bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1867: Pre-clinical characterization of anti-CEACAM1 antibody
Authors: Dong Jinyu , Zhang Yu , Wang Baiyang , Pu Tingting , Shao Liegang , Wang Binbin , Wang Dong , Ni Jie , Li Sunan , Dong Xin 
Published: June 2023

Abstract
Targeting checkpoint molecules cytotoxic T lymphocyte antigen-4 (CTLA-4) or programmed death receptor-1 (PD-1) expressed on immune cells has shown promising results in the treatment of cancer patients. Nevertheless only a small portion of population benefited from current ICI treatments, so there should be other mechanisms for immune evasion potentially. The carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) is an activation-induced inhibitory molecule on T and NK cells. In a wide range of cancers, it’s also expressed on tumor cells and other immune cells including macrophages and neutrophils. Homophilic interaction between CEACAM1 expressed on tumor cells and immune cells dampens NK and T cell function, mediates tumor migration, and promotes tumor angiogenesis, which implies that this homophilic interaction is an important mechanism for tumor progression. Here, we describe the identification and characterization of a novel humanized anti-human CEACAM1 therapeutic antibody developed via Neologics’ novel target validation and antibody screening Tier-A platform. This anti-CEACAM1 antibody specifically binds to recombinant human CEACAM1 with nM level affinity and significantly enhances T cell activities and NK killing on CEACAM1 expressing tumor cells, inhibits tumor cell migration in vitro as well. In humanized mouse models, this antibody evidently reduces tumor growth alone or combined with other immune checkpoint blockers. Taken together, we have demonstrated this anti-CEACAM1 antibody specifically enhance NK cell activity, modulate T cell immune activation and inhibit tumor migration supporting further clinical investigation for various indications.
Citation Format: Jinyu Dong, Yu Zhang, Baiyang Wang, Tingting Pu, Liegang Shao, Binbin Wang, Dong Wang, Jie Ni, Sunan Li, Xin Dong. Pre-clinical characterization of anti-CEACAM1 antibody [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1867.
Abstract 2111: Identification of molecular markers of pseudomyxoma peritonei using integrative analysis of bulk and single cell RNA-seq data
Authors: Park Seong-Hwan , Go Hanyong , Kim Jae-Yoon , Kim Seon-Young , Lee Jong Lyul , Ha Ye Jin , Kim Seon-Kyu 
Published: June 2023

Abstract
Backgrounds: Psuedomyxoma peritonei (PMP) is a rare colon disease, whose symptoms and treatments have been numerously investigated, however, there are insufficient known diagnostic or prognostic markers. Here, we aim to identify molecular markers exhibiting distinct characteristics of PMP.
Methods: We analyzed RNA-seq data to identify gene signatures associated with PMP development using 19 fresh frozen tissue samples including 12 PMPs (discovery cohort). For validation, we applied those signatures into an independent cohort containing 34 formalin-fixed paraffin embedded (FFPE) samples including 25 PMPs (validation cohort). We also verified protein expression levels in the signature using immunohistochemical staining (IHC) in other independent cohort in PMP. Additionally, a transcriptomic profiling using single-cell RNA-seq was carried out to confirm the cell type-specific gene expression patterns in a separated patient group with five PMPs.
Results: In the discovery cohort of fresh-frozen tissues, unsupervised hierarchical clustering analysis exhibited a distinct gene expression pattern clearly dichotomizing normal and PMP samples. Genes involved in cell movement or immune response were highly expressed in PMPs. Interestingly, we found that PMP disease had a molecular heterogeneity showing epithelial as well as mesenchymal characteristics, in which both CDH1 and CDH2 were significantly elaborated in PMPs. We also estimated protein expression levels of PMP-associated key markers using IHC, in which a significant positive correlation between transcript and protein expressions in CDH1, whereas we could not observe such a significance but a clear tendency toward highly expression of CDH2 in PMPs. However, in a single-cell RNA-seq analysis, we discovered distinct eight cell type-specific clusters including an epithelial cell group, in which CDH1 was highly expressed, and a mesenchymal cell group, in which CDH2 showed a significant higher expression pattern, suggesting that PMP show dual molecular characteristics of epithelial as well as mesenchymal.
Conclusion: We explore genetic characteristics and suggest key markers of PMP development. Our findings would be practically utilized for clinical practice in PMP diagnosis or prognosis.
Citation Format: Seong-Hwan Park, Hanyong Go, Jae-Yoon Kim, Seon-Young Kim, Jong Lyul Lee, Ye Jin Ha, Seon-Kyu Kim. Identification of molecular markers of pseudomyxoma peritonei using integrative analysis of bulk and single cell RNA-seq data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2111.
Abstract 2184: Short Peptides derived from MIEN1 and their analogs exhibit anti-cancer activity in breast and prostate cancer cells
Authors: Tripathi AMIT Kumar , Vishwanatha Jamboor K. 
Published: June 2023

Abstract
Migration and invasion enhancer 1 (MIEN1) is overexpressed in various cancers and plays an important role in cancer cell migration and invasion. Conserved regions of ITAM and prenylation motif in MIEN1 were used as a template to identify anti-cancer peptides. RNA-seq, qPCR analysis and western blots showed changes in the transcriptome and protein expression after peptide treatment. The two bioactive peptides inhibited genes and proteins responsible for cancer cell migration and invasion in both MDA-MB-231 breast cancer and DU-145 prostate cancer cells. The mechanism of the action of the peptides involves the inhibition of key pathways like Epithelial-Mesenchymal transition and Epidermal Growth Factor-mediated NF-κB pathway to exert their anti-cancer activity. Interestingly, the peptides targeted the same signal transduction pathways followed by parental MIEN1 to show its cancer properties. Thus, the two peptides acted as dominant negative effectors of MIEN1 activity. Additionally, Peptide-treatments induced apoptosis in mice groups bearing tumors derived from MDA-MB-231 cells as evidenced by increased levels of cleaved caspase-3 and PARP proteins in western blots. Interestingly, the MIEN1 mRNA and protein expression was lowered in the in vivo breast cancer tumor models which remained unchanged in MDA-MB-231 breast cancer cells indicating an improved therapeutic activity in living system. The peptides did not cause any toxicity in the mice group which received peptides only, at three times the dose used during in vivo assays.
Citation Format: AMIT Kumar Tripathi, Jamboor K. Vishwanatha. Short Peptides derived from MIEN1 and their analogs exhibit anti-cancer activity in breast and prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2184.
Abstract 289: B7-H3 mediated metabolic reprogramming promotes small cell lung cancer progression
Authors: Fatima Mahek , Khan Parvez , Rehman Asad Ur , Khan Md Arafat , Maurya Shailendra Kumar , Ahmad Aatiya , Zaidi Mohd Ali , Gautam Shailendra , Lele Subodh , Batra Surinder Kumar , Nasser Mohd Wasim 
Published: June 2023

Abstract
Lung cancer is the leading cause of cancer-related deaths worldwide. Small cell lung cancer (SCLC) is an aggressive subtype of lung cancer. The overall survival rate of SCLC is dismal owing to early metastasis, chemoresistance, higher rate of recurrence, and lack of available treatment options. Although some immunotherapeutic drugs have been approved for SCLC, they are effective only in a small fraction of the patient population. This necessitates the quest to find promising vulnerabilities against SCLC. Bioinformatic analysis on SCLC data set in the backdrop of various immune checkpoint regulators revealed B7-H3 as a promising target. The bioinformatics data was recapitulated in SCLC cell lines and human SCLC tissues. To delineate the effects of B7-H3 targeting, we performed CRISPR-Cas9 mediated B7-H3 knockout in SCLC cell lines. B7-H3 knockout in SCLC cells showed a decrease in colony formation, migration, and wound healing properties. Our results suggest that deletion of B7-H3 decrease the functional activities and activation of oncogenic signaling pathways, such as Erk, Akt, and Stat3. Further, we assessed if B7-H3 regulates SCLC metabolism. Preliminary data showed that B7-H3 knockout in SCLC cells inhibits glucose uptake, extracellular acidification rate (ECAR), and oxygen consumption rate (OCR), suggesting its role in SCLC metabolic reprogramming. Altogether, our data indicate that B7-H3 plays a crucial role in SCLC pathogenesis and could serve as a potential therapeutic target for SCLC.
Citation Format: Mahek Fatima, Parvez Khan, Asad Ur Rehman, Md Arafat Khan, Shailendra Kumar Maurya, Aatiya Ahmad, Mohd Ali Zaidi, Shailendra Gautam, Subodh Lele, Surinder Kumar Batra, Mohd Wasim Nasser. B7-H3 mediated metabolic reprogramming promotes small cell lung cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 289.
Abstract 309: ATM phosphorylation of NRF2 promotes DNA damage repair
Authors: Schneider Cheyenne A. , Lin Tin-Yu , Falzone Aimee , Caldwell Samantha , Johnson Jared L. , DeNicola Gina M. 
Published: June 2023

Abstract
Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor that responds to cellular and oxidative stress by promoting the transcription of antioxidant response element-containing genes. In an unstressed cellular environment, NRF2 is bound by Kelch-like ECH-associated protein 1 (KEAP1) and tagged for proteasomal degradation. In many cancers, the interaction between NRF2 and KEAP1 is interrupted due to mutations in either protein. Previous work has suggested that NRF2 can promote DNA damage repair, and our preliminary data demonstrates that NRF2 is phosphorylated at Serine-40 by the DNA damage response kinase, Ataxia Telangiectasia Mutated (ATM) in response to DNA damage. To create a system to better study the relationship between NRF2 Serine-40 phosphorylation and DNA damage, we modified the mouse Nfe2l2 locus to generate a mouse model in which Nrf2 Serine-40 is mutated to Alanine on a C57BL/6 background. Utilizing this model, we administered 7.5 Gy of total body irradiation and found that Nrf2S40A/S40A mice had significantly shortened survival compared to Nrf2WT mice. Immunohistochemical analysis of radiation-sensitive tissues including bone marrow and spleen revealed a prolonged persistence of the DNA damage marker γH2AX following irradiation in the Nrf2S40A/S40A group compared to Nrf2WT. We also observed a significantly higher level of cell death in the Nrf2S40A/S40A splenic tissue compared with Nrf2WT as indicated by the marker of apoptotic cell death, Cleaved Caspase-3. Our findings indicate that phosphorylation of Nrf2 at Serine-40 in response to DNA damage promotes DNA damage repair. Our ongoing work is focused on examining these phenotypes in cellular systems to determine the specific mechanisms by which NRF2 promotes DNA damage repair. Future work will include incorporating the systems generated thus far into non-small cell lung cancer (NSCLC) and liver cancer mouse models to further investigate the impact of this phosphorylation site on tumorigenesis and radio-resistance.
Citation Format: Cheyenne A. Schneider, Tin-Yu Lin, Aimee Falzone, Samantha Caldwell, Jared L. Johnson, Gina M. DeNicola. ATM phosphorylation of NRF2 promotes DNA damage repair [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 309.
Abstract 3818: Isoandrographolide derivative, (3,19)-4-Bromobenzylidene-isoandrographolide induces apoptosis and causes loss of mitochondrial membrane potential in ER positive Breast cancer
Authors: Karanam Balasubramanyam , Tamang Nitesh , Inabathina Yashwanth , Mavileti Sai Kiran , Sripada Lakshminath , Nanduri Srinivas , Golakoti Nageswara Rao 
Published: June 2023

Abstract
Natural product, Andrographolide.is diterpene lactone extracted from Andrographis paniculata. In traditional form of medicine, it is being used in India, China and Malaysia for treating various diseases. While in the last two decades there are many reports on andrographolides and its derivatives with various biological activities such as anti-cancer and anti-inflammatory. We synthesized compounds along with isoandrographolide were characterized and tested for their anticancer activity against 60 cancer cell line at NCI. Most compounds were found to be active against leukemia and breast cancer with (3,19)-4-Bromobenzylidene-isoandrographolide having best growth inhibition of 76.90% and 87.54% against leukemia (MOLT-4) and breast cancer (BT-549) respectively. Upon further testing compound (3,19)-4-Bromobenzylidene-isoandrographolide was found to be more activate than the tamoxifen against MCF-7. Compound (3,19)-4-Bromobenzylidene-isoandrographolide arrested cell cycle at G1-Phase of MCF-7 and was observed to be inducing apoptosis and loss of mitochondrial membrane potential. We discuss our studies on crystal structure, cell cycle progression assay, apoptotic studies on ER-positive breast cancer MCF-7.
Citation Format: Balasubramanyam Karanam, Nitesh Tamang, Yashwanth Inabathina, Sai Kiran Mavileti, Lakshminath Sripada, Srinivas Nanduri, Nageswara Rao Golakoti. Isoandrographolide derivative, (3,19)-4-Bromobenzylidene-isoandrographolide induces apoptosis and causes loss of mitochondrial membrane potential in ER positive Breast cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3818.
Abstract 3861: c-MYC mediated resistance to trametinib plus hydroxychloroquine in pancreatic cancer is overcome by CDK4/6 and lysosomal inhibition
Authors: Silvis Mark , Silva Dilru , Riley Rohweder , Schuman Sophia , Gudipaty Swapna , Truong Amanda , Yap Jeffery , Affolter Kajsa , McMahon Martin , Kinsey Conan 
Published: June 2023

Abstract
Pharmacological inhibition of KRAS&gt;RAF&gt;MEK&gt;ERK signaling has provided no clinical benefit to patients with pancreatic ductal adenocarcinoma (PDA). Interestingly, combined inhibition of MEK1/2 (with trametinib, T) plus autophagy (with chloroquine, CQ, or hydroxychloroquine, HCQ) demonstrated striking anti-tumor effects in preclinical models and in a patient (Patient 1). However, not all patients respond to the T/HCQ regimen, and Patient 1 eventually developed resistant disease. Here we report that primary or acquired resistance is associated with focal DNA copy number gains encompassing c-MYC. Furthermore, ectopic expression of c-MYC in PDA cell lines rendered them T/HCQ resistant. Interestingly, a CDK4/6 inhibitor, palbociclib (P), also induced autophagy and overrode c-MYC-mediated T/HCQ resistance, such that P/HCQ promoted regression of T/HCQ resistant PDA tumors with elevated c-MYC expression. Finally, P/HCQ treatment of Patient 1 resulted in a biochemical disease response. These data suggest that elevated c-MYC expression is both a marker and a mediator of T/HCQ resistance, which may be overcome by the use of palbociclib plus hydroxychloroquine.
Citation Format: Mark Silvis, Dilru Silva, Rohweder Riley, Sophia Schuman, Swapna Gudipaty, Amanda Truong, Jeffery Yap, Kajsa Affolter, Martin McMahon, Conan Kinsey. c-MYC mediated resistance to trametinib plus hydroxychloroquine in pancreatic cancer is overcome by CDK4/6 and lysosomal inhibition. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3861.
Abstract 5368: AI-enabled prediction of lung cancer specific hot spot gene alterations from histology images
Authors: Shafi Gowhar , Shivamurthy Shiva , Ulle Anand , Chinglemba Chongtham Cha , Haldar Sumit , Moubeen Fauzul , Uttarwar Mohan 
Published: June 2023

Abstract
Background: The clinical intervention relies on molecular testing of primary biomarkers. We developed an AI enabled platform to predict NCCN guidelines recommended hot-spot genomic alterations from the image analysis using H&E slide.
Methods: AI engine was trained using clinically observed hot spot genomic alterations present in lung cancer patients as a ground truth based on histological FFPE whole-slide images. The H & E stained histological images of the tumor having matching pathogenic mutations were downloaded from the TCGA database for the training and testing purpose. The program extracted histopathological features, followed by pattern mapping to predict genomics status based on the results of NGS testing from 480 samples. ResNet AI algorithm was trained to predict lung specific hot spot genomic alterations. An H & E stained slide was imaged with a 40x objective lens to obtain a brightfield image as an input data. The input image was segmented into 65 x 103 tiles, each of 64 µm2 in size for an individual pathological class. 80% of the data set was used for training the engine while validation and blinded study was respectively performed on remaining 10% data.
Results: Using single blinded clinical samples. AI model analyzed whole slides. Table 1 summarize parameters for clinically significant variants. Higher sensitivity and specificity was observed for variants encoding mutated cell surface proteins compared to variants encoding intracellular mutant targets when compared on similar training and testing parameters.
Conclusions: AI-enabled prediction of hotspot genomic alterations resulted comparable to NGS with shortest TAT, cost and resources. It predicted actionable gene alterations with high positive and negative prediction values.
Table 1. Gene Sample (n = 480) Evaluation parameters for tested samples Training Testing Sensitivity (%) Specificity (%) PPV (%) NPV (%) F1-score (%) Accuracy (%) KRAS 248 62 100 94 94 100 97 97 ALK 16 4 100 100 100 100 100 100 EGFR 72 18 88 100 100 90 94 94 MET 16 4 50 100 100 66 66 75 ROS 16 4 100 100 100 100 100 100 STK11 88 22 82 73 75 80 78 77 RET 24 6 50 100 100 60 50 67 BRAF 14 2 100 100 100 100 100 100 NTRK 92 24 78 56 64 71 70 67 ERBB2 12 4 50 50 50 50 50 50
Citation Format: Gowhar Shafi, Shiva Shivamurthy, Anand Ulle, Chongtham Cha Chinglemba, Sumit Haldar, Fauzul Moubeen, Mohan Uttarwar. AI-enabled prediction of lung cancer specific hot spot gene alterations from histology images. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5368.
Abstract 5520: Research Ready graphic-style story to support future research participation among adolescents
Authors: Bates Lauren , Gertz Susan , Hershberger Susan , Kovacic Melinda Butsch ,   We Engage 4 Health Community-Academic Partnership
Published: June 2023

Abstract
Historically, marginalized adults are more likely to be mistrustful of health research worrying both about its invasiveness and their own safety. As a result, many decline to participate. Adolescents have a much lower perception of risk compared to adults and are also susceptible to peer pressure and socialized trust or mistrust from their parents and family members, which can influence risk perception. As encouraging equitable participation in research becomes an important tool in the fight against cancer disparities, We Engage 4 Health created a graphic-style story “Research Ready” to help community members learn the 3 P’s: the purpose of cancer research, how they are kept safe while participating, and why people from diverse backgrounds are needed to participate. An accompanying Research Review Activity was also included to further support participants’ decision-making regarding research participation. Two groups of diverse adolescents were asked to read the story aloud together in small groups and then discuss an active research study targeting adolescents using the review activity with a scientist to consider whether the first the teen story character (Vito) and ultimately themselves, should consider participation in the study and to identify what information was needed from study staff to better be able to make a decision based on their values and accurate information provided by study staff. Group 1 included 45 adolescents that were 68% African American and 10% European American. Group 2 included 73 high schoolers that were 78% Asian, 15% European American, and 5% African American. Post-discussion surveys indicated that only 9% and 3% in group 1 and group 2 respectively had previously participated in health research. However, after the story discussion, 83% and 89% indicated they thought it would be safe to participate in research and 76% and 89% indicated a willingness to participate in research in the future. Finally, 60% collectively enjoyed the story’s graphic-style format. These data suggest Research Ready to be potentially useful in promoting future research participation and may be especially useful in engaging ethnic/racial groups commonly underrepresented in cancer research.
Citation Format: Lauren Bates, Susan Gertz, Susan Hershberger, Melinda Butsch Kovacic, We Engage 4 Health Community-Academic Partnership. Research Ready graphic-style story to support future research participation among adolescents. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5520.