bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B070: Loss of cytoskeletal protein palladin desensitizes pancreatic cancer associated fibroblast to TGFβ1-dependent desmoplastic induction
Authors: Alexander Jennifer , Cukierman Edna 
Published: August 2020

Abstract
Pancreatic ductal adenocarcinoma (PDAC) claims ~93% of patient lives in less than 5 years proceeding diagnosis. Therapeutic options for PDAC are challenged by the deposition of a fibrous-like extracellular matrix (ECM) known as desmoplasia. This desmoplastic-ECM (D-ECM) forms the bulk of the tumor mass while remodeling the once tumor-suppressive microenvironment to become tumor permissive. Ironically, ablation of the D-ECM results in an even more aggressive PDAC. Thus, unraveling the mechanism of D-ECM induction is vital to reinstating the natural tumor-restrictive microenvironment of the pancreas. Although the underlying biology remains unclear, the D-ECM is initiated and maintained by activated cancer associated fibroblasts (CAFs). CAF activation is primarily driven by TGFβ1 signaling, which causes cytoskeletal rearrangements in support of CAF-dependent D-ECM onset. As such, the goal of this study is to define the cytoskeletal regulation needed to restore the natural tumor-suppressive properties of the pancreas. Therefore, we focused on the actin cross-linker palladin whose expression is regulated by TGFβ1 and has been identified as an independent prognostic marker for PDAC progression as well as CAF activation. We postulate palladin has an isoform-specific role in PDAC-associated desmoplasia that ultimately fuels cancer progression. Using an in vivo-mimetic 3D stroma model, I used a CRISPR/Cas9 approach to delete one or both of the major palladin isoforms in patient-derived CAFs and assessed CAF's activation via quantitative immunoblots, real-time polymerase chain reaction, and multiplex confocal microscopy in addition to palladin knockout CAF-derived ECM's ability to influence PDAC cell viability and invasive spread. My data indicate that palladin isoforms 3 and 4 are required for TGFβ1-depdendent CAF activation as well as for CAF-dependent D-ECM induction whereby knockdown of either isoform in CAFs results in a normalized ECM that restrains the inherent aggressive nature of PDAC cells. These findings suggest that targeting palladin alters the desmoplastic compartment by impeding tumor progression. Taken together, these results propose a strategy to restore a normal tumor-suppressive stroma in PDAC that will complement current PDAC treatment dogmas.
Citation Format: Jennifer Alexander, Edna Cukierman. Loss of cytoskeletal protein palladin desensitizes pancreatic cancer associated fibroblast to TGFβ1-dependent desmoplastic induction [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B070.
Abstract B084: Factors associated with longer time to surgical treatment in melanoma
Authors: Baranowski Marissa L.H. , Yeung Howa , Chen Suephy C. , Gillespie Theresa W. , Goodman Michael 
Published: August 2020

Abstract
Background: Timely treatment for melanoma may affect survival, and characterizing predictors of treatment delay may inform intervention strategies.
Objective: To determine patient-, provider-, and facility-level characteristics associated with a delay to treatment in melanoma.
Methods: The National Cancer Database was used to examine factors associated with an increased interval between diagnosis and definitive surgical treatment among 205,665 patients with Stage I, II, or III cutaneous melanoma between 2004 and 2015 using multivariable Cox proportional hazards modeling.
Results: The data demonstrated that the direction of the association between age at diagnosis and timing of surgery differed depending on insurance status. Among 115,461 privately insured patients, delay in surgical treatment was associated with older age (HR 0.85 in 70+ years, p &lt;0.0001; HR 0.97 in 50-70 years, p &lt;0.0001). By contrast, in 90,204 patients without private insurance, the association with age was weaker and in the opposite direction (HR 1.09 in 70+ years, p &lt;0.0001; HR 1.09 in 50-70 years, p &lt;0.0001). After adjustment for important patient and disease characteristics, other factors significantly associated with a longer time from diagnosis to surgery included non-white race, higher comorbidity burden, thicker tumor, higher disease stage, and head or neck melanoma location.
Conclusion: Melanoma patients experience disparities in timely receipt of surgery. Identifying groups at risk of delay reveals who would benefit most from patient navigation or care-coordination programs. Public health intervention is warranted to address specific roadblocks contributing to surgical delay to improve care for all patients with melanoma.
Citation Format: Marissa L.H. Baranowski, Howa Yeung, Suephy C. Chen, Theresa W. Gillespie, Michael Goodman. Factors associated with longer time to surgical treatment in melanoma [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B084.
Abstract B124: Indigenizing cancer biobanks as a form of cultural resistance
Authors: Haring Rodney C. , Rodriguez Elisa M. , Henry Whitney Ann E. 
Published: August 2020

Abstract
Purpose/Objective(s): Roswell Park is the oldest comprehensive cancer center in the US, founded in 1868. Roswell is also situated within the largest confederacy of Native American Nations in the Northeast, the Haudenosaunee, People of the Longhouse, also known as the Iroquois. Holdings of Indigenous biospecimens collected and housed in Roswell's biorepository were reported back to Indigenous urban communities and the largest Haudenosaunee Nation in the region. The purpose of the presentation was to share and engage discussion on indigenizing biorepository collections, procedures, storage, and utilization for investigation as a means of cultural resistance.
Materials/Methods: Two projects were conducted. The first reviewed feedback on clincial trial recruitment methods in urban indigenous communiteis related to biospecimen research (n=16, phase 1; n=20, phase 2) and a second study is under way investigating reservation-based and urban perspectives on biobanking storage, perceptions of genetic research, ethics, and policy (n=35 interviews; n=6 focus groups). Both studies utilized a qualitative framework to collect, analyze, and report experiences, perceptions on clinical research, recruitment, biospecimen donation, and investigation. Mulitple analysts were incorporated from interdisciplinary qualitative paradigms, training, cultural backgrounds, and experience to enhance rigor.
Summary: Preliminary results included the process of creating trust through respectful partnerships, understanding the consenting process, respecting traditional views, the need for education on the field of genetics, being congnizant of environmental spaces, and benefit to family and future generations. Other conclusions focused on macro level recommendations for indigenizing cancer-based biorepository collections, procedures, storage, and utilization for investigation as a means of cultural resistance and honoring.
Conclusions: Conversations included conceptualization of macro-level policy initiatives that have the ability to enlighten the process of “Western science” in creating new narratives for future generations and building meaningful biologic specimen research agendas towards culturally attuned prevention and personalized medicine. It is important that unique societies contribute to the science and crucial that science respects the sovereignty of Native Nations to contribute for the benefit of all generations.
Citation Format: Rodney C. Haring, Elisa M. Rodriguez, Whitney Ann E. Henry. Indigenizing cancer biobanks as a form of cultural resistance [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B124.
Abstract C010: The wiring between genes and short noncoding RNAs in cancer depends on race/ethnicity and sex
Authors: Telonis Aristeidis G. , Rigoutsos Isidore 
Published: August 2020

Abstract
Short noncoding RNAs (ncRNAs) have been attracting increasing interest as regulators of messenger RNA (mRNA) abundance. Such regulatory molecules can have influence the abundance of mRNAs both positively and negatively. Two important categories of short ncRNAs are microRNAs (miRNAs) and their isoforms (isomiRs), and the tRNA-derived fragments (tRFs). We previously showed that their “wiring” with mRNA abundance strongly depends on the race/ethnicity in triple-negative breast cancer. Here, we focused on two cancers, bladder urothelial carcinoma (BLCA) and stomach adenocarcinoma (STAD). Men and women have been known to exhibit different incidence rates of BLCA, as well as differences in invasion, and overall aggressiveness. Analogous observations hold true when comparing White and Asian individuals in the case of STAD. We mined a total of 615 primary tumors, 337 from STAD and 278 from BLCA patients. After stringent abundance filtering, we identified 1,478 distinct isomiRs and 355 distinct tRFs. We found that the abundance profiles of these molecules exhibited strong tissue dependencies. We constructed gene co-expression networks for the healthy and disease states. Mining the correlations of isomiRs/tRFs with mRNAs, we found that core cancer pathways are wired with small ncRNAs. We carried out a large-scale computational analysis of the correlation patterns to dissect the dependencies on race/ethnicity and sex in STAD and BLCA, respectively. We found that core pathways are differentially wired in each case. For example, in BLCA, cell cycle genes are linked with several tRFs in one sex but not in the other. While the contribution of isomiRs in sex disparities in BLCA is limited, we find that isomiRs exhibit strong sex-independent associations with immune system responses and extracellular matrix and cell adhesion. In the case of STAD, we observed several instances of differential-by-race/ethnicity correlations of tRFs with genes involved in cell signaling, like ITPA and PICK1 and numerous cell adhesion genes differentially wired with isomiRs. Our data provide a detailed perspective of the structure and hubs of the gene expression networks in BLCA and STAD as well as their sex- and race/ethnicity-specific components. The identification and discovery of context-specific potential regulators have considerable ramifications for precision medicine and can be leveraged to facilitate the design of better-targeted treatments that are tuned to the patient's sex and race.
Citation Format: Aristeidis G. Telonis, Isidore Rigoutsos. The wiring between genes and short noncoding RNAs in cancer depends on race/ethnicity and sex [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C010.
Abstract C028: Hypoxia-associated genes on disparities in the aggressiveness of prostate cancer
Authors: Espinoza Ingrid C. , Moreno Carlos S. , Gomez Christian R. 
Published: August 2020

Abstract
The incidence of prostate cancer (PCa) is 70% greater and the mortality rate 137% higher in African-American men (AAM) relative to Caucasian-American men (CAM) (Siegel et al., 2016). AAM also show faster tumor growth, higher levels of PSA, and more aggressive disease relative to CAM (Martin et al., 2013). These data, related to the biology of PCa, suggest that biologic mechanisms contribute to PCa health disparities. Because stratification by clinical parameters alone is not sufficient to predict aggressive PCa, there is an unmet need of reliable biomarkers to anticipate outcome and disease progression. This study was designed to identify hypoxia-associated genes with the potential to anticipate the risk of aggressive PCa in a race-specific manner. Seventy annotated cases with documented follow-up for evidence of biochemical recurrence (BCR) were located. Of these, 22 were AAM (8 with BCR and 14 without BCR) and 48 were CAM (31 with BCR and 17 without BCR). Next, we performed a global sequencing analysis in RNA extracted from formalin-fixed, paraffin-embedded blocks. Among 27 hypoxia-associated genes associated with race and PCa by use of Cox proportional hazards regression analysis (p ≤ 0.05), we identified three genes related with BCR and race: regulator of G-protein signaling 1 (RGS1), nuclear receptor subfamily 3, group C, member 1-glucocorticoid receptor (NR3C1), and myosin light chain kinase (MYLK). A race-independent in silico analysis utilizing TCGA data suggested tumor-specific association between transcripts of RGS1, NR3C1, and MYLK and Gleason score. Likewise, low expression of these transcripts was suggestive of poor survival. Currently, we are analyzing transcripts of these three hypoxia-associated genes by independent techniques. Integration of gene expression data with clinical parameters of prognosis will allow us to develop predictive scores. These studies may enable race-specific differentiation of patients at higher and lower risk of BCR. Our findings underscore the prognostic value of hypoxia-regulated genes in aggressive PCa. They also warrant studies to establish the relevance of RGS1, NR3C1, and MYLK as race-specific markers.
Funding sources: GMaP 2 Pilot Grant (IE).
Citation Format: Ingrid C. Espinoza, Carlos S. Moreno, Christian R. Gomez. Hypoxia-associated genes on disparities in the aggressiveness of prostate cancer [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C028.
Abstract C029: Exosomes-associated miR-5001, miR-3692 and miR-4529 are novel biomarkers for aggressive prostate cancer and associated with poor prognosis in African American patients
Authors: Gaballa Rofaida , Gaballah Mohamed , Ali Hamdy E.A. , Sholl Andrew S. , Ali Hamed I. , Elmageed Zakaria Y. Abd 
Published: August 2020

Abstract
Background: Although microRNA (miR) profiling has been widely used to predict clinical outcomes, differential miR expressions that can segregate prostate cancer (PCa) patients based on their races and tumor aggressiveness have not been fully investigated. We aimed to determine the diagnostic and prognostic abilities of exosomal miRs to identify the aggressive phenotypes of PCa in African American (AA) men.
Methods: Exosomes were isolated from blood of twenty AA and European Americans (EuA) PCa patients at low and high Gleason scores and their aged-matched healthy subjects (n=20) as well as AA and EuA normal and PCa cells. miR profiling was performed on PCa exosomes derived from blood and PCa cells. The expression level was correlated with clinical outcomes of PCa patients. The sensitivity and specificity of exosomal miRs were assessed using receiver operating characteristic (ROC) curve.
Results: Results from miR profiling showed a number of exosomal miRs that were able to differentiate normal from PCa, low from high Gleason scores and AA from EuA PCa patients. These dysregulated miRs were validated in another cohort of forty PCa patients in addition to a large panel of PCa cell lines. In the validation cohort, miR-5001, miR-3692 and miR-4529 were upregulated in the exosomes derived from blood of AA compared to EuA men. These miRs were correlated with age, T-stage, residual tumor, involvement of lymph nodes, Gleason score, and overall survival of AA patients. The combination of these miRs showed high discriminatory power (AUC=0.91) for segregation of PCa patients according to their clinical outcomes.
Conclusion: miR profiling identified a new set of miRs that can differentiate PCa specimens based on their race and Gleason score. The differential expression of these miRs demonstrates their potential role as biomarkers in the context of racial disparity. Further studies are warranted to determine their role in PCa at advanced stages.
Citation Format: Rofaida Gaballa, Mohamed Gaballah, Hamdy E.A. Ali, Andrew S. Sholl, Hamed I. Ali, Zakaria Y. Abd Elmageed. Exosomes-associated miR-5001, miR-3692 and miR-4529 are novel biomarkers for aggressive prostate cancer and associated with poor prognosis in African American patients [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C029.
Abstract C037: Racial disparity in systemic growth-related oncogene-alpha (GRO-α) expression in head and neck cancer patients
Authors: Moore-Medlin Tara , Mijalis Eleni , Ma Xiaohui , McLarty Jerry , Mills Glenn , Nathan Cherie-Ann 
Published: August 2020

Abstract
Introduction: The objective of this study was to perform an analysis of cytokines reported to be upregulated in cancer patients to determine differences that may exist between Caucasians and African-Americans. Cancer biomarkers aid in identifying therapeutic targets as well as providing information on the involved signaling pathways. As African-Americans are known to present with advanced disease and have poorer survival even in nonmetastatic head and neck cancer, findings may be indicative of a potential therapeutic target for this population.
Methods: In this IRB approved study, we utilized a multiplex bead-based immunoassay by Millipore to compare serum levels of 13 cytokines (FGF-2, GM-CSF, GRO-α, IFNγ, IL-1β, IL-6, IL-8, IL-10, IL-13, IP-10, MIP-1β, TNFα and VEGF) in African-Americans and Caucasians at diagnosis of primary head and neck cancer. Cytokine expression was detected using Luminex xMAP technology with xPonent software, then analyzed using Milliplex Analyst.
Results: Growth-related oncogene-alpha (GRO-α) was the only significantly different cytokine analyzed in regard to ethnicity, where African-Americans (n=36) exhibited higher serum levels in pg/ml compared to Caucasians (n=85) (1287±303.9 and 415.5±50.1, respectively; 95% CI 453.1 to 1290; p&lt;0.0001).
Conclusions: Systemic levels of GRO-α were higher in African-American compared to Caucasian head and neck cancer patients. There is accumulating evidence that GRO-α is overexpressed in human skin, breast, colorectal and hepatocellular cancers. GRO-α has been most notably implicated in cell proliferation, immune response, and as a regulator of tumor invasion and chemoresistance. With the present survival disparities in head and neck cancer patients, this striking overexpression warrants further study into a possible biomarker or targeted therapeutic agent for African-American patients.
Citation Format: Tara Moore-Medlin, Eleni Mijalis, Xiaohui Ma, Jerry McLarty, Glenn Mills, Cherie-Ann Nathan. Racial disparity in systemic growth-related oncogene-alpha (GRO-α) expression in head and neck cancer patients [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C037.
Abstract C038: MHC class I polypeptide related sequence A (MICA) race-related differential expression in prostate cancer
Authors: Pound Charles R. , Sakiyama Marcelo J. , Reddy Amit , Espinoza Ingrid , Bhanat Eldrin , Syrigos Krista , Gordji Roya , Kumar Deepak , Lewin Jack , Zhou Xinchun , Monico Jesus , Gomez Christian 
Published: August 2020

Abstract
Prostate cancer (PCa) is the second most common cancer in American men, with higher incidence and death rates in African Americans (AA) relative to Caucasian Americans (CA); nevertheless, these disparities are still poorly understood. MHC class I polypeptide related sequence A (MICA) is a cell surface protein able to promote activation of natural killer cells. Cleavage of MICA and generation of its soluble form (sMICA) has been described as an immunoevasion mechanism presented by different types of aggressive tumors. In agreement with the role of MICA on tumor immunoevasion, recent studies correlated better prognosis for patients expressing higher levels of MICA in different types of cancer. We speculated that MICA expression would be different between AA and CA PCa tumors. To access MICA expression in PCa patients, we stained a TMA containing 30 AA and 27 CA tumor cores. Our results showed that CA PCa tumor cores had higher expression of MICA than the AA (p=0.0019). In order to establish an in vitro system to study the biologic effects of MICA in the context of disparity in PCa, we assessed the expression of surface MICA and release rate of sMICA in different PCa cell lines: MDA-PCa-2b and E006AA-hT, derived from AA, and DU-145 and LNCaP, derived from CA. Flow cytometry analysis showed baseline cell fraction expression positive for surface MICA of 3% in MDA-PCa-2b, 18% in E006AA-hT, 54% in DU-145, and 67% in LNCaP, with significant difference between each cell line (p&lt;0.0001). Baseline release rate of sMICA was nondetectable for MDA-PCa-2b, 5pg/ml/106 cells in E006AA-hT, 120pg/ml/106 cells in DU-145, and 54pg/ml/106 cells for LNCaP cells. Overall, our results show that MICA expression is race related. Further studies are necessary to address the biologic function of the expression and the impact in the immune system.
Citation Format: Charles R. Pound, Marcelo J. Sakiyama, Amit Reddy, Ingrid Espinoza, Eldrin Bhanat, Krista Syrigos, Roya Gordji, Deepak Kumar, Jack Lewin, Xinchun Zhou, Jesus Monico, Christian Gomez. MHC class I polypeptide related sequence A (MICA) race-related differential expression in prostate cancer [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C038.