Please follow the criteria my assignment is important for me its worth 30% , so I don’t need to information that’s not relevant , please talk specifically about the topic and questions that in background and main body ( what you mentioned in background talk about it in main body)
Topic of assignment
Anthracycline antibiotics are very commonly used chemotherapeutic agents, and one of their most serious side effects is cardiac toxicity. Describe the likely mechanism, any risk factors and an overview of how this toxicity may be prevented, focussing on the underlying pathophysiology and pharmacology.
Assessment Criteria
Present your assignment using the following information as a guide. Please copy the question that you are answering and place this at the top of your assignment.
The maximum length of the assignment is 1000 words. For each 100 words that you exceed the word limit, you will be penalised 5% of your overall mark. For example, for an assignment that is 1200 words long, your assignment will be marked according to the criteria, and the overall mark will be reduced by 10%. The question and references will not count towards your word count.
Your assignment should include the following sections:
Background: An overview of the main issue that you are discussing, more specifically a
ief background to the disease and/or the drug(s)/treatment that you are discussing. For example, you could provide a general overview of the disease and the treatment approach, including the mechanism of action of the drug/treatments that you are going to discuss in the remainder of your assignment. Approximate length 200 words.
Main Body: This will include a detailed discussion of the main question(s) within your selected assignment. Remember that this should focus on the underlying pharmacology and/or pathophysiology of the relevant disease and/or the drug(s)/treatment and specifically answer the primary question(s) – it should be in much more detail that was covered in the background. Approximate length 700 words
Overview/Conclusion: Based upon what you have written in previous sections, state the most important messages that you would like someone to have after reading your assignment. For example, can you provide a
ief overview of your assignment and/or what is your conclusion from your assignment, is this a medication/treatment that should be used for the condition or what are the risks of using this medication/treatment. Approximate length 100 words
You will also be awarded marks for appropriate referencing, presentation, layout and design as described below. Referencing should be performed according to the UniSA Harvard referencing guidelines (information is available at http:
i.unisa.edu.au/students/student-support- services/study-support/academic-integrity-and-referencing/).
Assessment Criteria
Maximum marks
Background
4
Main Body
10
Overview/Conclusion
2
References. Use of 5-10 independently sourced references that are appropriately cited and presented.
1
Presentation. No e
ors in grammar, punctuation, or spelling.
2
Layout and Design. The overall organization, design, use of space help to make the assignment interesting and to communicate the message.
1
Total
20
Length (5% penalty for each 100 additional words)
Overall Mark
20
First, just I want to clarify some points. My topic is not about anthracycline antibiotic or cancer, it is about the main side effect of this group of medications which is cardiotoxicity. In introduction , if you can change it and you can talk about anthracycline antibiotic and their mechanism of action as background in two to three lines because it is not the main point even the cancer not the main point in this assignment and then general overview of the diseases that result from using anthracycline and cause cardiotoxicity and approach of treatment. including the mechanism of action of the drug/treatments that you are going to discuss in the remainder of your assignment ( 2 or 3 mechanisms of action of cardiac toxicity that you will discuses in the main body paragraph) 200wards
In the main body, focus on the underlying pharmacology and/or pathophysiology of the relevant disease and/or the drug(s)/treatment and specifically answer the primary question(s) – it should be in much more detail that was covered in the background
If you can please talk about these diseases in more details please that you mentioned in introduction in more details. For example if can talk about Role of reactive oxidation species (ROS) and Role of topisomerase and anythings that you think it can cause cardiac toxicity explain how that happen and another thing like (Describe the likely mechanism, any risk factors and overview of how its toxicity may be prevented) AND risk factors that can related to anthracycline like (female gender , oxidative and so on…..)
In prevention if you can write it as paragraph and you can summaries to be in the range of 700wards.
In conclusion general overview.
Thank You ,,,,
Other References you can use some of them if you like
Bharti, R., Dey, G. and Mandal, M., 2016. Cancer development, chemoresistance, epithelial to mesenchymal transition and stem cells: A snapshot of IL-6 mediated involvement. Cancer letters,
Bhattacharya, B. and Mukherjee, S., 2015. Cancer therapy using antibiotics. Journal of Cancer Therapy
Greaves, P., 2011. Histopathology of preclinical toxicity studies: interpretation and relevance in drug safety evaluation.
Marosi, C., 2012. Complications of chemotherapy in neuro-oncology. In Handbook of clinical neurology Menna, P. and Salvatorelli, E., 2017. Primary Prevention Strategies for Anthracycline Cardiotoxicity: A Brief Overview. Chemotherapy, 62, pp XXXXXXXXXX.
Rizvi, S.F.A., 2018. Anthracyclines: Mechanism of Action, Classification, Pharmacokinetics and Future–A Mini Review.
Mechanisms of Anthracycline Cardiac Injury: Can we identify
strategies for cardio-protection?
Douglas B. Sawyer1, Xuyang Peng1, Billy Chen2, Laura Pentassuglia1, and Chee Chew
Lim1
1Department of Medicine, Vande
ilt University
2Department of Molecular Medicine, Boston University
Summary
Anthracycline antibiotics have saved the lives of many cancer victims in the 50 plus years since thei
discovery. A major limitation of their use is the dose-limiting cardiotoxicity. Efforts focusing on
understanding the biochemical basis for anthracycline cardiac effects have provided several strategies
cu
ently in clinical use: limit dose exposure; encapsulate anthracyclines in liposomes to reduce
myocardial uptake; administer concu
ently with the iron chelator dexrazoxane to reduce free iron-
catalyzed reactive oxygen species formation; modification of anthracycline structure in an effort to
educe myocardial toxicity. In spite of these efforts, anthracycline-induced heart failure continues to
occur with consequences for both mo
idity and mortality. Our inability to predict and prevent
anthracycline cardiotoxicity is in part due to the fact that the molecular and cellular mechanisms
emain controversial and incompletely understood. Studies examining the effects of anthracyclines
in cardiac myocytes in vitro and small animals in vivo have demonstrated several forms of cardiac
injury, and it remains unclear how these translate to the clinical setting. Given the clinical evidence
that myocyte death occurs after anthracycline exposure in the form of elevations in serum troponin,
myocyte cell death appears to be a probable mechanism for anthracycline-induced cardiac injury.
Other mechanisms of myocyte injury include the development of cellular ‘sarcopenia’ characterized
y disruption of normal sarcomere structure. Anthracyclines suppress expression of several cardiac
transcription factors, and this may play a role in the development of myocyte death as well as
sarcopenia. Degradation of the giant myofilament protein titin may represent an important proximal
step that leads to accelerated myofilament degradation. An interesting interaction has been noted
clinically between anthracyclines and newer cancer therapies that target the e
B2 receptor tyrosine
kinase. There is now evidence that e
B2 signaling in response to the ligand neuregulin regulates
anthracycline uptake into cells via the multidrug-resistance protein. Therefore upregulation of cardiac
neuregulin signaling may be one strategy to limit myocardial anthracycline injury. Moreover,
assessing an individual’s risk for anthracycline injury may be improved by having some measure of
endogenous activity of this and other myocardial protective signals.
© 2010 Elsevier Inc. All rights reserved.
Co
espondence: Douglas B. Sawyer, 383 Preston Research Building, 2220 Pierce Avenue, Vande
ilt University, Nashville, TN 37232,
Douglas.b.sawyer@vande
ilt.edu, Phone: XXXXXXXXXX, Fax: XXXXXXXXXX.
Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting
proof before it is published in its final citable form. Please note that during the production process e
ors may be discovered which could
affect the content, and all legal disclaimers that apply to the journal pertain.
NIH Public Access
Author Manuscript
Prog Cardiovasc Dis. Author manuscript; available in PMC 2011 September 1.
Published in final edited form as:
Prog Cardiovasc Dis. 2010 ; 53(2): 105–113. doi:10.1016/j.pcad XXXXXXXXXX.
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IH
-PA Author M
anuscript
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Muhammad Yasi
Highlight
Muhammad Yasi
Highlight
Overview of Anthracycline cardiotoxicity
Anthracycline antibiotics are highly effective and widely used cytotoxic agents with
applications in the treatment of multiple cancers. The mechanisms of cytotoxicity of
anthracyclines in cancer cells are diverse including (reviewed in [1]): 1) inhibition of both
DNA replication and RNA transcription; 2) free radical generation, leading to DNA damage
or lipid peroxidation; 3) DNA alkylation; 4) DNA cross-linking; 5) interference with DNA
unwinding of DNA strand separation and helicase activity; 6) direct mem
ane damage due to
lipid oxidation; 7) inhibition of topoisomerase II. In response to some or all of these effects,
tumor cell growth is inhibited and cells are more likely to die by one or more mechanisms.
A major limitation of anthracycline use is a cumulative dose-dependent cardiac toxicity.
Cardiotoxicity has long been considered to occur by mechanisms other than those mediating
their antitumor effectiveness, a concept that raises hope for development of strategies fo
protecting the heart while not diminishing tumor response [2]. Early strategies to prevent
cardiac toxicity included reductions in single doses of anthracyclines as well prolonging the
infusion of drug to limit peak serum concentrations [3]. However, in spite of these efforts the
cardiotoxicity remains [4].
Multiple mechanisms of anthracycline-induced cardiac cellular injury have been proposed
ased upon studies in animals and cell culture systems, and it remains unclear which of these
are at work in the clinical context of anthracycline use (see Figure). Most mechanisms proposed
involve oxidative stress induced by the anthracyclines, though it is not clear why this would
esult in preferential toxicity to the myocardium. Anthracyclines induce mem
ane damage
via lipid peroxidation in all tissues, including the heart [5]. While formation of reactive oxygen
species is induced by the quinone moiety of anthracyclines, oxidative stress can also occur via
induction of nitric oxide synthase, leading to nitric oxide and peroxynitrite formation [6]. This
mechanism has been linked to nitration and inactivation of key enzymes in the heart including
myofi
illar creatine kinase [7]. Anthracyclines also cause impairment of mem
ane binding,
assembly, and enzymatic