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Full-Text Articles in Cancer Biology

Anti-Cancer Effects Of Oleocanthal And Extra Virgin Olive Oil, Limor Goren Sep 2019

Anti-Cancer Effects Of Oleocanthal And Extra Virgin Olive Oil, Limor Goren

All Dissertations, Theses, and Capstone Projects

Oleocanthal is a phenolic compound found in varying concentrations in extra virgin olive oil. Oleocanthal has been shown to be active physiologically, benefiting several diseased states by conferring anti-inflammatory and neuroprotective benefits. Recently, we and other groups have demonstrated its specific and selective toxicity toward cancer cells; however, the mechanism leading to cancer cell death is still disputed. The current study demonstrates that oleocanthal induced damage to cancer cells’ lysosomes leading to cellular toxicity in vitro. Non-cancer cells were significantly less affected. Lysosomal membrane permeabilization following oleocanthal treatment in various cell lines was assayed via three complementary methods. Additionally, we ...


Fasting Reduces Intestinal Radiotoxicity Enabling Dose-Escalated Radiotherapy For Pancreatic Cancer, Marimar De La Cruz Bonilla Aug 2019

Fasting Reduces Intestinal Radiotoxicity Enabling Dose-Escalated Radiotherapy For Pancreatic Cancer, Marimar De La Cruz Bonilla

UT GSBS Dissertations and Theses (Open Access)

Surgical resection is the only potentially curative treatment for pancreatic cancer, but only 15-20% of patients have resectable tumors. In unresectable cases, stereotactic body radiotherapy (SBRT) may be used to give tumor-directed radiotherapy (RT). Unfortunately, this can cause severe gastrointestinal (GI) toxicity due to proximity of the pancreatic head to the duodenum. Protecting the intestine from the toxic side-effects of radiation may enable dose-escalation that could achieve more effective local control of disease. We and others have previously shown that a fast of 24 hours protects mice from lethal doses of the DNA-damaging agent etoposide. In this study, we demonstrate ...


Characterization Of A More Clinically Relevant Human Leukemia Xenograft Model To Examine Perturbation Of Met/Sam Metabolism As A Novel Therapeutic Paradigm For Mll-R Leukemia In Vivo., Aditya Barve Aug 2019

Characterization Of A More Clinically Relevant Human Leukemia Xenograft Model To Examine Perturbation Of Met/Sam Metabolism As A Novel Therapeutic Paradigm For Mll-R Leukemia In Vivo., Aditya Barve

Electronic Theses and Dissertations

Acute myeloid leukemia (AML), is a heterogeneous clonal disorder characterized by an accumulation of malignant myeloid progenitors in the bone marrow (BM), hindering normal hematopoiesis. AML exhibits dramatic heterogeneity in terms of cytogenetics, morphology, and chemotherapeutic sensitivity. Therefore, the investigation of novel, efficacious AML therapeutics will require advanced preclinical in vivo model systems, capable of recapitulating patient specific disease heterogeneity, and induction chemotherapy outcomes. A major focus and eventual outcome of this work was the establishment and development of a more clinically relevant mouse xenograft model of patient AML, that efficiently harbors patient derived xenografts (PDXs), and unlike more prevalent ...


Identification Of Essential Genes In Hepatocellular Carcinomas Using Crispr Screening, Ankur Sheel Jul 2019

Identification Of Essential Genes In Hepatocellular Carcinomas Using Crispr Screening, Ankur Sheel

GSBS Dissertations and Theses

Hepatocellular carcinoma (HCC) is an aggressive subtype of liver cancer with a poor prognosis. Currently, prognosis for HCC patients remains poor as few therapies are available. The clinical need for more effective HCC treatments remains unmet partially because HCC is genetically heterogeneous and HCC driver genes amenable to targeted therapy are largely unknown. Mutations in the TP53 gene are found in ~30% of HCC patients and confer poor prognosis to patients. Identifying genes whose depletion can inhibit HCC growth, and determining the mechanisms involved, will aid the development of targeted therapies for HCC patients. Therefore, the first half of this ...


Differential Roles Of Mammalian Target Of Rapamycin Complexes 1 And 2 In Migration Of Prostate Cancer Cells, Smrruthi Vaidegi Venugopal May 2019

Differential Roles Of Mammalian Target Of Rapamycin Complexes 1 And 2 In Migration Of Prostate Cancer Cells, Smrruthi Vaidegi Venugopal

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

In this study, we investigated differential activation and the role of two mTOR complexes in cell migration of prostate cancer cells. Specific knock-down of endogenous RAPTOR and RICTOR by siRNA resulted in decreased cell migration in LNCaP, DU145, and PC3 cells indicating that both mTORC1 and mTORC2 are required for cell migration. EGF treatment induced the activation of both mTORC1 and mTORC2 as determined by complex-specific phosphorylation of mTOR protein. Specific knock-down or inhibition of Rac1 activity in PC3 cells blocked EGF-induced activation of mTORC2, but had no effect on mTORC1 activation. Furthermore, the over-expression of constitutively active Rac1 (Rac1Q61L ...


Extraction, Purification And Evaluation Of Prmt5-Inhibitory Phytochemical Compounds For The Treatment Of Prostate Adenocarcinoma, Oliver H. Richmond Iii May 2019

Extraction, Purification And Evaluation Of Prmt5-Inhibitory Phytochemical Compounds For The Treatment Of Prostate Adenocarcinoma, Oliver H. Richmond Iii

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

The development and advancement of prostate cancer is supported by a plethora of genetic and proteomic abnormalities, including events of post-translational modifications. The protein arginine methyltransferase 5 (PRMT5) enzyme regulates epigenetic events of histone modifications and protein post-translational modifications within protein signaling pathways. PRMT5 functions by catalyzing the symmetric dimethylation of terminal arginine residues on target protein substrates. Under abnormal conditions of overexpression and upregulation, PRMT5 methyltransferase activity constitutively drives the growth and proliferation of dysregulated cells. Overexpression or upregulation of PRMT5 correlates with disease progression as observed among numerous cancer types, including breast, colorectal, leukemia, lung, melanoma and prostate ...


Loss Of Id4 Promotes Stemness In Prostate Cancer Cells, Dhanushka Hewabostanthirige May 2019

Loss Of Id4 Promotes Stemness In Prostate Cancer Cells, Dhanushka Hewabostanthirige

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

Inhibitor of differentiation 4 (ID4), a member of the helix-loop-helix family of transcriptional regulators has emerged as a tumor suppressor in prostate cancer (PCa). Recent studies have shown that Id4 is highly expressed in the normal prostate and decreases in prostate cancer due to epigenetic silencing. Id4 knockdown in androgen sensitive LNCaP cells has been shown to lead to castration resistant prostate cancer (CRPC) in vitro and in vivo. Id4-/- mice leads to underdeveloped prostate with PIN like lesions without the loss of Androgen Receptor (AR) expression. In this study we demonstrate that the loss of ID4 expression in PCa ...


Establishment Of Crispr/Cas-9 Aided Knockout Of The Zic2 Gene In The African-American Prostate Cancer Cell Line E006aa-Pr, Janelle Moore May 2019

Establishment Of Crispr/Cas-9 Aided Knockout Of The Zic2 Gene In The African-American Prostate Cancer Cell Line E006aa-Pr, Janelle Moore

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

The largest U.S. cancer health disparity exists in prostate cancer, with African American men having the highest incidence and mortality rates. The present study evaluated the effects of ZIC2 and the underlying mechanisms in the E006 parental African-American cell line that produces tumors at accelerated growth rates because of the increase of ZIC2 genes in African-American males. We analyzed the experimental research that the overexpression of ZIC2 contributes to progression of prostate cancer. E006AA cells with overexpressed or suppressed ZIC2 were analyzed to determine phenotypic differences, PCR, cell proliferation and immunoblot assays. The expression levels of ZIC2 were analyzed ...


Reversal Of P-Glycoprotein And Breast Cancer Resistance Protein Mediated Multidrug Resistance In Vitro Using In Silico Identified Novel Compounds, Amila Nanayakkara May 2019

Reversal Of P-Glycoprotein And Breast Cancer Resistance Protein Mediated Multidrug Resistance In Vitro Using In Silico Identified Novel Compounds, Amila Nanayakkara

Biological Sciences Theses and Dissertations

Multidrug resistance (MDR) is a major cause of chemotherapy failure. Overexpression of ATP-binding cassette (ABC) transporters, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are two well-studied drug transporters which are associated with MDR. These two transporters also act as a major functional unit of the blood brain barrier to protect the brain from xenobiotics and toxins. Lack of clinically approved P-gp and BCRP inhibitors renders chemotherapy treatments of many MDR cancers ineffective and obstructs drug uptake into the brain.

Using computational methods, we have identified new compounds that inhibit P-gp (Brewer et al., Mol. Pharmacol. 2014). Several of these ...


Reversal Of P-Glycoprotein And Breast Cancer Resistance Protein Mediated Multidrug Resistance In Vitro Using In Silico Identified Novel Compounds, Amila Nanayakkara May 2019

Reversal Of P-Glycoprotein And Breast Cancer Resistance Protein Mediated Multidrug Resistance In Vitro Using In Silico Identified Novel Compounds, Amila Nanayakkara

Biological Sciences Theses and Dissertations

Multidrug resistance (MDR) is a major cause of chemotherapy failure. Overexpression of ATP-binding cassette (ABC) transporters, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are two well-studied drug transporters which are associated with MDR. These two transporters also act as a major functional unit of the blood brain barrier to protect the brain from xenobiotics and toxins. Lack of clinically approved P-gp and BCRP inhibitors renders chemotherapy treatments of many MDR cancers ineffective and obstructs drug uptake into the brain.

Using computational methods, we have identified new compounds that inhibit P-gp (Brewer et al., Mol. Pharmacol. 2014). Several of these ...


Prevalence Of A Variant Gastrin Receptor Rna And Correlating Genomic Polymorphism In Human Pancreatic Cancer, Rebekah Jones May 2019

Prevalence Of A Variant Gastrin Receptor Rna And Correlating Genomic Polymorphism In Human Pancreatic Cancer, Rebekah Jones

Honors Projects and Presentations: Undergraduate

Currently, the five-year survival rate of pancreatic cancer is an abysmal 5%. Our lab has focused on the etiology of CCK2i4svR, a hyperactive splice variant of the gastrin receptor (CCK2R), which has been associated with increased pancreatic tumor aggressiveness. To determine if a correlation exists between a single nucleotide polymorphism (SNP) in the receptor, and expression of the variant RNA in patients, we aim to genotype human pancreatic tumor samples and quantify CCK2R and CCK2i4svR mRNA. Initial analysis of RNA samples by Real Time RT‐PCR has demonstrated successful quantification of CCK2R expression in both tumor and normal tissue samples ...


Med12 Mutations Promote Castration-Resistant Prostate Cancer Through Hyperactivated Gli3/Shh Signalling, Soundharrya Muthukumar May 2019

Med12 Mutations Promote Castration-Resistant Prostate Cancer Through Hyperactivated Gli3/Shh Signalling, Soundharrya Muthukumar

Theses & Dissertations

When cells of the prostate gland start growing uncontrollably, it results in cancer due to genetic aberrations. The development and progression of prostate cancer depend on androgenic stimulation. Although prostate cancer is temporarily treated by depriving a tumor of androgen, the patient relapses getting a castration-resistant form of the disease called castration-resistant prostate cancer (CRPC). CRPC can specifically develop through crosstalk of androgen receptor signalling pathways. One such pathway that is of specific interest in this paper is the MED12 regulated SHH signalling pathway. The mediator is a signal processor that helps in the transduction of gene-specific transcription factors to ...


Targeting Sec61Α By Ipomoeassin F Leads To Highly Cytotoxic Effect, Zhijian Hu May 2019

Targeting Sec61Α By Ipomoeassin F Leads To Highly Cytotoxic Effect, Zhijian Hu

Theses and Dissertations

Ipomoeassin F is a flagship congener of a resin glycoside family that inhibits growth of many tumor cell lines with only single-digital nanomolar IC50 values. However, biological and pharmacological mechanisms of ipomoeassin F have been undefined. To facilitate exploration of the biological and pharmacological properties, we performed sophisticate SAR (Structure–activity relationship) studies of ipomoeassin F to understand its pharmacophore and structure properties so that we can design favorable probes for further biological investigation. By applying appropriate deviates that possess fluorescent groups and similar bio-activity, the target protein was found to be localized in endoplasmic reticulum (ER). Through biotin affinity ...


Diffuse Reflectance Spectroscopy To Quantify In Vivo Tissue Optical Properties: Applications In Human Epithelium And Subcutaneous Murine Colon Cancer, Gage Joseph Greening May 2019

Diffuse Reflectance Spectroscopy To Quantify In Vivo Tissue Optical Properties: Applications In Human Epithelium And Subcutaneous Murine Colon Cancer, Gage Joseph Greening

Theses and Dissertations

Colorectal cancer is the 4th most common and 2nd deadliest cancer. Problems exist with predicting which patients will respond best to certain therapy regimens. Diffuse reflectance spectroscopy has been suggested as a candidate to optically monitor a patient’s early response to therapy and has been received favorably in experimentally managing other cancers such as breast and skin. In this dissertation, two diffuse reflectance spectroscopy probes were designed: one with a combined high-resolution microendoscopy modality, and one that was optimized for acquiring data from subcutaneous murine tumors. For both probes, percent errors for estimating tissue optical properties (reduced scattering coefficient ...


Paraoxonase 2 Is Critical For Non-Small Cell Lung Carcinoma Proliferation., Aaron Whitt May 2019

Paraoxonase 2 Is Critical For Non-Small Cell Lung Carcinoma Proliferation., Aaron Whitt

Electronic Theses and Dissertations

Non-small cell lung carcinoma (NSCLC) comprises 85% of lung cancer diagnoses and is plagued by drug resistance. Thus, elucidating the underlying mechanisms of NSCLC is paramount to expand future treatment options. Paraoxonase 2 (PON2), an intracellular enzyme with arylesterase and lactonase functions, has well-established anti-atherosclerotic activity. Recent studies show PON2 is overexpressed in a variety of tumors and confers drug resistance, although these interactions have not been thoroughly examined in NSCLC. Thus, we sought to investigate the role of PON2 in cellular proliferation using PON2-knockout mice, primary mouse cells, and NSCLC cell lines. Using these approaches, we demonstrate that PON2 ...


Comparative Plasma Proteomics In Muscle Atrophy Induced By Cancer Cachexia And Hindlimb Unloading, Kirsten Rene Dunlap May 2019

Comparative Plasma Proteomics In Muscle Atrophy Induced By Cancer Cachexia And Hindlimb Unloading, Kirsten Rene Dunlap

Theses and Dissertations

Introduction: Muscle atrophy results from a dysfunction in protein turnover that leads to loss of mass and function and occurs concurrently with multiple pathologies such as cancer and extended bed rest. Atrophy reduces overall quality of life while increasing morbidity and mortality. Currently, efficacious therapeutic interventions to treat and prevent muscle wasting in all its forms are lacking, however if conserved mechanisms can be identified between wasting conditions, this would aid in the development of multipurpose therapeutics to ameliorate this pathology. Purpose: To examine circulating factors present across atrophic pathologies. Methods: 35 male C57BL/6J mice were assigned to hindlimb ...


The Molecular Mechanisms Underlying The Cancer Killing Effect Of Interleukin-24, Leah Eshanie Persaud May 2019

The Molecular Mechanisms Underlying The Cancer Killing Effect Of Interleukin-24, Leah Eshanie Persaud

All Dissertations, Theses, and Capstone Projects

Interleukin-24 (IL-24) is an immunomodulatory cytokine that also displays specific anti-tumor effects across many cancer cell types. The tumor suppressor activities of IL-24 include inhibition of angiogenesis, metastasis, toxic autophagy, cancer-specific apoptosis, and sensitization to traditional cancer treatments like chemotherapy and radiation. Overexpression of IL-24 can selectively induce apoptosis in various cancer cells while having no adverse effects on normal cells. Due to this favorable killing effect, IL-24 is currently in phase II clinical trials. There is accumulating evidence that IL-24’s anti-cancer activity is primarily through the endoplasmic reticulum (ER) stress pathway but other pathways leading to cell death ...


Context Dependent Roles Of Mdmx (Mdm4) And Mdm2 In Breast Cancer Proliferation And Circulating Tumor Cells, Chong Gao May 2019

Context Dependent Roles Of Mdmx (Mdm4) And Mdm2 In Breast Cancer Proliferation And Circulating Tumor Cells, Chong Gao

All Dissertations, Theses, and Capstone Projects

Many human breast cancers overexpress the E3 ubiquitin ligase MDM2 and its homolog MDMX. Expression of MDM2 and MDMX occurs in both estrogen receptor α positive (ER+) and triple negative breast cancer (TNBC). We and others have reported that estrogen activated MDM2 strongly promotes proliferation in ER+ T47D breast cancer cells in a p53-independent manner. Whether MDM2 elicits in vivo p53-independent proliferative functions in T47D breast cancer cells has not been determined. Furthermore it has been shown that ectopic expression of MDM2 targets E-Cadherin for degradation thus leading to increased cell migration and invasion. Therefore we assessed the in vivo ...


Mechanisms Of Oriented Cell Division And Their Roles In Tissue Development, Evan Blake Dewey Apr 2019

Mechanisms Of Oriented Cell Division And Their Roles In Tissue Development, Evan Blake Dewey

Biology ETDs

Properly executed cell division is crucial to development, maintenance, and longevity of multicellular organisms. Defects in both symmetric and asymmetric divisions can lead to improper developmental patterning, as well as genomic instability, disruption of tissue homeostasis, and cancer. Our research focuses on how regulators orchestrate proper cell divisions. Mushroom Body Defect (Mud) is one such regulator, and here we describe how Mud is regulated via the Hippo signaling pathway kinase Warts (Wts), showing Wts phosphorylates Mud to enhance interaction with the polarity protein Partner of Inscuteable, promoting spindle orientation activity. We next focus on another regulator, Shortstop (Shot), describing a ...


Eralpha Isoforms Modulate The Tumorigenicity Of 24r,25(Oh)2d3 In Estrogen-Responsive Cancer, Anjali Verma Jan 2019

Eralpha Isoforms Modulate The Tumorigenicity Of 24r,25(Oh)2d3 In Estrogen-Responsive Cancer, Anjali Verma

Theses and Dissertations

Over 200,000 cases of breast cancer are diagnosed every year. Nearly 20% of these patients supplement their diets with some form of vitamin D. This high frequency of vitamin D supplement use may be due in part to research suggesting that cancer patients with higher serum vitamin D3 levels have better prognoses than patients with low serum vitamin D3. However, double-blind clinical trials on the efficacy of vitamin D3 supplementation in breast cancer have been inconclusive. A recent meta-analysis showed evidence of reduced cancer recurrence in patients taking vitamin D3 supplements who had ‘estrogen receptor ...


Regorafenib Enhances Lethality Of Sildenafil And Curcumin In Colorectal Cancer Cells, Kervin Benjamin Owusu Jan 2019

Regorafenib Enhances Lethality Of Sildenafil And Curcumin In Colorectal Cancer Cells, Kervin Benjamin Owusu

Theses and Dissertations

In the United States, more than 130,000 people will be diagnosed with colorectal cancer (CRC) each year and an estimated 50,000 people will die from the disease. Standard of care (SOC) therapies for CRC combine multiple cytotoxic chemotherapeutic drugs. These combinations have varying degrees of effectiveness and can often result in significant patient morbidity. For second recurrence patients, the multi-kinase inhibitor, regorafenib, is an approved agent, but is often poorly tolerated at current doses. In the current study, we propose to develop therapeutic regime of combining agents with modest toxicity profiles: curcumin and sildenafil with regorafenib. Using clinically ...


Effects Of Pag1 On Src-Family Kinase Trafficking In Neuroblastoma Cells, Makenzie E. Mayfield Jan 2019

Effects Of Pag1 On Src-Family Kinase Trafficking In Neuroblastoma Cells, Makenzie E. Mayfield

Undergraduate Theses and Professional Papers

The receptor tyrosine kinases (RTKs) are known to help regulate cell behaviors including differentiation, proliferation and migration during embryonic development of the neural crest. RTKs are believed to initiate signaling cascades in response to extracellular cues in part by controlling localization of Src-family kinases (SFKs). The scaffolding protein PAG1 binds SFKs and is believed to influence SFK activity and location within the cell by promoting interaction of SFKs with regulatory proteins and by drawing SFKs into different components of the endocytic pathway. By targeting the PAG1 gene in SH-SY5Y neuroblastoma cells with CRISPR/Cas9 plasmids, we created PAG1-mutant cell-lines in ...


Clarifying The Connection Between Oncgenic Kras And Gastrin/Cck2r Signaling In Pancreatic Tumorigensis, Andrew Larow, John F. Harms Jan 2019

Clarifying The Connection Between Oncgenic Kras And Gastrin/Cck2r Signaling In Pancreatic Tumorigensis, Andrew Larow, John F. Harms

Honors Projects and Presentations: Undergraduate

Pancreatic ductal adenocarcinoma (PDAC) is an extremely deadly cancer: the overall five-year survival rate is 8%. This is mainly due to the difficulty of diagnosing PDAC in its early stage: only 9% of patients are diagnosed with localized cancer. Cancer cells display rapid growth and cell division, due in part to oncogene activation and stimulation of mitogenic pathways. In PDAC, mutant K-ras, an oncogene and intracellular signaling protein, is present in 90% of all cases. Because of this high correlation and the role of mutant K-ras in PDAC, it has been repeatedly targeted for cancer therapy, but with little success ...


Regulation Of The Long Non-Coding Rna Fam83h-As1 By Human Papillomavirus In Cervical Cancer, Jamie Ann Barr Ph.D. Jan 2019

Regulation Of The Long Non-Coding Rna Fam83h-As1 By Human Papillomavirus In Cervical Cancer, Jamie Ann Barr Ph.D.

Graduate Theses, Dissertations, and Problem Reports

Non-coding RNAs (NcRNAs), such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have been found to be involved in a variety of critical biological processes, and dysregulation of ncRNAs have been involved with several human diseases including cancer.

High-risk human papillomavirus (HPV) infection is one of the first events in the process of carcinogenesis in cervical and a subset of head and neck cancers. The expression of the viral oncoproteins E6 and E7 is essential in this process by inactivating the tumor suppressor proteins p53 and Rb, respectively, in addition to their interactions with other host proteins and regulation of ...


The Role Of Kras In Mechanosensing In Non-Small Cell Lung Cancer, Krista M. Powell Jan 2019

The Role Of Kras In Mechanosensing In Non-Small Cell Lung Cancer, Krista M. Powell

Theses and Dissertations

Lung cancer is the number one cause of cancer related death worldwide, with more than 1.6 million fatalities each year. Non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancers, with KRAS being one of the most prevalent oncogenic driver mutations. Therapeutic approaches for KRAS-mutated NSCLC have been extensively explored due to the US National Cancer Institute RAS Initiative, but methods of directly targeting KRAS or downstream effectors, such as MEK, still have poor results. Previous reports have shown that KRAS-mutated NSCLC activate distinct receptor tyrosine kinases (RTKs) depending on the epithelial or mesenchymal state. Epithelial-to-mesenchymal transition ...


Evaluating Lactobacillus Acidophilus As A Model Organism For Co-Culture Cancer Studies, Samuel A. Mikhail Jan 2019

Evaluating Lactobacillus Acidophilus As A Model Organism For Co-Culture Cancer Studies, Samuel A. Mikhail

Honors Undergraduate Theses

The causality dilemma between dysbiosis and cancer has given rise to numerous studies both exploring the mechanisms behind cancer progression and the associative shifts in the microbiota upon carcinogenesis. Aside from the hallmark study of Dr. Barry Marshall in establishing the true causal relationship between Helicobacter pylori and gastric adenocarcinoma, studies have only been successful in adding associative links of carcinogenesis mediated by bacteria to the literature. The current field is limited in its ability to establish causative relationships, and further work is needed to construct a reference community whose physiological responses reflect global community responses. In this thesis, the ...


Regulation Of Canonical And Non-Canonical Hippo Pathway Components In Mitosis And Cancer, Seth Stauffer Dec 2018

Regulation Of Canonical And Non-Canonical Hippo Pathway Components In Mitosis And Cancer, Seth Stauffer

Theses & Dissertations

The Hippo pathway is conserved regulator of organ size through control of proliferation, apoptosis, and stem-cell self-renewal. In addition to this important function, many of the canonical signaling members have also been shown to be regulated during mitosis. Importantly, Hippo pathway components are frequently dysregulated in cancers and have attracted attention as possible targets for improved cancer therapeutics. Further exploration of Hippo-YAP (yes-associated protein) signaling has revealed new regulators and effectors outside the canonical signaling network and has revealed a larger non-canonical network of signaling proteins in which canonical Hippo pathway components crosstalk with important cellular homeostasis and apoptosis signaling ...


Frost450, A Novel Microtubule Targeting Agent: Resistance And Cross-Resistance In An Ovarian Cancer Cell Line, Jonathan Chancellor Fox Dec 2018

Frost450, A Novel Microtubule Targeting Agent: Resistance And Cross-Resistance In An Ovarian Cancer Cell Line, Jonathan Chancellor Fox

Undergraduate Honors Theses

Drug resistance remains problematic for chemotherapy treatments. As primary treatment strategies tend to lose potency against cancer, there is a need for treatment options that overcome drug resistance mechanisms. FROST450, a novel microtubule destabilizing agent, has proven anticancer effects that overcome taxane and multidrug resistance. However, to better understand the clinical potential of FROST450, in this study we examine the mechanisms and implications of acquired FROST450 resistance in an A2780 ovarian cancer cell line. Results indicate FROST450 resistance is associated with increased mitochondrial respiration and with changes in gene sequence or expression level of proteins associated with microtubules, and that ...


Role Of P300 Zz Domain In Chromatin Association And Histone Acetylation, Yongming Xue Dec 2018

Role Of P300 Zz Domain In Chromatin Association And Histone Acetylation, Yongming Xue

UT GSBS Dissertations and Theses (Open Access)

Transcription is strictly regulated by numerous factors including transcription coactivators. The p300 protein and its close paralogue CREB-binding protein (CREBBP, aka CBP) are well-known transcriptional coactivators that have intrinsic lysine acetyltransferase activity. The functions of p300/CBP largely rely on their capabilities to bind to chromatin and to acetylate the histone substrates. However, the molecular mechanisms underlying the regulation of these processes are not fully understood.

Through combination of various biochemical, biophysical and molecular approaches, we show that the ZZ-type zinc finger (ZZ) domain of p300 functions as a histone reader that specifically binds the N-terminal tail of histone H3 ...


Molecular Dynamics Of P21 And Fluorescent Sphingomyelin In Keratinocytes Exposed To Uvb, Tyler Malcolm Fraser Dec 2018

Molecular Dynamics Of P21 And Fluorescent Sphingomyelin In Keratinocytes Exposed To Uvb, Tyler Malcolm Fraser

Master's Theses and Project Reports

Non-melanoma skin cancer (NMSC) is the most common malignant tumor, representing more than a third of all malignant tumors combined and the incidence is increasing every year. Ultraviolet (UV) radiation from the sun is the most dominant factor contributing to tumor initiation and progression. The condition is most prevalent in populations with lighter skin and older age. Current pharmaceutical molecular research targets the inhibition of the Epidermal Growth Factor Receptor (EGFR), a receptor which is commonly over-expressed or dysregulated in skin malignancies. This study evaluates the content and location of the damage marker p21 within keratinocytes that were incubated in ...