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Title: USING THE KETOGENIC DIET AS AN ADJUVANT TO CANCER THERAPY: A SYSTEMATIC REVIEW.
Creator: Risola, Melanie L, Lee, Eunkyung, University of Central Florida
Abstract / Description: Cancer is the second leading cause of death in the United States. Evidence shows that a conventional western diet may contribute to the proliferation of cancer cells, affecting their prognosis. The aim of this review is to examine the efficacy and safety of using the ketogenic diet as an adjuvant to traditional cancer therapy. The systematic literature search was performed in October 2018 on two search engines: EBSCOhost (Medline, CINHAL, Cochrane Central Register of Controlled Trials) and...
Show moreCancer is the second leading cause of death in the United States. Evidence shows that a conventional western diet may contribute to the proliferation of cancer cells, affecting their prognosis. The aim of this review is to examine the efficacy and safety of using the ketogenic diet as an adjuvant to traditional cancer therapy. The systematic literature search was performed in October 2018 on two search engines: EBSCOhost (Medline, CINHAL, Cochrane Central Register of Controlled Trials) and Web of Science using the following key terms: ketogenic diet, high fat and low-carbohydrate diet, Atkins diet, cancer or neoplasms+. The search limitations included clinical studies among adult cancer patients. A total of 544 publications were initially identified. After the first title/abstract screening, 22 articles were eligible for full-text screening; finally, 3 were eligible for data extraction. We synthesized the effects of the ketogenic diet on cancer progression and safety by extracting and summarizing data on 4 items: 1) study characteristics, 2) characteristics of study participants, 3) diet composition and duration, and 4) key findings for efficacy and safety. Although only 3 studies were included, it was observed that more patients who adhered to the ketogenic diet than patients who did not experienced stability of disease and response to treatment. Patients who received the ketogenic diet also experienced a decrease in tumor size, cholesterol, fasting glucose, and triglyceride levels at 90 days. No statistically significant anthropometric changes were experienced; patients weight was maintained. However, more clinical evidence is necessary before applying the ketogenic diet in an oncological setting.
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Date Issued: 2019
Identifier: CFH2000499, ucf:45661
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFH2000499

Title: NURSING INTERVENTIONS THAT FACILITATE END-OF-LIFE DECISION-MAKING IN PEDIATRIC ONCOLOGY.
Creator: Baeringer, Lauren, Wink, Diane, University of Central Florida
Abstract / Description: Nearly one-third of all pediatric oncology patients die from their disease, so nurses need to have an evidence-based standard of practice to guide their role in end-of-life decision-making. The purpose of this integrative review is to analyze current research on end-of-life decision-making within pediatric oncology to create a practice guideline for nurses working with this patient population. Eleven studies were examined to identify nursing interventions regarding the role of the nurse in...
Show moreNearly one-third of all pediatric oncology patients die from their disease, so nurses need to have an evidence-based standard of practice to guide their role in end-of-life decision-making. The purpose of this integrative review is to analyze current research on end-of-life decision-making within pediatric oncology to create a practice guideline for nurses working with this patient population. Eleven studies were examined to identify nursing interventions regarding the role of the nurse in end-of-life care, the role of the nurse in end-of-life decision-making, parent involvement in end-of-life decision-making, and child involvement in end-of-life decision-making, including the child's ability to participate in end-of-life decision-making. Based on the findings, the researcher identified several interventions that can be used by nurses to facilitate end-of-life discussion and decision-making that includes both parent and, when appropriate, the child.
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Date Issued: 2013
Identifier: CFH0004443, ucf:45081
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFH0004443

Title: SQUARAINE DYES FOR TWO-PHOTON FLUORESCENCE BIOIMAGING APPLICATIONS.
Creator: Colon Gomez, Maria, Belfield, Kevin, University of Central Florida
Abstract / Description: Near-infrared emitting squaraine dyes are promising candidates for bioimaging applications. Two-photon fluorescence microscopy (2PFM) imaging is a powerful tool being used for studying biological function since it produces 3D images with minimal damage to cells and lower fluorophore photobleaching. The fluorescence wavelength of squaraine dyes normally falls in the near infrared region, providing deeper penetration through biological samples such as thick tissue sections. Squaraine dyes that...
Show moreNear-infrared emitting squaraine dyes are promising candidates for bioimaging applications. Two-photon fluorescence microscopy (2PFM) imaging is a powerful tool being used for studying biological function since it produces 3D images with minimal damage to cells and lower fluorophore photobleaching. The fluorescence wavelength of squaraine dyes normally falls in the near infrared region, providing deeper penetration through biological samples such as thick tissue sections. Squaraine dyes that could work for imaging cells and tissues for 2PFM imaging were synthesized and underwent comprehensive photophysical characterization, such as UV-Vis absorption, fluorescence, and anisotropy. The squaraine dyes were tested for cell toxicity to determine the concentration at which the cells should be incubated with the dye for 2PFM. In addition, the squaraine dyes were incubated with cancer cells to evaluate their utility in the bioimaging process. The squaraine dye that is not soluble in water can be incorporated in silica nanoparticles or micelles to facilitate dispersal in water for evaluation of its use as a probe. The prospective squaraine dyes can be used in cells and tissues for imaging that can then be analyzed to ascertain its use as a probe for biomedical applications, such as early cancer detection.
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Date Issued: 2013
Identifier: CFH0004338, ucf:45020
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFH0004338

Title: AN EVALUATION OF TRACHEOSTOMY CARE ANXIETY RELIEF THROUGH EDUCATION AND SUPPORT (T-CARES): A PILOT STUDY.
Creator: Crosby, William, Sole, Mary Lou, University of Central Florida
Abstract / Description: Background: Home care of a patient with a tracheostomy after surgery for head and neck cancer requires the caregiver to be proficient with new equipment and required skills. The responsibility of managing an artificial airway, may lead to an increase in caregiver anxiety. Education of caregivers varies; it is often a 1:1 impromptu instruction provided by the patient's nurse and/or respiratory therapist. The purpose of this study was to evaluate the effect of the T-CARES course on caregiver...
Show moreBackground: Home care of a patient with a tracheostomy after surgery for head and neck cancer requires the caregiver to be proficient with new equipment and required skills. The responsibility of managing an artificial airway, may lead to an increase in caregiver anxiety. Education of caregivers varies; it is often a 1:1 impromptu instruction provided by the patient's nurse and/or respiratory therapist. The purpose of this study was to evaluate the effect of the T-CARES course on caregiver anxiety and tracheostomy suctioning competency. Method: A quasi-experimental non-randomized control group design was used. The independent variable was method of instruction (T-CARES versus standard). Dependent variables were caregiver anxiety and tracheostomy suction competence. Caregivers (n=12) self selected into groups based on availability to attend T-CARES course. The control group was to receive the unit-based standard of education. The experimental group participated in the T-CARES course. Only one person chose to be in the control group; therefore, data were analyzed for the experimental group only (N=11). The T-CARES course, created by the researcher, was standardized and instructor-led; it incorporated media and simulated practice. Caregiver anxiety for both groups was obtained before (State/Trait Anxiety) and after (State Anxiety) tracheostomy care instruction was provided. Tracheostomy suctioning competence was assessed using a standardized checklist for participants in the T-CARES study group only. Demographic data were summarized with frequencies and descriptive statistics. Given the small sample size, non-parametric statistics were used for data analysis. Results: Data were analyzed from the experimental group only (n=11). The majority of caregivers were women (n=7), white/caucasian (n=10), married (n=8), employed full time (n=7), and were high school graduates or higher (n=10). The mean age of participants was 50.8 years. Seven of the participants reported previous caregiver experience. Mean score of caregiver trait anxiety was 36.8. Mean caregiver state anxiety score was 50.5 before, and 34.3 after the T-CARES intervention. A Related-Samples Wilcoxon Signed Rank Test was performed on the pre and post T-CARES intervention state anxiety scores. The T-CARES intervention significantly reduced anxiety (p=.008). Tracheostomy suctioning competency for 9 of the participants was evaluated upon completion of T-CARES. Mean score was10.8 skills performed correctly out of a possible 14. Caregivers' responses regarding their biggest fear/concern about tracheostomy care included "not doing it right," "trach coming out or being blocked," "hurting the patient," and "not being able to help in an emergency." Participants' suggestions for future improvements were creation of a Spanish language course and the addition of supplementary training to include CPR, First Aid, and the management of feeding tubes. Discussion: Research supported the hypothesis that the T-CARES course would be successful in reducing state anxiety. The T-CARES course also had a positive impact on tracheostomy suctioning competency, though without a control group it is difficult to quantify the effect. The continued development and dissemination of T-CARES to all tracheostomy patients and their caregivers may ease their transition home. The views expressed are those of the author and do not reflect the official policy or position of the US Air Force, Department of Defense or the US Government.
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Date Issued: 2012
Identifier: CFH0004138, ucf:44824
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFH0004138

Title: SPIRITUAL CARE INTERVENTIONS TO IMPROVE THE QUALITY OF LIFE IN PATIENTS WITH ADVANCED CANCER RECEIVING PALLIATIVE CARE.
Creator: Ballen-Sanchez, Maria, Conner, Norma, University of Central Florida
Abstract / Description: Title: Spiritual Care Interventions and Quality of Life in Cancer Patients Receiving Palliative Care Background: Despite the evidence supporting spiritual care in nursing and an increased quality of life among patients, patients feel that their spiritual needs are not being supported by medical professionals. Nurses agree that the role they play is significant in addressing the needs of cancer patients; however, they feel that they lack the knowledge for addressing spirituality concerns at...
Show moreTitle: Spiritual Care Interventions and Quality of Life in Cancer Patients Receiving Palliative Care Background: Despite the evidence supporting spiritual care in nursing and an increased quality of life among patients, patients feel that their spiritual needs are not being supported by medical professionals. Nurses agree that the role they play is significant in addressing the needs of cancer patients; however, they feel that they lack the knowledge for addressing spirituality concerns at the end of life. The purpose of this study is to identify spiritual care interventions that nurses can implement to improve quality of life (QOL) in patients with advanced cancer receiving palliative care. Method: This literature review consisted of articles retrieved from several databases, including CINAHL, PubMED, and PsychINFO , PsychARTICLES, ATLA Religion databases using the key words "cancer*" and "quality of life" "therapeutic communication", "spirit* therapy", "relaxation therapy", and "self-care". Inclusion criteria consisted of research conducted after the year 2000, peer reviewed work and research studies written in the English language. Results: Results from this literature review include recommended nursing interventions that provide spiritual care to patients with advanced cancer receiving palliative care for the purpose of improved quality of life. Spiritual care interventions identified in this study include Meaning Centered Group Psychotherapy (MCGP), Supportive Group Psychotherapy (SGP), mental relaxation, mental images, TM, art therapy, socializing, communicative acts, aromatherapy, massage, exercise, hatha yoga, meditation, and activities such as gardening, watching TV, resting/sleeping and socializing.
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Date Issued: 2012
Identifier: CFH0004245, ucf:44925
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFH0004245

Title: Identification and Functional Characterization of a Long Non-coding RNA associated with Prostate Cancer.
Creator: Hasan, Md Faqrul, Chakrabarti, Ratna, Zhao, Jihe, Zhang, Shaojie, University of Central Florida
Abstract / Description: Prostate cancer is the most common cancer in men in the western world. Although early stage prostate cancer is treatable late stage, more specifically, metastatic and drug resistant prostate cancers are mostly incurable. The failure of current treatments obligates the research community to explore novel areas in prostate cancer biology and find better therapeutic targets. Emerging evidences show that non-coding RNAs specifically long non-coding RNAs (lncRNAs) play regulatory roles in various...
Show moreProstate cancer is the most common cancer in men in the western world. Although early stage prostate cancer is treatable late stage, more specifically, metastatic and drug resistant prostate cancers are mostly incurable. The failure of current treatments obligates the research community to explore novel areas in prostate cancer biology and find better therapeutic targets. Emerging evidences show that non-coding RNAs specifically long non-coding RNAs (lncRNAs) play regulatory roles in various cellular processes and are frequently dysregulated in cancer including prostate cancer. These aberrantly expressed lncRNAs mostly with unexplored genetic information may drive cancer progression. Previous studies done in our laboratory showed a tumor suppressor role of a cluster of small non-coding RNAs or microRNA (miRNA) miR-17-92a in PC-3 prostate cancer cells. To learn the underlying mechanism, transcriptome analysis with or without expression of miR-17-92a was conducted in our laboratory. RNA-sequencing data analysis identified reduced expression of a set of lncRNAs and oncogenes, and up regulation of several tumor suppressor genes upon expression of miR-17-92a cluster miRNAs. One of the down regulated intergenic lncRNAs, PAINT (Prostate Cancer Associated Intergenic Non-coding Transcript) (LINC00888), was selected for determining its functional role in prostate cancer. TCGA and GEO profiles analyses revealed up regulation of PAINT in prostate tumors with higher Gleason Scores, in highly aggressive metastatic prostate cancer cell lines, and upon androgen deprivation therapy of prostate cancer cells. This observation was supported by our studies on expression analysis of PAINT in prostate tumor tissues using RNA in-situ hybridization in tissue microarrays (TMA) containing tissues from different stages of prostate cancer and normal prostate tissues, which showed higher expression of PAINT in prostate cancer tissues compared to normal tissues. Furthermore, late stage (stage III and stage IV) prostate tumors showed significant overexpression of PAINT compared to early stage (stage II) prostate cancer tissues. We examined the functional relevance of PAINT in promoting tumor progression next using different prostate cancer cell lines. Silencing of PAINT using siRNAs showed decreased cell proliferation, reduced S-phase progression and activation of pro-apoptotic proteins PARP and Caspase-3. Silencing of PAINT also showed decreased cell migration and increased expression of the epithelial marker, E-cadherin while reduced expression of mesenchymal markers Slug and Vimentin. Ectopic expression of PAINT reversed the effects observed upon silencing of PAINT. Increased cell proliferation, cell cycle progression and cell migration were noted in prostate cancer cells overexpressing PAINT. Additionally, cancer promoting phenotype such as larger colony formation and higher expression of mesenchymal marker Slug, was detected upon overexpression of PAINT. Our study also determined the therapeutic benefit of inhibition of expression showing an increased sensitivity of metastatic prostate cancer cells to the chemotherapeutic agent docetaxel (DTX) and selective Aurora kinase inhibitor VX-680. Taken together, our study establishes an oncogenic function of PAINT, its clinical relevance as a marker for advanced stage prostate cancer and its potential as a therapeutic target for metastatic prostate cancer.
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Date Issued: 2019
Identifier: CFE0007466, ucf:52681
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0007466

Title: X-ray Radiation Enabled Cancer Detection and Treatment with Nanoparticles.
Creator: Hossain, Mainul, Su, Ming, Behal, Aman, Gong, Xun, Hu, Haiyan, Kapoor, Vikram, Deng, Weiwei, University of Central Florida
Abstract / Description: Despite significant improvements in medical sciences over the last decade, cancer still continues to be a major cause of death in humans throughout the world. Parallel to the efforts of understanding the intricacies of cancer biology, researchers are continuously striving to develop effective cancer detection and treatment strategies. Use of nanotechnology in the modern era opens up a wide range of possibilities for diagnostics, therapies and preventive measures for cancer management....
Show moreDespite significant improvements in medical sciences over the last decade, cancer still continues to be a major cause of death in humans throughout the world. Parallel to the efforts of understanding the intricacies of cancer biology, researchers are continuously striving to develop effective cancer detection and treatment strategies. Use of nanotechnology in the modern era opens up a wide range of possibilities for diagnostics, therapies and preventive measures for cancer management. Although, existing strategies of cancer detection and treatment, using nanoparticles, have been proven successful in case of cancer imaging and targeted drug deliveries, they are often limited by poor sensitivity, lack of specificity, complex sample preparation efforts and inherent toxicities associated with the nanoparticles, especially in case of in-vivo applications. Moreover, the detection of cancer is not necessarily integrated with treatment. X-rays have long been used in radiation therapy to kill cancer cells and also for imaging tumors inside the body using nanoparticles as contrast agents. However, X-rays, in combination with nanoparticles, can also be used for cancer diagnosis by detecting cancer biomarkers and circulating tumor cells. Moreover, the use of nanoparticles can also enhance the efficacy of X-ray radiation therapy for cancer treatment.This dissertation describes a novel in vitro technique for cancer detection and treatment using X-ray radiation and nanoparticles. Surfaces of synthesized metallic nanoparticles have been modified with appropriate ligands to specifically target cancer cells and biomarkers in vitro. Characteristic X-ray fluorescence signals from the X-ray irradiated nanoparticles are then used for detecting the presence of cancer. The method enables simultaneous detection of multiple cancer biomarkers allowing accurate diagnosis and early detection of cancer. Circulating tumor cells, which are the primary indicators of cancer metastasis, have also been detected where the use of magnetic nanoparticles allows enrichment of rare cancer cells prior to detection. The approach is unique in that it integrates cancer detection and treatment under one platform, since, X-rays have been shown to effectively kill cancer cells through radiation induced DNA damage. Due to high penetrating power of X-rays, the method has potential applications for in vivo detection and treatment of deeply buried cancers in humans. The effect of nanoparticle toxicity on multiple cell types has been investigated using conventional cytotoxicity assays for both unmodified nanoparticles as well as nanoparticles modified with a variety of surface coatings. Appropriate surface modifications have significantly reduced inherent toxicity of nanoparticles, providing possibilities for future clinical applications. To investigate cellular damages caused by X-ray radiation, an on-chip biodosimeter has been fabricated based on three dimensional microtissues which allows direct monitoring of responses to X-ray exposure for multiple mammalian cell types. Damage to tumor cells caused by X-rays is known to be significantly higher in presence of nanoparticles which act as radiosensitizers and enhance localized radiation doses. An analytical approach is used to investigate the various parameters that affect the radiosensitizing properties of the nanoparticles. The results can be used to increase the efficacy of nanoparticle aided X-ray radiation therapy for cancer treatment by appropriate choice of X-ray beam energy, nanoparticle size, material composition and location of nanoparticle with respect to the tumor cell nucleus.
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Date Issued: 2012
Identifier: CFE0004547, ucf:49242
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0004547

Title: DISCOVERY AND OPTIMIZATION OF NOVEL SMALL-MOLECULAR INHIBITORS SUPPRESSING STAT3-DEPENDENT TUMOR PROCESS.
Creator: Zhang, Xiaolei, Turkson, James, University of Central Florida
Abstract / Description: With the critical role of aberrantly active Signal Transducer and Activator of Transcription (Stat) 3 protein in many human cancers, selective small-molecule inhibitors targeting the dimerization event which is required for stat3 activation, would be valuable as therapeutic agents. And the inhibitors will be useful chemical probes to clarify the complex biological functions of Stat3. By computational and structural analyses of the interaction between Stat3 and the lead dimerization disruptor,...
Show moreWith the critical role of aberrantly active Signal Transducer and Activator of Transcription (Stat) 3 protein in many human cancers, selective small-molecule inhibitors targeting the dimerization event which is required for stat3 activation, would be valuable as therapeutic agents. And the inhibitors will be useful chemical probes to clarify the complex biological functions of Stat3. By computational and structural analyses of the interaction between Stat3 and the lead dimerization disruptor, S3I-201, we have designed a diverse set of analogs. One of the most active analogs, S3I-201.1066 is derived to contain a cyclo-hexyl benzyl moiety on the amide nitrogen, which increases the binding to the Stat3 SH2 domain. Evidence is presented from in vitro biochemical and biophysical studies that S3I-201.1066 directly interacts with Stat3 or the SH2 domain, with an affinity (KD) of 2.74 [micro]M, and disrupts the binding of Stat3 to the cognate pTyr-peptide, GpYLPQTV-NH2, with an IC50 of 23 [micro]M. Moreover, S3I-201.1066 selectively blocks the association of Stat3 with the epidermal growth factor receptor (EGFR), and inhibits Stat3 tyrosine phosphorylation and nuclear translocation in EGF-stimulated mouse fibroblasts. In cancer cells that harbor aberrant Stat3 activity, S3I-201.1066 inhibits constitutive Stat3 DNA-binding and transcriptional activities. By contrast, S3I-201.1066 has no effect on Src activation or the EGFR-mediated activation of the Erk1/2MAPK pathway. S3I-201.1066 selectively suppresses the viability, survival, and malignant transformation of the human breast and pancreatic cancer lines and the v-Src-transformed mouse fibroblasts harboring persistently active Stat3. Treatment with S3I-201.1066 on malignant cells harboring aberrantly active Stat3 down regulated the expression of c-Myc, Bcl-xL, Survivin, matrix metalloproteinase 9, and VEGF, which are known Stat3-regulated genes important in diverse tumor processes. The in vivo administration of S3I-201.1066 induced significant anti-tumor response in mouse models of human breast cancer, which correlates with the inhibition of constitutively active Stat3 and the suppression of known Stat3-regulated genes. Further computer-aided lead optimization derives higher-affinity (KD, 504 nM), orally bioavailable Stat3 SH2 domain-binding ligand, BP-1-102 as a structural analog of S3I-201.1066. The most significant modification is the pentafluorobenzene sulfonamide component of BP-1-102, which permits accessibility of a third sub-pocket of the Stat3 SH2 domain surface. BP-1-102-mediated inhibition of aberrantly-active Stat3 in human pancreatic cancer, Panc-1, breast cancer, MDA-MB-231, and prostate (DU145) cancer cells and in the mouse transformed fibroblasts harboring aberrantly-active Stat3. It also disrupts Stat3-NFkB cross-talk and suppresses the release of granulocyte colony-stimulating factor, soluble intercellular adhesion molecule-1, macrophage-migration-inhibitory factor/glycosylation-inhibiting factor, interleukin-1 receptor antagonist and the serine protease inhibitor (serpin) protein 1, and the expression of c-Myc, Cyclin D1, Bcl-xL, Survivin, and vascular endothelial growth factor expression in vitro and in vivo. Inhibition of tumor cell-associated constitutively-active Stat3 further suppresses focal adhesion kinase and paxillin induction, enhances E-cadherin expression, and down-regulates Kruppel-like factor 8 (KLF8)expression. Consequently, BP-1-102 selectively suppresses anchorage-dependent and independent growth, survival, migration and invasion of Stat3-dependent tumor cells in vitro. Intravenous or oral gavage delivery of BP-1-102 furnishes micromolar or microgram levels in tumor tissues and inhibits growth of mouse xenografts of human breast and lung tumors. Computer-aided lead optimization has therefore derived a more suitable small-molecule inhibitor as a drug candidate. Our studies of the Stat3 SH2 protein surface and of the interactions between lead agents and the SH2 domain provided significant data to facilitate the structural optimization. From S2I-201 to S3I-201.1066 and to BP-1-102, we note the substantial gain in potency and efficacy, and the pharmacokinetic improvements. The oral bioavailability of BP-1-102 represents a substantial advancement in the discovery of small-molecule Stat3 inhibitors as novel anticancer agents.
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Date Issued: 2011
Identifier: CFE0003976, ucf:48669
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0003976

Title: STEM CELL BIOLOGY AND STRATEGIES FOR THERAPEUTIC DEVELOPMENT IN DEGENERATIVE DISEASES AND CANCER.
Creator: Alvarez, Angel, Sugaya, Kiminobu, University of Central Florida
Abstract / Description: Stem cell biology is an exciting field that will lead to significant advancements in science and medicine. We hypothesize that inducing the expression of stem cell genes, using the embryonic stem cell gene nanog, will reprogram cells and dedifferentiate human mesenchymal stem cells into pluripotent stem cells capable of neural differentiation. The aims of initial studies are as follows: Aim 1: Demonstrate that forced expression of the embryonic stem cell gene nanog induces changes in human...
Show moreStem cell biology is an exciting field that will lead to significant advancements in science and medicine. We hypothesize that inducing the expression of stem cell genes, using the embryonic stem cell gene nanog, will reprogram cells and dedifferentiate human mesenchymal stem cells into pluripotent stem cells capable of neural differentiation. The aims of initial studies are as follows: Aim 1: Demonstrate that forced expression of the embryonic stem cell gene nanog induces changes in human mesenchymal stem cells to an embryonic stem cell-like phenotype. Aim 2: Demonstrate that induced expression of nanog up-regulates the expression of multiple embryonic stem cell markers and expands the differentiation potential of the stem cells. Aim 3: Demonstrate that these nanog-expressing stem cells have the ability to differentiate along neural lineages in vitro and in vivo, while mock-transfected cells have an extremely limited capacity for transdifferentiation. Alternatively, we hypothesize that embryonic stem cell genes can become activated in malignant gliomas and differentially regulate the subpopulation of cancer stem cells. This study examines the role of embryonic stem cell genes in transformed cells, particularly cancer stem cells. These studies explore has the following objectives: Aim 1: Isolate different sub-populations of cells from tumors and characterize cells with stem cell-like properties. Aim 2: Characterize the expression of embryonic stem cell markers in the sub-population of cancer stem cells. Aim 3: Examine the effects of histone deacetylase inhibitors at inhibiting the growth and reducing the expression of stem cell markers. Our research has demonstrated the potential of the embryonic transcription factor, nanog, at inducing dedifferentiation of human bone marrow mesenchymal stem cells and allowing their recommitment to a neural lineage. Specifically, we used viral and non-viral vectors to induce expression of NANOG, which produced an embryonic stem cell-like morphology in transduced cells. We characterized these cells using real-time PCR and immunohistochemical staining and find an up-regulation of genes responsible for pluripotency and self-renewal. Embryonic stem cell markers including Sox2, Oct4 and TERT were up-regulated following delivery of nanog. The role of nanog in the expression of these markers was further demonstrated in our induced-differentiation method where we transfected embryonic stem cell-like cells, that have been transduced with nanog flanked by two loxP sites, with a vector containing Cre-recominase. We tested the ability of these nanog-transfected cells to undergo neural differentiation in vitro using a neural co-culture system or in vivo following intracranial transplantation. Our next study characterized patient-derived glioblastoma cancer stem cells. We found that cells isolated from serum-free stem cell cultures were enriched for stem cell markers and were more proliferative than the bulk population of cells grown in convention serum-supplemented media. These cancer stem cells expressed embryonic stem cell markers NANOG and OCT4 whereas non-tumor-derived neural stem cells do not. Moreover, the expression of stem cell markers was correlated with enhanced proliferation and could serve as a measure of drug effectiveness. We tested two different histone deacetylase inhibitors, trichostatin A and valproic acid, and found that both inhibited proliferation and significantly reduced expression of stem cell markers in our cancer stem cell lines. These data demonstrate the potential use of stem cell genes as therapeutic markers and supports the hypothesis that cancer stem cells are a major contributor to brain tumor malignancy.
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Date Issued: 2011
Identifier: CFE0003641, ucf:48845
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0003641

Title: A Solid Phase Assay for Topoisomerase I interfacial Poisons and Catalytic Inhibitors.
Creator: Cyril Sagayaraj, Vidusha, Muller, Mark, Zhao, Jihe, Chakrabarti, Debopam, University of Central Florida
Abstract / Description: We report a mechanism based screening technique to rapidly identify eukaryotic topoisomerase I targeting agents. The method is based on genetic tagging of topoisomerase I to immobilize the enzyme on a solid surface in a microtiter well format. DNA is added to the wells and retained DNA is detected by Picogreen fluorescence. Compounds that result in an increase in Picogreen staining represent potential topoisomerase interfacial poisons while those that reduce fluorescence report catalytic...
Show moreWe report a mechanism based screening technique to rapidly identify eukaryotic topoisomerase I targeting agents. The method is based on genetic tagging of topoisomerase I to immobilize the enzyme on a solid surface in a microtiter well format. DNA is added to the wells and retained DNA is detected by Picogreen fluorescence. Compounds that result in an increase in Picogreen staining represent potential topoisomerase interfacial poisons while those that reduce fluorescence report catalytic inhibitors; therefore, the solid phase assay represents a 'bimodal' readout that reveals mechanisms of action. The method has been demonstrated to work with known interfacial poisons and catalytic inhibitors. In addition to specific topoisomerase targeting drugs, the method also weakly detects other relevant anticancer agents, such as potent DNA alkylating and intercalating compounds; therefore, topoisomerase I HTS represents an excellent tool for searching and identifying novel genotoxic agents. This method is rapid, robust, economical and scalable for large library screens.
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Date Issued: 2011
Identifier: CFE0004473, ucf:49304
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0004473

Title: Evaluation of a Mind-Body Website by Women with Breast Cancer.
Creator: Beck, Laura, Loerzel, Victoria, Sole, Mary, Morrison, Kimberly, University of Central Florida
Abstract / Description: Despite having access to volumes of information, women newly diagnosed with breast cancer report a moderate level of distress related to their diagnosis, treatment, life expectancy, threat to current roles, and life-changing surgery and treatment choices. Web sites designed to teach people strategies to reduce distress are readily available online. The online format may be useful and practical for women who can access the site at their convenience, learn the components of the interventions at...
Show moreDespite having access to volumes of information, women newly diagnosed with breast cancer report a moderate level of distress related to their diagnosis, treatment, life expectancy, threat to current roles, and life-changing surgery and treatment choices. Web sites designed to teach people strategies to reduce distress are readily available online. The online format may be useful and practical for women who can access the site at their convenience, learn the components of the interventions at their own pace, and practice the strategies in the comfort of their home. The purpose of this study was to evaluate an online Mind-Body web site (http://www.www.preparingforyoursurgery.com) designed to reduce distress related to surgery for its usability, practicality, and appropriateness for women newly diagnosed with breast cancer. Results of this study will be used to either adopt use of the web site into standard of care at our cancer center or explore development of a similar web site to meet the needs of women newly diagnosed with breast cancer. Women recently diagnosed with breast cancer, who had breast cancer surgery in the past 60 days, were asked to evaluate an online Mind-Body web site and then respond to an online questionnaire measuring the web site usability, practicality, and appropriateness. Thirty-one women evaluated the web site and completed the online survey. The majority of women agreed the web site is useful, practical, appropriate, and would recommend to others. There was no significant relationship between age, income, level of education, frequency of Internet use, or experience with Mind-Body techniques and women who agreed the web site is useful, appropriate, or practical compared to women who were neutral or disagreed the web siteis useful, appropriate, or practical. The results of this study suggest the web site could be introduced to women newly diagnosed with breast cancer at our cancer center regardless of age, income, education, frequency of Internet use, or experience with Mind-Body techniques.
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Date Issued: 2013
Identifier: CFE0005085, ucf:50752
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0005085

Title: Cerium Oxide Nanoparticles Sensitize Pancreatic Cancer Cells to Radiation by Promoting Acidic pH, ROS, and JNK Dependent Apoptosis.
Creator: Wason, Melissa, Zhao, Jihe, Self, William, Altomare, Deborah, Baker, Cheryl, University of Central Florida
Abstract / Description: Side effects of radiation therapy (RT) remain the most challenging issue for pancreatic cancer treatment. In this report we determined whether and how cerium oxide nanoparticles (CONPs) sensitize pancreatic cancer cells to RT. CONP pretreatment enhanced radiation-induced reactive oxygen species (ROS) production preferentially in acidic cell-free solutions as well as acidic human pancreatic cancer cells. In acidic environments, CONPs favor the scavenging of superoxide radical over the hydroxyl...
Show moreSide effects of radiation therapy (RT) remain the most challenging issue for pancreatic cancer treatment. In this report we determined whether and how cerium oxide nanoparticles (CONPs) sensitize pancreatic cancer cells to RT. CONP pretreatment enhanced radiation-induced reactive oxygen species (ROS) production preferentially in acidic cell-free solutions as well as acidic human pancreatic cancer cells. In acidic environments, CONPs favor the scavenging of superoxide radical over the hydroxyl peroxide resulting in accumulation of the latter whereas in neutral pH CONPs scavenge both. CONP treatment prior to RT markedly potentiated the cancer cell apoptosis both in culture and in tumors and the inhibition of the pancreatic tumor growth without harming the normal tissues or host mice. Mechanistically, CONPs were not able to significantly impact RT-induced DNA damage in cancer cells, thereby ruling out sensitization through increased mitotic catastrophe. However, JNK activation, which is known to be a key driver of RT-induced apoptosis, was significantly upregulated by co-treatment with CONPs and RT in pancreatic cancer cells in vitro and human pancreatic tumors in nude mice in vivo compared to CONPs or RT treatment alone. Further, CONP-driven increase in RT-induced JNK activation was associated with marked increases in Caspase 3/7 activation, indicative of apoptosis. We have shown CONPs increase ROS production in cancer cells; ROS has been shown to drive the oxidation of thioredoxin (TRX) 1 which results in the activation of Apoptosis Signaling Kinase (ASK) 1. The dramatic increase in ASK1 activation following the co-treatment of pancreatic cancer cells with CONPs followed by RT in vitro suggests that increased the c-Jun terminal kinase (JNK) activation is the result of increased TRX1 oxidation. The ability of CONPs to sensitize pancreatic cancer cells to RT was mitigated when the TRX1 oxidation was prevented by mutagenesis of a cysteine residue, or the JNK activation was blocked by an inhibitor,. Additionally, angiogenesis in pancreatic tumors treated with CONPs and RT was significantly reduced compared to other treatment options. Taken together, these data demonstrate an important role and mechanisms for CONPs in specifically killing cancer cells and provide novel insight into the utilization of CONPs as a radiosensitizer and therapeutic agent for pancreatic cancer.
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Date Issued: 2013
Identifier: CFE0005116, ucf:50725
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0005116

Title: Development of Cytotoxic Natural Killer Cells for Ovarian Cancer Treatment.
Creator: Pandey, Veethika, Altomare, Deborah, Zhao, Jihe, Khaled, Annette, Estevez, Alvaro, University of Central Florida
Abstract / Description: Ovarian cancer is a leading cause of gynecological malignancy. Cytoreductive surgery and frontline platinum/taxane-based chemotherapy provides good initial efficacy in the treatment, but poor long-term patient survival. This is mainly caused by tumor relapse due to intraperitoneal spreading and ineffective alternate therapies to treat these resistant tumors. The challenge in the field is to develop strategies that would prove effective in these patients and extend overall survival.Over the...
Show moreOvarian cancer is a leading cause of gynecological malignancy. Cytoreductive surgery and frontline platinum/taxane-based chemotherapy provides good initial efficacy in the treatment, but poor long-term patient survival. This is mainly caused by tumor relapse due to intraperitoneal spreading and ineffective alternate therapies to treat these resistant tumors. The challenge in the field is to develop strategies that would prove effective in these patients and extend overall survival.Over the years, various treatments have been developed for the treatment of cancer amongst which, adoptive cell immunotherapy has shown promising results. But despite the efficacy seen in the clinic, there are concerns with the complexity of treatment and associated side effects. Therefore, there is still a need for better understanding of how different components of the immune system react to the presence of tumor. In this study, healthy human peripheral blood mononuclear cells (PBMCs) were used to examine the immune response in a mouse model with residual human ovarian tumor, where natural killer (NK) cells were found to be the effector cells that elicited an anti-tumor response. Presence of tumor was found to stimulate NK cell expansion and cytotoxicity in mice treated intraperitoneally (IP) with PBMCs+Interleukin-2 (IL- 2). Intravenous (IV) adoptive transfer of isolated NK cells has been attempted in ovarian cancer patients before, but showed lack of persistence in patients resulting in lack of anti-tumor efficacy. Experiments in this study highlight the significance of NK cell-cytotoxic response to tumor, which may be attributed to interacting immune cell types in the PBMC population (when treated IP), as opposed to clinically used isolated NK cells showing lack of anti-tumor efficacy in ovarian cancer patients (when treated IV).iiiNK cell immunotherapy is mainly limited by insufficient numbers generated for adoptive transfer, limited in vivo life span after adoptive transfer, lack of cytotoxicity and some logistical concerns that impede its widespread implementation. Therefore there is a need to develop methods of NK cell expansion that provide stimulation similar to other immune cell types in the PBMC population. The second part of this study utilizes a method of in vivo NK cell expansion using a particle-based approach in which plasma membranes of K562-MB21-41BBL cells (K562 cells expressing membrane-bound IL-21 and 41BB ligand) are used for specific NK cell expansion from PBMCs. NK cells expanded with this method were cytotoxic, showed in vivo persistence and biodistribution in different organs.Collectively, these studies show that NK cells are a major innate immune component that can recognize and kill the tumor. Their cytotoxic ability, using particle-based stimulation, can be enhanced for a second-line treatment of relapsed tumors such as in ovarian cancer as well as other cancer types.
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Date Issued: 2015
Identifier: CFE0006369, ucf:51531
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0006369

Title: A major double strand repair pathway and cancer-associated circulating proteins are effecters of epigenetic revision.
Creator: Allen, Brittany, Masternak, Michal, Khaled, Annette, Zhao, Jihe, Muller, Mark, Siddiqi, Shadab, University of Central Florida
Abstract / Description: DNA methylation is a vital epigenetic process that acts as a major control mechanism for gene expression. In addition to its essential role in many normal cellular processes, it is also implicated in a wide variety of disease states and processes including cancer. Along with genetic mutations, aberrant DNA methylation patterns, specifically the inappropriate DNA methylation or demethylation of CpG residues, may activate oncogenes or suppress tumor suppressor genes, respectively. These changes...
Show moreDNA methylation is a vital epigenetic process that acts as a major control mechanism for gene expression. In addition to its essential role in many normal cellular processes, it is also implicated in a wide variety of disease states and processes including cancer. Along with genetic mutations, aberrant DNA methylation patterns, specifically the inappropriate DNA methylation or demethylation of CpG residues, may activate oncogenes or suppress tumor suppressor genes, respectively. These changes can generate or facilitate the progression of tumorigenesis and tend to accumulate throughout the development of cancer. Although they play such a major role in cancer and in other diseases, it remains unclear what causes these epigenetic revisions to occur. This dissertation will focus on uncovering mechanisms that are sources of epigenetic revision, specifically as they relate to cancer. Due to rapid cell division and increased DNA damage, cells are increasingly dependent on DNA repair as they continue on a path of tumorigenic progression. We hypothesize that DNA repair, specifically the repair of DNA double strand breaks (DSB) by Non-Homologous End Joining (NHEJ) may play a role in inappropriate epigenetic revision. Using a GFP reporter system inserted into the genome of HeLa cells, we are able to induce targeted DNA damage that enables the cells, after successfully undergoing NHEJ repair, to express WT GFP. These GFP+ cells were segregated into two expression classes, one with robust expression (Bright) and the other with reduced expression (Dim). Using a DNA hypomethylating drug (AzadC) we were able to demonstrate that the different GFP expression levels was due to differential methylation statuses of CpGs in regions on either side of the break site. Deep sequencing analysis of this area in sorted Bright and Dim populations revealed a collection of different epi-alleles that display patterns of DNA methylation following repair by NHEJ. These patterns differ between Bright and Dim cells which are hypo- and hypermethylated, respectively, and between the post-repair populations and the original, uncut cells. These data suggest that NHEJ repair facilitates a rewrite of the methylation landscape in repaired genes, elucidating one potential source for the altered methylation patterns seen in cancer cells.The Dim cells generated during this study are known to have a hypermethylated GFP gene that is correlated with reduced expression, allowing it to be used as a screening tool for hypomethylating agents. We used this tool to screen the blood serum of patients with head and neck squamous cell carcinoma (HNSCC). We found that the serum from HNSCC patients, but not from healthy individuals, contains some factor that causes hypomethylation in exposed cells. Further, we were able to identify this factor as a protein capable of effecting changes in DNA methylation, gene expression, and miRNA levels in the treated Dim cells. The novel concept presented in this study has immense implications on the study of cancer progression as it evidences circulating proteins, presumably released by cancer cells, which are able to effect gene expression in cells that are distal to the location of the cancer. Further, the fact that these proteins are in circulation makes them a potential target for use in diagnostics. Changes in DNA methylation play a major role in the development of cancer and understanding the mechanisms by which this occurs could provide new therapeutic targets for preventing this process from contributing to tumorigenesis. This dissertation presents potential sources of epigenetic revision in cancer and thus provides answers to a major question that has yet to be answered in the area of cancer research.
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Date Issued: 2017
Identifier: CFE0006555, ucf:51333
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0006555

Title: Investigating changes in quiescence in oral and esophageal epithelium in response to injury.
Creator: Rothaus, Alexandra, Andl, Claudia, Chakrabarti, Ratna, Singla, Dinender, University of Central Florida
Abstract / Description: More than 570,000 new cases of esophageal cancer are estimated to be diagnosed annually worldwide. Risk factors include gender, age, tobacco use and dietary habits leading to tissue injury and ultimately cancer. While prognoses for other cancers have improved, the 5-year survival for patients with esophageal cancer is only 20%. During the repair process, cell proliferation is increased and is associated with inflammation. Slow-cycling lifetime residential stem cells, called quiescent cells,...
Show moreMore than 570,000 new cases of esophageal cancer are estimated to be diagnosed annually worldwide. Risk factors include gender, age, tobacco use and dietary habits leading to tissue injury and ultimately cancer. While prognoses for other cancers have improved, the 5-year survival for patients with esophageal cancer is only 20%. During the repair process, cell proliferation is increased and is associated with inflammation. Slow-cycling lifetime residential stem cells, called quiescent cells, facilitate repair but are thought to accumulate mutations during DNA replication eventually giving rise to cancer. We hypothesize that esophageal stem cells become activated upon injury and are regulated by Transforming Growth Factor beta 1 (TGF?1), a known regulator of cell proliferation and differentiation. We established an in vitro model of quiescence using normal esophageal epithelial (STR) and oral (OKF6) cells treated with recombinant human TGF?1. Flow cytometry showed increases in cells arrested in G1/G0 phase of the cell cycle in TGF?1 treated cells for both cell lines (STR p(<)0.01, OKF6 p(<)0.05). EdU (5-ethynyl-2'-deoxyuridine) positive recovery cells indicated quiescence in both cell lines (p(<)0.01). Analysis of TGF?1 regulation of putative stem cell markers via western blot and qRT-PCR showed increases in ITGB1, PDPN and K15 as well as XPC, and MeCP2 in treated cells. To apply our in vitro findings, we performed immunohistochemistry staining on tissue microarrays. Proliferation marker Ki67 increased in disease progression from normal to inflammation to hyperplasia (p(<)0.001) while TGF?1 target markers decrease. Our data indicate that the onset of cancer-associated inflammation correlates with the loss of TGF?1 mediated stemness markers and increased basal proliferation suggesting cancer is a stem cell disease.
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Date Issued: 2019
Identifier: CFE0007903, ucf:52754
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0007903

Title: Involvement of miRNAs in the Development of Androgen Independent Prostate Cancer.
Creator: Ottman, Richard, Chakrabarti, Ratna, Cole, Alexander, Khaled, Annette, Zervos, Antonis, University of Central Florida
Abstract / Description: Development of resistance to androgen deprivation therapy (ADT) is a major obstacle for the management of advanced prostate cancer. Therapies with androgen receptor (AR) antagonists and androgen withdrawal initially result in tumor regression but development of compensatory mechanisms including AR bypass signaling leads to tumor re-growth, independent of circulating androgens. The result is the emergence of castration resistant prostate cancer (CRPC), a highly morbid disease exhibiting...
Show moreDevelopment of resistance to androgen deprivation therapy (ADT) is a major obstacle for the management of advanced prostate cancer. Therapies with androgen receptor (AR) antagonists and androgen withdrawal initially result in tumor regression but development of compensatory mechanisms including AR bypass signaling leads to tumor re-growth, independent of circulating androgens. The result is the emergence of castration resistant prostate cancer (CRPC), a highly morbid disease exhibiting aberrant expression of many protein-coding and non-coding genes. Under the umbrella of non-coding RNAs is a class of small regulatory RNAs referred to as microRNAs (miRNAs). MicroRNAs are believed to function in the maintenance of cell homeostasis but are often differentially expressed in many different types of cancer including CRPC.In this study, the association of genome wide miRNA expression (1113 unique miRNAs) with development of resistance to ADT was determined. Androgen sensitive prostate cancer cells that progressed to ADT and AR antagonist Casodex (CDX) resistance upon androgen withdrawal and treatment with CDX were used. Validation of expression of a subset of 100 miRNAs led to identification of 43 miRNAs that are significantly altered during progression of cells to treatment resistance. A correlation of altered expression of 10 proteins targeted by some of these miRNAs in these cells was shown.Additionally, profiles of miRNA expressions in cancerous prostate tissues were created and compared with profiles of paired adjacent uninvolved areas of prostate tissue. Among the miRNAs identified from these analyses, a cluster of miRNAs, miR-17-92a, that is under-expressed in prostate tumors and in androgen independent prostate cancer cells was highlighted. The miR-17-92a cluster miRNAs are transcribed from a polycistronic transcription unit C13orf25 that generates six mature miRNAs: miR-17, miR-18a, miR-19a, miR-19b, miR-20a and miR-92a, and is commonly de-regulated in many cancers. In this research, the expression of miR-17-92a miRNAs was found to be reduced in cancerous prostate tissues when compared to uninvolved areas and also in aggressive prostate cancer cells. Restoration of expression of all members of miR-17-92a cluster showed decreased expression of cell cycle regulatory proteins cyclin D1 and SSH1; as well as LIMK1 and FGD4 of the RhoGTPase signaling pathway. Expression of miR-17-92a miRNAs caused decreased cell proliferation, reduced activation of AKT and MAP kinases, delayed tumorigenicity and reduced tumor growth in animals. Additionally, miR-17-92a miRNA expression inhibited EMT via reduced cell migration and expression of mesenchymal markers while elevating expression and surface localization of the epithelial marker e-cadherin. Expression of miR-17-92a miRNAs improved sensitivity of androgen dependent LNCaP104-S prostate cancer cells to the Androgen Receptor antagonist bicalutamide (CDX), AKT inhibitor MK-2206 2HCl, and docetaxel. Androgen refractory PC-3 cells also showed increased sensitivity to docetaxel, MK-2206 2HCl, and Aurora kinase inhibitor VX680 upon ectopic expression of miR-17-92a cluster miRNAs. In conclusion, dynamic alterations in miRNA expression occur early on during androgen deprivation therapy and androgen receptor blockade. The cumulative effect of these altered miRNA expression profiles is the temporal modulation of multiple signaling pathways promoting survival and acquisition of resistance. These early events are driving the transition to castration resistance and cannot be studied in already developed CRPC cell lines or tissues. Notably, these data demonstrate a tumor suppressor effect of miR-17-92a cluster miRNAs in prostate cancer cells and restoration of expression of these miRNAs has a therapeutic benefit for both androgen-dependent and -independent prostate cancer cells. Furthermore, these results can be used as a prognostic marker of cancers with a potential to be resistant to ADT.
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Date Issued: 2016
Identifier: CFE0006697, ucf:52866
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0006697

Title: DEMAND STUDY FOR DENTAL HYGIENE BACHELOR DEGREE PROGRAM.
Creator: Driscoll, Annelise, Liberman, Aaron, University of Central Florida
Abstract / Description: The following is a study to determine if sufficient demand exists to start a Bachelor of Science and Master of Science degree program in dental hygiene through a joint agreement for completion degrees between Valencia Community College and the University of Central Florida. To accomplish this objective two survey instruments were administered to randomly selected licensed dentists and dental hygienists in the state of Florida. Dental hygienists represented the potential student base for the...
Show moreThe following is a study to determine if sufficient demand exists to start a Bachelor of Science and Master of Science degree program in dental hygiene through a joint agreement for completion degrees between Valencia Community College and the University of Central Florida. To accomplish this objective two survey instruments were administered to randomly selected licensed dentists and dental hygienists in the state of Florida. Dental hygienists represented the potential student base for the proposed programs, and dentists represented the potential and prospective employers of graduated students of the proposed programs. To determine demand and demand characteristics, one survey instrument was mailed to 1,000 dental hygienists who were randomly selected using SAS software from a population of N=12,066 dental hygienists actively licensed to practice in the state of Florida. This sample of hygienists was approximately 8.3% of the total population. Of the 1,000 samples, 134 (or 13.4%) were returned. Of the 134 surveys returned, 123 (n=123) were included in this study. Eleven surveys were not included because of a majority of missing data or because the respondent indicated he or she already possessed a Bachelor or Master degree. A Likert-scale questionnaire was sent to each group of actively licensed dentists and actively licensed dental hygienists from the state of Florida. Responses from dental hygienists were overwhelmingly positive towards the addition of the Bachelor of Science degree program with an online distance-learning component. Those in favor of the Bachelor of Science degree program also provided a favorable response towards adding a Master of Science degree program in dental hygiene. The dentists, as potential future employers, also showed strong support in their responses for the additional degree programs with an additional management track component and believed it would elevate the professional standards of the dental hygiene field.
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Date Issued: 2009
Identifier: CFE0002842, ucf:48048
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0002842

Title: Light Scattering Property of Gold Nanoparticles with Applications to Biomolecule Detection and Analysis.
Creator: Zheng, Tianyu, Huo, Qun, Zou, Shengli, Gesquiere, Andre, Kang, Hyeran, Zhai, Lei, University of Central Florida
Abstract / Description: Gold nanoparticles (AuNPs) have unique optical and chemical properties. Dynamic light scattering (DLS) is an analytical tool used routinely for nanoparticle size measurement. The combined use of AuNPs and DLS has led to a novel analytical assay technology called D2Dx (from diameter to diagnostics). Herein, my dissertation highlights the extended use of D2Dx for biomolecule detection and analysis. Under this general theme, Chapter 1 provides some background information of AuNPs, DLS, the...
Show moreGold nanoparticles (AuNPs) have unique optical and chemical properties. Dynamic light scattering (DLS) is an analytical tool used routinely for nanoparticle size measurement. The combined use of AuNPs and DLS has led to a novel analytical assay technology called D2Dx (from diameter to diagnostics). Herein, my dissertation highlights the extended use of D2Dx for biomolecule detection and analysis. Under this general theme, Chapter 1 provides some background information of AuNPs, DLS, the principle of D2Dx technique and its potential applications. Chapter 2 summarizes a study on the effect of AuNP concentrations and laser power on the hydrodynamic size measurement of AuNPs by DLS. This study demonstrated the multiple scattering effect on DLS analysis, and how to use the exceptionally high sensitivity of DLS in AuNP aggregate detection for bioassay design and development. Chapter 3 explores a cooperative interaction between AuNP and certain proteins in blood serum that are key to the immune system, leading to a novel diagnostic tool that can conveniently monitor the humoral immunity development from neonates to adults and detect active infections in animals. Chapter 4 reports an application of D2Dx technique for acute viral infection detection based on the active immune responses elicited from mouse models infected with influenza virus. Chapter 5 describes another application of D2Dx for prostate cancer detection. The D2Dx assay identifies prostate cancer patients from non-cancer controls with improved specificity and sensitivity than PSA test. Chapter 6 demonstrates the use of AuNPs and DLS for hydrodynamic size measurement of protein disulfide isomerase with two different conformations. Chapter 7 investigates the concentration-dependent self-assembling behavior of ribostamycin through its interaction with AuNPs in aqueous solution. Overall, this dissertation established several lines of applications of using AuNPs and DLS for biomolecular research and in vitro diagnostics.
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Date Issued: 2018
Identifier: CFE0007385, ucf:52056
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0007385

Title: Biomechanical Models of Human Upper and Tracheal Airway Functionality.
Creator: Kuruppumullage, Don Nadun, Ilegbusi, Olusegun, Kassab, Alain, Moslehy, Faissal, Santhanam, Anand, Mansy, Hansen, Hoffman Ruddy, Bari, University of Central Florida
Abstract / Description: The respiratory tract, in other words, the airway, is the primary airflow path for several physiological activities such as coughing, breathing, and sneezing. Diseases can impact airway functionality through various means including cancer of the head and neck, Neurological disorders such as Parkinson's disease, and sleep disorders and all of which are considered in this study. In this dissertation, numerical modeling techniques were used to simulate three distinct airway diseases: a weak...
Show moreThe respiratory tract, in other words, the airway, is the primary airflow path for several physiological activities such as coughing, breathing, and sneezing. Diseases can impact airway functionality through various means including cancer of the head and neck, Neurological disorders such as Parkinson's disease, and sleep disorders and all of which are considered in this study. In this dissertation, numerical modeling techniques were used to simulate three distinct airway diseases: a weak cough leading to aspiration, upper airway patency in obstructive sleep apnea, and tongue cancer in swallow disorders. The work described in this dissertation, therefore, divided into three biomechanical models, of which fluid and particulate dynamics model of cough is the first. Cough is an airway protective mechanism, which results from a coordinated series of respiratory, laryngeal, and pharyngeal muscle activity. Patients with diminished upper airway protection often exhibit cough impairment resulting in aspiration pneumonia. Computational Fluid Dynamics (CFD) technique was used to simulate airflow and penetrant behavior in the airway geometry reconstructed from Computed Tomography (CT) images acquired from participants. The second study describes Obstructive Sleep Apnea (OSA) and the effects of dilator muscular activation on the human retro-lingual airway in OSA. Computations were performed for the inspiration stage of the breathing cycle, utilizing a fluid-structure interaction (FSI) method to couple structural deformation with airflow dynamics. The spatiotemporal deformation of the structures surrounding the airway wall was predicted and found to be in general agreement with observed changes in luminal opening and the distribution of airflow from upright to supine posture. The third study describes the effects of cancer of the tongue base on tongue motion during swallow. A three-dimensional biomechanical model was developed and used to calculate the spatiotemporal deformation of the tongue under a sequence of movements which simulate the oral stage of swallow.
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Date Issued: 2018
Identifier: CFE0007034, ucf:51986
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0007034

Title: Photoactivatable Organic and Inorganic Nanoparticles in Cancer Therapeutics and Biosensing.
Creator: Mathew, Mona, Gesquiere, Andre, Hickman, James, Ye, Jingdong, Campiglia, Andres, Schoenfeld, Winston, University of Central Florida
Abstract / Description: In photodynamic therapy a photosensitizer drug is administered and is irradiated with light. Upon absorption of light the photosensitizer goes into its triplet state and transfers energy or an electron to oxygen to form reactive oxygen species (ROS). These ROS react with biomolecules in cells leading to cell damage and cell death. PDT has interested many researchers because of its non-invasiveness as compared to surgery, it leaves little to no scars, it is time and cost effective, it has...
Show moreIn photodynamic therapy a photosensitizer drug is administered and is irradiated with light. Upon absorption of light the photosensitizer goes into its triplet state and transfers energy or an electron to oxygen to form reactive oxygen species (ROS). These ROS react with biomolecules in cells leading to cell damage and cell death. PDT has interested many researchers because of its non-invasiveness as compared to surgery, it leaves little to no scars, it is time and cost effective, it has potential for targeted treatment, and can be repeated as needed. Different photosensitizers such as porphyrines, chlorophylls, and dyes have been used in PDT to treat various cancers, skin diseases, aging and sun-damaged skin. These second generation sensitizers have yielded reduced skin sensitivity and improved extinction coefficients (up to ~ 105 L mol-1 cm-1). While PDT based on small molecule photosensitizers has shown great promise, several problems remain unsolved. The main issues with current sensitizers are (i) hydrophobicity leading to aggregation in aqueous media resulting in reduced efficacy and potential toxicity, (ii) dark toxicity of photosensitizers, (iii) non-selectivity towards malignant tissue resulting in prolonged cutaneous photosensitivity and damage to healthy tissue, (iv) limited light absorption efficiency, and (v) a lack of understanding of where the photosensitizer ends up in the tissue. In this dissertation research program, these issues were addressed by the development of conducting polymer nanoparticles as a next generation of photosensitizers. This choice was motivated by the fact that conducting polymers have large extinction coefficients ((>) 107 L mol-1 cm-1), are able to undergo intersystem crossing to the triplet state, and have triplet energies that are close to that of oxygen. It was therefore hypothesized that such polymers could be effective at generating ROS due to the large excitation rate that can be generated. Conducting polymer nanoparticles (CPNPs) composed of the conducting polymer poly[2-methoxy-5-(2-ethylhexyl-oxy)-p-phenylenevinylene] (MEH-PPV) were fabricated and studied in-vitro for their potential in PDT application. Although not fully selective, the nanoparticles exhibited a strong bias to the cancer cells. The formation of ROS was proven in-vitro by staining of the cells with CellROX Green Reagent, after which PDT results were quantified by MTT assays. Cell mortality was observed to scale with nanoparticle dosage and light dosage. Based on these promising results the MEH-PPV nanoparticles were developed further to allow for surface functionalization, with the aim of targeting these NPs to cancer cell lines. For this work targeting of cancers that overexpress folate receptors (FR) were considered. The functionalized nanoparticles (FNPs) were studied in OVCAR3 (ovarian cancer cell line) as FR+, MIA PaCa2 (pancreatic cell line) as FR-, and A549 (lung cancer cell line) having marginal FR expression. Complete selectivity of the FNPs towards the FR+ cell line was found. Quantification of PDT results by MTS assays and flow cytometry show that PDT treatment was fully selective to the FR+ cell line (OVCAR3). No cell mortality was observed for the other cell lines studied here within experimental error. Finally, the issue of confirming and quantifying small molecule drug delivery to diseased tissue was tackled by developing quantum dot (Qdot) biosensors with the aim of achieving fluorescence reporting of intracellular small molecule/drug delivery. For fluorescence reporting prior expertise in control of the fluorescence state of Qdots was employed, where redox active ligands can place the Qdot in a quenched OFF state. Ligand attachment was accomplished by disulfide linker chemistry. This chemistry is reversible in the presence of sulfur reducing biomolecules, resulting in Qdots in a brightly fluorescent ON state. Glutathione (GSH) is such a biomolecule that is present in the intracellular environment. Experimental in-vitro data shows that this design was successfully implemented.
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Date Issued: 2014
Identifier: CFE0005839, ucf:50923
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0005839

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