Medicine and Health Sciences Commons^™

Identifying And Targeting Cancer Stem Cells In Colorectal Cancer, Amber Harnett

Electronic Thesis and Dissertation Repository

The cancer stem cell hypothesis posits that cancer stem cells (CSCs) are the driving force behind tumour progression and metastasis, making them ideal therapeutic targets. Previous research identified Leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) as a marker of CSCs in colorectal cancer (CRC). However, it is not known whether more than one CSC population exists in CRC. Identifying and targeting CSCs in CRC is important for effective treatment of cancer patients. Here, I show that Keratin-19 (K19) labels intestinal CSCs in mouse tumours that recapitulate the early stages of CRC. Moreover, selective ablation of Lgr5 has no effect on tumour …

The Impact Of Mental Health On Cancer Preventative Screenings, Chelsea Edirisuriya, Amy Leader, Phd

Phase 1

Among the mental health population of the United States, overall preventative health services, such as cancer screening rates, are remarkably low. Additionally, there is a significant 30% higher mortality rate due to cancer in psychiatric patients. This project established if there are disparities in cancer screening rates between the general population and the mental health population of Southeastern Pennsylvania. The project analyzed and compared the differences in cancer screenings for colorectal, breast, and cervical cancer among those currently diagnosed with a mental condition and the general population. Through p-value and Pearson chi-square statistical analysis of the Community Health Data Base …

A Learning Community Approach To Identifying Interventions In Health Systems To Reduce Colorectal Cancer Screening Disparities., Lillian C. Man, Melissa Dicarlo, Emily Lambert, Randa Sifri, Martha Romney, Linda Fleisher, Ronald Myers

Department of Medical Oncology Faculty Papers

Although colorectal cancer (CRC) screening in the United States has been increasing, screening rates are not optimal, and there are persistent disparities in CRC screening and mortality, particularly among minority patients. As most CRC screening takes place in primary care, health systems are well-positioned to address this important population health problem. However, most health systems have not actively engaged in identifying and implementing effective evidence-based intervention strategies that can raise CRC screening rates and reduce disparities. Drawing on the Collective Impact Model and the Interactive Systems Framework for Dissemination and Implementation, our project team applied a learning community strategy to …

The Meaning Of A Family History Of Colorectal Cancer In Black Families In The United States, Cassandra Loggins

Dissertations

The purpose of this study is to understand the meaning of a family history of colorectal cancer (CRC) for first-degree relatives of Blacks diagnosed with CRC. Even though CRC is more preventable than other cancers because of effective screening tests for prevention and early detection, Blacks experience a disproportionate burden of CRC compared to other groups. Interventions to increase CRC screening among Blacks have not produced a significant reduction in CRC disparity. Underutilization of CRC screening and low perceived risk of CRC are major factors contributing to CRC disparity. The informing methodological approach employed in this study was hermeneutic phenomenology, …

Patients Educating Health Care Providers On Lynch Syndrome, Kelsey Hennig, Barry Decoster, Rebecca Chu, Wendy Parker, Lisa Campo-Engelstein, Allison M. Burton-Chase

Patient Experience Journal

Objective: Lynch syndrome (LS) patients are at an elevated risk for early-onset cancers, including endometrial and colorectal (CRC). Prior research has shown a deficit in provider knowledge of LS, which may affect patient satisfaction and adherence to recommended screening and surveillance regimens. Studies suggest patients with LS may educate providers perceived as lacking LS knowledge; however, little is known about these interactions. The goal of this study is to assess patient-reported outcomes from clinical interactions where LS patients educate their providers.

Methods: Participants (n=55) were asked to complete an in-depth telephone interview.

Results: Out of 55 participants, …

The Anti-Cancer Effect Of Retinoic Acid Signaling In Crc Occurs Via Decreased Growth Of Aldh+ Colon Cancer Stem Cells And Increased Differentiation Of Stem Cells, Shirin R. Modarai, Anindita Gupta, Lynn M. Opdenaker, Ryan Kowash, Gabriel Masters, Vignesh Viswanathan, Tao Zhang, Jeremy Z. Fields, Bruce M. Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Background: Tumorigenesis is driven by stem cell (SC) overpopulation. BecauseALDH is both a marker for SCs in many tissues and a key enzyme in retinoid acid (RA)signaling, we studied RA signaling in normal and malignant colonic SCs.Hypothesis: RA signaling regulates growth and differentiation of ALDH+ colonicSCs dysregulation of RA signaling contributes to SC overpopulation and colorectalcancer (CRC) development.Methods: We analyzed normal and malignant colonic tissues and CRC cell linesto see if retinoid receptors (RXR &RAR) are exclusively expressed in ALDH+ SCs,and if RA signaling changes during CRC development. We determined whether RAsignaling regulates cancer SC (CSC) proliferation, differentiation, sphere formation,and …

The Guanylate Cyclase C-Cgmp Signaling Axis Opposes Intestinal Epithelial Injury And Neoplasia., Jeffrey A. Rappaport, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Guanylate cyclase C (GUCY2C) is a transmembrane receptor expressed on the luminal aspect of the intestinal epithelium. Its ligands include bacterial heat-stable enterotoxins responsible for traveler's diarrhea, the endogenous peptide hormones uroguanylin and guanylin, and the synthetic agents, linaclotide, plecanatide, and dolcanatide. Ligand-activated GUCY2C catalyzes the synthesis of intracellular cyclic GMP (cGMP), initiating signaling cascades underlying homeostasis of the intestinal epithelium. Mouse models of GUCY2C ablation, and recently, human populations harboring GUCY2C mutations, have revealed the diverse contributions of this signaling axis to epithelial health, including regulating fluid secretion, microbiome composition, intestinal barrier integrity, epithelial renewal, cell cycle progression, responses …

Genomic And Transcriptomic Landscape Of Colorectal Premalignancy, Kyle Chang

Dissertations and Theses (Open Access)

Colorectal cancer (CRC) is the third most commonly diagnosed cancer among men and women in the United States, with 3 to 5 percent of the cases diagnosed in the background of a hereditary form of the disease. Biologically, CRC is divided into two groups: microsatellite instable (MSI) and chromosomally unstable (CIN). Genomic and transcriptomic characterization of CRC has emerged from large-scale studies in recent years due to the advancement of next-generation sequencing technologies. These studies have identified key genes and pathways altered in CRC and provided insights to the discovery of therapeutic targets. Despite the wealth of knowledge acquired in …

Cancer Prevalence In Pakistan: Meta-Analysis Of Various Published Studies To Determine Variation In Cancer Figures Resulting From Marked Population Heterogeneity In Different Parts Of The Country, Romana Idress, Saira Fatima, Jamshid Abdul Ghafar, Ahmed Raheem, Zubair Ahmad

Department of Pathology and Laboratory Medicine

Background: Pakistan’s population is ethnically diverse with distinct ethnic groups inhabiting various parts of the country. Cancer statistics obtained from specific regions populated by distinct ethnic groups may vary considerably. There is no national cancer registry. To determine whether there are indeed significant statistical differences in cancer incidence and prevalence, data was recorded from different parts of Pakistan based on the ethnic composition of the population in those parts.
Methods: Ten papers (original articles) on cancer incidence and prevalence in Pakistan published in the last two decades were selected from PubMed and Google Scholar. Meta-analysis of findings of these studies …

Alcohol Consumption Promotes Colorectal Carcinoma Metastasis Via A Ccl5-Induced And Ampk-Pathway-Mediated Activation Of Autophagy, Haodong Zhao, Danlei Chen, Rui Cao, Shiqing Wang, Dandan Yu, Yakun Liu, Yu Jiang, Mei Xu, Jia Luo, Siying Wang

Pharmacology and Nutritional Sciences Faculty Publications

There is a definite relationship between alcohol consumption and colorectal cancer (CRC) development. We investigated effect of alcohol consumption on CRC patients’ progression and prognosis by utilizing epidemiological data and found patients with alcohol consumption increased risks of tumor-node-metastasis (TNM), organ metastasis and poorer prognosis. Because their tumor tissues displayed increased expression of C-C chemokine ligand 5 (CCL5), we hypothesized CCL5 might participate in cancer progression in such patients. Ethanol increased the secretion of CCL5 in two CRC cell lines, HT29 and DLD-1. Treatment with CCL5 directly increased migratory ability of these cells, whereas neutralization or knockdown of CCL5 can …

Preclinical Evaluation Of Novel Fatty Acid Synthase Inhibitors In Primary Colorectal Cancer Cells And A Patient-Derived Xenograft Model Of Colorectal Cancer, Yekaterina Y. Zaytseva, Piotr G. Rychahou, Anh-Thu Le, Timothy L. Scott, Robert M. Flight, Ji Tae Kim, Jennifer Harris, Jinpeng Liu, Chi Wang, Andrew J. Morris, Theru A. Sivakumaran, Teresa Fan, Hunter Moseley, Tianyan Gao, Eun Young Lee, Heidi L. Weiss, Timothy S. Heuer, George Kemble, B. Mark Evers

Toxicology and Cancer Biology Faculty Publications

Fatty Acid Synthase (FASN), a key enzyme of de novo lipogenesis, is upregulated in many cancers including colorectal cancer (CRC); increased FASN expression is associated with poor prognosis. Potent FASN inhibitors (TVBs) developed by 3-V Biosciences demonstrate anti-tumor activity in vitro and in vivo and a favorable tolerability profile in a Phase I clinical trial.

However, CRC characteristics associated with responsiveness to FASN inhibition are not fully understood. We evaluated the effect of TVB-3664 on tumor growth in nine CRC patient-derived xenografts (PDXs) and investigated molecular and metabolic changes associated with CRC responsiveness to FASN inhibition.

CRC cells and PDXs …

Does Sex Of The Patient Play A Role In Survival For Msi Colorectal Cancer?, Adrian Tulin, Iulian Slavu, Raluca Tulin, Lucian Alecu, Radu C. Jecan, Cristina Orlov, Cristian I. Iaciu, Dana L. Stanculeanu, Razvan Hainarosie, Silviu Pituru, Anca Pantea Stoian, Cornelia Nitipir

Journal of Mind and Medical Sciences

Microsatellite instability (MSI) is a feature of colorectal tumors that develops as a result of inactivation of the DNA mismatch repair system. It is found in about 15% of all colorectal cancers and is an important prognostic molecular marker when assessing patients with colorectal cancer. It can influence prognosis and treatment decisions in both the advanced and early stages. Although in early stages this marker suggests a favorable prognosis and presents an important argument against adjuvant treatment in stage II disease, in metastatic stages it no longer associated with such an optimistic outcome. The present trial is a prospective, single-center …

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

Will Lehmann, MD

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 …

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

Jeffrey Stearns, MD

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 …

Factors Affecting Colorectal Cancer Screening Among African-Born Immigrants In The United States, Chidoziri Chibundu

Walden Dissertations and Doctoral Studies

Despite the evidence that colorectal cancer screening is effective in reducing the incidence of and mortality from colorectal cancer, racial and ethnic disparities in colorectal cancer screening persist in the United States. African-born immigrants in the United States have lower colorectal cancer screening rates than native-born Americans. The purpose of this quantitative, retrospective, cross-sectional study was to examine how family income, health insurance status, language of interview, length of stay in the United States, perceived health status, level of education, and having a usual place for medical care affect colorectal cancer screening among African-born immigrants in the United States. The …

Can Adding Black Raspberries To The Western Diet Reduce Factors That Lead To Colorectal Cancer?, Tess Armbrust, Canyon Neal

Research on Capitol Hill

• Americans with leaky gut, or increased intestinal permeability, often develop chronic inflammation (colitis) and are at a greater risk for developing colorectal cancer (CRC).
• A poor diet, high in processed foods but low in fruits and vegetables, is another notable risk factor for CRC.
• Micronutrient supplementation reduces colitis and prevents progression to colitis associated colorectal cancer (CAC).
• Due to their high concentration of anthocyanins, black raspberries have demonstrated protective effects against inflammation in the body.
• Certain antibodies are indicative of inflammation which leads to CRC.

Perceptions Of Shared Care Among Survivors Of Colorectal Cancer From Non-English-Speaking And English-Speaking Backgrounds: A Qualitative Study, Lawrence Tan, Gisselle Gallego, Thi T.C Nguyen, Les Bokey, Jennifer Reath

Medical Papers and Journal Articles

Background: Colorectal cancer (CRC) survivors experience difficulty navigating complex care pathways. Sharing care between GPs and specialist services has been proposed to improve health outcomes in cancer survivors following hospital discharge. Culturally and Linguistically Diverse (CALD) groups are known to have poorer outcomes following cancer treatment but little is known about their perceptions of shared care following surgery for CRC. This study aimed to explore how non-English-speaking and English-speaking patients perceive care to be coordinated amongst various health practitioners.

Methods: This was a qualitative study using data from face to face semi-structured interviews and one focus group in a culturally …

Colorectal Cancer Awareness And Screening Guideline For African American Populations, Keyna Omenukor

Walden Dissertations and Doctoral Studies

Colorectal cancer is the 3rd leading cause of cancer-related deaths. Early screening

provides the best prospects for preventing the morbidity and mortality associated with the

disease. Nurses have the duty to promote health and prevent diseases. However, low rates

of colorectal cancer screening continue to be reported, especially among African

Americans who continue to suffer disproportionately from the disease. There is a need for

a culturally-sensitive clinical practice guideline that nurses can use to educate patients

appropriately on colorectal cancer. The practice focused question for this project was

designed to explore whether a culturally-sensitive clinical practice guideline to increase

colorectal …

Increasing Colorectal Cancer (Crc) Screening In Michigan, Sharde' Burton Mph

Michigan Journal of Public Health

These "Notes from the Field" serve as a report on the early detection priority of the Michigan Cancer Consortium (MCC). This article describes the colorectal cancer work-group's priorities and the results of collaborative efforts to address them.

Geographical Variations In The Clinical Management Of Colorectal Cancer In Australia: A Systematic Review, Fiona Crawford-Williams, Sonja March, Michael Ireland, Arlen Rowe, Belinda Goodwin, Melissa Hyde, Suzanne K. Chambers, Joanne Aitken, Jeff Dunn

Research outputs 2014 to 2021

Background: In Australia, cancer survival is significantly lower in non-metropolitan compared to metropolitan areas. Our objective was to evaluate the evidence on geographical variations in the clinical management and treatment of colorectal cancer (CRC).

Methods: A systematic review of published and gray literature was conducted. Five databases (CINAHL, PubMed, Embase, ProQuest, and Informit) were searched for articles published in English from 1990 to 2018. Studies were included if they assessed differences in clinical management according to geographical location; focused on CRC patients; and were conducted in Australia. Included studies were critically appraised using a modified Newcastle–Ottawa Scale. PRISMA systematic review …

Feasibility And Preliminary Efficacy Of A 10-Week Resistance And Aerobic Exercise Intervention During Neoadjuvant Chemoradiation Treatment In Rectal Cancer Patients, Favil Singh, Daniel A. Galvão, Robert Newton, Nigel A. Spry, Michael K. Baker, Dennis Taaffe

Research outputs 2014 to 2021

Background:

Neoadjuvant chemoradiation treatment (CRT) in rectal cancer patients is associated with a reduction in physical capacity, lean mass and increased fatigue. As a countermeasure to these treatment-related adverse effects, we examined the feasibility and preliminary efficacy of a 10-week exercise program during CRT.

Methods:

Ten rectal cancer patients (7 men, aged 27-70 years, body mass index = 26.4 ± 3.8 kg/m2) receiving CRT undertook supervised resistance and aerobic exercise twice weekly. Assessments were undertaken pre- and post-intervention for upper and lower body muscle strength by 1-RM, muscle endurance, physical performance tests, body composition by dual X-ray absorptiometry, quality of …

Geographic Disparities In Previously Diagnosed Health Conditions In Colorectal Cancer Patients Are Largely Explained By Age And Area Level Disadvantage, Belinda C Goodwin, Sonja March, Michael J Ireland, Fiona Crawford-Williams, Shu-Kay Ng, Peter D Baade, Suzanne K. Chambers, Joanne F Aitken, Jeff Dunn

Research outputs 2014 to 2021

Background: Geographical disparity in colorectal cancer (CRC) survival rates may be partly due to aging populations and disadvantage in more remote locations; factors that also impact the incidence and outcomes of other chronic health conditions. The current study investigates whether geographic disparity exists amongst previously diagnosed health conditions in CRC patients above and beyond age and area-level disadvantage and whether this disparity is linked to geographic disparity in CRC survival.

Methods: Data regarding previously diagnosed health conditions were collected via computer-assisted telephone interviews with a cross-sectional sample of n = 1,966 Australian CRC patients between 2003 and 2004. Ten-year survival …