bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4165: Influence of halogens in squaraine dye on optoacoustic signal
Authors: Belligund Kavita , MacCuaig William , Wickizer Carly , Shao Yihan , McNally Lacey R. 
Published: March 2024

Abstract
Optoacoustic imaging has grown in clinical relevance due to inherent advantages in sensitivity, resolution, and contrast, compared to standard modalities, such as fluorescence. However, guiding principles for development of small molecule contrast agents specific for optoacoustic imaging is lacking. This study assesses the influence of specific structural features of small molecule dyes, specifically squaraine dyes, that result in optoacoustic activity. Through computational models, in vitro testing, and in vivo experimentation this study assesses the effects of halogens on small molecule squaraine dyes to increase optoacoustic signal. By using the aid of our computational model, we decorated the squaraine scaffold with heavy halogenation of squaraines increased optoacoustic activity (2.12 a.u. vs. 0.21 a.u., p&lt;0.001). Density functional theory models suggest the origin of increased optoacoustic signal is due to increases in transition dipole moment which manifested experimentally as increased absorbance in the NIR wavelength range and decreased fluorescence quantum yield, respectively. This study provides an insight into the structure-function relationships that lead to guiding principles for designing optoacoustic-specific contrast agents. Further developments of squaraines and other types of optoacoustic agents will further increase relevance of optoacoustic imaging in a clinical setting.
Citation Format: Kavita Belligund, William MacCuaig, Carly Wickizer, Yihan Shao, Lacey R. McNally. Influence of halogens in squaraine dye on optoacoustic signal [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 4165.
Abstract 4178: Non-invasive shortwave infrared imaging of cytotoxic T lymphocyte infiltration for monitoring responses to combination immunotherapy and chemotherapy
Authors: Shah Jay V. , Siebert Jake N. , Zhao Xinyu , He Shuqing , Riman Richard E. , Tan Mei Chee , Pierce Mark C. , Lattime Edmund C. , Ganapathy Vidya , Moghe Prabhas V. 
Published: March 2024

Abstract
Although triple-negative breast cancer (TNBC) can be treated with anti-PD-1 checkpoint immunotherapy in combination with chemotherapy, there remains a challenge in effectively monitoring therapeutic responses. Current non-invasive clinical imaging tools to evaluate response to treatment are reliant upon measurements of tumor volume and may fail to distinguish true progression from increased immune cell infiltration. Invasive biopsy sampling and immunohistochemistry (IHC) can elucidate changes in the immune landscape of treated tumors, but these methods are not conducive to providing real-time information. This study presents shortwave infrared (SWIR) imaging as a potential tool to detect treatment-induced cytotoxic T lymphocyte (CTL) infiltration non-invasively and in real time using rare earth metal-doped nanoparticles encapsulated in human serum albumin nanocomposites (ReANCs). ReANCs were chemically conjugated with anti-CD8α antibodies as targeting ligands to facilitate binding of the nanoprobes to CTLs with high specificity in a syngeneic mouse model of breast cancer. After treating the mice with combination anti-PD-1 and doxorubicin, volumetric analysis of the mammary fat pad tumors did not show any significant impact of treatment compared to single treatment and untreated control mice. However, increased CTL infiltration in the tumors of mice that received combination treatment was detected by in vivo SWIR imaging. CTL infiltration was validated with ex vivo IHC staining, and a monotonic relationship was observed between SWIR fluorescence and CD8 positivity. IHC staining of other immune markers, including CD45, CD3, CD4, and PD-L1, showed that combination treatment may influence in the expression of these markers, presenting additional targets that could be imaged with ReANCs in the future. In conclusion, the increase in SWIR signal from CD8-targeted ReANCs in tumors treated with combination immunotherapy and chemotherapy and the relationship with IHC staining highlight the ability to use SWIR imaging for non-invasive assessment of changes in immune dynamics following treatment.
Citation Format: Jay V. Shah, Jake N. Siebert, Xinyu Zhao, Shuqing He, Richard E. Riman, Mei Chee Tan, Mark C. Pierce, Edmund C. Lattime, Vidya Ganapathy, Prabhas V. Moghe. Non-invasive shortwave infrared imaging of cytotoxic T lymphocyte infiltration for monitoring responses to combination immunotherapy and chemotherapy [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 4178.
Abstract 4226: Human-derived hydrogels for 3D models of bone and osteosarcoma organoids and adipose tissue interactions
Authors: Sanchez Cecilia G. , Raz Arman , Lassiter Haley , Frazier Trivia 
Published: March 2024

Abstract
The goal of the study was to determine the metabolic and morphological changes, via high Content Imaging, in 3D models of osteosarcoma cancer cells using human derived hydrogels with different protein composition, Obagel and Obagel ECM. Furthermore, we evaluated the relevance of the adipose tissue microenvironment in Adipose Derived Stem Cells (ADSC) linage and Tumoroids development.
Methods: Adipose derived Stem cells were cultured in a modified 3D human and fat and bone linage differentiation as studied via histology and Immunofluorescence. Osteosarcoma spheroids were cultured in Obatala Sciences’ human-derived hydrogels ObaGel and ObaGelECM and control media. Organoid structure and phenotypic changes were analyzed via live cell imaging on the Incucyte S3 and Nikon high content imaging device. Then, adipocyte- cancer cell crosstalk was evaluated using pooled adipocytes co-cultured with KHOS spheroids. Adipose derived Stem cells were cultured in a modified 3D human derived hydrogel dictates that promotes the differentiation potential toward fat and adipose tissue simultaneously in microenvironments within the organoid. Furthermore, the results demonstrated that ObaGel and ObaGel-ECM 3D cultures can support the growth and proliferation of KHOS tumor spheres during an extended culture period. Metabolic changes and phenotypic changes associated to ObaGel and ObaGel-ECM differentially facilitated tumoroids growth and migratory behavior.
Conclusions: Human derived hydrogels are developed to support 3D culture of Bone and Osteosarcoma cells to recapitulate the phenotypic changes associated with their metastatic potential. The use of human derived 3D culture systems can accelerate the understanding of the role of the microenvironment in bone development and the pathogenesis and progression of Cancers like Osteosarcoma as well as screening for drug development.
Citation Format: Cecilia G. Sanchez, Arman Raz, Haley Lassiter, Trivia Frazier. Human-derived hydrogels for 3D models of bone and osteosarcoma organoids and adipose tissue interactions [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 4226.
Abstract 4236: PDX-derived organoids (PDXO) are valuable tools to unveil the shortcomings of new anti-cancer drug candidates
Authors: Wang Yuhui , Feng Lin , Liu Han , Zhang Junwen , Hu Kaiqiang , Pan Pengwei , He Fang 
Published: March 2024

Abstract
Introduction: Tumor organoids are increasingly being used as predictive preclinical cancer models, as they reflect the original tumor features and patient drug responses. However, systematic comparisons between organoids and traditional 2D cell lines or 3D spheroids are lacking.
Method: We established over 30 PDX-derived organoid (PDXO) models with KRAS mutations and tested three inhibitors targeting the KRAS pathway: VS-6766(RAF/MEK inhibitor), Trametinib (MEK inhibitor), and MRTX1133 (a Phase II drug targeting KRASG12D) against these models.
Results: IC50 results indicated that most models responded to treatment. For some cell lines we detected differential drug responses in 2D vs. 3D testing with 3Dspheroids being more sensitive to inhibitors than 2D cell lines (on average ~10 fold). PDXO models exhibited greater individual differences in drug response, with a subset of models demonstrating no sensitivity to MRTX1133. This is consistent with published results showing that some KRASG12D-mutant PDX models were less sensitive to MRTX11331. Similarly, the clinical trial data for the KRASG12C inhibitor Adagrasib revealed distinctions in the response of patients2. Further analysis with WES (whole exome sequencing) and RNA-sequencing identified potential genotypic mutations and differential expressions of signaling pathways related to drug resistance. Subsequent drug combination testing showed that targeting these pathways could enhance the MRTX1133 efficacy in the resistant PDXO models.
Summary: Our research confirms that drug testing on organoids predicts responses in mouse models and clinical trials. In combination with multi-omics and bioinformatics analysis, the platform can be used for evaluating drug resistances, identifying new targets, developing new drug combination therapies, and ultimately improving the creation of new cancer therapeutics.
Citation Format: Yuhui Wang, Lin Feng, Han Liu, Junwen Zhang, Kaiqiang Hu, Pengwei Pan, Fang He. PDX-derived organoids (PDXO) are valuable tools to unveil the shortcomings of new anti-cancer drug candidates [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 4236.
Abstract 4245: Selection of AAV capsids by evaluating transgene delivery using human organoid models
Authors: Fu Yingying , Qi Zhen , Zuo Zhanguan , Chiang Spencer , Ouyang An , Gao Glory , Guan Shuge , Chen Jin-Qiu (Jessie) , Zhang Rosanna , Wang Cheng 
Published: March 2024

Abstract
Recombinant adeno-associated viruses (AAVs) play a pivotal role in gene therapy, a promising approach aimed at treating various genetic disorders by introducing modified genetic material into cells or tissues. These AAV capsids are utilized as a vector in transferring genetic material into host cells. In discovery research, many AAV serotypes are developed in parallel to identify the optimal subtype for subsequent preclinical and clinical use. However, gene therapies have found limited success in clinical translation, in part, due to variable transgene delivery efficacy between traditional in vitro and in vivo models and human models. This study presents an organoid-based approach that mimics human physiology, as well as organ-specific features and cell diversity within an organ. Organoids are 3D structures derived from stem cells that resemble the cellular architecture and functionality of a specific organ. Compared to conventional 2D cell cultures, organoids provide a more comprehensive modeling of complex cell signaling, cell-cell and cell-extracellular matrix interactions, simulating the complex interplay between various cell types and functions. Within this study, several human-based organoid models were built, cerebral and cardiac, and verified by identifying the expression level of known marker genes through RNA sequencing. Five different AAV serotypes were utilized to evaluate transgene efficacy using each type of organoid model. Expression of delivered GFP transgene within each organoid was then compared to evaluate transduction and select the optimal AAV serotype in comparison to commercial wild-type AAVs. We outline the use of human organoid as an improved preclinical model for selecting AAV serotypes and evaluating transgene delivery efficacy to help provide better guidance for gene therapy development when moving into clinical research.
Citation Format: Yingying Fu, Zhen Qi, Zhanguan Zuo, Spencer Chiang, An Ouyang, Glory Gao, Shuge Guan, Jin-Qiu (Jessie) Chen, Rosanna Zhang, Cheng Wang. Selection of AAV capsids by evaluating transgene delivery using human organoid models [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 4245.
Abstract 4254: Genetically engineered human lung organoid models for lung cancer evolution study
Authors: Moon Sungji , Kim Rokhyun , Lee Dakyung , Park Kyunghyuk , Lee Woochan , Lee Seyoon , Park Young Jun , Kim Jongil 
Published: March 2024

Abstract
Initial cellular events in a transitional period from normal to cancer cells, such as transcriptomic or epigenetic dynamics, are poorly understood. Observing these is more challenging than in cancer progression, especially for humans. Mapping this phenomenon in early cancer evolution is crucial, as we can identify targetable molecules to inhibit cancer development at the precancerous stage. Immortalized human cancer cell lines hardly capture these appropriately as they have lost usual cellular characteristics. Normal organoids harbor stem cells and their differentiated cells, reflecting the epithelial physiology of tissues, and are more suitable models for cancer evolution studies. To establish a human cancer development model in vitro, we genetically engineered normal human airway organoids derived from adult stem cells into small cell lung cancer (SCLC). We used CRISPR-Cas9 systems to induce non-homologous end-joining in both TP53 and RB1, the most frequently mutated genes of SCLC. First, we knocked out TP53 of the airway organoids, selected by Nutlin-3a, an MDM2 antagonist, for 3-4 weeks, demonstrating 88-89% editing efficiencies calculated from Sanger sequencing results. Most mutations were one base pair deletion or insertion, which induced frameshift mutation in TP53. They did not show a significant difference from wild-type organoids morphologically at bright-field microscopy. Subsequently, we targeted RB1 on TP53-/- airway organoids to induce SCLC. We used Palbociclib, a CDK4/6 inhibitor, to enrich the mutated cells. They had 67.1% efficiency, and 20.4% had a 7-base pair deletion mutation. In the initial period, they seemed to have similar shapes to TP53-/- organoids. Unexpectedly and interestingly, however, we noticed more rapidly proliferating and disorganized organoids disrupting their original round shapes appeared in 4-5 weeks. The cells were indiscriminately piled up on the airway organoids' apical and basolateral surfaces, indicating their malignant traits. Their chaotic proliferation represented the rapidly progressing clinical feature of SCLC with a median survival of 7-16 months with treatment. This is the first work constructing the SCLC development model from the normal human airway organoid. By sequentially single-cell sequencing this organoid model changing to tumorous condition, we can capture the multi-omics landscape during the initial evolution of SCLC.
Citation Format: Sungji Moon, Rokhyun Kim, Dakyung Lee, Kyunghyuk Park, Woochan Lee, Seyoon Lee, Young Jun Park, Jongil Kim. Genetically engineered human lung organoid models for lung cancer evolution study [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 4254.
Abstract 4259: A novel human model of lung squamous cell carcinoma to deconvolve the cell-intrinsic effects of key dysregulated pathways
Authors: Ogden Julia , Sellers Robert , Oojageer Anthony , Sahoo Sudhakar , Chaturvedi Anshuman , Lopez-Garcia Carlos 
Published: March 2024

Abstract
Tractable, patient relevant models are needed to investigate the essential components of normal cell transformation. We developed a unique in vitro model of early lung squamous cell carcinoma (LUSC) genetic alterations and driver pathway dysregulation using genetically modified primary human bronchial basal cells (hBCs) from three independent donors. The co-operation of ubiquitous and early LUSC alterations (TP53 and CDKN2A loss) and commonly deregulated pathways including squamous differentiation (SOX2), PI3K signaling (PTEN) and the oxidative stress response (KEAP1) was investigated using a combinatorial approach, culminating in eight unique hBC mutants harboring cumulative pathway alterations in a TP53-/-/CDKN2A-/- background. Phenotypes indicative of mutant hBC transformation were investigated using proliferation assays, organotypic cultures and anchorage independent growth assays. Organotypic cultures revealed LUSC pathway alterations to drive dramatic changes in airway histology, ranging from a normal epithelium to severe dysplasia. Furthermore, these analyses confirmed the role of SOX2-overexpression in initiating transformation by inducing squamous cell commitment and anchorage independent growth. We also identified a co-operation of SOX2-overexpression with the oxidative stress response and PI3K pathways to drive more advanced lesions in-vivo and in-vitro. Importantly, we were able to map changes in the expression of immunomodulatory factors with the pathway dysregulation. We demonstrated that this strategy constitute an alternative and patient-relevant system to model LUSC and identify genotype-phenotype correlations of clinical relevance.
Citation Format: Julia Ogden, Robert Sellers, Anthony Oojageer, Sudhakar Sahoo, Anshuman Chaturvedi, Carlos Lopez-Garcia. A novel human model of lung squamous cell carcinoma to deconvolve the cell-intrinsic effects of key dysregulated pathways [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 4259.
Abstract 4272: Disruption of hyaluronan metabolism alters glioma cell proliferation by ligand dependent and independent mechanisms
Authors: Neves Edward R. , Mueller Joseph , Anand Achal , Selting Kimberly , Xu Hui , Remy Roddel , Harley Brendan , Pedron-Haba Sara 
Published: March 2024

Abstract
Hyaluronan (HA) is the main constituent of the brain extracellular matrix and is an essential component of the glioblastoma (GBM) tumor microenvironment. The biosynthesis and catabolism of hyaluronan has multiple roles in tissue architecture and cell signaling. Dysregulation of these mechanisms is crucial in pathological processes such as cancer, inflammation or tissue remodeling. The role of HA is believed to be strongly dependent on its size (molecular weight), location, and cell receptor density and activity. HA is produced intracellularly by HA synthases (HAS1-3) and can also be catabolized endogenously by hyaluronidases (HYAL1-3).The fabrication of controlled microenvironments provided by three dimensional (3D) models helps to elucidate the role of HA signaling in GBM tumors. We exploit here the advantages of these models to understand the role of hyaluronan in the local behavior of GBM after radiation therapy and selected targeted inhibitors. We have established engineered brain tumor biomaterials based on functionalized hydrogels to monitor the response of patient-derived xenograft cell populations with different molecular signatures in combination with microfluidic devices. We have analyzed shifts in metabolism, hyaluronan secretion, as well as hyaluronan synthetic enzymes (HAS) and hyaluronidases (HYAL) activity in an array of patient derived GBM cells. We reveal that endogenous HA plays a role in mitochondrial respiration and cell proliferation in a tumor subtype dependent manner. We also show that HA fragments can enhance tumor metabolism and growth through ligand dependent and independent mechanisms. We provide bioengineered platforms and strategies to predict and stratify tumors in order to achieve more efficient combinatorial treatments targeting endogenous hyaluronan production. This work emphasizes the potential of these preclinical models to predict and accelerate cancer treatments, more relevant in malignancies with limited treatment options.
Citation Format: Edward R. Neves, Joseph Mueller, Achal Anand, Kimberly Selting, Hui Xu, Roddel Remy, Brendan Harley, Sara Pedron-Haba. Disruption of hyaluronan metabolism alters glioma cell proliferation by ligand dependent and independent mechanisms [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 4272.
Abstract 4293: Chromosomal instability causes epigenetic aberrations in cancer
Authors: Agustinus Albert S. , Al-Rawi Duaa , Dameracharla Bhargavi , Raviram Ramya , Jones Bailey S. , Stransky Stephanie , Scipioni Lorenzo , Luebeck Jens , Bona Melody Di , Norkunaite Danguole , Myers Robert M. , Duran Mercedes , Choi Seongmin , Weigelt Britta , Yomtoubian Shira , McPherson Andrew , Toufektchan Eleonore , Keuper Kristina , Mischel Paul S. , Mittal Vivek , Shah Sohrab P. , Maciejowski John , Storchova Zuzana , Gratton Enrico , Ly Peter , Landau Dan , Bakhoum Mathieu F. , Koche Richard P. , Sidoli Simone , Bafna Vineet , David Yael , Bakhoum Samuel F. 
Published: March 2024

Abstract
Chromosomal instability and changes in the epigenome are defining features in most metastatic cancers. Our research links chromosomal missegregation, their containment in micronuclei, and subsequent rupture of the micronuclear envelope to histone post-translational modification aberrations. This relationship was across all tested human and murine cancer cell lines, as well as non-transformed cells. Furthermore, we discovered that the observed changes in histone PTMs were caused by either micronuclear rupture or the persistence of histone PTM status during cell division. Moreover, we revealed substantial chromatin accessibility differences in micronuclei. Notably, there is a distinct bias in chromatin accessibility between promoter regions compared to distal and intergenic regions of the genome, which aligned well with observed changes in histone modifications. The induction of chromosomal instability leads to widespread, heterogeneous, and heritable abnormalities in the epigenetic landscape of cancer cells. Therefore, on top of genomic copy number changes, chromosomal instability causes epigenetic reprogramming, which adds another layer to cancer heterogeneity.
Citation Format: Albert S. Agustinus, Duaa Al-Rawi, Bhargavi Dameracharla, Ramya Raviram, Bailey S. Jones, Stephanie Stransky, Lorenzo Scipioni, Jens Luebeck, Melody Di Bona, Danguole Norkunaite, Robert M. Myers, Mercedes Duran, Seongmin Choi, Britta Weigelt, Shira Yomtoubian, Andrew McPherson, Eleonore Toufektchan, Kristina Keuper, Paul S. Mischel, Vivek Mittal, Sohrab P. Shah, John Maciejowski, Zuzana Storchova, Enrico Gratton, Peter Ly, Dan Landau, Mathieu F. Bakhoum, Richard P. Koche, Simone Sidoli, Vineet Bafna, Yael David, Samuel F. Bakhoum. Chromosomal instability causes epigenetic aberrations in 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 4293.