Medicine and Health Sciences Commons^™

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

Dissertations & 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 …

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 …

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 …

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 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.

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, …

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 …