bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract PR009: Discovery of covalent NRAS inhibitors targeting the Palmitoylation site through imaging-based high-throughput screening
Authors: Wang Zhao , Moore Keith , Ng Simon , Wang Chao , Tomlinson Ronald , Loke Huay-Keng , Rice Jamie , Cornella Ivan
Published: December 2023

NRAS mutations play a crucial role as oncogenic drivers of tumor cell growth and chemo-resistance in melanoma and acute myeloid leukemia (AML). In melanoma, NRAS mutations occur in approximately 25% of cases, and are generally mutually exclusive with BRAF-mutations. NRAS mutant tumors often exhibit an aggressive phenotype, such as thicker lesions, increased mitotic activity, and higher rates of lymph node metastasis. Surgical resection of NRAS mutant melanoma has a poor prognosis with a lower median overall survival (OS) compared to non-NRAS-mutant melanoma (8.2 vs. 15.1 months for stage IV disease). Current treatment strategies for stage III/IV non-resectable metastatic NRAS mutant melanoma include immunotherapy and indirect targeting of NRAS associated signaling pathways, highlighting the urgent need to develop small molecule NRAS inhibitors. NRAS palmitoylation is essential for its oncogenic function by regulating its trafficking and anchoring to the plasma membrane. Unlike other RAS isoforms, NRAS relies on a single palmitoylation site (C181) for its plasma membrane localization and this unique dependency makes NRAS more sensitive to palmitoylation inhibitors. To identify selective NRAS inhibitors that covalently modify C181 and prevent its palmitoylation, we employed an imaging-based NRAS translocation high-throughput screen using a library of 23,000 covalent molecules. We identified a set of covalent inhibitors that selectively target NRAS translocation but do not affect HRAS localization. We further confirmed the direct binding of these compound hits to NRAS at its palmitoylation site (C181) using intact mass spectrometry and chemo-proteomic peptide mapping techniques. Moreover, we validated the functional impact of these compound hits by demonstrating their selective inhibition of cell growth in mutant NRAS-driven melanoma cell lines. In conclusion, our study presents the first direct inhibitor for NRAS, discovered through a high-throughput covalent screening approach. This finding holds promising implications for the development of novel targeted therapies for NRAS mutant tumors.

Citation Format: Zhao Wang, Keith Moore, Simon Ng, Chao Wang, Ronald Tomlinson, Huay-Keng Loke, Jamie Rice, Ivan Cornella. Discovery of covalent NRAS inhibitors targeting the Palmitoylation site through imaging-based high-throughput screening [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr PR009.
Abstract A030: Identifying LGBTQ+-related barriers and gaps in patient and workplace environments: An LGBTQ+ environmental needs assessment at Perlmutter Cancer Center
Authors: Trifonov Alexandr , Monahan Rachel , Haseltine Megan C. , Moore Kevin , Quinn Gwendolyn P. , Nelson Rachel , Chachoua Abraham , Domogauer Jason
Published: December 2023

Background: The LGBTQ+ community faces disproportionately higher cancer-related health disparities compared to the general population. Lack of access, knowledge, and cultural attitudes are known factors attributing to lower rates of receiving cancer-preventative services, as well as higher rates of later-stage cancer diagnoses. Many factors contribute to these disparities, including finding a trusted provider, poor visual representation at clinics, missing sexual orientation and gender identity (SOGI) data, and negative patient experiences. To address these issues and to promote equitable care it is important to identify gaps and barriers that present in patient and healthcare staff environments. The LGBTQ+ Staff Task Force (STF) at NYU Langone Health Perlmutter Cancer Center (PCC) will utilize the Exploration, Planning, Implementation, Sustainment (EPIS) framework to address these inequities.    Methods: As part of the “Exploratory” phase, the STF will deploy an environmental needs assessment survey, to evaluate patient and employee areas. The assessment includes the following LGBTQ+ domains to evaluate the environments: Policy; Visualization and Safety; Knowledge and awareness education; Complaint and Feedback Reporting; Workplace Inclusions and Non-discrimination; Resources. The survey will be administered to all clinical and non-clinical departments of PCC and will be completed by STF members from their respective departments and by managers or supervisors from each department location. Surveys will be submitted electronically via REDCap Data will be analyzed by the research team and discussed in small focus groups.     Discussion: The LGBTQ+ Needs Assessment will be carried out across all PCC departments and locations within an 8-week period between May and July 2023. The findings from utilizing the EPIS framework will enable the identification of gaps and barriers to inclusive patient care and evaluate the efficacy of current processes and resources in place for LGBTQ+ patients and employees. Findings will inform strategies and planning to decrease identified factors impacting access to equitable healthcare.  

Citation Format: Alexandr Trifonov, Rachel Monahan, Megan C. Haseltine, Kevin Moore, Gwendolyn P. Quinn, Rachel Nelson, Abraham Chachoua, Jason Domogauer. Identifying LGBTQ+-related barriers and gaps in patient and workplace environments: An LGBTQ+ environmental needs assessment at Perlmutter Cancer Center [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A030.
Abstract A036: The role of multisectoral partnerships in the dissemination of HPV vaccination campaigns in Puerto Rico
Authors: Valencia-Torres Ileska M. , Sánchez-Cabrera Yara , Fernández María E. , Colón-López Vivian
Published: December 2023

INTRODUCTION: The Human Papillomavirus (HPV) is the most common sexually transmitted infection worldwide. Despite the availability of an effective vaccine, HPV vaccination uptake is suboptimal in Puerto Rico (PR). Knowledge and understanding of the benefits of HPV vaccination can influence the intention to vaccinate. The Puerto Rico Community Cancer Control Outreach Program (PRCCCOP) and our network of multisectoral partners disseminated an HPV vaccination educational campaign tailored to promote HPV vaccination among kids and adolescents aged 9-26. OBJECTIVE: To effectively disseminate Human Papillomavirus (HPV) prevention educational campaigns through a network of multisectoral collaborators to increase HPV vaccination uptake in PR. METHODS: The PRCCCOP trained collaborators on basic HPV, HPV-caused cancers, and HPV vaccine knowledge and the use of educational materials. Collaborators distributed educational materials to their clientele who visited in person, participated in sponsored events, and accessed their virtual platforms or via email. In addition to printable educational materials, PRCCOP public service announcement videos about HPV vaccination were transmitted at our participating Federally Qualified Health Centers (FQHC). The PRCCOP provided all collaborators with continued training, assistance, and educational materials. RESULTS: Our program impacted 65 municipalities (83.3% of the island). Electronic and printed versions of our educational materials were disseminated in 40 clinics and vaccination centers across the island, including all 22 FQHCs in Puerto Rico (PR). Over 2,000 people were reached via in-person events and health fairs. Additionally, 18 workshops were imparted in clinical and academic settings. CONCLUSION: Community outreach can be an expensive and labor-intensive task. By establishing partnerships and sharing resources, the PRCCCOP has lowered costs while widely disseminating its educational campaigns and expanding its network outside the traditional academic/health services arena. Collaborating with multisectoral organizations allowed us to increase our presence throughout the island, diversify the types of dissemination mediums, and reach vulnerable and hard-to-reach populations.

Citation Format: Ileska M. Valencia-Torres, Yara Sánchez-Cabrera, María E. Fernández, Vivian Colón-López. The role of multisectoral partnerships in the dissemination of HPV vaccination campaigns in Puerto Rico [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A036.
Abstract A071: Results from cancer clinical trials health education in racial/ethnically diverse populations
Authors: Moseley Michelle , Pardo Eva , Andemeskel Ghila , Rhoads Kim
Published: December 2023

Background: The University of California, San Francisco (UCSF), a National Cancer Institute (NCI) designated comprehensive cancer center implemented NCI’s  Clinical Trials (CT) Education Initiative to promote awareness and conduct culturally tailored clinical trials engagement and education in racial/ethnically diverse populations. CT are studies that test ways to prevent, find and treat disease and ensure safety & effectiveness. Racial/ethnic groups have both the highest death rate and shortest survival rate for most cancers. Minority population CT participation is low and more diverse enrollment is needed for progress toward health equity. Methods: UCSF Community Health Educators engaged community partners and conducted CT education. Topics included what are clinical trials, how they work and advance progress, the value of diversity & inclusion, types and phases of CTs, informed consent, myths & facts, mistrust, other concerns & barriers, how to find & enroll in CT & sources for more information. Education sessions were evaluated using a 17-item pre-/post- survey to measure changes in CT knowledge and intention to participate. Changes in knowledge scores were assessed using the Wilcoxon Signed-rank sum test; changes in intent were assessed using the McNemar test. Results: There were 300 total participants (N=300 completed pre/post). Respondents: 76.5% female, 23.5% male; 53 average age; 70.9% African American, 1.4% American Indian, 8.4% Asian, 10.9% Latino, 1.7% Pacific Islander, 3.9% White & 2.8% Multiracial.  CT education significantly increased overall knowledge, the intention to seek out CT information and join CT.  Clinical trials knowledge score ranged from 0 to 11 pre-education, 4 to 11 post, and improved by 0.50 points (4.6%).  Post-education respondents strongly agreed or agreed: 74% to talk to a healthcare provider about CT; 77% importance of people of color CT participation; 48% intend to join a CT. Conclusion:  CT education is a strategy to address cancer health disparities through community engaged partnerships & education and demonstrated efficacy in increasing awareness & knowledge of CT and advanced intent to enroll.

Citation Format: Michelle Moseley, Eva Pardo, Ghila Andemeskel, Kim Rhoads. Results from cancer clinical trials health education in racial/ethnically diverse populations [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A071.
Abstract A088: The impact of race and rurality on employment disparities for cancer survivors
Authors: Allen Jaimi Mimi L.
Published: December 2023

Purpose: Advancements in cancer diagnosis and treatment have resulted in improvements in survivor outcomes; however, cancer survivors are more likely to experience adverse employment outcomes such as job loss, reduced working hours, and early retirement. These adverse experiences are exacerbated by race/ethnicity and rurality. Thus, the purpose of this study was to examine employment disparities among a diverse group of cancer survivors. Methods: Our study collected data from 29,136 cancer survivors (ages 18–65) between 2015 and 2021 using electronic health records (EHR) and linked to cancer registry data. Multivariable linear regression models were used to estimate the association between employment and study variables (race, ethnicity, rurality, sex, education, marital status, age at diagnosis, cancer type). Results: A total of 7,296 patients had available information on employment. Approximately 61% of cancer survivors were employed, 28% were not employed, 9% were disabled, 2% were retired. Logistic regression adjusted results revealed a positive association between employment and marriage or having a significant other, while racial and ethnic minority adults, rurality, and certain age categories were less likely to be employed. Unadjusted results showed a positive association between employment and education. Conclusion: The positive impact of education and relationship status (married or having a significant other) should be further explored to find mitigating strategies for adverse health and employment outcomes for cancer survivors. With the rise of cancer survivorship, more research should focus on finding equitable interventions and strategies for cancer survivors to return to work if desired.

Citation Format: Jaimi Mimi L. Allen. The impact of race and rurality on employment disparities for cancer survivors [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A088.
Abstract A089: Examining the role of Social Determinants of Health (SDoH) on adherence to cancer prevention recommendations: Evidence from a national representative sample
Authors: Aroh Adaeze , Madujibeya Ifeanyi N.
Published: December 2023

The role of Social Determinants of Health (SDoH)  on adherence to cancer prevention recommendations has not been systematically examined among adults in the United States adults despite  the influential role of SDoH in shaping individuals' health behaviors and outcomes. Our purpose was to  explore the effects of SDoH on adherence to cancer prevention recommendations among  adults in the United States Methods: We used data from the Health Information National Trends Survey (HINTS), 6 cycle (2022).  Adults aged 18 years and above were included. Adherence to cancer prevention recommendations was measured with the 2018 World Cancer Research Fund (WCRF)/American Institute for Cancer Research (WCRF/AICR) Cancer Prevention Recommendations Score.  SDoH was measured based on the American Cancer society's five core SDOH domains (economic stability, social and community context, neighborhood and built environment, education access, and healthcare access). Weighted hierarchical multiple regression models were conducted using each domain of SDOH as a block, controlling for age, gender, race, selfcare efficacy, cormorbidity, cancer risk perception and  belief about cancer,  Jackknife replicate weights were incorporated into the analyses. Results: The sample consisted of 6252 respondents with a mean age of 55.6 (SD, 17.4) years,  The  estimated mean adherence rate  to cancer prevention recommendations among adults in the United States was  40.4% (SD 21.8) .Adherence to  cancer prevention recommendations was positively associated with  having a college education compare to less than high school education (Odd Ratio [OR], 6.29, P = .019),  combined household income of $75,000 and above compare to combined household income of less than $20,000 ( OR, 5.11 , P= .014) , retired compared to full-time employement ( OR, 4.87, P < .001), access to health insurance compared to lack of health insurance  (OR, 4.01, P= .020). These findings suggest that  interventions targeting  the effects of SDoH on cancer on adherence to cancer prevention recommendations may consider the  socioeconomic context of targeted individuals. Such interventions should focus on addressing barriers related to education access, income stability, employment status  and healthcare access.  

Citation Format: Adaeze Aroh, Ifeanyi N. Madujibeya. Examining the role of Social Determinants of Health (SDoH) on adherence to cancer prevention recommendations: Evidence from a national representative sample [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A089.
Abstract A102: Evaluating relationship between food environment and pancreatic cancer demographics and outcomes
Authors: Vudatha Vignesh , Liu Christopher , He Jian , Freudenberger Devon , Wages Nolan , Trevino Jose
Published: December 2023

Introduction: Various socioeconomic factors have been investigated in the context of pancreatic cancer outcomes. However, the impact of factors relating to one’s ability to access healthy food such as food desert residence have not been studied. This study aimed to utilize a state-wide cancer database to explore the intersectionality of food desert residence with other patient socioeconomic factors as well their respective relationships with pancreatic cancer survival. Methods: The Virginia Department of Health Cancer Registry was queried for patients between 18 and 89 years of age who were diagnosed with a primary pancreatic malignancy during the 2009-2018 time frame. Patient addresses at presentation were mapped onto the United States Department of Agriculture (USDA) Food Access Research Atlas to determine food desert residence. Demographics, tumor characteristics, treatment characteristics, and survival data were collected. R version 4.3.0 (Vienna, Austria) was utilized to assess data via descriptive statistics, bivariate and multivariate analysis. Results: Patients’ age at diagnosis, insurance types, and race were significantly associated with their food desert residential status at baseline. Kaplan-Meier analysis demonstrated that while receipt of surgery and chemotherapy (p < 0.0001) were associated with decreased mortality, food desert status was not substantially associated with mortality risk within this cohort. In the fully adjusted Cox regression model, patients in the Other race category (mostly Asian Americans) had a statistically lower hazard ratio compared to Caucasian patients (adjusted HR 0.62; 95% CI 0.39-0.97). Patients with private insurance (adjusted HR 0.45; 95% CI 0.24-0.87), Medicare/Medicaid (adjusted HR 0.46; 95% CI 0.24-0.88), or other type insurance (adjusted HR 0.36; 95% CI 0.17-0.78) had lower hazard ratios compared to those who were uninsured. Conclusions: Patient food desert residence status and other socioeconomic factors are interconnected. While living in a food desert alone was not associated with pancreatic cancer survival, race and insurance status were found to be predictors of decreased mortality risk. Future studies are warranted to investigate the disease characteristics and survival profile of patients with both low access to healthy foods and low income. 

Citation Format: Vignesh Vudatha, Christopher Liu, Jian He, Devon Freudenberger, Nolan Wages, Jose Trevino. Evaluating relationship between food environment and pancreatic cancer demographics and outcomes [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A102.
Abstract A117: Operational strategies for achieving NCI comprehensive cancer center community outreach and engagement objectives: Impact and logic models
Authors: Salinas Manisha , Albertie Monica , Murrell Doug , Odedina Folakemi
Published: December 2023

Background: The National Cancer Institute’s (NCI) Cancer Center Support Grants (CCSGs) encourages Cancer Centers to address health disparities and reduce the cancer burden in their Catchment Area (CA) through an organized Community Outreach and Engagement (COE) structure.  COE activities focus on engaging communities to address cancer needs through bidirectional partnership, facilitation of research that meets community needs, and the implementation of evidence-based practices. Methods: Following a 2018 “satisfactory to good” rating for COE, the Mayo Clinic Comprehensive Cancer Center (MCCCCC) developed a transition team to specifically address the critique and create a transformative plan for engaging communities to address cancer burden in the CA.  An impact model was developed to illustrate the components of the CCSG and connect those components to short- and long-term COE outcomes. A logic model was developed to track and monitor activities for continuous process improvement for all COE activities. Results: The impact and logic model serve as a roadmap to monitor progress towards short- and long-term COE goals of the MCCCC. The COE operational strategies draw upon bidirectional partnership, evidence-based practices, and research facilitation to respond to the CCSG critique. Conclusion: These strategies demonstrate successful practices in addressing cancer burden, promoting health equity and eliminating cancer disparities in the MCCCC CA.

Citation Format: Manisha Salinas, Monica Albertie, Doug Murrell, Folakemi Odedina. Operational strategies for achieving NCI comprehensive cancer center community outreach and engagement objectives: Impact and logic models [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A117.
Abstract B001: The effect of chronic psychological stress during puberty and early adulthood on breast cancer risk and development
Authors: Banks Briana , Brady Matthew
Published: December 2023

Breast cancer is the second most common cancer among women in the United States. Puberty is a well-established sensitive period in women when breast cancer (BC) risk is increased by the physical environment for example exposure to chemical carcinogens, synthetic estrogens, endocrine disrupters, radiation, etc. However, relatively little is known about effects of exposure to chronic psychological stress from the social environment during this time period (puberty and early adulthood). In previous studies using the Sprague-Dawley rat model of spontaneous mammary cancer, chronically heightened glucocorticoid stress reactivity arising from imposed social isolation after weaning increased duration of glucocorticoid release in response to everyday stressors, impeded mammary gland ductal development, and caused earlier and more aggressive mammary gland cancer incidence during adulthood. However due to the period of isolation lasting from weaning to death, a critical time period in which these changes occurred was not established. Here we found that chronic social isolation only during puberty and early adulthood results in alterations in mammary gland gene expression patterns and preservation of mammary stem/progenitor cells. We have observed that social isolation beginning at five weeks and ending at 21 weeks leads to a 4-fold increase in the key metabolic lipogenic enzymes ATP citrate lyase (ACLY; p-value = 0.008), 2-fold increase in acetyl-CoA carboxylase (Acaca; p-value=0.01), and 1.88-fold change in stearoyl-CoA desaturase 1 (Scd1; p-value = 0.50). Interestingly, we have also observed that social isolation during this time period, leads to a slight decrease (0.70-fold change) in hexokinase 2 (HK2; p-value= 0.007). Regarding mammary stem/progenitor cell preservation, we found that social isolation beginning at five weeks and ending at 17 weeks leads to a significant increase in the number of mammary gland stem/progenitor cells (isolated by FACS sorting). This correlation was only observed in response to corticosterone reactivity, and null to exposure to estrogen or progesterone. In summary, our findings suggest that social isolation during puberty and early adulthood correlates to increased glucocorticoid exposure resulting in metabolic reprogramming in the mammary gland and inappropriate preservation of mammary stem/progenitor cells. Altogether these factors may increase the risk of mammary cancer occurrence later in adulthood.

Citation Format: Briana Banks, Matthew Brady. The effect of chronic psychological stress during puberty and early adulthood on breast cancer risk and development [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B001.
Abstract B003: Inhibition of cell growth and migration by polyisoprenylated cysteinyl amide inhibitors of a mutant KRAS Black American lung cancer cell line involves MAPK pathway activation and disruption of the cytoskeleton
Authors: Ofosu-Asante Kweku
Published: December 2023

KRAS mutations are the most common oncogenic mutations in lung adenocarcinoma in Black Americans. Polyisoprenylated Cysteinyl Amide Inhibitors (PCAIs) constitute a group of potential cancer therapy agents that we designed to specifically disrupt and suppress hyperactive G-protein signaling, as caused by mutated RAS proteins. Here we investigate the effects of PCAIs on the viability, G-protein levels, downstream mediators, cytoskeletal structure, focal adhesion protein and apoptosis-related proteins on the KRAS-mutated, Black American-derived lung adenocarcinoma cell line, NCI-H23. Western blotting was used to determine the effect of the PCAIs on the phosphorylation levels of MAPK pathway enzymes. After 48-hour exposure to 5 μM of the PCAIs, 57 ± 3.6 to 150 ± 4.1 % increases of BRAF, MEK1/2, ERK1/2, and p90RSK phosphorylation along with a 60 ± 6.5 to 78 ± 4.0 % decrease of pRAF1 phosphorylation were observed, indicating significant changes in RAS signaling. Furthermore, 5 μM of NSL-YHJ-2-27 depleted the singly polyisoprenylated monomeric G-proteins RAC 1/2/3 and CDC42 by 77 ± 5.5 and 76 ± 2.0 %, respectively. The depletion of these key cytoskeletal proteins, and collapse of F-actin and vinculin punctates, may account for the observed inhibition of cell migration after 72-hour exposure to NSL-YHJ-2-27 and NSL-YHJ-2-46, respectively. The invasion area of 3D NCI-H23 spheroids after treatment with 10 μM of NSL-YHJ-2-27 and NSL-YHJ-2-46 decreased by 87 ± 0.1% and 92 ± 0.3 %, respectively. Treatment with 0.5 μM NSL-YHJ-2-27 and NSL-YHJ-2-46 caused cell rounding and reduction of mean cell areas by 30 ± 5.0 and 42 ± 0.6 %, respectively. Mean cell area occupied by vinculin punctates decreased by 51 ± 2.6 % and 31 ± 2.8 % after exposure to 0.5 μM NSL-YHJ-2-27 and NSL-YHJ-2-46, respectively. NSL-YHJ-2-27 (5 μM) depleted full-length inactive caspase 3 and 7 levels by 72 ± 5.8 and 91 ± 7.0 %, respectively. These findings show the direct effects of the PCAIs on the KRAS signaling pathway thereby supporting their continuous development as potential targeted therapies for cancers with RAS mutations.

Citation Format: Kweku Ofosu-Asante. Inhibition of cell growth and migration by polyisoprenylated cysteinyl amide inhibitors of a mutant KRAS Black American lung cancer cell line involves MAPK pathway activation and disruption of the cytoskeleton [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B003.
Abstract B028: Antiproliferative effect of a cathepsin L inhibitor on hepatocellular carcinoma
Authors: Crown Olamide O. , Ogungbe Ifedayo V. , Noubissi Felicite K.
Published: December 2023

Liver cancer has emerged as one of the fastest-growing malignancies in the United States, despite an overall decline in  cancer incidence and mortality rates. Hepatocellular carcinoma (HCC) exhibits significant gender and race/ethnicity differences in incidence and mortality. The need to address this escalating problem necessitates the development of novel and effective chemotherapeutic agents for HCC. The antiproliferative actions of two cathepsin L inhibitors (compounds 1 and 2) using in vitro and mice HCC xenograft models were investigated in this study. In addition, the ability of the compounds to inhibit CatB and generate ROS in HCC cell lines was investigated. The inhibitors have antiproliferative effects on Hep G2 and Hep 3B cell lines with low micromolar IC 50 values. Compound 1 preferentially inhibits both recombinant and endogenous CatL in a time-dependent manner compared to CatB. The levels of ROS produced when cells were treated with compound 1 were non-significant compared with vehicle-treated controls . Given the superior efficacy of compound 1 over its analog in antiproliferative studies, it was advanced to in vitro ADME studies. The inhibitor has bidirectional cellular permeability and is not a substrate for the P-glycoprotein efflux pump (P-gp). In mice, it produced a significant reduction in the sizes of subcutaneous tumors with no gross toxicity. Transcriptomics analysis using RNA-Seq revealed that the cell migration pathway was enriched in a time and dose-dependent manner. In addition, genes responsible for apoptosis and cell structural  organization were overexpressed. Overall, the CatL inhibitors under investigation appear as promising starting points for investigation as potential chemotherapy against HCC.

Citation Format: Olamide O. Crown, Ifedayo V. Ogungbe, Felicite K. Noubissi. Antiproliferative effect of a cathepsin L inhibitor on hepatocellular carcinoma [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B028.
Abstract B029: Genetic changes & polymorphisms of neurotransmitter receptors associated with chemotherapy-induced nausea and vomiting in cancer patients
Authors: Obadipe John Abiodun , Samuel Titilola Aderonke , Akinloye Oluyemi , Jimoh Mutiu Alani , Alabi Adewunmi Olabimpe , Alabi Babatunde M. , Adewusi Oluwabanke Temitope , Odero-marah Valerie
Published: December 2023

Chemotherapy-induced nausea and vomiting (CINV) affect cancer patients’ survival and quality of life, despite antiemetic intervention. Polymorphisms in genes involved in nausea and vomiting pathways may influence the risk of CINV response in most cancer patients, who still present with acute and delayed CINV. Hence, this study aimed at profiling Single Nucleotide Polymorphisms (SNPs) of three clinically significant neurotransmitter-receptor encoding genes in cancer patients undergoing chemotherapy. This is a prospective cross-sectional study of 299 cancer patients undergoing chemotherapy, ages 18-75 years, who were selected across three tertiary healthcare institutions in South-west, Nigeria. Socio-demographic, clinical data and CINV occurrence responses were obtained using a self-designed questionnaire and patient interview post-chemotherapy. Target genes from genomic DNA extracted in collected blood samples were amplified by multiplex polymerase chain reaction. Nucleotide sequences were identified by Next Generation Sequencing and analyzed using bioinformatics software. P<0.05 was considered statistically significant for the association between identified SNPs and CINV. The majority of participants presented with advanced-stage cancer (stage 3) as compared to that early-stage 1. Cancer patients who experienced CINV were highly prevalent in breast cancer [84(62.9%); 41(30.60%)] and cervical cancer [33(50%); 33(45.46%)]. SNPs alongside their positions and frequencies were identified in the participants; HTR3A [(5’UTR; rs1062613(C>T), 9(45%)], DRD2 [Exon7; rs6277(G>A), 16(80%), intron 6; rs1076560 (C>A), 16(80%)], COMT [Exon 4; rs4680(G>A), 19(95%)] and TACR1 [Exon2; Y192H(T>C), 11(55%) and Exon 4; (rs17838409 (G>A)] respectively. None of the SNPs was significantly (P>0.05) associated with CINV occurrence. However, rs1062613, rs6277, and rs4680 were significantly (P<0.05) associated with vomiting grade, while rs4680 was found to be significantly associated with nausea severity. The identified neurotransmitter receptors SNPs exert influence on CINV response in cancer patients.

Citation Format: John Abiodun Obadipe, Titilola Aderonke Samuel, Oluyemi Akinloye, Mutiu Alani Jimoh, Adewunmi Olabimpe Alabi, Babatunde M. Alabi, Oluwabanke Temitope Adewusi, Valerie Odero-marah. Genetic changes & polymorphisms of neurotransmitter receptors associated with chemotherapy-induced nausea and vomiting in cancer patients [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B029.
Abstract B088: Association of neighborhood gentrification with prostate cancer in African American and European American men
Authors: Pichardo Catherine M. , Ezeani Adaora , Pichardo Margaret , Agurs-Collins Tanya , Powell-Wiley Tiffany M. , Ryan Brid , Minas Tsion , Bailey-Whyte Maeve , Tang Wei , Dorsey Tiffany H. , Wooten William , Loffredo Christopher A.
Published: December 2023

Abstract Background: Prior studies showed that neighborhood deprivation increases the risk of lethal prostate cancer. However, the role of neighborhood gentrification in prostate cancer development and outcome remains poorly understood. We examined the relationships of gentrification with prostate cancer in a diverse cohort. Methods: This case-control study included 769 cases [405 African American (AA), 364 European American (EA) men] and 1023 controls (479 AA, 544 EA), with 219 all-cause and 59 prostate cancer-specific deaths among cases. Geocodes were linked to a neighborhood gentrification index (NGI) derived from US Census data. Cox and logistic regression  were used to determine associations between NGI, as continuous or quintiles (Q), and outcomes. Results: Adjusting for individual socioeconomic status (SES), continuous NGI was associated with prostate cancer among all men (odds ratio (OR) 1.07, 95%CI 1.01-1.14). AA experienced the highest odds of prostate cancer when residing in tracts with moderate gentrification (Q3 OR 1.79, 95%CI 1.11-2.88). However, EA men experienced a reduced risk of regional/metastatic cancer (risk ratio 0.62, 95%CI 0.40-0.97) with increased gentrification, adjusting for SES. Continuous NGI was associated with mortality among men presenting with localized disease (all-cause HR 1.10, 95%CI 1.01-1.20; disease-specific SHR 1.16, 95%CI: 1.01-1.33).  Conclusions: Findings show that neighborhood gentrification modestly associates with prostate cancer and mortality in this diverse population. They suggest that changing neighborhood socioeconomic environments may affect prostate cancer risk and outcome, likely through multifactorial mechanisms.

Citation Format: Catherine M. Pichardo, Adaora Ezeani, Margaret Pichardo, Tanya Agurs-Collins, Tiffany M. Powell-Wiley, Brid Ryan, Tsion Minas, Maeve Bailey-Whyte, Wei Tang, Tiffany H. Dorsey, William Wooten, Christopher A. Loffredo. Association of neighborhood gentrification with prostate cancer in African American and European American men [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B088.
Abstract B118: Racial and ethnic minorities remain underrepresented in cancer clinical trials despite local cancer incidence
Authors: Herremans Kelly M. , Riner Andrea N. , Vudatha Vignesh , Freudenberger Devon C. , Trevino Jose G.
Published: December 2023

Introduction: Over the last two decades, racial and ethnic minorities have been underrepresented in cancer clinical trials. Some have suggested that location is a barrier to inclusion in cancer clinical trials. The aim of this project is to assess how diversity of cancer clinical trials reflect their surrounding communities. Methods: Cancer clinical trials for the top five most deadly cancers including lung, breast, prostate, colon and pancreatic were selected from ClinicalTrials.gov. Trials were excluded if they were conducted outside the US or in multiple NIH-designated health service areas (HSA). Location-specific enrollment fractions were determined by comparing the proportion of trial participants to the local cancer incidence. National Cancer Institute (NCI) and Centers for Disease Control and Prevention (CDC) state cancer profiles (statecancerprofiles.cancer.gov) were used to determine HSA-specific data of cancer incidence by race and ethnicity. Results: 904 cancer clinical trials were identified from 2008-2022, including lung (n=157), breast (n= 330), prostate (n=219), colon (n=111) and pancreas (n=87). Overall, reporting of race and ethnicity was poor with only 53.6% of total trials reporting race and 35.9% reporting ethnicity. Compared to the local cancer incidence surrounding trial centers, White patients were overrepresented (p<0.0001), whereas Black (p<0.0001), Asian/Pacific Islander (p<0.0001), American Indian/Alaskan (p<0.0001) and Hispanic (p=0.004) were underrepresented. Furthermore, Black patients were underrepresented across breast (p=0.009), prostate (p<0.0001), lung (p<0.0001), colon (p=0.027) and pancreas (p<0.0001) cancer clinical trials when compared to the local cancer incidence. Conclusion: Racial and ethnic minority patients remain underrepresented in cancer clinical trials when compared to local cancer incidence. These findings reaffirm that location is not the only barrier to cancer clinical trial participation. Further efforts are needed to reduce healthcare disparities and improve patient care.

Citation Format: Kelly M. Herremans, Andrea N. Riner, Vignesh Vudatha, Devon C. Freudenberger, Jose G. Trevino. Racial and ethnic minorities remain underrepresented in cancer clinical trials despite local cancer incidence [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B118.
Abstract B120: Association of allostatic load with prostate-specific antigen level among Nigerian men
Authors: Olowokere Olanike , Olasehinde Olutola , De Campos Opeyemi C. , Adebesin Ayomide , Bisi-Adeniyi Titilayomi , Tolulope Olawole , Onyia Abimbola , Rotimi Oluwakemi , Rotimi Solomon Oladapo
Published: December 2023

Objective: Prostate cancer is a prevalent disease among men worldwide, and early detection plays a crucial role in improving patient outcomes. It has been suggested that chronic stress could increase the risk of developing prostate cancer, however, the association between prostate-specific antigen (PSA) levels and chronic stress, as measured by allostatic load (AL) - remains poorly understood. Hence, this study aims to investigate the association between PSA levels and allostatic load among Nigerian men. Methods: A cross-sectional study was conducted involving 80 males in Ota, Nigeria. Data on demographic characteristics, lifestyle factors, medical history, and occupational stressors were collected through structured questionnaires. Blood samples were obtained to measure PSA levels, and the allostatic load was assessed using a composite index based on physiological indicators such as blood pressure, lipid profile, glycemic control, and inflammatory markers. Multiple linear regression analysis will be used to examine the association between PSA, AL, lifestyle factors, and socioeconomic status. Expected Results: We hypothesize a positive correlation between PSA levels and allostatic load among Nigerian men. Hence, this suggests that higher levels of allostatic load, an indicator of chronic stress and physiological dysregulation, may be associated with elevated PSA levels. Conclusion: If a positive correlation between PSA and allostatic load is established, it could suggest that managing chronic stress and improving physiological regulation might have a positive impact on prostate health.

Citation Format: Olanike Olowokere, Olutola Olasehinde, Opeyemi C. De Campos, Ayomide Adebesin, Titilayomi Bisi-Adeniyi, Olawole Tolulope, Abimbola Onyia, Oluwakemi Rotimi, Solomon Oladapo Rotimi. Association of allostatic load with prostate-specific antigen level among Nigerian men [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B120.
Abstract B124: An assessment of awareness on oral cancer among smokeless tobacco users in the rural skirts of Tamil Nadu, India
Authors: Francis Delfin Lovelina , SP Saravanan
Published: December 2023

Background In India, the number of newly diagnosed tobacco related cancers has been estimated at approximately 250 000 out of a total of 700 000–900 000 new cancers diagnosed each year. Smokeless tobacco (ST) is tobacco consumed orally, not smoked. It has been in use for as long as other forms of tobacco consumption and its use have increased. The deleterious effects of smokeless tobacco use are perhaps not as well-known as those produced by smoking.  Smokeless tobacco use has been recognized as a cause of cancer. In developing countries, tobacco is mostly chewed with other ingredients. The aim of this study is to assess the awareness of health hazards of tobacco among smokeless tobacco users in Kancheepuram District, Tamil Nadu, India. METHODOLOGY The inhabitants of the villages in Kancheepuram district were recruited after ethical clearance from the institutional ethical board, permission from the Village panchayat leader and informed consent from the participants to conduct the study. Inhabitants of the villages aged 18 to 75 years and present on the day data collection and who were willing to participate in the study were included.Random sampling method was used and data was collected from a cross-sectional survey, using a pretested Questionnaire, which included Demographic data, tobacco habits, its frequency and form.Anti-tobacco counselling was given on the spot and followed.The data collected was analysed using SPSS version21. RESULT: The study population consisted of total 800 individuals, male 400 and females 400. From the results it is observed that more than 70% were unaware of the harmful effects of using tobacco products. Majority of the females use smokeless tobacco and smoking tobacco was common among males. Most common cause of tobacco use was pleasure 32.5% and inducing factor were friends 43.7%. High prevalence of potentially malignant lesion were found among this population. Effectiveness of anti-tobacco counselling is greater among the females compared to males. CONCLUSION: The dangers from smoking and chewing tobacco are well documented within the literature but the public’s lack of knowledge of the risks is a concern. Health professionals are encouraged to disseminate information on the subject as widely as possible and improve existing screening programmes to ensure that the public is made aware of these risks, especially those within high-risk groups.  

Citation Format: Delfin Lovelina Francis, Saravanan SP. An assessment of awareness on oral cancer among smokeless tobacco users in the rural skirts of Tamil Nadu, India [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B124.
Abstract B125: Reproductive factors and thyroid cancer risk: The multiethnic cohort study
Authors: Abe Janine V. , Park Song-Yi , Haiman Christopher A. , Marchand Loïc Le , Hernandez Brenda Y. , Wilkens Lynne R.
Published: December 2023

Background : Thyroid cancer is the most common endocrine cancer worldwide, with the incidence in women being three times that of men. Several reproductive and hormonal factors have been proposed as possible contributors to thyroid cancer risk, including age at menarche, parity, age at menopause, oral contraceptive use, surgical menopause, and hormone replacement therapy. Our study aimed to investigate potential reproductive/hormonal factors in a multiethnic population. Methods : A prospective cohort study of women of diverse racial and ethnic groups in the Multiethnic Cohort Study (n=118,344) was used. Included were 373 papillary thyroid cancer cases, linked to SEER cancer incidence and statewide death certificate files in Hawaii and California. Exposures investigated include age at menarche, parity, menopausal status and type, birth control use, and outcomes of first pregnancy. Cox proportional hazards models of papillary thyroid cancer were used to obtain relative risk (RR) and 95% confidence intervals (CI) to examine the associations with reproductive/hormonal factors. Results : We observed a statistically significant increased risk of papillary thyroid cancer for hysterectomy, oophorectomy, surgical menopause, and not having a child by age 20. The adjusted estimates for oophorectomy RR 1.66 (95% CI: 1.31, 2.11) and hysterectomy RR 1.82 (95% CI: 1.42, 2.34). Menopause due to surgery was associated with a 55% increase in risk (RR 1.55, 95% CI: 1.22, 1.97) and nulliparity vs ≤ 20 years of age at first livebirth was related to a 51% increased risk (adjusted RR 1.51, 95% CI: 1.07, 2.15). Adjustment factors included age and race/ethnicity and menopausal status, menopausal type, and oral contraception where appropriate. Former use of estrogen menopausal hormone therapy was associated with a 35% increased risk (adjusted RR: 1.35, 95% CI: 1.02, 1.79). No significant heterogeneity was seen in these associations by race/ethnicity (p het >0.48). Conclusion : The reproductive risk factors for papillary thyroid cancer reported in the literature were largely confirmed in our multiethnic population. Our analysis finds having a hysterectomy or oophorectomy and the use of MHT are associated with an increased risk of papillary thyroid cancer, and having a child at a younger age is associated with a reduction in thyroid cancer risk.

Citation Format: Janine V. Abe, Song-Yi Park, Christopher A. Haiman, Loïc Le Marchand, Brenda Y. Hernandez, Lynne R. Wilkens. Reproductive factors and thyroid cancer risk: The multiethnic cohort study [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B125.