publisher:("Texas Medical Center")

Texas Medical Center

1. Chaganty, Bharat Kumar Reddy. REROUTING PRE-EXISTING HOST VACCINE-INDUCED IMMUNITY TOWARDS BREAST CANCER.

Degree: PhD, 2016, Texas Medical Center

URL: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/663

► For decades, investigators have attempted to activate the immune system to prevent cancer metastasis or recurrence; however, owing to host immune tolerance to cancer… (more)

▼ For decades, investigators have attempted to activate the immune system to prevent cancer metastasis or recurrence; however, owing to host immune tolerance to cancer antigens and the immunosuppressive environment at tumor sites, many such attempts have failed. The recent success of anti-CTLA4, PD-L1 and PD-1 antibodies targeting immune checkpoint pathways and HPV vaccines has renewed hope that patient survival can be increased through enhancing T-cell responses. We propose to test a novel approach that may bypass host immune tolerance to cancer cells. We hypothesize that host T-cell immunity acquired through vaccination against or natural infection with infectious diseases—e.g., influenza—can be re-routed to breast cancer cells if the cancer cells also express the vaccine antigens and present the antigens in complex with MHC on the cell surface. We chose HER2-breast cancer as a model for proof-of-principle. In our study, we first examined MHC-I expression, which is required for mediating T cell-mediated response, in a panel of breast cancer cell lines with low or high levels of HER2. A previous study in literature reported an inverse correlation between the levels of HER2 and MHC-I expression in breast cancer cells. In contrast to that finding, we found no significant direct inverse correlation between the levels of HER2 and MHC-I expression. In the presence of peripheral blood mononuclear cells (PBMC), trastuzumab treatment resulted in a significant increase not only in MHC-I expression but also CD86 expression in the panel of breast cell lines. We demonstrated that this increase in MHC-I expression was correlated with an increase in IFN-γ in the co-culture of breast cancer cells and PMBC through trastuzumab-engaged PBMC. We further showed that trastuzumab treatment enhanced MHC-I expression in vivo in 4T1 mouse mammary tumors engineered to overexpress human HER2. To test our hypothesis of therapeutically redirecting preexisting non-cancer immunity developed through vaccination or contract with an infectious disease to cancer in vivo, we first immunized BALB/c mice with influenza PR8 virus to mimic flu vaccination, and then we challenged the mice with the highly aggressive 4T1 mouse mammary tumor cells or 4T1 cells lentivirally transduced to express hemagglutinin (HA) and nucleoprotein (NP) antigens of PR8 influenza virus, termed 4T1-HA+NP cells. We found a 70% rejection of 4T1-HA+NP tumors by day 12 and a significant reduction in tumor size and metastasis compared to mock (PBS) immunized mice. We also found that the anti-tumor responses in the influenza immunized group are associated with high percentage of memory CD8+ T cells, NK cells, mature DC’s, and low percentage of Treg cells and MDSC infiltration to the 4T1-HANP tumors. We next developed a trastuzumab-based immunoliposome to test our hypothesis of redirecting host influenza-induced immunity to cancer by therapeutic delivering influenza antigens to HER2-overexpressing breast cancer cells. The HER2-targeting immunoliposome was confirmed to… Advisors/Committee Members: Zhen Fan, M.D., Bingliang Fang, M.D., Ph.D., Gregory A. Lizee, Ph.D..

Subjects/Keywords: trastuzumab; immunoliposome; PD-L1; HLA-ABC; HER2; Breast cancer; Biotechnology; Cancer Biology; Immunity

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APA (6^th Edition):

Chaganty, B. K. R. (2016). REROUTING PRE-EXISTING HOST VACCINE-INDUCED IMMUNITY TOWARDS BREAST CANCER. (Doctoral Dissertation). Texas Medical Center. Retrieved from http://digitalcommons.library.tmc.edu/utgsbs_dissertations/663

Chicago Manual of Style (16^th Edition):

Chaganty, Bharat Kumar Reddy. “REROUTING PRE-EXISTING HOST VACCINE-INDUCED IMMUNITY TOWARDS BREAST CANCER.” 2016. Doctoral Dissertation, Texas Medical Center. Accessed February 22, 2020. http://digitalcommons.library.tmc.edu/utgsbs_dissertations/663.

MLA Handbook (7^th Edition):

Chaganty, Bharat Kumar Reddy. “REROUTING PRE-EXISTING HOST VACCINE-INDUCED IMMUNITY TOWARDS BREAST CANCER.” 2016. Web. 22 Feb 2020.

Vancouver:

Chaganty BKR. REROUTING PRE-EXISTING HOST VACCINE-INDUCED IMMUNITY TOWARDS BREAST CANCER. [Internet] [Doctoral dissertation]. Texas Medical Center; 2016. [cited 2020 Feb 22]. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/663.

Council of Science Editors:

Chaganty BKR. REROUTING PRE-EXISTING HOST VACCINE-INDUCED IMMUNITY TOWARDS BREAST CANCER. [Doctoral Dissertation]. Texas Medical Center; 2016. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/663

Texas Medical Center

2. Dasgupta, Pushan R; and#60;pand#62;0000-0002-1999-8494and#60;/pand#62. WISP1 IS AN OVEREXPRESSED DRIVER OF GLIOBLASTOMA.

Degree: PhD, 2017, Texas Medical Center

URL: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/780

► Despite current multimodal therapies for glioblastoma (GBM) the prognosis remains very grim. There is a tremendous need to identify new genetic drivers which can… (more)

Subjects/Keywords: functional genomics; oncogene; glioblastoma; driver; gain-of-function screen; Cancer Biology; Medicine and Health Sciences; Molecular Genetics

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APA (6^th Edition):

Dasgupta, P. R. a. (2017). WISP1 IS AN OVEREXPRESSED DRIVER OF GLIOBLASTOMA. (Doctoral Dissertation). Texas Medical Center. Retrieved from http://digitalcommons.library.tmc.edu/utgsbs_dissertations/780

Chicago Manual of Style (16^th Edition):

Dasgupta, Pushan R; and#60;pand#62;0000-0002-1999-8494and#60;/pand#62. “WISP1 IS AN OVEREXPRESSED DRIVER OF GLIOBLASTOMA.” 2017. Doctoral Dissertation, Texas Medical Center. Accessed February 22, 2020. http://digitalcommons.library.tmc.edu/utgsbs_dissertations/780.

MLA Handbook (7^th Edition):

Dasgupta, Pushan R; and#60;pand#62;0000-0002-1999-8494and#60;/pand#62. “WISP1 IS AN OVEREXPRESSED DRIVER OF GLIOBLASTOMA.” 2017. Web. 22 Feb 2020.

Vancouver:

Dasgupta PRa. WISP1 IS AN OVEREXPRESSED DRIVER OF GLIOBLASTOMA. [Internet] [Doctoral dissertation]. Texas Medical Center; 2017. [cited 2020 Feb 22]. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/780.

Council of Science Editors:

Dasgupta PRa. WISP1 IS AN OVEREXPRESSED DRIVER OF GLIOBLASTOMA. [Doctoral Dissertation]. Texas Medical Center; 2017. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/780

Texas Medical Center

3. Ganguly, Dipyaman. Immune recognition of self nucleic acids driven by endogenous antimicrobial peptides: role in autoimmunity.

Degree: PhD, 2010, Texas Medical Center

URL: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/53

► Innate immune recognition of extracellular host-derived self-DNA and self-RNA is prevented by endosomal seclusion of the Toll-like receptors (TLRs) in the dendritic cells (DCs). However,… (more)

▼ Innate immune recognition of extracellular host-derived self-DNA and self-RNA is prevented by endosomal seclusion of the Toll-like receptors (TLRs) in the dendritic cells (DCs). However, in psoriasis plasmacytoid dendritic cells have been found to be able to sense self-DNA molecules in complex with the endogenous cationic antimicrobial peptide LL37, which are internalized into the endosomal compartments and thus can access TLR9. We investigated whether this endogenous peptide can also interact with extracellular self-RNA and lead to DC activation. We found that LL37 binds self-RNA as well as self-DNA going into an electrostatic interaction; forms micro-aggregates of nano-scale particles protected from enzymatic degradation and transport it into the endosomal compartments of both plasmacytoid and myeloid dendritic cells. In the plasmacytoid DCs, the self-RNA-LL37 complexes activate TLR7 and like the self-DNA-LL37 complexes, trigger the production of IFN-α in the absence of induction of maturation or production of IL-6 and TNF-α. In contrast to the self-DNA-LL37 complexes, the self-RNA-LL37 complexes are also internalized into the endosomal compartments of myeloid dendritic cells and trigger activation through TLR8, leading to the production of TNF-α and IL-6, and the maturation of the myeloid DCs. Furthermore, we found that these self nucleic acid-LL37 complexes can be found in vivo in the skin lesions of the cutaneous autoimmune disease psoriasis, where they are associated with mature mDCs in situ. On the other hand, in the systemic autoimmune disease systemic lupus erythematosus, self-DNA-LL37 complexes were found to be a constituent of the circulating immune complexes isolated from patient sera. This interaction between the endogenous peptide with the self nucleic acid molecules present in the immune complexes was found to be electrostatic and it confers resistance to enzymatic degradation of the nucleic acid molecules in the immune complexes. Moreover, autoantibodies to these endogenous peptides were found to trigger neutrophil activation and release of neutrophil extracellular traps composed of DNA, which are potential sources of the self nucleic acid-LL37 complexes present in SLE immune complexes. Our results demonstrate that the cationic antimicrobial peptide LL37 drives the innate immune recognition of self nucleic acid molecules through toll-like receptors in human dendritic cells, thus elucidating a pathway for innate sensing of host cell death. This pathway of autoreactivity was found to be pathologically relevant in human autoimmune diseases psoriasis and SLE, and thus this study provides new insights into the mechanisms autoimmune diseases. Advisors/Committee Members: Michel Gilliet, MD, Stephen E. Ullrich, PhD, Chen Dong, PhD.

Subjects/Keywords: pDC; DNA; RNA; LL37; dendritic cells; TLR; psoriasis; Biological Phenomena, Cell Phenomena, and Immunity; Cell Biology; Immune System Diseases; Immunity; Immunopathology; Medical Cell Biology; Medical Immunology; Medical Pathology; Pathological Conditions, Signs and Symptoms

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APA (6^th Edition):

Ganguly, D. (2010). Immune recognition of self nucleic acids driven by endogenous antimicrobial peptides: role in autoimmunity. (Doctoral Dissertation). Texas Medical Center. Retrieved from http://digitalcommons.library.tmc.edu/utgsbs_dissertations/53

Chicago Manual of Style (16^th Edition):

Ganguly, Dipyaman. “Immune recognition of self nucleic acids driven by endogenous antimicrobial peptides: role in autoimmunity.” 2010. Doctoral Dissertation, Texas Medical Center. Accessed February 22, 2020. http://digitalcommons.library.tmc.edu/utgsbs_dissertations/53.

MLA Handbook (7^th Edition):

Ganguly, Dipyaman. “Immune recognition of self nucleic acids driven by endogenous antimicrobial peptides: role in autoimmunity.” 2010. Web. 22 Feb 2020.

Vancouver:

Ganguly D. Immune recognition of self nucleic acids driven by endogenous antimicrobial peptides: role in autoimmunity. [Internet] [Doctoral dissertation]. Texas Medical Center; 2010. [cited 2020 Feb 22]. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/53.

Council of Science Editors:

Ganguly D. Immune recognition of self nucleic acids driven by endogenous antimicrobial peptides: role in autoimmunity. [Doctoral Dissertation]. Texas Medical Center; 2010. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/53

Texas Medical Center

4. O'Day, Diana. GENETIC ANALYSIS OF THE FUNCTION OF THE DROSOPHILA DOUBLESEX-RELATED FACTOR dmrt93B.

Degree: PhD, 2010, Texas Medical Center

URL: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/54

► DMRT (Doublesex and Mab-3 related transcription factor) proteins generally associated with sexual differentiation in many organisms share a common DNA binding domain and are often… (more)

▼ DMRT (Doublesex and Mab-3 related transcription factor) proteins generally associated with sexual differentiation in many organisms share a common DNA binding domain and are often expressed in reproductive tissues. Aside from doublesex, which is a central factor in the regulation of sex determination, Drosophila possesses three different dmrt genes that are of unknown function. Because the association with sexual differentiation and reproduction is not universal and some DMRT proteins have been found to play other developmental roles we chose to further characterize one of these Drosophila genes. We carried out genetic analysis of dmrt93B, which was previously found to be expressed sex-specifically in the developing somatic gonad and to affect testis morphogenesis in RNAi knockdowns. In order to disrupt this gene, the GAL4 yeast transcriptional activator followed by a polyadenylation signal was inserted after the dmrt93B start codon and introduced into the genome by homologous recombination. Analysis of the knock-in mutation as well as a small deletion removing all dmrt93B sequence demonstrate that loss of function causes partial lethality at the late pupal stage. Surprisingly, these mutations have no significant effect on gonad formation or male fertility. Analysis of GAL4-driven GFP reporter expression indicates that the dmrt93B promoter activity is highly specific to neurons in the suboesophageal and proventricular ganglion in larva and adult of both sexes suggesting a possible role in digestive tract function. Using the Capillary Feeder (CAFÉ) assay to measure daily food intake we find that reduction in this gene’s function leads to an increase in food consumption. These results suggest dmrt93 plays an important role in the formation or maintenance of neurons that affect feeding and support the idea that dmrt genes may not be restricted to roles in sexual differentiation. Advisors/Committee Members: William Mattox, Ph.D., Richard Behringer, Ph.D., Andreas Bergmann, Ph.D..

Subjects/Keywords: dmrt93B; Doublesex and Mab-3 related transcription factor; Drosophila; GAL4 knock-in; Capillary Feeder (CAFÉ) assay; ends-out gene replacement; homologous recombination <; em>; in vivo<; /em>;

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APA (6^th Edition):

O'Day, D. (2010). GENETIC ANALYSIS OF THE FUNCTION OF THE DROSOPHILA DOUBLESEX-RELATED FACTOR dmrt93B. (Doctoral Dissertation). Texas Medical Center. Retrieved from http://digitalcommons.library.tmc.edu/utgsbs_dissertations/54

Chicago Manual of Style (16^th Edition):

O'Day, Diana. “GENETIC ANALYSIS OF THE FUNCTION OF THE DROSOPHILA DOUBLESEX-RELATED FACTOR dmrt93B.” 2010. Doctoral Dissertation, Texas Medical Center. Accessed February 22, 2020. http://digitalcommons.library.tmc.edu/utgsbs_dissertations/54.

MLA Handbook (7^th Edition):

O'Day, Diana. “GENETIC ANALYSIS OF THE FUNCTION OF THE DROSOPHILA DOUBLESEX-RELATED FACTOR dmrt93B.” 2010. Web. 22 Feb 2020.

Vancouver:

O'Day D. GENETIC ANALYSIS OF THE FUNCTION OF THE DROSOPHILA DOUBLESEX-RELATED FACTOR dmrt93B. [Internet] [Doctoral dissertation]. Texas Medical Center; 2010. [cited 2020 Feb 22]. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/54.

Council of Science Editors:

O'Day D. GENETIC ANALYSIS OF THE FUNCTION OF THE DROSOPHILA DOUBLESEX-RELATED FACTOR dmrt93B. [Doctoral Dissertation]. Texas Medical Center; 2010. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/54

Texas Medical Center

5. Hennessey, Violeta G. A BAYESIAN APPROACH TO DOSE-RESPONSE ASSESSMENT AND DRUG-DRUG INTERACTION ANALYSIS: APPLICATION TO IN VITRO STUDIES.

Degree: PhD, 2010, Texas Medical Center

URL: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/55

► The considerable search for synergistic agents in cancer research is motivated by the therapeutic benefits achieved by combining anti-cancer agents. Synergistic agents make it possible… (more)

▼ The considerable search for synergistic agents in cancer research is motivated by the therapeutic benefits achieved by combining anti-cancer agents. Synergistic agents make it possible to reduce dosage while maintaining or enhancing a desired effect. Other favorable outcomes of synergistic agents include reduction in toxicity and minimizing or delaying drug resistance. Dose-response assessment and drug-drug interaction analysis play an important part in the drug discovery process, however analysis are often poorly done. This dissertation is an effort to notably improve dose-response assessment and drug-drug interaction analysis. The most commonly used method in published analysis is the Median-Effect Principle/Combination Index method (Chou and Talalay, 1984). The Median-Effect Principle/Combination Index method leads to inefficiency by ignoring important sources of variation inherent in dose-response data and discarding data points that do not fit the Median-Effect Principle. Previous work has shown that the conventional method yields a high rate of false positives (Boik, Boik, Newman, 2008; Hennessey, Rosner, Bast, Chen, 2010) and, in some cases, low power to detect synergy. There is a great need for improving the current methodology. We developed a Bayesian framework for dose-response modeling and drug-drug interaction analysis. First, we developed a hierarchical meta-regression dose-response model that accounts for various sources of variation and uncertainty and allows one to incorporate knowledge from prior studies into the current analysis, thus offering a more efficient and reliable inference. Second, in the case that parametric dose-response models do not fit the data, we developed a practical and flexible nonparametric regression method for meta-analysis of independently repeated dose-response experiments. Third, and lastly, we developed a method, based on Loewe additivity that allows one to quantitatively assess interaction between two agents combined at a fixed dose ratio. The proposed method makes a comprehensive and honest account of uncertainty within drug interaction assessment. Extensive simulation studies show that the novel methodology improves the screening process of effective/synergistic agents and reduces the incidence of type I error. We consider an ovarian cancer cell line study that investigates the combined effect of DNA methylation inhibitors and histone deacetylation inhibitors in human ovarian cancer cell lines. The hypothesis is that the combination of DNA methylation inhibitors and histone deacetylation inhibitors will enhance antiproliferative activity in human ovarian cancer cell lines compared to treatment with each inhibitor alone. By applying the proposed Bayesian methodology, in vitro synergy was declared for DNA methylation inhibitor, 5-AZA-2'-deoxycytidine combined with one histone deacetylation inhibitor, suberoylanilide hydroxamic acid or trichostatin A in the cell lines HEY and SKOV3. This suggests potential new epigenetic therapies in cell growth inhibition of ovarian… Advisors/Committee Members: Gary L. Rosner, ScD, J. Jack Lee, DDS, PhD, Yuan Ji, PhD.

Subjects/Keywords: Combination Index method; Drug interaction; Emax model; Interaction index; Median-effect principle; Loewe additivity model; Non-parametric regression methods; Monotone regression splines; Biometry; Biostatistics; Other Pharmacy and Pharmaceutical Sciences; Statistical Models

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APA (6^th Edition):

Hennessey, V. G. (2010). A BAYESIAN APPROACH TO DOSE-RESPONSE ASSESSMENT AND DRUG-DRUG INTERACTION ANALYSIS: APPLICATION TO IN VITRO STUDIES. (Doctoral Dissertation). Texas Medical Center. Retrieved from http://digitalcommons.library.tmc.edu/utgsbs_dissertations/55

Chicago Manual of Style (16^th Edition):

Hennessey, Violeta G. “A BAYESIAN APPROACH TO DOSE-RESPONSE ASSESSMENT AND DRUG-DRUG INTERACTION ANALYSIS: APPLICATION TO IN VITRO STUDIES.” 2010. Doctoral Dissertation, Texas Medical Center. Accessed February 22, 2020. http://digitalcommons.library.tmc.edu/utgsbs_dissertations/55.

MLA Handbook (7^th Edition):

Hennessey, Violeta G. “A BAYESIAN APPROACH TO DOSE-RESPONSE ASSESSMENT AND DRUG-DRUG INTERACTION ANALYSIS: APPLICATION TO IN VITRO STUDIES.” 2010. Web. 22 Feb 2020.

Vancouver:

Hennessey VG. A BAYESIAN APPROACH TO DOSE-RESPONSE ASSESSMENT AND DRUG-DRUG INTERACTION ANALYSIS: APPLICATION TO IN VITRO STUDIES. [Internet] [Doctoral dissertation]. Texas Medical Center; 2010. [cited 2020 Feb 22]. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/55.

Council of Science Editors:

Hennessey VG. A BAYESIAN APPROACH TO DOSE-RESPONSE ASSESSMENT AND DRUG-DRUG INTERACTION ANALYSIS: APPLICATION TO IN VITRO STUDIES. [Doctoral Dissertation]. Texas Medical Center; 2010. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/55

Texas Medical Center

6. Taylor, Brian A. Dynamic Chemical Shift Imaging for Image-Guided Thermal Therapy.

Degree: PhD, 2010, Texas Medical Center

URL: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/57

► Magnetic resonance temperature imaging (MRTI) is recognized as a noninvasive means to provide temperature imaging for guidance in thermal therapies. The most common method of… (more)

Subjects/Keywords: Magnetic Resonance; Chemical Shift Imaging; Thermal Therapy; Steighlitz-McBride; Autoregressive Moving Average (ARMA); k-means; Other Physics; Radiology

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APA (6^th Edition):

Taylor, B. A. (2010). Dynamic Chemical Shift Imaging for Image-Guided Thermal Therapy. (Doctoral Dissertation). Texas Medical Center. Retrieved from http://digitalcommons.library.tmc.edu/utgsbs_dissertations/57

Chicago Manual of Style (16^th Edition):

Taylor, Brian A. “Dynamic Chemical Shift Imaging for Image-Guided Thermal Therapy.” 2010. Doctoral Dissertation, Texas Medical Center. Accessed February 22, 2020. http://digitalcommons.library.tmc.edu/utgsbs_dissertations/57.

MLA Handbook (7^th Edition):

Taylor, Brian A. “Dynamic Chemical Shift Imaging for Image-Guided Thermal Therapy.” 2010. Web. 22 Feb 2020.

Vancouver:

Taylor BA. Dynamic Chemical Shift Imaging for Image-Guided Thermal Therapy. [Internet] [Doctoral dissertation]. Texas Medical Center; 2010. [cited 2020 Feb 22]. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/57.

Council of Science Editors:

Taylor BA. Dynamic Chemical Shift Imaging for Image-Guided Thermal Therapy. [Doctoral Dissertation]. Texas Medical Center; 2010. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/57

Texas Medical Center

7. Ozawa, Michael G. Targeting the Blood-brain Barrier with a Non-canonical Iron-mimicry Mechanism.

Degree: PhD, 2010, Texas Medical Center

URL: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/58

► Treatment of central nervous system (CNS) diseases is limited by the blood-brain barrier (BBB), a selective vascular interface restricting passage of most molecules from blood… (more)

Subjects/Keywords: Glioblastoma; angiogenesis; gene therapy; HSVtk; phage display; molecular imaging

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APA (6^th Edition):

Ozawa, M. G. (2010). Targeting the Blood-brain Barrier with a Non-canonical Iron-mimicry Mechanism. (Doctoral Dissertation). Texas Medical Center. Retrieved from http://digitalcommons.library.tmc.edu/utgsbs_dissertations/58

Chicago Manual of Style (16^th Edition):

Ozawa, Michael G. “Targeting the Blood-brain Barrier with a Non-canonical Iron-mimicry Mechanism.” 2010. Doctoral Dissertation, Texas Medical Center. Accessed February 22, 2020. http://digitalcommons.library.tmc.edu/utgsbs_dissertations/58.

MLA Handbook (7^th Edition):

Ozawa, Michael G. “Targeting the Blood-brain Barrier with a Non-canonical Iron-mimicry Mechanism.” 2010. Web. 22 Feb 2020.

Vancouver:

Ozawa MG. Targeting the Blood-brain Barrier with a Non-canonical Iron-mimicry Mechanism. [Internet] [Doctoral dissertation]. Texas Medical Center; 2010. [cited 2020 Feb 22]. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/58.

Council of Science Editors:

Ozawa MG. Targeting the Blood-brain Barrier with a Non-canonical Iron-mimicry Mechanism. [Doctoral Dissertation]. Texas Medical Center; 2010. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/58

Texas Medical Center

8. Lee, Alessandro K. A NEW TUMOR SUPPRESSOR GENE CANDIDATE REGULATED BY THE NON-CODING RNA PCA3 IN HUMAN PROSTATE CANCER.

Degree: PhD, 2010, Texas Medical Center

URL: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/22

► Prostate cancer is the second leading cause of cancer-related death and the most common non-skin cancer in men in the USA. Considerable advancements in the… (more)

▼ Prostate cancer is the second leading cause of cancer-related death and the most common non-skin cancer in men in the USA. Considerable advancements in the practice of medicine have allowed a significant improvement in the diagnosis and treatment of this disease and, in recent years, both incidence and mortality rates have been slightly declining. However, it is still estimated that 1 man in 6 will be diagnosed with prostate cancer during his lifetime, and 1 man in 35 will die of the disease. In order to identify novel strategies and effective therapeutic approaches in the fight against prostate cancer, it is imperative to improve our understanding of its complex biology since many aspects of prostate cancer initiation and progression still remain elusive. The study of tumor biomarkers, due to their specific altered expression in tumor versus normal tissue, is a valid tool for elucidating key aspects of cancer biology, and may provide important insights into the molecular mechanisms underlining the tumorigenesis process of prostate cancer. PCA3, is considered the most specific prostate cancer biomarker, however its biological role, until now, remained unknown. PCA3 is a long non-coding RNA (ncRNA) expressed from chromosome 9q21 and its study led us to the discovery of a novel human gene, PC-TSGC, transcribed from the opposite strand and in an antisense orientation to PCA3. With the work presented in this thesis, we demonstrate that PCA3 exerts a negative regulatory role over PC-TSGC, and we propose PC-TSGC to be a new tumor suppressor gene that contrasts the transformation of prostate cells by inhibiting Rho-GTPases signaling pathways. Our findings provide a biological role for PCA3 in prostate cancer and suggest a new mechanism of tumor suppressor gene inactivation mediated by non-coding RNA. Also, the characterization of PCA3 and PC-TSGC led us to propose a new molecular pathway involving both genes in the transformation process of the prostate, thus providing a new piece of the jigsaw puzzle representing the complex biology of prostate cancer. Advisors/Committee Members: Dr. Wadih Arap, MD, PhD, Dr. Renata Pasqualini, PhD, Dr. Neal Pellis, PhD.

Subjects/Keywords: PCA3; PC-TSGC; prostate cancer; non coding RNA; PRUNE2; BMCC1; tumor suppressor; Biology; Genomics; Male Urogenital Diseases; Molecular Biology; Oncology

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APA (6^th Edition):

Lee, A. K. (2010). A NEW TUMOR SUPPRESSOR GENE CANDIDATE REGULATED BY THE NON-CODING RNA PCA3 IN HUMAN PROSTATE CANCER. (Doctoral Dissertation). Texas Medical Center. Retrieved from http://digitalcommons.library.tmc.edu/utgsbs_dissertations/22

Chicago Manual of Style (16^th Edition):

Lee, Alessandro K. “A NEW TUMOR SUPPRESSOR GENE CANDIDATE REGULATED BY THE NON-CODING RNA PCA3 IN HUMAN PROSTATE CANCER.” 2010. Doctoral Dissertation, Texas Medical Center. Accessed February 22, 2020. http://digitalcommons.library.tmc.edu/utgsbs_dissertations/22.

MLA Handbook (7^th Edition):

Lee, Alessandro K. “A NEW TUMOR SUPPRESSOR GENE CANDIDATE REGULATED BY THE NON-CODING RNA PCA3 IN HUMAN PROSTATE CANCER.” 2010. Web. 22 Feb 2020.

Vancouver:

Lee AK. A NEW TUMOR SUPPRESSOR GENE CANDIDATE REGULATED BY THE NON-CODING RNA PCA3 IN HUMAN PROSTATE CANCER. [Internet] [Doctoral dissertation]. Texas Medical Center; 2010. [cited 2020 Feb 22]. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/22.

Council of Science Editors:

Lee AK. A NEW TUMOR SUPPRESSOR GENE CANDIDATE REGULATED BY THE NON-CODING RNA PCA3 IN HUMAN PROSTATE CANCER. [Doctoral Dissertation]. Texas Medical Center; 2010. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/22

Texas Medical Center

9. Zhou, Yang. THE ROLE OF A2B ADENOSINE RECEPTOR SIGNALING IN ADENOSINE DEPENDENT LUNG DISEASE.

Degree: PhD, 2010, Texas Medical Center

URL: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/13

► Chronic lung diseases and acute lung injuries are two distinctive pulmonary disorders that result in significant morbidity and mortality. Adenosine is a signaling nucleoside generated… (more)

Subjects/Keywords: Adenosine; Lung; COPD; Pulmonary Fibrosis; Biochemistry

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APA (6^th Edition):

Zhou, Y. (2010). THE ROLE OF A2B ADENOSINE RECEPTOR SIGNALING IN ADENOSINE DEPENDENT LUNG DISEASE. (Doctoral Dissertation). Texas Medical Center. Retrieved from http://digitalcommons.library.tmc.edu/utgsbs_dissertations/13

Chicago Manual of Style (16^th Edition):

Zhou, Yang. “THE ROLE OF A2B ADENOSINE RECEPTOR SIGNALING IN ADENOSINE DEPENDENT LUNG DISEASE.” 2010. Doctoral Dissertation, Texas Medical Center. Accessed February 22, 2020. http://digitalcommons.library.tmc.edu/utgsbs_dissertations/13.

MLA Handbook (7^th Edition):

Zhou, Yang. “THE ROLE OF A2B ADENOSINE RECEPTOR SIGNALING IN ADENOSINE DEPENDENT LUNG DISEASE.” 2010. Web. 22 Feb 2020.

Vancouver:

Zhou Y. THE ROLE OF A2B ADENOSINE RECEPTOR SIGNALING IN ADENOSINE DEPENDENT LUNG DISEASE. [Internet] [Doctoral dissertation]. Texas Medical Center; 2010. [cited 2020 Feb 22]. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/13.

Council of Science Editors:

Zhou Y. THE ROLE OF A2B ADENOSINE RECEPTOR SIGNALING IN ADENOSINE DEPENDENT LUNG DISEASE. [Doctoral Dissertation]. Texas Medical Center; 2010. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/13

Texas Medical Center

10. Latham, (Leigh) Beth T. Protein-Protein Interactions That Regulate Neurotransmitter Release from Retinal Ribbon Synapses.

Degree: PhD, 2010, Texas Medical Center

URL: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/29

► Protein-Protein Interactions That Regulate Neurotransmitter Release from Retinal Ribbon Synapses Photoreceptors and bipolar cells in the retina form specialized chemical synapses called ribbon synapses. This… (more)

Subjects/Keywords: syntaxin 3B; retinal ribbon synapses; Molecular and Cellular Neuroscience

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APA (6^th Edition):

Latham, (. B. T. (2010). Protein-Protein Interactions That Regulate Neurotransmitter Release from Retinal Ribbon Synapses. (Doctoral Dissertation). Texas Medical Center. Retrieved from http://digitalcommons.library.tmc.edu/utgsbs_dissertations/29

Chicago Manual of Style (16^th Edition):

Latham, (Leigh) Beth T. “Protein-Protein Interactions That Regulate Neurotransmitter Release from Retinal Ribbon Synapses.” 2010. Doctoral Dissertation, Texas Medical Center. Accessed February 22, 2020. http://digitalcommons.library.tmc.edu/utgsbs_dissertations/29.

MLA Handbook (7^th Edition):

Latham, (Leigh) Beth T. “Protein-Protein Interactions That Regulate Neurotransmitter Release from Retinal Ribbon Synapses.” 2010. Web. 22 Feb 2020.

Vancouver:

Latham (BT. Protein-Protein Interactions That Regulate Neurotransmitter Release from Retinal Ribbon Synapses. [Internet] [Doctoral dissertation]. Texas Medical Center; 2010. [cited 2020 Feb 22]. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/29.

Council of Science Editors:

Latham (BT. Protein-Protein Interactions That Regulate Neurotransmitter Release from Retinal Ribbon Synapses. [Doctoral Dissertation]. Texas Medical Center; 2010. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/29

Texas Medical Center

11. Newman, Leslie A. Attitudes of Parents at risk of inheriting Li-Fraumeni Syndrome towards predictive genetic testing in their minor-aged children.

Degree: MS, 2010, Texas Medical Center

URL: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/38

► Li-Fraumeni Syndrome (LFS) is a hereditary cancer syndrome which predisposes individuals to cancer beginning in childhood. These risks are spread across a lifetime, from early… (more)

▼ Li-Fraumeni Syndrome (LFS) is a hereditary cancer syndrome which predisposes individuals to cancer beginning in childhood. These risks are spread across a lifetime, from early childhood to adulthood. Mutations in the p53 tumor suppressor gene are known to cause the majority of cases of LFS. The risk for early onset cancer in individuals with Li-Fraumeni Syndrome is high. Studies have shown that individuals with LFS have a 90% lifetime cancer risk. Children under 18 have up to a 15% chance of cancer development. Effectiveness of cancer screening and management in individuals with Li-Fraumeni Syndrome is unclear. Screening for LFS-associated cancers has not been shown to reduce mortality. Due to the lack of effective screening techniques for childhood cancers, institutions vary with regard to their policies on testing children for LFS. There are currently no national guidelines regarding predictive testing of children who are at risk of inheriting LFS. No studies have looked at parental attitudes towards predictive p53 genetic testing in their children. This was a cross-sectional pilot study aimed at describing these attitudes. We identified individuals whose children were at risk for inheriting p53 genetic mutations. These individuals were provided with surveys which included validated measures addressing attitudes and beliefs towards genetic testing. The questionnaire included qualitative and quantitative measures. Six individuals completed and returned the questionnaire with a response rate of 28.57%. In general, respondents agreed that parents should have the opportunity to obtain p53 genetic testing for their child. Parents vary in regard to their attitudes towards who should be involved in the decision making process and at what time and under what considerations testing should occur. Testing motivations cited most important by respondents included family history, planning for the future and health management. Concern for insurance genetic discrimination was cited as the most important “con” to genetic testing. Although limited by a poor response rate, this study can give health care practitioners insight into testing attitudes and beliefs of families considering pediatric genetic testing. Advisors/Committee Members: Louise Strong, MD, Susan K Peterson , PhD, Christopher Amos, PhD.

Subjects/Keywords: Li-Fraumeni Syndrome; genetic testing; children; Bioethics and Medical Ethics; Genetics

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APA (6^th Edition):

Newman, L. A. (2010). Attitudes of Parents at risk of inheriting Li-Fraumeni Syndrome towards predictive genetic testing in their minor-aged children. (Masters Thesis). Texas Medical Center. Retrieved from http://digitalcommons.library.tmc.edu/utgsbs_dissertations/38

Chicago Manual of Style (16^th Edition):

Newman, Leslie A. “Attitudes of Parents at risk of inheriting Li-Fraumeni Syndrome towards predictive genetic testing in their minor-aged children.” 2010. Masters Thesis, Texas Medical Center. Accessed February 22, 2020. http://digitalcommons.library.tmc.edu/utgsbs_dissertations/38.

MLA Handbook (7^th Edition):

Newman, Leslie A. “Attitudes of Parents at risk of inheriting Li-Fraumeni Syndrome towards predictive genetic testing in their minor-aged children.” 2010. Web. 22 Feb 2020.

Vancouver:

Newman LA. Attitudes of Parents at risk of inheriting Li-Fraumeni Syndrome towards predictive genetic testing in their minor-aged children. [Internet] [Masters thesis]. Texas Medical Center; 2010. [cited 2020 Feb 22]. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/38.

Council of Science Editors:

Newman LA. Attitudes of Parents at risk of inheriting Li-Fraumeni Syndrome towards predictive genetic testing in their minor-aged children. [Masters Thesis]. Texas Medical Center; 2010. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/38

Texas Medical Center

12. Schaeffer, Daneen. THE DOMAINS OF THE CATALYTIC SUBUNIT OF THE EUKARYOTIC RNA DEGRADING EXOSOME, RRP44P, HAVE DISTINCT FUNCTIONS.

Degree: PhD, 2010, Texas Medical Center

URL: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/56

► The exosome is a 3’ to 5’ exoribonuclease complex that consists of ten essential subunits. In the cytoplasm, the exosome degrades mRNA in a general… (more)

▼ The exosome is a 3’ to 5’ exoribonuclease complex that consists of ten essential subunits. In the cytoplasm, the exosome degrades mRNA in a general mRNA turnover pathway and in several mRNA surveillance pathways. In the nucleus, the exosome processes RNA precursors to form small, stable, mature RNA species, including rRNA, snRNA, and snoRNA. In addition to processing these RNAs, the nuclear exosome is also involved in degrading aberrantly processed forms of these RNAs, and others, including mRNA. The 3’ to 5’ exoribonuclease activity of the exosome is contributed by the RNB domain of the only catalytically active subunit, Rrp44p, a member of the RNase II family of enzymes. In addition to the RNB domain, Rrp44p consists of three putative RNA binding domains and has an uncharacterized N-terminus, which includes a CR3 region and PIN domain. In an effort to characterize the cellular functions of the domains of Rrp44p, this study identified a second nuclease active site in the PIN domain. Specifically, the PIN domain exhibits endoribonuclease activity in vitro and is essential for exosome function. Further analysis of the nuclease activities of Rrp44p indicate a role for the exoribonuclease activity of Rrp44p in the cytoplasmic and nuclear exosome. This work has also characterized the CR3 region of Rrp44p, a region that has not yet been characterized in any other protein. This region is needed for the majority, if not all, of the cytoplasmic exosome functions as well as for interaction with the exosome. The CR3 region, along with a histidine residue in the N-terminus of Rrp44p, may coordinate a zinc atom. Preliminary evidence supports a role for this coordination in exosome function. Further investigation, however, is needed to determine the molecular dependence of the exosome on the CR3 region of Rrp44p. Despite its initial discovery thirteen years ago, the essential function of Rrp44p, and the exosome, is not yet known. The studies presented here, however, indicate that the essential function of Rrp44p and the exosome is in the nucleus and depends on the nuclease activities of Rrp44p. Advisors/Committee Members: Dr. Ambro van Hoof, Dr. Heidi B. Kaplan, Dr. William Margolin.

Subjects/Keywords: S. cerevisiae; mRNA degradation; eukaryotic gene expression; Molecular Genetics; Other Microbiology

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APA (6^th Edition):

Schaeffer, D. (2010). THE DOMAINS OF THE CATALYTIC SUBUNIT OF THE EUKARYOTIC RNA DEGRADING EXOSOME, RRP44P, HAVE DISTINCT FUNCTIONS. (Doctoral Dissertation). Texas Medical Center. Retrieved from http://digitalcommons.library.tmc.edu/utgsbs_dissertations/56

Chicago Manual of Style (16^th Edition):

Schaeffer, Daneen. “THE DOMAINS OF THE CATALYTIC SUBUNIT OF THE EUKARYOTIC RNA DEGRADING EXOSOME, RRP44P, HAVE DISTINCT FUNCTIONS.” 2010. Doctoral Dissertation, Texas Medical Center. Accessed February 22, 2020. http://digitalcommons.library.tmc.edu/utgsbs_dissertations/56.

MLA Handbook (7^th Edition):

Schaeffer, Daneen. “THE DOMAINS OF THE CATALYTIC SUBUNIT OF THE EUKARYOTIC RNA DEGRADING EXOSOME, RRP44P, HAVE DISTINCT FUNCTIONS.” 2010. Web. 22 Feb 2020.

Vancouver:

Schaeffer D. THE DOMAINS OF THE CATALYTIC SUBUNIT OF THE EUKARYOTIC RNA DEGRADING EXOSOME, RRP44P, HAVE DISTINCT FUNCTIONS. [Internet] [Doctoral dissertation]. Texas Medical Center; 2010. [cited 2020 Feb 22]. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/56.

Council of Science Editors:

Schaeffer D. THE DOMAINS OF THE CATALYTIC SUBUNIT OF THE EUKARYOTIC RNA DEGRADING EXOSOME, RRP44P, HAVE DISTINCT FUNCTIONS. [Doctoral Dissertation]. Texas Medical Center; 2010. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/56

Texas Medical Center

13. Ester, Audrey R. Analysis of Variation in Clubfoot Candidate Genes.

Degree: PhD, 2010, Texas Medical Center

URL: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/7

► Isolated clubfoot, a common birth defect occurring in more than 135,000 livebirths worldwide each year, is associated with significant health care and financial burdens. Clubfoot… (more)

Subjects/Keywords: genotyping; clubfoot; complex disease; limb development; Genetics; Molecular Genetics

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APA (6^th Edition):

Ester, A. R. (2010). Analysis of Variation in Clubfoot Candidate Genes. (Doctoral Dissertation). Texas Medical Center. Retrieved from http://digitalcommons.library.tmc.edu/utgsbs_dissertations/7

Chicago Manual of Style (16^th Edition):

Ester, Audrey R. “Analysis of Variation in Clubfoot Candidate Genes.” 2010. Doctoral Dissertation, Texas Medical Center. Accessed February 22, 2020. http://digitalcommons.library.tmc.edu/utgsbs_dissertations/7.

MLA Handbook (7^th Edition):

Ester, Audrey R. “Analysis of Variation in Clubfoot Candidate Genes.” 2010. Web. 22 Feb 2020.

Vancouver:

Ester AR. Analysis of Variation in Clubfoot Candidate Genes. [Internet] [Doctoral dissertation]. Texas Medical Center; 2010. [cited 2020 Feb 22]. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/7.

Council of Science Editors:

Ester AR. Analysis of Variation in Clubfoot Candidate Genes. [Doctoral Dissertation]. Texas Medical Center; 2010. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/7

Texas Medical Center

14. Kurinna, Svitlana M. NEW TARGET GENES FOR TUMOR SUPPRESSORS p53 AND p73 IN REGENERATING LIVER.

Degree: PhD, 2010, Texas Medical Center

URL: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/20

► The p53-family of proteins regulates expression of target genes during tissue development and differentiation. Within the p53-family, p53 and p73 have hepatic-specific functions in development… (more)

▼ The p53-family of proteins regulates expression of target genes during tissue development and differentiation. Within the p53-family, p53 and p73 have hepatic-specific functions in development and tumor suppression. Despite a growing list of p53/p73 target genes, very few of these have been studied in vivo, and the knowledge regarding functions of p53 and p73 in normal tissues remains limited. p53+/-p73+/- mice develop hepatocellular carcinoma (HCC), whereas overexpression of p53 in human HCC leads to tumor regression. However, the mechanism of p53/p73 function in liver remains poorly characterized. Here, the model of mouse liver regeneration is used to identify new target genes for p53/p73 in normal quiescent vs. proliferating cells. In response to surgical removal of ~2/3 of liver mass (partial hepatectomy, PH), the remaining hepatocytes exit G0 of cell cycle and undergo proliferation to reestablish liver mass. The hypothesis tested in this work is that p53/p73 functions in cell cycle arrest, apoptosis and senescence are repressed during liver regeneration, and reactivated at the end of the regenerative response. Chromatin immunoprecipitation (ChIP), with a p73-antibody, was used to probe arrayed genomic sequences (ChIP-chip) and uncover 158 potential targets of p73-regulation in normal liver. Global microarray analysis of mRNA levels, at T=0-48h following PH, revealed sets of genes that change expression during regeneration. Eighteen p73-bound genes changed expression after PH. Four of these genes, Foxo3, Jak1, Pea15, and Tuba1 have p53 response elements (p53REs), identified in silico within the upstream regulatory region. Forkhead transcription factor Foxo3 is the most responsive gene among transcription factors with altered expression during regenerative, cellular proliferation. p53 and p73 bind a Foxo3 p53RE and maintain active expression in quiescent liver. During liver regeneration, binding of p53 and p73, recruitment of acetyltransferase p300, and an active chromatin structure of Foxo3 are disrupted, alongside loss of Foxo3 expression. These parameters of Foxo3 regulation are reestablished at completion of liver growth and regeneration, supporting a temporary suspension of p53 and p73 regulatory functions in normal cells during tissue regeneration. Advisors/Committee Members: Michelle Barton, Ph.D., Sharon Dent, Ph.D., Guillermina Lozano, Ph.D..

Subjects/Keywords: p53; p73; forkhead; transcription; liver; regeneration; Biology; Cell and Developmental Biology; Laboratory and Basic Science Research; Medicine and Health Sciences

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APA (6^th Edition):

Kurinna, S. M. (2010). NEW TARGET GENES FOR TUMOR SUPPRESSORS p53 AND p73 IN REGENERATING LIVER. (Doctoral Dissertation). Texas Medical Center. Retrieved from http://digitalcommons.library.tmc.edu/utgsbs_dissertations/20

Chicago Manual of Style (16^th Edition):

Kurinna, Svitlana M. “NEW TARGET GENES FOR TUMOR SUPPRESSORS p53 AND p73 IN REGENERATING LIVER.” 2010. Doctoral Dissertation, Texas Medical Center. Accessed February 22, 2020. http://digitalcommons.library.tmc.edu/utgsbs_dissertations/20.

MLA Handbook (7^th Edition):

Kurinna, Svitlana M. “NEW TARGET GENES FOR TUMOR SUPPRESSORS p53 AND p73 IN REGENERATING LIVER.” 2010. Web. 22 Feb 2020.

Vancouver:

Kurinna SM. NEW TARGET GENES FOR TUMOR SUPPRESSORS p53 AND p73 IN REGENERATING LIVER. [Internet] [Doctoral dissertation]. Texas Medical Center; 2010. [cited 2020 Feb 22]. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/20.

Council of Science Editors:

Kurinna SM. NEW TARGET GENES FOR TUMOR SUPPRESSORS p53 AND p73 IN REGENERATING LIVER. [Doctoral Dissertation]. Texas Medical Center; 2010. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/20

Texas Medical Center

15. Vishwamitra, Deeksha. TYPE I INSULIN-LIKE GROWTH FACTOR RECEPTOR TYROSINE KINASE AS A MOLECULAR TARGET IN MANTLE CELL LYMPHOMA.

Degree: MS, 2010, Texas Medical Center

URL: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/21

► Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoid malignancy representing 5-10% of all non-Hodgkin’s lymphomas. It is distinguished by the t(11;14)(q13;q32) chromosomal translocation that… (more)

▼ Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoid malignancy representing 5-10% of all non-Hodgkin’s lymphomas. It is distinguished by the t(11;14)(q13;q32) chromosomal translocation that juxtaposes the proto-oncogene CCND1, which encodes cyclin D1 at 11q13 to the IgH gene at 14q32. MCL patients represent about 6% of all new cases of Non-Hodgkin’s lymphomas per year or about 3,500 new cases per year. MCL occurs more frequently in older adults – the average age at diagnosis is the mid-60s with a male-to-female ratio of 2-3:1. It is typically characterized by the proliferation of neoplastic B-lymphocytes in the mantle zone of the lymph node follicle that have a prominent inclination to disseminate to other lymphoid tissues, bone marrow, peripheral blood and other organs. MCL patients have a poor prognosis because they develop resistance/relapse to current non-specific therapeutic regimens. It is of note that the exact molecular mechanisms underlying the pathogenesis of MCL are not completely known. It is reasonable to anticipate that better characterization of these mechanisms could lead to the development of specific and likely more effective therapeutics to treat this aggressive disease. The type I insulin-like growth factor receptor (IGF-IR) is thought to be a key player in several different solid malignancies such as those of the prostate, breast, lung, ovary, skin and soft tissue. In addition, recent studies in our lab showed evidence to support a pathogenic role of IGF-IR in some types of T-cell lymphomas and chronic myeloid leukemia. Constitutively active IGF-IR induces its oncogenic effects through the inhibition of apoptosis and induction of transformation, metastasis, and angiogenesis. Previous studies have shown that signaling through IGF-IR leads to the vi activation of multiple signaling transduction pathways mediated by the receptor-associated tyrosine kinase domain. These pathways include PI3K/Akt, MAP kinase, and Jak/Stat. In the present study, we tested the possible role of IGF-IR in MCL. Our results demonstrate that IGF-IR is over-expressed in mantle cell lymphoma cell lines compared with normal peripheral blood B- lymphocytes. Furthermore, inhibition of IGF-IR by the cyclolignan picropodophyllin (PPP) decreased cell viability and cell proliferation in addition to induction of apoptosis and G2/M cell cycle arrest. Screening of downstream oncogenes and apoptotic proteins that are involved in both IGF-IR and MCL signaling after treatment with PPP or IGF-IR siRNA showed significant alterations that are consistent with the cellular changes observed after PPP treatment. Therefore, our findings suggest that IGF-IR signaling contributes to the survival of MCL and thus may prove to be a legitimate therapeutic target in the future. Advisors/Committee Members: Hesham M. Amin, M.D., Russell Broaddus, M.D., Ph.D, Joya Chandra, Ph.D.

Subjects/Keywords: IGF-IR; mantle cell lymphoma; cyclin D1; picropodophyllin; Medical Pathology

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APA (6^th Edition):

Vishwamitra, D. (2010). TYPE I INSULIN-LIKE GROWTH FACTOR RECEPTOR TYROSINE KINASE AS A MOLECULAR TARGET IN MANTLE CELL LYMPHOMA. (Masters Thesis). Texas Medical Center. Retrieved from http://digitalcommons.library.tmc.edu/utgsbs_dissertations/21

Chicago Manual of Style (16^th Edition):

Vishwamitra, Deeksha. “TYPE I INSULIN-LIKE GROWTH FACTOR RECEPTOR TYROSINE KINASE AS A MOLECULAR TARGET IN MANTLE CELL LYMPHOMA.” 2010. Masters Thesis, Texas Medical Center. Accessed February 22, 2020. http://digitalcommons.library.tmc.edu/utgsbs_dissertations/21.

MLA Handbook (7^th Edition):

Vishwamitra, Deeksha. “TYPE I INSULIN-LIKE GROWTH FACTOR RECEPTOR TYROSINE KINASE AS A MOLECULAR TARGET IN MANTLE CELL LYMPHOMA.” 2010. Web. 22 Feb 2020.

Vancouver:

Vishwamitra D. TYPE I INSULIN-LIKE GROWTH FACTOR RECEPTOR TYROSINE KINASE AS A MOLECULAR TARGET IN MANTLE CELL LYMPHOMA. [Internet] [Masters thesis]. Texas Medical Center; 2010. [cited 2020 Feb 22]. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/21.

Council of Science Editors:

Vishwamitra D. TYPE I INSULIN-LIKE GROWTH FACTOR RECEPTOR TYROSINE KINASE AS A MOLECULAR TARGET IN MANTLE CELL LYMPHOMA. [Masters Thesis]. Texas Medical Center; 2010. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/21

Texas Medical Center

16. Jen, Emily. IL-2 REGULATION OF IL-24 EXPRESSION LEADS TO GROWTH SUPPRESSION OF MELANOMA CELLS.

Degree: PhD, 2010, Texas Medical Center

URL: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/32

► Melanoma is known to be highly resistant to chemotherapy. Treatment with high dose IL-2 has shown significant clinical benefit in a minority of metastatic melanoma… (more)

▼ Melanoma is known to be highly resistant to chemotherapy. Treatment with high dose IL-2 has shown significant clinical benefit in a minority of metastatic melanoma patients and has lead to long term survival in a few cases. However, this treatment is associated with excessive multiorgan toxicities, which severely limits its use. We hypothesize that one mechanism of effective IL-2 therapy is through the direct upregulation of IL-24 production in melanoma tumors and subsequent IL-24 mediated tumor growth suppression. Five melanoma cell lines were treated with high dose recombinant hIL-2 at 1000U/ml. Three of the cell lines (A375, WM1341, WM793) showed statistically significant increases in their levels of IL-24 protein when measured by Western blotting, while the remaining two lines (WM35, MeWo) remained negative for IL-24 message and protein. This increase in IL-24 was abolished by either preincubating with an anti-IL-2 antibody or by blocking the IL-2 receptor directly with antibodies against the receptor chains. We also demonstrated by ELISA that these three cell lines secrete IL-24 protein in higher amounts when stimulated with IL-2 than do untreated cells. These cells were found to contain IL-2R beta and gamma message by RT-PCR and also expressed higher levels of IL-24 when treated with IL-15, which shares the IL-2R beta chain. Thus we propose that IL-2 is signaling through IL-2R beta on some melanoma cells to upregulate IL-24 protein expression. To address the biological function of IL-2 in melanoma cells, five cell lines were treated with IL-2 and cell viability determined. Cell growth was found to be significantly decreased by day 4 in the IL-24 positive cell lines while no effect on growth was seen in WM35 or MeWo. Incubating the cells with anti-IL-24 antibody or transfecting with IL-24 siRNA effectively negated the growth suppression seen with IL-2. These data support our hypothesis that in addition to its immunotherapeutic effects, IL-2 also acts directly on some melanoma tumors and that the IL-24 and IL-2R beta status of a tumor may be useful in predicting patient response to high dose IL-2. Advisors/Committee Members: Dr. Elizabeth A. Grimm, Dr. Russell R. Broaddus, Dr. Nancy J. Poindexter.

Subjects/Keywords: IL-24; melanoma; IL-2; predictive marker; growth suppression; Medical Cell Biology; Oncology

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

APA (6^th Edition):

Jen, E. (2010). IL-2 REGULATION OF IL-24 EXPRESSION LEADS TO GROWTH SUPPRESSION OF MELANOMA CELLS. (Doctoral Dissertation). Texas Medical Center. Retrieved from http://digitalcommons.library.tmc.edu/utgsbs_dissertations/32

Chicago Manual of Style (16^th Edition):

Jen, Emily. “IL-2 REGULATION OF IL-24 EXPRESSION LEADS TO GROWTH SUPPRESSION OF MELANOMA CELLS.” 2010. Doctoral Dissertation, Texas Medical Center. Accessed February 22, 2020. http://digitalcommons.library.tmc.edu/utgsbs_dissertations/32.

MLA Handbook (7^th Edition):

Jen, Emily. “IL-2 REGULATION OF IL-24 EXPRESSION LEADS TO GROWTH SUPPRESSION OF MELANOMA CELLS.” 2010. Web. 22 Feb 2020.

Vancouver:

Jen E. IL-2 REGULATION OF IL-24 EXPRESSION LEADS TO GROWTH SUPPRESSION OF MELANOMA CELLS. [Internet] [Doctoral dissertation]. Texas Medical Center; 2010. [cited 2020 Feb 22]. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/32.

Council of Science Editors:

Jen E. IL-2 REGULATION OF IL-24 EXPRESSION LEADS TO GROWTH SUPPRESSION OF MELANOMA CELLS. [Doctoral Dissertation]. Texas Medical Center; 2010. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/32

Texas Medical Center

17. Sommer, Amy M. Xenobiotic Metabolism Genes and Clubfoot.

Degree: MS, 2010, Texas Medical Center

URL: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/35

► Idiopathic or isolated clubfoot is a common orthopedic birth defect that affects approximately 135,000 children worldwide. It is characterized by equinus, varus and adductus deformities… (more)

▼ Idiopathic or isolated clubfoot is a common orthopedic birth defect that affects approximately 135,000 children worldwide. It is characterized by equinus, varus and adductus deformities of the ankle and foot. Correction of clubfoot involves months of serial manipulations, castings and bracing, with surgical correction needed in forty percent of cases. Multifactorial etiology has been suggested in numerous studies with both environmental and genetic factors playing an etiologic role. Maternal smoking during pregnancy is the only common environmental factor that has consistently been shown to increase the risk for clubfoot. Moreover, a positive family history of clubfoot and maternal smoking increases the risk of clubfoot twenty fold. These findings suggest that genetic variation in smoking metabolism genes may increase susceptibility to clubfoot. Based on this reasoning, we interrogated eight candidate genes, chosen based on their involvement in phase 1 and 2 cigarette smoke metabolism. Twenty-two SNPs and two null alleles in eight genes (CYP1A1, CYP1A2, CYP1B1, CYP2A6, EPHX1, NAT2, GSTM1 and GSTT1) were genotyped in a dataset composed of nonHispanic white and Hispanic multiplex and simplex families. Only one SNP in CYP1A1, rs1048943, had significantly altered transmission in the aggregate and multiplex NHW datasets (p=0.003 and p=0.009). Perturbation of CYP1A1 by rs1048943 polymorphism causes an increase in the amount of harmful, adduct forming metabolic intermediates. A significant gene interaction between EPHX1 and NAT2 was also found (p=0.007). This interaction may affect the metabolism of harmful metabolic intermediates. Additionally, marginal interactions were found for other xenobiotic genes and these interactions may play a contributory role in clubfoot. Importantly, for CYP1A2, significant maternal (p=0.03; RR=1.24; 95% CI: 1.04-1.44) and fetal (p=0.01; RR=1.33; 95% CI: 1.13-1.54) genotypic effects were identified suggesting that both maternal and fetal genotypes impact normal limb development. No association was found for maternal smoking status and tobacco metabolism genes. Together, these results suggest that xenobiotic metabolism genes may play a contributory role in the etiology of clubfoot regardless of maternal smoking status and may impact foot development through perturbation of tobacco metabolic pathways. Advisors/Committee Members: Jacqueline T. Hecht, PhD, Susan H. Blanton, PhD, Stephen P. Daiger, PhD.

Subjects/Keywords: clubfoot; xenobiotic metabolism; tobacco smoke; birth defects; talipes; Genetics; Medical Genetics; Molecular Genetics

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

APA (6^th Edition):

Sommer, A. M. (2010). Xenobiotic Metabolism Genes and Clubfoot. (Masters Thesis). Texas Medical Center. Retrieved from http://digitalcommons.library.tmc.edu/utgsbs_dissertations/35

Chicago Manual of Style (16^th Edition):

Sommer, Amy M. “Xenobiotic Metabolism Genes and Clubfoot.” 2010. Masters Thesis, Texas Medical Center. Accessed February 22, 2020. http://digitalcommons.library.tmc.edu/utgsbs_dissertations/35.

MLA Handbook (7^th Edition):

Sommer, Amy M. “Xenobiotic Metabolism Genes and Clubfoot.” 2010. Web. 22 Feb 2020.

Vancouver:

Sommer AM. Xenobiotic Metabolism Genes and Clubfoot. [Internet] [Masters thesis]. Texas Medical Center; 2010. [cited 2020 Feb 22]. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/35.

Council of Science Editors:

Sommer AM. Xenobiotic Metabolism Genes and Clubfoot. [Masters Thesis]. Texas Medical Center; 2010. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/35

Texas Medical Center

18. Nguyen, Vuvi H. THE EXPRESSION AND CELLULAR LOCALIZATION OF CC-CHEMOKINE RECEPTOR 5 (CCR5) AFTER TRAUMATIC BRAIN INJURY.

Degree: MS, 2010, Texas Medical Center

URL: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/37

► Traumatic brain injury results from a primary insult and secondary events that together result in tissue injury. This primary injury occurs at the moment of… (more)

▼ Traumatic brain injury results from a primary insult and secondary events that together result in tissue injury. This primary injury occurs at the moment of impact and damage can include scalp laceration, skull fraction, cerebral contusions and lacerations as well as intracranial hemorrhage. Following the initial insult, a delayed response occurs and is characterized by hypoxia, ischemia, cerebral edema, and infection. During secondary brain injury, a series of neuroinflammatory events are triggered that can produce additional damage but may also help to protect nervous tissue from invading pathogens and help to repair the damaged tissue. Brain microglia and astrocytes become activated and migrate to the site of injury where these cells secrete immune mediators such as cytokines and chemokines. CC-chemokine receptor 5 (CCR5) is a member of the CC chemokine receptor family of seven transmembrane G protein coupled receptors. CCR5 is expressed in the immune system and is found in monocytes, leukoctyes, memory T cells, and immature dendritic cells. Upon binding to its ligands, CCR5 functions in the chemotaxis of these immune cells to the site of inflammation. In the CNS, CCR5 and its ligands are expressed in multiple cell types. In this study, I investigated whether CCR5 expression is altered in brain after traumatic brain injury. I examined the time course of CCR5 protein expression in cortex and hippocampus using quantitative western analysis of tissues from injured rat brain after mild impact injury. In addition, I also investigated the cellular localization of CCR5 before and after brain injury using confocal microscopy. I have observed that after brain injury CCR5 is upregulated in a time dependent manner in neurons of the parietal cortex and hippocampus. The absence of CCR5 expression in microglia and its delayed expression in neurons after injury suggests a role for CCR5 in neuronal survival after injury. Advisors/Committee Members: Andrew Bean Ph.D., Pramod Dash Ph.D., Raymond Grill Ph.D..

Subjects/Keywords: CCR5; CC-Chemokine Receptor 5; Chemokines; Traumatic Brain Injury; Neuroinflammation; Molecular and Cellular Neuroscience; Neuroscience and Neurobiology

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APA (6^th Edition):

Nguyen, V. H. (2010). THE EXPRESSION AND CELLULAR LOCALIZATION OF CC-CHEMOKINE RECEPTOR 5 (CCR5) AFTER TRAUMATIC BRAIN INJURY. (Masters Thesis). Texas Medical Center. Retrieved from http://digitalcommons.library.tmc.edu/utgsbs_dissertations/37

Chicago Manual of Style (16^th Edition):

Nguyen, Vuvi H. “THE EXPRESSION AND CELLULAR LOCALIZATION OF CC-CHEMOKINE RECEPTOR 5 (CCR5) AFTER TRAUMATIC BRAIN INJURY.” 2010. Masters Thesis, Texas Medical Center. Accessed February 22, 2020. http://digitalcommons.library.tmc.edu/utgsbs_dissertations/37.

MLA Handbook (7^th Edition):

Nguyen, Vuvi H. “THE EXPRESSION AND CELLULAR LOCALIZATION OF CC-CHEMOKINE RECEPTOR 5 (CCR5) AFTER TRAUMATIC BRAIN INJURY.” 2010. Web. 22 Feb 2020.

Vancouver:

Nguyen VH. THE EXPRESSION AND CELLULAR LOCALIZATION OF CC-CHEMOKINE RECEPTOR 5 (CCR5) AFTER TRAUMATIC BRAIN INJURY. [Internet] [Masters thesis]. Texas Medical Center; 2010. [cited 2020 Feb 22]. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/37.

Council of Science Editors:

Nguyen VH. THE EXPRESSION AND CELLULAR LOCALIZATION OF CC-CHEMOKINE RECEPTOR 5 (CCR5) AFTER TRAUMATIC BRAIN INJURY. [Masters Thesis]. Texas Medical Center; 2010. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/37

Texas Medical Center

19. Crain, Carrie A. An assessment of obesity and hyperphagia in individuals with Smith-Magenis syndrome.

Degree: MS, 2010, Texas Medical Center

URL: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/39

► Smith-Magenis syndrome (SMS;OMIM# 182290) is a multiple congenital anomalies and mental retardation syndrome caused by a 3.7- Mb deletion on chromosome 17p11.2 or a mutation… (more)

▼ Smith-Magenis syndrome (SMS;OMIM# 182290) is a multiple congenital anomalies and mental retardation syndrome caused by a 3.7- Mb deletion on chromosome 17p11.2 or a mutation in the RAI1 gene. Although the majority of the SMS phenotype has been well described, limited studies are available describing growth patterns in SMS. There is some evidence that individuals with SMS develop obesity. Thus, this study aims to characterize the growth and potential influence of hyperphagia in a cohort of individuals with SMS. A retrospective chart review was conducted of 78 individuals with SMS through Baylor College of Medicine (BCM) at Texas Children¡¯s Hospital (TCH.) All documented height and weight measurements were abstracted and Z-scores (SD units) for height-for-age, length-for-age and BMI-for-age were calculated. Mail-out questionnaires were provided to the corresponding parents of the cohort to assess for the presence of hyperphagia through a validated hyperphagia questionnaire (HQ). Analysis of this data demonstrates that by the age ¡Ý 20 years males with SMS have mean BMI¡¯s in the 85th-90th percentile corresponding to an overweight BMI, and females with SMS had mean BMI¡¯s in the 95th -97th percentile corresponding to an obese BMI. Parents indicated that hyperphagia is present in individuals with SMS as 76% of parent¡¯s report having to lock food away from their child. Females¡¯ age ¡Ý 20 years of age had the highest mean behavior, drive and severity scores as well as the highest BMI. Thus, this study concludes that it appears overweight and obesity, as well as hyperphagia, are present in this cohort of SMS individuals. The results of this study will hopefully enable parents and caregivers of children with SMS to take preventative measures in order to control food related behaviors present in their children as well as to prevent overweight and obesity and the associated negative health consequences. Advisors/Committee Members: Marianna Raia, Lorraine Potocki, Patti Robbins-Furman.

Subjects/Keywords: Smith Magenis syndrome; obesity; hyperphagia; BMI; food seeking; behavior; genetic; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Medical Genetics

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APA (6^th Edition):

Crain, C. A. (2010). An assessment of obesity and hyperphagia in individuals with Smith-Magenis syndrome. (Masters Thesis). Texas Medical Center. Retrieved from http://digitalcommons.library.tmc.edu/utgsbs_dissertations/39

Chicago Manual of Style (16^th Edition):

Crain, Carrie A. “An assessment of obesity and hyperphagia in individuals with Smith-Magenis syndrome.” 2010. Masters Thesis, Texas Medical Center. Accessed February 22, 2020. http://digitalcommons.library.tmc.edu/utgsbs_dissertations/39.

MLA Handbook (7^th Edition):

Crain, Carrie A. “An assessment of obesity and hyperphagia in individuals with Smith-Magenis syndrome.” 2010. Web. 22 Feb 2020.

Vancouver:

Crain CA. An assessment of obesity and hyperphagia in individuals with Smith-Magenis syndrome. [Internet] [Masters thesis]. Texas Medical Center; 2010. [cited 2020 Feb 22]. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/39.

Council of Science Editors:

Crain CA. An assessment of obesity and hyperphagia in individuals with Smith-Magenis syndrome. [Masters Thesis]. Texas Medical Center; 2010. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/39

Texas Medical Center

20. Melancon, Adam D. RANGE ADAPTIVE PROTON THERAPY FOR PROSTATE CANCER.

Degree: PhD, 2010, Texas Medical Center

URL: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/44

► Purpose: The rapid distal falloff of a proton beam allows for sparing of normal tissues distal to the target. However proton beams that aim directly… (more)

▼ Purpose: The rapid distal falloff of a proton beam allows for sparing of normal tissues distal to the target. However proton beams that aim directly towards critical structures are avoided due to concerns of range uncertainties, such as CT number conversion and anatomy variations. We propose to eliminate range uncertainty and enable prostate treatment with a single anterior beam by detecting the proton’s range at the prostate-rectal interface and adaptively adjusting the range in vivo and in real-time. Materials and Methods: A prototype device, consisting of an endorectal liquid scintillation detector and dual-inverted Lucite wedges for range compensation, was designed to test the feasibility and accuracy of the technique. Liquid scintillation filled volume was fitted with optical fiber and placed inside the rectum of an anthropomorphic pelvic phantom. Photodiode-generated current signal was generated as a function of proton beam distal depth, and the spatial resolution of this technique was calculated by relating the variance in detecting proton spills to its maximum penetration depth. The relative water-equivalent thickness of the wedges was measured in a water phantom and prospectively tested to determine the accuracy of range corrections. Treatment simulation studies were performed to test the potential dosimetric benefit in sparing the rectum. Results: The spatial resolution of the detector in phantom measurement was 0.5 mm. The precision of the range correction was 0.04 mm. The residual margin to ensure CTV coverage was 1.1 mm. The composite distal margin for 95% treatment confidence was 2.4 mm. Planning studies based on a previously estimated 2mm margin (90% treatment confidence) for 27 patients showed a rectal sparing up to 51% at 70 Gy and 57% at 40 Gy relative to IMRT and bilateral proton treatment. Conclusion: We demonstrated the feasibility of our design. Use of this technique allows for proton treatment using a single anterior beam, significantly reducing the rectal dose. Advisors/Committee Members: Lei Dong, Ph.D., Sam Beddar, Ph.D., Rajat J. Kudchadker, Ph.D..

Subjects/Keywords: adaptive radiotherapy; proton therapy; in vivo dosimetry; image-guided radiation therapy; scintillation dosimetry; Other Physics

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

APA (6^th Edition):

Melancon, A. D. (2010). RANGE ADAPTIVE PROTON THERAPY FOR PROSTATE CANCER. (Doctoral Dissertation). Texas Medical Center. Retrieved from http://digitalcommons.library.tmc.edu/utgsbs_dissertations/44

Chicago Manual of Style (16^th Edition):

Melancon, Adam D. “RANGE ADAPTIVE PROTON THERAPY FOR PROSTATE CANCER.” 2010. Doctoral Dissertation, Texas Medical Center. Accessed February 22, 2020. http://digitalcommons.library.tmc.edu/utgsbs_dissertations/44.

MLA Handbook (7^th Edition):

Melancon, Adam D. “RANGE ADAPTIVE PROTON THERAPY FOR PROSTATE CANCER.” 2010. Web. 22 Feb 2020.

Vancouver:

Melancon AD. RANGE ADAPTIVE PROTON THERAPY FOR PROSTATE CANCER. [Internet] [Doctoral dissertation]. Texas Medical Center; 2010. [cited 2020 Feb 22]. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/44.

Council of Science Editors:

Melancon AD. RANGE ADAPTIVE PROTON THERAPY FOR PROSTATE CANCER. [Doctoral Dissertation]. Texas Medical Center; 2010. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/44

Texas Medical Center

21. Nabilsi, Nancy H. Regulation of survivin gene expression in the human endometrium and endometrial cancer.

Degree: PhD, 2009, Texas Medical Center

URL: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/1

► In the United States, endometrial cancer is the leading cancer of the female reproductive tract. There are 40,100 new cases and 7,470 deaths from endometrial… (more)

Subjects/Keywords: Endometrial Cancer; Genes; Molecular biomarkers; Survivin; Medical Genetics; Medicine and Health Sciences; Oncology

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APA (6^th Edition):

Nabilsi, N. H. (2009). Regulation of survivin gene expression in the human endometrium and endometrial cancer. (Doctoral Dissertation). Texas Medical Center. Retrieved from http://digitalcommons.library.tmc.edu/utgsbs_dissertations/1

Chicago Manual of Style (16^th Edition):

Nabilsi, Nancy H. “Regulation of survivin gene expression in the human endometrium and endometrial cancer.” 2009. Doctoral Dissertation, Texas Medical Center. Accessed February 22, 2020. http://digitalcommons.library.tmc.edu/utgsbs_dissertations/1.

MLA Handbook (7^th Edition):

Nabilsi, Nancy H. “Regulation of survivin gene expression in the human endometrium and endometrial cancer.” 2009. Web. 22 Feb 2020.

Vancouver:

Nabilsi NH. Regulation of survivin gene expression in the human endometrium and endometrial cancer. [Internet] [Doctoral dissertation]. Texas Medical Center; 2009. [cited 2020 Feb 22]. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/1.

Council of Science Editors:

Nabilsi NH. Regulation of survivin gene expression in the human endometrium and endometrial cancer. [Doctoral Dissertation]. Texas Medical Center; 2009. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/1

Texas Medical Center

22. Ragan, Dustin K. Measurement of the vascular input function in mice for DCE-MRI.

Degree: PhD, 2010, Texas Medical Center

URL: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/11

► DCE-MRI is an important technique in the study of small animal cancer models because its sensitivity to vascular changes opens the possibility of quantitative assessment… (more)

▼ DCE-MRI is an important technique in the study of small animal cancer models because its sensitivity to vascular changes opens the possibility of quantitative assessment of early therapeutic response. However, extraction of physiologically descriptive parameters from DCE-MRI data relies upon measurement of the vascular input function (VIF), which represents the contrast agent concentration time course in the blood plasma. This is difficult in small animal models due to artifacts associated with partial volume, inflow enhancement, and the limited temporal resolution achievable with MR imaging. In this work, the development of a suite of techniques for high temporal resolution, artifact resistant measurement of the VIF in mice is described. One obstacle in VIF measurement is inflow enhancement, which decreases the sensitivity of the MR signal to the presence of contrast agent. Because the traditional techniques used to suppress inflow enhancement degrade the achievable spatiotemporal resolution of the pulse sequence, improvements can be achieved by reducing the time required for the suppression. Thus, a novel RF pulse which provides spatial presaturation contemporaneously with the RF excitation was implemented and evaluated. This maximizes the achievable temporal resolution by removing the additional RF and gradient pulses typically required for suppression of inflow enhancement. A second challenge is achieving the temporal resolution required for accurate characterization of the VIF, which exceeds what can be achieved with conventional imaging techniques while maintaining adequate spatial resolution and tumor coverage. Thus, an anatomically constrained reconstruction strategy was developed that allows for sampling of the VIF at extremely high acceleration factors, permitting capture of the initial pass of the contrast agent in mice. Simulation, phantom, and in vivo validation of all components were performed. Finally, the two components were used to perform VIF measurement in the murine heart. An in vivo study of the VIF reproducibility was performed, and an improvement in the measured injection-to-injection variation was observed. This will lead to improvements in the reliability of quantitative DCE-MRI measurements and increase their sensitivity. Advisors/Committee Members: James A. Bankson, John D. Hazle, Edward F. Jackson.

Subjects/Keywords: magnetic resonance imaging; DCE-MRI; VIF; AIF; small animal imaging; constrained reconstruction; flow enhancement; reproducibility; Medical Biophysics

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APA (6^th Edition):

Ragan, D. K. (2010). Measurement of the vascular input function in mice for DCE-MRI. (Doctoral Dissertation). Texas Medical Center. Retrieved from http://digitalcommons.library.tmc.edu/utgsbs_dissertations/11

Chicago Manual of Style (16^th Edition):

Ragan, Dustin K. “Measurement of the vascular input function in mice for DCE-MRI.” 2010. Doctoral Dissertation, Texas Medical Center. Accessed February 22, 2020. http://digitalcommons.library.tmc.edu/utgsbs_dissertations/11.

MLA Handbook (7^th Edition):

Ragan, Dustin K. “Measurement of the vascular input function in mice for DCE-MRI.” 2010. Web. 22 Feb 2020.

Vancouver:

Ragan DK. Measurement of the vascular input function in mice for DCE-MRI. [Internet] [Doctoral dissertation]. Texas Medical Center; 2010. [cited 2020 Feb 22]. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/11.

Council of Science Editors:

Ragan DK. Measurement of the vascular input function in mice for DCE-MRI. [Doctoral Dissertation]. Texas Medical Center; 2010. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/11

Texas Medical Center

23. Grant, Ryan L. Implementation of an Anthropomorphic Phantom for the Evaluation of Proton Therapy Treatment Procedures.

Degree: MS, 2010, Texas Medical Center

URL: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/8

► With an increasing number of institutions offering proton therapy, the number of multi-institutional clinical trials involving proton therapy will also increase in the coming years.… (more)

▼ With an increasing number of institutions offering proton therapy, the number of multi-institutional clinical trials involving proton therapy will also increase in the coming years. The Radiological Physics Center monitors sites involved in clinical trials through the use of site visits and remote auditing with thermoluminescent dosimeters (TLD) and mailable anthropomorphic phantoms. Currently, there are no heterogeneous phantoms that have been commissioned to evaluate proton therapy. It was hypothesized that an anthropomorphic pelvis phantom can be designed to audit treatment procedures (patient simulation, treatment planning and treatment delivery) at proton facilities to confirm agreement between the measured dose and calculated dose within 5%/3mm with a reproducibility of 3%. A pelvis phantom originally designed for use with photon treatments was retrofitted for use in proton therapy. The relative stopping power (SP) of each phantom material was measured. Hounsfield Units (HU) for each phantom material were measured with a CT scanner and compared to the relative stopping power calibration curve. The tissue equivalency for each material was calculated. Two proton treatment plans were created; one which did not correct for material SP differences (Plan 1) and one plan which did correct for SP differences (Plan 2). Film and TLD were loaded into the phantom and the phantom was irradiated 3 times per plan. The measured values were compared to the HU-SP calibration curve and it was found that the stopping powers for the materials could be underestimated by 5-10%. Plan 1 passed the criteria for the TLD and film margins with reproducibility under 3% between the 3 trials. Plan 2 failed because the right-left film dose profile average displacement was -9.0 mm on the left side and 6.0 mm on the right side. Plan 2 was intended to improve the agreements and instead introduced large displacements along the path of the beam. Plan 2 more closely represented the actual phantom composition with corrected stopping powers and should have shown an agreement between the measured and calculated dose within 5%/3mm. The hypothesis was rejected and the pelvis phantom was found to be not suitable to evaluate proton therapy treatment procedures. Advisors/Committee Members: Geoffrey S. Ibbott, Ph.D., David S. Followill, Ph.D., X. Ronald Zhu, Ph.D..

Subjects/Keywords: proton therapy; dosimetry; phantoms; quality assurance; Medical Sciences; Physics

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

APA (6^th Edition):

Grant, R. L. (2010). Implementation of an Anthropomorphic Phantom for the Evaluation of Proton Therapy Treatment Procedures. (Masters Thesis). Texas Medical Center. Retrieved from http://digitalcommons.library.tmc.edu/utgsbs_dissertations/8

Chicago Manual of Style (16^th Edition):

Grant, Ryan L. “Implementation of an Anthropomorphic Phantom for the Evaluation of Proton Therapy Treatment Procedures.” 2010. Masters Thesis, Texas Medical Center. Accessed February 22, 2020. http://digitalcommons.library.tmc.edu/utgsbs_dissertations/8.

MLA Handbook (7^th Edition):

Grant, Ryan L. “Implementation of an Anthropomorphic Phantom for the Evaluation of Proton Therapy Treatment Procedures.” 2010. Web. 22 Feb 2020.

Vancouver:

Grant RL. Implementation of an Anthropomorphic Phantom for the Evaluation of Proton Therapy Treatment Procedures. [Internet] [Masters thesis]. Texas Medical Center; 2010. [cited 2020 Feb 22]. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/8.

Council of Science Editors:

Grant RL. Implementation of an Anthropomorphic Phantom for the Evaluation of Proton Therapy Treatment Procedures. [Masters Thesis]. Texas Medical Center; 2010. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/8

Texas Medical Center

24. Stewart, Keri L. Delta like ligand 4 is a critical regulator of bone marrow cell differentiation into pericytes/vascular smooth muscle cells and is essential for the vasculogenesis that supports the growth of Ewing’s sarcoma.

Degree: PhD, 2010, Texas Medical Center

URL: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/30

► We have previously shown that vasculogenesis, the process by which bone marrow-derived cells are recruited to the tumor and organized to form a blood vessel… (more)

▼ We have previously shown that vasculogenesis, the process by which bone marrow-derived cells are recruited to the tumor and organized to form a blood vessel network de novo, is essential for the growth of Ewing’s sarcoma. We further demonstrated that these bone marrow cells differentiate into pericytes/vascular smooth muscle cells(vSMC) and contribute to the formation of the functional vascular network. The molecular mechanisms that control bone marrow cell differentiation into pericytes/vSMC in Ewing’s sarcoma are poorly understood. Here, we demonstrate that the Notch ligand Delta like ligand 4 (DLL4) plays a critical role in this process. DLL4 is essential for the formation of mature blood vessels during development and in several tumor models. Inhibition of DLL4 causes increased vascular sprouting, decreased pericyte coverage, and decreased vessel functionality. We demonstrate for the first time that DLL4 is expressed by bone marrow-derived pericytes/vascular smooth muscle cells in two Ewing’s sarcoma xenograft models and by perivascular cells in 12 out of 14 patient samples. Using dominant negative mastermind to inhibit Notch, we demonstrate that Notch signaling is essential for bone marrow cell participation in vasculogenesis. Further, inhibition of DLL4 using either shRNA or the monoclonal DLL4 neutralizing antibody YW152F led to dramatic changes in blood vessel morphology and function. Vessels in tumors where DLL4 was inhibited were smaller, lacked lumens, had significantly reduced numbers of bone marrow-derived pericyte/vascular smooth muscle cells, and were less functional. Importantly, growth of TC71 and A4573 tumors was significantly inhibited by treatment with YW152F. Additionally, we provide in vitro evidence that DLL4-Notch signaling is involved in bone marrow-derived pericyte/vascular smooth muscle cell formation outside of the Ewing’s sarcoma environment. Pericyte/vascular smooth muscle cell marker expression by whole bone marrow cells cultured with mouse embryonic stromal cells was reduced when DLL4 was inhibited by YW152F. For the first time, our findings demonstrate a role for DLL4 in bone marrow-derived pericyte/vascular smooth muscle differentiation as well as a critical role for DLL4 in Ewing’s sarcoma tumor growth. Advisors/Committee Members: Eugenie S. Kleinerman, MD, Patrick Zweidler-McKay, MD, PhD, Lee M Ellis, MD.

Subjects/Keywords: Notch; DLL4; vasculogenesis; Ewing's sarcoma; pericytes; vascular smooth muscle cells; Cancer Biology

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APA (6^th Edition):

Stewart, K. L. (2010). Delta like ligand 4 is a critical regulator of bone marrow cell differentiation into pericytes/vascular smooth muscle cells and is essential for the vasculogenesis that supports the growth of Ewing’s sarcoma. (Doctoral Dissertation). Texas Medical Center. Retrieved from http://digitalcommons.library.tmc.edu/utgsbs_dissertations/30

Chicago Manual of Style (16^th Edition):

Stewart, Keri L. “Delta like ligand 4 is a critical regulator of bone marrow cell differentiation into pericytes/vascular smooth muscle cells and is essential for the vasculogenesis that supports the growth of Ewing’s sarcoma.” 2010. Doctoral Dissertation, Texas Medical Center. Accessed February 22, 2020. http://digitalcommons.library.tmc.edu/utgsbs_dissertations/30.

MLA Handbook (7^th Edition):

Stewart, Keri L. “Delta like ligand 4 is a critical regulator of bone marrow cell differentiation into pericytes/vascular smooth muscle cells and is essential for the vasculogenesis that supports the growth of Ewing’s sarcoma.” 2010. Web. 22 Feb 2020.

Vancouver:

Stewart KL. Delta like ligand 4 is a critical regulator of bone marrow cell differentiation into pericytes/vascular smooth muscle cells and is essential for the vasculogenesis that supports the growth of Ewing’s sarcoma. [Internet] [Doctoral dissertation]. Texas Medical Center; 2010. [cited 2020 Feb 22]. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/30.

Council of Science Editors:

Stewart KL. Delta like ligand 4 is a critical regulator of bone marrow cell differentiation into pericytes/vascular smooth muscle cells and is essential for the vasculogenesis that supports the growth of Ewing’s sarcoma. [Doctoral Dissertation]. Texas Medical Center; 2010. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/30

Texas Medical Center

25. Babcock, Daniel T. DAMAGE-INDUCED INFLAMMATION AND NOCICEPTIVE HYPERSENSITIVITY IN DROSOPHILA LARVAE.

Degree: PhD, 2010, Texas Medical Center

URL: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/6

► Mounting an effective response to tissue damage requires a concerted effort from a number of systems, including both the immune and nervous systems. Immune-responsive blood… (more)

Subjects/Keywords: Drosophila; nociception; inflammation; damage; allodynia; hyperalgesia; ultraviolet; Genetics; Molecular and Cellular Neuroscience; Neuroscience and Neurobiology

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APA (6^th Edition):

Babcock, D. T. (2010). DAMAGE-INDUCED INFLAMMATION AND NOCICEPTIVE HYPERSENSITIVITY IN DROSOPHILA LARVAE. (Doctoral Dissertation). Texas Medical Center. Retrieved from http://digitalcommons.library.tmc.edu/utgsbs_dissertations/6

Chicago Manual of Style (16^th Edition):

Babcock, Daniel T. “DAMAGE-INDUCED INFLAMMATION AND NOCICEPTIVE HYPERSENSITIVITY IN DROSOPHILA LARVAE.” 2010. Doctoral Dissertation, Texas Medical Center. Accessed February 22, 2020. http://digitalcommons.library.tmc.edu/utgsbs_dissertations/6.

MLA Handbook (7^th Edition):

Babcock, Daniel T. “DAMAGE-INDUCED INFLAMMATION AND NOCICEPTIVE HYPERSENSITIVITY IN DROSOPHILA LARVAE.” 2010. Web. 22 Feb 2020.

Vancouver:

Babcock DT. DAMAGE-INDUCED INFLAMMATION AND NOCICEPTIVE HYPERSENSITIVITY IN DROSOPHILA LARVAE. [Internet] [Doctoral dissertation]. Texas Medical Center; 2010. [cited 2020 Feb 22]. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/6.

Council of Science Editors:

Babcock DT. DAMAGE-INDUCED INFLAMMATION AND NOCICEPTIVE HYPERSENSITIVITY IN DROSOPHILA LARVAE. [Doctoral Dissertation]. Texas Medical Center; 2010. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/6

Texas Medical Center

26. Nguyen, Vuvi H. THE EXPRESSION AND CELLULAR LOCALIZATION OF CC-CHEMOKINE RECEPTOR 5 (CCR5) AFTER TRAUMATIC BRAIN INJURY.

Degree: MS, 2010, Texas Medical Center

URL: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/36

► Traumatic brain injury results from a primary insult and secondary events that together result in tissue injury. This primary injury occurs at the moment of… (more)

▼ Traumatic brain injury results from a primary insult and secondary events that together result in tissue injury. This primary injury occurs at the moment of impact and damage can include scalp laceration, skull fraction, cerebral contusions and lacerations as well as intracranial hemorrhage. Following the initial insult, a delayed response occurs and is characterized by hypoxia, ischemia, cerebral edema, and infection. During secondary brain injury, a series of neuroinflammatory events are triggered that can produce additional damage but may also help to protect nervous tissue from invading pathogens and help to repair the damaged tissue. Brain microglia and astrocytes become activated and migrate to the site of injury where these cells secrete immune mediators such as cytokines and chemokines. CC-chemokine receptor 5 (CCR5) is a member of the CC chemokine receptor family of seven transmembrane G protein coupled receptors. CCR5 is expressed in the immune system and is found in monocytes, leukoctyes, memory T cells, and immature dendritic cells. Upon binding to its ligands, CCR5 functions in the chemotaxis of these immune cells to the site of inflammation. In the CNS, CCR5 and its ligands are expressed in multiple cell types. In this study, I investigated whether CCR5 expression is altered in brain after traumatic brain injury. I examined the time course of CCR5 protein expression in cortex and hippocampus using quantitative western analysis of tissues from injured rat brain after mild impact injury. In addition, I also investigated the cellular localization of CCR5 before and after brain injury using confocal microscopy. I have observed that after brain injury CCR5 is upregulated in a time dependent manner in neurons of the parietal cortex and hippocampus. The absence of CCR5 expression in microglia and its delayed expression in neurons after injury suggests a role for CCR5 in neuronal survival after injury. Advisors/Committee Members: Andrew Bean Ph.D., Pramod Dash Ph.D., Raymond Grill Ph.D..

Subjects/Keywords: CCR5; chemokine receptor; traumatic brain injury; neuroinflammation; Molecular and Cellular Neuroscience; Neuroscience and Neurobiology

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APA (6^th Edition):

Nguyen, V. H. (2010). THE EXPRESSION AND CELLULAR LOCALIZATION OF CC-CHEMOKINE RECEPTOR 5 (CCR5) AFTER TRAUMATIC BRAIN INJURY. (Masters Thesis). Texas Medical Center. Retrieved from http://digitalcommons.library.tmc.edu/utgsbs_dissertations/36

Chicago Manual of Style (16^th Edition):

Nguyen, Vuvi H. “THE EXPRESSION AND CELLULAR LOCALIZATION OF CC-CHEMOKINE RECEPTOR 5 (CCR5) AFTER TRAUMATIC BRAIN INJURY.” 2010. Masters Thesis, Texas Medical Center. Accessed February 22, 2020. http://digitalcommons.library.tmc.edu/utgsbs_dissertations/36.

MLA Handbook (7^th Edition):

Nguyen, Vuvi H. “THE EXPRESSION AND CELLULAR LOCALIZATION OF CC-CHEMOKINE RECEPTOR 5 (CCR5) AFTER TRAUMATIC BRAIN INJURY.” 2010. Web. 22 Feb 2020.

Vancouver:

Nguyen VH. THE EXPRESSION AND CELLULAR LOCALIZATION OF CC-CHEMOKINE RECEPTOR 5 (CCR5) AFTER TRAUMATIC BRAIN INJURY. [Internet] [Masters thesis]. Texas Medical Center; 2010. [cited 2020 Feb 22]. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/36.

Council of Science Editors:

Nguyen VH. THE EXPRESSION AND CELLULAR LOCALIZATION OF CC-CHEMOKINE RECEPTOR 5 (CCR5) AFTER TRAUMATIC BRAIN INJURY. [Masters Thesis]. Texas Medical Center; 2010. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/36

Texas Medical Center

27. gomez, fabiola c. MECHANISM-BASED STRATEGIES TO ENHANCE THE ACTIONS OF A.

Degree: PhD, 2010, Texas Medical Center

URL: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/31

► Heat shock protein 90 (HSP90) is an abundant molecular chaperone that regulates the functional stability of client oncoproteins, such as STAT3, Raf-1 and Akt, which… (more)

▼ Heat shock protein 90 (HSP90) is an abundant molecular chaperone that regulates the functional stability of client oncoproteins, such as STAT3, Raf-1 and Akt, which play a role in the survival of malignant cells. The chaperone function of HSP90 is driven by the binding and hydrolysis of ATP. The geldanamycin analog, 17-AAG, binds to the ATP pocket of HSP90 leading to the degradation of client proteins. However, treatment with 17-AAG results in the elevation of the levels of antiapoptotic proteins HSP70 and HSP27, which may lead to cell death resistance. The increase in HSP70 and HSP27 protein levels is due to the activation of the transcription factor HSF-1 binding to the promoter region of HSP70 and HSP27 genes. HSF-1 binding subsequently promotes HSP70 and HSP27 gene expression. Based on this, I hypothesized that inhibition of transcription/translation of HSP or client proteins would enhance 17-AAG-mediated cytotoxicity. Multiple myeloma (MM) cell lines MM.1S, RPMI-8226, and U266 were used as a model. To test this hypothesis, two different strategies were used. For the first approach, a transcription inhibitor was combined with 17-AAG. The established transcription inhibitor Actinomycin D (Act D), used in the clinic, intercalates into DNA and blocks RNA elongation. Stress inducible (HSP90á, HSP70 and HSP27) and constitutive (HSP90â and HSC70) mRNA and protein levels were measured using real time RT-PCR and immunoblot assays. Treatment with 0.5 µM 17-AAG for 8 hours resulted in the induction of all HSP transcript and protein levels in the MM cell lines. This induction of HSP mRNA levels was diminished by 0.05 µg/mL Act D for 12 hours in the combination treatment, except for HSP70. At the protein level, Act D abrogated the 17-AAG-mediated induction of all HSP expression levels, including HSP70. Cytotoxic evaluation (Annexin V/7-AAD assay) of Act D in combination with 17-AAG suggested additive or more than additive interactions. For the second strategy, an agent that affected bioenergy production in addition to targeting transcription and translation was used. Since ATP is necessary for the proper folding and maturation of client proteins by HSP90, ATP depletion should lead to a decrease in client protein levels. The transcription and translation inhibitor 8-Chloro-Adenosine (8-Cl-Ado), currently in clinical trials, is metabolized into its cytotoxic form 8-Cl-ATP causing a parallel decrease of the cellular ATP pool. Treatment with 0.5 µM 17-AAG for 8 hours resulted in the induction of all HSP transcript and protein levels in the three MM cell lines evaluated. In the combination treatment, 10 µM 8-Cl-Ado for 20 hours did not abrogate the induction of HSP mRNA or protein levels. Since cellular bioenergy is necessary for the stabilization of oncoproteins by HSP90, immunoblot assays analyzing for expression levels of client proteins such as STAT3, Raf-1, and Akt were performed. Immunoblot assays detecting for the phosphorylation status of the translation repressor 4E-BP1, whose activity is modulated by upstream… Advisors/Committee Members: Varsha Gandhi, Ph.D., Juan Fueyo-Margareto, M.D., Peng Huang, M.D. Ph.D..

Subjects/Keywords: 17-allylamino-17demethoxygeldanamycin; 8-chloro-adenosine; actinomycin D; heat shock proteins; heat shock factor; multiple myeloma; transcription inhibitor; Cancer Biology; Therapeutics

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

APA (6^th Edition):

gomez, f. c. (2010). MECHANISM-BASED STRATEGIES TO ENHANCE THE ACTIONS OF A. (Doctoral Dissertation). Texas Medical Center. Retrieved from http://digitalcommons.library.tmc.edu/utgsbs_dissertations/31

Chicago Manual of Style (16^th Edition):

gomez, fabiola c. “MECHANISM-BASED STRATEGIES TO ENHANCE THE ACTIONS OF A.” 2010. Doctoral Dissertation, Texas Medical Center. Accessed February 22, 2020. http://digitalcommons.library.tmc.edu/utgsbs_dissertations/31.

MLA Handbook (7^th Edition):

gomez, fabiola c. “MECHANISM-BASED STRATEGIES TO ENHANCE THE ACTIONS OF A.” 2010. Web. 22 Feb 2020.

Vancouver:

gomez fc. MECHANISM-BASED STRATEGIES TO ENHANCE THE ACTIONS OF A. [Internet] [Doctoral dissertation]. Texas Medical Center; 2010. [cited 2020 Feb 22]. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/31.

Council of Science Editors:

gomez fc. MECHANISM-BASED STRATEGIES TO ENHANCE THE ACTIONS OF A. [Doctoral Dissertation]. Texas Medical Center; 2010. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/31

Texas Medical Center

28. Gonzalez-McGehee, Jennifer. AMPA RECEPTOR ALLOSTERISM: MEASUREMENT OF THE CONFORMATIONAL CHANGES IN THE LIGAND BINDING DOMAIN OF A FUNCTIONAL RECEPTOR.

Degree: PhD, 2010, Texas Medical Center

URL: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/33

► Ionotropic glutamate receptors are important excitatory neurotransmitter receptors in the mammalian central nervous system that have been implicated in a number of neuropathologies such as… (more)

▼ Ionotropic glutamate receptors are important excitatory neurotransmitter receptors in the mammalian central nervous system that have been implicated in a number of neuropathologies such as epilepsy, ischemia, and amyotrophic lateral sclerosis. Glutamate binding to an extracellular ligand binding domain initiates a series of structural changes that leads to the formation of a cation selective transmembrane channel, which consequently closes due to desensitization of the receptor. The crystal structures of the AMPA subtype of the glutamate receptor have been particularly useful in providing initial insight into the conformational changes in the ligand binding domain; however, these structures are limited by crystallographic constraint. To gain a clear picture of how agonist binding is coupled to channel activation and desensitization, it is essential to study changes in the ligand binding domain in a dynamic, physiological state. In this dissertation, a technique called Luminescence Resonance Energy Transfer was used to determine the conformational changes associated with activation and desensitization in a functional AMPA receptor (ÄN*-AMPA) that contains the ligand binding domain and transmembrane segments; ÄN*-AMPA has been modified such that fluorophores can be introduced at specific sites to serve as a readout of cleft closure or to establish intersubunit distances. Previous structural studies of cleft closure of the isolated ligand binding domain in conjunction with functional studies of the full receptor suggest that extent of cleft closure correlates with extent of activation. Here, LRET has been used to show that a similar relationship between cleft closure and activation is observed in the “full length” receptor showing that the isolated ligand binding domain is a good model of the domain in the full length receptor for changes within a subunit. Similar LRET investigations were used to study intersubunit distances specifically to probe conformational changes between subunits within a dimer in the tetrameric receptor. These studies show that the dimer interface is coupled in the open state, and decoupled in the desensitized state, similar to the isolated ligand binding domain crystal structure studies. However, we show that the apo state dimer interface is not pre-formed as in the crystal structure, hence suggesting a mechanism for functional transitions within the receptor based on LRET distances obtained. Advisors/Committee Members: Vasanthi Jayaraman, Ph.D., Renhao Li, Ph.D., John Spudich, Ph.D..

Subjects/Keywords: AMPA receptor; Luminescence Resonance Energy Transfer; structure-function; ion channel; Biochemistry, Biophysics, and Structural Biology

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

APA (6^th Edition):

Gonzalez-McGehee, J. (2010). AMPA RECEPTOR ALLOSTERISM: MEASUREMENT OF THE CONFORMATIONAL CHANGES IN THE LIGAND BINDING DOMAIN OF A FUNCTIONAL RECEPTOR. (Doctoral Dissertation). Texas Medical Center. Retrieved from http://digitalcommons.library.tmc.edu/utgsbs_dissertations/33

Chicago Manual of Style (16^th Edition):

Gonzalez-McGehee, Jennifer. “AMPA RECEPTOR ALLOSTERISM: MEASUREMENT OF THE CONFORMATIONAL CHANGES IN THE LIGAND BINDING DOMAIN OF A FUNCTIONAL RECEPTOR.” 2010. Doctoral Dissertation, Texas Medical Center. Accessed February 22, 2020. http://digitalcommons.library.tmc.edu/utgsbs_dissertations/33.

MLA Handbook (7^th Edition):

Gonzalez-McGehee, Jennifer. “AMPA RECEPTOR ALLOSTERISM: MEASUREMENT OF THE CONFORMATIONAL CHANGES IN THE LIGAND BINDING DOMAIN OF A FUNCTIONAL RECEPTOR.” 2010. Web. 22 Feb 2020.

Vancouver:

Gonzalez-McGehee J. AMPA RECEPTOR ALLOSTERISM: MEASUREMENT OF THE CONFORMATIONAL CHANGES IN THE LIGAND BINDING DOMAIN OF A FUNCTIONAL RECEPTOR. [Internet] [Doctoral dissertation]. Texas Medical Center; 2010. [cited 2020 Feb 22]. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/33.

Council of Science Editors:

Gonzalez-McGehee J. AMPA RECEPTOR ALLOSTERISM: MEASUREMENT OF THE CONFORMATIONAL CHANGES IN THE LIGAND BINDING DOMAIN OF A FUNCTIONAL RECEPTOR. [Doctoral Dissertation]. Texas Medical Center; 2010. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/33

Texas Medical Center

29. Greathouse, Kristen L. XENOESTROGEN-SPECIFIC MECHANISMS OF DEVELOPMENTAL REPROGRAMMING CORRELATE WITH GENE EXPRESSION AND TUMOR DEVELOPMENT.

Degree: PhD, 2010, Texas Medical Center

URL: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/51

► Environmental exposures during sensitive windows of development can reprogram normal physiological responses and alter disease susceptibility later in life in a process known as developmental… (more)

▼ Environmental exposures during sensitive windows of development can reprogram normal physiological responses and alter disease susceptibility later in life in a process known as developmental reprogramming. We have shown that neonatal exposure to the xenoestrogen diethylstilbestrol (DES) can developmentally reprogram the reproductive tract in genetically susceptible Eker rats giving rise to complete penetrance of uterine leiomyoma. Based on this, we hypothesized that xenoestrogens, including genistein (GEN) and bisphenol A (BPA), reprogram estrogen-responsive gene expression in the myometrium and promote the development of uterine leiomyoma. We proposed the mechanism that is responsible for the developmental reprogramming of gene expression was through estrogen (E2)/ xenoestrogen inducedrapid ER signaling, which modifies the histone methyltransferase Enhancer of Zeste homolog 2 (EZH2) via activation of the PI3K/AKT pathway. We further hypothesized that there is a xenostrogen-specific effect on this pathway altering patterns of histone modification, DNA methylation and gene expression. In addition to our novel finding that E2/DES-induced phosphorylation of EZH2 by AKT reduces the levels of H3K27me3 in vitro and in vivo, this work demonstrates in vivo that a brief neonatal exposure to GEN, in contrast to BPA, activates the PI3K/AKT pathway to regulate EZH2 and decreases H3K27me3 levels in the neonatal uterus. Given that H3K27me3 is a repressive mark that has been shown to result in DNA methylation and gene silencing we investigated the methylation of developmentally reprogrammed genes. In support of this evidence, we show that neonatal DES exposure in comparison to VEH, leads to hypomethylation of the promoter of a developmentally reprogrammed gene, Gria2, that become hyper-responsive to estrogen in the adult myometrium indicating vi that DES exposure alter gene expression via chromatin remodeling and loss of DNA methylation. In the adult uterus, GEN and BPA exposure developmentally reprogrammed expression of estrogen-responsive genes in a manner opposite of one another, correlating with our previous data. Furthermore, the ability of GEN and BPA to developmental reprogram gene expression correlated with tumor incidence and multiplicity. These data show that xenoestrogens have unique effects on the activation of non-genomic signaling in the developing uterus that promotes epigenetic and genetic alterations, which are predictive of developmental reprogramming and correlate with their ability to modulate hormone-dependent tumor development. Advisors/Committee Members: Cheryl L. Walker, Ph.D., David Johnson, Ph.D., Stephen Hursting, Ph.D., M.P.H..

Subjects/Keywords: Xenoestrogens; developmental reprogramming; uterine leiomyoma; epigenetics; non-genomic signaling; estrogen receptor; Cancer Biology; Developmental Biology; Molecular Biology; Other Pharmacology, Toxicology and Environmental Health

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

APA (6^th Edition):

Greathouse, K. L. (2010). XENOESTROGEN-SPECIFIC MECHANISMS OF DEVELOPMENTAL REPROGRAMMING CORRELATE WITH GENE EXPRESSION AND TUMOR DEVELOPMENT. (Doctoral Dissertation). Texas Medical Center. Retrieved from http://digitalcommons.library.tmc.edu/utgsbs_dissertations/51

Chicago Manual of Style (16^th Edition):

Greathouse, Kristen L. “XENOESTROGEN-SPECIFIC MECHANISMS OF DEVELOPMENTAL REPROGRAMMING CORRELATE WITH GENE EXPRESSION AND TUMOR DEVELOPMENT.” 2010. Doctoral Dissertation, Texas Medical Center. Accessed February 22, 2020. http://digitalcommons.library.tmc.edu/utgsbs_dissertations/51.

MLA Handbook (7^th Edition):

Greathouse, Kristen L. “XENOESTROGEN-SPECIFIC MECHANISMS OF DEVELOPMENTAL REPROGRAMMING CORRELATE WITH GENE EXPRESSION AND TUMOR DEVELOPMENT.” 2010. Web. 22 Feb 2020.

Vancouver:

Greathouse KL. XENOESTROGEN-SPECIFIC MECHANISMS OF DEVELOPMENTAL REPROGRAMMING CORRELATE WITH GENE EXPRESSION AND TUMOR DEVELOPMENT. [Internet] [Doctoral dissertation]. Texas Medical Center; 2010. [cited 2020 Feb 22]. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/51.

Council of Science Editors:

Greathouse KL. XENOESTROGEN-SPECIFIC MECHANISMS OF DEVELOPMENTAL REPROGRAMMING CORRELATE WITH GENE EXPRESSION AND TUMOR DEVELOPMENT. [Doctoral Dissertation]. Texas Medical Center; 2010. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/51

Texas Medical Center

30. Kapuria, Vaibhav. Inhibition of Deubiquitinase Activity and Ubiquitination of Jak2 Blocks Cytokine Signaling and Induces Tumor Cell Apoptosis.

Degree: PhD, 2010, Texas Medical Center

URL: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/42

► The Jak-stat pathway is critical for cellular proliferation and is commonly found to be deregulated in many solid tumors as well as hematological malignancies. Such… (more)

Subjects/Keywords: Ubiquitination; Deubiquitination; Small molecule inhibitor; Jak-Stat pathway; Deubiquitinating Enzymes; Cancer Biology; Cell Biology

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

APA (6^th Edition):

Kapuria, V. (2010). Inhibition of Deubiquitinase Activity and Ubiquitination of Jak2 Blocks Cytokine Signaling and Induces Tumor Cell Apoptosis. (Doctoral Dissertation). Texas Medical Center. Retrieved from http://digitalcommons.library.tmc.edu/utgsbs_dissertations/42

Chicago Manual of Style (16^th Edition):

Kapuria, Vaibhav. “Inhibition of Deubiquitinase Activity and Ubiquitination of Jak2 Blocks Cytokine Signaling and Induces Tumor Cell Apoptosis.” 2010. Doctoral Dissertation, Texas Medical Center. Accessed February 22, 2020. http://digitalcommons.library.tmc.edu/utgsbs_dissertations/42.

MLA Handbook (7^th Edition):

Kapuria, Vaibhav. “Inhibition of Deubiquitinase Activity and Ubiquitination of Jak2 Blocks Cytokine Signaling and Induces Tumor Cell Apoptosis.” 2010. Web. 22 Feb 2020.

Vancouver:

Kapuria V. Inhibition of Deubiquitinase Activity and Ubiquitination of Jak2 Blocks Cytokine Signaling and Induces Tumor Cell Apoptosis. [Internet] [Doctoral dissertation]. Texas Medical Center; 2010. [cited 2020 Feb 22]. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/42.

Council of Science Editors:

Kapuria V. Inhibition of Deubiquitinase Activity and Ubiquitination of Jak2 Blocks Cytokine Signaling and Induces Tumor Cell Apoptosis. [Doctoral Dissertation]. Texas Medical Center; 2010. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/42

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Open Access Theses and Dissertations