bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3383: Growth suppression and selective disruption of actin by alpha-santalol in human melanoma SK-MEL2 cells
Authors: Bommareddy Ajay , Chandrasekaran Ritesh , Lu Michael , Penate Delilah 
Published: March 2024

Abstract
Alpha-santalol, a major component of sandalwood oil has been shown to have chemopreventive and anti-tumor effects in different pre-clinical cancer models. The present study was undertaken to determine the in vitro efficacy of alpha-santalol on SK-MEL2 human melanoma cells and an immortalized human keratinocyte cell line (HACaT). In this study, we employed MTT assay, Trypan blue assay, wound healing assay, and confocal microscopy for imaging phalloidin/DAPI stained cells to investigate the cytotoxicity, cell viability, migratory potential respectively of the cells treated with different concentrations of alpha-santalol and DMSO for given time periods. Results showed that alpha-santalol treatment significantly decreased SK-MEL2 cell viability, wound healing, while only affecting HACaT cells at higher concentrations. Alpha-santalol treatment also disrupted actin cytoskeleton in SK-MEL2 cells, whereas HACaT cells were more resistant to this effect. In conclusion, the present study reveals selective growth inhibitory and anti-migratory effects of alpha-santalol in human melanoma cells and warrants future studies to systemically explore the mechanistic details involved in its growth inhibitory and antimigratory effects.
Citation Format: Ajay Bommareddy, Ritesh Chandrasekaran, Michael Lu, Delilah Penate. Growth suppression and selective disruption of actin by alpha-santalol in human melanoma SK-MEL2 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 3383.
Abstract 3388: Targeting liver specific βII-Spectrin to prevent the development of metabolic dysfunction associated steatohepatitis (MASH) through CEACAM1 axis
Authors: Bhowmick Krishanu , Ohshiro Kazufumi , Xiang Xiyan , John Sahara , Yang Xiaochun , Beauchemin Nicole , Hassan Mohammad I. , Mohammad Taj , Mishra Lopa 
Published: March 2024

Abstract
Background: Obesity and pro-inflammatory alteration of the gut microbiome are risk factors for gastrointestinal (GI) cancers, including liver cancer (HCC). Dysregulated TGF-β signaling and loss of CEACAM1 activity are implicated in fatty liver disease. Clinically, 40% of human liver and GI cancers have genetic alterations in the TGF-β pathway members. CEACAM1 expression is significantly decreased in the liver of patients with Metabolic dysfunction-associated steatohepatitis (MASH). In contrast, in hepatocellular carcinoma (HCC), high CEACAM1 is associated with invasion, metastasis and poor prognosis. We hypothesized that TGF-β signaling and βII-Spectrin modulate MASH and HCC through CEACAM1.
Methods: Wild type and the liver-specific βII-Spectrin (Sptbn1) knockout (LSKO) mice fed a high-fat diet (HFD) or Western diet (WD) and analyzed for Ceacam1 expression, changes in immune cell population, liver inflammation, and cancer. We used Alphafold and molecular modeling to identify the CEACAM1 and SPTBN1 interaction sites.
Results: Single cell sequencing analysis of MASH mice liver revealed that Ceacam1 expression is significantly decreased in hepatocytes. Interestingly, we found that CEACAM1 levels are restored to normal in tissues from liver-specific βII-Spectrin knockout (LSKO) mice. Transcriptomic and multiplex imaging analysis suggest that proinflammatory TGF-β signaling is activated and infiltration of CD11b+ cells is increased in MASH liver. These phenotypes are blocked in LSKO mice. Furthermore, siRNA-knockdown of βII-Spectrin blocks diet-induced obesity, fibrosis, lipid accumulation, tissue damage, and cancer susceptibility. We have also found that CEACAM1 interacts with the Smad3 adaptor, βII-Spectrin. Furthermore, structural analysis of CECAM1 and βII-Spectrin revealed critical residues involved in the interaction.
Conclusion: These data suggest that βII-Spectrin regulates CEACAM1 expression in the liver and is a potential target for therapeutic intervention to treat MASH and prevent progression to HCC.
Citation Format: Krishanu Bhowmick, Kazufumi Ohshiro, Xiyan Xiang, Sahara John, Xiaochun Yang, Nicole Beauchemin, Mohammad I. Hassan, Taj Mohammad, Lopa Mishra. Targeting liver specific βII-Spectrin to prevent the development of metabolic dysfunction associated steatohepatitis (MASH) through CEACAM1 axis [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 3388.
Abstract 3426: Real-world biomarker testing rates and trends among patients with advanced non-small cell lung cancer in the US
Authors: Chen Yiyu , Carlson Angeline 
Published: March 2024

Abstract
Background: Broad biomarker profiling before treatment initiation for non-small cell lung cancer (NSCLC) is recommended. Patients may not receive or receive inadequate biomarker testing before treatment initiation. This study assesses rates and trends of biomarker testing in community and academic oncology practices in the US.
Methods: A descriptive cohort study was conducted using electronic health records from an NSCLC registry. Patients who initiated NSCLC treatment following diagnosis of advanced NSCLC (stage IIIB/IIIC/IV) from 01/01/2015-12/31/2021 were identified. Patient demographics (age, gender, race, region) along with histology type (squamous/non-squamous) and hospital type (academic/community) were included. The percentage of patients receiving tests for any of the nine biomarkers before and during therapy was calculated and compared.
Results: 8,769 patients were identified with advanced NSCLC; 65.9% having non-squamous cell carcinoma; 22.4% having squamous cell carcinoma; 11.7% unknown. 13.4% of patients were from academic centers, 78.7% from community hospitals, 8.0% unknown. The majority (59%) were 65+ years; 47.3% were female. Overall, 83.2% had biomarker testing at some point in treatment; only 66.3% before treatment initiation. Over time, biomarker testing rates prior to treatment initiation increased (46.9% in 2015 to 73.8% in 2021). The use of biomarker testing in non-squamous cell carcinoma was greater than in squamous cell carcinoma. The most frequent biomarker testing before treatment initiation were PD-L1 (52.2%), EGFR (51.6%), and ALK (50.7%), followed by ROS1 (46.9%), BRAF (39.5%), and KRAS (34.1%). Testing rates for the newest biomarkers NTRK, MET, and RET were 20.4%, 28.4%, and 28.0%, respectively. Testing rates were similar between academic centers and community-based hospitals, except for the newest biomarkers, where use in academic settings was greater. Biomarker testing rates were higher among female patients (χ2 P-value&lt;0.001); rates by race were similar (χ2 P-value=0.83).
Conclusion: While the use of biomarker testing in advanced NSCLC is growing, 26% of patients remained untested before treatment initiation. Biomarker testing in non-squamous cell carcinoma is higher than in squamous cell carcinoma, in keeping with the guideline emphasis on biomarker testing for that histology type. Results suggest that further dissemination of guideline recommendations to obtain biomarker test results prior to treatment initiation is important to optimize treatment decisions in the NSCLC landscape.
Citation Format: Yiyu Chen, Angeline Carlson. Real-world biomarker testing rates and trends among patients with advanced non-small cell lung cancer in the US [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 3426.
Abstract 346: Trop-2 induces apoptosis via transcriptional activation of TRAIL, FAS-FASL, CD40-TNFRSF5
Authors: Alberti Saverio , Guerra Emanuela , Moschella Antonino , Ceci Martina , Pantalone Ludovica , Di Pietro Roberta , Trerotola Marco 
Published: March 2024

Abstract
Trop-2 is a transmembrane signal transducer that activates cancer growth and metastatic diffusion (1). However, this does not occur in all tumor types, as Trop-2 is associated to better disease outcome in some cancers, e.g. breast and lung tumors. A prototypic pattern of Trop-2 expression in normal multistratified epithelia, e.g. epidermis, esophagus, is that of preferential expression in non-proliferating, terminally differentiated cells. The corresponding expression gradient parallels that of induction of programmed cell death, e.g. in the corneum layer of skin keratinocytes. This led us to explore Trop-2 function as a trigger of apoptosis. We thus assessed NS-0 myeloma Trop-2 transfectants for apoptosis induction by dynamic cell morphometry and quantification of membrane blebbing and cell fragmentation. This was shown to be preceded by phosphatidyl-serine membrane exposure, and was followed by nuclear pyknosis and karyorrhexis. DNA fragmentation was shown by TUNEL and DNA laddering, and was accompanied by a dramatic increase of apoptotic death of Trop-2-expressing cells. Transcriptomic analysis at early time points of apoptosis induction indicated overexpression of TRAIL, FAS/FASL and CD40/TNFRSF5 transmembrane death receptors. This paralleled upregulation of downstream death-inducing signaling complex components and of executioner Caspases 8 and 3, suggesting Trop-2 as a trigger of extrinsic apoptosis pathways. Apoptosis induction translated into diminished tumor growth in vivo, which was shown to be proportional to Trop-2 expression levels. However, apoptosis induction was found to parallel stimulation of NS-0 cell growth and of defence mechanisms from apoptosis, as increased levels of inhibitory transcription factors, Rb-binding protein, survivin, Myd-118. These findings suggest a previously unappreciated balance between stimulation of cell growth and triggering of cell death by Trop-2, and may pave the way for selective anticancer therapy approaches in Trop-2-expressing cancers.(1) Trerotola M. et al., Neoplasia 23: 415-428 (2021).
Citation Format: Saverio Alberti, Emanuela Guerra, Antonino Moschella, Martina Ceci, Ludovica Pantalone, Roberta Di Pietro, Marco Trerotola. Trop-2 induces apoptosis via transcriptional activation of TRAIL, FAS-FASL, CD40-TNFRSF5 [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 346.
Abstract 3475: Prediction of nausea or vomiting, and fatigue or malaise in cancer care
Authors: Vienne Raphael , Filori Quentin , Susplugas Vincent , Crochet Hugo , Verlingue Loic 
Published: March 2024

Abstract
Introduction: Natural language processing has recently achieved unprecedented performances for several medical tasks, but requires additional improvements in oncology. Moreover, very few projects have assessed the potential of language models to help prevent the most frequent serious or severe medical events in medical oncology. We aim at predicting nausea or vomiting (ICD10 code R11), and fatigue or malaise (ICD10 code R53) from patients' medical reports.
Material and methods: The study included all the patients of Centre Léon Bérard between 2000 and 2023 that have not refused to share their data for this analysis. We have retrieved all the clinical notes and manual coding of hospitalization stays in ICD10, in French. We have pretrained a BERT language model with a masking strategy on this data and then fine-tuned it and compared it to several medical pretrained open source models (DrBert and K-memBERT). The labels were medical events leading to or associated with a hospitalization in the 90 days after every patients’ notes. For OncoBERT, we included sequential reports from the patients’ history, along with a time-encoding layer, and integrated it in a final transformer layer.
Results: We analyzed 140,523 patients, representing 2,515,957 pseudo-anonymized text reports and 6.6M hospitalizations codes in total. The medical texts were consultations reports (56%), end-of-stay reports (17%) and hospitalization summaries (9%). The most frequent types of oncology treatments received by the patients at each time point were 18.8% for chemotherapy, 10.8% for targeted therapies and 1.3% for immunotherapies. The most frequent medical events were nausea or vomiting (20% of patients with 1 or more events), and fatigue or malaise (18% of patients with 1 or more events). In the final dataset, nausea and vomiting (R11) accounted for 16% of the labels while malaise and fatigue (R53) accounted for 24.7% of the labels. We performed random undersampling of reports without any event to balance the label dataset. The fine-tuning on R11 and R53 achieved the performances of 0.58 macro-aucpr (OncoBERT) and 0.50 macro-aucpr (best open-source model) on the validation set.
Conclusion: The language models achieved high performance on the prediction of the most frequent serious medical events in our hospital dedicated to cancer care. We plan to validate the external performances of these models on collaborating hospitals and prospectively and improve the interpretations that we will present at the congress.
Citation Format: Raphael Vienne, Quentin Filori, Vincent Susplugas, Hugo Crochet, Loic Verlingue. Prediction of nausea or vomiting, and fatigue or malaise in cancer care [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 3475.
Abstract 3479: Evaluation of subclonal deconvolution pipelines using reference cell-lines and patient plasma samples
Authors: Dong Xiaoxi , Huang Yong , Zhang Tom , Jia Shidong , Du Pan 
Published: March 2024

Abstract
Background: Intratumor heterogeneity plays a pivotal role in treatment resistance, emphasizing the need for a comprehensive understanding of tumor clonal architecture. While various methods exist for extracting this information from bulk tumor sequencing data, few studies have evaluated the entire workflow, from sample processing to subclone calls.
Methods: To address this gap, we utilized cell lines with known copy number changes and somatic mutations, constructing 12 ground truth sample sets with varying cellular proportions and tumor purities. These cell lines underwent NGS pipeline using PredicineWES+ with increased sequencing depth across ~600 cancer-related genes. Subclonal analysis workflows, including FACETS, PyClone, and ECLIPSE, were implemented to to assess variant assignment and cellular fractions. The subclone analysis was extended to 91 plasma samples from cancer patients.
Results: Our findings indicate that subclonal decomposition effectively segregates mutations from distinct cell lines. Notably, analyzing multiple samples with different proportions of the same subclones outperformed deconvolution from single mixture samples. In plasma samples from cancer patients, nearly one-third exhibited subclonal clinically actionable variants.
Conclusions: The established subclonal deconvolution pipeline enhances biomarker analysis from assays utilizing WES with boosted sequencing depth for selected genes.
Citation Format: Xiaoxi Dong, Yong Huang, Tom Zhang, Shidong Jia, Pan Du. Evaluation of subclonal deconvolution pipelines using reference cell-lines and patient plasma samples [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 3479.
Abstract 3484: Mechanism of BRAF V600E resistance revealed by cell panel screening and bioinformatics
Authors: Hu Kaiqiang , Yang Qiuyuan , Pan Pengwei , He Fang 
Published: March 2024

Abstract
The BRAF V600E mutation is pivotal target in the treatment of melanoma. Dabrafenib, one of the most potent inhibitors approved by the FDA, exhibits differential sensitivity across different cancer types. To explore the underlying mechanisms responsible for the resistance of certain cancers to Dabrafenib, we tested a panel of 20 BRAF V600E positive cancer cell lines. Our results showed that 15 of these cell lines demonstrated sensitivity to Dabrafenib, whereas the remaining 5 exhibited resistance. We then investigated the correlation between Dabrafenib potency and gene expression patterns based on public high throughput sequencing data via bioinformatics methods. The results uncovered that the cell lines resistant to Dabrafenib showed low expression of MAP3K1, alongside with elevated expression of G0S2 and PIK3CG. These alterations are known to promote tumor cell proliferation, migration, and invasion, thereby contributing to a reduced sensitivity to BRAF inhibitors. Subsequent in vitro experiments validated the findings derived from our analysis. This unbiased, bioinformatics-driven approach provides valuable insight into the reasons behind treatment resistance and aids in the development of next-generation treatment approaches for inhibitor-resistant cancers.
Citation Format: Kaiqiang Hu, Qiuyuan Yang, Pengwei Pan, Fang He. Mechanism of BRAF V600E resistance revealed by cell panel screening and bioinformatics [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 3484.
Abstract 3503: New generation drug development from in-silico identification to preclinical evaluation in glioblastoma
Authors: Arunachalam Mahesh , Gaikwad Shreyas , Ramachandran Sharavan , Srivastava Sanjay K. 
Published: March 2024

Abstract
Glioblastoma(GBM) is the most common malignancy of the central nervous system in adults. Despite medical advancements, stagnant survival rate improvements (&lt;13%) and failure of conventional treatments such as temozolomide, have warranted the need for novel drug discovery methodologies. Considering the enormous potential of drug repurposing, we developed a method to identify a safe, active, and effective treatment for GBM. This method comprises two key stages, drug-target prediction and preclinical functional evaluation. Stage 1 fabricated a novel five phase in-silico pipeline for drug-target prediction against Ephrin-Type-A Receptor 2, chosen through preliminary literature and genomic analysis. Around 1562 FDA approved drugs were screened against the developed criterion and analyzed for bond type, location, repulsion, Gibbs free energy, stability, interactions over time, blood brain barrier permeability, and possible false positives (PAINS). Our results provided five plausible hits: Empagliflozin, Mycophenolate mofetil, Canagliflozin, Rivaroxaban, and Carvedilol. We subsequently evaluated the anti-proliferative effects of these hits using Sulforhodamine-B cytotoxicity assay on glioblastoma cell lines U251 and SF295. Our results demonstrated that Canaglifozin and Empagliflozin reduced the proliferation of GBM cell lines with IC50 value ranging from 30-40 μM. On the other hand, Mycophenolate mofetil (IC50: 5μM) and Carvedilol (IC50:16μM) also exhibited significant cytotoxic effects. Effects of Mycophenolate mofetil and Carvedilol were further evaluated in pancreatic cell line SUIT-2 where results exhibited cytotoxic responses similar to those observed in GBM. Furthermore, Annexin V/FITC analysis showed apoptosis in SUIT-2 cells by Carvedilol. Taken together, our results show the anti-cancer repurposing candidates extracted from our in-silico pipeline show significant cytotoxic effects of compounds identified through in-silico screening. Further studies are currently underway in our laboratory to delineate the anti-cancer mechanism, toxicity and off-target effects of these compounds.
Citation Format: Mahesh Arunachalam, Shreyas Gaikwad, Sharavan Ramachandran, Sanjay K. Srivastava. New generation drug development from in-silico identification to preclinical evaluation in glioblastoma [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 3503.
Abstract 353: Investigate the role of homoharringtonine in treating B-cell acute lymphoblastic leukemia
Authors: Jiao Emilie An An , Yuen Kei Ching , Li Bai Lin , Sin Chun Fung 
Published: March 2024

Abstract
B lymphoblastic leukemia (B-ALL) is an aggressive and highly lethal hematolymphoid malignancy and it is the most common cancer in children. Although the incidence of B-ALL in adult is lower than that in children, adult patients with B-ALL have a poor prognosis. Relapse/refractory disease is still the main cause of death in B-ALL patients. Homoharringtonine (HHT) is a plant alkaloid that was approved to treat chronic myeloid leukemia (CML) by FDA. Herein, we aimed to investigate the anti-leukemic activity of HHT in B-ALL. Cell viability was reduced in a time and dose-dependent manner upon treatment with HHT. Moreover, HHT was able to induce apoptosis in B-ALL cell lines by downregulating the MCL-1 protein level after 24 hours of treatment. Cell cycle analysis indicated G1 phase arrest, and western blot analysis demonstrated downregulation of CDK-4 and CDK-6. A proteomics study using label-free protein quantitation revealed enrichment of proteins involved in fatty acid oxidation, and further analysis showed downregulation of acyl-CoA desaturase after HHT treatment. Additionally, HHT significantly reduced the leukemic burden and prolonged survival in NSG mice injected with the PALL-2 cell line. Overall, the findings suggest that HHT is effective in treating B-ALL by inducing cell cycle arrest, with a potential inhibitory effect on fatty acid oxidation. Further studies will be conducted to evaluate the mechanism of modulation of fatty acid oxidation.
Citation Format: Emilie An An Jiao, Kei Ching Yuen, Bai Lin Li, Chun Fung Sin. Investigate the role of homoharringtonine in treating B-cell acute lymphoblastic leukemia [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 353.