Medicine and Health Sciences Commons^™

Crosstalk Between The Extracellular Matrix And The Cell- Cell Junction - Associated Rnai Machinery Regulates Colon Cancer Cell Behavior, Amanda Daulagala

MUSC Theses and Dissertations

Colon cancer is the third most common and second deadliest type of cancer. Colon cancer is broadly characterized by compromised epithelial integrity and by aberrant extracellular matrix (ECM) remodeling. However, a potential mechanistic connection between epithelial integrity and ECM remodeling that could be contributing to the disease progression, has not been explored yet. The Adherens Junction (AJ) is a cell-cell adhesion complex composed of cadherin and catenin family proteins and essential for establishing and maintaining epithelial tissue integrity. Our previous work revealed that PLEKHA7, an E-cadherin-p120 catenin partner, recruits the microprocessor and the RNA-induced silencing complex (RISC), key components of …

Marketing Efforts To Reengage Consumers In Cancer Screenings During The Covid-19 Pandemic, Angela M. Kasel

Walden Dissertations and Doctoral Studies

In 2020, U.S. hospitals became overwhelmed by patients with the viral illness COVID-19. Health systems were advised by the U.S. Surgeon General and Centers for Disease Control and Prevention to suspend elective procedures, including mammograms, colonoscopies, and lung computed tomography scans. The purpose of this quantitative study was to investigate whether there was a significant difference in completed appointments, cancer screenings, and cancer diagnoses in consumers receiving targeted direct mail and email communications during the COVID-19 pandemic, based on age, gender, and geographic location. The elaboration likelihood model of persuasion, which emphasized the use of marketing to change consumer behaviors …

Developing A Quality Improvement Process: Impacting Patient Outcomes And Achieving Ambulatory Accreditation, Colleen E. Nappi

Doctors of Nursing Practice (DNP) Final Projects, 2020-current

Colon cancer is the second leading cause of cancer deaths in the United States (US) and colonoscopy is the best method for screening and detecting cancer before symptoms are present. A colonoscopies' ability to detect precancerous lesions or identify colorectal cancer (CRC) relies on patients having a high-quality bowel preparation. The US Multi Society Task Force (USMSTF) on colorectal cancer set quality standards for colonoscopy including bowel preparation quality, adenoma detection, and cecal intubation times. As a private gastroenterology practice in Northern Virginia was preparing for re-accreditation with the Accreditation Association for Ambulatory Health Care (AAAHC) it was determined that …

Utilizing Multimodal Communication Strategies To Improve Average Risk Women Veteran Patient Participation In Returning Colorectal Fecal Immunochemical Test Kits, Shuntae Hooten

Doctor of Nursing Practice Projects

Background: Cancer is one of the most dreadful diseases present in today’s world. It is responsible for millions of deaths worldwide. The disease is debilitating to one’s physical and emotional well-being. Cancer impacts not only the affected individual but also those close to them. When colorectal cancer is identified early via preventive screenings, it has a greater chance of responding to treatment, therefore, increasing the chances of survival. The fecal immunochemical test (FIT) kit plays a pivotal role in the early detection of colon cancer. Schreuders et al. (2016) revealed that FIT kits have better adherence, usability, and accuracy, citing …

Nonparametric Estimation Of Transition Probabilities In Illness-Death Model Based On Ranked Set Sampling, Ying Ma

USF Tampa Graduate Theses and Dissertations

The ranked set sampling (RSS) design is applied widely in agriculture, environmental science, and medical research where the exact measurements of sampling units is costly, but sampling units can be ranked by a correlated concomitant variable. RSS is usually a cost-efficient alternate to simple random sampling (SRS) for selecting more representative samples. This study presents a novel methodology to investigate the nonparametric estimation of transition probabilities in illness-death model using the RSS design. We study the Aalen–Johansen estimator of transition probabilities in illness-death Markov model based on RSS design under random right censoring time and propose nonparametric estimators of the …

Transitions In Palliative Care: Referral Time And Healthcare Utilization In Advanced Stage Colon, Rectal And Lung Cancer Patients., Ann Lawani

Dissertations

Background: Despite lung, colon, and rectal cancer being the leading and third leading cause of cancer-related death among both men and women respectively, few studies have examined Palliative Care Consultation (PCC) on healthcare utilization (HCU) in individuals with advanced stage diagnosis in this disease cohort. Extant research shows advanced stage cancer patients receive aggressive treatments, within the last 30 days of life. Palliative care is linked to less aggressive cancer treatment, and palliative interventions applied early, at diagnosis of advanced cancer, is more favorable for improving symptom and disease management. Patients and family members with early PCC are better informed …

The Role Of Obesity In Macrophage-Mediated Mechanisms Promoting Early-Onset Colon Cancer., Katharina Marietta Scheurlen

Electronic Theses and Dissertations

Early-onset colon cancer (EOCC) is a leading cause of cancer death among people younger than 50 years of age in the United States and is associated with metabolic dysfunction and obesity. Anti-inflammatory tumor-associated macrophages (TAM) and low Peroxisome Proliferator Activated Receptor Gamma (PPARγ) gene expression in colon cancer (CC) tissue promote tumor progression and decreased patient survival. Obesity-related hormones, such as leptin and adiponectin, have the potential to affect gene expression in TAM to promote CC progression and thereby link obesity and EOCC. The aim of this project was to identify target genes in human CC and to investigate the …

Glycemic Variability In Patients With Stage Ii-Iii Colon Cancer, Natalie Mandolfo

Theses & Dissertations

Patients with cancer experience metabolic changes such as hypoglycemia, hyperglycemia, and glycemic variability; collectively termed malglycemia. Glycemic variability, defined as fluctuations in glucose, is a marker of metabolic instability. Higher glycemic variability is associated with adverse health outcomes in the general population and in those with diabetes. Little is known about glycemic variability in patients with cancer, especially those with solid tumor malignancies. Glycemic variability is associated with increased infection, shorter periods of remission, and higher mortality in patients with hematological cancer. This body of work describes the concept and measurement of glycemic variability to assess glycemic control in patients …

The Role Of Histone Chaperone Fact Complex In Base Excision Repair Pathway And Its Therapeutic Potential In Colon Cancer And Medulloblastoma, Heyu Song

Theses & Dissertations

Base excision repair (BER) pathway is required for the removal of damaged bases caused by alkylation, oxidation and ring-saturation. Human apurinic/apyrimidinic endonuclease 1 (APE1) plays a central role in BER pathway. Although repair of damaged bases by recombinant APE1 has been well investigated in vitro, how APE1 gains access to damaged bases in the context of chromatin is largely unknown. A prominent member of the histone chaperone family, FACT (Facilitates Chromatin Transcription) is thought to reorganize nucleosomes through the destabilization of multiple intra-nucleosome contacts. FACT complex is composed of two polypeptides identified as SPT16 (Suppressor of Ty 16) and SSRP1 …

The Identification Of Long Non-Coding Rna Zfas1 Through An Exploratory Rna-Sequencing Analysis And Its Association With Epithelial-To-Mesenchymal Transition In Colon Cancer Adenocarcinoma., Stephen J. O'Brien

Electronic Theses and Dissertations

Colorectal adenocarcinoma is the fourth most common cancer diagnosed worldwide and is a significant cause of morbidity and mortality. This dissertation performed an exploratory RNA-sequencing analysis comparing gene expression between colon adenocarcinoma tissue and paired normal colon epithelium. After identification of a number of lncRNAs that were increased in expression in colon adenocarcinoma compared to normal colon epithelium, we aimed to validate the expression and investigate their function in vitro. Specifically, we focused on the lncRNA ZFAS1 and its association with epithelial-to-mesenchymal transition. These studies found the following: 1. Seven candidate lncRNAs were identified from the exploratory RNA-sequencing analysis to …

The Contribution Of Adipose Tissue From Ovariectomized Mice To Colon Cancer, Meredith Smith Carson

Theses and Dissertations

Obesity is considered a major public health concern worldwide due to the increased incidences of metabolic dysfunction and cancer risk. The obese state is, in part, attributable to the overconsumption of calorie-dense foods commonly seen in a standard Western diet, which aids in the progression of chronic, lowgrade inflammation. The role of estrogen varies depending on menopausal status, where estrogen deficiency coupled with increased visceral fat associated with post-menopause leads to increased secretions of pro-inflammatory adipokines and cytokines. However, the presence of estrogen in a premenopausal state has been shown to attenuate the pro-inflammatory response, which has been demonstrated when …

The Role Of Cdk8 In Metastatic Growth Of Colon Cancer, Jiaxin Liang

Theses and Dissertations

Unresectable hepatic metastases of colon cancer poorly respond to existing therapies and are a major cause of colon cancer lethality. Transcription- regulating Mediator kinase CDK8, an early clinical stage drug target, is amplified or overexpressed in many colon cancers and CDK8 expression correlates with shorter patient survival. Here we show that CDK8 inhibition does not generally suppress proliferation of CDK8-overexpressing colon cancer cells but nevertheless CDK8 knockdown by shRNA or CDK8 kinase inhibition by a selective small-molecule drug candidate suppresses metastatic growth of mouse and human colon cancer cells in the liver. This effect is due at least in part …

Combination Oral Immunotherapy With Il-10 And Il-12 Effectively Treats Colon Tumors Via Synergistic Effects On Il-17 Producing T Cells And Colon Epithelial Barrier Integrity., Neal Bhutiani

Electronic Theses and Dissertations

In this dissertation, the relationship between colon cancer and inflammation, the utility of novel imaging modalities for diagnosis of colitis and cancer, and the therapeutic efficacy of orally delivered, particle-based immunotherapy for the treatment of colon cancer are evaluated. In Chapters One and Two, multispectral optoacoustic tomography (MSOT) is demonstrated to effectively detect colon inflammation without the use of exogenous contrast prior to detection using conventional colonoscopy. Oral particle uptake is demonstrated in the distal small intestine and proximal colon, confirming site-specific delivery. In Chapter Three, administration of IL-10 and IL-12 containing particles is shown to act synergistically to significantly …

Functional Signature Ontology-Based Identification And Validation Of Novel Therapeutic Targets And Natural Products For The Treatment Of Cancer, Beth Neilsen

Theses & Dissertations

Multiple studies have revealed that Ras-driven tumors acquire vulnerabilities by adapting cellular mechanisms that promote uncontrolled proliferation and suppress apoptosis. Kinase Suppressor of Ras 1 (KSR1) modulates ERK activation downstream of oncogenic Ras, and knockdown of KSR1 selectively kills malignant, Ras-driven cancer cells, but does not kill immortalized, non-transformed human colon epithelial cells (HCECs). KSR1^-/- mice are fertile and phenotypically normal, but resistant to Ras-driven tumor formation suggesting KSR1 represents a vulnerability in cancer cells.

To identify additional vulnerabilities in cancer, a screening approach termed Functional Signature Ontology (FUSION) was used to screen 14,355 genes and 1,200 natural product …

Investigations On Cancer Cell Biological Effects Of Cdk8 Inhibitor Q-12, Zhixin Lu

University of the Pacific Theses and Dissertations

Over the past two decades, protein kinases have been intensively investigated as targets to treat neoplastic diseases. Many protein kinase inhibitors not only have therapeutic potential but are becoming invaluable reagents for the study of cell signaling.

We aspired to use our Cyclin-Dependent Kinase 8 inhibitor, Q-12, as a probe for biomarker discovery for CDK8 inhibitor sensitive tumor types. Q-12 shows potent inhibition of cell viability and induction of apoptosis process in some triple-negative breast cancer and colorectal cancer cell lines in vitro. Western blot results indicate that the reduction of STAT1 phosphorylation could be a robust indicator of CDK8 …

Barriers To Colorectal Cancer Screening Within A Rural Community In Ohio, Kristina Knoll

DNP Projects

Purpose: The purpose of this study was to perform a needs assessment within the primary care practice of ProMedica Family Medicine in Fostoria, OH. The needs assessment will specifically identify intentions and behaviors, attitudes and beliefs, subjective norms about behavioral control, and healthcare provider or healthcare system barriers related to colorectal cancer screening.

Methods: This was a cross-sectional study using a survey among a convenience sample of patients who were 50 - 75 years of age and were not currently up-to-date with their colorectal cancer screening. In total, 222 patients were screened, 133 patients were determined to not be up-to-date, …

Identifying Protein Kinase Tbk1 As A Novel Inhibitor Of Intestinal Tumorigenesis, Amber L. Mathews

Dissertations & Theses (Open Access)

Colorectal cancer (CRC) is the third most common cancer diagnosed in women and men， causing almost 600,000 annual deaths worldwide. There is a clear need to understand how CRC forms and progresses in order to improve the strategies of CRC prevention and therapy. A major factor that drives the development of CRC is genetic mutations that lead to activation of oncogenes and inactivation of tumor suppressor genes in intestinal epithelial cells (IECs). In addition, the initiation and progression of CRC involve environmental and immunological factors. In particular, chronic inflammatory conditions are known as an important risk factor for CRC. Intestinal …

Investigating The Interaction Of Aurka And Ube2c In Colorectal Cancer Cells, Apurva M. Hegde

Dissertations & Theses (Open Access)

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in the US. Among the many genomic aberrations previously implicated in colorectal cancer, recurrent amplification of chromosome 20q is frequently associated with liver metastasis. Previous research in our lab identified a gene signature on chromosome 20q associated with colorectal cancer progression. In this study, one of the genes in the signature, the ubiquitin conjugating enzyme UBE2C, was identified through preliminary bioinformatics analysis as a candidate for further examination of its role in CRC progression. Co-expression analysis of UBE2C in tumor-normal datasets from the public database Oncomine revealed all the …

Anti-Neoplastic Effects Of Extracts From Gnaphalium Gracile On Colon, Pancreatic, And Prostate Cancer Cells, Joshua R. Canter

Undergraduate Honors Theses

Over 4,000 flavonoids have been identified, and among these, many of them are known to possess cardioprotective, anti-inflammatory, antimicrobial, and antitumor effects. However, most of these properties have yet to be fully understood. In this study, extracts from Gnaphalium gracile, thought to possess a mixture of flavonoids, have been tested for cytotoxic activity on pancreatic (MiaPaca, Panc28), colon (HCT-116, Caco-2), and prostate (PC3, LNCaP), cancer cell lines. Polar extracts from the leaves of G. gracile have the most cytotoxic effect on these cancer cell lines, particularly the prostate cancer cell lines PC3 and LNCaP. Evidence suggests the extracts have …

Will The Addition Of Oxaliplatin To 5-Fluorouracil (5fu), And Leucovorin Improve Disease Free Survival Of Patients With Stage Iii Colon Cancer Who Had Surgical Resection Of The Tumor?, Sarah Cotter

PCOM Physician Assistant Studies Student Scholarship

Objective: The objective of this selective EBM review is to determine whether or not the addition of oxaliplatin to 5FU and leucovorin will improve disease free survival of patients with stage III colon cancer who had surgical resection of the tumor.

Study Design: Review of three published, double blind randomized control trials in the English language in 2004, 2007, and 2009.

Outcomes Measured: The outcome is disease free survival of colon cancer. It is measured using periodic patient follow-up. History and PE, neuro assessment, liver and kidney function tests, CEA test, CBC, and imaging studies such as colonoscopy or barium …

Molecular And Functional Investigation Of Cancer-Type And Liver-Type Variants Of Organic Anion Transporting Polypeptide 1b3, Nilay Thakkar

Theses and Dissertations--Pharmacy

OATP1B3 belongs to the OATP (organic anion transporting polypeptides) superfamily, responsible for mediating the transport of various endogenous and xenobiotic substrates. OATP1B3 was initially reported to be expressed exclusively in the hepatocytes where it mediates the uptake of numerous endogenous substrates (e.g. bile acids, steroid hormone conjugates) and several clinically relevant drugs including anticancer drugs. Later, a number of studies reported that OATP1B3 is also frequently expressed in multiple types of cancers and may be associated with differing clinical outcomes. However, a detailed investigation on the expression, localization and functions of OATP1B3 expressed in cancer has been lacking. In this …

Mismatch Repair Deficient Tumors Lacking Known Sporadic Causes: Are They All Due To Lynch Syndrome?, Katherine M. Dempsey

Dissertations & Theses (Open Access)

BACKGROUND: Mismatch repair deficient (MMRD) colorectal (CRC) or endometrial (EC) cancers in the absence of MLH1 promoter hypermethylation and BRAF mutations are suggestive of Lynch syndrome (LS). Positive germline genetic test results confirm LS. It is unclear if individuals with MMRD tumors but no identified germline mutation or sporadic cause (MMRD+/germline-) have LS.

HYPOTHESIS: Since LS is hereditary, individuals with LS should have a stronger family history of LS-related cancers than individuals with sporadic tumors. We hypothesized that MMRD+/germline- CRC and/or EC patients would have less suggestive family histories than LS CRC and/or EC patients.

METHODS: 253 individuals with an …

Modeling Sporadic Tumor Formation Driven By Telomere Dysfunction In The Gastrointestinal Tract, Suzanne S. Chan

Dissertations & Theses (Open Access)

Colorectal cancer is a complex disease that is thought to arise when cells accumulate mutations that allow for uncontrolled growth. There are several recognized mechanisms for generating such mutations in sporadic colon cancer; one of which is chromosomal instability (CIN). One hypothesized driver of CIN in cancer is the improper repair of dysfunctional telomeres. Telomeres comprise the linear ends of chromosomes and play a dual role in cancer. Its length is maintained by the ribonucleoprotein, telomerase, which is not a normally expressed in somatic cells and as cells divide, telomeres continuously shorten. Critically shortened telomeres are considered dysfunctional as they …

Effect Of Dietary Folate Restriction On Colon Carcinogenesis In Dna Polymerase Β Haploinsufficient Mice, Lisa F. Ventrella Lucente

Wayne State University Dissertations

The data presented in this research is central to establishing the role that the base excision repair pathway (BER) plays in the development and progression of colon cancer when dietary folate is deficient. Both cellular folate restriction and BER deficiencies have been shown to result in the accumulation of endogenous damage and lesions that could eventually develop into carcinogenesis. In this study, a dietary folate deficiency (FD) resulted in a significant increase in aberrant crypt foci (ACF) formation and triggered liver tumorogenesis in wildtype (WT) animals, as did a BER deficiency in DNA polymerase Β haploinsufficient (Β-pol+/-) mice exposed to …

Enzymology And Molecular Biology Of Bile Acid 7alpha- And 7beta- Dehydroxylation By The Intestinal Bacteria Clostridium Scindens And Clostridium Hylemonae, Jason Michael Ridlon

Theses and Dissertations

The collective microbial genomes within our gut(microbiome) represent a powerful metabolic force, leading many authors to call our GI flora an "organ within an organ", and the metagenomic sequencing of our microbiome, "the second human genome project". Bile acids, endogenously produced by the host liver, represent both a strong selective pressure for potential colonizers, aswell as substrates for microbial metabolism. Indeed, microbes have evolved enzymes to deconjugate bile salts, epimerize bile acid hydroxyl groups, and 7alpha-dehydroxylateprimary bile acids. The products of microbial 7alpha-dehydroxylation, secondary bile acids, are suggested by numerous lines of evidence to be involved in promoting colon carcinogenesis. …

The Antitumor Agent, Arglabin-Dma, Preferentially Induces Apoptosis In Human Colon Tumor Cells, Sung Wook Kwon

Theses and Dissertations in Biomedical Sciences

Arglabin-DMA, an analog of farnesyl pyrophosphate (FPP), reportedly inhibits farnesyltransferase (FTase) directly by competitively blocking the binding of Ras protein and its posttranslational modification, as suggested in previous studies. But, the mechanisms by which Arglabin-DMA inhibits tumor growth in vivo and in vitro are still relatively poorly characterized. To determine the mechanism by which this drug inhibits tumor growth, the effects of Arglabin-DMA in two human colon tumor cell lines (mutant K-ras HCT 116 and wild-type ras HT-29) were explored on cell proliferation, apoptosis, and cell cycle kinetics in vitro. In cell viability studies, we showed that Arglabin-DMA …