bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB044: Modeling the role of ARID1A in colon cancer using patient-derived organoids
Authors: Deary Luke T. , Sugiarto Nicholas , Pigeon Cameron , Mayo Sara W. , Wilson Matthew Z. , Wang Xiaofeng 
Published: April 2023

Abstract
Loss-of-function (LOF) mutations in genes encoding subunits of SWI/SNF chromatin remodeling complexes are found in approximately 25% of human cancers. Colorectal cancers (CRC), the second leading cause of cancer related deaths, are particularly vulnerable to SWI/SNF driver mutations, harboring subunit alterations in up to 55% of patient tumors. ARID1A, a BAF subcomplex specific subunit, is the most frequently mutated subunit in human cancers (12%) and CRCs (10-12%). Additionally, ARID1A was recently identified as a leading genetic alteration in inflammatory bowel diseases such as Crohn’s and Ulcerative Colitis, conditions which are at higher risk of developing CRC. These data suggest an important role in ARID1A regulation of colonic tissue homeostasis and the potential for ARID1A mutation as an initiating or early driving event in CRC, which has not yet been modeled in human colon tissues. To examine the role of ARID1A in colon cancer development, we took a bottom-up strategy using CRISPR edited patient-derived colon organoids to model ARID1A LOF mutations in combination with classic CRC mutations APC and TP53. We evaluated the functional consequences of ARID1A mutation on cell growth using colony formation and proliferation assays. To systematically investigate the phenotypic contribution of ARID1A loss in these cell contexts, we employed transcriptomic and epigenomic profiling with RNAseq and ATACseq. We found that triple knock-out (TKO) of ARID1A, APC and TP53 confers a growth advantage in colon organoids, and induces dramatic morphological changes such as loss of symmetry and the breakdown of cystic architectures. At the gene expression level, ARID1A mutations led to shared and cell context specific transcriptional changes enriched for pathways such as G2M checkpoint, KRAS Signaling, and STAT5 signaling. Mechanistically, we show that ARID1A dependent chromatin accessibility changes at putative enhancers are linked to promoters of differentially expressed genes. These data suggest that ARID1A can regulate multiple cancer hallmark pathways depending on the cellular context and indicate a pleiotropic tumor suppressive function requiring further investigation in clinically relevant genetic backgrounds.
Citation Format: Luke T. Deary, Nicholas Sugiarto, Cameron Pigeon, Sara W. Mayo, Matthew Z. Wilson, Xiaofeng Wang. Modeling the role of ARID1A in colon cancer using patient-derived organoids [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB044.
Abstract LB059: DNA damage and somatic mutations in mammalian cells after irradiation with a nail polish dryer
Authors: Zhivagui Maria , Hoda Areebah , Valenzuela Noelia , Yeh Yi-yu , Dai Jason , He Yudou , Nandi Shuvro P. , Otlu Burcak , Van Houten Bennett , Alexandrov Ludmil 
Published: April 2023

Abstract
Ultraviolet A (UVA) rays are long wavelengths that can penetrate the deeper layer of the skin and are responsible for the immediate tanning effect. A multitude of natural and artificial sources of UV exposure exist, including UV-emitting lamps that are commonly used in dentistry, cosmetics, and medical laboratories. Recently, several reports suggested that long-term use of UV-nail polish dryers, used for curating nail polish formulas, known as gel, may increase the risk for developing skin cancer. However, no experimental evaluation has been conducted to reveal the effect of radiation released by UV-nail polish dryers on mammalian cells. Here, we address the continuous exposure of clients and employees to UVA light by employing both murine and human primary cell models for irradiation, in an acute and chronic manner, using a UV-dryer machine. We, then, subject the cells to DNA sequencing either by bulk whole-genome sequencing after clonal expansion or by single-molecule duplex sequencing without clonal expansion. Our findings show that UVA-exposed samples manifest an increase of C:G&gt;A:T transversions compared to control cells. The patterns of mutations found in these cells can be recapitulated by mutational signatures previously attributed to reactive oxygen species (ROS), namely COSMIC signatures SBS18/36. These results are further corroborated by the presence of high levels of ROS in irradiated samples, consistent with 8-oxo-7,8-dihydroguanine damage and mitochondrial dysfunction. Importantly, we show that in contrast to UVB exposure, UVA does not induce an increase of C:G&gt;T:A transitions, indicating that different types of ultraviolet light radiation affect DNA through distinctive molecular mechanisms. Finally, re-examination of somatic mutations from skin cancers reported by the International Cancer Genome Consortium (ICGC) reveals that SBS18/36 are ubiquitously present in melanoma and account for 12% of the previously annotated driver mutations. In summary, this study demonstrates that radiation emitted by UV-nail polish dryers can both damage DNA and permanently engrave mutations on the genomes of mammalian cells.
Citation Format: Maria Zhivagui, Areebah Hoda, Noelia Valenzuela, Yi-yu Yeh, Jason Dai, Yudou He, Shuvro P. Nandi, Burcak Otlu, Bennett Van Houten, Ludmil Alexandrov. DNA damage and somatic mutations in mammalian cells after irradiation with a nail polish dryer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB059.
Abstract LB082: The CytoR1: a standardized dielectrophoretic platform for label free sorting
Authors: Thomas Dean E. , Degen Katherine E. , Barua Ridi , Bertke Andrea , Henslee Erin A. , Hyler Alexandra R. 
Published: April 2023

Abstract
Dielectrophoresis (DEP), a label-free electrokinetic technique, has a long history of being used to characterize and separate target subpopulations from mixed samples. A large body of literature has investigated these parameters with unique setups and limited cell varieties. The technical challenge of the technique coupled with the uncertainty in the breadth of data has limited the commercialization and widespread adoption of DEP for biological applications. The work presented here aims to evaluate a range of prior applications of DEP on a standardized platform. A variety of cell types were characterized and compared to literature values considering variables such as frequency, voltage, and flow rate. Once a cell type’s frequency response curve is generated, it is possible to design workflows to enrich that cell type from a bulk mixture, without antibody labeling. Here, we test various cell types and characteristics on a microfluidics-based, benchtop cell sorting technology, the CytoR1. First, the CytoR1 successfully facilitated the separation of ovarian cancer stem cells (CSCs) from peripheral blood mononuclear cells (PBMCs), both from mice. From a 56.2% CSCs and 43.8% PMBCs co-culture, we were able to deplete 50% of the PMBCs while retaining the original CSC population. Further work investigated the ability to sort neuron subpopulations. Live neurons can be isolated from a bulk preparation and further enriched by size and phenotype with varying voltage and frequency settings. By modulating voltage and flow rate in addition to frequency, a distinct population of small neurons can be isolated for further study. Finally, cell state can be investigated. Red blood cells were characterized in both their native and oxidatively stressed states. Curves show a distinct shift towards higher frequencies with increasing oxidative stress suggesting the ability to separate these populations from each other. Together these data suggest the versatility of a robust, DEP-based sorting platform, the CytoR1, for label free cell sorting.
Citation Format: Dean E. Thomas, Katherine E. Degen, Ridi Barua, Andrea Bertke, Erin A. Henslee, Alexandra R. Hyler. The CytoR1: a standardized dielectrophoretic platform for label free sorting [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB082.
Abstract LB098: Combination of a PD-1/CTLA-4 bispecific antibody with orally active PD-L1 inhibitor MAX-10181 effectively increased the percentage of tumors inhibited in animal model study
Authors: Wang Yuguang , Gao Yuan , Mao Chenyu , Xu Nong , Zhang Qiang , Wang Jing , Feng Zhenhua , Zhu Yonghong , Wang Zhongmin , Li Baiyong 
Published: April 2023

Abstract
The key players in the current immuno checkpoint inhibition (ICI) treatment are antibodies or bispecific antibodies targeting PD-1. PD-L1 or CTLA-4. While these drugs provided a small number of patients with tumor shrinking (ORR between 10-30%) as a single agent, they did not lead to desirable treatment survival as measured by OS/PFS. Many combination studies are in progress in both preclinical and clinical settings to find an effective way to achieve prolonged OS/PFS in ICI treatment. Herein, we would like to report our most recent findings of combination of a PD-1/CTLA-4 bispecific antibody with our orally active, clinical stage PD-L1 inhibitor MAX-10181 in animal model study. The key observations are as follow:
•The PD-1/CTLA-4 bispecific antibody group (n=10, average starting tumor volume= 68 mm3) demonstrated (a) 2 tumors (20%) in the slow volume shrinking mode with volume between 60-20 mm3, and (b) 4 tumors (40%) in the fast volume growing mode with volume above 500 mm3
•The combination group (n=10, average starting tumor volume= 68 mm3) demonstrated (a) 2 tumors (20%) in the fast volume shrinking mode with volume less than 20 mm3, (b) 1 tumor (10%) in the slow volume shrinking mode with volume between 60-20 mm3, and (c) only 1 tumor (10%) in the fast volume growing mode with volume above 500 mm3
These results indicate the potential of prolonged OS/PFS to combine PD-1/CTLA-4 bispecific antibody with orally active, small molecule MAX-10181 which recently completed Phase I trial. We will present the full study results in the coming AACR meeting.
Citation Format: Yuguang Wang, Yuan Gao, Chenyu Mao, Nong Xu, Qiang Zhang, Jing Wang, Zhenhua Feng, Yonghong Zhu, Zhongmin Wang, Baiyong Li. Combination of a PD-1/CTLA-4 bispecific antibody with orally active PD-L1 inhibitor MAX-10181 effectively increased the percentage of tumors inhibited in animal model study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB098.
Abstract LB099: Organoid-based drug efficacy evaluation model for immunotherapy
Authors: Lee Boeun , Yang Woo Kyeom , Kim Sarang , Lee Hee-Ra , Kim Donghyeon , Yoo Jongman 
Published: April 2023

Abstract
The endogenous immune system of patients are known to be activated through immuno-oncology drug, which activates the patient’s own immune system to target and attack tumors. Due to the relatively low occurrence of side effects and sustained success, these therapeutic techniques have gradually replaced the traditional cancer treatment regimen. The creation of an in-vitro screening platform for pre-evaluating the efficacy of immunotherapeutic drug candidates was highly essential despite the fact that many of the new emerging therapies had failed clinical trials.An in-vitro platform mirroring the interaction between a patient's unique Major Histocompatibility Complex (MHC) and T-cell receptor (TCR) is necessary for predicting the precise efficacy of immunotherapies. The tumor cells' MHC antigen molecule attaches to the T-cell receptor (TCR), allowing T-cells to manifest their tumor-killing activities as a result. The link between immunological checkpoint (ICP) in tumor cells and their receptors in T cells allows tumor cells to evade the effects of T-cell-mediated tumor death.We would like to introduce our "ODISEI" platform, a robust efficacy evaluation tool that enables the recapitulation of a patient's unique immune system, utilizing tumor organoids and PBMC from the same donors. Using PD-1/PD-L1 inhibiting antibodies, the enhanced functionality of our ODISEI platform as an effective evaluation platform for immunotherapy drugs was thoroughly examined. Additionally, we created several ODISEI platforms in order to recreate the precise interactions between tumor organoids and various immune sub-populations (T-cells, macrophages, regulatory T-cells, and dendritic cells). Our ODISEI platforms were validated by utilizing a variety of different drug candidates and evaluating their ability to eradicate tumors upon interaction with various reactive immune cells and tumors. As a result, our highly innovative ODISEI platform can be used to screen a variety of different immunotherapeutic drug candidates and distinguish their precise efficacy.
Citation Format: Boeun Lee, Woo Kyeom Yang, Sarang Kim, Hee-Ra Lee, Donghyeon Kim, Jongman Yoo. Organoid-based drug efficacy evaluation model for immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB099.
Abstract LB137: Ovulatory years prior to menopause and postmenopausal endogenous hormone levels
Authors: Cramer Daniel W. , Vitonis Allison F. , Huang Tianyi , Shafrir Amy L. , Eliassen Heather , Barbieri Robert L. , Hankinson Susan E. 
Published: April 2023

Abstract
Background: Estimated lifetime ovulatory years (LOY) is the difference between ages at menopause and menarche subtracting time for events interrupting ovulation. We tested whether LOY influence sex-hormone levels in postmenopausal women not using hormone therapy.
Methods: Hormones, including estradiol and testosterone, were measured in 1976 postmenopausal women from the Nurses’ Health Study in plasma collected in 1990. Effects of age, years since menopause, body mass index (BMI), smoking status, and hysterectomy on hormone levels were assessed by t-tests and ANOVA. Multivariable linear regression was used to assess associations between LOY and hormones adjusted for potential confounders and the trend in hormone levels per 5-year increases in LOY estimated.
Results: Women in the sample averaged: 61.4 years old at blood draw, 11.0 years since menopause, with a BMI of 25.8 kg/m2. 17.5% had a hysterectomy and 13.8% were current smokers. These characteristics were associated with one or more hormone levels and included as adjustment variables. Each 5-year increase in LOY was associated with a 6.0% increase in testosterone (95% CI 3.3%, 8.7%) in all women. In women with above-average BMI, each 5-year increase in LOY was associated with a 7.3% (3.5%, 11.2%) increase in testosterone, a 6.9% (2.7%,11.3%) increase in estradiol, and a 6.9% (2.9%,10.9%) increase in estrone.
Conclusion: Greater LOY is associated with higher testosterone in postmenopausal women as well as greater estradiol in those with above-average BMI. This may be due to an accumulation of functioning stromal and thecal cells from repeated ovulation and peripheral conversion of testosterone.
Citation Format: Daniel W. Cramer, Allison F. Vitonis, Tianyi Huang, Amy L. Shafrir, Heather Eliassen, Robert L. Barbieri, Susan E. Hankinson. Ovulatory years prior to menopause and postmenopausal endogenous hormone levels [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB137.
Abstract LB168: Efficacy analysis of the DeepNeo neoantigen prediction tool for antitumor vaccine development
Authors: Lee Eun Ji , Park Min Ji , Kim Soo Jin , Noh Seung-Jae , Shin Inkyung , Kim Jeong Yeon , Shin Incheol , Choi Jung Kyoon , Cho Dae-Yeon , Chang Suhwan 
Published: April 2023

Abstract
Antitumor peptide vaccine is an alternative and attractive way to eradicate tumors by the aid of host immune system. The current peptide vaccine development is hampered by several hurdles. These include heterogeneity of tumor cells, applicable in vivo stability of peptides, and others. One of the major obstacles is the precise prediction of cancer antigen, which can be loaded efficiently onto antigen presenting cells. We present here a neoantigen prediction algorithm DeepNeo comprised of DeepNeo-MHC and DeepNeo-TCR, which calculates the antigenicity of neoantigen based on the MHC binding and TCR activation potential. We examined the efficacy of DeepNeo using ELISPOT and two allogenic mouse tumor models. By treating the combination of long peptides targeting MC38 colon or B16F10 melanoma cell lines, we have shown the DeepNeo effectively determines neoantigens for the development of antitumor peptide vaccine. Analysis of tumor-infiltrated lymphocytes (TIL) supported our results. Undergoing study using patient-derived xenograft model treated with autologous, trained PBMC with personalized peptide vaccine will be discussed further.
Citation Format: Eun Ji Lee, Min Ji Park, Soo Jin Kim, Seung-Jae Noh, Inkyung Shin, Jeong Yeon Kim, Incheol Shin, Jung Kyoon Choi, Dae-Yeon Cho, Suhwan Chang. Efficacy analysis of the DeepNeo neoantigen prediction tool for antitumor vaccine development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB168.
Abstract LB171: WSI based prediction of TP53 mutations identifies aggressive disease phenotype in prostate cancer
Authors: Pizurica Marija , Larmuseau Maarten , Van der Eecken Kim , de Schaetzen van Brienen Louise , Carrillo-Perez Francisco , Isphording Simon , Lumen Nicolaas , Van Dorpe Jo , Ost Piet , Verbeke Sofie , Gevaert Olivier , Marchal Kathleen 
Published: April 2023

Abstract
In prostate cancer, there is an urgent need for objective prognostic biomarkers that identify a tumor’s metastatic potential at an early stage. While recent analyses indicated TP53 mutations as candidate biomarker, molecular profiling in a clinical setting is complicated by tumor heterogeneity. Deep learning models that predict the spatial presence of TP53 mutations in Whole Slide Images (WSIs) offer the potential to mitigate this issue. To assess the potential of WSIs as proxy for spatially resolved profiling or as biomarker for aggressive disease, we developed TiDo, a deep learning model that achieves state-of-the-art performance in predicting TP53 mutations from WSIs of primary prostate tumors. On an independent multi-focal cohort, we could show successful generalization of the model, both at patient and lesion level. Hence, the model offers insight into which lesions on a WSI most likely contain a TP53 mutation.
Analysis of model predictions revealed that false positive (FP) predictions could at least partially be explained by TP53 deletions. This suggests that some FP carry another alteration of which the effect converges in the same histological phenotype. Comparative expression analysis and histological cell type analysis identified such common phenotype (related to stromal composition) in both TP and FP predictions. This indicates that WSI-based models might not be able to perfectly predict the spatial presence of individual TP53 mutations. However, we show they have the potential of capturing a tumor’s aggressive potential by observing a downstream phenotype of the tumor cells and TME associated with a biomarker of aggressive disease (TP53).
Citation Format: Marija Pizurica, Maarten Larmuseau, Kim Van der Eecken, Louise de Schaetzen van Brienen, Francisco Carrillo-Perez, Simon Isphording, Nicolaas Lumen, Jo Van Dorpe, Piet Ost, Sofie Verbeke, Olivier Gevaert, Kathleen Marchal. WSI based prediction of TP53 mutations identifies aggressive disease phenotype in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB171.
Abstract LB174: Diabetes-associated breast cancer is molecularly distinct and shows DNA repair deficiency
Authors: Panigrahi Gatikrushna , Candia Julián , Dorsey Tiffany H. , Tang Wei , Ohara Yuuki , Byun Jung S. , Minas Tsion Zewdu , Zhang Amy , Ajao Anuoluwapo , Cellini Ashley , Yfantis Harris G. , Mann Dean , Ioffe Olga , Wang Xin W. , Liu Huaitian , Loffredo Christopher A. , Napoles Ana Maria , Ambs Stefan 
Published: April 2023

Abstract
Diabetes commonly affects cancer patients. In breast cancer, it decreases patient survival. Diabetes also impacts African American women more so than European American women, potentially contributing to the breast cancer health disparity. In this study, we investigated the influence of diabetes on breast cancer biology in a diverse patient cohort using a three-pronged approach that included analysis of orthotopic human tumor xenografts, patient tumors, and breast cancer cells exposed to diabetes/hyperglycemia-like conditions. We aimed to identify shared phenotypes and molecular signatures by investigating the metabolome, transcriptome, and tumor mutational burden. Diabetes does not enhance cell proliferation but induces mesenchymal and stem cell-like phenotypes linked to increased mobility and odds of metastasis. It also promotes oxyradical formation and both transcriptome and mutational signatures of DNA repair deficiency. Moreover, food- and microbiome-derived metabolites tend to accumulate in breast tumors in presence of diabetes, potentially affecting tumor biology. Breast cancer cells cultured under hyperglycemia-like conditions acquire increased DNA damage and sensitivity to DNA repair inhibitors. Based on these observations, diabetes-associated breast tumors may show an increased drug response to DNA damage repair inhibitors that are cancer therapeutics.
Key words: Breast cancer, diabetes, metabolome, transcriptome, metastasis, DNA repair, mutational signature, health disparity
Citation Format: Gatikrushna Panigrahi, Julián Candia, Tiffany H. Dorsey, Wei Tang, Yuuki Ohara, Jung S. Byun, Tsion Zewdu Minas, Amy Zhang, Anuoluwapo Ajao, Ashley Cellini, Harris G. Yfantis, Dean Mann, Olga Ioffe, Xin W. Wang, Huaitian Liu, Christopher A. Loffredo, Ana Maria Napoles, Stefan Ambs. Diabetes-associated breast cancer is molecularly distinct and shows DNA repair deficiency [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB174.