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You searched for subject:(exosome engineering). Showing records 1 – 3 of 3 total matches.

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University of California – Santa Cruz

1. Sun, Haofan. Exosome-Based Early Detection of Cancer and Parkinson’s Disease.

Degree: Electrical Engineering, 2019, University of California – Santa Cruz

Exosomes have emerged as novel biomarkers for disease diagnostics and prognosis. Exosomes are present in bodily fluids and closely resemble the contents of their parental cells; thus, they have a huge potential to serve as a liquid biopsy tool in the diagnosis of multiple diseases. In particular, tumor exosomes have the potential as biomarkers for the early detection of cancer since their contents reflect the genomic and metabolic abnormalities in their parental cells. With the development of techniques for high-throughput purification and isolation of exosomes and exosome content analysis, exosomal proteins is rapidly becoming an important tool for the early diagnosis of cancer. Exosomes are extracellular vesicles with a diameter of 30 - 150 nm. These nanovesicles are produced by almost all types of mammalian cells and cancer cells through fusion of an intermediate endocytic compartment, namely, multivesicular bodies, with the plasma membrane. In the introduction part of this thesis, I introduce the concept of the exosome, its definition, biogenesis and characteristics, and composition. Then I discuss the use of exosomes for cancer prognosis, and α-synuclein circulating exosomes as an example to explain how exosomal proteins work and its high specificity to Parkinson Disease. Finally, I discuss the different methods of isolating and collecting specific types of exosomes. One unanswered question is at what stage of disease and cancer development can the exosome-based method be useful for diagnosis. To test the practicability of exosome-based methods in cancer and diseases diagnosis, I will establish a mathematical model and analytically calculate the concentrations of cancer-specific exosomes based on tumor growth. Then I will predict how early the exosome-based method can detect cancer and other diseases considering the detection limits of current diagnostic technologies. In addition, I will introduce and discuss the parameters required to inspect and verify the feasibility of my mathematical model. This thesis is focused on two specific exosomes: α-synuclein circulating exosomes for Parkinson disease and HSP70 proteins for liver cancer. After the exosomes are extracted and purified, they can be resuspended into a small volume solution. Therefore, exosomal samples yield higher concentrations of biomarkers in a resuspension solution than those in blood. In the following, we show that it takes about 2.05 years for a parental cell to expand to a cell population that can secrete a baseline value of the α-synuclein circulating exosomes in Parkinson disease (PD) patients, and 0.73 years for a parental tumor cell to expand to a cell population that can secrete the baseline number of HSP70 proteins circulating exosomes in liver cancer patients. In conclusion, the mathematical model I established can help us predict how exosomal protein can be used to detect cancer and PD.

Subjects/Keywords: Biology; Health sciences; Biomedical engineering; Cancer; Exosome; model; Parkinson's disease; Protein

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Sun, H. (2019). Exosome-Based Early Detection of Cancer and Parkinson’s Disease. (Thesis). University of California – Santa Cruz. Retrieved from http://www.escholarship.org/uc/item/29t198np

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Sun, Haofan. “Exosome-Based Early Detection of Cancer and Parkinson’s Disease.” 2019. Thesis, University of California – Santa Cruz. Accessed July 13, 2020. http://www.escholarship.org/uc/item/29t198np.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Sun, Haofan. “Exosome-Based Early Detection of Cancer and Parkinson’s Disease.” 2019. Web. 13 Jul 2020.

Vancouver:

Sun H. Exosome-Based Early Detection of Cancer and Parkinson’s Disease. [Internet] [Thesis]. University of California – Santa Cruz; 2019. [cited 2020 Jul 13]. Available from: http://www.escholarship.org/uc/item/29t198np.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Sun H. Exosome-Based Early Detection of Cancer and Parkinson’s Disease. [Thesis]. University of California – Santa Cruz; 2019. Available from: http://www.escholarship.org/uc/item/29t198np

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation


University of Oklahoma

2. Zhai, Mengmeng. LIPID-BASED NANOPARTICLES FOR TISSUE REGENERATION AND CANCER PHOTOTHERMAL THERAPY.

Degree: PhD, 2020, University of Oklahoma

Exosome, a cell budded nanovesicle in diameter around 30 nm to 200 nm, has been found useful for the gene and drug delivery in bone tissue regeneration and cancer therapy. Exosome derived from donor cells has some specific physical properties, such as stability, permeability, low toxicity, lower immune response, and biocompatibility for gene and drug delivery. In this dissertation, stem cell-derived exosomes were used to induce bone tissue regeneration in vitro and in vivo. In addition, exosomes were modified with tumor-homing peptide for target breast cancer therapy. In chapter 2, this study confirmed that exosomes could be employed to induce osteogenic differentiation of human mesenchymal stem cells (hMSCs) and decorate 3D-printed titanium alloy scaffolds to achieve cell-free bone regeneration on a bone radial defect rat model. Specifically, the exosomes secreted by hMSCs osteogenically pre-differentiated for different periods were applied to induce the osteogenesis of hMSCs. It was discovered that pre-differentiation for 10 and 15 days led to the production of osteogenic exosomes. Then purified exosomes were loaded into the scaffolds and the current researchers found that the cell-free exosome-coated scaffolds regenerated bone tissue as efficiently as the well-reorganized hMSC-seeded exosome-free scaffolds within 12 weeks. RNA-sequencing results suggested that these osteogenic exosomes induced the osteogenic differentiation by using their upregulated osteogenic miRNA cargos (such as Hsa-miR-146a-5p, Hsa-miR-503-5p, Hsa-miR-483-3p, and Hsa-miR-129-5p) or downregulated osteogenic miRNAs cargos (such as Hsa-miR-32-5p, Hsa-miR-133a-3p, and Hsa-miR-204-5p) to activate the PI3K/Akt and MAPK signaling pathways. Consequently, identification of osteogenic exosomes secreted by pre-differentiated stem cells and the use of them to replace stem cells represent a novel cell-free bone regeneration strategy. In Chapter 3, phage display and nanotechnology were integrated to develop novel exosome-based nanoparticles for delivering platinum nanoparticles (PtNPs), a photothermal reagent, for targeted breast cancer therapy. An exosome-internalizing peptide was first identified through a phage display technique. Then a novel nano complex (defined as the EAPW- nano complex) was developed by loading the peptide modified PtNPs into exosomes, of which the surface has been engineered to display breast cancer tumor-homing peptides. The tumor-homing peptides on exosomes led to enhanced delivery of PtNPs to the breast cancer cells in vitro and the tumors in vivo, resulting in significantly improved cancer-killing efficiency and inhibition of tumor growth. Advisors/Committee Members: Mao, Chuanbin (advisor), Rajan, Rakhi (advisor), Yip, Wai Tak (committee member), Wu, Si (committee member), Harrison, Roger (committee member).

Subjects/Keywords: photothermal therapy on breast cancer; biomaterials; bone tissue regeneration; exosome engineering

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Zhai, M. (2020). LIPID-BASED NANOPARTICLES FOR TISSUE REGENERATION AND CANCER PHOTOTHERMAL THERAPY. (Doctoral Dissertation). University of Oklahoma. Retrieved from http://hdl.handle.net/11244/324412

Chicago Manual of Style (16th Edition):

Zhai, Mengmeng. “LIPID-BASED NANOPARTICLES FOR TISSUE REGENERATION AND CANCER PHOTOTHERMAL THERAPY.” 2020. Doctoral Dissertation, University of Oklahoma. Accessed July 13, 2020. http://hdl.handle.net/11244/324412.

MLA Handbook (7th Edition):

Zhai, Mengmeng. “LIPID-BASED NANOPARTICLES FOR TISSUE REGENERATION AND CANCER PHOTOTHERMAL THERAPY.” 2020. Web. 13 Jul 2020.

Vancouver:

Zhai M. LIPID-BASED NANOPARTICLES FOR TISSUE REGENERATION AND CANCER PHOTOTHERMAL THERAPY. [Internet] [Doctoral dissertation]. University of Oklahoma; 2020. [cited 2020 Jul 13]. Available from: http://hdl.handle.net/11244/324412.

Council of Science Editors:

Zhai M. LIPID-BASED NANOPARTICLES FOR TISSUE REGENERATION AND CANCER PHOTOTHERMAL THERAPY. [Doctoral Dissertation]. University of Oklahoma; 2020. Available from: http://hdl.handle.net/11244/324412

3. Watson, Dionysios - Christos. Translational development of heterodimeric interleukin-15 for immunotherapy of HIV-1 and cancer.

Degree: 2019, University of Patras; Πανεπιστήμιο Πατρών

Background: Heterodimeric interleukin-15 (hetIL-15) is a cytokine that sustains the growth and activation of NK and cytotoxic T cells. It consists of a membrane-anchored polypeptide (IL-15 receptor α), which interacts and stabilizes the bioactive polypeptide (IL-15). This plasma membrane-anchored complex is cleaved and liberated as a bioactive heterodimeric cytokine (hetIL-15). Recombinant single-chain IL-15 and other forms of the cytokine have been shown to lead to expansion of T cells with an effector-memory, cytotoxic phenotype and enhanced cytotoxic function. hetIL-15 and other forms of IL-15 have also been shown to have anti-tumor effects in mouse models of cancer; hetIL-15 is currently being tested in humans for treatment of metastatic cancer, delivered as fixed-dose subcutaneous injections. In Rhesus macaques, high- dose hetIL-15 led to early toxicity, while immune activation decreased towards the end of treatment cycles, suggesting a need to optimize the treatment regimen. The ability of hetIL-15 to increase the abundance of cytotoxic cells makes it an appealing drug for use in HIV-1 infection, especially if activated cells infiltrate tissues known to comprise the viral reservoir, such as in lymph node follicles and the gastrointestinal tract-associated lymphoid tissues (GALT). For cancer therapy, the efficacy of IL-15 and other drugs has been shown to be significant when they are targeted to the sites of tumors. Eukaryotic cells secrete ~100 nm vesicles (extracellular vesicles; EV), which can be engineered to carry therapeutic molecules. In the emerging field of EV therapeutics, these vesicles are being designed as biological nanoparticles to deliver multiple therapeutics to tumors and other tissues. Aims: This study sought to: (a) develop an optimized dosing regimen for hetIL-15 based on its mechanism of action, in order to minimize toxicity and maximize immunological activation, (b) explore the use of hetIL-15 as part of an immunotherapeutic approach to treatment of HIV-1 infection, and (c) develop the technology and tools necessary for further development of EV as a platform to deliver hetIL-15 and other therapeutics to tumors. Methods: Healthy and SHIV-infected Rhesus macaques were treated with a 2-week cycle of increasing hetIL-15 dosages (2-64 μg/kg; “step-dose”), either subcutaneously or intraperitoneally. At the end of treatment, animals were sacrificed. Blood was collected throughout the study, lymph nodes (LN) were biopsied before/after treatment, and multiple organs (including the gastrointestinal tract) were sampled at necropsy. Vital signs, blood chemistry, clinical observation, and hetIL-15 drug level measurements were carried out throughout the study. Sampled tissues were analyzed for immune cell frequencies and phenotype by flow cytometry and/or multiplex confocal imaging with Histocytometry. Plasma viral load and cell associated viral burden was measured by qPCR and qRT-PCR using primers for SIV gag. For EV studies, a new form of the cytokine was generated by recombinant technology,…

Subjects/Keywords: Μακάκος; Ιός ανθρώπινης ανοσοανεπάρκειας; Καρκίνος; Σύνδρομο επίκτητης ανθρώπινης ανοσοανεπάρκειας; Ιό ανοσοανεπάρκειας σιμιΐδων; Ιντερλευκίνη-15; Ετεροδιμερική ιντερλευκίνη-15; Κυτταροκίνη; Ανοσοθεραπεία; Φαρμακολογία; Φαρμακοκινητική; Φαρμακοδυναμική; Ιική δεξαμενή; Τοξικολογία; Ενδοπεριτοναϊκή; Υποδόρια; Βλαστικό κέντρο; Θυλάκιο; Λεμφικό σύστημα σχετιζόμενο με τον γαστρεντερικό σωλήνα; Κυτταροτοξικά λεμπφοκύτταρα; Κύτταρα φυσικοί φονείς; Θρυματίνη Β; Εξυκυτταρικό κυστίδιο; Εξώσωμα; Τροποίηση εξωσωμάτων; Βιοπαραγωγή; Μεγάλη κλίμακα; Βιοαντιδραστήρας; Διήθηση εγκαρσίας ροής; Χρωματογραφία αποκλεισμού μεγεθών; Υπερφυγοκέντρηση; Απομώνοση; Βιοκατανομή; Δικτυοενδοθηλιακό σύστημα; Μακροφάγο; Ήπαρ; Υποδοχέας ρακοσυλλέκτης τύπου Α; Θειϊκή δεξτράνη; Φαινόμενο αυξημένης διαπερατότητας και συγκράτησης; Στόχευση κακοήθους όγκου; Νανοσωματίδιο; Πρόσληψη; Rhesus macaque; HIV-1; Cancer; AIDS; SIV; SHIV; Interleukin-15; HetIL-15; Cytokine; Immunotherapy; Pharmacology; Pharmacokinetics; Pharmacodynamics; Viral reservoir; Toxicology; Intraperitoneal; Subcutaneous; Lymph node; Germinal center; Follicle; Gastrointestinal tract associated lymphoid tissue; Cytotoxic lymphocytes; CD8+ T cells; NK cells; Granzyme B; Extracellular vesicles; Exosomes; Exosome engineering; Bioproduction; Large-scale; Bioreactor; Tangential flow filtration; Size exclusion chromatography; Ultracentrifugation; Purification; Lactadherin; MFGE8; Reticuloendothelial system; Macrophage; Liver; Scavenger receptor Class A; Dextran sulfate; Enhanced permeability and retention effect; Tumor targeting; Uptake

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Watson, D. -. C. (2019). Translational development of heterodimeric interleukin-15 for immunotherapy of HIV-1 and cancer. (Thesis). University of Patras; Πανεπιστήμιο Πατρών. Retrieved from http://hdl.handle.net/10442/hedi/47231

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Watson, Dionysios - Christos. “Translational development of heterodimeric interleukin-15 for immunotherapy of HIV-1 and cancer.” 2019. Thesis, University of Patras; Πανεπιστήμιο Πατρών. Accessed July 13, 2020. http://hdl.handle.net/10442/hedi/47231.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Watson, Dionysios - Christos. “Translational development of heterodimeric interleukin-15 for immunotherapy of HIV-1 and cancer.” 2019. Web. 13 Jul 2020.

Vancouver:

Watson D-C. Translational development of heterodimeric interleukin-15 for immunotherapy of HIV-1 and cancer. [Internet] [Thesis]. University of Patras; Πανεπιστήμιο Πατρών; 2019. [cited 2020 Jul 13]. Available from: http://hdl.handle.net/10442/hedi/47231.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Watson D-C. Translational development of heterodimeric interleukin-15 for immunotherapy of HIV-1 and cancer. [Thesis]. University of Patras; Πανεπιστήμιο Πατρών; 2019. Available from: http://hdl.handle.net/10442/hedi/47231

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

.