bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract C038: MHC class I polypeptide related sequence A (MICA) race-related differential expression in prostate cancer
Authors: Pound Charles R. , Sakiyama Marcelo J. , Reddy Amit , Espinoza Ingrid , Bhanat Eldrin , Syrigos Krista , Gordji Roya , Kumar Deepak , Lewin Jack , Zhou Xinchun , Monico Jesus , Gomez Christian
Published: August 2020

Prostate cancer (PCa) is the second most common cancer in American men, with higher incidence and death rates in African Americans (AA) relative to Caucasian Americans (CA); nevertheless, these disparities are still poorly understood. MHC class I polypeptide related sequence A (MICA) is a cell surface protein able to promote activation of natural killer cells. Cleavage of MICA and generation of its soluble form (sMICA) has been described as an immunoevasion mechanism presented by different types of aggressive tumors. In agreement with the role of MICA on tumor immunoevasion, recent studies correlated better prognosis for patients expressing higher levels of MICA in different types of cancer. We speculated that MICA expression would be different between AA and CA PCa tumors. To access MICA expression in PCa patients, we stained a TMA containing 30 AA and 27 CA tumor cores. Our results showed that CA PCa tumor cores had higher expression of MICA than the AA (p=0.0019). In order to establish an in vitro system to study the biologic effects of MICA in the context of disparity in PCa, we assessed the expression of surface MICA and release rate of sMICA in different PCa cell lines: MDA-PCa-2b and E006AA-hT, derived from AA, and DU-145 and LNCaP, derived from CA. Flow cytometry analysis showed baseline cell fraction expression positive for surface MICA of 3% in MDA-PCa-2b, 18% in E006AA-hT, 54% in DU-145, and 67% in LNCaP, with significant difference between each cell line (p<0.0001). Baseline release rate of sMICA was nondetectable for MDA-PCa-2b, 5pg/ml/106 cells in E006AA-hT, 120pg/ml/106 cells in DU-145, and 54pg/ml/106 cells for LNCaP cells. Overall, our results show that MICA expression is race related. Further studies are necessary to address the biologic function of the expression and the impact in the immune system.

Citation Format: Charles R. Pound, Marcelo J. Sakiyama, Amit Reddy, Ingrid Espinoza, Eldrin Bhanat, Krista Syrigos, Roya Gordji, Deepak Kumar, Jack Lewin, Xinchun Zhou, Jesus Monico, Christian Gomez. MHC class I polypeptide related sequence A (MICA) race-related differential expression in prostate cancer [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C038.
Abstract C043: Meat and fish intake and the risk of breast cancer in the Carolina Breast Cancer Study (CBCS)
Authors: Omofuma Omonefe , Steck Susan , Troester Melissa , Olshan Andrew
Published: August 2020

Introduction: Cooking meat at high temperatures and charring of meat increases the production of heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs), which are implicated in breast carcinogenesis. Several epidemiologic studies have reported increased risk of breast cancer with higher intake of HCAs or red meat intake. However, few studies have examined these associations in racially diverse populations. The goal of the study was to examine the associations between various meat and fish preparation methods and breast cancer using the Carolina Breast Cancer Study (CBCS) Phase 2.

Methods: African American (AA) and European American (EA) women aged 20-74 years with a first diagnosis of invasive or in situ breast cancers were enrolled. Controls were identified through the DMV and Medicare lists and were frequency matched to cases by race and age group (AA: 548 cases and 452 controls; EA: 858 cases and 748 controls). Preparation methods and intake frequencies were obtained through self-report questionnaires. Multivariable logistic regression analysis was used to obtain odds ratios and 95% CIs of breast cancer by frequency of intake of meat and fish cooked by various preparation methods.

Results: Using no reported meat intake as the referent, positive associations with breast cancer were observed for intakes of grilled/barbecued hamburger (one or more times per week, OR: 1.30; 95% CI: 1.02, 1.66), and for pan-fried/oven-broiled beef steak (one or more times per week, OR: 1.38; 95% CI: 1.09, 1.74). Inverse associations with breast cancer were observed for pan-fried fish (one or more times per week, OR: 0.77; 95% CI: 0.61, 0.99) and for grilled/barbecued pork chops (OR: 0.82, 95% CI: 0.69, 0.98). Overall, the associations appeared to be stronger among EA women but showed inconsistency within meat categories (fish, pork, beef) depending upon method of cooking.

Conclusion: Among AA and EA women, more frequently consuming beef prepared with high-temperature methods (such as grilling or oven-broiling) was associated with higher odds of breast cancer, and the associations were stronger among EA women compared to AA women. In contrast, consuming pan-fried fish or grilled/barbecued pork chops weekly was associated with lower odds of breast cancer compared to less frequent consumption.

Citation Format: Omonefe Omofuma, Susan Steck, Melissa Troester, Andrew Olshan. Meat and fish intake and the risk of breast cancer in the Carolina Breast Cancer Study (CBCS) [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C043.
Abstract C075: Indoor radon exposure and thyroid cancer incidence among Guam residents
Authors: Arceo Candice S. , Badowski Grazyna , Denton Gary R.W. , Bordallo Renata
Published: August 2020

The natural radioactive decay of radon (222Rn) gas gives rise to many products that release ionizing radiation, proven to be harmful to human health. Perhaps the best-known source of radiation that has been linked to thyroid cancer (TC) is the chronic inhalation of radon gas. Indoor 222Rn levels in Guam have been documented to be as high as 220 picocuries per liter (pCi/L), exponentially higher than the United States Environmental Protection Agency (USEPA) baseline standard of just 4 pCi/L. Thyroid cancer is the fifth common cancer in women on Guam and Filipinos had the highest thyroid cancer incidence rates compared to other ethnic groups in Guam. The objective of this study is to determine whether there is an association between thyroid cancer incidence, geographic location (village/zone), ethnicity, and amount of indoor radon exposure in Guam. The data sets used in this ecological study came from three major independent data collecting sources: Guam Environmental Protection Agency (GEPA) indoor 222Rn data (2002-2009), Guam Cancer Registry thyroid cancer incidence data (1998-2013), and Guam Census 2000 and 2010 demographic data. Simple linear regression analysis was performed to determine the relationship between mean indoor 222Rn levels and thyroid cancer incidence in Guam villages. Multiple regression analysis was conducted to account for the confounding effects of ethnicity (% Filipino), and zone. Results indicated that radon in Guam was found to be highest in Zone 1, the geographic villages situated atop a limestone plateau in the northern region where approximately 66% of Guam residents and over 90% of Filipinos live. In both univariate and ethnicity-adjusted regression analysis, a significant positive association was found between mean 222Rn level and thyroid cancer incidence (P = .024, and P = .048, respectively). When univariate and multiple regression analysis was conducted on the two GEPA 222Rn zone strata (Zone 1 and Zone 2/3), the relationship remained positive but not statistically significant. The positive correlation between mean 222Rn levels and thyroid cancer incidence suggested that more exposed individuals have increased susceptibility to cancer and possibly explained higher rate among Filipinos.

Citation Format: Candice S. Arceo, Grazyna Badowski, Gary R.W. Denton, Renata Bordallo. Indoor radon exposure and thyroid cancer incidence among Guam residents [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C075.
Abstract C095: A quality review and content analysis of mobile applications for smoking cessation
Authors: Ibe Ifeoma , Laracuente Antonio , Joseph Samantha , Huo Jinhai , Salloum Ramzi
Published: August 2020

Introduction: Mobile applications (apps) for smoking cessation promise to increase access to and uptake of smoking cessation services. However, limited information exists on the quality and content of available apps in this category. The purpose of this review was to evaluate the quality and content of free smoking-cessation mobile apps and examine whether they adhered to US Public Health Service Guideline for treating tobacco use and dependence.

Methods: A purposive sample of 180 apps was downloaded from the App Store (Apple) and the Google Play Store in January 2018. The top-ranking 30 apps were retrieved for 3 smoking cessation-related search terms (“smoking cessation,” “quit smoking,” “stop smoking”) from the App Store and Google Play. Two reviewers independently coded each app. The technical quality of the included apps was rated using the Mobile Application Rating Scale (MARS), which includes five domains: Engagement (fun, interesting, customizable,), Functionality (easy to learn, navigation), Aesthetics (graphic design, overall visual appeal), and Information (e.g., text, feedback, measures, refences). Apps were also reviewed for other technical characteristics (e.g., allows sharing, app community, and password protection), behavioral change strategies (e.g., assessment, feedback) and whether they adhered to the US Public Health Service's 5As (i.e., Ask, Advise, Assess, Assist, and Arrange).

Results: After removing duplicates and apps that were not free to download, 69 apps were identified for full review (41 from the App Store and 28 from the Google Play Store). Across these apps, the average score for MARS was 14.0/19, distributed as follows: Engagement (2.8/5), Functionality (4/5), Aesthetics (4/5), and Information (3/5). Among the 69 included apps, 45 allowed sharing, 15 allowed for an app community, and 6 required a password. The following features were included as follows: assessment (52), feedback (44), information/education (46), monitoring (52), and goal setting (28). The 5As features were included as follows: Ask (44), Advise (2), Assess (2), Assist (2), and Arrange (0).

Conclusions: Given the growing availability of smoking-cessation apps as potential cessation aides, future efforts should focus on improving the technical quality of these apps and the adherence to evidence-based guidelines for treating tobacco use and dependence.

Note: This abstract was not presented at the conference.

Citation Format: Ifeoma Ibe, Antonio Laracuente, Samantha Joseph, Jinhai Huo, Ramzi Salloum. A quality review and content analysis of mobile applications for smoking cessation [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C095.
Abstract C113: Antibody microarray analysis of signaling networks regulated by the CCR9/CCL25 axis in African American and Caucasian American triple-negative breast cancer
Authors: Thomas Jeronay King , Kapur Neeraj , Mir Hina , Gales Dominique N. , Lillard James W. , Singh Shailesh
Published: August 2020

Therapeutic outcome of breast cancer (BrCa) is impeded due to the intratumoral heterogeneity, as well as differences among cancer-bearing individuals. Triple-negative breast cancer (TNBC) is a highly aggressive subtype that disproportionally affects African-American (AA) women. However, the molecular basis of racial disparity in therapeutic response and clinical outcome of TNBC in AA compared to Caucasian American (CA) patients is still obscure. Our group was the first to show the involvement of CCR9 and its natural ligand, CCL25 in cancer progression and therapeutic response, including BrCa. In this study, using proteomic and bioinformatics approach we have quantified the race-specific differences in biologic pathways modulated by the CCR9/CCL25 in TNBC cells. The difference in signaling cascades following CCR9 activation by CCL25 in BrCa cell derived from AA and CA were determined using cancer signaling phospho-protein antibody microarray, which featured 269 antibodies. A heat map was generated to visualize differences in phosphorylation status among cell line derived from AA and CA patients, as well as differences between the cell lines after CCL25 treatment. Graphics of biologic functions and oncogenic signaling networks, which were altered by CCR9/CCL25 axis, were produced using GeneMANIA and Ingenuity Pathway Analysis (IPA) software. Cells derived from AA (MDA-MB-468), show activation/phosphorylation of GSK3α, Elk-1, p70S6K, BCL-2, MEK2, NFkB and STAT3 involved in cell survival and migration. However, cells derived from CA (MDA-MB-231) show activation/phosphorylation of VEGFR2, CTNNB1, FAK, and SHC, suggesting involvement of distinct pathway supporting cell survival following CCR9 activation. Hence, our data suggest that CCR9/CCL25 contributes to the race-specific difference in signaling pathways and these race-specific differences in the biology of TNBC could be the reasons for the disparity in disease and therapeutic outcome.

Citation Format: Jeronay King Thomas, Neeraj Kapur, Hina Mir, Dominique N. Gales, James W. Lillard Jr., Shailesh Singh. Antibody microarray analysis of signaling networks regulated by the CCR9/CCL25 axis in African American and Caucasian American triple-negative breast cancer [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C113.
Abstract C115: [Advocate Abstract] Financial disparities associated with treating colorectal cancer in the minority (African American) community
Authors: Johnson Wenora
Published: August 2020

According to the NIH website, “Members of minority racial/ethnic groups in the United States are more likely to be poor and medically underserved (that is, to have little or no access to effective health care) than whites, and limited access to quality health care is a major contributor to disparities. For example, regardless of their racial/ethnic background, the poor and medically underserved are less likely to have recommended cancer screening tests than those who are medically well served. They are also more likely to be diagnosed with late-stage cancer that might have been treated more effectively if diagnosed earlier.” Currently referred to as “financial toxicity,” many individuals are suffering from the high cost of treating cancer. Particularly in the minority (African American) community, this problem is even greater. People often overlook health care treatment due to concerns of affordability and trying to take care of their daily living needs such as housing, food and travel.

Citation Format: Wenora Johnson. [Advocate Abstract] Financial disparities associated with treating colorectal cancer in the minority (African American) community [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C115.
Abstract C117: [Advocate Abstract] Saving lives through advocacy
Authors: Nathaniel Diane
Published: August 2020

I am a stage 3 colon cancer survivor and patient advocate. My poster is a reflection of my experience with cancer and journey as a survivor. My life was spared so that that I could become a change agent in my community. Every time I share my story, I create pathways to saving lives by connecting people with doctors, information and health care services. African-Americans are affected at the highest rate and have the highest mortality rate as it relates to GI cancers. My poster shares my personal story, my advocacy efforts and how I am changing the narrative in my community by joining forces with the medical community to reduce the number of people being affected by cancer.

Citation Format: Diane Nathaniel. [Advocate Abstract] Saving lives through advocacy [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C117.
Abstract IA10: Progress in colorectal cancer screening: Past, present, and future
Authors: Gray Darrell M.
Published: August 2020

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and second leading cause of cancer-related death among men and women in the US, but it is largely preventable with screening. The implementation of screening programs, in addition to risk factor modification and, to a lesser degree, improvements in treatment, have contributed to a downward trend in CRC incidence and mortality rates for greater than three decades. However, the burden of disease has and continues to be unequally distributed. Striking disparities by race, ethnicity, socioeconomic status, and geography persist. Such differences are multifactorial and are, in part, driven by variation in screening access, uptake, adherence, and abnormality follow-up. There is a growing body of evidence that outreach, patient navigation, provider education, and multilevel population health strategies to address these challenges are effective. Intensifying such efforts and promoting earlier initiation of screening in high-risk populations are other promising yet controversial approaches. A recent change in the American Cancer Society guideline recommendations to lower the age for initiation of screening from 50 to 45 is being heavily debated—one concern being the potential unintended consequence of exacerbating existing disparities in CRC outcomes. Moreover, there is a dire need for a risk-stratification model that will determine CRC risk and the age at which individuals should begin screening more accurately than our current guideline models of family and personal medical history. Personalized prescriptions for screening are the future, and we are getting closer to this being a reality. Yet, while these are necessary, it is unclear if they will be sufficient to eliminate the observed disparities.

Citation Format: Darrell M. Gray II. Progress in colorectal cancer screening: Past, present, and future [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr IA10.
Abstract IA12: Follow-up of abnormal colorectal cancer screening: Challenges and solutions
Authors: May Folasade P.
Published: August 2020

Colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States but is largely preventable by screening. Both observational and randomized control trial data demonstrate that screening for CRC with colonoscopy, flexible sigmoidoscopy, or stool-based studies can effectively identify and remove premalignant lesions, reduce incidence of CRC, and decrease CRC mortality. Stool-based screening modalities like high-sensitivity fecal occult blood testing (FOBT) and fecal immunochemical testing (FIT) are inexpensive, noninvasive, and accessible screening modalities that are commonly used in underinsured and underserved patient populations. A major challenge of these stool-based methods, however, is that abnormal (i.e., positive) results are common (5-14%) and warrant subsequent follow-up with diagnostic colonoscopy to avoid poor CRC outcomes. Currently, follow-up rates across health care settings range from 40% to over 80%. Safety-net populations have the lowest rates at 40% to 58%, substantially shy of the national benchmark to achieve colonoscopy in 80% of patients with abnormal results. These low rates reflect patient-, provider-, and system-level barriers to diagnostic colonoscopy after positive screening and a lack of clinical resources and optimal system processes to facilitate access to and patient utilization of diagnostic colonoscopy. The goals of this talk are to (1) provide an overview of low follow-up after abnormal CRC screening, with a focus on Federally Qualified Health Centers (FQHCs) and safety-net institutions; (2) summarize the available data on barriers to follow-up after an abnormal screening result; and (3) present an overview of effective interventions to improve the timelines of follow-up colonoscopy and colonoscopy follow-up rates. The presentation will also address directions for future research in follow-up after abnormal CRC screening.

Citation Format: Folasade P. May. Follow-up of abnormal colorectal cancer screening: Challenges and solutions [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr IA12.
Abstract IA13: Advocate Perspective: Improving outcomes for all colorectal cancer survivors
Authors: Smith Judith Lee
Published: August 2020

Recent studies document striking differences in colorectal cancer (CRC) survival by race, stage at diagnosis, and state. These data demonstrate that more work is crucial to address persistent disparities in survival. Cancer survivors face many types of challenges following active treatment: physical, mental, emotional, financial, and psychosocial. CRC survivors share concerns similar to those of other cancer survivors but may also have CRC-specific concerns in survivorship due to medical interventions. Survivorship care plans (SCP) were identified as a possible way to ease the challenges experienced by cancer survivors, but results have been mixed. While some studies showed that CRC survivors appreciated a personalized SCP, many survivors needed additional detail about which providers were responsible for the varied components of their care. Importantly, diverse CRC survivors may be unaware of appropriate surveillance and follow-up recommendations. Survivors need to have the best information to support their health and well-being, and these information needs may change over time. However, there are multiple gaps in the literature, as most studies have focused on first-time CRC survivors or survivors with no additional cancers. Consequently, less is known about the experience of CRC survivors who develop new primary cancers, recurrent cancer, or metastatic cancer. Further, more information is needed about the experiences of CRC survivors who present with or are diagnosed post-treatment with additional chronic conditions. Finally, while some recent studies exist, further research could explicate the needs of survivors who have been traditionally under-represented in CRC survivorship research. Self-management is a component of achieving and maintaining health and well-being in survivorship but is not sufficient. Interventions are warranted to improve system coordination that address pervasive social determinants of health. Improving outcomes for CRC survivors will require coordinated effort at many levels, tailored to patient needs and community context. Public health organizations and their partners can play an important role in meeting the needs of diverse CRC survivors, as well as advancing the application of proven strategies in communities with the lowest CRC survival and greater deleterious outcomes post-diagnosis. Our goal remains ensuring that all men and women diagnosed with CRC experience the highest possible survival and quality of life in survivorship.

Citation Format: Judith Lee Smith. Advocate Perspective: Improving outcomes for all colorectal cancer survivors [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr IA13.
Abstract IA14: Emerging priorities for the Center to Reduce Cancer Health Disparities in diversity workforce training and cancer health disparities research
Authors: Springfield Sanya A.
Published: August 2020

This panel presentation will provide an overview of the current training and research funding priorities at National Cancer Institute's (NCI) Center to Reduce Cancer Health Disparities (CRCHD). CRCHD is NCI's focal point for the training of competitive cancer researchers from diverse populations and supporting cancer health disparities research across the cancer continuum. The NCI's CRCHD's Continuing Umbrella of Research Experiences (CURE), Intramural CURE (iCURE), and the Partnerships to Advance Cancer Health Equity (PACHE) will be highlighted as successful models for diversity training and cancer health disparities research. The CURE Program supports extramural research training and education experiences for under-represented individuals beginning in middle school and continuing through to first academic appointment. The newly launched iCURE Program supports mentored research experiences within the NCI Intramural Research Program for students and fellows. In addition, the PACHE Program supports cancer and cancer health disparities research, education, and outreach through partnerships between Minority-Serving Institutions and NCI-designated Cancer Centers. New and established NCI funding opportunities in cancer health disparities research, including opportunities supporting both basic and translational research addressing cancer health disparities, will also be presented. Additionally, strategies will be explored for navigating successful cancer research careers and for developing competitive grant applications.

Citation Format: Sanya A. Springfield. Emerging priorities for the Center to Reduce Cancer Health Disparities in diversity workforce training and cancer health disparities research [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr IA14.
Abstract IA45: Coverage ≠ access: State Medicaid policies and disparities in receiving high-quality cancer care
Authors: Halpern Michael T.
Published: August 2020

Medicaid is a joint state-federal program that provides health insurance coverage to certain low-income populations. While the federal government provides funding for at least half of each state's Medicaid costs and requires coverage for certain health care services, each state has broad flexibility to design its own Medicaid policies. These policies include reimbursement rates for medical care services, requirements for patient copayments, and duration of Medicaid enrollment before required eligibility recertification. Furthermore, following the 2012 Supreme Court decision, states can choose whether to participate in expansion of Medicaid to enroll individuals with incomes up to 138% of the Federal Poverty Level. As these policies differ substantially among states, Medicaid is not a single health insurance plan but a set of different plans for each state. Medicaid provides coverage for cancer screening and treatment for many low-income individuals. However, differences in state Medicaid policies may affect receipt of timely and high-quality cancer care for this underserved population. In addition, social determinants of health such as race/ethnicity, sex, and age may also affect receipt of cancer care among Medicaid beneficiaries. This presentation will review findings examining the effects of state Medicaid policies and individual characteristics on receiving cancer screening, treatment, supportive care, and survivorship care services among Medicaid beneficiaries. Using Medicaid claims and enrollment data, research has found that both state policies and social determinants of health can impact receipt of recommended cancer screenings and treatment for individuals with Medicaid coverage. The impacts of Medicaid policies vary for different types of cancer care services and among individuals with different types of cancer. State decisions to participate in Medicaid expansion also affect receipt of cancer care. These findings highlight the need for state Medicaid policies designed to improve access to cancer care and enhance outcomes among Medicaid beneficiaries. Given the large—and growing—Medicaid population, even small improvements in access to high-quality cancer care can translate into substantial changes in health outcomes.

Citation Format: Michael T. Halpern. Coverage ≠ access: State Medicaid policies and disparities in receiving high-quality cancer care [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr IA45.
Abstract IA51: Federally supported tools and resources to support data integration efforts for health disparities research
Authors: Moser Richard P.
Published: August 2020

The etiology of many cancer-related health disparities that continue to persist is oftentimes complex, interactive, and multifactorial. Because of this complexity and to understand these causes, it behooves cancer researchers to utilize data that represent different types and sources of these determinants measured at multiple levels of abstraction, from biology to policy. By incorporating these different data sources into their studies, researchers can answer novel (and better) cancer control research questions that cannot be answered with any one data set. To do these types of integrative analyses, however, researchers will most likely need to merge or link independent data, and this may be difficult or impossible if the data are too heterogeneous in regard to the instruments or measures used to represent variables in the data. To increase the ability to do data integration, it typically requires harmonized data that contain common data elements of the important constructs of interest. In this presentation, Dr. Moser will highlight tools and resources, especially those supported by the federal government, that can be used for data integration to conduct health disparities research. These tools include ontologies, standardized measures, collaborative sites, and data repositories that promote the use of common data elements to create or analyze harmonized data. This presentation will also mention National Institutes of Health (NIH) funding announcements that could be used to support data integration efforts and health disparities research.

Citation Format: Richard P. Moser. Federally supported tools and resources to support data integration efforts for health disparities research [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr IA51.
Abstract 15: Imputing a more targeted therapy for triple-negative breast cancers
Authors: Gruener Robert F. , Greene Geoffrey L. , Huang R. Stephanie
Published: August 2020

Triple-negative breast cancer (TNBC) is a clinically defined subset of breast cancers that are inherently difficult to treat since, unlike the other breast cancer subtypes, they are defined by their lack of a distinct molecular target. Previously our lab developed a computational framework to impute drug response in patients that accurately mirrored the observed patient response. In short, this methodology involves building unsupervised linear regression models between cell line baseline gene expression values and the respective drug sensitivity metric (EC50 or AUC), which allows us to generate imputed sensitivity scores for cell line or patient tumor samples for which we have gene expression data. For this study, we applied this methodology to prospectively identify agents that are predicted to be more effective specifically in triple-negative breast cancer. We began by expanding the drug imputation training dataset to the Broad’s Cell Therapeutics Response Portal, which contains 545 drugs and over 1,000 cancer cell lines (CCLs) and imputed sensitivity in The Cancer Genome Atlas’s (TCGA’s) breast cancer cohort. Our imputation data indicated that TNBC tumors were expected to be comparatively sensitive to cell cycle pathway inhibitors. Among these compounds, the Wee1 inhibitor MK1775 (aka adavosertib and AZD1775) was identified for having the most significant predicted effect in TNBC patients compared to the receptor-positive patients. We were able to validate the accuracy of the MK1775 imputation model using traditional cross-validation approaches as well as in independent cell line dataset and showed that the measured and our predicted response to Wee1 inhibition strongly correlated. Additionally, we were able to uses our predicted MK1775 response scores to recapitulate the significant association between MK1775 response and p53 mutation status. We then looked to validate the efficacy of MK1775’s efficacy in TNBC cell line and xenograft experiments. We observed strong inhibition of cancer growth by MK1775 alone but also identified a combination effect between MK1775 and the TNBC standard-of-care agent paclitaxel as assayed by both in vitro viability experiments as well as in vivo tumor growth assays. We believe these results indicate that this methodology could generally be applied as a hypothesis-generating tool for identifying targeted agents for other disease subtypes as well as supporting the use of MK1775, especially in combination with paclitaxel, for TNBC.

Citation Format: Robert F. Gruener, Geoffrey L. Greene, R. Stephanie Huang. Imputing a more targeted therapy for triple-negative breast cancers [abstract]. In: Proceedings of the AACR Special Conference on Advancing Precision Medicine Drug Development: Incorporation of Real-World Data and Other Novel Strategies; Jan 9-12, 2020; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_1):Abstract nr 15.
Abstract 17: MBQ-167, a Rac/Cdc42 targeted therapeutic, in combination with paclitaxel for TNBC treatment
Authors: Ruiz-Calderon Jean , Lopez-Lopez Irmaris , Cruz-Collazo Ailed , Dharmawardhane Suranganie
Published: August 2020

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer, with a high predisposition for locally advanced and metastatic cancer. While targeted therapies for TNBC are in various stages of development, current standard chemotherapies include taxanes such as paclitaxel and anthracycline agents. With the objective of specifically targeting invasive cancer, our group has been developing small-molecule inhibitors of the Rho GTPases Rac and Cdc42, which are known drivers of cancer cell invasion and metastasis. Of these, MBQ-167 inhibits both Rac and Cdc42 with IC50s of 103 and 78 nmol/L, respectively, and consequently inhibits p21-activated kinase (PAK) signaling, metastatic cancer cell proliferation, migration, tumor growth, and metastasis (Humphries-Bickley et al., Mol Cancer Ther 2017). We found that in addition to blocking HER2-type breast cancer progression, MBQ-167 is also highly effective against TNBC cell and tumor growth, as well as metastasis in mouse models. The purpose of this study was to test the efficacy of MBQ-167 in combination with the current chemotherapeutic paclitaxel. We hypothesized that the combination of paclitaxel and MBQ-167 is a rational strategy to inhibit tumor growth and metastasis in TNBC. To test this hypothesis, we administered a nontoxic dosage of individual MBQ-167, paclitaxel, or combined MBQ-167 and paclitaxel to immunocompromised mice bearing mammary fat pad tumors from GFP-tagged MDA-MB-468 or MDA-MB-231 human TNBC cells. Tumor growth was monitored weekly and metastasis was quantified at the end of the study. Treatment with MBQ-167 and/or paclitaxel resulted in reduced tumor growth by 70-80% in both models. In the MDA-MB-231 model, MBQ-167 paralleled paclitaxel treatment with a modest benefit in combined therapy. However, in the epidermal growth factor receptor (EGFR)-positive TNBC model MDA-MB-468, MBQ-167 alone or in combination significantly reduced metastasis to the lungs and spleen, while paclitaxel alone increased metastasis to the liver, lungs, and spleen. These results show that MBQ-167 is a promising antimetastatic agent that can be effective in combination with current chemotherapeutic agents.

Citation Format: Jean Ruiz-Calderon, Irmaris Lopez-Lopez, Ailed Cruz-Collazo, Suranganie Dharmawardhane. MBQ-167, a Rac/Cdc42 targeted therapeutic, in combination with paclitaxel for TNBC treatment [abstract]. In: Proceedings of the AACR Special Conference on Advancing Precision Medicine Drug Development: Incorporation of Real-World Data and Other Novel Strategies; Jan 9-12, 2020; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_1):Abstract nr 17.
Abstract IA02: The Treehouse Childhood Cancer Initiative
Authors: Haussler David
Published: August 2020

Each year over 4,000 children with cancer in the US lack adequate treatment options for their disease, underscoring the urgent need for new therapeutic targets and new therapies. Cancer genomic investigations focusing on the identification of recurrent DNA changes in tumors that could be targeted by therapies have been disappointing in the majority of pediatric cancers, as these diseases have lower rates of somatic mutation compared to adult cancers. To address this challenge, the UC Santa Cruz Genomics Institute launched the Treehouse Childhood Cancer Initiative, an innovative program that identifies novel therapeutic targets for difficult-to-treat pediatric cancers through leveraging the power of large, shared tumor RNA-sequencing datasets. Treehouse partners with pediatric cancer hospitals, including Lucille Packard Children’s Hospital at Stanford, UCSF Benioff Children’s Hospital, Children’s Hospital of Orange County, Nationwide Children’s Hospital, and British Columbia Children’s Hospital, to investigate whether the comparative RNA-seq approach is feasible and useful when applied to patients prospectively. A preliminary analysis of 126 patients from four hospitals showed that comparative RNA-seq analysis can identify druggable targets for over 74.3% of difficult-to-treat pediatric cancer patients, while state-of-the-art DNA analysis finds potential therapeutic options for only 45.9% of patients. Current work focuses on determining the clinical utility of the Treehouse approach.

Citation Format: David Haussler. The Treehouse Childhood Cancer Initiative [abstract]. In: Proceedings of the AACR Special Conference on Advancing Precision Medicine Drug Development: Incorporation of Real-World Data and Other Novel Strategies; Jan 9-12, 2020; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_1):Abstract nr IA02.
Abstract IA19: The Drug Rediscovery Protocol: Getting the most out of approved drugs
Authors: Voest Emile E.
Published: August 2020

Large-scale genetic tumor profiling can identify increasing numbers of potentially actionable molecular variants for which approved anticancer drugs are available. In daily practice, however, when patients with such variants are treated with drugs outside of their approved label, successes and failures are not systematically collected or shared. Therefore, we initiated the Drug Rediscovery Protocol (DRUP), an innovative and adaptive precision oncology trial aimed at identifying signals of activity in cohorts of patients with defined tumor types and molecular variants, treated with anticancer drugs outside their approved label. Eligible patients have exhausted (or declined) standard therapies and have malignancies with potentially actionable variants for which no approved anticancer drugs are available. We use a stepwise approach per cohort of first 8 patients, and when at least one patient experienced clinical benefit that cohort expands to 24 patients. Presently, we have reviewed >1,100 submitted patient cases and included and treated >500 patients. We found an overall clinical benefit rate (defined as complete or partial response, or stable disease ≥16 weeks) of 29% although the formal analysis is per cohort. The potential of DRUP was illustrated by the identification of a successful cohort of patients with microsatellite instable tumors receiving nivolumab or durvalumab, and tumors with HRD treated with olaparib. Our results have led to a personalized reimbursement model for nivolumab in patients with MSI tumors that is supported by all regulatory parties. The DRUP hereby facilitates defined use of approved drugs beyond their label in (rare) cancer subgroups, identifies early signals of activity in these subgroups, accelerates clinical translation of new insights, and creates a publicly available knowledge-base for future decision making.

Citation Format: Emile E. Voest. The Drug Rediscovery Protocol: Getting the most out of approved drugs [abstract]. In: Proceedings of the AACR Special Conference on Advancing Precision Medicine Drug Development: Incorporation of Real-World Data and Other Novel Strategies; Jan 9-12, 2020; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_1):Abstract nr IA19.
Hedgehog Pathway Inhibitors: A New Therapeutic Class for the Treatment of Acute Myeloid Leukemia
Authors: Jamieson Catriona , Martinelli Giovanni , Papayannidis Cristina , Cortes Jorge E.
Published: August 2020

Targeting Hedgehog (Hh) pathway components, such as Smoothened (SMO), is a developing strategy for the treatment of acute myeloid leukemia (AML) and for overcoming relapsed/refractory forms of this disease. Several SMO inhibitors are in clinical development for the treatment of various tumor types and the results from some clinical trials in AML have been reported. This review will discuss the role of Hh signaling in AML pathogenesis, describe the preclinical and clinical development of Hh pathway inhibitors for the treatment of AML, and examine the current evidence on Hh pathway inhibitor resistance and the implications for treatment selection in AML.

Significance:

In acute myeloid leukemia (AML), components of the Hedgehog (Hh) signaling pathway, such as Smoothened (SMO), have been implicated in the development, maintenance, and expansion of leukemic stem cells (LSC), as well as sensitization to chemotherapy and the development of drug resistance in AML. Observations in preclinical studies of AML, as well as from samples of patients with AML, demonstrate that Hh pathway inhibitors act primarily on the stem cell pathway as differentiation agents. The current data for hematologic malignancies indicate the potential for a synergistic effect when a Hh pathway inhibitor is administered in combination with chemotherapy or investigational agents. It is thought that Hh pathway inhibitors act as agents that reduce LSC dormancy and promote LSC differentiation, thus the newly dividing LSCs can then be targeted by other chemotherapeutic drugs.
Effect of a Dual-Strain Probiotic on Necrotizing Enterocolitis in Neonates with Ductal-Dependent Congenital Heart Disease: A Retrospective Cohort Study
Authors: Kocjancic Liz , Bührer Christoph , Berger Felix , Boos Vinzenz
Published: August 2020

Background: Newborns with ductal-dependent congenital heart disease (CHD) are at increased risk for developing necrotizing enterocolitis (NEC). Objectives: To investigate whether the use of dual-strain probiotics is beneficial for prevention of NEC in CHD patients, as demonstrated for premature infants. Study Design: Single-center retrospective cohort study of newborns with ductal-dependent CHD before and after implementation of oral dual-strain probiotics containing Bifidobacterium infantis and Lactobacillus acidophilus, on each day of exposure to prostaglandin E1 (PGE1). Results: Birth weight, gestational age, and distribution of heart defects were similar in both cohorts. NEC occurred in 6 of 247 (2.4%) patients without probiotics, and in 3 of 242 (1.2%) patients who received probiotics (p = 0.504). NEC-related mortality (0.4 vs. 0.4%, p = 1.000) and overall mortality (11.0 vs. 8.7%, p = 0.448) were likewise not different. PGE1 exposure was 1,788 and 2,455 days, respectively. In subgroup analysis of 152 infants with aortic arch malformations, such as coarctation of the aorta and interrupted aortic arch, we observed a significant reduction of NEC frequency (5.6 vs. 0.0%, p = 0.048). Conclusions: This is the first study to investigate the effect of a dual-strain probiotic on NEC in CHD patients. Infants with aortic arch malformations appear to benefit from dual-strain probiotics. Due to the scarcity of concurrence of ductal-dependent CHD and NEC, a clinical trial on probiotics to decrease risk of NEC in infants with ductal-dependent CHD would require several thousand infants.
Escherichia coli Panophthalmitis after Pecking by a Great Egret (Ardea alba)
Authors: Ono Takashi , Abe Kentaro , Mori Yosai , Nejima Ryohei , Iwasaki Takuya , Aihara Makoto , Miyata Kazunori
Published: August 2020

We report a case of open globe injury caused by Ardea albapecking that resulted in Escherichia colipanophthalmitis. A woman in her 70s complaining of ocular pain was referred to our hospital because her right eye had been pecked by an A. alba2 days earlier. Visual acuity in her right eye was reduced to light sensation. The right conjunctiva became hyperemic and edematous with swelling of the right upper eyelid. The upper side of the right cornea was densely cloudy with focal defect. Ultrasonography showed a thick sclera and choroid-like structure. Pathological investigation of a scraped sample from the infected site revealed gram-negative rods; E. coli was isolated. She had fever with elevated serum C-reactive protein levels and leukocytosis confirmed by laboratory examination. Topical levofloxacin and cefmenoxime and intravenous fosfomycin and aspoxicillin were initiated, but the right cornea melted near the perforated site with leakage of the eyeball contents on the next day. We decided to perform eye evisceration because of difficulty in controlling corneal melting and panophthalmitis. Her general state recovered the day after surgery. Orbital cellulitis improved gradually with normal C-reactive protein levels and white blood cell counts. As ocular injury caused by birds could become severe and cause ocular infection and visual dysfunction, it is important to exercise caution in the vicinity of wild birds, especially when they are aggressive.