bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 7452: ApoE genotype influences susceptibility to doxorubicin-induced cognitive impairment in juvenile rats
Authors: Patel Chadni , Willekens Jeremy , Diglio Frank , Cole Peter 
Published: March 2024

Abstract
Many pediatric cancer survivors experience chemotherapy-induced cognitive impairment (CICI), which negatively impacts the quality of life. Despite extensive research into the multifactorial causes of CICI, there are no FDA approved drugs available to prevent it and the interpatient variability in susceptibility to CICI is not well understood. Among pediatric cancer survivors, those with the E4 allele of Apolipoprotein E (ApoE) are more likely to exhibit cognitive dysfunction than those with the more prevalent ApoE3 allele, suggesting the ApoE4 allele increases susceptibility to CICI. To mimic a curative pediatric treatment regimen, in our experimental model, five-week-old rats homozygous for either human ApoE3 or ApoE4 allele were treated with doxorubicin (DOXO) (2mg/kg/week for 4 weeks) or saline. ApoE4 rats were more likely than ApoE3 rats to exhibit DOXO-induced impairments in visual memory. However, there was no difference between ApoE3 and ApoE4 rats in sensitivity to DOXO-induced spatial memory impairments. Contrast-enhanced magnetic resonance imaging (MRI) was done to evaluate the blood-brain barrier (BBB) integrity because of literature suggesting that the ApoE4 allele contributes to BBB weakness. However, no significant difference was observed in the BBB integrity between ApoE3 and ApoE4 rats. To delve deeper into the neuropathological basis of DOXO-induced cognitive impairment on the ApoE4 allele, ongoing experiments involve immunohistochemical analyses targeting neurogenic changes in neural stem cell proliferation (DCX), neuronal maturation (Syn and PSD95), as well as glial differentiation (Iba1 and GFAP) in brain regions including hippocampus (dentate gyrus) and cortex. Additionally, to determine the effect of DOXO treatment on ApoE4, we are investigating the role of mitogen-activated protein kinase (MAPK) signaling pathways within brain regions pertinent to memory and recognition. In summary, ApoE genotype contributes to differential susceptibility to CICI.
Citation Format: Chadni Patel, Jeremy Willekens, Frank Diglio, Peter Cole. ApoE genotype influences susceptibility to doxorubicin-induced cognitive impairment in juvenile rats [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 7452.
Abstract 7476: Obtusifolin attenuates LPS-induced inflammation and NLRP3 inflammasome activation by suppressing the MAPK/NF-κB signaling pathway and ROS production in BV2 cells
Authors: Lin Hsin Yi , Lee Che-Hsin , Li Chia-Yang 
Published: March 2024

Abstract
Neuroinflammation, along with activation of microglia and oxidative stress, plays an important role in the development and progression of neurodegenerative diseases. During the inflammation process, immune cells release inflammatory mediators such as cytokines and chemicals that may promote the formation and growth of cancer cells. Obtusifolin, an anthraquinone extracted from the seeds of Senna obtusifolin, has anti-inflammatory properties. However, the effect of obtusifolin on neuroinflammation and its regulatory mechanism have not been yet investigated. In the present study, BV2 microglial cells were used to investigate the effects of obtusifolin on LPS-induced inflammatory responses, NLRP3 inflammasome activation, and reactive oxygen species (ROS) production. The secretion of nitric oxide (NO) was analyzed by Griess reagent assay, and the cell viability was detected by the CCK-8 assay. The expressions of iNOS, COX-2, STAT3, ERK, JNK, and p38 were examined using Western blotting, and the production of IL-6 and TNF-α was measured by ELISA. To examine whether obtusifolin affected NLRP3 inflammasome activation, BV2 cells were pretreated with LPS and then stimulated with ATP or nigericin. The secretion of IL-1β was measured by ELISA, whereas the expression of NLRP3 inflammasome-related proteins was detected using Western blotting. The production of ROS was analyzed by flow cytometry. Our experimental results showed that obtusifolin suppressed the production of NO and the secretion of proinflammatory cytokines by LPS-induced BV2 cells under noncytotoxic concentrations. In addition, obtusifolin decreased the expression of iNOS, COX-2, phospho-STAT3, phospho-ERK, phosphor-JNK and phospho-p38, and also attenuated the expression of NLRP3 and ASC, cleaved caspase-1 and cleaved IL-1β by LPS- induced BV2 cells. Moreover, obtusifolin reduced the production of both intracellular and mitochondrial ROS by LPS-induced BV2 cells. Overall, these results demonstrated that obtusifolin attenuated LPS-induced inflammation by suppressing the activation of MAPK and NF-κB signaling pathways, inhibiting NLRP3 inflammasome activation, and reducing the production of ROS in microglia, suggesting that obtusifolin might have benefits in the treatment of neurodegenerative diseases.
Citation Format: Hsin Yi Lin, Che-Hsin Lee, Chia-Yang Li. Obtusifolin attenuates LPS-induced inflammation and NLRP3 inflammasome activation by suppressing the MAPK/NF-κB signaling pathway and ROS production in BV2 cells [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 7476.
Abstract 7497: Advancing multi-biomarker CTC assay and CDx development through the automated GenoCTC system
Authors: Chelakkot Chaithanya , Park Jieun , Kim Chae Rin , Lee Yeonu , Lee Yu Rim , Lee Saehyung , Choi Jun Young , Moon Young Ho , Choi Yoon-La , Shin Young Kee , Lee Hun Seok 
Published: March 2024

Abstract
Introduction: The successful outcomes observed in clinical trials emphasize the effectiveness of therapeutic approaches relying on biomarker tests, particularly in the development of cancer drugs. The parallel development of a drug and its associated predictive biomarker is considered an ideal strategy for achieving rapid and successful drug development in precision medicine. In this context, we employ an automated circulating tumor cell (CTC) isolation platform, known as GenoCTC, to facilitate the development of biomarker-driven CTC assays, with the ultimate goal of developing companion diagnostic (CDx) tests. Method: This study employed the 5th generation GenoCTC device, a fully automated system designed for marker-based CTC enrichment using immune magnetophoresis. We confirmed the isolation of CTCs through spiking tests, utilizing cancer biomarkers such as cMET, Mesothelin (MSLN), and Claudin 3 (CLDN3). cMET is a biomarker extensively studied in various cancers, particularly non-small cell lung cancer. We previously showed the prognostic significance of cMET expressing CTCs in HR+ and HER2- metastatic breast cancer patients. MSLN and CLDN3 are tumor-associated proteins showing overexpression across diverse cancer types, with a potential for the development of antibody-based cytotoxic drugs. The GenoCTC device allows efficient separation of CTCs expressing these biomarkers, ensuring high accuracy, precision, specificity, and sensitivity. Simultaneously, therapeutic drugs directed at these markers are progressing through phase trials or preclinical studies. Conclusion: Our results show that cMET, MSLN, and CLDN3 are potential markers for the development of biomarker tests, that can improve the patient selection process for personalized therapy targeting these biomarkers.
Citation Format: Chaithanya Chelakkot, Jieun Park, Chae Rin Kim, Yeonu Lee, Yu Rim Lee, Saehyung Lee, Jun Young Choi, Young Ho Moon, Yoon-La Choi, Young Kee Shin, Hun Seok Lee. Advancing multi-biomarker CTC assay and CDx development through the automated GenoCTC 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 7497.
Abstract 7520: NRT-YHD_001, targeting CD47 for liver cancer immunotherapy
Authors: Nam Suk Woo , Kim Sangyean , Na Minjeong , Shin Eunbi , Ha Jin Woong , Jeon Soyoung , Yoon Sungpil 
Published: March 2024

Abstract
Previously, we demonstrated that recovery of histone deacetylase 6 (HDAC6) suppressed let-7i-5p expression to de-repress the thrombospondin-1 (TSP1) expression, and thereby it occupied CD47 receptor to block CD47-SIRPα mediated anti-phagocytosis of macrophage in liver cancer. NRT-YHD_001 is a modified antisense miRNA of let-7i-5p for liver cancer treatment. In addition, N-acetylgalactosamine was attached to NRT-YHD_001 for specific delivery to the liver. In vitro phagocytosis assay showed better macrophage phagocytosis activity than non-modified antisense let-7i-5p. To investigate the in vivo efficacy of NRT-YHD_001, spontaneous (Ras-transgenic) mouse liver cancer model was used and compared with that of sorafenib treatment. This mouse liver cancer model usually develops spontaneous liver cancer mass after 15 ~ 20 weeks of birth. We confirmed that both weekly i.v. injection of 1mg/kg and biweekly i.v. injection of 2mg/kg NRT-YHD_001 showed more significant therapeutic efficacy than the sorafenib-treated group. Furthermore, xenograft assay with Hep3B human liver cancer cells in athymic-nude mouse also showed that weekly i.v. injection of 1mg/kg NRT-YHD_001 exhibited better survival and tumor growth inhibition compared to non-treated group. In mouse and cynomolgus monkey maximum tolerated dose (MTD) studies, no toxicity of NRT-YHD_001 was found at doses up to 500 mg/kg intravenously. These results showed that NRT-YHD_001 had a robust anticancer effect by converting the macrophage of “don't eat me” into “eat me signal” in the tumor microenvironment of liver cancer, thereby removing or inhibiting liver cancer cells.
Keywords: let-7i-5p, macrophage, phagocytosis, liver cancer, CD47
Citation Format: Suk Woo Nam, Sangyean Kim, Minjeong Na, Eunbi Shin, Jin Woong Ha, Soyoung Jeon, Sungpil Yoon. NRT-YHD_001, targeting CD47 for liver 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 7520.
Abstract 7546: Targeting NSD2 to reverse lineage plasticity and drug resistance in neuroendocrine prostate cancer and subtypes of mCRPC
Authors: Li Jia J. , Vasciaveo Alessandro , Karagiannis Dimitrios , Chen Xiao , Yu Chen , Califano Andrea , Lu Chao , Shen Michael M. 
Published: March 2024

Abstract
Treatment with highly potent anti-androgens, such as enzalutamide and abiraterone promotes lineage plasticity in metastatic castration-resistant prostate cancer (mCRPC), which results in intra-tumor heterogeneity and emergence of mCRPC subtypes. The histological transformation from adenocarcinoma to aggressive neuroendocrine prostate cancer (CRPC-NE) has been associated with a loss of dependency on lineage-survival signals, leading to targeted drug resistance. Epigenomic reprogramming might be a fundamental driver of lineage plasticity. To determine CRPC-NE vulnerabilities, we have performed image-based screening using a small library of antibodies targeting different histone marks on CRPC-NE organoids derived from genetically engineered mice. We find that the histone mark H3K36me2 and the histone methyltransferase NSD2 play important roles in maintain the CRPC-NE epigenetic state. Knockout of NSD2 or ablation of H3K36me2 using an oncohistone mutant H3.3K36M reverted CRPC-NE to an adenocarcinoma phenotype. Simultaneous profiling of the transcriptome and epigenome from single cells verified this lineage conversion and the generation of cell states with canonical AR signaling. Moreover, H3K36me2 or NSD2 depleted mouse and human CRPC-NE organoids responded to enzalutamide treatment in vitro and in vivo, suggesting a reversal of castration-resistance. Most importantly, a small molecule inhibitor of NSD2 in combination with enzalutamide leads to growth suppression or apoptosis of mouse and human CRPC-NE organoids, as well as organoids of other CRPC subtypes. In conclusion, inhibition of NSD2 reverts the epigenomic state of CRPC-NE, reversing lineage plasticity and restoring anti-androgen sensitivity. Thus, we suggest that the combination of NSD2 inhibition with AR inhibition may represent a novel therapeutic approach for patients with CRPC-NE or even other CRPC subtypes.
Citation Format: Jia J. Li, Alessandro Vasciaveo, Dimitrios Karagiannis, Xiao Chen, Chen Yu, Andrea Califano, Chao Lu, Michael M. Shen. Targeting NSD2 to reverse lineage plasticity and drug resistance in neuroendocrine prostate cancer and subtypes of mCRPC [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 7546.
Abstract 755: Fecal microbial dysbiosis is associated with colorectal cancer risk
Authors: Kim Jeongseon , Gunathilake Madhawa , Yeo Hyun Yang , Oh Jae Hwan , Kim Byung Chang , Han Nayoung , Kim Bun , Pyun Hyojin , Lim Mi Young , Nam Young-Do , Chang Hee Jin 
Published: March 2024

Abstract
Although there is evidence of an association between the fecal microbiota and colorectal cancer (CRC) risk in epidemiologic studies, there is a lack of data from large-scale population-based studies. To address this gap, we assessed the dysbiosis of the fecal microbiome in a large-scale study in Korea. We recruited 287 CRC patients from the Center for Colorectal Cancer, National Cancer Center Hospital, Korea to perform 16S rRNA gene sequencing of fecal samples. A total of 287 age- and sex-matched healthy participants were selected from 890 cohort of healthy Koreans that are publicly available (PRJEB33905). The microbial dysbiosis index (MDI) was calculated based on the differentially abundant species. The association between MDI and CRC risk was observed using conditional logistic regression. Alpha-diversity indices were not significantly different between CRC cases and controls. The first three principal coordinates derived by a principal coordinate analysis (PCoA) based on weighted UniFrac distance explained 41.24% of the overall microbial diversity, with a significant divergence of the microbial composition between CRC patients and controls (PERMANOVA p=0.001). Three enterotypes were found based on CRC patients’ microbial composition. Those who were in the third tertile of the MDI showed a significantly increased risk of CRC in the total population (OR: 6.59, 95% CI: 3.83-11.33, p-trend&lt;0.001) compared to those in the lowest tertile. Similar results were found for men (OR: 6.58, 95% CI: 3.17-13.63, p-trend&lt;0.001) and women (OR: 6.69, 95% CI: 2.91-15.37, p-trend&lt;0.001). Dysbiosis in the fecal microbiota may be associated with an increased risk of CRC. Due to the potentially modifiable nature of the gut microbiota, our findings may have implications for CRC prevention among Koreans.
Key words: Fecal microbiome, 16S rRNA gene sequencing, Microbial dysbiosis, Colorectal cancer
Citation Format: Jeongseon Kim, Madhawa Gunathilake, Hyun Yang Yeo, Jae Hwan Oh, Byung Chang Kim, Nayoung Han, Bun Kim, Hyojin Pyun, Mi Young Lim, Young-Do Nam, Hee Jin Chang. Fecal microbial dysbiosis is associated with colorectal cancer risk [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 755.
Abstract 7659: AI-driven hypothesis-free analysis for biomarker discovery: Introducing the Biomarkers Navigator Framework
Authors: Kagiampakis Ioannis , Gidwani Mishka , Korkodinov Iaroslav , Ponomarev Georgiy , Jacob Etai 
Published: March 2024

Abstract
The pivotal role of biomarkers in personalizing patient treatment and guiding drug development is well-recognized, with the ultimate goal of enhancing therapeutic efficacy and patient quality of life by minimizing adverse events. Their development, however, is challenged by strict regulations and high costs, leading to sparse and varied data collected over extended periods and through diverse technologies. These variations complicate the harmonization and analysis of the data. Traditional methods struggle to navigate these complexities, further obscuring biomarker identification. For instance, PDL-1, approved as a biomarker by the FDA, has its effectiveness debated in several studies. To address these issues, we introduce Biomarkers Navigator, a flexible and automated analysis framework engineered explicitly for the robust identification of biomarkers. This framework is designed to aggregate, standardize, and store expansive biomarker information, ensuring efficient and traceable knowledge retrieval. By pre-calculating each potential biomarker, Biomarkers Navigator enables immediate and comprehensive meta-analyses, facilitating rapid decision-making tailored to the level of risk acceptance. Large Language Models (LLMs) further enhance the framework's capability to uncover signatures of response and resistance. LLM integration has accelerated the discovery of new potential biomarkers for hematological malignancies by combining prior knowledge and previously obscured associations. Our approach demonstrates the feasibility of large-scale hypothesis-free analysis and substantiates the utility of AI in unveiling hidden biological connections within clinical data. Our findings underscore the potential of AI-augmented frameworks in revolutionizing biomarker discovery and advancing personalized medicine.
Citation Format: Ioannis Kagiampakis, Mishka Gidwani, Iaroslav Korkodinov, Georgiy Ponomarev, Etai Jacob. AI-driven hypothesis-free analysis for biomarker discovery: Introducing the Biomarkers Navigator Framework [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 7659.
Abstract 7663: Identification of high-risk patients in multiple myeloma using a clonal gene signature
Authors: Li Jian-Rong , Wang Christiana , Cheng Chao 
Published: March 2024

Abstract
Introduction: Multiple myeloma (MM) is a heterogeneous disease with a small subset of high-risk patients associated with poor prognosis. The identification of these patients is crucial for treatment management and strategic decisions.
Methods: We developed a novel computational framework that only requires gene expression profiles to define prognostic gene signatures by selecting genes with expression driven by inferred clonal copy number alterations. We applied this framework to MM and developed a clonal gene signature (CGS) consisting of only 22 genes. This prognostic signature was evaluated in 5 independent datasets with gene expression data of a total of 2,155 MM samples. For each patient, we calculated a prognostic score based on the expression of the signature genes. Multivariate Cox regression analyses were performed to investigate the association of these signature scores with patient prognosis after adjusting established clinical factors. The performances of CGS and the only commercialized MM gene signatures, GEP70 and SKY92, in identifying high-risk patients were carefully compared by multiple different approaches.
Results: Our results indicated that CGS provided significant prognostic values after adjusting for well-established prognostic factors including cytogenetic abnormalities, International Staging System (ISS), and Revised ISS (R-ISS). In addition, it showed significant prognostic associations in patient subsets stratified by these conventional prognostic factors. Importantly, CGS demonstrated a better performance in identifying high-risk patients compared to the GEP70 and SKY92 signatures, which have been recommended for prognostic stratification in MM. Moreover, CGS can further stratify patients into subgroups with significantly differential prognoses when applied to the high-risk and low-risk groups already identified by GEP70 and SKY92. The higher CGS score of patients is significantly associated with poor response to dexamethasone, a commonly used drug for MM treatment.
Conclusions: In summary, we proposed a computational framework that only requires gene expression data to identify clonal gene signatures for prognosis prediction. The CGS provides a useful biomarker for improving prognostic stratification in MM, especially for the identification of patients with the highest risk. The computational framework used for defining this signature provides a useful tool, which can be readily applied to many other cancer types.
Citation Format: Jian-Rong Li, Christiana Wang, Chao Cheng. Identification of high-risk patients in multiple myeloma using a clonal gene signature [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 7663.