Medicine and Health Sciences Commons^™

Impact Of Kras/Nras Mutational Heterogeneity On Clinical Outcomes In Colorectal Cancer, Jonathan M. Loree

Dissertations and Theses (Open Access)

Introduction: Mutations in KRAS/NRAS (RAS) predict a lack of benefit from anti-EGFR agents in metastatic colorectal cancer (mCRC). As next generation sequencing (NGS) has advanced, we are discovering atypical and low allele frequency mutations. We aimed to evaluate how NGS can optimally define RAS mutant CRC and the role of relative mutant allele frequency (rMAF) as a biomarker.

Methods: Using institutional and public cohorts of mCRC patients with NGS results, we described the prevalence and clinical impact of atypical (not in current guidelines) and low rMAF RAS mutations (RAS MAF by the MAF of the mutated gene with …

The Role Of Pre-Existing Type 2 Diabetes Mellitus In Colorectal Cancer Stage And Survival In Elderly Americans: A Seer-Medicare Population-Based Study 2002-~2011, Sanae El Ibrahimi

UNLV Theses, Dissertations, Professional Papers, and Capstones

Diabetes is a common comorbid condition among colorectal cancer (CRC) patients, yet its effects in CRC outcomes, particularly stage at diagnosis, risk of death and variations by diabetes severity (complications vs no complications) and Hispanic ethnicity have not been adequately studied. The purpose of this study was to investigate the association between pre-existing T2DM and advanced stage at diagnosis in elderly patients with CRC; to examine whether diabetes is an independent predictor of poor survival from all-cause and CRC-specific mortality; to assess whether variations exist by diabetes severity and to analyze the outcomes for the Hispanic group.

The Surveillance Epidemiology …

Identifying And Targeting Age-Related Colorectal Cancer Screening Rate Disparities In Family Medicine Residency Clinics, Jonathan J. Blaza, Jasmine R. Wiley, Matthew Gill, Alonzo Jalan, Will Lehmann, Deborah Simpson, Jeffrey A. Stearns

Journal of Patient-Centered Research and Reviews

Background: Health care systems continuously seek to improve patient care through population-level analysis of clinical quality metrics and patient characteristics to identify disparities in care. Nationally, disparities in colorectal cancer (CRC) screening rates have been identified with lower screening rates reported for patients who are uninsured and/or lower socioeconomic status, African American/black, Asian, and non-English-speaking Hispanic patients. No age-related CRC screening rate disparities with associated interventions have been reported.

Purpose: Determine and address CRC screening disparities in care provided to eligible patients > 50 years old in two primary care residency clinics.

Methods: Retrospective analysis using REAL-G (race, ethnicity, age, preferred …

Generalized Linear Mixed Model Analysis Of Urban-Rural Differences In Social And Behavioral Factors For Colorectal Cancer Screening, Ke-Sheng Wang, Xuefeng Liu, Muyiwa Ategbole, Xin Xie, Ying Liu, Chun Xu, Changchun Xie, Zhanxin Sha

Health & Biomedical Sciences Faculty Publications and Presentations

Objective: Screening for colorectal cancer (CRC) can reduce disease incidence, morbidity, and mortality. However, few studies have investigated the urban-rural differences in social and behavioral factors influencing CRC screening. The objective of the study was to investigate the potential factors across urban-rural groups on the usage of CRC screening.

Methods: A total of 38,505 adults (aged ≥40 years) were selected from the 2009 California Health Interview Survey (CHIS) data - the latest CHIS data on CRC screening. The weighted generalized linear mixed-model (WGLIMM) was used to deal with this hierarchical structure data. Weighted simple and multiple mixed logistic regression analyses …

Dietary Inflammatory Index And Colorectal Cancer Risk – A Meta-Analysis, Nitin Shivappa, Justyna Godos, James R. Hébert, Michael David Wirth, Gabriele Piuri, Attilio Speciani, Giuseppe Grosso

Faculty Publications

Diet and chronic inflammation of the colon have been suggested to be risk factors in the development of colorectal cancer (CRC). The possible link between inflammatory potential of diet, measured through the Dietary Inflammatory Index (DII®), and CRC has been investigated in several populations across the world. The aim of this study was to conduct a meta-analysis on studies exploring this association. Data from nine studies were eligible, of which five were case-control and four were cohort studies. Results from meta-analysis showed a positive association between increasing DII scores, indicating a pro-inflammatory diet, and CRC. Individuals in the highest versus …

Readability Of Colorectal Cancer Online Information: A Brief Report, Corey Basch, Danna Ethan, Sarah A. Maclean, Philip Garcia, Charles E. Basch

Publications and Research

Purpose: Colorectal cancer (CRC) is the third leading cause of cancer-related death in the United States. A decline in deaths caused by CRC has been largely attributable to screening and prompt treatment. Motivation, shown to influence cancer-related screening and treatment decisions, can be shaped by information from the Internet. The extent to which this information is easily readable on cancer-related websites is not known. The purpose of this study was to assess the readability levels of CRC information on 100 websites.

Methods: Using methods from a prior study, the keyword, “colorectal cancer,” was searched on a cleared Internet browser. Scores …

The Heat-Stable Enterotoxin Receptor, Guanylyl Cyclase C, As A Pharmacological Target In Colorectal Cancer Immunotherapy: A Bench-To-Bedside Current Report., Trevor R. Baybutt, Allison A. Aka, Adam E. Snook

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Cancer immunotherapy is becoming a routine treatment modality in the oncology clinic, in spite of the fact that it is a relatively nascent field. The challenge in developing effective immunotherapeutics is the identification of target molecules that promote anti-tumor efficacy across the patient population while sparing healthy tissue from damaging autoimmunity. The intestinally restricted receptor guanylyl cyclase C (GUCY2C) is a target that has been investigated for the treatment of colorectal cancer and numerous animal, and clinical studies have demonstrated both efficacy and safety. Here, we describe the current state of GUCY2C-directed cancer immunotherapy and the future directions of this …

St-Producing E. Coli Oppose Carcinogen-Induced Colorectal Tumorigenesis In Mice., Peng Li, Jieru E. Lin, Adam E. Snook, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

There is a geographic inequality in the incidence of colorectal cancer, lowest in developing countries, and greatest in developed countries. This disparity suggests an environmental contribution to cancer resistance in endemic populations. Enterotoxigenic bacteria associated with diarrheal disease are prevalent in developing countries, including enterotoxigenic E. coli (ETEC) producing heat-stable enterotoxins (STs). STs are peptides that are structurally homologous to paracrine hormones that regulate the intestinal guanylyl cyclase C (GUCY2C) receptor. Beyond secretion, GUCY2C is a tumor suppressor universally silenced by loss of expression of its paracrine hormone during carcinogenesis. Thus, the geographic imbalance in colorectal cancer, in part, may …

Mk2 Promotes Colorectal Cancer Development, Invasion, And Growth Through Mk2-Induced Cytokines, Anita Lynne Ray

Biomedical Sciences ETDs

Colorectal cancer (CRC) is the third most common malignancy in the United States for men and women. A major risk factor for CRC development and progression is inflammation, in particular the inflammatory cytokines IL-1, IL-6, and TNF-α. These proteins promote critical cancer functions, such as proliferation, invasion, survival, and migration. Control of inflammation is one potential area of therapeutic intervention for some cancers. Because signaling of these cytokines overlaps in many of the same pathways, targets upstream of protein production could prove an effective strategy to reduce inflammation. MAPK-activated protein kinase 2 (MK2) pathway controls production of these cytokines within …

Trends And Determinants Of Up-To-Date Status With Colorectal Cancer Screening In Tennessee, 2002-2008, Sreenivas P. Veeranki, Shimin Zheng

Shimin Zheng

BACKGROUND: Screening rates for colorectal cancer (CRC) are increasing nationwide including Tennessee (TN); however, their up-to-date status is unknown. The objective of this study is to determine the trends and characteristics of TN adults who are up-to-date status with CRC screening during 2002-2008. METHODS: We examined data from the TN Behavioral Risk Factor Surveillance System for 2002, 2004, 2006 and 2008 to estimate the proportion of respondents aged 50 years and above who were up-to-date status with CRC screening, defined as an annual home fecal occult blood test and/or sigmoidoscopy or colonoscopy in the past 5 years. We identified trends …

Guanylate Cyclase C As A Target For Prevention, Detection, And Therapy In Colorectal Cancer., Allison A. Aka, Jeff A. Rappaport, Amanda M. Pattison, Takami Sato, Adam E. Snook, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

INTRODUCTION: Colorectal cancer remains the second leading cause of cancer death in the United States, and new strategies to prevent, detect, and treat the disease are needed. The receptor, guanylate cyclase C (GUCY2C), a tumor suppressor expressed by the intestinal epithelium, has emerged as a promising target. Areas covered: This review outlines the role of GUCY2C in tumorigenesis, and steps to translate GUCY2C-targeting schemes to the clinic. Endogenous GUCY2C-activating ligands disappear early in tumorigenesis, silencing its signaling axis and enabling transformation. Pre-clinical models support GUCY2C ligand supplementation as a novel disease prevention paradigm. With the recent FDA approval of the …

Validation Of Standard Operating Procedures In A Multicenter Retrospective Study To Identify-Omics Biomarkers For Chronic Low Back Pain, Concetta Dagostino, Manuela De Gregori, Christian Gieger, Judith Manz, Ivan Gudelj, Gordon Lauc, Laura Divizia, Wei Wang, Moira Sim, Iain K. Pemberton, Jane Macdougall, Frances Williams, Jan Vn Zundeert, Dragan Primorac, Yurii Aulchenko, Leonardo Kapural, Massimo Allegri

Research outputs 2014 to 2021

Chronic low back pain (CLBP) is one of the most common medical conditions, ranking as the greatest contributor to global disability and accounting for huge societal costs based on the Global Burden of Disease 2010 study.

Large genetic and -omics studies provide a promising avenue for the screening, development and validation of biomarkers useful for personalized diagnosis and treatment (precision medicine). Multicentre studies are needed for such an effort, and a standardized and homogeneous approach is vital for recruitment of large numbers of participants among different centres (clinical and laboratories) to obtain robust and reproducible results. To date, no validated …

Fluorinated N,N'-Diarylureas As Novel Therapeutic Agents Against Cancer Stem Cells, Dasha E. Kenlan, Piotr G. Rychahou, Vitaliy M. Sviripa, Heidi L. Weiss, Chunming Liu, David S. Watt, B. Mark Evers

Markey Cancer Center Faculty Publications

Colorectal cancer is the second-leading cause of cancer-related mortality in the United States. More than 50% of patients with colorectal cancer will develop local recurrence or distant organ metastasis. Cancer stem cells play a major role in the survival and metastasis of cancer cells. In this study, we examined the effects of novel AMP-activated protein kinase (AMPK) activating compounds on colorectal cancer metastatic and stem cell lines as potential candidates for chemotherapy. We found that activation of AMPK by all fluorinated N,N-diarylureas (FND) compounds at micromolar levels significantly inhibited the cell-cycle progression and subsequent cellular proliferation. In addition, we demonstrated …

Role Of Modern Immunotherapy In Gastrointestinal Malignancies: A Review Of Current Clinical Progress, Zin W. Myint, Gaurav Goel

Markey Cancer Center Faculty Publications

Gastrointestinal (GI) cancers are a group of highly aggressive malignancies with a huge disease burden worldwide. There is clearly a significant unmet need for new drugs and therapies to further improve the treatment outcomes of GI malignancies. Immunotherapy is a novel treatment strategy that is emerging as an effective and promising treatment option against several types of cancers. CTLA-4 and PD-1 are critical immune checkpoint molecules that negatively regulate T cell activation via distinct mechanisms. Immune checkpoint blockade with antibodies directed against these pathways has already shown clinical efficacy that has led to their FDA approval in the treatment of …

Identifying Disparities In Colorectal Cancer Screening Rates In Milwaukee-Based Academic And Nonacademic Clinics, Jasmine Wiley, Jonathan J. Blaza, Will Lehmann, Deborah Simpson, Jeffrey A. Stearns, Shelby L. Pischke, Tracy L. Greiten

Will Lehmann, MD

Background: The Institute for Healthcare Improvement’s Triple Aim focuses on improving the patient’s experience of care, improving population health and reducing the per capita cost of health care. Health care systems and providers continuously seek to improve quality of care through understanding what percentage of their patients are achieving quality-of-care standards for various indicators, including immunizations, tobacco cessation, asthma and cancer screening. As health care moves toward reimbursing for value-based care, deepening our understanding of patient population characteristics within each of these conditions is vital to continuous quality improvement.

Purpose: To determine if there are race/ethnicity/age/preferred language (REAL) disparities in …

A Systematic Review Of Geographical Differences In Management And Outcomes For Colorectal Cancer In Australia, Michael J. Ireland, Sonja March, Fiona Crawford-Williams, Joanne F. Aitken, Melissa K. Hyde, Suzanne K. Chambers, Jiandong Sun, Jeff Dunn

Research outputs 2014 to 2021

Background:

Australia and New Zealand have the highest incidence of colorectal cancer (CRC) in the world, presenting considerable health, economic, and societal burden. Over a third of the Australian population live in regional areas and research has shown they experience a range of health disadvantages that result in a higher disease burden and lower life expectancy. The extent to which geographical disparities exist in CRC management and outcomes has not been systematically explored. The present review aims to identify the nature of geographical disparities in CRC survival, clinical management, and psychosocial outcomes.

Methods:

The review followed PRISMA guidelines and searches …

A Comparison Between Lynch Syndrome And Sporadic Colorectal Cancer Survivors’ Satisfaction With Their Healthcare Providers, Allison M. Burton-Chase, Wendy M. Parker, Katrina M. Polivka, Ellen R. Gritz

Dartmouth Scholarship

This study evaluated provider satisfaction in a sample of colorectal cancer (CRC) survivors with and without Lynch syndrome (LS). Participants were case–case-matched CRC survivors with (n=75) or without (n=75) LS (mean age of 55; range: 27–93). Participants completed a mailed questionnaire assessing demographics, clinical characteristics, healthcare utilization, psychosocial variables, and provider satisfaction. LS CRC survivors reported lower provider satisfaction scores on three subscales of the Primary Care Assessment Survey: communication (78.14 vs. 83.96; P<0.05), interpersonal treatment (78.58 vs. 85.30; P<0.05), and knowledge of the patient (60.34 vs. 69.86; P<0.01). Among LS CRC survivors, predictors for mean communication and trust subscale scores were location of treatment and socioeconomic status. Higher mean depression scores also were associated with trust, while social support predicted higher satisfaction with communication. Sporadic CRC survivor satisfaction is driven largely by age (communication, interpersonal treatment) and patient anxiety (communication), while seeing a provider more often was associated with increased satisfaction with knowledge of the patient. LS CRC survivors reported lower levels of provider satisfaction than sporadic CRC survivors. LS survivors who received care at The University of Texas MD Anderson Cancer Center, a comprehensive cancer center (CCC), reported higher satisfaction than those receiving care at other institutions. Depressive symptoms and socioeconomic status may impact provider satisfaction ratings. Exploration of other potential predictors of provider satisfaction should be examined in this population. Additionally, further research is needed to examine the potential impact of provider satisfaction on adherence to medical recommendations in LS CRC survivors, particularly those being treated outside of CCCs.

Optimizing Patient Risk Stratification For Colonoscopy Screening And Surveillance Of Colorectal Cancer: The Role For Linked Data, David B. Preen, Iris Lansdorp-Vogelaar, Hooi C. Ee, Cameron Platell, Dayna R. Cenin, Lakkhina Troeung, Max Bulsara, Peter O'Leary

Health Sciences Papers and Journal Articles

No abstract available for this article.

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, …

Polymorphisms Of Cancer-Related Genes And Risk Of Multipleprimary Malignancies Involving Colorectal Cancer, Peiguo Cao, Li Yu, Anshan Wu, Jingjing Li, Ling Liu, Chunlan Liu, Jianda Zhou, Ke Cao, Chengxian Guo

Turkish Journal of Medical Sciences

Background/aim: This study aimed to investigate the relationship between single nucleotide polymorphisms (SNPs) of cancer-related genes and the risk of multiple primary malignancies involving colorectal cancer.Materials and methods: We collected tissue samples from 22 multiple primary cancer patients with primary colorectal cancer and performed genotyping assay for 116 SNP loci from 62 genes encoding peptides functioning in various signaling pathways using the DNA MassARRAY system. The chi-square test was used to compare the differences in base frequencies between patients and a control Chinese population from HapMap through the NCBI database.Results: No significant differences in frequencies were detected for 81 SNPs …

Serum Peptidome Profiling For The Diagnosis Of Colorectal Cancer: Discovery And Validation In Two Independent Cohorts, Hao Wang, Chenghua Luo, Shengtao Zhu, Honghong Fang, Qing Gao, Siqi Ge, Haixia Qu, Qingwei Ma, Hongwei Ren, Youxin Wang, Wei Wang

Research outputs 2014 to 2021

Colorectal cancer (CRC) is one of the most common malignant neoplasms worldwide. Except for the existing fecal occult blood test, colonoscopy and sigmoidoscopy, no widely accepted in vitro diagnostic methods have been available. To identify potential peptide biomarkers for CRC, serum samples from a discovery cohort (100 CRC patients and 100 healthy controls) and an independent validation cohort (91 CRC patients and 91 healthy controls) were collected. Peptides were fractionated by weak cation exchange magnetic beads (MB-WCX) and analysed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDITOF MS). Five peptides (peaks at m/z 1895.3, 2020.9, 2080.7, 2656.8 and 3238.5) were …

Evaluation Of Risk Factors For The Recurrence Of Colorectal Polyps And Colorectal Cancer, Öztürk Ateş, Bülent Si̇vri̇, Saadetti̇n Kiliçkap

Turkish Journal of Medical Sciences

Background/aim: Colorectal adenomatous polyps are precursors of colorectal cancer (CRC), which can be prevented with surveillance colonoscopy. This study aimed to assess risk factors for the recurrence of colorectal polyps and CRC following polypectomy. Materials and methods: In this single-center trial, a total of 510 patients who applied to the endoscopy unit of Hacettepe University Hospital for various reasons and who were diagnosed with at least one colorectal adenomatous polyp between 2000 and 2010 were retrospectively analyzed. Patients with colorectal adenomatous polyps or CRC recurrences were examined in terms of clinical and histological risk factors. Results: A total of 190 …

Type 2 Diabetes Mellitus And Colorectal Cancer Risk And Survival In Oman, Rose Ngozi Mafiana

Walden Dissertations and Doctoral Studies

Type 2 diabetes mellitus (T2DM) and colorectal cancer (CRC) are 2 chronic diseases with common risk factors related to physical inactivity, obesity, and diet. Literature on T2DM as a risk factor for CRC development and survival in Oman is scarce. Using de-identified archival data provided by Sultan Qaboos University Hospital (SQUH) Oman, a retrospective, case-control, and time-to-event study designs were used to compare odds of developing CRC, and survival rates among adults with and without T2DM. The ecosocial theory provided the theoretical base for this research. Logistic regression was used to examine the odds of developing CRC among 114 cases …