understood. Quercetinââ¬â¢s effect on CYP2C8 activity and ROS production might explain its role in inhibiting carcinogenesis. Table 1: The effect of Quercetin on the cell cycle and apoptosis of MCF-7 cells shown in a study carried out by Deng et al. Quercetin inhibition on cell growth activity was dose-dependent. The concentration of Quercetin was also found to be positively correlated with apoptosis rate of the cells.(67) Reactive Oxygen Species (ROS) Reactive oxygen species are the by-products of normal respiration process in the mitochondria.(70, 71) Apart from mitochondria, ROS is also produced from biochemical reactions that use oxygen molecules, such as the P450 monooxygenase system (MMO) in the endoplasmic reticulum.(70) Free radical ROS are highly reactive oxygen molecules which carrying an unpaired electron in their outer shell and seek for another electron in order to become stable.(72) Some examples of ROS include superoxides, peroxides and hydroxyl radicals.(72) A recent study had demonstrated increased intracellular ROS levels in MCF-7 and MDA-MB-231 cells following overexpression with CYP2E1.(48) This suggests that an alteration in the levels of the P450 enzymes might play a role in the production of intracellular ROS hence proliferation of cancer cells. Figure 14: The monooxygenase P450 cycle. Binding of substrate (RH) leads to conformational change which favours the reduction of ferric iron (Fe3+) in P450. An addition of single electron from NADPH to P450 via NADPH-P450 reductase converts Fe3+ to ferrous iron (Fe2+). An oxygen molecule binds to the Fe2+RH to form the Fe2+O2.RH complex. Addition of a second electron from either the NADPH-P450 reductase or the cytochrome b5 and a proton form a Fe2+OOH.RH peroxide complex. The complex then accepts a second proton which leads to cleavage of the Fe2+OOH.RH complex into ferric oxene substrate complex, (FeO) 3+.RH and a water molecule. The ferric oxene extracts a hydrogen atom from the substrate to yield a pair of radicals Rà ¢-à and Fe2+OHà ¢-à . The last step involves binding of Rà ¢-à with the hydroxyl radical OHà ¢-à to generate the hydroxylated drug (ROH) to be realised from the complex. The P450 is then regenerated in its initial state.(73) Diagram adapted from refere nce (74). At low levels, ROS maintains normal physiological functions such as modulation of signal transduction pathways and cell proliferation.(75) However high levels of ROS can cause cellular toxicity, lipid peroxidation, DNA damage, cell proliferation arrest and apoptosis.(76-78). The antioxidant defence systems in cells comprise of a group of antioxidant compounds such as Vitamin E, superoxide dismutase, catalase and glutathione peroxidase which function to cope with the high intracellular ROS levels. However, an excessive production of ROS or a lack of antioxidants can disrupt the balance and result in oxidative stress. (72) Intracellular oxidative stress can cause DNA damage, endoplasmic reticulum (ER) stress and apoptosis.(77, 79) Oxidative stress caused by elevated levels of ROS is implicated in cancer as it is associated with alteration in DNA sequence which leads to activation of proto-oncogenes or inactivation of tumour suppression genes.(77) Such mutations may initiate cancer and provide malignant cells with advantageous characteristics as described in Figure 1 ââ¬ËHallmarks of cancerââ¬â¢ to facilitate growth and metastasis.(25, 77, 80) Increased DNA base damage resulted from hydroxyl radical attack has been reported in inflammatory breast cancer.(81) Figure 15: High levels of ROS in cell results in DNA damage, misfolded proteins, lipid peroxidation, mitochondrial dysfunction and apoptosis. The antioxidant defence systems counteract with the excessive production of ROS. An imbalance between ROS generation and antioxidant action can result in oxidative stress and threaten cell survival. Diagram adapted from reference(82).à à Ã
Wednesday, November 13, 2019
Essay --
In my opinion, the most influential time period in American history since 1945 would have to be the 1960s. So much was going on in America during this time period. Such as the civil rights movement, the counterculture, the war and so much more. I am going to focus on the counterculture because I think that out of all of the commotion that was going on in the 1960s, the counterculture has the most lasting affects and the most came out of it that we still have in our society today. They shaped music, politics, and the culture of America. They had fresh ideas that most were scared to act on or did not believe in. They had open minds and wanted everyone else to try to as well. ââ¬Å"Your mind is like a parachute, it doesn't work unless it's open.â⬠-Jordan Maxwell â⬠¨ The counterculture was so important to America because it changed norms of the early 1900s to the norms of today. The definition of the Counterculture is as follows. ââ¬Å"The counterculture of the 1960s refers to an anti-establishment cultural phenomenon that developed first in the United States and United Kingdom and spread throughout much of the Western world between the early 1960s and the early 1970s. The movement gained momentum as the African-American Civil Rights Movement continued to grow, and became revolutionary with the expansion of the US government's extensive military intervention in Vietnam.â⬠(Previous Quote taken from an online source) During the counterculture movement, peopleââ¬â¢s lifestyles started to change. People started dressing differently and acting differently. Peopleââ¬â¢s clothes transformed. They changed from vary tailored styles into looser fitting and much more revealing especially for women in public. Men started growin g their hair out and... ...id, ââ¬Å"The thing the sixties did was to show us the possibilities and the responsibility that we all had. It wasn't the answer. It just gave us a glimpse of the possibility.â⬠ââ¬âJohn Lennon that is a perfect example of how people felt and why they wanted to change so much. As you can see, the 1960s was a turning point for America. Not only did we break free of social norms in society but also the generation fought for what they thought was right. Yes maybe they were looked at a little bit strangely but in the end the ended up changing America and molding it into the place that we all call home today. "If someone thinks that love and peace is a clichà © that must have been left behind in the Sixties, that's his problem. Love and peace are eternal.â⬠ââ¬âJohn Lennon That is why, I believe the 1960s were the most influential years of American history since 1945.
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