bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3430: CD47 x ICAM-1 bispecific antibody represents a novel approach for treating ICAM-1 overexpressing tumors
Authors: Wang Xinhua , Wong Oi Kwan , Post Leonard , Chen Xiaocheng 
Published: June 2022

Abstract
CD47/SIRPa axis is an important checkpoint of innate immune system, CD47 interacts with its ligand signal regulatory protein-alpha (SIRPa) on myeloid cells, conveys a “don’t eat me” signal and blocks macrophage mediated phagocytosis. Tumor cells, which express high level of CD47, exploit this mechanism to evade from immune surveillance. CD47 is considered a prominent target for cancer treatment. However, the wide expression of CD47 on normal cells could cause antigen sink and lead to safety issues, such as anemia and thrombocytopenia. ICAM-1 is constitutively present at low levels on endothelial cells, but its overexpression has been observed on various types of tumors, such as primary myeloma, lymphoma and kidney cancer. Here we describe a novel CD47 x ICAM-1 bispecific antibody, which specifically targets CD47+/ICAM-1+ tumors in preclinical studies.A novel anti-CD47 antibody and an anti-ICAM-1 antibody were used for the generation of a CD47 x ICAM-1 bispecific antibody. In vitro assays including FACS binding, FACS-based SIRPa blocking, ADCP, RBC binding and hemagglutination were performed to characterize the bispecific CD47 x ICAM-1 antibody. In vivo efficacies of CD47 x ICAM-1 bispecific antibody were evaluated in xenograft tumor models with high ICAM-1 expression.The CD47 x ICAM-1 bispecific antibody selectively exhibited potent SIRPa blocking and antibody-dependent cellular phagocytosis (ADCP) activity on CD47+/ICAM-1+ tumor cells, but not on cells lacking ICAM-1 expression. Minimal RBC binding and RBC phagocytosis were observed upon treatment with CD47 x ICAM-1 bispecific antibody. The bispecific antibody did not cause any appreciable hemagglutination with up to 1µM antibody treatment. Most importantly, the CD47 x ICAM-1 bispecific antibody demonstrated potent anti-tumor activities in in vivo CDX and PDX models that overexpress both CD47 and ICAM-1. Our findings suggest that the novel CD47 x ICAM-1 bispecific antibody selectively binds to CD47 and blocks CD47/SIRPa binding on ICAM1 overexpressing tumor cells. The bispecific antibody has minimal RBC binding compared to the bivalent CD47 monoclonal antibodies and benchmark anti-CD47 antibodies. The bispecific antibody shows potent in vivo efficacy and specificity toward ICAM-1+/CD47+ positive tumor cells and represents a novel approach for treating ICAM-1+/CD47+ tumors.
Citation Format: Xinhua Wang, Oi Kwan Wong, Leonard Post, Xiaocheng Chen. CD47 x ICAM-1 bispecific antibody represents a novel approach for treating ICAM-1 overexpressing tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3430.
Abstract 3452: Morphological phenotyping of organotropic brain- and bone-seeking triple negative metastatic breast tumor cells
Authors: DeCastro Ariana Joy L. , Pranda Marina , Gray Kelsey , Merlo-Coyne John , Girma Nathaniel , Hurwitz Madelyn , Zhang Yuji , Stroka Kimberly 
Published: June 2022

Abstract
Triple negative breast cancer (TNBC) follows a non-random pattern of metastasis to the bone and brain tissue. Prior work has found that brain-seeking breast tumor cells display altered proteomic profiles, leading to alterations in pathways related to cell signaling, cell cycle, metabolism, and extracellular matrix remodeling. Given the unique microenvironmental characteristics of brain and bone tissue, we hypothesized that brain- or bone-seeking TNBC cells may have altered morphologic or migratory phenotypes from each other, or from the parental TNBC cells, as a function of the biochemical or mechanical microenvironment. In this study, we utilized TNBC cells (MDA-MB-231) that were conditioned to metastasize solely to brain (MDA-BR) or bone (MDA-BO) tissue. We quantified characteristics such as cell morphology, migration, and stiffness in response to cues that partially mimic their final metastatic niche. We have shown that MDA-BO cells have a distinct protrusive morphology not found in MDA-P or MDA-BR. Further, MDA-BO cells migrate over a larger area when on a collagen I (abundant in bone tissue) substrate when compared to fibronectin (abundant in brain tissue). However, migration in highly confined environments was similar across the cell types. Modest differences were found in the stiffness of MDA-BR and MDA-BO cells plated on collagen I vs. fibronectin-coated surfaces. Lastly, MDA-BO cells were found to have larger focal adhesion area and density in comparison with the other two cell types. These results initiate a quantitative profile of mechanobiological phenotypes in TNBC, with future impacts in helping to predict metastatic propensities to organ-specific sites in a clinical setting.
Citation Format: Ariana Joy L. DeCastro, Marina Pranda, Kelsey Gray, John Merlo-Coyne, Nathaniel Girma, Madelyn Hurwitz, Yuji Zhang, Kimberly Stroka. Morphological phenotyping of organotropic brain- and bone-seeking triple negative metastatic breast tumor cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3452.
Abstract 3496: Transcriptomic classification of lung adenocarcinoma identifies a novel subgroup with a poor survival prognosis
Authors: Satter Khaled Bin , Tran Paul MH , Tran Lynn KH , Nechtman John , Patel Nikhil , Santos Bruno , Hopkins Diane , Karim Nagla Abdel , She Jin-Xiong , Purohit Sharad B. 
Published: June 2022

Abstract
Lung adenocarcinoma is one-half of all lung cancer and the third deadliest cancer in the world. The traditional classification of lung adenocarcinoma involves invasiveness, growth pattern, presence of mucin, and other histological features. However, this classification provides limited prognostic predictability. Molecular profiles based The Cancer genome Atlas lung adenocarcinoma cohort classified the tumors into the terminal respiratory unit (TRU), proximal proliferative (PP), and proximal infiltrative (PI) based on unsupervised classification, which did not address clinical applicability to the classification. Here, we developed an unsupervised classification with Density-based UMAP (DBU), which identified four transcriptomic profiles for lung adenocarcinoma (Transcriptomic profile, TP1-TP4). We identified a gene signature with 299 genes to develop a supervised classifier, called Ensemble Transcriptomic classifier (ETC), to identify these four subgroups within the total cohort. All TP1 is PI. TP2 is 49.0% TFU and 45.0% PP. TP3 is 76.2% PI and 23.8% PP. TP4 is 54.5% TFU and 45.5% PI. TP1 is characterized by neuroendocrine-like features and clusters with large cell neuroendocrine tumors in cluster analysis. TP3 is squamous-like enriched with cell cycle and DNA repair high and worse prognosis and groups with squamous cell carcinoma in cluster analysis. TP2 has high immune cell infiltration, and TP4 showed low mutational burden and low immune cell infiltration. We validated these subgroups identified in the TCGA cohort in a microarray meta-dataset with DBU, ETC. This classification showed four subgroups in lung adenocarcinoma, which shows potential clinical actionable findings.
Citation Format: Khaled Bin Satter, Paul MH Tran, Lynn KH Tran, John Nechtman, Nikhil Patel, Bruno Santos, Diane Hopkins, Nagla Abdel Karim, Jin-Xiong She, Sharad B. Purohit. Transcriptomic classification of lung adenocarcinoma identifies a novel subgroup with a poor survival prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3496.
Abstract 363: Intracellular redox milieu regulates Mcl-1 and decreases overall mitochondrial priming in hematopoietic cancers
Authors: Lai Jolin Xiao , Chong Stephen Jun , Davids Matthew , Pervaiz Shazib 
Published: June 2022

Abstract
Background: The dichotomy of redox signaling in cancer cell fate decisions has emerged as a topic of importance over the years. In particular, our group has highlighted the role of superoxide (O2 .-)-mediated signaling in the acquisition of drug resistance and cancer survival. Mechanistically, this involves post-translational modification of proteins involved in oncogenic signaling, such as c-Myc and NF-κB, as well as apoptosis resistance like Bcl-2 at the serine 70 phosphorylation site. Here we present evidence that O2 .--mediated signaling stabilizes anti-apoptotic protein Mcl-1, a commonly amplified gene in human cancers and is implicated in resistance to venetoclax, the Bcl-2 specific BH3 mimetic.
Methods: Intracellular O2 .- levels was increased either pharmacologically or by siRNA mediated knockdown of SOD1 in MOLM14, RPMI8226, OCI-AML3 hematopoietic cell lines. Cell viability and apoptosis were assessed by MTT and Annexin V/DAPI staining. Protein expression was determined by Western blot analysis. BH3 profiling of patient-derived CLL cells was used to assess mitochondrial priming.
Results: Elevated O2 .- levels increased Mcl-1 stability through Thr163 phosphorylation of Mcl-1, which in turn reduced ubiquitination-dependent degradation. Furthemore, venetoclax resistant cells possessed higher O2 .- levels and increase in intracellular O2 .- levels promoted resistance to Mcl-1 inhibitor, S63845 through increased binding between Mcl-1 and pro-apoptotic proteins NOXA and Bak. Contrarily, scavenging of O2 .- re-sensitized venetoclax-resistant leukemia cells to venetoclax. Importantly, BH3 profiling revealed that increase in intracellular O2 .- levels decreased overall mitochondrial priming in primary CLL cells by promoting sequestration of pro-apoptotic proteins that specifically target Mcl-1.
Conclusion: Oncogenic activity of O2 .- is mediated by increased Mcl-1 stability through Thr163 phosphorylation, which resulted in a reduction in overall mitochondrial priming and increased binding of Mcl-1 to NOXA and Bak. Scavenging O2 .- reduces Mcl-1 levels and sensitizes resistant cells to venetoclax-induced apoptosis thereby demonstrating that manipulation of the redox microenvironment could be a potential vulnerability to be exploited in venetoclax resistant cancers
Citation Format: Jolin Xiao Lai, Stephen Jun Chong, Matthew Davids, Shazib Pervaiz. Intracellular redox milieu regulates Mcl-1 and decreases overall mitochondrial priming in hematopoietic cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 363.
Abstract 3642: The aged lung promotes reactivation from metastatic melanoma dormancy
Authors: Fane Mitchell , Weeraratna Ashani 
Published: June 2022

Abstract
Our previous data have indicated that while tumors grow more slowly in aged mouse skin, they form more lung metastases. We queried whether the lung microenvironment undergoes age-related changes that provide a permissive niche for metastatic outgrowth. Our data showed that secreted factors by lung fibroblasts changed during aging that promoted proliferation of melanoma cells via expression of the tyrosine kinase receptor MER. Further investigation of this MER-high phenotype revealed that these melanoma cells induce dramatic changes to the lung microenvironment via secretion of its primary ligand PROS1, which creates a more permissive niche for metastasis. It first acts in a paracrine manner to induce proliferation of previously dormant melanoma cells in the lung. MER induced secretion of PROS1 by melanoma cells also regulates the production of extracellular matrix (ECM) from lung fibroblasts. Specifically, healthy human lung fibroblasts produce thick, unified cellular derived matrices (CDMs) in vitro that are growth-restrictive to melanoma cells. Treatment of lung fibroblasts with conditioned media from MER-High melanoma cells or with recombinant-PROS1 alters CDM density and orientation, which resulted in a CDM that dramatically increased melanoma proliferation. Finally, we found that MER induced metastatic outgrowth of melanoma cells within the lungs of mice decreased CD4 and CD8 T-cells whilst increasing infiltration of and immunosuppressive T-regulatory cells (Tregs) and Myeloid Derived Suppressor Cells (MDSCs).
Overall, we find that age-induced activation of melanoma cells towards a MER-high state within the lung can induce a cancer phenotype which dramatically alters fibroblast ECM production and immune cell infiltration to promote aggressive and efficient metastatic outgrowth and a growth permissive microenvironment for dormant melanoma cells.
Citation Format: Mitchell Fane, Ashani Weeraratna. The aged lung promotes reactivation from metastatic melanoma dormancy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3642.
Abstract 3653: The moderating role of dietary patterns on physical health and risk of cancer mortality in the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort
Authors: Aduboffour Akwasi O. , Carter Stephen J. , Howard George , Khan Saira , Lewis-Thames Marquita , Moore Justin Xavier , Moore MPH X. 
Published: June 2022

Abstract
Diet and physical activity share an association with cancer mortality. We investigated whether empirically-defined dietary patterns modified the association between a composite of physical health and cancer mortality.
METHODS: We performed analysis among participants from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. Physical health (PH) composite was assessed by the product of baseline heart rate and systolic blood pressure, a reliable measurement of myocardial oxygen demand, and self-reported physical activity. Participant adherence was assessed with empirically-defined dietary patterns including: Convenience (including Chinese and Mexican foods, pasta, pizza), Plant-based (including fruits, vegetables), Southern (including added fats, fried foods, sugar-sweetened beverages), Sweets/Fats (including sugary foods) and Alcohol/Salads (including alcohol, green-leafy vegetables, salad dressing) was examined as an effect modifier. We performed comparisons across PH composite risk groups (i.e., severe, high, moderate, and low risk). We estimated hazard ratios (HRs) and associated 95% confidence intervals (CIs) by PH composite groups, stratified by dietary patterns.
RESULTS: Among 20,857 participants, 18% were defined as severe-risk PH, 30% were high-risk, 15% were moderate-risk PH, and 38% were low-risk PH. The most common dietary pattern adhered to by severe-risk PH participants was the southern based diet (30% adhering, p value &lt;0.01). Severe-risk PH participants generally had higher risks for cancer mortality, corresponding to a 2.4-fold increased risk of cancer mortality (adjusted HR: 2.42; 95% CI: 1.52 - 3.85) even with limited southern diet consumption (1st quartile).
CONCLUSIONS: Dietary patterns influence cancer mortality risk; however cardiovascular health is independently associated with greater long-term risk of cancer death.
Citation Format: Akwasi O. Aduboffour, Stephen J. Carter, George Howard, Saira Khan, Marquita Lewis-Thames, Justin Xavier Moore, PhD, MPH X. Moore. The moderating role of dietary patterns on physical health and risk of cancer mortality in the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3653.
Abstract 3674: Differential expression of stress-survival pathway genes related to Hispanic colorectal cancer disparities
Authors: Kulkarni Aditi , Basnet Urbashi , Patil Abhijeet R. , DeJesus Rebecca , Roy Sourav 
Published: June 2022

Abstract
Colorectal cancer (CRC) accounts for 12% and 8% of all estimated new cases of cancer and 11% and 9% of all cancer deaths in Hispanic men and women, respectively. Stress-survival pathways have been implicated in tumorigenesis of CRC and in providing resistance to chemotherapy-induced cell-death by suppressing reactive oxygen species (ROS), repairing DNA damage, and by regulating cell signaling pathways. However, studies related to the role of these pathways in CRC from the Hispanic health disparities perspective, are limited. Essential to improving treatment, prognosis, and detection strategies is the identification and validation of new ethnicity-specific transcriptomic markers within the stress-survival pathways as effective predictors of CRC. In this study, we have explored the role of stress-survival pathway genes in Hispanic and Non-Hispanic White (NHW) CRC tissues. We have used microarray and RNA-seq datasets obtained from the gene expression omnibus (GEO) and the cancer genome atlas (TCGA) to identify 28 genes associated with CRC. These genes were screened for transcript level expression in one normal colon and two CRC cell lines, and in cDNA arrays containing tumor (n=40) from different stages, and control (n=8) samples. The protein level expressions were evaluated by immunohistochemistry (IHC) in CRC tissue microarrays (TMAs) containing different stages of tumor (n = 108) and control (n = 12) tissues. All 28 genes were also analyzed for their transcript level expressions in Hispanic and NHW tissues. Genes related to apoptosis like FOXM1, CDK1, CDK4, Chek1, and MCM10 showed consistent upregulation in CRC cell lines, cDNA arrays and TMAs when compared to normal samples. We could also detect a correlation between the differential expression of these genes and the tumor stages. CDK4, Chek1, FOXM1, and CDC25, were observed to be downregulated in the Hispanic CRC tissues. On the other hand, oxidative stress markers were not seen to be differentially expressed in the two CRC cell lines when compared to the normal cell line. However, some of the known oxidative stress markers like PRDX4, GPX1, and SOD2 were found to be upregulated in Hispanics when compared to NHW tissues. Our results suggest that some of these stress-survival pathway genes could be explored as interesting candidates for ethnicity-specific CRC biomarkers and as novel therapeutic targets in the future.
Citation Format: Aditi Kulkarni, Urbashi Basnet, Abhijeet R. Patil, Rebecca DeJesus, Sourav Roy. Differential expression of stress-survival pathway genes related to Hispanic colorectal cancer disparities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3674.
Abstract 3680: Distinctive metabolomics profiles associated with African American current smokers who have high aggressive prostate cancer
Authors: Jun Se-Ran , Su L. Joseph , Matich Eryn , Hsu Ping-Ching 
Published: June 2022

Abstract
Background: Smoking has not been an established risk factor for prostate cancer (PCa), and has not been emphasized in PCa prevention. However, recent studies have shown increasing evidence that there is a higher risk of biochemical recurrence, PCa mortality, and metastasis among current smokers, presenting an urgent need in re-evaluating the association between smoking and aggressive PCa. This study aimed to determine whether smoking increase the likelihood of developing a more aggressive prostate cancer.
Methods: Equal numbers of African Americans (AAs) and European Americans (EAs) by smoking status (never/former/current) matched with PCa aggressiveness, BMI, 5-year age group, and year of baseline recruitment, totaling 480 participants, were included in the metabolomics study. For metabolomics analysis, fold change and BH-adjusted p-value from t-test adjusted for age for univariate analysis, and PCA adjusted for age and PLS-DA supervised statistical analysis for multivariate analysis were employed to decipher the underlying metabolomic patterns, and identify significantly dysregulated metabolites for the variables of interest.
Results: AA participants were significantly younger (mean=61.4, SD=7.7) compared with EAs (mean=63.5, SD=7.5). Current smokers had a 2.4 times higher risk of high aggressive PCa. When stratified by race, the risk diminished for EAs but increased for AAs. Global metabolic profiles detected a total of 1,487 compounds of known identity. After excluding metabolites with missing values in more than 20% of the samples and with small standard variation, we observed a distinct cluster of participants from AA aggressive PCa patients and current smokers that were separated from EAs and never smokers. With BH-adjusted p-value &lt; 0.05 and fold change &gt; 2, we identified 10 significantly dysregulated metabolites between AA and EA among high aggressive PCa and current smokers. Further, 36 metabolites between current and never smokers among AA high aggressive PCa were significantly dysregulated, but none of them are annotated as tobacco metabolites.
Conclusion: Our study presented distinctive metabolomics profiles specific to AA current smokers who had high aggressive PCa. Furthermore, the distinctive patterns were not driven by the tobacco metabolites, with the potential to identify metabolites that might help to understand the relationships between smoking and aggressive PCa in AA.
Citation Format: Se-Ran Jun, L. Joseph Su, Eryn Matich, Ping-Ching Hsu. Distinctive metabolomics profiles associated with African American current smokers who have high aggressive prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3680.