Oncology 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 …

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.

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 …

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

Aurora Family Medicine Residents

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 …

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

Journal of Patient-Centered Research and Reviews

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 …

Colorectal Cancer On The Decline, Albert B. Lowenfels, Patrick Maisonneuve, Ravinder Mamtani

NYMC Faculty Publications

No abstract provided.

Potentially Inappropriate Medication Use In Older Patient With Breast And Colorectal Cancer, Meghan S. Karuturi

Dissertations & Theses (Open Access)

Our objective was to determine predictors of potentially inappropriate medication (PIM) use and its impact on outcomes (including ER visits, hospitalization, all cause death, and composite of three) in breast and colorectal cancer patients receiving chemotherapy. We used data from the SEER database linked to Medicare claims. Our cohort included patients ≥ 66 years diagnosed with of Stage II/III breast or colorectal cancer between 7/1/2007-12/31/2009. Baseline PIM was defined using the Drugs to Avoid in the Elderly list (DAE) or Beers criteria. Univariate and multivariable logistic regression were used to determine the associations of baseline PIMs with different covariates. Event-free …

Epigenetic Modulation In Braf Mutated Metastatic Colorectal Cancer, Van Morris

Dissertations & Theses (Open Access)

Introduction: BRAF V600E mutations are associated with poor clinical outcomes for patients with metastatic colorectal cancer (mCRC). Unlike other tumors with the same mutation, BRAF inhibitors are ineffective as monotherapy. CRC tumors with BRAF V600E mutations are associated with global hypermethylation, which may turn off tumor suppressor gene expression. We studied demethylation in BRAF V600E mCRC to restore sensitivity to BRAF inhibitors.

Methods: Tumor databanks were investigated for genes differentially expressed according to BRAF mutation status to identify genes which may be particularly susceptible to epigenetic influence. Mouse xenograft models of BRAFV600E mCRC were treated with vemurafenib or azacitidine, alone …

Bh3 Mimetic Abt-737 Sensitizes Colorectal Cancer Cells To Ixazomib Through Mcl-1 Downregulation And Autophagy Inhibition., Lifeng Yang, Juefeng Wan, Sheng Xiao, Darryll Barkhouse, Ji Zhu, Guichao Li, Bo Lu, Zhen Zhang

Department of Radiation Oncology Faculty Papers

The proteasome inhibitor MLN9708 is an orally administered drug that is hydrolyzed into its active form, MLN2238 (ixazomib). Compared with Bortezomib, MLN2238 has a shorter proteasome dissociation half-life and a lower incidence and severity of peripheral neuropathy, which makes it an attractive candidate for colorectal cancer treatment. In the present study, we observed that MLN2238 induced autophagy, as evidenced by conversion of the autophagosomal marker LC3 from LC3I to LC3II, in colorectal cancer cell lines. Mcl-1, an anti-apoptotic Bcl-2 family protein, was markedly elevated after treating a colorectal cancer cell line with MLN2238. We proved that inhibiting Mcl-1 expression enhances …

Colorectal Cancer Prevention: Perspectives Of Key Players From Social Networks In A Low-Income Rural Us Region, Nancy E. Schoenberg, Kathryn Eddens, Adam Jonas, Claire Snell-Rood, Christina R. Studts, Benjamin Broder-Oldach, Mira L. Katz

Behavioral Science Faculty Publications

Social networks influence health behavior and health status. Within social networks, “key players” often influence those around them, particularly in traditionally underserved areas like the Appalachian region in the USA. From a total sample of 787 Appalachian residents, we identified and interviewed 10 key players in complex networks, asking them what comprises a key player, their role in their network and community, and ideas to overcome and increase colorectal cancer (CRC) screening. Key players emphasized their communication skills, resourcefulness, and special occupational and educational status in the community. Barriers to CRC screening included negative perceptions of the colonoscopy screening procedure, …

Screening Of Exosomal Micrornas From Colorectal Cancer Cells, Cillian Clancy, Sonja Khan, Claire L. Glynn, Emma Holian, Peter Dockery, Pierce Lalor, James A.L. Brown, Myles Joyce, Michael J. Kerin, Roisin M. Dwyer

Forensic Science Publications

BACKGROUND: Cells release extracellular membrane vesicles including microvesicles known as exosomes. Exosomes contain microRNAs (miRNAs) however the full range within colorectal cancer cell secreted exosomes is unknown. OBJECTIVE: To identify the full range of exosome encapsulated miRNAs secreted from 2 colorectal cancer cell lines and to investigate engineering of exosomes over-expressing miRNAs. METHODS: Exosomes were isolated from HCT-116 and HT-29 cell lines. RNA was extracted from exosomes and microRNA array performed. Cells were engineered to express miR-379 (HCT-116-379) or a non-targeting control (HCT-116-NTC) and functional effects were determined. Exosomes secreted by engineered cells were transferred to recipient cells and the …

Sporadic Early Onset Colorectal Cancer In Pakistan: A Case- Control Analysis Of Microsatellite Instability, Sabeehuddin Siddique, Kanwal Tariq, Sobia Rafiq, Ahmed Raheem, Rashida Ahmed, Munira Shabbir-Moosajee, Kulsoom Ghias

Department of Pathology and Laboratory Medicine

Background: Early onset sporadic colorectal cancer (CRC) is a biologically and clinically distinct entity hypothesized to exhibit differences in histological features and microsatellite instability (MSI) as compared to typical onset CRC. This study compared the MSI status, mismatch repair enzyme deficiency and clinicopathological features of early onset (aged ≤45 years) with controls (>45 years).
Materials and Methods: A total of 30 cases and 30 controls were analyzed for MSI status using the Bethesda marker panel. Using antibodies against hMLH1, hMSH2 and hMSH6, mismatch repair protein expression was assessed by immunohistochemistry. Molecular characteristics were correlated with clinicopathological features.
Results: …

The Regulatory Function Of Sphingosine-1-Phosphate Signaling Axis On Regulatory T Cells In Colorectal Cancer, Andrew V. Nguyen, Yuan-Yuan Wu, Elaine Y. Lin

Publications and Research

In tumors associated with inflammation such as inflammatory bowel disease (IBD) and colorectal cancer (CRC), high numbers of regulatory T cells (Tregs) are associated with both favorable and poor prognoses. The functions of Tregs in CRC remain elusive and have yet to be clearly defined. With new evidence supporting many subsets of Tregs, the research on the development and functions of these cells has begun to come to fruition. The sphingosine 1 phosphate (S1P) pathway was recently reported to regulate the development and function of regulatory T cells. This pathway may shine new light into the pleiotropic nature of these …

Activation Of C-Met And Upregulation Of Cd44 Expression Are Associated With The Metastatic Phenotype In The Colorectal Cancer Liver Metastasis Model, Victoria Allison Elliott, Piotr G. Rychahou, Yekaterina Y. Zaytseva, B. Mark Evers

Markey Cancer Center Faculty Publications

Background

Liver metastasis is the most common cause of death in patients with colorectal cancer. Despite extensive research into the biology of cancer progression, the molecular mechanisms that drive colorectal cancer metastasis are not well characterized.

Methods

HT29 LM1, HT29 LM2, HT29 LM3 cell lines were derived from the human colorectal cancer cell line HT29 following multiple rounds of in vivo selection in immunodeficient mice.

Results

CD44 expression, a transmembrane glycoprotein involved in cell-cell and cell-matrix adhesions, and cancer cells adhesion to endothelial cells was increased in all in vivo selected cell lines, with maximum CD44 expression and cancer cells …

Positive Patient Experiences In An Australian Integrative Oncology Centre, Bonnie J. Furzer, Anna S. Petterson, Kemi E. Wright, Karen E. Wallman, Timothy R. Ackland, David J. Joske

Research outputs 2014 to 2021

Background: The purpose of this study was to explore the experiences of cancer patients' utilising complementary and integrative therapies (CIT) within integrative oncology centres across Western Australia.Methods: Across four locations 135 patients accessed CIT services whilst undergoing outpatient medical treatment for cancer. Of the 135 patients, 66 (61 ± 12 y; female n = 45; male n = 21) agreed to complete a personal accounts questionnaire consisting of open-ended questions designed to explore patients' perceptions of CIT. All results were transcribed into nVivo (v9) and using thematic analysis, key themes were identified.Results: Of the 66 participants, 100% indicated they would …

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 …

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. …

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, …

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 …

Ron - The Con In Colorectal Carcinoma, Shikha Tarang, J. Wang

Journal Articles: Eppley Institute

The recepteur d’origine nantais (RON) is a member of MET family of receptor tyrosine kinase (RTKs), an overexpression of which has been observed in several cancers. The expression of RON gene is required during embryonic development and also plays critical roles in regulating macrophage inflammatory response. In CRC, the overexpression of moderate RON activity contributes to their oncogenic potential by regulating several key processes such as proliferation, motility and resistance to apoptosis. Interestingly, an aberrant RON expression is often associated with the generation of several splice variants with unique transforming activities. The targeting of RON signaling pathway by the use …

A Conserved Tissue-Specific Homeodomain-Less Isoform Of Meis1 Is Downregulated In Colorectal Cancer., Richard C Crist, Jacquelyn J Roth, Scott A Waldman, Arthur M Buchberg

Department of Microbiology and Immunology Faculty Papers

Colorectal cancer is one of the most common cancers in developed nations and is the result of both environmental and genetic factors. Many of the genetic lesions observed in colorectal cancer alter expression of homeobox genes, which encode homeodomain transcription factors. The MEIS1 homeobox gene is known to be involved in several hematological malignancies and solid tumors and recent evidence suggests that expression of the MEIS1 transcript is altered in colorectal cancer. Despite this potential connection, little is known about the role of the gene in the intestines. We probed murine gastrointestinal tissue samples with an N-terminal Meis1 antibody, revealing …

Prediction And Testing Of Biological Networks Underlying Intestinal Cancer, Vishal N. Patel, Gurkan Bebek, Mark R. Chance

Faculty Scholarship

Colorectal cancer progresses through an accumulation of somatic mutations, some of which reside in so-called "driver" genes that provide a growth advantage to the tumor. To identify points of intersection between driver gene pathways, we implemented a network analysis framework using protein interactions to predict likely connections - both precedented and novel - between key driver genes in cancer. We applied the framework to find significant connections between two genes, Apc and Cdkn1a (p21), known to be synergistic in tumorigenesis in mouse models. We then assessed the functional coherence of the resulting Apc-Cdkn1a network by engineering in vivo single node …

Effects Of Colon Cancer Risk Counseling For First-Degree Relatives, Karen Glanz, Alana D. Steffen, Lauren Taglialatela

Faculty and Research Publications

Background: Individuals with a first-degree relative who has had colorectal cancer are at increased risk for colorectal cancer and thus can benefit from early detection. Tailored risk counseling may increase adherence to screening guidelines in these persons. The present study evaluated a culturally sensitive Colon Cancer Risk Counseling (CCRC) intervention for relatives of colorectal cancer patients.

Methods: A randomized trial evaluated personalized CCRC sessions with print materials and follow-up phone calls compared with a comparable General Health Counseling (GHC) intervention. One hundred and seventy-six siblings and children of colorectal cancer patients, living in Hawaii, were assessed at baseline and 4 …

Immune Response To The Carcinoembryonic Antigen In Patients Treated With An Anti-Idiotype Antibody Vaccine, Kenneth A. Foon, Mala Chakraborty, William J. John, Amanda Sherratt, Heinz Köhler, Malaya Bhattacharya-Chatterjee

Markey Cancer Center Faculty Publications

We have generated an IgG1 murine monoclonal anti-idiotype antibody (Ab2) designated 3H1, which mimics a specific epitope on the carcinoembryonic antigen (CEA). Patients with CEA positive tumors are immunologically "tolerant" to CEA. We used 3H1 as a surrogate for CEA for vaccine therapy of 12 patients with advanced colorectal cancer. Each of the patients received a minimum of four intracutaneous injections of aluminum hydroxide precipitated 3H1 at either 1, 2, or 4 mg dosage per injection. 9 of 12 patients demonstrated anti-anti-idiotypic (Ab3) response to 3H1. All nine patients generated specific anti-CEA antibody demonstrated by reactivity with radiolabeled purified CEA; …