bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract B44: Exosomes-associated miR-3128 and miR-3613 are dysregulated in African American men with prostate cancer and correlated with poor prognosis
Authors: Ali Hamdy , Sholl Andrew B. , Lung Pei-Yau , Bustamante Juan , Zhang Jinfeng , Coffield King S. , Elmageed Zakaria Y. Abd
Published: February 2019

Background: The mortality rate of prostate cancer (PCa) is two times higher in African American (AA) than in Caucasian American (CA) men. The molecular mechanisms underlying these discrepancies among AA men have yet to be fully elucidated. We aimed to evaluate the role of exosomes (Exo)-associated microRNAs (miR-3613 and miR-3128) as epigenetic determinant for the racial disparity of PCa patients.

Methods: Exosomes were isolated from the conditioned medium of MDA-PCa-2b and E006-A (AA-origin), and PC-3 and Du-145 (CA origin) cell lines. Exo-miRs profiling was performed to study the differential expression of AA vs CA in cells. The potential candidates were validated in Exo procured from plasma of forty AA and CA PCa patients and their aged-matched healthy subjects (n=20) using real-time PCR analysis. Circulating miRs were also determined in the plasma. The sensitivity and specificity of Exo-miRs were assessed using receiver operating characteristic (ROC) curve analysis.

Results: Exosomes-associated miR-3613 and miR-3128 were downregulated (P<0.001) in PCa regarding normal subjects. These Exo-miRs were also downregulated (p<0.01) in AA versus CA PCa. Exo-miR-3128 was able to discriminate PCa patients from normal subjects (AUC=0.70) and when age and Gleason score were combined to miR-3128, the discriminatory power was increased (AUC=1.00). Exo-miR-3128 was able to segregate AA from CA PCa (AUC=0.63) and when Exo-miR-3128 combined with -miR-3613, the power was increased (AUC=0.84, P<0.01).

Conclusion: Our findings underline the role of exosomes-associated miRs in health disparity of PC. The differential expression of miRs in AA men demonstrates their potential role as prognostic markers in the context of racial disparity.

Citation Format: Hamdy Ali, Andrew B. Sholl, Pei-Yau Lung, Juan Bustamante, Jinfeng Zhang, King S. Coffield, Zakaria Y. Abd Elmageed. Exosomes-associated miR-3128 and miR-3613 are dysregulated in African American men with prostate cancer and correlated with poor prognosis [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr B44.
Abstract B50: The role of CXCL13-CXCR5 signaling in triple-negative breast cancer progression
Authors: Dill Courtney D. , Okoro Adaugo , Chen Dongquan , Lillard James W.
Published: February 2019

Triple-negative breast cancer (TNBC) is an aggressive cancer with poor prognosis and is difficult to treat. There is a major health disparity associated with TNBC; the number of fatalities associated with this disease is significantly higher in African American women compared to their Caucasian counterparts. The mechanisms behind these differences have not been entirely elucidated. There are no targeted therapies for TNBC; instead, standard therapy for this disease includes a combination of chemotherapeutic drugs: doxorubicin (DOX), paclitaxel (TAX), and/or cyclophosphamide (CTX). Even more troubling, the efficacy of standard TNBC therapies is marginal and patients eventually become resistant to this intervention. TNBC patients suffer from chemoresistance and metastasis and ultimately succumb to this disease. Understanding TNBC and its health disparity requires a better understanding of the race-specific differences in breast tumor biology, molecules leading to breast inflammation, and the mechanisms associated with TNBC chemoresistance. Chemokines and their receptors play a significant role in TNBC. Our laboratory was the first to show that CXCL13-CXCR5 signaling mediates prostate cancer cell growth, migration, invasion, and survival (1-3). We also demonstrated that CXCL13-CXCR5 signaling induces cancer progression signaling pathways PI3K, AKT, ERK, and Jun (1;4). These preliminary and published findings provide the rationale or scientific premise in support of our hypothesis that CXCL13-CXCR5 signaling promotes TNBC progression migration, invasion, proliferation, and chemoresistance. To determine whether CXCL13-CXCR5 signaling induces TNBC, the expression profile of CXCL13 and CXCR5 RNA, associated miRNAs, and cancer progression genes (epithelial mesenchymal transition [EMT] markers) will be correlated with disease-free and overall survival of TNBC patients in silico using RNA-seq datasets from the Sequence Read Archive (SRA). Fastq data set files were downloaded from SRA, checked for quality control, aligned, and normalized using open-source platforms. Hierarchical clustering, gene set enrichment analysis, disease progression analysis, and statistics were conducted using Partek Genomic Suite. Pathway enrichment analysis was conducted using Ingenuity Pathway Studios. Overall, CXCL13-CXCR5 signaling is implicated in TNBC progression, migration, and invasion.

Citation Format: Courtney D. Dill, Adaugo Okoro, Dongquan Chen, James W. Lillard, Jr.. The role of CXCL13-CXCR5 signaling in triple-negative breast cancer progression [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr B50.
Abstract B56: Regulation of CXCR5-CXCL13 signaling in prostate cancer etiologic disparities
Authors: Ohandjo Adaugo Queen , Dill Courtney , Dongquan Chen , Lillard James W.
Published: February 2019

The prevalence of prostate cancer (PCa) has been a worldwide burden. Cancer of the prostate is the most prevalent form of cancer in men and the second leading cause of death due to cancer in men in the United States and Europe. There is a major health disparity associated with PCa; the number of fatalities associated with this disease is more significant in African-American (AA) men than in European American (EA) men. Disease progression occurs despite hormone ablation therapy, which leads to a condition called castration-resistant prostate cancer (CRPC). Further complicating the matter, CRPC is a disease that affects a variety of patients differently, which can be problematic for physicians to provide standardized treatments with similar outcomes. AAs with CRPC can experience significantly lower rates of overall survival, faster rates of tumor progression, and poor responses to chemotherapy compared to EAs with this disease.

We previously showed that CXCL13:CXCR5 axis plays a role in PCa pathobiology and is also associated with PCa aggressiveness; CXCR5 signaling mediates PCa cell growth, migration, invasion, and docetaxel resistance. To further understand the implication of CXCR5-CXCL13 in CRPC, we characterize the reason behind the health disparities seen across groups of PCa patients by evaluating the difference in regulatory molecules (miRNAs) on CXCL13-CXCR5 signaling.

We found the expression profile of CXCL13 and CXCR5 RNA to be associated with miRNAs (miR-140-3p.1, miR-24-3p, miR-200c, miR-221-3p/22-3p, miR-192-5p/215-5p, miR-214-5p). Using RNA-seq datasets from the Gene Expression Omnibus (GEO) and the Sequence Read Archive (SRA), CXCL13 and CXCR5 RNA as well as associated miRNAs (miR-140-3p.1, miR-24-3p, miR-221-3p/22-3p, miR-192-5p/215-5p, and miR-214-5p) were defined by etiologic disparities among PCa patients; this correlation is different among AA men compared to EA men.

Understanding PCa and specifically CRPC disparities requires a better understanding of the race-specific differences in prostate tumor biology, molecules leading to prostate inflammation, and the mechanisms associated with CRPC therapeutic resistance and its aggressive phenotype.

Citation Format: Adaugo Queen Ohandjo, Courtney Dill, Chen Dongquan, James W. Lillard, Jr.. Regulation of CXCR5-CXCL13 signaling in prostate cancer etiologic disparities [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr B56.
Abstract B60: Nanoparticles directed to IL13RA2 for targeted therapy of basal-like breast cancer
Authors: Wong Chen Khuan , Zhang Sandy , Reinhard Bjorn , Thiagalingam Sam
Published: February 2019

Basal-like breast cancer (BLBC) is among the most aggressive forms of breast cancer and is highly prevalent in young African-American women. It is nonresponsive to targeted hormonal therapy due to the lack of estrogen receptor, progesterone receptor, and HER2 expression. To identify effective targetable biomarkers for BLBC, we performed gene expression profiling of a breast cancer progression model system representing the different stages of the cancer. We discovered in metastatic BLBC cells high expression of IL13RA2, a cell surface receptor, which corresponded to poor survival in patients with high-grade tumors based on in silico meta-analysis of publicly available microarray datasets. To assess its functional roles in breast cancer progression, we knocked down IL13RA2 in BLBC cells and found that it is essential for lung colonization and tumorigenesis in vivo. Next, to establish the clinical utility of this candidate biomarker to inform prognosis, we performed immunohistochemical analysis of breast cancer tissue microarrays and found that IL13RA2 is overexpressed in a subset of lymph node metastases, hence supporting its role as a metastasis promoter. Based on these observations, we hypothesize that IL13RA2 may serve as a biomarker for disease stage and an active target for nanoparticle-mediated delivery of therapeutic agents to eradicate metastatic BLBC cells. We are in the process of conjugating gold nanoparticles with monoclonal antibodies to assess their binding specificity to IL13RA2-overexpressing cells in vitro and in vivo. Ultimately, these nanoparticles could be used to monitor disease spread as well as to actively target metastatic BLBC cells overexpressing IL13RA2 to block metastasis.

Citation Format: Chen Khuan Wong, Sandy Zhang, Bjorn Reinhard, Sam Thiagalingam. Nanoparticles directed to IL13RA2 for targeted therapy of basal-like breast cancer [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr B60.
Abstract B64: Race and prostate cancer: miRNA isoforms and tRNA fragments could hold some of the answers
Authors: Magee Rogan G. , Telonis Aristeidis G. , Loher Phillipe , Londin Eric , Rigoutsos Isidore
Published: February 2019

Prostate cancer is the most frequently occurring cancer in men. Compared to White (Wh) men, Black/African American (B/Aa) men exhibit higher mortality and higher incidence rates of prostate cancer. This difference remains even after modifiable factors are taken into account, which suggests an underlying cause. Recent studies greatly improved our understanding of the biochemistry of prostate cancer. Nonetheless, many open questions remain, especially with regard to the molecular underpinnings of the observed race disparities.

In this study, we analyzed 526 transcriptomic datasets from prostate adenocarcinoma (PRAD) patients. We obtained the data from The Cancer Genome Atlas (TCGA) repository. We focused on two categories of noncoding RNAs that regulate messenger RNA (mRNA) and protein abundance: (1) microRNAs (miRNAs) and their isoforms (isomiRs) and (2) tRNA-derived fragments (tRFs). Both tRFs and isomiRs regulate mRNAs and their proteins through the RNA induced silencing complex (RISC). Furthermore, tRFs have a number of other regulatory roles in healthy and diseased cells, including direct physical interactions with ribosomal proteins and initiation factors. Notably, we have demonstrated and reported previously that isomiRs and tRFs are constitutive and transcribed in a manner that depends strongly on a person's gender, race, and population origin, as well as on tissue type, tissue state, and disease type/subtype.

Our analyses of the TCGA PRAD datasets revealed that both isomiRs and tRFs are disrupted in PRAD. By extension, the regulatory networks that link isomiRs and tRFs to mRNAs are also disrupted. We also uncovered transcriptomic differences and differential regulatory relationships that are aligned with patient race. Moreover, we found that the molecular differences between B/Aa and Wh PRAD patients extend to normal prostate tissue as well. These findings mirror earlier results that we obtained from both healthy individuals and cancer patients.

The race-dependent regulatory profiles highlight differences in the underlying biology in B/Aa and Wh individuals that have yet to be explored. For example, the corresponding molecules could potentially be leveraged as novel biomarkers or alternative therapeutic targets. This study represents the first characterization of isomiRs and tRFs in a large cohort of PRAD patients.

Citation Format: Rogan G. Magee, Aristeidis G. Telonis, Phillipe Loher, Eric Londin, Isidore Rigoutsos. Race and prostate cancer: miRNA isoforms and tRNA fragments could hold some of the answers [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr B64.
Abstract B76: High glucose induces breast cancer progression through upregulating PP2Cδ
Authors: Wu Ke , Yu Xiaoting , Yi Xianghua , Ma Lynn , Elshimali Yahya , Liu Yanjun , Zhu Donghui , Wu Yong , Vadgama Jaydutt V.
Published: February 2019

Breast cancer has a high incidence worldwide. African-American and Hispanic/Latina women have higher mortality from breast cancer than other ethnic groups. Epidemiologic evidence suggests that women with diabetes have increased risk of breast cancer. Diabetes and cancer share many risk factors, but the pathophysiologic relationship between the two diseases is incompletely understood in detail. We observed that exposure of cultured transformed (MCF-7) and normal (MCF-12A) breast epithelial cells to clinically relevant levels of glucose (HG, 22 mM) dramatically suppresses the tumor suppressor p53 acetylation, and, consequently, additively promotes tumor cell proliferation, migration, and invasion. Importantly, we found that activation of nuclear phosphatase PP2Cδ (Ppm1d, WIP1) plays a role in the enhancing effects of HG on aggressive phenotypes of these cells. The mechanisms underlying high-glucose stimulation of PP2Cδ involve classical/novel PKCs activation and its downstream target protein GSK3β phosphorylation and inactivation. In addition, HG-induced reactive oxygen species (ROS) generation and subsequent NF-κB activation play a partial role in HG induction of PP2Cδ. HG inhibition of p53 activity and DNA damage-induced apoptosis, as well as induction of cancer cell proliferation, migration, and invasion, were significantly blocked by CCT007093, a known PP2Cδ inhibitor. We conclude that hyperglycemia, via PKC/GSK3β and ROS/NF-κB pathways that are involved in PP2Cδ activation, suppresses the tumor suppressor p53 function and inhibits DNA damage-induced apoptosis, inducing proliferation in the epithelium and the development of breast cancer.

Citation Format: Ke Wu, Xiaoting Yu, Xianghua Yi, Lynn Ma, Yahya Elshimali, Yanjun Liu, Donghui Zhu, Yong Wu, Jaydutt V. Vadgama. High glucose induces breast cancer progression through upregulating PP2Cδ [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr B76.
Abstract B80: A new inherited gastric cancer form caused by mutations in homologous recombination genes
Authors: Carmona Luis G. Carvajal
Published: February 2019

Gastric cancer (GC) is the third leading cause of cancer mortality worldwide and its risk is partially mediated by inherited factors. The majority of GC heritability, however, remains to be discovered. To identify novel GC genes, we undertook a multistaged approach of whole-exome sequencing (WES), followed by targeted sequencing and genotyping in germline DNA samples from hereditary diffuse GC (HDGC) and isolated GC cases recruited in Europe and Latin America. We also performed WES in 4 available tumor samples to analyze loss of heterozygosity and somatic mutation signature. Our study identified eleven cases with mutations in homologous recombination repair (HR) genes, including seven with PALB2 mutations, three with BRCA1 mutations, and one with a RAD51C mutation. Out of 361 total unrelated GC cases analyzed, 6.45% of the HDGC cases (2 out of 31) and 2.7% (9 out of 330) of isolated/non-HDGC cases had mutations in PALB2, BRCA1, or RAD51C. Most of these mutations are known as pathogenic in other cancer types and three were shared by multiple Hispanic and European cases. None of these mutations were present in 1,170 population-matched controls (P=5.75x10-7). Tumor samples from four mutation carriers exhibited mutational signature indicative of defects in HR pathway. Our results suggest that mutations in HR genes are likely involved in GC susceptibility. Our findings have potential clinical implications as these cases and their families could benefit from risk-reducing surveillance and possibly benefit from platinum or PARP inhibitor-based therapies.

Citation Format: Luis G. Carvajal Carmona, International Gastric Cancer Genetics Collaboration. A new inherited gastric cancer form caused by mutations in homologous recombination genes [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr B80.
Abstract B90: [Advocate Abstract:] Armorup for life
Authors: Hernandez-Aldama Loriana
Published: February 2019

ArmorUp for LIFE is a nonprofit founded by Loriana Hernandez-Aldama, former news anchor and fitness and health reporter turned leukemia survivor during her one-year fierce battle with AML. Loriana was a clean eat, green drinking yoga enthusiast and at the time of her diagnosis felt like she was in the best shape of her life. She had to put her reporter hat on and dig for answers. Cancer taught her that bad things can still happen but what matters most is how prepared you show up for the fight. Doctors explained that the more fit you are, the more chemotherapy you can get. The more fit you show up the better your chances of success and that those who show up with health issues (diabetes, heart disease and obesity) have their doses lessened because doctors are forced to tiptoe around their illnesses. In the doctors' words, “We can't kill you trying to save you.” From that day forward, Loriana knew this would be the biggest story of her career. ArmorUp for LIFE was born and based on the 5 pillars of helping patients show up fit to the fight so they can meet the medicine halfway and become their own hero. Fighting cancer is a joint effort and Loriana is trying to educate everyone before, during, and after the fight to take action.

Citation Format: Loriana Hernandez-Aldama. [Advocate Abstract:] Armorup for life [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr B90.
Abstract C10: Raising HPV awareness in immigrant populations: Are health educators prepared to address health literacy challenges?
Authors: Dawkins-Moultin Lenna , McKyer E. Lisako , McDonald Andrea
Published: February 2019

Background: Rates of human papillomavirus virus (HPV) and HPV-related cancers are higher among immigrants, especially those from Africa, Latin America, and the Caribbean. Limited health literacy is also more prevalent among immigrant groups. While education is central to HPV prevention and reduction, there is a dearth of research on health educators' understanding of how to educate populations with health literacy deficits. The purpose of this study was to assess the health literacy knowledge and experience of advanced health education students.

Methods: A modified Health Literacy Knowledge and Experience Survey (HL-KES) was used to collect data from 250 junior and senior students who reported an intention to take the Certified Health Education Specialists (CHES) examination. Descriptive and Spearman rho correlational analyses were conducted.

Results: Composite scores on the 29-item knowledge scale ranged from 5-28. Most students (84%) scored below 70%, and only five percent of the sample scored above 80%. Majority of students reported “never” or only “sometimes” engaging in experiences related to health literacy. There was a significant negative correlation between health literacy knowledge and health literacy experience (ρ = -.189, p < .05).

Conclusion: The results suggest health education students have deficient health literacy knowledge and limited opportunities to develop practical health literacy experience. Professional preparation programs may need to revise their curricula to address health literacy deficiencies in course offerings.

Citation Format: Lenna Dawkins-Moultin, E. Lisako McKyer, Andrea McDonald. Raising HPV awareness in immigrant populations: Are health educators prepared to address health literacy challenges? [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr C10.
Abstract C34: [Advocate Abstract:] Does culture play a role in cancer survivorship?
Authors: Walker Desiree
Published: February 2019

What is culture and how does it define a cancer patient's survivorship?

Citation Format: Desiree Walker. [Advocate Abstract:] Does culture play a role in cancer survivorship? [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr C34.
Abstract C45: Development and validation of Children Dietary Inflammatory Index (CDII)
Authors: Khan Samira , Alvarado Christian , Wirth Michael , Shivappa Nitin , Hebert James R.
Published: February 2019

Introduction: Chronic inflammation is a risk factor for many chronic diseases. The Dietary Inflammatory Index (DII) is a literature-derived index developed to measure the inflammatory potential of diet. A Children's Dietary Inflammatory Index (CDII) was developed to understand the association between diet and chronic inflammation-related health outcomes in children.

Methods: Food parameters that comprise the CDII include several nutrients like carbohydrates, various vitamins, minerals, and whole foods. To develop a reliable CDII scoring algorithm, aggregate data on children ages 6-14 were obtained from 16 different countries. This forms the basis for a world standard database to which all individuals' intakes can be standardized. Using this global database, CDII scores were calculated using dietary data from children between 6 and 14 years of age (n=3300) who participated in the U.S. National Health and Nutrition Examination Survey (NHANES) from 2005 to 2010. Construct validation was performed using linear regression models with CDII as the independent variable and C-reactive protein (CRP) as the outcome.

Results: Positive associations were observed between the CDII and CRP (mg/l) (p-value<0.01) among all children. For each one-point increase in CDII (i.e., corresponding to a 12.5% increase in inflammatory potential of the diet as observed in NHANES) CRP increased by 0.053 mg/dl (standard error = 0.01).

Conclusion: Results indicate that the CDII predicts CRP among children aged 6-14 years. Further validation and analyses using NHANES, as well as other data sets, are required to deepen understanding of inflammation in child health and the CDII in predicting inflammation levels in children.

Learning Objectives:

Describe how the CDII was created

Describe the process of construct validation

Discuss the use of CDII as a means for informing primary prevention and for educating physician, parents, and children on the importance of healthy diet to reduce chronic disease rates and to enhance feels of well-being and to improve quality of life.

Acknowledgment: All authors received funding from USDA 2016-01022.

Citation Format: Samira Khan, Christian Alvarado, Michael Wirth, Nitin Shivappa, James R. Hebert. Development and validation of Children Dietary Inflammatory Index (CDII) [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr C45.
Abstract C83: Dynamic Optical Contrast Imaging (DOCI): Oral screening in the underserved
Authors: Pellionisz Peter A. , Harrison Cheng , Taylor Zachary D. , Grundfest Warren , John Maie A. St.
Published: February 2019

Objective: Oral and head and neck squamous cell carcinoma (OSCC) is the sixth most common cancer and disproportionately affects racial minorities via increased incidence and poorer rate of survival. Stage at presentation is one of the strongest prognostic indicators in new diagnoses; patients who present with advanced stage have 5-year survival rates of 42%, compared to patients who present at stage I with 5-year survival rates of 79%. Because five-year survival is directly related to stage at diagnosis, early detection of precancerous OSCC lesions could greatly reduce morbidity and improve patient survival. We aim to demonstrate the utility of a novel tool (Dynamic Optical Contrast Imaging; DOCI) in reliably and accurately delineating tumor tissue from surrounding normal tissues for earlier patient screening.

Methods: OSCC specimens and surrounding tissues from the surgical bed were collected; fluorescence decay images were acquired using our DOCI system. Samples (55 patients) were subsequently processed and histologically assessed by head and neck pathologists. Mean relative fluorescence decay signatures were calculated for tumor, fat, muscle and collagen tissues. Statistical analyses were performed using the Wilcoxon signed rank test.

Results: Statistical significance (P<.05) between muscle and tumor was established for 10 emission wavelengths, collagen and tumor for 8 emission wavelengths, and between fat and tumor for 2 wavelengths.

Conclusion: We demonstrate the utility of DOCI in distinguishing OSCC from surrounding normal tissue. This novel screening tool would permit noninvasive tissue identification in underserved populations by reducing the stage of tumor presentation at diagnoses and subsequently improving patient outcomes.

Citation Format: Peter A. Pellionisz, Cheng Harrison, Zachary D. Taylor, Warren Grundfest, Maie A. St. John. Dynamic Optical Contrast Imaging (DOCI): Oral screening in the underserved [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr C83.
Abstract IA02: Colorectal cancer
Authors: Carethers John M.
Published: February 2019

Colorectal cancer (CRC) is the third most prevalent and second deadliest cancer in the U.S. with 135,430 cases and 50,260 deaths in 2017. Its pathogenesis stems from genetic susceptibility coupled with environmental interactions in the colon and rectum that synergize ideal conditions for neoplastic growth, initially from benign adenomatous polyps that might progress to carcinoma over several years. However, there is a disparity in morbidity and mortality among races, with African Americans demonstrating the highest incidence and mortality rates and a distribution of cancer that favors metastatic disease at presentation. The causes are likely multifactorial and include environmental factors that directly or indirectly influence the colonic epithelium and stem cells to be primed to commence the neoplastic process; societal factors such as socioeconomic class and access to health insurance; biologic factors such as earlier age development of adenomas and more proximal colon distribution of cancers or the gut microbiome; genetic factors such as higher frequency of somatic KRAS mutations that increase the aggressiveness of CRCs and shifts of the type of microsatellite instability that affect outcome; and immunologic factors such as less granzyme B-expressing T cells within CRCs. Most of these observations have just come in the past 10 years of research. Further biologic studies on environmental and genetic influences would be enhanced with adequate biorepository sources for CRC specimens from a variety of racial backgrounds, as most published data are not obtained from diverse specimens. CRC is preventable, and there is evidence that enhanced screening rates among African Americans can reduce or abolish the observed disparity. The 2017 U.S. Multi-Society Task Force on Colorectal Cancer for the first time included race as a factor in their screening recommendations, moving African Americans from age 50 years to age 45 years to commence CRC screening. Other opportunities to reduce the disparity include improved provider and patient education for screening and patient navigation for screening. Including a diverse population for trials of CRC screening, genome-wide association and other genetic studies, and treatment trials would further identify unique issues for higher-risk populations.

Citation Format: John M. Carethers. Colorectal cancer [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr IA02.
Abstract IA16: Identifying an epigenetic basis for arsenic-associated bladder cancer in a population in Chihuahua Mexico
Authors: Fry Rebecca C. , Fry Rebecca C.
Published: February 2019

Epidemiologic evidence links chronic exposure to inorganic arsenic (iAs) to a host of adverse health effects, including cancer of the bladder. This study aimed to identify DNA methylation patterns associated with arsenic and its metabolites in exfoliated urothelial cells (EUCs) that originate primarily from the urinary bladder, one of the targets of arsenic-induced carcinogenesis. EUCs from 46 residents of Chihuahua, Mexico were analyzed for genome-wide, gene-specific promoter DNA methylation levels. These were analyzed in relation to intracellular concentrations of total arsenic and arsenic species. A set of 49 differentially methylated genes was identified with increased promoter methylation associated with EUC tAs, iAs, and/or monomethylated As (MMAs) enriched for their roles in metabolic disease and cancer. Notably, no genes had differential methylation associated with EUC dimethylated As (DMAs), suggesting that DMAs may influence DNA methylation-mediated urothelial cell responses to a lesser extent than iAs or MMAs. Further analysis showed that 22 of the 49 arsenic-associated genes (45%) are also differentially methylated in bladder cancer tissue identified using The Cancer Genome Atlas (TCGA) repository. Both the arsenic- and cancer-associated genes were enriched for the binding sites of common transcription factors known to play roles in carcinogenesis, demonstrating a novel potential mechanistic link between iAs exposure and bladder cancer.

Citation Format: Rebecca C. Fry, Rebecca C. Fry. Identifying an epigenetic basis for arsenic-associated bladder cancer in a population in Chihuahua Mexico [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr IA16.
Abstract IA18: Liver cancer among minority populations in the United States
Authors: McGlynn Katherine A.
Published: February 2019

Liver cancer incidence, the dominant histology of which is hepatocellular carcinoma (HCC), has been increasing in the U.S. for more than three decades. In comparison with non-Hispanic whites, all other racial/ethnic groups have notably higher incidence rates. For many years, the highest HCC rates occurred among Asians/Pacific Islanders. Recently, however, rates among Asians/Pacific Islanders have declined while rates among all other racial/ethnic groups have increased. As a consequence of the divergent trends, Hispanics are poised to become the group with the highest liver-cancer incidence in the U.S. The group that has seen the greatest increase in rates in the past twenty years, however, is non-Hispanic blacks. By 2030, forecasting models suggest that Hispanics and non-Hispanic blacks will have the highest rates and Asians/Pacific Islanders will have the lowest rates.

Among all racial/ethnic groups in the U.S., males have higher rates of liver cancer than females. The male:female ratio varies from a low of 2.5:1 among American Indians/Alaska Natives to a high of 4.1:1 among non-Hispanic blacks. Males also are diagnosed at a younger average age than females, with the least discrepancy in age occurring among non-Hispanic blacks (2.7 years) and the greatest discrepancy in age occurring among Asians/Pacific Islanders (5.9 years).

A likely explanation for declining HCC rates among Asian/Pacific Islanders is a declining prevalence of hepatitis B virus (HBV) infection in the population. Likely explanations for the increasing HCC rates in other racial/groups are the high rate of hepatitis C virus (HCV) infection in prior years and the increased prevalence of obesity/diabetes in the population. An analysis of population-attributable risk among persons of ages 65 and older, however, found differences in attributable risk by racial ethnic group. Among non-Hispanic whites and Hispanics, the dominant risk factor was obesity/diabetes. In contrast, HCV infection was the dominant risk factor among non-Hispanic blacks and Asians/Pacific Islanders. These differences in key factors suggest that cancer prevention strategies should be tailored to each specific racial/ethnic group.

Citation Format: Katherine A. McGlynn. Liver cancer among minority populations in the United States [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr IA18.
Abstract IA26: Developing effective community and health system partnerships to advance health equity and health disparities research
Authors: Barrett Nadine , Ingraham Kearston , Williams Kevin , Lin Pao-Hwa , Eisenson Howard , Chirinos Maritza , Harvey Demetrius , Patierno Steven
Published: February 2019

Establishing sustainable and impactful partnerships to advance health equity and health disparities research requires a multipronged approach to assessing and aligning community and organizational priorities toward common goals and objectives. Partnerships to advance health equity and to ensure ongoing and meaningful health disparities research should ideally provide a win-win for community stakeholders and the health system. This often requires a cultural shift regarding how and to what extent academic/medical institutions value and fully engage diverse stakeholders as experts in the research process and delivery of care. At the Duke Cancer Institute, through the Office of Health Equity and Disparities, our intentional stakeholder engagement has led to robust partnerships with diverse community organizations and leaders capitalizing on each other's strengths and expertise. Through this process the DCI, together with the community, has built a sustainable platform to advance health equity through research, capacity building, and open communication.

Citation Format: Nadine Barrett, Kearston Ingraham, Kevin Williams, Pao-Hwa Lin, Howard Eisenson, Maritza Chirinos, Demetrius Harvey, Steven Patierno. Developing effective community and health system partnerships to advance health equity and health disparities research [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr IA26.
Abstract IA31: Not showing up empty-handed: A multicommunity collaboration for cancer prevention and control
Authors: Tanjasiri Sora Park , Palmer Paula Healani
Published: February 2019

While cancer mortality is on the decline in the U.S., Pacific Islanders continue to experience high rates of cancer incidence, prevalence, and mortality due to the lack of appropriate, understandable, and accessible prevention, early detection, and treatment/survivorship information and services. California is home to the second-largest populations of Pacific Islanders, including Chamorros, Marshallese, Native Hawaiians, Samoans, and Tongans. In 2005 community and university researchers formed a multicommunity collaboration for cancer prevention and control called WINCART: Weaving an Islander Network for Cancer Awareness, Research and Training. Using a community-based participatory research (CBPR) approach, this collaboration developed decision-making processes, protocols, and MOUs that prioritized community benefits in the design and implementation of studies spanning the cancer control continuum including tobacco cessation, nutrition and physical activity promotion, colorectal screening, breast screening, Pap testing, cancer survivorship, and biospecimen collection. Specifically, this presentation will cover the elements that contributed to WINCART's successful CBPR collaborations, provide examples from selected studies, and share lessons learned for researchers interested in initiating or sustaining community-university partnerships in the future.

Citation Format: Sora Park Tanjasiri, Paula Healani Palmer. Not showing up empty-handed: A multicommunity collaboration for cancer prevention and control [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr IA31.
Abstract IA36: Structural and social determinants of cancer disparities
Authors: Pérez-Stable Eliseo J. , Lin-Gomez Scarlett , Lin-Gomez Scarlett , Brown Arleen
Published: February 2019

Biologic and behavioral factors are considered the predominant contributors to incidence of cancer from most sites, and interactions between behavior and biology are well described. Contributions from social determinants of health to cancer rates and outcomes have mostly focused on access to preventive services and screening and to quality of cancer-related health care once diagnosed. For example, presentation with advanced stages of disease is most often ascribed to inadequate early detection when screening tests are recommended or to delay in consulting for symptoms when present. Both African American and Latina women have higher breast cancer mortality after completion of treatment for early-stage disease, in part as a result of inadequate annual screening following cure. Other factors such as health literacy, limited English proficiency, and low numeracy may exacerbate race/ethnic and socioeconomic disparities in cancer clinical care based on poor or ineffective communication. Structural determinants of cancer disparities refer to the built environment, the social and political system in which the patient lives, and the geographic location of home and health care. For example, an unsafe neighborhood may interfere with medical visits, obtaining medications and tests, and maintaining health-promoting activities after cancer diagnosis. Lack of adequate transportation and geographic isolation will further exacerbate access to care barriers. Race/ethnic minorities disproportionately engage with the criminal justice system, and this may interfere with obtaining quality clinical care. On the other hand, some concentrated minority neighborhoods may have tightly-woven social networks and provide community collective efficacy that can help patients and survivors going through treatment and survivorship care. Social and structural determinants of health can impact cancer outcomes across the continuum, from risk to death. Moreover, these characteristics are often highly correlated and can interact to influence disparate cancer outcomes above and beyond their individual health effects. The intersectional approach considers the impact on health and health equity of intersecting social positions and processes. To date, the intersectional approach has primarily been applied to qualitative research. In this panel, we will discuss the social and structural determinants, and the interaction among these determinants, of cancer disparities drawing on examples from the authors' work and the published literature.

Citation Format: Eliseo J. Pérez-Stable, Scarlett Lin-Gomez, Scarlett Lin-Gomez, Arleen Brown. Structural and social determinants of cancer disparities [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr IA36.
Abstract IA44: Disparate exposures of Native Americans to metal mixtures in abandoned mine waste in the West: Implications for cancer risk
Authors: Lewis Johnnye
Published: February 2019

More than 160,000 abandoned hard rock mines are located in the Western United States that is home to the majority of Native American lands. These mines are estimated to result in more than 500,000 discrete contamination sources. More than 600,000 Native Americans live within 10 kilometers of these mines, which are known to have contaminated at least 40% of the headwaters of western U.S. watersheds. Abandoned gold mines and uranium mines dominate the inventory in proximity to tribal lands, with more than 4,000 abandoned uranium mines associated with more than 10,000 individual waste sites. The proximity of Native populations to these sources, and their greater reliance on local resources, creates a pattern of greater than anticipated exposures to the waste through multiple pathways including ingestion of unregulated drinking water, plant and animal products raised in contaminated soils, inhalation of windblown dusts containing waste metals, and direct contact with indoor dusts. Native communities have greatly reduced access to regulated drinking water sources, creating a reliance on unregulated sources potentially contaminated by waste. These waste sites all include a combination of heavy metals geologically collocated with the primary metal of concern, and often are combined with chemicals used in the extraction process. Data compiled by Indian Health Services illustrate significant health disparities within these communities, including a shorter life expectancy and double the mortality rate for those under 44 years of age. Cancer mortality rates for the Native American population increased over the 20-year period from 1990-2009, a period during which rates for the White population have decreased. Exposure to metals such as cadmium and arsenic has been directly linked to cancer mortality in Native populations, and epidemiologic data from one community proximal to an abandoned uranium mill report 4 of every 10 residents have died of cancer. Recent work in our laboratories has shown inhibition of DNA repair as well as dysregulation of immune function to be associated with exposures to these metal mixtures, providing possible pathways underlying increased cancer risk. Disparities do not end with exposures, but continue as patients seek care. With the closest treatment options often hundreds of miles away over extremely rough roads, using gasoline significantly more expensive than in many urban areas, the impact of increased risk continues to manifest throughout diagnosis and treatment.

Citation Format: Johnnye Lewis. Disparate exposures of Native Americans to metal mixtures in abandoned mine waste in the West: Implications for cancer risk [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr IA44.
Abstract A24: Using single-cell RNA-seq approaches to decipher heterogeneity in autochthonous mouse models of small cell lung cancer
Authors: Marjanovic Nemanja Despot , Ng Sheng Rong , Regev Aviv , Jacks Tyler
Published: February 2019

Small cell lung cancer (SCLC) is one of the most aggressive cancer types, and patients in clinic usually (>60% cases) present with metastasis. Current therapies for SCLC have not changed from 1980, and they include a combination therapy of cisplatin and etoposide. Most patients relapse after initial response, and the 5-year survival for extensive stage SCLC is 2%. One possible explanation for the failure of conventional and targeted therapies in cancers is the cellular heterogeneity that exists within tumors. Thus, understanding phenotypic heterogeneity at the single-cell level can be leveraged to predict mechanisms of resistance, which enables the design of effective combination therapies. In this project, we used as a model system an autochthonous mouse model of human SCLC, in which we deleted p53, RB, and p130. We collected multiple primary tumors, circulating tumor cells (CTC), and lymph node (proximal site) and liver (distant site) metastases from the same mouse, and across different mice. These samples were collected at the stage that should correspond to the limited/extensive stage of human SCLC, which is most commonly seen in clinic. Then we used single-cell RNA-seq (sc-RNAseq) methods to define and understand transcriptional heterogeneity in these samples. Furthermore, we aimed to understand the evolutionary relationships between primary tumors, CTCs, lymph node and liver metastases using different computational approaches such as diffusion maps. Further defining and functionally annotating transcriptional heterogeneity will help us better understand the disease, and find the new Achilles heel for targeting.

Note: This abstract was not presented at the conference.

Citation Format: Nemanja Despot Marjanovic, Sheng Rong Ng, Aviv Regev, Tyler Jacks. Using single-cell RNA-seq approaches to decipher heterogeneity in autochthonous mouse models of small cell lung cancer [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr A24.