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Technology Development for Detection...
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Balcioglu, Mustafa.
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Technology Development for Detection of Circulating Disease Biomarkers from Liquid Biopsies Using Multifunctional Nanomaterials.
紀錄類型:
書目-電子資源 : Monograph/item
正題名/作者:
Technology Development for Detection of Circulating Disease Biomarkers from Liquid Biopsies Using Multifunctional Nanomaterials./
作者:
Balcioglu, Mustafa.
出版者:
Ann Arbor : ProQuest Dissertations & Theses, : 2018,
面頁冊數:
233 p.
附註:
Source: Dissertation Abstracts International, Volume: 79-07(E), Section: B.
Contained By:
Dissertation Abstracts International79-07B(E).
標題:
Biochemistry. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10744219
ISBN:
9780355673883
Technology Development for Detection of Circulating Disease Biomarkers from Liquid Biopsies Using Multifunctional Nanomaterials.
Balcioglu, Mustafa.
Technology Development for Detection of Circulating Disease Biomarkers from Liquid Biopsies Using Multifunctional Nanomaterials.
- Ann Arbor : ProQuest Dissertations & Theses, 2018 - 233 p.
Source: Dissertation Abstracts International, Volume: 79-07(E), Section: B.
Thesis (Ph.D.)--State University of New York at Albany, 2018.
Despite the advance health care, devastating health conditions such as cancer and infectious diseases that affect populations worldwide are too often not diagnosed until morbid symptoms become apparent in the late phase. Obtaining an early and accurate diagnosis that reveal a hidden lethal threat before the disease becomes complicated may dramatically reduce the severity of its impact on the patient's life and increase the probability of survival. For example, in the case of ovarian cancer, which is the fifth most common malignancy and the fifth leading cause of cancer mortality in women in the US, the 5-year relative survival is 45%. If the diagnosis is made in stages III and IV when the cancer is well established and spreading, 17% of the women survive at five years. However, if ovarian cancer is found (and treated) before the cancer has spread outside the ovary, the survival rate can reach 93%. The sad fact is only 15% of all ovarian cancers are found at this early stage, whereas the vast majority, 70%, are detected in stages three and four. There is therefore an apparent need for the development of highly sensitive and specific noninvasive diagnostic assays for early detection, prognostic evaluation, and recurrence monitoring. This uneasy task, however, is hindered by three existing major limitations; (1) lack of an easy, inexpensive and noninvasive serial sampling method that can replace medical procedures, which is like colonoscopy for colon cancer or mammography for breast cancer. Second, lack of definitive molecular biomarkers for specific diseases as an alternative to protein biomarkers, like PSA for prostate cancer and (3) lack of a rapid multi-marker detection platform with high sensitivity and excellent specificity.
ISBN: 9780355673883Subjects--Topical Terms:
518028
Biochemistry.
Technology Development for Detection of Circulating Disease Biomarkers from Liquid Biopsies Using Multifunctional Nanomaterials.
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Despite the advance health care, devastating health conditions such as cancer and infectious diseases that affect populations worldwide are too often not diagnosed until morbid symptoms become apparent in the late phase. Obtaining an early and accurate diagnosis that reveal a hidden lethal threat before the disease becomes complicated may dramatically reduce the severity of its impact on the patient's life and increase the probability of survival. For example, in the case of ovarian cancer, which is the fifth most common malignancy and the fifth leading cause of cancer mortality in women in the US, the 5-year relative survival is 45%. If the diagnosis is made in stages III and IV when the cancer is well established and spreading, 17% of the women survive at five years. However, if ovarian cancer is found (and treated) before the cancer has spread outside the ovary, the survival rate can reach 93%. The sad fact is only 15% of all ovarian cancers are found at this early stage, whereas the vast majority, 70%, are detected in stages three and four. There is therefore an apparent need for the development of highly sensitive and specific noninvasive diagnostic assays for early detection, prognostic evaluation, and recurrence monitoring. This uneasy task, however, is hindered by three existing major limitations; (1) lack of an easy, inexpensive and noninvasive serial sampling method that can replace medical procedures, which is like colonoscopy for colon cancer or mammography for breast cancer. Second, lack of definitive molecular biomarkers for specific diseases as an alternative to protein biomarkers, like PSA for prostate cancer and (3) lack of a rapid multi-marker detection platform with high sensitivity and excellent specificity.
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Liquid biopsy, a simple non-invasive blood test, is an emerging novel technology has the potential to overcome these restrictions. Because of its non-invasive nature, liquid biopsy can be serially collected to provide a personalized global snapshot of the total tumor burden at certain time points as well as identify specific mutations that arise during therapy. This potential in large part is driven by the fact that dying tumor cells or pathogens release their genetic materials into body fluids such as blood, urine, and saliva, and the load of circulating cell-free biomarkers are treasure trove for molecular diagnostics as they represent physiological or disease states. These biomarkers could be from whole cancer cells (CTC), to exosomes 'vesicles' containing tumor material, to proteins and peptides, to fragments of circulating cell free nucleic acids; cfDNA and cfRNA (mRNAs, lncRNAs, miRNAs).
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MicroRNAs (miRNAs) are small non-coding RNAs that act as master regulators of many cellular processes. Because aberrant miRNA expression is an early event in tumorigenesis, circulating miRNAs might reflect tumor status and predict therapy response as noninvasive diagnostic biomarkers. They have been isolated from most of the body fluids and are highly stable in the circulation system, which makes miRNAs attractive diagnostic markers. As several miRNAs may be simultaneously involved in disease progression and development, it is inadequate to generate any meaningful or conclusive information for clinical diagnostics using only a single marker. Therefore having a platform capable of performing multiplexed biological detection is an indispensable tool for accurate clinical diagnostics.
520
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To overcome these limitations, this research project exploits the unique tools provided by DNA nanotechnology, which combines two emerging fields---nano-graphene, MoS2, MNcy5.5, and AuNPs as two/three-dimensional nanoparticles in biomedicine and the role of blood-based circulating disease biomarkers (DNA/RNA) in cancer and infectious diseases---to address the challenges in diagnosis, prognosis and therapeutics. Taking advantage of controllable and programmable features of oligonucleotides, in our laboratory, two different multiplexed biomarker detection methods were developed by utilizing nanomaterials as a capture nanoplatform, DNA/RNA as circulating diseases-specific biomarkers and biofluids as minimally invasive sources.
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The first multi-marker detection approach is to engineer water-soluble two-dimensional nanoassemblies and develop methodologies to detect circulating miRNAs and DNAs in human body fluids for the state-of-the art diagnostics. Nano-graphene oxide in this approach serves as a highly stable and functional template with extraordinary ssDNA adsorption capacity and fast and ultra-efficient fluorescence quenching capability lead us to engineer a fluorescently silent nano-platform. As a first application, we demonstrate the successful utilization of nano-graphene oxide based nanoplatform for the simultaneous detection of circulating prostate cancer biomarkers from various body fluids including blood, urine, and saliva. Later, we advanced nGO-based detection nanoplatform to an easily tunable and very highly controllable stimuli-responsive nano-device by attaching thermo-responsive polymers to advance its applications and minimize the drawbacks. (Abstract shortened by ProQuest.).
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