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You searched for subject:( Microbubbles 60). Showing records 1 – 3 of 3 total matches.

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1. Warram, Jason M. (Jason Morgan). Strategies for combined screening and imaging of breast cancer.

Degree: PhD, 2011, University of Alabama – Birmingham

Successful treatment of breast cancer directly correlates with tumor stage and grade at diagnosis. Early diagnosis leads to a five-year relative survival rate of 96.8% as opposed to only a 22.5% five-year survival rate when diagnosed at late stage. Cancerspecific mechanisms need to be extended to enable cancer detection in an individual patient, in particular, the metastatic burden that currently cannot be assessed by conventional imaging. This approach for cancer detection would remove the biases of patient characteristics, permit immediate diagnostic feedback, improve sensitivity for early detection of small metastatic lesions, and be cost effective. Toward this goal, the cancer-specific diagnostic adenovirus (Ad) vector (Ad5/3-Id1-SEAP-Id1-mCherry) was produced that includes a human secreted embryonic alkaline phosphatase (SEAP) reporter for blood-based screening and a fluorescent reporter (mCherry) for localized imaging. Importantly, the cancer-specific promoter Id1 was selected to drive both reporters due to the correlation between aggressive cancer phenotypes and high Id1 expression. Safety and efficacy issues have limited the use of recombinant Ad for routine clinical applications. To overcome this impediment, ultrasound microbubbles (MB) were developed to improve Ad delivery to the tumor vasculature. This was achieved by targeting the Ad packaged MB to receptors overexpressed in the tumor, namely αVβ3 integrin, P-selectin, and VEGFR2. During in vitro assessment, both SEAP and mCherry reporter expression was shown to correlate with cancer cell phenotype. In a tumorbearing mouse model, SEAP reporter expression was found to be 14-fold over background when as little as 2.5% of tumor cells were infected. Triple-targeted MBs displayed enhanced affinity for tumor vasculature when assessed in vitro and in vivo. Packaging of the targeted MBs with diagnostic Ad was confirmed and the approach was tested in a tumor-bearing mouse model. Groups receiving the targeted Ad packaged MBs displayed a 4-fold increase in SEAP reporter expression over groups receiving equivalent unpackaged Ad dosing. In addition, the mCherry fluorescence reporter was localized in the tumor. Safe delivery of a non-invasive diagnostic reporter system using FDA approved MBs has the potential for immediate application, allowing this diagnostic system to impact populations currently in need of more advanced and sensitive detection modalities.

1 online resource (xi, 111 p. : ill., digital, PDF file)

Pathology

Joint Health Sciences;

breast cancer screening gene therapy microbubbles ultrasound contrast agent adenovirus delivery

UNRESTRICTED

Advisors/Committee Members: Sanderson, Ralph D., Borovjagin, Anton V.<br>, Feng, Xu<br>, Frost, Andra R.<br>, Lopez, Richard D.<br>, Ponnazhagan, Selvarangan<br>, Zinn, Kurt R..

Subjects/Keywords: Adenoviridae  – genetics<; br>; Breast Neoplasms  – diagnosis<; br>; Gene Therapy<; br>; Mass Screening  – methods<; br>; Microbubbles<; br>; Neoplasm Metastasis<; br>; Promoter Regions, Genetic  – genetics<; br>; Vascular Endothelial Growth Factor Receptor-2  – immunology

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APA (6th Edition):

Warram, J. M. (. M. (2011). Strategies for combined screening and imaging of breast cancer. (Doctoral Dissertation). University of Alabama – Birmingham. Retrieved from http://contentdm.mhsl.uab.edu/u?/etd,881

Chicago Manual of Style (16th Edition):

Warram, Jason M (Jason Morgan). “Strategies for combined screening and imaging of breast cancer.” 2011. Doctoral Dissertation, University of Alabama – Birmingham. Accessed March 29, 2020. http://contentdm.mhsl.uab.edu/u?/etd,881.

MLA Handbook (7th Edition):

Warram, Jason M (Jason Morgan). “Strategies for combined screening and imaging of breast cancer.” 2011. Web. 29 Mar 2020.

Vancouver:

Warram JM(M. Strategies for combined screening and imaging of breast cancer. [Internet] [Doctoral dissertation]. University of Alabama – Birmingham; 2011. [cited 2020 Mar 29]. Available from: http://contentdm.mhsl.uab.edu/u?/etd,881.

Council of Science Editors:

Warram JM(M. Strategies for combined screening and imaging of breast cancer. [Doctoral Dissertation]. University of Alabama – Birmingham; 2011. Available from: http://contentdm.mhsl.uab.edu/u?/etd,881

2. Saini, Reshu. Model system using controlled receptor expression for molecular ultrasound imaging applications.

Degree: MS, 2012, University of Alabama – Birmingham

Ultrasound is a noninvasive, inexpensive imaging modality used to characterize biological tissues. Targeted contrast-enhanced ultrasound imaging is an emerging preclinical strategy which uses contrast agents for characterization of biological processes on a molecular level. These microbubble agents are lipid shelled micron-sized particles that have the capability to be coated with ligands such as antibodies or small peptides in order to bind to their target receptors. Molecular ultrasound imaging, using these targeted contrast agents, allows for a quantitative assessment of molecular targets with a high sensitivity. Although this technique is in preclinical research, further advances in contrast agent design and potential may soon bring clinical translation into human studies. This research proposal explores a novel model system for evaluating targeted ultrasound contrast agents using adenoviral vectors to regulate targeted receptor expression. Target receptors were induced using a green fluorescent protein (GFP) reporter adenoviral (Ad) vector for gene transfer and expression of the hemagglutinin (HA) tag. Receptors were modulated in vitro and in vivo by varying the viral dose. Targeted contrast agents, or microbubbles (MB), were conjugated with antibodies (anti-HA) using biotin-streptavidin chemistry and MB accumulation to target receptors is quantitatively characterized through microscopy or ultrasound imaging. The correlation established between the binding of contrast agents to the induced modulated receptors has the potential to contribute to therapeutic monitoring of various diseases such as cancer, inflammation, and thrombosis.

M.S.

1 online resource (x, 47 p.) :ill. (some col.), facsim.

Biomedical Engineering

Engineering

ultrasound, microbubbles, contrast agents, adenoviral vector

UNRESTRICTED

Advisors/Committee Members: Kenneth Hoyt.

Subjects/Keywords: Contrast-enhanced ultrasound<; br>; Microbubbles – Diagnostic use<; br>; Ultrasound contrast media<; br>; Adenoviruses<; br>; Genetic vectors<; br>; Viruses – Receptors<; br>; Genetic regulation

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

APA (6th Edition):

Saini, R. (2012). Model system using controlled receptor expression for molecular ultrasound imaging applications. (Masters Thesis). University of Alabama – Birmingham. Retrieved from http://contentdm.mhsl.uab.edu/u?/etd,1327

Chicago Manual of Style (16th Edition):

Saini, Reshu. “Model system using controlled receptor expression for molecular ultrasound imaging applications.” 2012. Masters Thesis, University of Alabama – Birmingham. Accessed March 29, 2020. http://contentdm.mhsl.uab.edu/u?/etd,1327.

MLA Handbook (7th Edition):

Saini, Reshu. “Model system using controlled receptor expression for molecular ultrasound imaging applications.” 2012. Web. 29 Mar 2020.

Vancouver:

Saini R. Model system using controlled receptor expression for molecular ultrasound imaging applications. [Internet] [Masters thesis]. University of Alabama – Birmingham; 2012. [cited 2020 Mar 29]. Available from: http://contentdm.mhsl.uab.edu/u?/etd,1327.

Council of Science Editors:

Saini R. Model system using controlled receptor expression for molecular ultrasound imaging applications. [Masters Thesis]. University of Alabama – Birmingham; 2012. Available from: http://contentdm.mhsl.uab.edu/u?/etd,1327

3. Nande, Rounak Paramjeet. Investigation Of Ultrasound Targeted Microbubbles As A Therapeutic Gene Delivery System For Prostate Cancer.

Degree: 2015, Marshall University

A major challenge for effective gene therapy is systemic delivery of viruses carrying therapeutic genes into affected tissue. The immunogenic nature of human adenoviruses (Ads) limits their use for intratumoral (IT) injection in gene therapy. Ads transfection is further hampered by the fluctuating presence of Coxsackie and Adenovirus Receptor (CAR) and integrins on the cells’ surface. To circumvent these limitations we developed a novel approach wherein Ads are encapsulated inside the shell of lyophilized, lipid-encapsulated, perfluorocarbon microbubbles (MBs)/ultrasound (US) contrast agents, which act as delivery vehicles for a sitespecific gene transfer system. We performed infection studies with Ad.GFP (Green Fluorescent Protein), Ad.mda-7 (melanoma differentiation associated gene 7) and CTV.mda-7 on human DU145 and mouse prostate cancer cells as well as observed enhanced GFP expression when Ad.GFP was delivered by MBs and US. Our results show that US breaks open the MB/Ads complexes by undergoing cavitation at the sonoporated site, which allows Ads to transfer their transgene only to the sonoporated region. Cavitation collapse of the MBs creates small shockwaves that increase cell permeability by forming temporary micropores on the cell surface bypassing the receptormediated dependence of Ads for transfection. Fetal bovine serum (FBS) containing complement did not allow the unprotected Ads to infect the cells; however, MBs complexed with Ad.GFP did infect DU145 and TRAMP-C2 cells in a FBS rich media. We studied MB assisted gene delivery of reporter (GFP) and therapeutic genes (p53, Rb, Rb2 (p130) and Mda-7/IL-24) into prostate cancer (PC) xenografted in immune-compromised athymic mice. The results demonstrated that MBs protect the host from unspecific viral immune response thus protecting the viral payload and allowing for intravenous (IV) injection rather than IT injection. Additionally, Ad gene transfer was enhanced at the targeted/sonoporated mice tumor xenografts. This research demonstrated mda-7’s efficacy in reducing primary (treated) and untreated tumors that simulated the presence of metastasis in athymic mice xenograft models bearing human PC cells. Bystander anti-tumor activity of mda-7, a secreted cytokine was noted for non-targeted tumors. Earlier in vitro studies on the combination of radiation and gene therapy (Ad.p53, Ad.Rb, and Ad.p130) demonstrated an increase in the percentage of cell death for DU145 cells. We also studied UTMD (ultrasound targeted microbubble destruction) gene therapy in combination with external beam radiation for radiation resistant PC. The results demonstrated an enhanced therapeutic benefit of tumor suppressor genes in radiation resistant PC. We also demonstrated an increase in the expression of tumor suppressor genes at the tumor site due to MBs and US. These findings highlight the potential therapeutic benefit of this novel image guided gene transfer technology alone or in combination with external beam radiation for prostate cancer patients with therapy resistant…

Subjects/Keywords: Apoptosis Induction; Microbubbles; Prostate Cancer; Systemic targeted viral gene delivery; Ultrasound; Ultrasound Contrast Agents; <; p>; Prostate<; strong>;  – <; /strong>; Cancer  – Research.<; /p>; <; p>; Gene therapy  – Research.<; /p>;

…22 Figure 5. Schematic representation of different coated microbubbles… …causing microbubbles to behave in different ways that leads to endothelial pore formation and… …microbubbles… …60 Figure 16. In vitro assessment of Ad.GFP uptake in murine and human carcinoma cell lines… …perfluorocarbon microbubbles (MBs)/ultrasound (US) contrast agents, which act as… 

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

APA (6th Edition):

Nande, R. P. (2015). Investigation Of Ultrasound Targeted Microbubbles As A Therapeutic Gene Delivery System For Prostate Cancer. (Thesis). Marshall University. Retrieved from http://mds.marshall.edu/etd/915

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):

Nande, Rounak Paramjeet. “Investigation Of Ultrasound Targeted Microbubbles As A Therapeutic Gene Delivery System For Prostate Cancer.” 2015. Thesis, Marshall University. Accessed March 29, 2020. http://mds.marshall.edu/etd/915.

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

MLA Handbook (7th Edition):

Nande, Rounak Paramjeet. “Investigation Of Ultrasound Targeted Microbubbles As A Therapeutic Gene Delivery System For Prostate Cancer.” 2015. Web. 29 Mar 2020.

Vancouver:

Nande RP. Investigation Of Ultrasound Targeted Microbubbles As A Therapeutic Gene Delivery System For Prostate Cancer. [Internet] [Thesis]. Marshall University; 2015. [cited 2020 Mar 29]. Available from: http://mds.marshall.edu/etd/915.

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

Council of Science Editors:

Nande RP. Investigation Of Ultrasound Targeted Microbubbles As A Therapeutic Gene Delivery System For Prostate Cancer. [Thesis]. Marshall University; 2015. Available from: http://mds.marshall.edu/etd/915

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

.