Anti-Insulin Resistance Treatments Suppress Her2+ Breast Cancer Growth Via Altering Metabolism, 2014 The University of Texas Graduate School of Biomedical Sciences at Houston
Anti-Insulin Resistance Treatments Suppress Her2+ Breast Cancer Growth Via Altering Metabolism, Ping-Chieh Chou
Dissertations & Theses (Open Access)
Epidemiological studies have identified that type 2 diabetes mellitus (DM2) is a significant risk factor for carcinogenesis and cancer death, including breast cancer. Our previous finding in patients showed that anti-insulin resistance treatments are associated with improved HER2+ breast cancer survival of diabetic women. However, there were no transgenic mouse models to study the correlation and explain the detailed mechanism. We generated a mouse model of HER2+ breast cancer with DM2 by crossing leptin receptor point mutation (Lepr db/+) and MMTV-ErbB2 (neu) mice. The MMTV-ErbB2/Lepr db/db mice had a poor survival rate compared …
Diabetes And Obesity Induce Transcriptomic And Metabolomic Changes Enhancing Pancreatic Cancer Aggressiveness, 2014 The University of Texas Graduate School of Biomedical Sciences at Houston
Diabetes And Obesity Induce Transcriptomic And Metabolomic Changes Enhancing Pancreatic Cancer Aggressiveness, Guermarie Velázquez Torres
Dissertations & Theses (Open Access)
Pancreatic cancer is one of the most aggressive types of cancer, with poor prognosis that lacks effective diagnostic markers and therapies. It is expected that in 2014 the incidence and the mortality of pancreatic cancer in the United States will be 46,420 and 39,590 respectively. Diabetes and obesity are modifiable risk factors associated with accelerated pancreatic carcinogenesis and tumor progression, but the biological mechanisms are not completely understood. The purpose of this study is to demonstrate direct evidence for the mechanisms mediating these epidemiologic phenomena. Our hypothesis is that obesity and diabetes mellitus type 2 (DM2) accelerate pancreatic cancer and …
The Regulation Of Microrna Biogenesis By Ribosome-Interacting Proteins, 2014 The University of Texas Graduate School of Biomedical Sciences at Houston
The Regulation Of Microrna Biogenesis By Ribosome-Interacting Proteins, Brian Pickering
Dissertations & Theses (Open Access)
MicroRNA (miRNA) are small, non-coding RNAs that affect gene expression through degradation of complementary mRNA targets or inhibition of translation. As they affect approximately 50% of all cellular processes, miRNA are tightly regulated by the cell through transcriptional and post-transcriptional mechanisms. Transcribed miRNA are capped and polyadenylated (referred to as pri-miRNA) which are cleaved by Drosha and DGCR8 to generate 60-90 nucleotide precursor miRNA. The precursors are cleaved again by Dicer and loaded into the RNA-induced silencing complex (RISC) of which Argonaute 2 is the functional component. Many of the proteins involved in miRNA biogenesis share a common role in …
Car-Modified T Cells Capable Of Distinguishing Normal Cells From Malignant Cells, 2014 The University of Texas Graduate School of Biomedical Sciences at Houston
Car-Modified T Cells Capable Of Distinguishing Normal Cells From Malignant Cells, Hillary G. Caruso
Dissertations & Theses (Open Access)
T cells can be redirected to target tumor-associated antigen (TAA) by genetic modification to express a chimeric antigen receptor (CAR), which fuses the specificity derived from an antibody to T-cell activation domains to result in lysis of TAA-expressing cells. Due to the potential for on-target, off-tissue toxicity, CAR+ T-cell therapy is currently limited to unique or lineage-restricted TAAs. Glioblastoma, a grade IV brain malignancy, overexpresses epidermal growth factor receptor (EGFR) in 40-50% of patients. EGFR also has widespread normal tissue expression. To target EGFR on glioblastoma while reducing the potential for normal tissue toxicity, EGFR-specific CAR generated from cetuximab, …
Regulation Of Mammary Gland Development And Tumorigenesis By 14-3-3 Zeta, 2014 The University of Texas Graduate School of Biomedical Sciences at Houston
Regulation Of Mammary Gland Development And Tumorigenesis By 14-3-3 Zeta, Sumaiyah Rehman
Dissertations & Theses (Open Access)
Signaling pathways that play critical roles in organ development are often aberrantly regulated during cancer initiation and progression. 14-3-3z is overexpressed in more than 40% of breast cancers and is associated with poor patient prognosis. Therefore, the function of 14-3-3z in cancer and normal mammary gland development was investigated utilizing multiple in vivo and in vitro approaches. 14-3-3z is a chaperone protein that interacts with a multitude of oncogenes and tumor suppressor genes, thereby functioning as a critical node in multiple oncogenic signaling networks. Mammary gland-specific 14-3-3z transgenic mouse models showed that 14-3-3z overexpression was sufficient to induce mammary tumorigenesis. …
Mechanisms Underlying Distinct Egfr Versus Fgfr-3 And -1 Dependency In Human Bladder Cancer Cells, 2014 The University of Texas Graduate School of Biomedical Sciences at Houston
Mechanisms Underlying Distinct Egfr Versus Fgfr-3 And -1 Dependency In Human Bladder Cancer Cells, Tiewei Cheng
Dissertations & Theses (Open Access)
The epidermal growth factor receptor (EGFR) and fibroblast growth factor receptor (FGFR) are activated by gene amplification, mutation and overexpression in bladder cancer, which drives tumor development and progression. Both EGFR and FGFR inhibitors are currently being tested in clinical trials. However, bladder cancer (BC) cells show remarkably heterogeneous sensitivities to both inhibitors, and the molecular determinants of this heterogeneity are presently unclear. Therefore, in this study, using selective EGFR and FGFR inhibitors in BC cells, we demonstrated that FGFR3 and FGFR1 play largely non-overlapping roles in mediating proliferation and invasion in the distinct “epithelial” and “mesenchymal” subsets of human …
Modulated Functions Of The Fanconi Anemia Core Complex, 2014 The University of Texas Graduate School of Biomedical Sciences at Houston
Modulated Functions Of The Fanconi Anemia Core Complex, Yaling Huang
Dissertations & Theses (Open Access)
Cells derived from Fanconi anemia (FA) patients are characterized by hypersensitivity to DNA interstrand crosslinks (ICLs), suggesting that FA genes play a role in ICL repair. Fanconi anemia core complex (including A, B, C, E, F, G, L, FAAP20, and FAAP100) activates the Fanconi pathway by providing the essential E3 ligase activity for FANCD2 mono-ubiquitination. Previous studies suggested the existence of three protein-protein interaction groups. However, the functions of most FA core complex protein are still limited to their presence in the complex. How the spatially-defined FANCD2 ubiquitination is accomplished by the core complex remains unknown.
To elucidate the roles …
Role Of Talin1 Phosphorylation In Beta1 Integrin Activation And Prostate Cancer Metastasis, 2014 The University of Texas Graduate School of Biomedical Sciences at Houston
Role Of Talin1 Phosphorylation In Beta1 Integrin Activation And Prostate Cancer Metastasis, Jung-Kang Jin
Dissertations & Theses (Open Access)
Talins are adaptor proteins that regulate focal adhesion signaling by conjugating integrins to the cytoskeleton. Talins directly bind and activate integrins but the mechanism by which this occurs is unknown. As integrin activation and overexpression of talins promote prostate cancer metastasis, understanding the mechanism by which talins activate integrins will better elucidate their roles in Prostate cancer metastasis. Phosphorylation of talins on serine 425 has been associated with β1 integrin functions. Work in this dissertation tested the hypothesis that increased talin1 S425 phosphorylation was required for β1 integrin activation and promotion of prostate cancer metastasis.
I first used shRNA to …
Sumoylation Status And Effects Of Sumylation On Dax-1, 2014 University of San Francisco
Sumoylation Status And Effects Of Sumylation On Dax-1, Amy E. Scandurra, Hai Nguyen, Christina Tzagarakis -‐Foster
Creative Activity and Research Day - CARD
DAX-1 (Dosage Sensitive Sex Reversal Adrenal Hypoplasia Congenita on the X Chromosome gene 1) is a Nuclear Hormone Receptor, which acts as a transcriptional repressor in the nucleus. DAX-1 plays an important role in development and also appears to have some influence on the progression of cancer. In an effort to better understand DAX-1 function both in normal and disease states we are examining one type of posttranslational modification, SUMOylation. SUMOylation involves the addition of the small polypeptide conjugate SUMO (Small Ubiquitin-like Modifier) to proteins, this can have a variety of effects on protein activity. To …
Sirna Targeting Of Thymidylate Synthase, Thymidine Kinase 1 And Thymidine Kinase 2 As An Anticancer Therapy: A Combinatorial Rnai Approach, 2014 The University of Western Ontario
Sirna Targeting Of Thymidylate Synthase, Thymidine Kinase 1 And Thymidine Kinase 2 As An Anticancer Therapy: A Combinatorial Rnai Approach, Christine Di Cresce
Electronic Thesis and Dissertation Repository
Thymidylate synthase (TS) is the only de novo source of thymidylate (dTMP) for DNA synthesis and repair. Drugs targeting TS protein are a mainstay in cancer treatment but off-target effects and toxicity limit their use. Cytosolic thymidine kinase (TK1) and mitochondrial thymidine kinase (TK2) contribute to an alternative dTMP-producing pathway, by salvaging thymidine from the tumour milieu, and may modulate resistance to TS-targeting drugs. We have previously shown that TS antisense molecules (oligodeoxynucleotides, ODNs, and small interfering siRNA, siRNA) sensitize tumour cells, both in vitro and in vivo, to TS targeting drugs. As both TS and TKs contribute to cellular …
The Effects Of Gold Nanorods On The Rate Of Apoptosis Of Triple Negative Breast Cancer Cells, 2014 Georgia Southern University
The Effects Of Gold Nanorods On The Rate Of Apoptosis Of Triple Negative Breast Cancer Cells, Mattie E. Raiford
Honors College Theses
Triple negative breast cancer (TNBC) is a subtype of breast cancer that is most often found in African American females that is characterized by the lack of the progesterone receptor (PR), the estrogen receptor (ER), and the human epithelial growth factor receptor two (HER2).TNBC is a very aggressive form of breast cancer because it does not respond to hormone therapy, due to the lack of the three vital receptors. Since the current treatment is not affective, the project used porphyrin to specifically target cancer in the body because it has an increased affinity for many cancer types. Gold nanorods were …
Analysis Of The Regulation And Function Of Cip2a To Identify Candidate Biomarkers For Prostate Cancer, 2014 Rowan University
Analysis Of The Regulation And Function Of Cip2a To Identify Candidate Biomarkers For Prostate Cancer, Diana Savoly
Graduate School of Biomedical Sciences Theses and Dissertations
Protein Phosphatase 2A (PP2A) is a tumor suppressor involved in the regulation of several signaling pathways and the cell cycle. PP2A becomes inactivated by several inhibitors, including Cancerous Inhibitor of PP2A (CIP2A). CIP2A has been identified as an oncogene, which is over-expressed in cancers and inhibits PP2A through direct interaction. CIP2A is recognized as a biomarker for cancer; however, it is not cancer-specific. Therefore, we identified and examined the use of CIP2A-regulated proteins as potential biomarkers in prostate cancer to better diagnose prostate cancer in patients. Currently, Prostate Specific Antigen (PSA) is widely used to detect prostate cancer; however, it …
Distinct Roles Of Bmp And Lkb1/Ampk Signalling Impacting Ovarian Cancer Spheroid Biology, 2014 The University of Western Ontario
Distinct Roles Of Bmp And Lkb1/Ampk Signalling Impacting Ovarian Cancer Spheroid Biology, Teresa M. Peart
Electronic Thesis and Dissertation Repository
High-grade serous (HGS) carcinoma, the most prevalent and most deadly subtype of epithelial ovarian cancer (EOC), presents unique therapeutic challenges since the majority of cases are diagnosed at advanced, metastatic stage. At this point widespread intraperitoneal metastatic lesions are numerous, which is why models that recapitulate disease dissemination are critical to uncover novel therapeutic targets. One of the initiating events in ovarian cancer metastasis is shedding from the primary tumour into the peritoneal cavity where cells must survive in suspension in order to seed secondary tumours. This non-adherent population of cells exists as multicellular aggregates, or spheroids; data from our …
The Effects Of Atypical Protein Kinase C On Tgfβ Signalling, 2014 The University of Western Ontario
The Effects Of Atypical Protein Kinase C On Tgfβ Signalling, Adrian D. Gunaratne
Electronic Thesis and Dissertation Repository
The transforming growth factor beta (TGFβ) signalling pathway is an essential regulator of many cellular processes including epithelial growth control, epithelial to mesenchymal transition (EMT), apoptosis, and the establishment of developmental fate. Alterations in TGFβ signalling patterns are associated with various pathological disorders such as fibrosis and cancer. In recent years it has become clear that regulation of TGFβ signalling is dependent on the trafficking and endocytosis of the TGFβ receptors, however, the factors that control these processes are still under investigation.
In this thesis, I examined the role of Protein Kinase C (PKC) in the regulation of TGFβ signalling …
Cell Morphometry, 2014 M.D. Anderson Cancer Center
Cell Morphometry, George Mcnamara
George McNamara
Cell Morphometry ZIP content by George McNamara
http://works.bepress.com/gmcnamara/41
Robert Murphy's TypIC (typical cell Chooser,
http://murphylab.web.cmu.edu/services/TypIC/
now superseded by PSLID and SLIF
http://murphylab.web.cmu.edu/services/ ), was a "game changer" for me with respect to cell shape analysis. Rather than trying to compute the average of (say) a triangle and a pentagon ... which might result in a square, or a rectange, or some bizarre quadrilateral ... R.M. advocated using the median. OK, in a 2 member dataset this would result in averaging the two shapes (if use the standard way to calculate median of even number datasets), but this could be avoided …
A Melanin-Independent Interaction Between Mc1r And Met Signalling Pathways Is Required For Hgf-Dependent Melanoma, 2014 George Washington University
A Melanin-Independent Interaction Between Mc1r And Met Signalling Pathways Is Required For Hgf-Dependent Melanoma, Agnieszka Wolnicka-Głubisz, Faith M. Strickland, Albert Wielgus, Miriam Anver, Glenn Merlino, Edward C. De Fabo, Frances P. Noonan
Microbiology, Immunology, and Tropical Medicine Faculty Publications
Melanocortin 1 receptor (MC1R) signaling stimulates black eumelanin production through a cAMP-dependent pathway. MC1R polymorphisms can impair this process, resulting in a predominance of red phaeomelanin. The red hair, fair skin and UV sensitive phenotype is a well-described melanoma risk factor. MC1R polymorphisms also confer melanoma risk independent of pigment. We investigated the effect of Mc1r deficiency in a mouse model of UV-induced melanoma. C57BL/6-Mc1r+/+-HGF transgenic mice have a characteristic hyperpigmented black phenotype with extra-follicular dermal melanocytes located at the dermal/epidermal junction. UVB induces melanoma, independent of melanin pigmentation, but UVA-induced and spontaneous melanomas are dependent on black eumelanin. We …
Plasma Selenium Biomarkers In Low Income Black And White Americans From The Southeastern United States, 2014 Meharry Medical College
Plasma Selenium Biomarkers In Low Income Black And White Americans From The Southeastern United States, Margaret K. Hargreaves, Jianguo Liu, Maciej S. Buchowski, Kushal A. Patel, Celia O. Larson, David G. Schlundt, Donna M. Kenerson, Kristina E. Hill, Raymond F. Burk, William J. Blot
Public Health, Health Administration, and Health Sciences Faculty Research
Biomarkers of selenium are necessary for assessing selenium status in humans, since soil variation hinders estimation of selenium intake from foods. In this study, we measured the concentration of plasma selenium, selenoprotein P (SEPP1), and glutathione peroxidase (GPX3) activity and their interindividual differences in 383 low-income blacks and whites selected from a stratified random sample of adults aged 40–79 years, who were participating in a long-term cohort study in the southeastern United States (US). We assessed the utility of these biomarkers to determine differences in selenium status and their association with demographic, socio-economic, dietary, and other indicators. Dietary selenium intake …
5Α-Dihydrotestosterone And The Wnt/Β-Catenin Pathway In Danio Rerio Ovarian Tissue Following 2 And 4 Hour Incubations, 2014 University of Puget Sound
5Α-Dihydrotestosterone And The Wnt/Β-Catenin Pathway In Danio Rerio Ovarian Tissue Following 2 And 4 Hour Incubations, Macaulie Casey
Summer Research
The Wnt/β-catenin signaling pathway regulates genes involved in proliferation and apoptosis. These two traits are hallmarks of cancer cells, which grow excessively and demonstrate low mortality. The Wnt/β-catenin pathway has been implicated in ovarian cancer, specifically epithelial ovarian cancer, wherein higher levels of β-catenin may be involved in the development of tumors. Ovarian epithelial tissue also displays high quantities of androgen receptors and thus may be more susceptible to changes in androgen concentration. This study investigated whether exogenous testosterone (DHT) utilized the Wnt/β-catenin pathway in Danio rerio ovarian tissue by monitoring β-catenin and GSK-3β mRNA expression through quantitative PCR analysis. …
Synthesis And Characterization Of Pt(Ii) Complexes For Anticancer Therapy, 2014 University of Nevada, Las Vegas
Synthesis And Characterization Of Pt(Ii) Complexes For Anticancer Therapy, Mihaela A. Ciulei, Pradip K. Bhowmik
McNair Poster Presentations
The first platinum-based drug was discovered and approved by Food and Drug Administration (FDA) in 1978 is cis-diamminedichloroplatinum (II) (cisplatin or CDDP). Cisplatin is used for about 50% of the chemotherapeutic cancer treatments along with its two analogues carboplatin and oxaliplatin. So far these drugs have been used extensively as treatment for ovarian, bladder, head and neck, and lung cancers. Although cisplatin has been used so often, it has toxic side effects and drug resistance.1-4 Due to these limitations other compounds have been synthesized. Specifically, our lab in conjunction with a biochemistry lab has recently published one article …
Synthetic Triterpenoids Can Protect Against Toxicity Without Reducing The Efficacy Of Treatment With Carboplatin And Paclitaxel In Experimental Lung Cancer, 2014 Dartmouth College
Synthetic Triterpenoids Can Protect Against Toxicity Without Reducing The Efficacy Of Treatment With Carboplatin And Paclitaxel In Experimental Lung Cancer, Karen T. Liby
Dartmouth Scholarship
Synthetic oleanane triterpenoids are multifunctional drugs being developed for the prevention and treatment of a variety of chronic diseases driven by inflammation and oxidative stress. Low nanomolar concentrations of triterpenoids inhibit the induction of inflammatory cytokines, and these drugs are potent activators of the Nrf2 cytoprotective pathway. In contrast, low micromolar concentrations of triterpenoids increased the production of ROS and induced apoptosis in a dose-dependent manner in malignant MCF10 CA1a breast cancer cells. Because cancer cells respond differently to ROS than normal cells, it should be possible to exploit these differences therapeutically. In an experimental model of lung cancer, the …