bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3765: Single cell spatial proteomics analysis and computational evaluation pipeline
Authors: Bozorgui Behnaz , Dereli Zeynep , Thibault Guillaume , Weinstein John N. , Korkut Anil 
Published: March 2024

Abstract
Resolving tissue and proteomic heterogeneity is critical to decoding the structure and function of tumor-immune microenvironment (TIME). Such understanding requires profiling of tumor and immune cell proteomic features with spatial resolution at the single-cell level. Although such spatially resolved methods and data sets are becoming increasingly available, analytical and computational methods that can extract the highly complex features and interactions within TIME are lacking. To address that problem, we have developed a computational pipeline we call the Spatial Proteomics Analysis and Computational Evaluation Pipeline (SPACE). The SPACE pipeline is composed of many analysis modules for processing and mining highly multiplexed imaging-based data types to explore TIME composition, organization, and heterogeneity. The pipeline generates and interprets biomarker expression and positional information from multiplexed images using algorithms for image indexing, image registration, quality control, segmentation, identification and removal of non-specific signals, data normalization, automatic identification of missing data, and adjustment for left-over signals. The accurate intensity measurements at single cell level are then used to calculate the proposed spatial features that represent cellular interactions in TIME. A hierarchical decision tree of cell markers is used to annotate types and identities for individual cells. The SPACE enables statistical and differential analyses of complex spatial features as well as cell types/identities with respect to clinical annotations and genomic alterations. The visualization of spatial and imaging data is made possible through an open-source OMERO image repository and spatial maps that integrate diverse markers in a single representation. Here, we demonstrate the applications of our pipeline in diverse gastrointestinal tumor types (e.g., small bowel adenocarcinoma) and validate the importance of integrating tissue heterogeneity at spatial and single-cell level. The framework is applicable to nearly all highly multiplexed imaging data platforms, including but not limited to, CycIF, CODEX, and imaging mass cytometry.
Citation Format: Behnaz Bozorgui, Zeynep Dereli, Guillaume Thibault, John N. Weinstein, Anil Korkut. Single cell spatial proteomics analysis and computational evaluation pipeline [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3765.
Abstract 3822: Oncotype DX testing and differences in use of chemotherapy by age in an integrated system
Authors: Aller Ashley , Lyon Liisa , Habel Laurel , Shirazi Aida , Liu Raymond 
Published: March 2024

Abstract
Introduction: Oncotype DX (ODX) identifies breast cancer patients who are less likely to benefit from chemotherapy. We investigated patient factors associated with clinical application of ODX testing and chemotherapy use.
Methods: We identified a cohort of adult breast cancer patients with stage I-IIA, estrogen receptor positive, human epidermal growth factor receptor 2 negative, lymph node negative disease diagnosed within Kaiser Permanente Northern California between 2015 - 2021 eligible for ODX testing. Chi-square tests were used for bivariate analysis of categorical variables. Multivariable logistic regression was used to identify independent predictors of chemotherapy use in female patients with high risk ODX scores (&gt;25).
Results: 8017 patients were eligible for ODX testing; of which 5,136 received testing (64%) and 576 patients (7%) had high risk ODX. ODX testing increased over the years (45% of eligible patients in 2015; 79% of eligible patients in 2021). Testing was frequent in larger lesions (74%), poorly differentiated tumors (73%), and younger patients (83% in patients &lt;40 years at diagnosis; 12% in patients &gt; 80 years). Chemotherapy was frequently administered in younger patient, and for larger, poorly differentiated tumors. For patients who possessed a high risk ODX score, chemotherapy administration differed by age. In comparison with the 90% of high risk patients &lt;45 years who received chemotherapy, 58% of patients 60+ years at diagnosis with high risk ODX received chemotherapy. Comorbidity index and chemotherapy administration was not statistically significant (Table 1).
Conclusion: Oncologists frequently use ODX testing to guide chemotherapy management. Despite high risk ODX scores, older patients received less chemotherapy compared to their younger counterparts. Further investigation is needed to determine how age impacts clinician decision making and clinical outcomes following ODX testing.
Table 1. Multivariable Logistic Regression Analysis of Factors Associated with Chemotherapy Women &gt; 60 years with high risk oncotype DX scores (N=467) Adjusted Odds Ratio (95% Confidence Interval) P-values (Calculated using the Wald χ2 Statistic) Age at Cancer Diagnosis (Reference: 60 - 69 years old) 70-79 0.62 (0.40-0.96) 0.03 &gt;79 0.11 (0.02-0.55) 0.01 Charlson Comorbidity Index (Reference = 0) 1 0.76 (0.48-1.22) 0.26 2 0.62 (0.30-1.29) 0.20 3 0.65 (0.26-1.60) 0.35 4 0.54 (0.20-1.44) 0.22 5+ 0.37 (0.10-1.35) 0.13
Citation Format: Ashley Aller, Liisa Lyon, Laurel Habel, Aida Shirazi, Raymond Liu. Oncotype DX testing and differences in use of chemotherapy by age in an integrated system [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3822.
Abstract 3824: Efficacy of trastuzumab in combination with capecitabine and cisplatin vs 5-FU and cisplatin therapy for Korean patients with HER2-positive advanced gastric cancer Health Insurance Review and Assessment service (HIRA) data retrospective analysis
Authors: Lee hyun woo , Kim Jang-Hee , Kang Seok Yun , Park Tae Jun , Choi Yong Won 
Published: March 2024

Abstract
The combinations of oral fluoropyrimidines and cisplatin such as capecitabine and cisplatin (XP) or 5-FU and cisplatin (FP) are regarded as a standard therapy against HER-2 positive advanced gastric cancer (AGC). Trastuzumab-XP(HXP) and trastuzumab-FP(HFP) is the most common regimen against AGC in Korea. The aim of the present study is to evaluate the effectiveness of trastuzumab-XP vs trastuzumab-FP.
Patients with HER2-positive AGC were assigned to the trastuzumabXP or trastuzumabFP group. We then retrospectively compared the efficacy and safety between both groups. As a first-line chemotherapy, trastuzumab in combination with XP or FP was administered to 2,399 patients: 1,913 with HXP and 486 with HFP. In the HXP group vs HFP group, median progression-free survival (mPFS), and median overall survival (mOS) were 8.02 vs 6.08 months (p &lt;0.0001) and 13.27 vs 9.89 months (p &lt;0.0001). In HFP group, mPFS and mOS were 10.15 vs 5.36 months (p &lt;0.0001) and 15.15 vs 8.90 months (p &lt;0.0001) in comparison HFP-H maintenance to HFP group. In HXP group, mPFS and mOS were 10.64 vs 13.44 vs 5.03 months (p &lt;0.0001) and 20.14 vs 22.18 vs 9.10 months (p &lt;0.0001) in comparison HXP-H maintenance, HXP-HX maintenance, and HXP group.
Trastuzumab in combination with XP and HX maintenance is a potential first-line therapeutic option for patients with HER2-positive AGC.
Citation Format: hyun woo Lee, Jang-Hee Kim, Seok Yun Kang, Tae Jun Park, Yong Won Choi. Efficacy of trastuzumab in combination with capecitabine and cisplatin vs 5-FU and cisplatin therapy for Korean patients with HER2-positive advanced gastric cancer Health Insurance Review and Assessment service (HIRA) data retrospective analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3824.
Abstract 3833: Primary cutaneous diffuse large B-cell lymphoma-leg type and clinicopathologic determinants of survival: Analysis of a pooled database
Authors: Haddad Philip A. , Amankwah Millicent 
Published: March 2024

Abstract
Background: Primary Cutaneous Diffuse Large B-cell Lymphoma-Leg Type (PCDLBCL-LT) is a rare but non-indolent subtype of B-cell lymphoma. While most PCDLBCL-LT starts over the lower extremities, some cases may present at other cutaneous sites. The determinants of survival outcomes in this disease are not very well defined. Therefore, we conducted this pooled database analysis to identify the prognostic factors, clinicopathological characteristics, and therapeutic strategies that influence survival in this disease.
Methods: To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 122 cases that fit the diagnostic criteria for PCDLBCL-LT. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS) and disease-free survival (DFS).
Results: A total of 122 patients with confirmed PCDLBCL-LT were identified. The median age was 76. There was a male preponderance with M:F of 2.4. Seventy-three percent involved the extremities. The median duration of symptoms before diagnosis was 3.5 months. Involvement of lymph nodes, bone marrow, bone, and CNS occurred in 11%, 3%, 4%, and 3%, respectively. Constitutional symptoms were reported in 5%. The median OS and DFS of the whole group were 39 and 32 months, respectively. Patients younger than 70 had better median DFS (NR vs. 24 months, p=0.02) with a non-significant better median OS. Lymphadenopathy (45 vs. 18 months, p=0.006) and stage T3 compared to T1/T2 (16 vs 41 months, p=0.006) were associated with worse OS. Sex, constitutional symptoms, IHC phenotype, extra-lymphatic/extra-cutaneous organ involvement, and histologic cutaneous patterns did not impact OS. Compared to no treatment, chemotherapy, XRT+/-surgery, and stem cell transplant had numerically better OS without reaching statistical significance (5 vs. 39 vs. 41 vs. NR months, p=0.15). Patients who attained CR as their best response also had a superior median OS compared to responses less than CR and none (61 vs. 23 vs. 11 months, p&lt;0.0001).
Conclusion: This study presents updated clinicopathologic data from a large, pooled cohort of patients with PCDLBCL-LT. It identifies age, lymph node involvement, T stage, type of therapy, and quality of response to treatment as critical determinants of OS.
Citation Format: Philip A. Haddad, Millicent Amankwah. Primary cutaneous diffuse large B-cell lymphoma-leg type and clinicopathologic determinants of survival: Analysis of a pooled database [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3833.
Abstract 3852: Comprehensive genomic profiling of recurrent or metastatic head and neck cancer presenting with combined positive score 90 or more
Authors: Saito Yuki , Hidenori Kage , Kobayashi Kenya , Fukuoka Osamu , Yamamura Koji , Shinozaki-Ushiku Aya , Oda Katsutoshi , Kondo Kenji 
Published: March 2024

Abstract
Background. Biomarkers that predict response to immune checkpoint inhibitor (ICI) in recurrent metastatic squamous cell carcinoma of the head and neck (RMHNSCC) are not well known. Previously, we have found that Combined positive score (CPS) ≥90 and albumin &gt;3.5 respond well to ICI treatment in patients with RMHNSCC treated with ICI irrespective of addition of chemotherapy. In the present study, we investigated whether RMHNSCC with CPS ≥90 has a characteristic genomic mutational profile.
Methods. CPS measurements were performed on a single tumor specimen at the time of diagnosis of RMHNSCC, as approved by Japanese health insurance. Tumor specimens were obtained from the primary tumor as much as possible, and sections that best reflected anti-tumor immunity were decided by a pathologist. We retrospectively reviewed the results obtained from comprehensive genomic profiling (CGP) testing of RMHNSCC cases with CPS ≥90 who were treated by ICI experienced at our institution.
Results. There were 117 eligible RMHNSCC cases. The number of primary lesions were oral cavity in 28 cases (23.9%), nasopharynx in 10 cases (8.5%), oropharynx in 21 cases (17.9%), hypopharynx in 33 cases (28.2%), and others in 18 cases (15.4%). Of 117 patients, 28 patients (23.9%) had a CPS ≥90. Of the 28 cases, the number of primary lesions were oral cavity in 12 cases (42.9%), nasopharynx in 4 cases (14.3%), oropharynx in 0 cases (0%), hypopharynx in 8 cases (28.6%), and others in 3 cases (10.7%). When ICI was administered, CPS ≥90 had a statistically significantly better prognosis than CPS &lt;90 for OS and PFS. Of the 28 cases with CPS ≥90, CGP test was performed in 6 cases. The primary lesions in the 6 cases consisted of 3 oral cavity, 2 nasopharynx, 1 hypopharynx, and 1 maxillary sinus. All three oral primary cases had co-mutations in the TERT promoter and HRAS. Two of the nasopharyngeal primary cases had mutations in JAK3 and STAT, respectively. One of the hypopharyngeal primary cases had mutations in FGFR3.
Conclusion. RMHNSCC with CPS ≥90 had unique mutations that could account the enhanced PD-L1 expression, such as TERT/HRAS co-mutation, JAK-STAT pathway mutation, and FGFR pathway mutation. The above findings may be useful for predicting the efficacy of ICI for RMHNSCC.
Citation Format: Yuki Saito, Kage Hidenori, Kenya Kobayashi, Osamu Fukuoka, Koji Yamamura, Aya Shinozaki-Ushiku, Katsutoshi Oda, Kenji Kondo. Comprehensive genomic profiling of recurrent or metastatic head and neck cancer presenting with combined positive score 90 or more [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3852.
Abstract 3879: Development of potent, highly selective and efficacious SMARCA2 degraders
Authors: Yang Lin , Tu Wenbin , Huang Liyue , Leng Lingying , Jiang Wei , Wang Meilin , Wen Bo , Sun Duxin , Stuckey Jeanne , Wang Shaomeng 
Published: March 2024

Abstract
In human lung, melanoma and other types of human cancers, the mammalian SWItch/Sucrose Non-Fermentable (SWI/SNF) helicase SMARCA4 is frequently mutated, which leads to inactivation of its functions. SMARCA2, a close homologous protein of SMARCA4, is an attractive synthetic lethality target for human cancers with SMARCA4 deficiency. Herein, we report the discovery and biological evaluation of potent, highly selective and efficacious SMARCA2 PROTAC degraders exemplified by UM-SMD-3236. UM-SMD-3236 has a DC50 value of &lt;1 nM in inducing degradation of SMARCA2 in cells and demonstrates &gt;400-fold selectivity over SMARCA4 protein. Of significance, while UM-SMD-3236 achieves a Dmax of &gt;95% against SMARCA2, it shows a Dmax of 50% against SMARCA4 in cells. In vivo, a single intravenous dose of UM-SMD-3236 attains 85-93% of SMARCA2 depletion in tumor tissues for 7 days, while showing no reduction of the SMARCA4 protein. Weekly intravenous administration of UM-SMD-3236 is highly effective in inhibition of tumor growth in SMARCA4 deficient xenograft models of human cancer. Importantly, UM-SMD-3236 shows no signs of toxicity in mice at highly efficacious doses. UM-SMD-3236 represents a highly promising SMARCA2 degrader for extensive evaluation as a potential new therapy for the treatment of SMARCA4-deficient human cancers.
References 1. Oike, T.; Ogiwara, H.; Tominaga, Y.; Ito, K.; Ando, O.; Tsuta, K.; Mizukami, T.; Shimada, Y.; Isomura, H.; Komachi, M.; Furuta, K.; Watanabe, S.-I.; Nakano, T.; Yokota, J.; Kohno, T. A Synthetic Lethality-Based Strategy to Treat Cancers Harboring a Genetic Deficiency in the Chromatin Remodeling Factor BRG1. Cancer Res. 2013, 73, 5508-5518. 2. Yang, L.; Tu, W.; Huang, L.; Miao, B.; Kaneshige, A.; Jiang, W.; Leng, L.; Wang, M.; Wen, B.; Sun, D.; Wang, S. Discovery of SMD-3040 as a Potent and Selective SMARCA2 PROTAC Degrader with Strong in vivo Antitumor Activity. J. Med. Chem. 2023, 66, 10761-10781.
Citation Format: Lin Yang, Wenbin Tu, Liyue Huang, Lingying Leng, Wei Jiang, Meilin Wang, Bo Wen, Duxin Sun, Jeanne Stuckey, Shaomeng Wang. Development of potent, highly selective and efficacious SMARCA2 degraders [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3879.
Abstract 3885: A ubiquitin-specific proximity labeling method to study drug-induced ubiquitylation
Authors: Huang Hai-Tsang , Lumpkin Ryan J. , Tsai Ryan W. , Donovan Katherine A. , Su Shuyao , Zhao Xu , Chen James , Fischer Eric S. , Sellers William R. 
Published: March 2024

Abstract
Targeted protein degradation is a promising therapeutic paradigm that offers new ways to disrupt protein functions. Currently, most studies that characterize the pharmacological effects of protein degraders utilize target-specific assays and global proteomics. However, information on the direct molecular consequence of protein degraders, i.e., induced protein ubiquitylation, is often lacking. Here we report the development of E-STUB (E3-substrate tagging by ubiquitin biotinylation), a ubiquitin-specific proximity labeling method that identifies ubiquitylated substrates in proximity to an E3 ligase of interest. We demonstrated that E-STUB can accurately identify the ubiquitylated targets induced by protein degraders in both CRBN and VHL systems—two of the most utilized E3 ligases by heterobifunctional degraders—and is likely generalizable to other E3 ligases. While we observed a high level of consistency between ubiquitylation and degradation for the induced substrates, E-STUB also detected ubiquitylation of non-degraded targets, providing novel and complementary insights to global proteomics. We also envision that E-STUB could be specifically used for the development of chemical inducers of proximity that catalyze non-degradative ubiquitylation events. In summary, we expect that the E-STUB approach can be widely useful for studying the principles of chemically induced ubiquitylation and the advancement of targeted protein degradation.
Citation Format: Hai-Tsang Huang, Ryan J. Lumpkin, Ryan W. Tsai, Katherine A. Donovan, Shuyao Su, Xu Zhao, James Chen, Eric S. Fischer, William R. Sellers. A ubiquitin-specific proximity labeling method to study drug-induced ubiquitylation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3885.
Abstract 3937: Investigating the role of fibulin 3 in pancreatic tumorigenesis
Authors: Song Hyemin , Hsu Jasper , Lin Xiaoxue , Ogawa Satoshi , Pantazopoulou Vasiliki , Peck Kristina , Bottomley Chelsea , Okhovat Shira , Stamp McKenna , Curtis Kassidy , Esko Jeffrey D. , Engle Dannielle D. 
Published: March 2024

Abstract
Pancreatic ductal adenocarcinoma (PDA) is a highly lethal malignancy with a five-year survival rate of less than 11%, making it one of the deadliest cancers. Notably, 95% of PDA cases exhibit KRAS mutations, contributing to highly dysregulated cell signaling networks. Despite extensive research into the interplay of various oncogenic pathways in pancreatic tumorigenesis, targeted therapies against these signaling networks have displayed modest efficacy, with most patients rapidly developing therapeutic resistance. Recent studies highlight the significance of the carbohydrate antigen 19-9 (CA19-9) as a functional biomarker linked to disease progression and resistance. However, understanding the detailed functions of CA19-9-modified proteins in PDA has been limited due to the lack of adequate models for synthesizing CA19-9. To address this challenge, we have developed unique mouse and 3D organoid culture models capable of producing CA19-9. CA19-9 elevation in mice with KRAS-mutations results in an aggressive PDA phenotype through increased tumor proliferation and microenvironment (TME) remodeling. Furthermore, our research has identified Fibulin 3 (FBLN3), an extracellular matrix glycoprotein, as a secreted, CA19-9-modified protein that stimulates tumorigenesis. In this study, we found that FBLN3 not only facilitates tumor proliferation but also drives epithelial-mesenchymal transition (EMT) and promotes STAT3 pathways activation in the CA19-9pos, KRAS-mutant PDA organoids. Additionally, in both CA19-9pos, KRAS-mutant PDA mouse models and human PDA, FBLN3 is expressed by cancer-associated fibroblasts (CAFs), suggesting its role in TME remodeling. These findings have significant implications for providing novel insights into PDA biology and paracrine signaling mechanisms, identifying FBLN3 as a potential therapeutic target for the improved treatment of this devastating disease.
Citation Format: Hyemin Song, Jasper Hsu, Xiaoxue Lin, Satoshi Ogawa, Vasiliki Pantazopoulou, Kristina Peck, Chelsea Bottomley, Shira Okhovat, McKenna Stamp, Kassidy Curtis, Jeffrey D. Esko, Dannielle D. Engle. Investigating the role of fibulin 3 in pancreatic tumorigenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3937.
Abstract 3961: Impact of CD8 resident memory T cells on antitumor immunity and response to cancer immunotherapy
Authors: Corgnac Stephanie , DAMEI Isabelle , Mami-Chouaib Fathia 
Published: March 2024

Abstract
CD8+ resident memory T (TRM) cells expressing the CD103 integrin accumulate in human lung tumors and are associated with a favorable prognosis. We have previously demonstrated that a high density of CD103+CD8+ T cells in human lung tumors is a biomarker of response to immune checkpoint blockade (ICB) immunotherapy. However, a large fraction of human tumors is only weakly infiltrated by CD8+ TRM cells, and the reason of this TRM desert is not explained. Therefore, defining the molecular signals that give rise and maintain TRM cells within the tumor microenvironment (TME) and the mechanisms that potentiate antitumor TRM functions are important challenges. Data obtained in pre-clinical mouse colorectal cancer and melanoma models demonstrate that knocking-out CD103 impairs antitumor T-cell immunity and response to ICB and therapeutic peptide vaccine. Moreover, immunization of melanoma-bearing mice with the cancer vaccine results in a dramatic decrease in the percentage of CD103+ TRM cells among CD8+ tumor-infiltrating T lymphocytes (TIL). Algorithm analyses applied to spectral cytometry data of TIL support the conclusion that upon activation with the peptide vaccine a TRM subset gives rise to tumor-specific effector T cells. The mechanisms associated with the decrease in CD103 expression on CD8+ T cells and lead to a TRM differentiation shift will be presented as well as the key role of TGF-b in CD8+CD103+ TRM formation and persistence in the TME. Our data demonstrate that tumor CD8+CD103+ TRM are capable of mounting a potent antitumor immunity and suggest that a fine balance between diverse signals in the tumor ecosystem is required to induce their differentiation and thereby optimize response to cancer immunotherapy.
Citation Format: Stephanie Corgnac, Isabelle DAMEI, Fathia Mami-Chouaib. Impact of CD8 resident memory T cells on antitumor immunity and response to cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3961.