Medicine and Health Sciences Commons^™

Biomarkers In The Development Of Individualized Treatment Regimens For Colorectal Cancer, Madison Crutcher, Scott A Waldman

Department of Surgery Faculty Papers

Introduction: Colorectal cancer (CRC) is the third most common and second most deadly malignancy in the world with an estimated 1. 9 million cases and 0.9 million deaths in 2020. The 5-year overall survival for stage I disease is 92% compared to a dismal 11% in stage IV disease. At initial presentation, up to 35% of patients have metastatic colorectal cancer (mCRC), and 20-50% of stage II and III patients eventually progress to mCRC. These statistics imply both that there is a proportion of early stage patients who are not receiving adequate treatment and that we are not adequately treating …

P118. Colonic Stent Presenting With Stent Impaction And Erosion Through The Colonic Wall, Benjamin Randall Hart, Jon Hain

Conference Presentation Abstracts

Background: Colonic stenting has been shown to be effective as a palliative measure in colorectal cancer when

patients present with obstructing symptoms. However, its efficacy when used for complications of colonic anastomoses are less well-studied. We present a case report of an elderly gentleman with a colonic stent placed for anastomotic stricture, which led to stent migration stent impaction with erosion in the sigmoid colon.

A 92-year-old gentleman presented to the ED with several days worth of nausea and vomiting. He had recently undergone a partial colectomy with an ileocolonic anastomosis approximately one year prior and then had a covered …

Upregulation Of Cd36, A Fatty Acid Translocase, Promotes Colorectal Cancer Metastasis By Increasing Mmp28 And Decreasing E-Cadherin Expression, James Drury, Piotr G. Rychahou, Courtney O. Kelson, Mariah E. Geisen, Yuanyuan Wu, Daheng He, Chi Wang, Eun Y. Lee, B. Mark Evers, Yekaterina Y. Zaytseva

Surgery Faculty Publications

Altered fatty acid metabolism continues to be an attractive target for therapeutic intervention in cancer. We previously found that colorectal cancer (CRC) cells with a higher metastatic potential express a higher level of fatty acid translocase (CD36). However, the role of CD36 in CRC metastasis has not been studied. Here, we demonstrate that high expression of CD36 promotes invasion of CRC cells. Consistently, CD36 promoted lung metastasis in the tail vein model and GI metastasis in the cecum injection model. RNA-Seq analysis of CRC cells with altered expression of CD36 revealed an association between high expression of CD36 and upregulation …

Spermine Synthase And Myc Cooperate To Maintain Colorectal Cancer Cell Survival By Repressing Bim Expression, Yubin Guo, Qing Ye, Pan Deng, Yanan Cao, Daheng He, Zhaohe Zhou, Chi Wang, Yekaterina Y. Zaytseva, Charles E. Schwartz, Eun Young Lee, B. Mark Evers, Andrew J. Morris, Side Liu, Qing-Bai She

Markey Cancer Center Faculty Publications

Dysregulation of polyamine metabolism has been linked to the development of colorectal cancer (CRC), but the underlying mechanism is incompletely characterized. Here, we report that spermine synthase (SMS), a polyamine biosynthetic enzyme, is overexpressed in CRC. Targeted disruption of SMS in CRC cells results in spermidine accumulation, which inhibits FOXO3a acetylation and allows subsequent translocation to the nucleus to transcriptionally induce expression of the proapoptotic protein Bim. However, this induction is blunted by MYC-driven expression of miR-19a and miR-19b that repress Bim production. Pharmacological or genetic inhibition of MYC activity in SMS-depleted CRC cells dramatically induces Bim expression and apoptosis …

Tumor Heterogeneity As A Predictor Of Response To Neoadjuvant Chemotherapy In Locally Advanced Rectal Cancer, Alissa Greenbaum, David R. Martin, Therese J. Bocklage, Ji-Hyun Lee, Scott A. Ness, Ashwani Rajput

Pathology and Laboratory Medicine Faculty Publications

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) is the standard of care for locally advanced adenocarcinoma of the rectum, but it is currently unknown which patients have disease that will respond. This study tested the correlation between response to nCRT and intratumoral heterogeneity using next-generation sequencing assays.

PATIENTS AND METHODS: DNA was extracted from formalin-fixed, paraffin-embedded biopsy samples from a cohort of patients with locally advanced rectal adenocarcinoma (T3/4 or N1/2 disease) who received nCRT. High read-depth sequencing of > 400 cancer-relevant genes was performed. Tumor mutations and variant allele frequencies were used to calculate mutant-allele tumor heterogeneity (MATH) scores as measures of intratumoral …

Impact Of The Affordable Care Act On Colorectal Cancer Screening, Incidence, And Survival In Kentucky, Tong Gan, Heather F. Sinner, Samuel C. Walling, Quan Chen, Bin Huang, Thomas C. Tucker, Jitesh A. Patel, B. Mark Evers, Avinash S. Bhakta

Surgery Faculty Publications

Background

Kentucky ranks first in the US in cancer incidence and mortality. Compounded by high poverty levels and a high rate of medically uninsured, cancer rates are even worse in Appalachian Kentucky. Being one of the first states to adopt the Affordable Care Act (ACA) Medicaid expansion, insurance coverage markedly increased for Kentucky residents. The purpose of our study was to determine the impact of Medicaid expansion on colorectal cancer (CRC) screening, diagnosis, and survival in Kentucky.

Study Design

The Kentucky Cabinet for Health and Family Services and the Kentucky Cancer Registry were queried for individuals (≥20 years) undergoing CRC …

Stage Of Disease And Likelihood Of Surgical Intervention In Colon Cancer Patients: An Exploratory Analysis Of The Seer Database, R. Denneny, D. Delgado, V. Nguyen, J. Subramoney, B. George, E. Mitchell, Md

Phase 1

Introduction/Objectives: Colorectal cancer (CRC) remains as the third-leading cause of cancer-related deaths amongst both men and women in the United States. However, the mortality rate from CRC continues to drop, which has been attributed to increased surgical polyp removal. This study explored the association between disease stage and the likelihood of surgical intervention as primary treatment for the disease.

Methods: Retrospective cohort study analysis using de-identified patient data from the NCI’s Surveillance, Epidemiology, and End Results (SEER) database from 1998-2015. Inclusion criteria included patients with colon cancer, over 18 years of age, with known disease in either the proximal or …

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 …