bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2070: Engineered Inhalation nanoparticle formulation for lung cancer
Authors: Tiwari Rahul , Ghali Eswara N. , Chauhan Neeraj , Kashyap Vivek , Chauhan Subhash C. , Yallapu Murali M. 
Published: March 2024

Abstract
Background: Lung cancer is a predominant cause of cancer-related morbidity and mortality across the world including in the United States. Treatment modalities for lung cancer include surgery, chemotherapy, radiotherapy, and/or targeted therapies depending on the cancer stage. Despite the survival benefits of chemotherapy, its value is offset by severe systemic side effects such as renal and/or hepatic toxicity or insufficient amounts of drug reaching to the target site. Such pitfalls can be handled by inhalable therapy which avoids first-pass metabolism and increases patients' compliance. In this study, we have investigated the inhalable therapy of cross-linked tannic acid-based nanoparticles (CTA NPs) into cancer cells and determined the synergistic effect of gambogic acid (GA) and gemcitabine (Gem).
Methods: The CTA NPs formulations were characterized for particle size, chemical composition, and drug loading efficiency using various physicochemical methods (FT-IR, DSC, SEM, and TGA). Cellular uptake of CTA NPs was evaluated in lung cancer cell lines (A549 and NCI-H1299) using fluorescence microscopy and flow cytometry analysis. Further, the therapeutic efficacy of GA-Gem encapsulated CTA NPs (G-G CTA NPs) formulation was determined by various in vitro assays (CCK-8, mucoadhesion Boyden chamber, and apoptosis assays). The molecular effects of G-G CTA NPs formulation were also observed in lung cancer cell lines.
Results: Our novel CTA NPs formulation provided an average size of 110 nm in dynamic light scattering with a sustained release of the drug(s). CTA NPs formulation showed a remarkable mucoadhesion and mucopenetration penetration potential in-vitro model(s). Cellular uptake studies show that CTA NPs formulation allows for effective endosomal release into the cytosol. Additionally, the G-G CTA NPs formulation showed superior in vitro anti-cancer activity in lung cancer cells (A549 and NCI-H1299) compared to free drugs.
Conclusions: Taken together, our results demonstrate that G-G CTA NPs formulation exhibits superior anti-cancer potential than free drug against lung cancer and could be a novel therapeutic modality for the management of lung cancer.
Citation Format: Rahul Tiwari, Eswara N. Ghali, Neeraj Chauhan, Vivek Kashyap, Subhash C. Chauhan, Murali M. Yallapu. Engineered Inhalation nanoparticle formulation for lung cancer [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 2070.
Abstract 2103: Small extracellular vesicles derived from macrophages show anti-tumor effects in MDA-MB-231 cells
Authors: Desai Parth , Kumari Anjali , Abdullah Saqer Al , Dellinger Kristen 
Published: March 2024

Abstract
Triple-negative breast cancer is the primary cause of death in women globally due to the absence of targeted receptors on the tumor, making it hard to treat. In addition, the rapid spread of triple-negative breast cancer makes it difficult to manage using current treatment options such as lumpectomies, mastectomies, radiation, and chemotherapy. The survival rate for patients with triple-negative breast cancer is only 8-16%. Therefore, there is a critical need to develop new and effective treatment options. The objective of this study was to investigate the potential of M1 macrophage-derived exosomes to induce cancer cell apoptosis. To test this, we isolated M1 macrophage-derived exosomes to see their effects on triple-negative breast cancer MDA-MB-231 cells. We induce polarization in RAW 264.7 macrophage cells via lipopolysaccharide (LPS). Macrophage polarization was characterized using an enzyme-linked immunosorbent assay (ELISA), real-time PCR, nitric oxide production, and bright field microscopy. We characterized exosomes using nanoparticle tracking analysis (NTA) and scanning electron microscopy (SEM). The apoptosis marker, caspase 3/7 activation, was assessed using confocal microscopy in MDA-MB-231 cells. M1 macrophage-derived exosomes were isolated, characterized, and incubated with breast cancer cells to see their anticancer effects. Data showed the induction of apoptosis in 48 hours in triple-negative breast cancer cells. We conclude that exosomes derived from M1 macrophages may have the capability to induce apoptosis in triple-negative breast cancer.
Citation Format: Parth Desai, Anjali Kumari, Saqer Al Abdullah, Kristen Dellinger. Small extracellular vesicles derived from macrophages show anti-tumor effects in MDA-MB-231 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 2103.
Abstract 2106: Creating a living public oncology drug resource using PRISM cell line viability screening
Authors: Rees Matthew G. , Kocak Mustafa , Mapa Claudine , Frederick Dennie , Nguyen Ellen , Kalathungal Alvin , Fazio Anthony , Davis John F. , Reeves Emily , Tucci Ariah , Barry Rachael , Harrington Colleen , Eskra Jillian , Ronan Melissa M. , Sellers William R. , Roth Jennifer A. 
Published: March 2024

Abstract
Cancer treatment options are rapidly expanding, with many new targeted agents and therapeutic modalities under development. However, systematic characterization of the cellular effects of emerging drug candidates is limited. Screening such agents against the approximately 900 diverse cancer cell lines in the PRISM assay can provide insights into drug specificity and cancer subtype selectivity and, leveraging the rich genomic and functional characterization of PRISM cell lines, support for annotated mechanisms of action. Our goal was to generate a large, high-quality, oncology-focused dataset that can benefit the cancer research community by characterizing new test agents of high clinical relevance. In the past year, this effort has been utilized to screen a total of 180 test agents with plans to extend testing to an additional 140 over the next year. The collection includes biologics (e.g., cytokines, antibodies, antibody-drug conjugates), targeted protein degraders, and small molecules. Supporting the quality of the screening collection and the robustness of the PRISM assay, the majority of inhibitors (including mutant-selective KRAS inhibitors, and inhibitors targeting the WRN helicase, a preferential vulnerability in cancers with microsatellite instability) tested to date closely mimic the effects of genetic knockout and/or knockdown of their annotated target, as measured by CRISPR and shRNA data available through the Dependency Map Portal (depmap.org). Further, while we observe strong modality-independent co-clustering of test agents annotated to act on the same target(s) (e.g., tucatinib with the antibody-drug conjugates T-DM1 and T-DXd for HER2), intriguing differences in efficacy and selectivity emerge in individual cell line models. All PRISM reference screening data and analyses will be made publicly available through depmap.org to serve as a benchmark for new drug development candidates and to further the efforts of researchers worldwide to match emerging cancer therapies to the patients most likely to benefit.
Citation Format: Matthew G. Rees, Mustafa Kocak, Claudine Mapa, Dennie Frederick, Ellen Nguyen, Alvin Kalathungal, Anthony Fazio, John F. Davis, Emily Reeves, Ariah Tucci, Rachael Barry, Colleen Harrington, Jillian Eskra, Melissa M. Ronan, William R. Sellers, Jennifer A. Roth. Creating a living public oncology drug resource using PRISM cell line viability screening [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 2106.
Abstract 2112: Identification of biomarkers associated with sensitivity to a novel PCNA inhibitor (AOH1996) by CRISPRi screening
Authors: Gu Long , li Ming , Chen Chun-Wei , Hickey Robert J. , Malkas Linda H. 
Published: March 2024

Abstract
Proliferating cell nuclear antigen (PCNA) plays an essential role in regulating DNA synthesis and repair and is essential for cancer cell growth and survival. We discovered a cancer-associated isoform of PCNA (caPCNA), which is ubiquitously and highly expressed in a broad range of cancer cells and tumor tissues but is not significantly expressed in non-malignant cells. Further studies of this novel caPCNA isoform as an anti-cancer drug target led to the identification of a cancer distinct region of PCNA which is partly delineated by the L126-Y133 peptide sequence and the discovery of a small molecule (AOH1996), which binds to this cancer distinct region as shown by crystallization studies. By targeting caPCNA, AOH1996 selectively kills cancer cells by interfering with the resolution of transcription-replication conflicts (TRC). Importantly, it causes no discernable toxicity at 6 times of its effective dose in mice. AOH1996 is currently in a phase 1 clinical trial for adult solid tumors at City of Hope (IND 138273). To identify genes that may be used as biomarkers for patient selection or potential targets for combination therapies, we screened a CRISPR interference (CRISPRi) library, which targets genes that are involved in cell signaling and cell cycle regulation. After culturing transduced cells in the presence of DMSO or 250 nM AOH1996 (corresponding to IC20) in triplicates for 14 generations, we measured the relative abundance of each guide RNA (gRNA) construct. Significant changes in the abundance of the gRNA constructs in AOH1996-treated cells relative to that in DMSO-treated cells were determined by the MAGeCK method. The target genes of the depleted or enriched gRNAs are predominantly involved in DNA repair, cell cycle regulation, and transcription regulation, which is consistent with the action mechanism of AOH1996. We validated the effect of these genes on sensitivity to AOH1996 and identified a panel of target proteins whose up or down-regulation is associated with sensitivity to AOH1996. Some of these proteins are targets of known chemotherapeutic drugs, which may be used in combination with AOH1996 in the clinic.
Citation Format: Long Gu, Ming li, Chun-Wei Chen, Robert J. Hickey, Linda H. Malkas. Identification of biomarkers associated with sensitivity to a novel PCNA inhibitor (AOH1996) by CRISPRi screening [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 2112.
Abstract 2187: Influences of high-fat diet on tumor biology in a mouse model of colorectal cancer
Authors: Mahanty Anindita , Wallingford Cara , Hammontree Revan , Njoka Muturi , Clark Zachary , Rekowski Michaella , Washburn Michael , Davis Jennifer S. 
Published: March 2024

Abstract
Purpose: To test the influence of high-fat diet on tumor biology in the inducible Kras, Apc and p53 (iKAP) model (Boutin, et al Genes & Development 2017, 31:370).
Methods: At weening, both male and female mice were fed either a high-fat (60%) or low-fat (10%) diet for 5-6 weeks prior to tumor induction. Mutant Kras expression was controlled using a tet-on system. Expression of mutant Kras was activated by the addition of doxycycline hyclate in the drinking water. Tumor growth was monitored by bi-weekly endoscopy and calculated as percent luminal occlusion. Tumor biology was assessed with proteomics and phospho-proteomics with comparisons by sex and diet.
Results: In the absence of mutant Kras expression (no doxycycline in drinking water), tumors were larger in females on high-fat diet compared to low-fat diet. Tumor sizes were not significantly different in males or in the presence of mutant Kras expression. Proteomics analyses of tumor tissue identified significantly different patterns by diet in female mice, including altered levels of KIF4, DAB2iP, JNK cascade and JUN kinase activity (Table).
Conclusion: Based on our preliminary data, high-fat diet may alter tumor kinase activities, even in a genetically engineered mouse model. Replication and validation studies are ongoing.
Table of significantly upregulated biologic processes in female mice on high-fat diet compared to lo XXXXXXXXXXXXXXXX XXXXXXXXXXXXXXX
Citation Format: Anindita Mahanty, Cara Wallingford, Revan Hammontree, Muturi Njoka, Zachary Clark, Michaella Rekowski, Michael Washburn, Jennifer S. Davis. Influences of high-fat diet on tumor biology in a mouse model of colorectal cancer [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 2187.
Abstract 2228: Long-term trajectories of functional disability in older adults with cancer
Authors: Nam Gina E. , Mayeda Elizabeth Rose , Zhang Zuo-Feng 
Published: March 2024

Abstract
Background: Older individuals with cancer history have lower risk of developing Alzheimer’s disease (AD). Cognitive impairment is associated with lower functioning in Instrumental Activities of Daily Living (IADL) and Activities of Daily Living (ADL). However, little is known about long-term IADL and ADL trajectories among individuals with cancer, hindering understanding of the underlying biological mechanisms between cancer and AD. We investigated the long-term functional disability trajectories of adults with cancer, comparing them with similarly aged individuals without a cancer diagnosis.
Methods: Our study included 16,006 individuals aged 50 and older without a cancer history at baseline from the Health and Retirement Study. Biennial assessments were conducted from 1998 to 2020, including self-reported cancer status, IADL, and ADL. Linear probability models with repeated measures were used to assess IADL and ADL independence probabilities, adjusting for demographic and socioeconomic covariates.
Results: Among 16,006 participants (mean [SD] baseline age, 66.1 [9.9] years; 9,169 [57.3%] female), 3,723 (23.3%) reported a cancer diagnosis during follow-up. Before cancer diagnosis, individuals who later developed cancer had a higher probability of IADL independence and experienced a slower decline in independence compared to their similarly aged counterparts who remained cancer-free. Probability of IADL independence was 0.05 lower immediately after cancer diagnosis compared to the pre-cancer phase, followed by accelerated independence losses relative to the pre-cancer period. After diagnosis, the rate of decline in probability of IADL independence remained slower for individuals with cancer than their cancer-free counterparts, but differences in the rate of decline were smaller than prior to cancer diagnosis. Similar trends were observed for ADL independence.
Conclusions: We observed a decline in both IADL and ADL independence around the time of cancer diagnosis, possibly attributed to treatments. Overall, individuals with cancer experienced a more gradual loss in functional independence compared to individuals who remained cancer-free, consistent with the documented inverse association between cancer and AD.
Funding information: The current research was supported by the National Cancer Institute of the National Institutes of Health (T32CA009142), T32 Training Grants from the NCI/NIH, and the National Institute on Aging (RF1AG059872).
Citation Format: Gina E. Nam, Elizabeth Rose Mayeda, Zuo-Feng Zhang. Long-term trajectories of functional disability in older adults with cancer [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 2228.
Abstract 2334: Computational methods for optimizing marker selection, clonal lineage reconstruction, and longitudinal tracking of clonal dynamics via circulating tumor DNA (ctDNA)
Authors: Fu Xuecong , Deng Yueqian , Luo Zhicheng , Laframboise William , Bartlett David , Schwartz Russell 
Published: March 2024

Abstract
Background: Technologies for blood-based profiling of tumor DNA (“liquid biopsy”) have offered great prospects for non-invasive early cancer diagnosis, treatment monitoring, and clinical guidance, but further advances in computational models and data analysis to optimize monitoring protocols and develop liquid biopsy as a robust quantitative assay of tumor clonal evolution.
Methods: We propose new computational methods to improve our ability to characterize tumor clonal dynamics from circulating tumor DNA (ctDNA). Our methods address how to apply ctDNA assays most effectively to two distinct questions in profiling tumor clonal dynamics: 1) How to apply longitudinal ctDNA data to refine phylogenetic tree models of clonal evolution, and 2) how to most effectively characterize changes in clonal frequencies that may be indicative of treatment response or tumor progression. We pose these questions computationally in terms of a probabilistic framework for optimally identifying maximum likelihood markers for the preceding tasks and applying measured marker concentrations to their solution. We apply this framework by first evaluating the distribution of plausible clonal lineage models using bootstrap samples over pre-treatment tissue-based genetic variation data, then refining these lineage models and the clonal frequencies we can infer from them over successive longitudinal samples of selected markers.
Results: We tested our method on synthetic data under various model assumptions and showed the method to be effective at refining distribution tree models and clonal frequencies over longitudinal samples so as to minimize measures of tree distance relative to the ground truth. We further apply the methods to a real ovarian cancer case and show their ability to develop and refine a clonal lineage model and assess clonal frequencies.
Conclusion: Our methods show the power of ctDNA assays in conjunction with computational optimization to lead to improved marker selection, clonal lineage reconstruction, and tracking of clonal dynamics, with potential for more precise and quantitative profiling of tumor progression enabling improved clinical decision-making.
Citation Format: Xuecong Fu, Yueqian Deng, Zhicheng Luo, William Laframboise, David Bartlett, Russell Schwartz. Computational methods for optimizing marker selection, clonal lineage reconstruction, and longitudinal tracking of clonal dynamics via circulating tumor DNA (ctDNA) [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 2334.
Abstract 234: Microfluidic chip for drug response studies in non-small cell lung carcinoma patient-derived organoids
Authors: Luan Qiyue , Pulido Ines , Isagirre Angelique , Zhou Jian , Shimamura Takeshi , Papautsky Ian 
Published: March 2024

Abstract
Background. Organoids have been widely accepted as 3D tumor models for patient-specific drug response. However, research involving non-small cell lung cancer (NSCLC) organoids is hampered by the lack of appropriate platforms. Although dome cultures show promising results, the relatively large size variability of patient-derived organoids (PDOs) hinders their application in drug response studies. Here, we report a microfluidic chip for maintaining high uniformity and requiring miniscule sample volume for PDO drug screening.
Methods. The microfluidic chip includes a bottom microwell layer and a top microchannel layer. Each chip has 5 channels for parallel treatment conditions, with 30 U-shaped microwells (400μm dia x 250μm deep) per channel. PDOs were loaded from side channels and trapped by filters adjacent to microwells. NSCLC PDOs F231/F671 (NCI PDMR) were cultured and treated by KRASG12C inhibitor adagrasib (0-2000nM, 72h). PDO drug response was assessed via viability using fluorescent dyes.
Results. On-chip PDO size after one-week incubation exhibited the coefficient of variation (CV) of 28% for F231 and 36% for F671, which was notably lower than measurements obtained using Matrigel dome (126%, n=3) and low attachment plate (80%, n=4). The F231/F671 showed viability &gt;81% after 1wk (n=20). On-chip cytotoxicity results showed that both KRASG12C PDOs exhibited sensitivity to adagrasib, matching the clinical response, with IC50 values of 830 nM (F231) and 1324nM (F671). When cultured with fibroblast (WI-38) supernatant, the cytotoxic effect was mitigated due to the fibroblast-induced resistance, with IC50 increasing ≥2 ×. No statistical difference was observed for the fibroblast effect in the open-format microwells and our microfluidic chip (69.6±16.9% to 80.2±9.0% vs. 69.0±12.2% to 82.2±4.1%, respectively, following 500nM adagrasib for 72h), further underscoring the reliability of our chip for PDOs’ drug response studies. Application of continuous perfusion at 70nL/min yielded no statistical difference in viability from static conditions.
Conclusions. Our microfluidic chip offers uniform PDO growth with perfusion allowing drug screening in almost real time. The on-chip response to adagrasib was clinically relevant. Resistance due to tumor microenvironment (TME) can be readily assessed using fibroblast supernatant, and could be expanded to other TME components in future studies to investigate their impact on treatment resistance.
Citation Format: Qiyue Luan, Ines Pulido, Angelique Isagirre, Jian Zhou, Takeshi Shimamura, Ian Papautsky. Microfluidic chip for drug response studies in non-small cell lung carcinoma patient-derived organoids [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 234.