Hyaluronan and CD44
Hyaluronic acid (HA, hyaluronan) is a negatively charged glycosaminoglycan composed of repeating disaccharide units of N-acetylglucosamine and d-glucuronic acid. Excess hyaluronan is present in various tumor types including breast, prostate, and pancreatic cancers.121–123 Accumulation of hyaluronan has been associated with increased aggressiveness, less treatable forms of the disease and poor prognoses.124 Hyaluronan is continuously secreted and due to its chemical structure, hyaluronan absorbs interstitial fluid which increases the pressure in the microenvironment of the tumor. More importantly, this increased pressure in the tumor microenvironment promotes poor perfusion which leads hypoxia.125 A hypoxic environment leads to increased production of hypoxia-inducible factor-1α (HIF-1α) which in turn increases the amount of hyaluronan production and accumulation, thus creating a positive feedback loop promoting increased interstitial pressure and hyaluronan accumulation.126,127 Hyaluronan is found in extremely high levels in most human pancreatic cancer cases. Greater than 80% of pancreatic tumors contain high levels of hyaluronan.122,123,125 Additionally, animal models of pancreatic cancer also demonstrate increased amounts on hyaluronan accumulation.122,125 In vitro studies also demonstrate that hyaluronan increases the rate of tumor cell growth and increased migratory capacity. Pancreatic cancer cell models grown in culture in a matrix made with hyaluronan grow faster and migrate more readily than pancreatic cancer cells cultured in matrices lacking hyaluronan.128,129 Hyaluronan removal from the interstitial fluid in cancer patients reduces interstitial fluid pressure, increases tumor perfusion, and decreases hyaluronan accumulation.126,127 In animal model studies, reducing hyaluronan synthesis is able to prevent the growth of pancreatic cancer.130,131 The hyaluronan synthesis inhibitor 4-methylumbelliferone and its derivatives suppress metastasis in various tumors.132–134 Other methods of reducing hyaluronan or its synthesis have also shown to be able to reduce pancreatic cell growth, metastasis, and make pancreatic cancer more amenable to additional therapeutic options.135,136
Another clinical focus on targeting HA takes advantage of its putative cell receptor CD44, cluster of differentiation 44. CD44 is a ubiquitously expressed glycol protein on the surface of mammalian cells that participates in the regulation in a number of normal and diseased-related biological functions. Just as hyaluronan has been shown to be overexpressed in pancreatic cancer, so too has CD44.137 Utilizing CD44 as a receptor-based target in treating aggressive cancers is in line with targeting receptors in other forms of less aggressive cancers. Recently, other receptors, transferrin, folate, epidermal growth factor along with CD44, have shown promise as selective targets for small-molecule therapy.138–146 More importantly, recent approaches have focused on targeting CD44 using various alternative approaches such as antibodies, aptamers, as well as peptides.147 CD44, a stem-like cell receptor, is known to be associated with promoting tumor progression in breast cancer cells.146 CD44 is widely known to promote tumor cell migration as well as increased drug resistance in advanced breast cancers.146 All of these characteristics are synonymous with aggressive forms of cancers, such as pancreatic cancer.
CD44 is a member of a family of glycoproteins that function in extracellular adhesion and signal transduction.148 CD44 is found on chromosome 11 in humans and is highly conserved. The protein contains a cytoplasmic domain, transmembrane domain, as well as an extracellular domain. In addition to these domains, the protein also includes a variable region and an N-terminal globular region that permits ligand binding, typically to HA.149 Due to the variable region, the CD44 family is comprised of more than 20 different isoforms that are derived from posttranscriptional modification as well as alternative splicing.148,150,151 The variability in CD44 expression is closely correlated to its role in tumor progression, metastasis, and drug resistance. CD44 variants 8–10 have been associated with increased invasive capacity in melanoma cancers.152 Melanoma cells expressing CD44 variants 8–10 (CD44v8–10, variable exons 8–10) demonstrated a significant loss of endothelial junctions and increased invasive capacity. Melanoma cells that expressed the standard version of CD44 maintained endothelial junction integrity and were not invasive.152 Another study, examining the expression level of CD44v9 isoform in human pancreatic cancer, demonstrated an increased expression of multidrug resistance protein 1 (MDR1).153
Since CD44 and more importantly its variants are associated with tumor progression and increased aggressiveness, efforts have been made to produce CD44-targeted therapies. The majority of CD44-based therapies have utilized monoclonal antibodies. CD44 antibody therapy has been shown to specifically target and inhibit CD44 receptors on cancer cells.154 Anti-CD44 antibodies prevent CD44 from interacting with its receptors and the tumor matrix. HI44, an anti-CD44 monoclonal antibody is able to block the progression on acute myeloid leukemia (AML).155 Other anti-CD44 monoclonal antibodies (H90 and A3D8) are able to block the progression of other forms of AML.156 In relationship to pancreatic cancer, CD44v6 (variant isoform 6) is highly expressed and utilizing an anti-CD44v6 antibody is able to inhibit tumor growth and metastasis.157,158 Moreover, this same anti-CD44v6 therapy has been tested in a Phase I clinical trial for head and neck squamous cell carcinoma, with promising results. Initial results demonstrate significant antitumor potential, accumulation of the antibody in tumors with no reported toxicity.159,160 In addition to these anti-CD44 antibody studies, recent advances in nanomaterials have utilized RNA aptamers conjugated to liposomes to specifically target tumor cells.161 Findings from these studies are promising albeit still in the experimental stage.
CD44 has become increasingly popular as an active target for cancer therapeutics. Although CD44 is ubiquitously expressed throughout the body, its expression is significantly higher in tumor cells, especially solid tumors like pancreatic and breast cancer.146,162 Its binding partner HA can be used as a delivery vehicle since it is easily modified to accommodate functional groups necessary to attach potential therapeutic molecules. Targeting the CD44/HA molecular relationship has revealed some very promising approaches. Many new trials are designed to target CD44/HA in various cancers and preliminary studies have demonstrated encouraging results.163–166 Together CD44 and HA serve as convenient and promising therapeutic targets in aggressive cancers including pancreatic cancer.
First of all, it is important to explain what the word "synthesis" means. It is a mix of elements used to draw the whole picture. That is how one can conclude that a synthesis essay stands for the sort of essay which combines various points into a whole to defend so-called thesis statement. A thesis is the main idea of the essay. Students should write it in the last sentence of their introduction. Frequently, it comes with a piece that a student has to observe.
The main success factor of writing a good synthesis essay is an in-depth research based on the relevant sources. A student has to perceive the goal of the analyzed content, its rhetoric, and the arguments suggested by the author. To make it short, the writer simply has to provide an answer to the question: "So what?" Type in your personal claim. The rest of your synthesis essay in English should be built around that main sentence.
Choose Synthesis Essay Topic Before You Write the First Page
Sometimes, the teacher does not provide a specific topic or question to answer. In that cases, the student has a right to select any topic for his synthesis essay. Mind that your entire writing will be limited to the chosen question, so make your decision wisely. Select a topic for which it would be easy to write as many arguments as needed. Usually, there are 3-5 arguments in the academic essay.
The prompt has to be debatable. It has to motivate the readers to continue the discussion. Several centuries ago, the US population would support the ideas of Andrew Jackson concerning the negative sides of Native American people. However, today the situation is completely different. Any sort of discrimination is forbidden in the United States. The way you select the primary questions depends on your specific task. Make sure to decide on the text that may have opposing views. In other words, choose an article with the strong argument which may encourage your readers not just to read the synthesis essay from cover to cover, but also go on discussing the selected questions.
The best topics for your essay writing would always sound negotiable like these examples:
- Minimum salary
- For and against abortions
- Global warming
- Regulations for immigrants
- Daylight storage
- Gun control
- Drug abuse
- Social media
- Artificial intelligence
- Political authorities
- Alcohol and tobacco restrictions
- Anorexia nervosa
It is easy to find the sufficient amount of information on any of these essay topics as they are relevant for people of all times, ages, and nationalities.
Writing Thesis Statement and Outline Page
After you decide on your topic or main questions to discuss, move to your sources. Make sure all gathered sources are related to your essay topic. Also, they have to be no older than 5-10 years as things change dynamically.
Thoroughly study all sources to get the main point. Select the best sources to use citations from them in your essay. It will serve as a perfect evidence to support your argument. Structure your claim. Write down thesis statement which is the main idea of the whole synthesis essay.
Thesis example: With the help of historical episodes, it is possible to point to the human evolution based on how infinity was interpreted in different epochs.
Another example: Only through an understanding of the causes of medical mistakes and their prevention on the early stages, the number of medical gaps will go down as well as the number of unintentional deaths in the United States.
You can view more example online without paying a cent.
As for the outline, this is a plan of your synthesis essay. Writing this part will assist you in maintaining the structure of your essay. In case your essay is going to have three main sections, divide the outline into three chunks respectively. Insert evidence to support your thesis, include sub-arguments along with all specific points. Every part should have a name (except for the introduction and conclusion- you may leave them this way). Every point (which is also an argument) must prove the major claim of your essay. Avoid additional information or tangents as these elements may hinder the essay. It is recommended to write down the information which contradicts with your thesis. It will make the essay more persuasive. Your synthesis essay has to be as strong as possible.
The Structure of Any Type of a Good Academic Essay
Read all sources thoroughly, especially when you work with articles instead of the thick books. Never summarize sources or copy-paste ideas of other authors. It is strictly forbidden. You may write summaries only if you have to write an annotated bibliography. Synthesis denotes analysis instead of the abstracts of your readings.
The example of your essay structure may be:
- Argument #1
- Argument #2
- Argument #3
- Argument 1
- Evidence (cite a source)
- Analysis of Evidence
- Argument 2
- Evidence (cite a source)
- Analysis of Evidence
- Argument 3
- Evidence (cite a source)
- Analysis of Evidence
- Argument 1
- Restate thesis and answer all the questions left behind
What about the Writing Style?
Formatting is an important condition of the successful synthesis essay. Academic writing defines several formats. Their names are related to the scientific or educational organizations that established these styles.
The most widespread formats are:
The first one is applied to the essays in Humanities. The second one is used while writing essays on Education, Psychology, and Science. Turabian or Chicago format is excellent for Business, History, and Fine Arts.
There is a Purdue Owl guide available online for free which can tell more about each of the existing academic writing styles. It has all the details about MLA and APA, while Easybib and some other online citation generators help students to format essays automatically. Simply insert your external sources to get proper citations for them.
Here are the basic nuances to consider:
- Times New Roman
- 12 pt font
- Double-spaced text
- 1" margins all around
- Top right of the page should have student's last name and page number
- Titles and headings are put in the center
- The header must have your name, your professor's name, course number, and the full date (dd/mm/yy)
- The last page is Bibliography page (a.k.a. Works Cited or References)
It is an example of MLA synthesis essay. Other examples and templates are available online for free. You can find an example of a page in APA style here.
Features of an AP Synthesis Essay in English
AP English Language and Composition is a separate academic course. Students who are enrolled in this class must perform a deep understanding of the subject matter through using various sources and operating with the information they already know. Grammar, spelling, structure, and originality might be insufficient to receive the highest score on your AP exam. The writing has to be "defending, challenging, qualifying the claim." Once you obtain the course syllabus, it is better to study it to learn the exact test dates and what it would look like.
It is important to concentrate on three main branches of the AP English and Composition. Those are argument, synthesis, and rhetoric. That is why all three elements should be present in your synthesis essay. Let’s have a closer look.
The argument is the simplest part; it's about writing your thesis and gathering evidence from the selected sources to defend your ideas. Prove to your reader that your point of view is correct.
Synthesis demands that a student reads multiple sources and defines pros and cons of the chosen topic (or for and against, if you wish). It is critical as it helps to create your personal claim.
Rhetorical analysis is all about the author and his goals. It has to explain the purpose of writing as well as describe the target audience. Finally, it explains the ways in which the writer attracts the readers and structures the claim.
Useful Prompts Associated with Writing Synthesis Essay
Memorize these acronyms to be able to answer all questions of your synthesis essay properly.
Advice #1: SOAPS
It's all about determining the speaker, occasion, audience, purpose, and subject.
Have a look at our example: The American Health Association believes that only through an understanding of the causes of medical mistakes and their prevention on the early stages, the number of medical gaps will go down as well as the number of unintentional deaths in the United States.
Speaker: The American Health Association has a bias against the inexperienced medical personnel.
Occasion: The American Health Association has held its meeting on Abbey Square, New York, on the 10th of November 2016.
Audience: The report written by The American Health Association was addressed to the doctors of the main regional hospitals in NY.
Purpose: The American Health Association tries to point to the main causes of unintentional deaths in the US hospitals. It performs against the improper medical treatment.
Subject: The subject is the increased number of fatal outcomes due to the lack of healthcare education and professionalism of the local personnel.
Advice #2: Logos, Ethos, and Pathos
We are speaking about the reasons, philosophy, and emotion respectively. AP Lang exam requires you to deal with all three Latin words effectively.
When there are some facts and statistics in the chosen text, the writer deals with Logos. Return to the background information all the time to make your synthesis essay as persuasive a possible.
The vivid imagery and powerful words are the signs of Pathos. It is effective for relating the readers to the essay on the emotional level.
If you aim to show the accountability and credibility of your synthesis essay, you deal with Ethos. State some facts that prove your competence in the chosen field so that the audience will have no doubt that you are right.
Watch out as often, Logos, Ethos, and Pathos may lead to the usage of logical fallacies.
It would be a great strategy for any sort of textual analysis. When you are reading the selected piece, make an attempt to pinpoint Diction, Imagery, Details, Language, and Sentence Structure. Add whatever seems more vivid to you into your analysis.
As you can see, it is not that easy to write a synthesis essay. Many students have problems either with writing or analyzing sources. Luckily, there is an opportunity to order an instant help with synthesis essay for an affordable price. When you face any doubts, turn to the expert online service which will write the whole essay to bring you to the highest score!
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