bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PO-145: Contribution of the GR-LEDGF/p75 axis to prostate cancer chemoresistance
Authors: Sanchez-Hernandez Evelyn S , Ortiz-Hernandez Greisha L. , Ochoa Pedro T. , Gomez Christian R , Casiano Carlos A 
Published: January 2022

Abstract
Prostate cancer (PCa) is the second leading cause of cancer deaths in the U.S., disproportionally affecting African American (AA) men. Glucocorticoids (GCs) are administered to PCa patients and have been implicated in therapy resistance. This may be critical to AA men with PCa since they have elevated endogenous GCs levels compared to Caucasian American (CA) men. GCs bind to the glucocorticoid receptor (GR) to exert their actions. The mechanisms of GR-mediated chemoresistance, and its possible contribution to PCa mortality disparities are unknown. We demonstrated that GCs upregulate the chemoresistance-associated protein and transcription co-activator LEDGF/p75 in PCa cells and identified consensus GR binding sites in the promoter region of this protein. Given that both GR and LEDGF/p75 are components of the RNA polymerase II transcription complex, we hypothesized that GR transcriptionally upregulates LEDGF/p75 and then interacts with it to enhance taxane resistance in PCa cells. Pharmacological and genetic inhibition of GR in a panel of docetaxel (DTX)-sensitive and -resistant PCa cells decreased the expression of LEDGF/p75, confirming its status as a candidate GR target gene. However, silencing of LEDGF/p75 had no effects on GR expression. Immunoprecipitation studies revealed that GR and LEDGF/p75 interact in DTX-sensitive and -resistant PCa cells. This interaction was confirmed by confocal microscopy. Immunohistochemical analysis of GR and LEDGF/p75 expression in normal and tumor prostate tissues was performed and the results are currently being analyzed. Our studies use a mechanistic approach to evaluate the potential contribution of the GR-LEDGF/p75 axis to PCa chemoresistance. Evaluating the co-expression of these proteins in racially diverse PCa tissues may also reveal race-related differential expression, providing insights into the potential contribution of this axis to PCa chemoresistance and mortality disparities.
Citation Format: Evelyn S Sanchez-Hernandez, Greisha L. Ortiz-Hernandez, Pedro T. Ochoa, Christian R Gomez, Carlos A Casiano. Contribution of the GR-LEDGF/p75 axis to prostate cancer chemoresistance [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-145.
Abstract PO-147: Targeting Notch signaling in cancer stem-like cells of triple-negative breast cancer
Authors: Murphy Adrienne M. , Ucar Ayse D. , Miele Lucio 
Published: January 2022

Abstract
Triple-Negative Breast Cancer (TNBC) is an aggressive form of breast cancer. This particular type expresses no Estrogen (ER) and Progesterone (PR) hormone receptors or Human epidermal growth factor receptor-2 amplifications. African American women are more frequently affected at a younger age by this aggressive breast cancer than any other ethnicity. Furthermore, heterogeneity of cells within a tumor challenges to identify specific targets to develop new drugs. Specifically, a subpopulation of cells within a tumor, called cancer stem-like cells (CSC) are known to grow slower, resist treatments, and be responsible for the relapse and metastasis of a tumor. Notch signaling pathway, which is one of the key regulatory signaling pathways in normal and cancer stem cells. We hypothesize that Notch1 signaling is a crucial signaling pathway for TNBC and worthwhile to target. To be able to identify and test Notch-specific targeted drugs, it is crucial to establish a cell line that overexpresses and knocks down the target gene. Therefore, in this project, we establish Notch1 modified stable TNBC cell lines and checked their morphological and physiological changes. Using MDA-MB-231 TNBC cell line, for the Notch1 knockout, we used crisper/cas9 gene-editing method and clonal selection of knockout cells. For the overexpression of NOTCH1 intracellular domain, we constructed and used pBABE-puro lentivirus system. Our results showed the Notch1 KO cells become more epithelial-like in appearance, with reduced expression of CD44+/CD24lo CSC markers, and reduced capacity to form mammospheres. On the other hand, overexpression of Notch1 the CSC become more mesenchymal and increase the expression of CSC markers. Also, we observed reduced metabolic activity of our Notch1KO cells while the overexpression of Notch1 increased the metabolic activity of the TNBC cells. Our preliminary results show that targeting Notch signaling is a promising approach to cure TNBC patients suffering from this aggressive cancer.
Citation Format: Adrienne M. Murphy, Ayse D. Ucar, Lucio Miele. Targeting Notch signaling in cancer stem-like cells of triple-negative breast cancer [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-147.
Abstract PO-148: The role of annexin A6 in triple-negative breast cancer metabolism and disease progression
Authors: Williams Stephen D. , Widatalla Sarrah E. , Sakwe Amos M. 
Published: January 2022

Abstract
Triple-negative breast cancer (TNBC), which accounts for up to 17% of all breast cancer cases in the Unites States, disproportionately affects premenopausal African American and Hispanic women. Here, we report the synergistic function of the tumor suppressor annexin-A6 (AnxA6) and Lapatinib-resistance (Lap-R) in the context of cellular bioenergetics. Metabolic profiling of TNBC cell lines show extensive diversity amongst basal-like (BSL) vs mesenchymal-like (MSL) molecular subtypes. Down regulation of AnxA6 in AnxA6- expressing and Lap-R cell lines attenuated mitochondrial respiration, glycolytic function, and cellular ATP production capacity, decreasing the overall metabolic plasticity of the cell. Additionally, AnxA6-depletion altered lipid metabolism by enhancing the mitochondrial uptake of cytosolic fatty acids for β-oxidation. NMR-based metabolomics revealed that AnxA6 depleted and/or Lap-R TNBC cells have a greater dependency on gluconeogenic precursors including glycine, alanine, lactic acid, and oxaloacetic acid as survival mechanisms. Taken together, this study proposes that altered expression of AnxA6 is accompanied by significant bioenergetic adaptations and hence provide novel insights into the failure of EGFR-targeted therapies as therapeutic options and disease progression in patients with triple-negative breast cancer.
Citation Format: Stephen D. Williams, Sarrah E. Widatalla, Amos M. Sakwe. The role of annexin A6 in triple-negative breast cancer metabolism and disease progression [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-148.
Abstract PO-181: Race, educational attainment and pancreatic cancer mortality among Latinos
Authors: Correa Tulio L. , Guelli Mariana S.T.C. 
Published: January 2022

Abstract
Background: Socioeconomic status, race, and educational attainment are known to impact outcomes of various cancers. Pancreatic cancer is one of the most aggressive types of cancer and accounts for a high number of deaths worldwide. This study aims to describe the mortality for pancreatic cancer by sex, race/skin color, and educational attainment in Brazil in the past decade. Methods: Descriptive ecological study, which evaluated the mortality rate for pancreatic cancer in the Brazilian National Health System from 2010-2019. The mortality rate was evaluated by sex, race/skin color, and educational attainment using the national database (DATASUS – Department of Informatics of the Unified Health System). The official classification of race/skin color in Brazil is composed of five categories: White, Brown [Pardo], Black, Yellow, and Indigenous. Results: During this time period, there was a total of 94024 deaths from pancreatic cancer in the Brazilian National Health System, of which 47295 (50.3%) were female. Regarding race/skin color; 58802 (62.5%) considered themselves white, 24845 (26.4%) brown, 5883 (6.3%) black, 954 (1%) others, and 3540 (3.8%) did not answer the question. Regarding educational attainment (n=76343); 9658 (12.7%) never had formal education, 41157 (53.9%) had &gt;0 to 7 years, 15632 (20.4%) had 8 to 11 years, and 9896 (13%) had &gt;12 years of educational attainment. Conclusions: The majority of patients who died from pancreatic cancer in our study were female, white, and had &gt;0 to 7 years of educational attainment. However, these associations are still little analyzed worldwide and need more attention.
Citation Format: Tulio L. Correa, Mariana S.T.C. Guelli. Race, educational attainment and pancreatic cancer mortality among Latinos [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-181.
Abstract PO-207: Impact of Medicaid expansion on stage at diagnosis for US adults with pancreatic cancer: A population-based study
Authors: Mobley Erin M. , Guerrier Christina , Tfirn Ian , Gutter Michael S. , Vigal Kimberly , Pather Keouna , Baskovich Brett , Awad Ziad , Parker Alexander S 
Published: January 2022

Abstract
Introduction: We evaluated whether expansion of state Medicaid programs is associated with earlier-stage at diagnosis for pancreatic cancer among those under the age of 65, before and after Medicaid expansion considering key demographic, clinical, and geographic covariates. Methods: We obtained Surveillance, Epidemiology, and End-Results (SEER-18) data on individuals under 65 years of age diagnosed with pancreatic cancer from 2007-2016, including Urban Influence Code (UIC) and Social Deprivation Index (SDI) data. We defined early stage as either local or regional disease (versus advanced disease). To estimate the effect of Medicaid expansion on stage at diagnosis, we used a Difference-in-Differences (DD) model, at the individual level, comparing those from early-adopting states in 2014 to non-early-adopting states. We utilized cluster-robust standard errors and explored the role of covariates including demographic factors (race, sex, insurance coverage at diagnosis), clinical indicators (disease located in the head of the pancreas), and county characteristics (UIC and SDI). Results: The probability of early-stage disease at diagnosis increased by 3.9 percentage points (ppt) for those from Medicaid expansion states post-expansion (n=36,609). After adjustment for key covariates, the ppt was attenuated to 2.7. Of note, we observed evidence of interactions with sex and race. Indeed, the beneficial effect of living in an expansion state on stage at diagnosis was less pronounced for men (increase in the probability of early stage at diagnosis by 2.1ppt) than women (3.6ppt) and non-existent for blacks (-3.1ppt) compared to whites (4.9ppt) and other races (4.8ppt). Redefining early stage to only local stage attenuated the beneficial effect for all groups and increased the negative effect for blacks. Conclusion: Medicaid expansion is associated with earlier stage at diagnosis for pancreatic cancer; however, this beneficial effect is not uniform across sex and race. This underscores the need to investigate the impact of policy changes and implementation strategies on disparities in pancreatic cancer survival.
Citation Format: Erin M. Mobley, Christina Guerrier, Ian Tfirn, Michael S. Gutter, Kimberly Vigal, Keouna Pather, Brett Baskovich, Ziad Awad, Alexander S Parker. Impact of Medicaid expansion on stage at diagnosis for US adults with pancreatic cancer: A population-based study [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-207.
Abstract PO-213: Financial implication of prostate cancer hypofractionated radiotherapy
Authors: Acharya Suryakanta 
Published: January 2022

Abstract
Background- Prostate cancer is the 2nd most common cancer in males, worldwide & not far behind lung cancer incidence. Radiation holds the potential to cure non-metastatic disease (T1b-T3a), however the old 8-week long conventional radiation treatment is too lengthy & costly for patients. Non-inferiority CHHiP trial established 4 week long hypofractionated radiation which provided a big relief to patients saving substantial cost & time. Method- From January 2020 to December 2020, I had adopted the shorter 4-week radiation regimen for all eligible prostate cancer patients (T1b-T3a N0 M0) needing radiation & the expenditure, both direct as well as indirect, was calculated. Direct cost includes cost of radiation, treatment planning & was obtained from hospital bills. Drug cost was excluded as the amount was too small & insignificant. Indirect cost includes the cost of staying in the city, food & the cost of commuting (local patients) which were obtained from each patient. Total cost during radiation was compared for both 8 week & 4-week regimen. 10 patients participated in the study. Result- Direct cost had reduced from 1750 USD to 1100 USD favoring the shorter 4-week regimen. This translates to 37% cost reduction. Indirect cost was reduced by 50% as the duration of stay reduced from 51 days (8 weeks RT) to 26 days (4 weeks RT) for patients who are from other cities. Those from local place had informed similar figure of commuting cost reduction. Overall, the total cost (direct & indirect) of radiation treatment was reduced by 40%. Conclusion- All patients were glad to know the reduced duration of radiation treatment & 40% cost saving. The time factor has not been taken into account, few patients on job were able join their workplace 4 weeks earlier.
Citation Format: Suryakanta Acharya. Financial implication of prostate cancer hypofractionated radiotherapy [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-213.
Abstract PO-217: Race and metastatic behavior of breast cancer subtypes
Authors: Han Yunan , Colditz Graham A. , Lian Min , Liu Ying 
Published: January 2022

Abstract
Introduction: Racial/ethnic differences exist in early-stage breast cancer, but less is known about whether there are racial differences in metastatic sites of breast cancer. Thus, we examined racial/ethnic differences in metastatic behavior of de novo metastatic breast cancer (MBC). Methods: We identified 28,072 adult women (63.9% non-Hispanic White [NHW], 16.6% non-Hispanic Black [NHB], 7.7% non-Hispanic Asian or Pacific Islander [API], 11.8% Hispanic) diagnosed with de novo MBC in the Surveillance, Epidemiology and End Results between 2010 and 2018. Sites of distant metastasis included bone, lung, liver, and brain. Age-standardized incidence rates and incidence rate ratios (IRRs) were calculated. Logistic regressions were used to estimate the multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results: NHBs had the highest incidence of MBC (13.2 per 100,000). Bone is the most common site of distant metastasis (63.1%). The risks of developing distant metastases to different sites varied by race/ethnicity. Compared with NHW women, NHB women had higher risks of bone (IRR=1.37, 95% CI 1.32-1.43), lung (IRR=1.91, 95% CI 1.80-2.03), liver (IRR=1.62, 95% CI 1.52-1.73), and brain (IRR=1.72, 95% CI 1.51-1.94) metastases. API and Hispanic women had lower risks of bone, lung, and liver metastases than NHW women, and API women also had a lower risk of brain metastasis. In women with hormone receptor-positive and HER2-negative MBC, NHBs, Hispanics, and APIs had a higher risk of lung metastasis and a lower risk of bone metastasis than NHWs after adjusting for age, year of diagnosis, marital status, tumor histology and grade. In women with hormone receptor-positive and HER2-positive MBC, NHB race was related to a higher risk of lung metastasis, and API race to a lower risk of bone metastasis. Hispanics with triple-negative MBC had a lower risk of liver metastasis than their NHW counterparts. A lower risk of liver metastasis was also observed in APIs and Hispanics with hormone receptor-negative and HER2-positive MBC than their NHW counterparts. Conclusions: The association of race and ethnicity with the risk of MBC differed by metastatic sites and tumor subtypes. Propensity to lung metastasis in NHB women with hormone receptor-positive MBC, Hispanics and APIs with hormone receptor-positive and HER2-negative MBC suggests the importance of preventive efforts targeting lung metastasis in these vulnerable patients.
Citation Format: Yunan Han, Graham A. Colditz, Min Lian, Ying Liu. Race and metastatic behavior of breast cancer subtypes [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-217.
Abstract PO-233: Effect of Lactobacillus on tumor growth and radiosensitivity
Authors: Reguero-Cadilla Laura P. , Klopp Ann 
Published: January 2022

Abstract
Cervical cancer is the most common HPV-associated cancer as it is diagnosed in more than half a million women a year. It specially affects low and middle-income countries. In terms of treatment options, microbiome may be a key element in achieving the desired effect of radiation treatment in cervical cancer. The objective here is to evaluate the effect of Lactobacillus iners on tumor growth and cell response to radiation therapy. A previous test cohort identified that poor responders had an abundance of the Lactobacillus genus in their microbiome, while early/exceptional responders had other microorganisms such as Porphyromonas augmented. Moreover, whole genome shot gun sequencing (WGS) demonstrated that Lactobacillus iners is the most common species of Lactobacillus in cervical samples of poor responders and is absent in exceptional responders. Based on these findings, we propose that Lactobacillus iners creates a microenvironment which supports tumor growth and facilitates resistance to radiation therapy. A clonogenics assay using SiHa, HeLa and CaSki cell lines with three bacterial supernatants at different radiation doses was performed. While another facet of our research was comparing tumor growth in C57 mice receiving Lactobacillus iners suspension and those not receiving it. In terms of the clonogenics assay: L. crispatus and L. iners supernatants may increase radiosensitivity of SiHa, HeLa, and CaSki cell lines. Cell survival may also be affected by nutrients in bacterial broths. In terms of the mice's tumors analyzed: no significant differences in tumor growth were found between the control and treatment groups. L. crispatus cohort showed tumor regression, which correlates with higher populations of innate immune cells. Further clonogenic and in vivo experiments are supported to obtain more precise results that could eventually be applied in radiation oncology treatments.
Citation Format: Laura P. Reguero-Cadilla, Ann Klopp. Effect of Lactobacillus on tumor growth and radiosensitivity [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-233.
Abstract PO-239: Patient and provider experiences with an incidentally diagnosed cancer precursor: A qualitative study
Authors: Castaneda-Avila Maira A. , Mazor Kathleen M. , Lapane Kate , Epstein Mara M. 
Published: January 2022

Abstract
Background: Monoclonal gammopathy of undetermined significance (MGUS) is a prevalent, yet incidentally diagnosed precursor to multiple myeloma. We sought to gather foundational knowledge about the experiences of patients and healthcare providers during the process of diagnosing MGUS. Methods: We conducted semi-structured qualitative interviews. We recruited 14 patients using ResearchMatch and Facebook, and eight local healthcare providers. Interviews were analyzed using thematic analysis. Results: We identified three themes focused on the process of receiving or giving an MGUS diagnosis, relating to: (1) providers' explanations, (2) patients' understanding, and (3) the response to diagnosis. Providers reported that they explained MGUS using similar language for all patients, regardless of literacy level or other factors. Providers also indicated the challenges of explaining MGUS to non-English speaking patients using an interpreter. Although all patients were able to offer some description of MGUS in their own words, several patients reported they really did not understand what this diagnosis means. Providers acknowledged that an MGUS diagnosis may lead some patients to experience anxiety. Providers also reported that the referral to a hematologist-oncologist could be inherently stressful for some patients and make them worried about having cancer. Patients reported varied responses to receiving an MGUS diagnosis ranging from relief to anxiety about MGUS progression to multiple myeloma. Conclusion: We observed that providers tend to use consistent language when explaining an MGUS diagnosis to patients. Patients diagnosed with MGUS have a basic understanding of their condition, yet some patients feel anxiety around the diagnosis, which may affect other aspects of their lives. For underserved populations, providers may need to use interpreters to ensure all patients understand their condition. These findings are an important first step in understanding patients' experiences as they are diagnosed with MGUS.
Citation Format: Maira A. Castaneda-Avila, Kathleen M. Mazor, Kate Lapane, Mara M. Epstein. Patient and provider experiences with an incidentally diagnosed cancer precursor: A qualitative study [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-239.