Medicine and Health Sciences Commons^™

Common Variation In A Long Non-Coding Rna Gene Modulates Variation Of Circulating Tgf-Β2 Levels In Metastatic Colorectal Cancer Patients (Alliance), Julia Quintanilha, Alexander Sibley, Yingmiao Liu, Donna Niedzwiecki, Susan Halabi, Layne Rogers, Bert O'Neil, Hedy Kindler, William Kelly, Alan Venook, Howard Mcleod, Mark Ratain, Andrew Nixon, Federico Innocenti, Kouros Owzar

Department of Medical Oncology Faculty Papers

BACKGROUND: Herein, we report results from a genome-wide study conducted to identify protein quantitative trait loci (pQTL) for circulating angiogenic and inflammatory protein markers in patients with metastatic colorectal cancer (mCRC). The study was conducted using genotype, protein marker, and baseline clinical and demographic data from CALGB/SWOG 80405 (Alliance), a randomized phase III study designed to assess outcomes of adding VEGF or EGFR inhibitors to systemic chemotherapy in mCRC patients. Germline DNA derived from blood was genotyped on whole-genome array platforms. The abundance of protein markers was quantified using a multiplex enzyme-linked immunosorbent assay from plasma derived from peripheral venous …

Incidental Ring-Hyperenhancing Liver Micronodules At Ct Hepatic Arteriography-Guided Percutaneous Thermal Ablation Of Colorectal Liver Metastases, Jessica Albuquerque, Yuan-Mao Lin, Iwan Paolucci, Caleb S O'Connor, Ching-Wei Tzeng, Jean-Nicolas Vauthey, Kristy K Brock, Bruno C Odisio

Student and Faculty Publications

CT during hepatic arteriography (CTHA) is a highly sensitive imaging method for detecting colorectal liver metastases (CLMs), which supports its use during percutaneous thermal liver ablation. In contrast to its high sensitivity, its specificity for incidental small CLMs not detected at preablation cross-sectional imaging is believed to be low given the absence of specific imaging signatures and the common presence of pseudolesions. In this retrospective study of 22 patients (mean age, 55 years ± 10.6 [SD]; 63.6% male, 36.4% female) with CLMs undergoing CTHA-guided microwave percutaneous thermal ablation between November 2017 and October 2022, the authors provided a definition of …

Scutellaria Baicalensis Enhances 5-Fluorouracil-Based Chemotherapy Via Inhibition Of Proliferative Signaling Pathways, Haizhou Liu, Hui Liu, Zhiyi Zhou, Jessica Chung, Guojing Zhang, Jin Chang, Robert A Parise, Edward Chu, John C Schmitz

Abington Jefferson Health Papers

Fluoropyridine-based chemotherapy remains the most widely used treatment for colorectal cancer (CRC). In this study, we investigated the mechanism by which the natural product Scutellaria baicalensis (Huang Qin; HQ) and one of its main components baicalin enhanced 5-fluorouracil (5-FU) antitumor activity against CRC. Cell proliferation assays, cell cycle analysis, reverse-phase protein array (RPPA) analysis, immunoblot analysis, and qRT-PCR were performed to investigate the mechanism(s) of action of HQ and its active components on growth of CRC cells. HQ exhibited in vitro antiproliferative activity against drug resistant human CRC cells, against human and mouse CRC cells with different genetic backgrounds and …

Barriers To Colorectal Cancer Screening For Low-Income Hispanic Men In Urban Areas Between 50-75, Alex Vega

Rowan-Virtua Research Day

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States. Although CRC screening rates have improved in non-Hispanic whites (NHW), Hispanic adult males (HAM) aged 50-75 in urban areas continue to experience low screening rates and higher CRC morbidity and mortality. This review aims to identify the barriers to CRC screening among HAM and propose targeted interventions to increase screening rates. A comprehensive literature review was conducted using databases such as PubMed, Scopus, and Google Scholar. Key search terms included "colorectal cancer", "screening", "Hispanic adult males", "urban", "barriers", and "interventions". Factors identified include poverty, language …

Targeted Exome-Based Predictors Of Patterns Of Progression Of Colorectal Liver Metastasis After Percutaneous Thermal Ablation, Iwan Paolucci, Yuan-Mao Lin, Yoshikuni Kawaguchi, Harufumi Maki, A Kyle Jones, Marco Calandri, Scott Kopetz, Timothy E Newhook, Kristy K Brock, Jean-Nicolas Vauthey, Bruno C Odisio

Student and Faculty Publications

BACKGROUND: Percutaneous thermal ablation is a curative-intent locoregional therapy (LRT) for selected patients with unresectable colorectal liver metastasis (CLM). Several factors have been identified that contribute to local tumour control after ablation. However, factors contributing to disease progression outside the ablation zone after ablation are poorly understood.

METHODS: In this retrospective study, using next-generation sequencing, we identified genetic biomarkers associated with different patterns of progression following thermal ablation of CLM.

RESULTS: A total of 191 ablation naïve patients between January 2011 and March 2020 were included in the analysis, and 101 had genomic profiling available. Alterations in the TGFβ pathway …

Effect Of Uracil Dna Glycosylase Activity On The Efficacy Of Thymidylate Synthase Inhibitor/Hdac Inhibitor Combination Therapies In Colon Cancer, Rashmi Kulkarni, Brian P Weiser

Rowan-Virtua Research Day

Human uracil DNA glycosylase (UNG2) is responsible for removing uracil bases from DNA and initiates base excision repair pathways. Accumulation of uracil or its fluorinated analogs in DNA is one of the killing mechanisms of thymidylate synthase (TS) inhibitors in cancer cells, and depletion of UNG2 often enhances the toxicity of these anticancer drugs. We tested the effect of UNG2 KO on the efficacy of multiple TS inhibitors (5-fluorouracil, fluorodeoxyuridine, and pemetrexed) and we determined that, except for 5-fluorouracil, all other TS inhibitors were significantly more potent in UNG2 KO cells compared to wild-type HT29 cells. Interestingly, UNG2 protein levels …

Short- And Long-Term Risk Of Colorectal Adenoma Recurrence Among Whites And Blacks, Adeyinka Laiyemo, Chyke Doubeni, Hassan Brim, Hassan Ashktorab, Robert Schoen, Samir Gupta, Aline Charabaty, Elaine Lanza, Duane Smoot, Elizabeth Platz, Amanda Cross

Chyke A. Doubeni

BACKGROUND: It is unclear whether the higher burden from colorectal cancer among blacks is due to an increased biological susceptibility. OBJECTIVE: To determine whether non-Hispanic blacks (blacks) have a higher risk of adenoma recurrence than non-Hispanic whites (whites) after removal of colorectal adenoma. DESIGN: Secondary analysis of the Polyp Prevention Trial (PPT) data. SETTING: United States. PATIENTS: Patients were 1668 self-identified whites and 153 blacks who completed the 4-year trial. Of these, 688 whites and 55 blacks enrolled in a posttrial, passive Polyp Prevention Trial Continued Follow-up Study (PPT-CFS) and underwent another colonoscopy. MAIN OUTCOME MEASUREMENTS: Recurrence and location of …

Screening Colonoscopy And Risk For Incident Late-Stage Colorectal Cancer Diagnosis In Average-Risk Adults: A Nested Case-Control Study, Chyke Doubeni, Sheila Weinmann, Kenneth Adams, Aruna Kamineni, Diana Buist, Arlene Ash, Carolyn Rutter, V. Paul Doria-Rose, Douglas Corley, Robert Greenlee, Jessica Chubak, Andrew Williams, Aimee Kroll-Desrosiers, Eric Johnson, Joseph Webster, Kathryn Richert-Boe, Theodore Levin, Robert Fletcher, Noel Weiss

Chyke A. Doubeni

BACKGROUND: The effectiveness of screening colonoscopy in average-risk adults is uncertain, particularly for right colon cancer. OBJECTIVE: To examine the association between screening colonoscopy and risk for incident late-stage colorectal cancer (CRC). DESIGN: Nested case-control study. SETTING: Four U.S. health plans. PATIENTS: 1039 average-risk adults enrolled for at least 5 years in one of the health plans. Case patients were aged 55 to 85 years on their diagnosis date (reference date) of stage IIB or higher (late-stage) CRC during 2006 to 2008. One or 2 control patients were selected for each case patient, matched on birth year, sex, health plan, …

Obesity, Weight Change, And Risk Of Adenoma Recurrence: A Prospective Trial, Adeyinka Laiyemo, Chyke Doubeni, Dilhana Badurdeen, Gillian Murphy, Pamela Marcus, Robert Schoen, E. Lanza, Duane Smoot, A. Cross

Chyke A. Doubeni

BACKGROUND AND STUDY AIMS: Obesity is a risk factor for colorectal neoplasia. Lifestyle modifications, including weight loss, have been advocated to reduce the risk. However, no prospective study has evaluated whether weight loss actually affects adenoma recurrence. The aim of this study was to examine whether weight change (loss or gain) over 4 years is associated with adenoma recurrence. PATIENTS AND METHODS: A total of 1826 patients with colorectal adenoma in the Polyp Prevention Trial had their height and weight measured at baseline. Adenoma recurrence was determined by end of trial colonoscopy 4 years after study entry when patients' weights …

Factors Associated With Inadequate Colorectal Cancer Screening With Flexible Sigmoidoscopy, Adeyinka Laiyemo, Chyke Doubeni, Paul Pinsky, V. Paul Doria-Rose, Andrew Sanderson, Robert Bresalier, Joel Weissfeld, Robert Schoen, Pamela Marcus, Phillip Prorok, Christine Berg

Chyke A. Doubeni

BACKGROUND AND STUDY AIM: Inadequate colorectal cancer screening wastes limited endoscopic resources. We examined patients factors associated with inadequate flexible sigmoidoscopy (FSG) screening at baseline screening and repeat screening 3-5 years later in 10 geographically-dispersed screening centers participating in the ongoing Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

METHODS: A total of 64,554 participants (aged 55-74) completed baseline questionnaires and underwent FSG at baseline. Of these, 39,385 participants returned for repeat screening. We used logistic regression models to assess factors that are associated with inadequate FSG (defined as a study in which the depth of insertion of FSG was …

Contribution Of Behavioral Risk Factors And Obesity To Socioeconomic Differences In Colorectal Cancer Incidence, Chyke Doubeni, Jacqueline Major, Adeyinka Laiyemo, Mario Schootman, Ann Zauber, Albert Hollenbeck, Rashmi Sinha, Jeroan Allison

Chyke A. Doubeni

BACKGROUND:Health behaviors are known risk factors for colorectal cancer and are more common in low socioeconomic status (SES) populations. We evaluated the extent to which behavioral risk factors and body mass index (BMI) explain SES disparities in colorectal cancer incidence, overall and by tumor location.

METHODS: We analyzed prospective National Institutes of Health-AARP Diet and Health Study data on 506 488 participants who were recruited in 1995-1996 from six US states and two metropolitan areas and followed through 2006. Detailed baseline data on risk factors for colorectal cancer, including health behaviors, were obtained using questionnaires. SES was measured by self-reported …

Variation Of Adenoma Prevalence By Age, Sex, Race, And Colon Location In A Large Population: Implications For Screening And Quality Programs, Douglas Corley, Christopher Jensen, Amy Marks, Wei Zhao, Jolanda De Boer, Theodore Levin, Chyke Doubeni, Bruce Fireman, Charles Quesenberry

Chyke A. Doubeni

BACKGROUND and AIMS: Reliable community-based colorectal adenoma prevalence estimates are needed to inform colonoscopy quality standards and to estimate patient colorectal cancer risks; however, minimal data exist from populations with large numbers of diverse patients and examiners. METHODS: We evaluated the prevalence of adenomas detected by sex, age, race/ethnicity, and colon location among 20,792 Kaiser Permanente Northern California members >/=50 years of age who received a screening colonoscopy exam (102 gastroenterologists, years 2006-2008). RESULTS: Prevalence of detected adenomas increased more rapidly with age in the proximal colon (adjusted odds ratio [OR], 2.39; 95% confidence interval [CI], 2.05-2.80; 70-74 vs 50-54 …

Self-Reported Colorectal Cancer Screening Of Medicare Beneficiaries In Family Medicine Vs. Internal Medicine Practices In The United States: A Cross-Sectional Study, Angela (Young) Higgins, Anna R. B. Doubeni, Karon L. Phillips, Adeyinka O. Laiyemo, Becky A. Briesacher, Jennifer Tjia, Chyke A. Doubeni

Jennifer Tjia

BACKGROUND: The benefit of screening for decreasing the risk of death from colorectal cancer (CRC) has been shown, yet many patients in primary care are still not undergoing screening according to guidelines. There are known variations in delivery of preventive health care services among primary care physicians. This study compared self-reported CRC screening rates and patient awareness of the need for CRC screening of patients receiving care from family medicine (FPs) vs. internal medicine (internists) physicians.

METHODS: Nationally representative sample of non-institutionalized beneficiaries who received medical care from FPs or internists in 2006 (using Medicare Current Beneficiary Survey). The main …

Self-Reported Colorectal Cancer Screening Of Medicare Beneficiaries In Family Medicine Vs. Internal Medicine Practices In The United States: A Cross-Sectional Study, Angela Higgins, Anna Doubeni, Karon Phillips, Adeyinka Laiyemo, Becky Briesacher, Jennifer Tjia, Chyke Doubeni

Chyke A. Doubeni

BACKGROUND: The benefit of screening for decreasing the risk of death from colorectal cancer (CRC) has been shown, yet many patients in primary care are still not undergoing screening according to guidelines. There are known variations in delivery of preventive health care services among primary care physicians. This study compared self-reported CRC screening rates and patient awareness of the need for CRC screening of patients receiving care from family medicine (FPs) vs. internal medicine (internists) physicians. METHODS: Nationally representative sample of non-institutionalized beneficiaries who received medical care from FPs or internists in 2006 (using Medicare Current Beneficiary Survey). The main …

Socioeconomic Status And The Risk Of Colorectal Cancer: An Analysis Of More Than A Half Million Adults In The National Institutes Of Health-Aarp Diet And Health Study, Chyke Doubeni, Adeyinka Laiyemo, Jacqueline Major, Mario Schootman, Min Lian, Yikyung Park, Barry Graubard, Albert Hollenbeck, Rashmi Sinha

Chyke A. Doubeni

BACKGROUND: No previous prospective US study has examined whether the incidence of colorectal cancer (CRC) is disproportionately high in low socioeconomic status (SES) populations of both men and women. This study examined the relationship between both individual and area-level SES and CRC incidence, overall and by tumor location. METHODS: Data were obtained from the ongoing prospective National Institutes of Health-AARP Diet and Health Study of persons (50-71 years old) who resided in 6 US states and 2 metropolitan areas at baseline in 1995-1996. Incident CRCs were ascertained from tumor registries through December 2006. SES was measured by self-reported education and …

P53 Inhibits Alpha 6 Beta 4 Integrin Survival Signaling By Promoting The Caspase 3-Dependent Cleavage Of Akt/Pkb, Robin E. Bachelder, Mark J. Ribick, Alessandra Marchetti, Rita Falcioni, Silvia Soddu, Kathryn R. Davis, Arthur M. Mercurio

Arthur M. Mercurio

Although the interaction of matrix proteins with integrins is known to initiate signaling pathways that are essential for cell survival, a role for tumor suppressors in the regulation of these pathways has not been established. We demonstrate here that p53 can inhibit the survival function of integrins by inducing the caspase-dependent cleavage and inactivation of the serine/threonine kinase AKT/PKB. Specifically, we show that the alpha6beta4 integrin promotes the survival of p53-deficient carcinoma cells by activating AKT/PKB. In contrast, this integrin does not activate AKT/PKB in carcinoma cells that express wild-type p53 and it actually stimulates their apoptosis, in agreement with …