bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthetic Lethal Interaction with BCL-XL Blockade Deepens Response to Cetuximab in Patient-Derived Models of Metastatic Colorectal Cancer
Authors: Leto Simonetta M. , Ferri Martina , Sassi Francesco , Zanella Eugenia R. , Cottino Francesca , Vurchio Valentina , Catalano Irene , Ferrero Alessandro , Zingaretti Caterina C. , Marchiò Caterina , Grassi Elena , Trusolino Livio , Bertotti Andrea
Published: January 2023

Purpose:

Approximately 20% of patients with RAS wild-type metastatic colorectal cancer (mCRC) experience objective responses to the anti-EGFR antibody cetuximab, but disease eradication is seldom achieved. The extent of tumor shrinkage correlates with long-term outcome. We aimed to find rational combinations that potentiate cetuximab efficacy by disrupting adaptive dependencies on antiapoptotic molecules (BCL2, BCL-XL, MCL1).

Experimental Design:

Experiments were conducted in patient-derived xenografts (PDX) and organoids (PDXO). Apoptotic priming was analyzed by BH3 profiling. Proapoptotic and antiapoptotic protein complexes were evaluated by co-immunoprecipitation and electroluminescence sandwich assays. The effect of combination therapies was assessed by caspase activation in PDXOs and by monitoring PDX growth.

Results:

A population trial in 314 PDX cohorts, established from as many patients, identified 46 models (14.6%) with appreciable (>50% tumor shrinkage) but incomplete response to cetuximab. From these models, 14 PDXOs were derived. Cetuximab primed cells for apoptosis, but only concomitant blockade of BCL-XL precipitated cell death. Mechanistically, exposure to cetuximab induced upregulation of the proapoptotic protein BIM and its sequestration by BCL-XL. Inhibition of BCL-XL resulted in displacement of BIM, which was not buffered by MCL1 and thereby became competent to induce apoptosis. In five PDX models, combination of cetuximab and a selective BCL-XL inhibitor triggered apoptosis and led to more pronounced tumor regressions and longer time to relapse after treatment discontinuation than cetuximab alone.

Conclusions:

In mCRC tumors that respond to cetuximab, antibody treatment confers a synthetic-lethal dependency on BCL-XL. Targeting this dependency unleashes apoptosis and increases the depth of response to cetuximab.
Discovery of a Novel ATP-Competitive MEK Inhibitor DS03090629 that Overcomes Resistance Conferred by BRAF Overexpression in BRAF-Mutated Melanoma
Authors: Takano Kohei , Munehira Yoichi , Hatanaka Mana , Murakami Ryo , Shibata Yoshihiro , Shida Takeshi , Takeuchi Kosuke , Takechi Sho , Tabata Toshiki , Shimada Takashi , Kishikawa Shuhei , Matsui Yumi , Ubukata Osamu , Seki Takahiko , Kaneta Yasuyuki
Published: January 2023

Patients with melanoma with activating BRAF mutations (BRAF V600E/K) initially respond to combination therapy of BRAF and MEK inhibitors. However, their clinical efficacy is limited by acquired resistance, in some cases driven by amplification of the mutant BRAF gene and subsequent reactivation of the MAPK pathway. DS03090629 is a novel and orally available MEK inhibitor that inhibits MEK in an ATP-competitive manner. In both in vitro and in vivo settings, potent inhibition of MEK by DS03090629 or its combination with the BRAF inhibitor dabrafenib was demonstrated in a mutant BRAF-overexpressing melanoma cell line model that exhibited a higher MEK phosphorylation level than the parental cell line and then became resistant to dabrafenib and the MEK inhibitor trametinib. DS03090629 also exhibited superior efficacy against a melanoma cell line–expressing mutant MEK1 protein compared with dabrafenib and trametinib. Biophysical analysis revealed that DS03090629 retained its affinity for the MEK protein regardless of its phosphorylation status, whereas the affinity of trametinib declined when the MEK protein was phosphorylated. These results suggest that DS03090629 may be a novel therapeutic option for patients who acquire resistance to the current BRAF- and MEK-targeting therapies.
Abstract A007: Racial disparities bias oncology AI models
Authors: Chen Richard J. , Williamson Drew F.K. , Lu Ming Y. , Chen Tiffany Y. , Lipkova Jana , Shaban Muhammad , Mahmood Faisal
Published: January 2023

Deep learning-based computational pathology models can be trained to make accurate diagnostic, prognostic, and therapeutic response predictions. Such models have also recently received regulatory approval in Europe and in the US. However, a majority of these models are trained and independently evaluated on large repositories of data representative of overall patient populations without extensive evaluation on underrepresented minorities or other subgroups. Here we show that such pathology AI models can be biased when independent and external evaluation test sets are stratified by race, demonstrating the need for more extensive evaluation of such models before regulatory approvals

Citation Format: Richard J. Chen, Drew F.K. Williamson, Ming Y. Lu, Tiffany Y. Chen, Jana Lipkova, Muhammad Shaban, Faisal Mahmood. Racial disparities bias oncology AI models [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A007.
Abstract A087: Developing immortalized human alveolar epithelial cell models to study lung adenocarcinoma in Black Americans
Authors: Puente Pablo E. , Yan Chunli , Gregory Matthew , Belony Nadine , Lamango Nazarius , Huang Yong , Offringa Ite A.
Published: January 2023

Lung cancer is a source of racial disparity among Black Americans, especially men. Despite lower tobacco exposure among Black men than White men, Black men are 37% more likely to develop lung cancer. Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer in all ethnic/racial groups, including Blacks. KRASis the most frequently mutated driver gene in Black LUAD (~30%), and NRAS mutations are also seen (1-2%). A given oncogenic mutation could have different effects on a patient based on their racial/ethnic genetic background. Thus, studying the appropriate driver mutations in the correct model and genetic background is essential. Unfortunately, to our knowledge, there is only one LUAD cell line from a Black subject. Therefore, we are deriving immortalized human alveolar epithelial cell (hAEC) lines from Black Americans to develop models to study lung adenocarcinoma in Blacks. The Offringa lab has recently developed a rapid method to generate hAEC lines. We have generated three distinct hAEC lines from de-identified remnant transplant lungs from White Americans. Here, we will use the same method to establish new hAEC lines from de-identified human remnant transplant lungs from Black American subjects. hAECs grow well in 2-dimensional (2D) cultures as epithelial monolayers are capable of forming alveolar-like organoids in 3-dimensional (3D) cultures with fibroblasts and Matrigel. We will introduce the KRAS driver mutation alone or in combination with other oncogenes into the hAECs using CRISPR/Cas9 editing. The cell lines will be used to test KRAS-targeting therapeutics, including polyisoprenylated cysteinyl amide inhibitors (PCAIs). These agents have been shown to disrupt RAS-mediated signaling in ethnically/racially diverse cell lines. Our approach yields new cell lines that provide a valuable system to study LUAD in Black Americans. Through our research, we intend to address one facet of the prominent lack of representation of Black Americans in LUAD studies.

Citation Format: Pablo E. Puente, Chunli Yan, Matthew Gregory, Nadine Belony, Nazarius Lamango, Yong Huang, Ite A. Offringa. Developing immortalized human alveolar epithelial cell models to study lung adenocarcinoma in Black Americans [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A087.
Abstract A098: Health access and willingness to screen for prostate cancer among black men in Nigeria, Cameroon, and United States
Authors: Bolajoko Opeyemi O. , Oladoyinbo Catherine A. , Odedina Folakemi T.
Published: January 2023

Background: Access to health care is important for prostate cancer (CaP) screening and control. There is evidence of the racial disparities in health access of black men and Hispanics; however, the comparison between black men's access to health in the United States and those in Africa has not been fully elucidated. Aim: This study aims to evaluate health access and willingness to screen for CaP among black men in Nigeria, Cameroon, and United States. Methods: The Prostate Cancer Transatlantic Consortium (CaPTC) family cohort study phase 1 data of 500 community-dwelling black men in Nigeria, Cameroon, and the United States between 35 and 70 years were used in this study. The association between healthcare access and the willingness to screen for CaP was assessed. The data were described using numbers and percentages; Chi-square was used to test for the association between healthcare access and willingness to screen for CaP. P-values < 0.05 was set as significant. Results: The study showed that 86.1% were from Nigeria, 6.1% from Cameroon, and 7.8% from the United States. Most (75.6%) had never had prostate specific antigen (PSA) screening, and 87.8% had never had digital rectal examination (DRE). Willingness to screen was found in 36.8%, while 11.6% could not decide to screen; 27.4% and 33% were willing to screen for DRE and PSA, respectively. Majority (83.8%) had no access to medical doctors in the last 12 months, and the country of residence was not found to improve access to health (p= 0.378). Healthcare insurance coverage was more available to the US participants with 68.4%, 42.9% in Nigeria, and 16.7% in Cameroon. Overall willingness to screen, willingness for DRE and PSA screening were significantly associated with the country of residence with p-values of 0.02, <0.01, and <0.01, respectively. Having healthcare coverage was also associated with overall willingness to screen (p=0.033). Conclusions: The study showed that country of residence was not associated with health access; however, willingness for CaP screening was significantly associated with the country of residence and healthcare insurance coverage.

Citation Format: Opeyemi O. Bolajoko, Catherine A. Oladoyinbo, Folakemi T. Odedina. Health access and willingness to screen for prostate cancer among black men in Nigeria, Cameroon, and United States [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A098.
Abstract B010: Systematic review to identify how nurses may improve communication with Black patients living beyond a cancer diagnosis
Authors: Hirschey Rachel , Guimond Elizabeth , Getachew Berhan , Sheffield-Abdullah Karen Miles , Conklin Jamie , Nolan Timiya S.
Published: January 2023

Compared to White patients, Black patients are more often diagnosed with several types of cancer, experience more treatment related complications and worse outcomes. Multi-level factors influence these disparities. At the interpersonal level, disparities in patient-clinician communication exist for patients of different races. For example, patient clinician conversations are often shorter for Black as compared to White patients. The purpose of this literature review is to examine factors that impact communication between Black patients and their oncology nurse clinicians and consider how communication can be improved. A systematic literature review was conducted following PRISMA guidelines. PubMed, CINAHL with Full Text (EBSCOhost), and Scopus were used to locate studies that met the following inclusion criteria: (1) focused on individual living beyond a cancer diagnosis, (2) contained results specific to Black or African American participants, and (3) focused on patient-clinician communication. Two researchers independently reviewed 935 title/abstracts, then 71 full-text articles, to identify a final 24 studies that met inclusion criteria. Each included study was evaluated for level of evidence strength to inform nursing practice. The Matrix Method was used to identify common themes across studies. Five themes were identified: (1) relationship building, (2) trust, (3) shared decision-making, (4) topics of patient concern, and (5) consideration of family. Results indicate several ways in which nurses can work to improve communication for Black patients.

Citation Format: Rachel Hirschey, Elizabeth Guimond, Berhan Getachew, Karen Miles Sheffield-Abdullah, Jamie Conklin, Timiya S. Nolan. Systematic review to identify how nurses may improve communication with Black patients living beyond a cancer diagnosis [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B010.
Abstract B023: The impact of the promotoras program on knowledge, attitudes, and cervical cancer screening among Hispanic/Latina women: Rapid review
Authors: Gareis Christina E. , Hunter Paul , Leader Amy
Published: January 2023

Cancer is one of the leading causes of death among Hispanics/Latinos adults. Within the Hispanic/Latino population, women have higher rates of infection-related cancers, such as cervical cancer, compared to other racial and ethnic minorities. Women who have a poor education, low socioeconomic status, and do not speak English have a greater incidence of cervical cancer. However, promotoras, who are health promoters, have been shown to be an effective public health intervention because they provide education, address barriers, and increase access to preventive care services. This rapid review identified and examined studies from PubMed and Scopus on the impact that promotoras had on Hispanic/Latina women regarding knowledge, attitudes, and cervical cancer screening uptake. Out of the 490 articles that met the search criteria, 14 met the inclusion criteria. Studies included various types of promotora interventions, varied in sample size, design, location, and in length of study. Several studies suggested that promotoras are effective in increasing knowledge and awareness of cervical cancer, Pap tests, and human papilloma virus (HPV). Additionally, promotoras are effective in positively changing attitudes, increasing self-efficacy, and perceived benefits of routine Pap test screening. Lastly, the promotoras demonstrate that they can change cancer screening behaviors and address financial and capacity barriers of cervical cancer screening. While most studies reported findings, a few studies showed no change in outcomes or mixed results. Overall, promotoras have a positive impact in overcoming challenges to cervical cancer screening in Hispanic/Latino communities.

Citation Format: Christina E. Gareis, Paul Hunter, Amy Leader. The impact of the promotoras program on knowledge, attitudes, and cervical cancer screening among Hispanic/Latina women: Rapid review [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B023.
Abstract B033: Increasing sexual transmitted diseases and promoting condom use among youth: Evaluation of year 2 data from the Proud Teens of Philly (PTOP) program
Authors: Truehart Jade A. , Merceir Ra'Ann , Bhimla Aisha , Tan Yin , Liao Sabrina , Wang Min Qi , Sileo Jane , Allen Maya , Ma Grace X.
Published: January 2023

Background: Rates of sexually transmitted disease (STD) and teen pregnancy are much higher in Philadelphia than the national average. Proud Teens of Philly (PTOP) is a sexual health program aimed at reducing the high teen birth rate and STD cases in Philadelphia. The program provides sexual health education to high-risk youth ages 12-19 in the Greater Philadelphia area. The materials used to implement the PTOP program, “Making Proud Choices”, is an evidence-based curriculum that was reviewed and tailored for its cultural and age appropriateness, and medical accuracy. Methods: During the second year of the program, PTOP was implemented virtually and in-person to 411 youth in Philadelphia schools and community-based organizations. Community-based participatory research (CBPR) strategies and systems thinking approach were used in site and participant recruitment, program implementation, and evaluation. The educational content consisted of 8 modules of the “Making Proud Choices” curriculum. Pre and post surveys were administered to participants at the first and last implementation sessions, respectively. During Year 2, 391 pre-surveys and 208 post-surveys were collected. Results: There were significant increases in knowledge about fluids that transmit HIV (pre=23.47 post=25.07 t=4.65 p=<.0001), behaviors that transmit HIV (pre=10.86 post= 19.05 t=9.37 p=<.0001), condoms preventing pregnancy (pre=59.57 post=76.41 t=2.8 p=0.0057) and condoms preventing HIV (pre=46.29 post=68.92 t=2.98 p=0.0035). There was also significant increase in knowledge about affirmative consent before sexual behaviors (pre=20.05 post= 0.42 t=3.71 p=0.0003) and preparedness to use condoms (pre=39.34 post=59.19 t=2.43 p=0.0169) Conclusion: PTOP, a sexual health program was effective in increasing knowledge of STD and condom use among high-risk teens in Philadelphia. We will discuss the use of CBPR strategies and systems thinking in the design and implementation of this program.

Citation Format: Jade A. Truehart, Ra'Ann Merceir, Aisha Bhimla, Yin Tan, Sabrina Liao, Min Qi Wang, Jane Sileo, Maya Allen, Grace X. Ma. Increasing sexual transmitted diseases and promoting condom use among youth: Evaluation of year 2 data from the Proud Teens of Philly (PTOP) program [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B033.
Abstract B099: Localized implicit and explicit forms of anti-gay prejudice and area-specific chronic disease prevalence
Authors: Garrido Carlos O.
Published: January 2023

Objectives. Ample evidence suggests that prejudice detrimentally affects individual-level health status, but little is known about associations between anti-gay/lesbian prejudice and prevalence for stress-modulated chronic diseases. Moreover, research examining implicit or “automatic” and explicit or “overt” prejudice in relation to the health status of sexual minorities and non-minorities remain scant. Thus, I examined the influence of dual forms of prejudice on chronic disease disparities among gay male and lesbians in relation to straight-identifying individuals. Methods. Using the Behavioral Risk Factor Surveillance System (BRFSS) survey responses collected in 2020 and localized measures of anti-gay prejudice from an online forum, I examined the association between geographic area-specific levels of implicit and explicit anti-gay/lesbian prejudice and prevalence for the following stress-modulated chronic conditions: heart disease, diabetes, stroke, and cancer. The sample included gay/lesbian and straight male and female adults living in 28 U.S. states. Results. Relative to areas with low prejudice, residents living in areas high in prejudice (both forms) reported higher prevalence for diabetes and COPD among sexual minorities. Both forms of prejudice predicted greater number of reported days of poor physical and mental health for gay male and lesbian residents. Among heterosexual residents, implicit prejudice predicted greater prevalence for all diseases and explicit prejudice predicted prevalence for all diseases but cancer. Conclusions. Findings show that both forms of anti-gay prejudice predict chronic disease diagnoses for gay/lesbian and straight residents. Theoretical insight using the minority-stress model and practical implications are discussed.

Citation Format: Carlos O. Garrido. Localized implicit and explicit forms of anti-gay prejudice and area-specific chronic disease prevalence [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B099.
Abstract B112: Overall satisfaction with cancer care in a lesbian, gay, bisexual, transgender, queer and intersex population
Authors: Burnett Colin , Jesdale William
Published: January 2023

Background: Lesbian, gay, bisexual, transgender, queer, and intersex (LGBTQI+) people living with cancer have unique health considerations that must be assessed to provide high quality, individualized patient care. LGBTQI+ health education materials may play a pivotal role in cancer survivors’ (“persons on a cancer journey”) experiences throughout their cancer care continuum. Methods: We identified 2,500 LGBTQI+ persons on a cancer journey who completed the “OUT: National Cancer Survey,” conducted by the National LGBT Cancer Network in 2020-2021, and classified participants by their self-reported level of satisfaction with their overall cancer care. We examined care satisfaction in relation to patient access to LGBTQI+-tailored health education resources and the influence of gender identity and/or sexual orientation on survivors’ experiences before, during, and after cancer treatment. Results: Most persons on a cancer journey reported lacking access to vital health education resources specific to their LGBTQI+ identities in areas of mental health (70%), physical activity (91%), tobacco cessation (89%), and alcohol consumption (86%), regardless of their satisfaction with overall care. Further, the majority of participants believe it would be valuable to receive tailored LGBTQI+ education materials specifically in areas of mental health (80%) and physical activity (67%), while also incorporating information specific to LGBTQI+ individuals into their post-treatment care plans (74%). Conclusion: LGBTQI+ persons on a cancer journey value information and health education materials that are tailored. Increased access to such materials may have large implications for the satisfaction of LGBTQI+ cancer persons on a cnacer journey with their overall cancer care.

Citation Format: Colin Burnett, William Jesdale. Overall satisfaction with cancer care in a lesbian, gay, bisexual, transgender, queer and intersex population [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B112.
Abstract C021: Fucoxanthin anti-tumor effects on the proliferation, angiogenesis, apoptosis, and migration of triple-negative breast cancer cells
Authors: Ahmed Shade' , Mendonca Patricia , Messeha Samia , Badisa Ramesh , Soliman Karam F.
Published: January 2023

Breast cancer is the most commonly occurring cancer in women worldwide and is the second most common cancer among women in the United States. Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer and accounts for about 10-15% of all breast cancers. TNBC is mainly found in Caucasian and African American women. The tumor microenvironment promotes tumor initiation and progression, preceding invasive metastasis, increased cell growth, and angiogenesis. Therefore, the inhibition of these processes may reduce breast cancer development. Several dietary natural products show the ability to ameliorate the aggressiveness of breast cancer, leading to the inhibition of proliferation and angiogenesis, induction of apoptosis, and reduction of breast cancer progression and tumor development. PURPOSE: In the current study, the pharmacological effect of the natural compound fucoxanthin, a xanthophyll subset of carotenoids in brown macroalgae, is investigated in genetically different MDA-MB-231 (Caucasian) and MDA-MB-468 (African American) TNBC cell lines. METHODS: Cytotoxic and cell growth assays, angiogenic arrays, RT-PCR, apoptotic, and migration assays were performed. RESULTS: Fucoxanthin (1.56 - 300 µM) decreased cell viability in a dose and time-response manner in both cell lines, showing a higher potency in MDA-MB-468 cells. Fucoxanthin presented anti-proliferative effects in lower concentrations in MDA-MB-468 compared to MDA-MB-231 cells after 48 h and 72 h. Angiogenesis studies showed that fucoxanthin (6.25 µM) downregulates VEGF-A and VEGF-C expression in TNF-α-stimulated (50 ng/ml) MDA-MB-231 cells, but not in MDA-MB-468 cells in the transcription and protein levels. Fucoxanthin induced apoptosis in MDA-MB-231 cells but did not affect MDA-MB-468 cells. Additionally, fucoxanthin inhibited migration and invasion in both cell lines, showing a higher percentage of the inhibition of migrated cells in MDA-MB-468 cells after 72 h. CONCLUSION: Fucoxanthin may be a promising candidate for breast cancer therapy by targeting VEGF-A, and VEGF-C, decreasing cell proliferation, inducing apoptosis, and inhibiting cell migration and invasion.

Citation Format: Shade' Ahmed, Patricia Mendonca, Samia Messeha, Ramesh Badisa, Karam F. Soliman. Fucoxanthin anti-tumor effects on the proliferation, angiogenesis, apoptosis, and migration of triple-negative breast cancer cells [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C021.
Abstract C087: Neighborhood influences on chronic hepatitis B monitoring behaviors among Asian Americans residing in Philadelphia county
Authors: Bhimla Aisha , Lu Wenyue , Zhu Lin , Tan Yin , Zhu Di , Truehart Jade , Yeh Ming-Chin , Nguyen Minhhuyen , Ma Grace X.
Published: January 2023

The incidence of liver and intrahepatic bile duct cancer for Asian Americans is almost 2 times greater in comparison to Non-Hispanic white women and men. A major factor that contributes to liver cancer is hepatitis b (HBV) infection, which disproportionally affects Asian Americans, who represent 7% of the total US population but makes up around 58% of HBV-linked hepatocellular carcinoma cases. The purpose of this study was to examine the relationship between the neighborhood environment, including neighborhood walkability, Asianicity, and neighborhood disadvantage on HBV monitoring related behavior such as doctors' visits and HBV blood testing among Asian HBV patients. A total of 160 study participants were recruited from March 2019 to March 2020 through combined recruitment approaches, including through medical record review by authorized staff from collaborating health clinics, pharmacies, or community health centers and community-based organizations including racial/ethnic based educational and community centers, religion-based organizations, and senior centers. Study measures included baseline assessment information including sociodemographics, HBV infection history, HBV monitoring behavior, and knowledge about HBV prevention, diagnosis and treatment. Neighborhood level measures included neighborhood disadvantage, Asianicity, and neighborhood walkability using census and online measures. Hierarchical generalized linear models (HGLM) were used to account for individual nested within neighborhoods for predicting factors associated with doctor’s visits and blood test. Greater neighborhood disadvantage (OR=0.97, 95% CI=0.95-0.99, p=0.0041) and Asianicity (OR=0.97, 95% CI=0.95-0.98, p=0.0003), and lower neighborhood walkability (OR=1.06, 95% CI=1.02-1.09, p=0.0039) were associated with a lower likelihood of doctor visits for CHB. Greater Asianicity (OR=0.97, 95% CI=0.96-0.99, p=0.0044) was associated with a lower likelihood of HBV blood testing in the past 6 months. Evident neighborhood environment effects suggest the need to incorporate these factors into interventions to enhance HBV self-monitoring behaviors and slow disease progression of chronic HBV.

Citation Format: Aisha Bhimla, Wenyue Lu, Lin Zhu, Yin Tan, Di Zhu, Jade Truehart, Ming-Chin Yeh, Minhhuyen Nguyen, Grace X. Ma. Neighborhood influences on chronic hepatitis B monitoring behaviors among Asian Americans residing in Philadelphia county [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C087.
Abstract C096: Obese adipose derived secretome stimulates triple negative breast cancer via stimulation of the mTOR pathway
Authors: Miracle Cora E. , Salisbury Travis , McCallister Chelsea
Published: January 2023

Background: Breast cancer remains the most common cancer amoung women with multipe risk factors including smoking, genetics, environmental factors, and obesity. Smoking and obesity are the top two risk factors for development of breast cancer, with smoking increasing the risk of development by 21% and obesity by 20-40%. Obesity increases the risk for all breast cancer subtypes, including triple negative breast cancer (TNBC) that is null for estrogen and progesterone receptors and the tyrosine kinase receptor, HER2. To this end, recent retrospective patient studies have shown that the majority of patients with TNBC were obese at the time of diagnosis. In addition, obese patients had a higher TNBC tumor grade and a higher staging. However, the signaling mechanisms that promote the progression of TNBC in obesity are not well understood. We published that adipose tissue (AT) derived secretome (ADS) in obesity promotes the invasiveness of estrogen receptor positive breast cancer cells. Based on these prior findings, we hypothesize ADS in obesity acts on TNBC cells to induce mTOR activity and in turn stimulates TNBC cell migration and invasiveness. Methods: De-identified peritumor (PT) breast AT samples were obtained with patient consent at the time of surgery for breast cancer treatment. Breast AT samples were cultured in serum free culture medium for 24 hours. After the incubation, the AT conditioned media was clarified by centrifugation. For this study, considered BMI less than 30 as lean-ADS (LADS) and BMI of 30 or greater as obese-ADS (OADS). ADS diluted 1:10 in serum free culture medium was applied to human MDA-MB-231 and MDA-MB-436 TNBC cells. Cell migration was assayed by the scratch assay. Images were taken at time 0, and 24 hours. Analysis was performed using image J. Western blot studies were performed to assay the levels of total and/or phosphorylated proteins. Results: OADS stimulated a statistically significant increase (1.5 fold) in TNBC cell migration compared with LADS. The increase in TNBC cell migration was associated with a significant increase (1.5 fold) in phosphorylated S6 in TNBC cells treated with OADS relative to LADS. Conclusion: Increases in mTOR activity in TNBC cells in response to OADS is associated with increased TNBC cell migration.

Citation Format: Cora E. Miracle, Travis Salisbury, Chelsea McCallister. Obese adipose derived secretome stimulates triple negative breast cancer via stimulation of the mTOR pathway [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C096.
Abstract C121: Epidemiological characteristics and patterns of recurrence of renal cell carcinoma in Hispanics: A single US center cohort study
Authors: Melo Abner Antonio Murray , Gallegos Jesus Antonio Ocejo , Merchan Jaime Rafael
Published: January 2023

Renal cell carcinoma (RCC) is amongst the ten most prevalent malignancies in the United States, with 76,000 new cases each year and almost 14,000 deaths. Over the past half-century, RCC has more than doubled in incidence. RCC seems to have a greater incidence among Hispanics with a nearly three-fold increase. The epidemiology of RCC has been studied. However, there is a gap in knowledge on disparities in RCC within minority populations. We aimed to analyze epidemiologic patterns of RCC within our community, where Hispanics alone make up 70% of the population. We conducted a retrospective study to describe characteristics and calculate rates of recurrence of RCC among patients treated at Sylvester Comprehensive Cancer Center in Miami, FL, from June 2010 to April 2020. The patients were aged 18 and older and had a pathologic diagnosis of RCC. We identified ethnicity as Hispanic/Latino (HL) or non-Hispanic/Latino (NHL). Clinical presentation was classified based on information from the last encounter as either local RCC without recurrence, metastatic RCC after nephrectomy, or metastatic RCC at diagnosis/de novo. We analyzed a total of 1168 patients, from which 661 patients (55.7%) were identified as NHL and 507 (42.7%) as HL. A subtotal of 333 patients (28.5%) had metastatic RCC at diagnosis/de novo, from which 199 (59.7%) were NHL, and 134 (40.2%) were HL. A subtotal of 835 patients (71.5%) were diagnosed with local RCC and underwent nephrectomy, from which 462 (55.3%) were identified as NHL and 373 (44.7%) as HL. From the NHL group that underwent nephrectomy, 189 patients (40.9%) had recurrent disease and 273 (59%) did not. From the HL group, 121 patients (32.4%) had recurrent disease and 252 (67.5%) did not. Overall, 310 patients had metastasis after nephrectomy, from which 121 (39%) were HL and 189 (60.9%) were NHL. In this cohort of patients with RCC, four out of every ten patients with metastasis at diagnosis were HL. NHL appeared to have more recurrence of disease after nephrectomy compared to Hispanics. Further histopathologic, clinical, and genomic characteristics will be presented, along with treatment outcomes and clinical trial participation in the NHL and HL cohorts.

Citation Format: Abner Antonio Murray Melo, Jesus Antonio Ocejo Gallegos, Jaime Rafael Merchan. Epidemiological characteristics and patterns of recurrence of renal cell carcinoma in Hispanics: A single US center cohort study [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C121.
Abstract IA011: mTOR pathway gene expression in association with race and clinicopathological characteristics in Black and White breast cancer patients
Authors: Ilozumba Mmadili N. , Yao Song , Llanos Adana A. M. , Omilian Angela R. , Zhang Weizhou , Datta Susmita , Hong Chi Chen , Davis Warren , Khoury Thaer , Bandera Elisa V. , Higgins Michael , Ambrosone Christine B. , Cheng Ting Yuan David
Published: January 2023

Background Aberrant activation of the mammalian Target of Rapamycin (mTOR) pathway has been linked to obesity and endocrine therapy resistance, factors that may contribute to Black White disparities in breast cancer outcomes. We evaluated associations of race and clinicopathological characteristics with mRNA expression of key mTOR pathway genes in breast tumors. Methods Surgical tumor tissue blocks were collected from 367 newly diagnosed breast cancer patients (190 Black and 177 White). Gene expression of AKT1, EIF4EBP1, MTOR, RPS6KB2, and TSC1 were quantified by NanoString nCounter. Differential gene expression was assessed using linear regression on log2-transformed values. Gene expression and DNA methylation data from TCGA were used for validation and investigation of race-related differences. Results Compared to White women, Black women had relative under-expression of AKT1 (log2 fold-change = - 0.31, 95% CI - 0.44, - 0.18) and RPS6KB2 (log2 fold-change = - 0.11, 95% CI - 0.19, - 0.03). Higher vs. lower tumor grade was associated with relative over-expression of EIF4EBP1 and RPS6KB2, but with lower expression of TSC1. Compared to luminal tumors, triple-negative tumors had relative under-expression of TSC1 (log2 fold-change = - 0.42, 95% CI - 0.22, - 0.01). The results were similar in the TCGA breast cancer dataset. Post-hoc analyses identified differential CpG methylation within the AKT1 and RPS6KB2 locus between Black and White women. Conclusions Over-expression of RPS6KB2 and EIF4EBP1 and under-expression of TSC1 might be indicators of more aggressive breast cancer phenotypes. Differential expression of AKT1 and RPS6KB2 by race warrants further investigation to elucidate their roles in racial disparities of treatment resistance and outcomes between Black and White women with breast cancer.

Citation Format: Mmadili N. Ilozumba, Song Yao, Adana A. M. Llanos, Angela R. Omilian, Weizhou Zhang, Susmita Datta, Chi Chen Hong, Warren Davis, Thaer Khoury, Elisa V. Bandera, Michael Higgins, Christine B. Ambrosone, Ting Yuan David Cheng. mTOR pathway gene expression in association with race and clinicopathological characteristics in Black and White breast cancer patients [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr IA011.
Abstract IA018: “Pursuing Wicozani for the Oceti Sakowin”: Reducing cancer disparities among AI/AN in the Great Plains
Authors: Mousseau Richard J.
Published: January 2023

American Indian and Alaska Native (AI/AN) populations are among the underserved minority groups in the country and have the lowest survival rates for nearly all types of cancer of any subpopulation in the United States. Great Plains AI/AN populations have the highest age-adjusted cancers mortality compared to Native Americans from any other region. Addressing disparities in cancer outcomes among Great Plains AI/AN populations poses challenges in transportation, access to services, linguistic, and cultural variates. The Great Plains Tribal Leaders Health Board Community Health Department offers a variety of programs and projects to address these challenges and reduce these cancer disparities.

Citation Format: Richard J. Mousseau. “Pursuing Wicozani for the Oceti Sakowin”: Reducing cancer disparities among AI/AN in the Great Plains [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr IA018.
Abstract IA027: Role of stress-survival pathways and transcriptomic alterations in progression of colorectal cancer: A Hispanic health disparities perspective
Authors: Kulkarni Aditi , Basnet Urbashi , Rangel Frances , Roy Sourav
Published: January 2023

Essential to improving treatment, prognosis, and detection strategies are the identification and validation of new ethnicity-specific genomic profiles in cellular stress and survival pathways as effective predictors of colorectal cancer (CRC). These pathways are increasingly implicated in tumorigenesis of CRC and in providing resistance to chemotherapy-induced cell death. In this study, we have explored the role of these pathways in the biological significance of the expression of stress-survival pathway-associated genes in CRC progression and their role in promoting tumor aggressiveness from the Hispanic health disparities perspective. Transcript expression of oxidative stress and apoptosis-associated gene was evaluated in CRC gene microarray and RNAseq datasets to obtain 28 target genes. These genes were screened for transcript-level expression in six CRC cell lines and cDNA arrays containing the tumor (n=40) from different stages, and control (n=8) samples. The protein expression was evaluated by immunohistochemistry (IHC) in CRC microarrays (TMAs) containing different stages of tumor (n = 108) and control (n = 12) tissues. Target genes were also analyzed in Hispanic and Non-Hispanic White (NHWs) tissues at the transcript level. The analysis of target genes FOXM1, CDK1, CDK4, Chek1, and MCM10 showed consistent upregulation in CRC cell lines, cDNA arrays, and TMAs. The differential expression was also associated with the tumor stages. Among the target genes, Chek1, MCM10, and FOXM1 were found to be differentially expressed in Hispanic tissues when compared to the NHW samples. No significant difference was observed in the expression levels of CDK1 and CDK4 between the Hispanic and NHW tissues. Eight genes that did not show differential expression in CRC cell lines, were also seen to be upregulated in the Hispanic tissues, suggesting the influence of ethnicity-specific genetic makeup on the expression of these genes. The genes identified to be upregulated in Hispanic tissues may be used as potential biomarkers or as therapeutic targets in the Hispanic population.

Citation Format: Aditi Kulkarni, Urbashi Basnet, Frances Rangel, Sourav Roy. Role of stress-survival pathways and transcriptomic alterations in progression of colorectal cancer: A Hispanic health disparities perspective [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr IA027.
Abstract IA042: Global disparities: A global approach to understanding the generative mechanisms underpinning cancer health disparities
Authors: Alaro James R. , Palafox Neal A. , Denny Lynette Ann
Published: January 2023

Advances in cancer research have resulted in a decline in overall cancer incidence and deaths, and an increase in the number of cancer survivors globally. However, this progress has not been shared equally in the global community with certain populations continuing to experience significant or worsening cancer disparities. There are gaps in our understanding of the etiologies and drivers of global cancer disparities. Studying cancer health disparities systematically with a coordinated global effort offers opportunities to understand and develop context-specific interventions which may be adapted and translated across multiple global settings. The science of health disparities has advanced significantly in the past decade, resulting in a strong foundational knowledge of the causes of disparities in specific communities. Future disparities research must now recognize the inherent complex and dynamic connections and interrelationships among multiple factors from which these cancer disparities emerge. Broader use of methodological approaches that more fully account for the complex socio-cultural context in which disparities occur will enable the development of sustainable, resource- and culturally-appropriate interventions to reduce disparities in multiple global settings. To prevent, reduce, and ultimately eliminate global cancer health disparities and achieve cancer health-equity globally, a value-driven, globo-centric effort is needed to unravel the complex generative mechanisms that underpin disparities in similar socio-biological contexts across Multiple settings globally. This session aims to discuss example approaches to systematically study and address cancer health disparities globally.

Citation Format: James R. Alaro, Neal A. Palafox, Lynette Ann Denny. Global disparities: A global approach to understanding the generative mechanisms underpinning cancer health disparities [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr IA042.
Feasibility of Non-Gated Dynamic Fetal Cardiac MRI for Identification of Fetal Cardiovascular Anatomy
Authors: Geiger Julia , Tuura Ruth O’Gorman , Callaghan Fraser M. , Burkhardt Barbara E.U. , Kellenberger Christian J. , Valsangiacomo Buechel Emanuela R.
Published: January 2023

Introduction: The aim of this study was to evaluate the feasibility of identifying the fetal cardiac and thoracic vascular structures with non-gated dynamic balanced steady-state free precession (SSFP) MRI sequences. Methods: We retrospectively assessed the visibility of cardiovascular anatomy in 60 fetuses without suspicion of congenital heart defect. Non-gated dynamic balanced SSFP sequences were acquired in three anatomic planes of the fetal thorax. The images were analyzed following a segmental approach in consensus reading by an experienced pediatric cardiologist and radiologist. An imaging score was defined by giving one point to each visualized structure, yielding a maximum score of 21 points. Image quality was rated from 0 (poor) to 2 (excellent). The influence of gestational age (GA), field strength, placenta position, and maternal panniculus on image quality and imaging score were tested. Results: 30 scans were performed at 1.5T, 30 at 3T. Heart position, atria, and ventricles could be seen in all 60 fetuses. Basic diagnosis (>12 points) was achieved in 54 cases. The mean imaging score was 16.8+/−3.8. Maternal panniculus (r = −0.3; p = 0.015) and GA (r = 0.6; p < 0.001) correlated with imaging score. Field strength influenced image quality, with 1.5T being better than 3T images (p = 0.012). Imaging score or quality was independent of placenta position. Conclusion: Fetal cardiac MRI with non-gated SSFP sequences enables recognition of basic cardiovascular anatomy.
Why Is Rapamycin Not a Rapalog?
Authors: Kuerec Ajla Hodzic , Maier Andrea B.
Published: January 2023

Rapamycin (sirolimus) is an immunosuppressive drug approved by the Food and Drug Administration (FDA). It is also a leading candidate for targeting aging. Rapamycin and its analogs (everolimus, temsirolimus, ridaforolimus) inhibit the mammalian target of rapamycin (mTOR) kinase by binding to FK506-binding proteins (FKBP) and have a similar chemical structure that only differs in the functional group present at carbon-40. Analogs of rapamycin were developed to improve its pharmacological properties, such as low oral bioavailability and a long half-life. The analogs of rapamycin are referred to as “rapalogs.” Rapamycin is the parent compound and should therewith not be called a “rapalog.”