Medicine and Health Sciences Commons^™

Effects Of Non-Steroidal Anti-Inflammatory Drugs On Cellular Structure And Adhesion Proteins In Human Colorectal Cancer, Jason Lee Liggett

Doctoral Dissertations

This dissertation explores the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on human colorectal cancer (CRC) cell proteins related to cellular structure and adhesion. NSAIDs are extensively used not only to treat inflammatory diseases but also to prevent cancer among high-risk groups. Their mechanisms are not fully understood, but both cyclooxygenase (COX) dependent and independent pathways play a role in NSAID-induced anti-tumorigenesis. Our lab previously reported that NSAIDs induce other anti-tumorigenic genes in a COX-independent manner (Chapter 1). Human CRC cells treated with the NSAID sulindac sulfide (SS) showed dramatic morphological changes under differential interference contrast and fluorescent microscopy, as well …

The Effect Of Race/Ethnicity On The Age Of Colon Cancer Diagnosis, Matthew Katz, Maryann E. Parrish, Ellen Li, Yuanhao Zhang, Wei Zhu, Kenneth Shroyer, Roberto Bergamaschi, Jennie L. Williams

Journal of Health Disparities Research and Practice

ABSTRACT

BACKGROUND: Colorectal cancer is the third most commonly diagnosed cancer in the United States. Notably, racial/ethnic disparities exist in both incidence and mortality.

PURPOSE: The aim of this case study was to investigate the impact of race/ethnicity on age at diagnosis of colorectal cancer in a defined population in Suffolk County, NY.

METHODS: Data were retrospectively collected on race/ethnicity, health insurance status, age at diagnosis, stage at diagnosis, gender, smoking status, alcohol intake, tumor location, and body mass index for colorectal cancer patients with medical records in the Stony Brook University Medical Center database (2005-2011). Population-based data on Hispanic …

Modeling Colorectal Cancer As A 3-Dimensional Disease In A Dish: The Case For Drug Screening Using Organoids, Zebrafish, And Fruit Flies, Michele Markstein

Michele Markstein

This review discusses recent shifts in the understanding of colorectal cancer as a stem cell based disease, based on findings that tie patient prognosis to the presence of cancer stem cells in colorectal tumors. Currently no drugs specifically target CSCs in colorectal tumors. However, recent advances in the culturing of colorectal stem cells using mammalian organoids, zebrafish, and Drosophila offer promising avenues for anti-CSC drug discovery.

Characteristics And Quality Of Life Of Patients Presenting To Cancer Support Centres: Patient Rated Outcomes And Use Of Complementary Therapies, Bonnie J. Furzer, Kemi E. Wright, Anna S. Petterson, Karen E. Wallman, Timothy R. Ackland, David Jl Joske

Research outputs 2013

Background: In order to effectively target and provide individualised patient support strategies it is crucial to have a comprehensive picture of those presenting for services. The purpose of this study was to determine the characteristics and patient rated outcomes of individuals presenting to SolarisCare cancer support centres and their choices regarding complementary and integrated therapies (CIT).Methods: A cohort with a current or previous cancer diagnosis aged 18 - 87 years presenting to a SolarisCare centre during a 5-day period completed a questionnaire. Four SolarisCare centres participated in the trial including regional and metropolitan locations. Outcomes included medical and demographic characteristics, …

Health-Related Quality Of Life And Life Satisfaction In Colorectal Cancer Survivors: Trajectories Of Adjustment, Jeff Dunn, Shu Kay Ng, William Breitbart, Joanne Aitken, Pip Youl, Peter D. Baade, Suzanne K. Chambers

Research outputs 2013

Background: This longitudinal study describes the five year trajectories of health-related quality of life (HR-QOL) and life satisfaction in long term colorectal cancer survivors.Patients and methods: A population-based sample of 1966 colorectal cancer survivors were surveyed at six time points from five months to five years post-diagnosis. Predictor variables were: socio-demographic variables, optimism; cancer threat appraisal; perceived social support. Quality of life was assessed with the Functional Assessment of Cancer Therapy-Colorectal (HR-QOL); and the Satisfaction with Life Scale. Growth mixture models were applied to identify trajectory classes and their predictors.Results: Distinct adjustment trajectories were identified for HR-QOL and life satisfaction. …

The Expression Of Cell Adhesion Molecules In Colorectal Cancer Tissue And Its Clinical Values, Dong Chen, Huiying Zhao, Feng Ye

Turkish Journal of Medical Sciences

To investigate the role of cell adhesion molecules CD44v6 and CEA in the occurrence, development, and metastasis of colorectal cancer (CRC). Materials and methods: The expression of CD44v6 and CEA in 76 CRC tissues and 43 normal colon tissues was detected using an immunohistological technique. The relationship between the 2 molecules’ expression and their pathologic characteristics, especially for metastasis, was investigated. Furthermore, the relevance between the expression of CD44v6 and of CEA was also assessed. Results: Expression of CD44v6 and CEA protein in CRC tissues was higher than in paracarcinoma tissue and normal colorectal mucosa (both P < 0.001). Positive expression of CD44v6 in CRC was associated with lymph node metastasis, Dukes’ stage, and histological differentiation. Higher expression intensity of CEA in CRC was related to lymph node involvement, distant metastasis, and invasion depth. Combining analysis of CD44v6 and CEA can improve the sensitivity and specificity in evaluating the metastatic potential of CRC (P < 0.05). There was no relevance between the expression of CD44v6 and CEA in CRC (P > 0.05). Conclusion: CD44v6 …

Associations Among Family History Of Cancer, Cancer Screening And Lifestyle Behaviors: A Population-Based Study, Georgiana Bostean, Catherine M. Crespi, William J. Mccarthy

Sociology Faculty Articles and Research

Purpose Some cancers are largely preventable through modification of certain behavioral risk factors and preventive screening, even among those with a family history of cancer. This study examined the associations between (1) family cancer history and cancer screening, (2) family history and cancer preventive lifestyle behaviors, and (3) cancer screening and lifestyle behaviors.

Methods Data were from the 2009 California Health Interview Survey (n = 12,603). Outcomes included screening for breast cancer (BC) and colorectal cancer (CRC) and six cancer preventive lifestyle behaviors, based on World Cancer Research Fund recommendations. Multivariate logistic regression analyses, stratified by gender and race–ethnicity, examined …

Molecular Staging Of Node Negative Patients With Colorectal Cancer., Terry Hyslop, Scott A Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Metastatic disease is the principle cause of death from colorectal cancer. In that context, the most significant indicator of overall survival and therapeutic response to adjuvant chemotherapy is the presence of metastatic tumor cells in regional lymph nodes. Although histopathologic analysis of lymph nodes is central to all colorectal cancer staging paradigms, its prognostic and predictive value is limited. Indeed, about 30% of patients with histopathology-negative lymph nodes (pN0) die from metastatic disease, reflected by microscopic lymph node metastases that are overlooked by standard techniques. These unrecognized tumor cells are especially important when considering racial disparities in outcomes in colorectal …

Plasma Soluble Thrombomodulin And Soluble Endothelial Protein C Receptor Levels In Colorectal Cancer Patients, Serap Ünal Ti̇lki̇, Hüseyi̇n Engi̇n, Ayla Gökmen, Cemi̇l Bi̇li̇r, Yücel Üstündağ

Turkish Journal of Medical Sciences

Thrombomodulin (TM) and endothelial protein C receptor (EPCR) are 2 transmembrane proteins that are thought to play an important role in cancer. We aimed to discover whether these 2 proteins are prognostic indicators in colorectal cancer. Materials and methods: Plasma TM and EPCR levels were measured using the ELISA method in 50 patients in different tumor stages that had been recently diagnosed with colorectal cancer and in a healthy control group of 50 people. Results: In colorectal cancer patients, higher plasma TM (21.3 ± 22.8 ng/mL, 13.2 ± 16.2 ng/mL, P = 0.010) and plasma EPCR levels (149.9 ± 79.6, …

Cyclic Gmp Phosphodiesterase As A Novel Target For Colorectal Cancer Chemoprevention, Nan Li

All ETDs from UAB

Nonsteroidal anti-inflammatory drugs (NSAIDs) display promising antineoplastic activity for colorectal and other cancers, but toxicity from cyclooxygenase (COX) inhibition limits their long-term use for chemoprevention. However, many investigators have concluded that COX-independent mechanisms are responsible for their antineoplastic activity. We previously reported that cyclic guanosine monophosphate phosphodiesterase (cGMP PDE) is a non-COX target of sulindac sulfide (SS). However, the specific isozyme families involved have not been well studied. Here we demonstrate that SS inhibits the growth of colon tumor cells through a novel mechanism involving inhibition of two cGMP degrading isozymes, PDE5 and PDE10, to activate cGMP-dependent protein kinase (PKG). …

Predictors Of Colorectal Cancer Surveillance Among Survivors Of Childhood Cancer At High Risk For Subsequent Colorectal Malignancies, Casey Leigh Daniel

All ETDs from UAB

Childhood cancer survivors who were treated with ionizing radiation are at a significantly higher risk of developing a subsequent colorectal cancer (CRC) compared to the general population. The Children's Oncology Group (COG) recommends that children and adolescents who were treated with radiation therapy of 30 Gy or more to the abdomen, pelvis, or spine undergo a colonoscopy every five years, beginning at age 35 or 10 years after completion of radiation. Despite these recommendations, research indicates low adherence rates to CRC screening among high-risk childhood cancer survivors. Determining the predictors of attending subsequent colorectal cancer surveillance among individuals in this …

Clinical Consequences Of Micrornas In Colorectal Cancer, Liselle C. Bovell

All ETDs from UAB

Colorectal cancer (CRC) is a heterogeneous disease, and factors such as tumor location, the environment, genetics, and ethnic differences, can influence its development and progression. Over the last few decades, overall CRC mortality rates have declined; however, racial disparities in mortality rates have increased. The discovery of biomarkers that focus on identifying individual differences based on confounders such as tumor stage and patient race/ethnicity is needed, for such biomarkers can lead to development of personalized therapeutic approaches to target these molecules. MicroRNAs (miRNAs) are a class of small molecules that regulate genes at the post-transcriptional level. Altered miRNA expression levels …

Association Between Cruciferous Vegetable Intake And Risk Of Colorectal Cancer Among Men In Shanghai, China, Emily Vogtmann

All ETDs from UAB

Colorectal cancer (CRC) is a major global health concern and the intake of certain foods, such as cruciferous vegetables, has been studied for their potential protective effects against cancer development. The observed association between cruciferous vegetable consumption and CRC has been inconsistent, possibly related to glutathione S-transferase (GST) gene polymorphisms. Therefore, we aimed to (1) evaluate the association between fruits and vegetables, including cruciferous vegetables, on the risk of CRC; (2) determine factors associated with urinary isothiocyanate (ITC), a biomarker of cruciferous vegetable intake; and (3) evaluate the association between cruciferous vegetable consumption and CRC and to estimate the potential …

Impact Of Physical Activity In The Prevention Of Colorectal Cancer, Sarah Ashley Barnes

Theses and Dissertations

This review evaluates the current understanding of research on the impact of physical activity in the prevention of colorectal cancer. Current biological mechanisms implicated in physical activity and colorectal cancer risk reduction are blood glucose regulation, insulin sensitivity, leptin and adiponectin profiles, inflammation as well as secreted protein acidic and rich in cysteine (SPARC), an exercise induced myokine. Recent literature indicates that 30-60 minutes of moderate to vigorous activity a day is effective against colorectal cancer development, and there is convincing evidence of aerobic exercise as differently beneficial in recruiting mechanisms identified as preventative against colorectal cancer. This article provides …

Linking Obesity To Colorectal Cancer: Recent Insights Into Plausible Biological Mechanisms, Catherine Guffey

Theses and Dissertations

Obesity has emerged as a leading environmental risk factor for the development of CRC. However, the mechanisms underlying this relationship have not yet been fully explained. Recent literature has focused on 1) inflammatory processes, 2) adipokines, and 3) estrogen. Obesity-enhanced inflammation is largely orchestrated by increases in adipose tissue macrophages leading to the secretion of TNF-alpha, MCP-1, and IL-6, all of which are linked to CRC. Adiponectin is decreased with obesity and has been reported to be negatively associated with CRC, while leptin, which is increased, is positively associated with the disease. Estrogen has been shown to influence CRC, although …

Universal Tumor Screening For Lynch Syndrome: Identification Of System-Level Implementation Factors Influencing Patient Reach, Deborah Le Cragun

USF Tampa Graduate Theses and Dissertations

Lynch syndrome (LS) is the most prevalent cause of hereditary colorectal cancer (CRC) and confers high risks for several other types of cancer. Universal tumor screening (UTS) of all newly diagnosed patients with CRC can improve LS identification and decrease associated morbidity and mortality among patients and family members. However, for UTS to be effective, patients who screen positive must pursue genetic counseling and confirmatory germline testing (i.e., high patient reach). The purposes of this study were to characterize UTS programs, identify barriers and facilitators to implementation, document whether there have been negative outcomes, and determine institutional and implementation conditions …

Expression Of Mismatch Repair Proteins In Colorectal Cancer At Aga Khan University Hospital, Nairobi, Charles M. Wahome

Theses & Dissertations

Introduction: Microsatellite instability is one of three molecular pathways described in the pathogenesis of colorectal carcinoma. The presence of microsatellite instability in patients with colorectal cancer has implications for prognosis and family counselling. Deficiency in mismatch repair genes leads to microsatellite instability and this can be reliably demonstrated in formalin fixed paraffin embedded tissue by methods, which include immunohistochemistry for the detection of mismatch repair proteins.

Local data show a disproportionately large number of younger patients with colorectal cancer compared to that documented in Caucasians. Colorectal cancer in younger ages is often attributed to deficient mismatch repair.

The objective of …

The Role Of Host-Tumor Interactions In Liver Metastasis Of Colorectal Cancer, Yu Zhang

Theses and Dissertations

Colon cancer is the third most frequent cancer and the second leading cause of cancer deaths in the United States. Liver metastasis is the major cause of death in colon cancer. Successful metastases depend on productive collaborations between tumor cells and host-derived cells in the tumor microenvironment, target organ environments, and cells in the hematopoietic compartment.

To identify the host-tumor interactions promoting liver metastasis and their molecular and cellular mediators, an orthotopic mouse model of liver metastasis of colon cancer was established that recapitulates all stages of tumor growth and metastasis. A highly metastatic mouse carcinoma cell line CT26-FL3 was …