bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 386: Non-intrusive, non-invasive and patient friendly focused ultrasound device as a delivery vehicle for CNS tumors
Authors: Ramamurthy Bhaskar , Keralapura Mallika , Marshall Jack , Need Dan , Dittamore Ryan , Kesari Santosh , Fonkem Ekokobe 
Published: June 2022

Abstract
A major impediment to treatment of brain cancers is the inability to transport drugs across the blood-brain barrier (BBB). The development of an effective, targeted, and non-invasive method to penetrate the BBB to deliver cancer therapeutics is an unmet need in the treatment of brain cancers. Large molecular weight chemo- and immuno-therapies such as doxorubicin and others may be potentially effective against brain cancers if such drugs are sufficiently bioavailable in the brain. Focused ultrasound techniques can safely and transiently open the BBB but current techniques require invasive/intrusive or expensive and high-touch procedures and are not optimal for wide adoption. To address this unmet need, we are developing an innovative technique to non-intrusively, non-invasively and transiently open the BBB in a specified location within the brain using guided ultrasound (US). Our device consists of a proprietary US generator that is controlled by a highly portable system that has a small physical footprint, enabling the US generator and system to be placed in confined spaces such as chemotherapy infusion centers. The US generator is cap-shaped device that is placed on a patient’s head. It includes multiple sets of ultrasound transducers that are distributed within the cap according to the anatomy of the skull. With our proprietary technique, we calculate the position of the cap in relation to the internal anatomy in a real-time manner with a non-intrusive and a non-invasive manner. We have recently concluded an extensive study that resulted in algorithms that can accurately guide the US to various targets within the brain across a spectrum of patients. We also have completed a pilot preclinical study on a large animal demonstrating our ability to open the BBB non-invasively and deposit a drug proxy (gadolinium and Evans Blue).
Citation Format: Bhaskar Ramamurthy, Mallika Keralapura, Jack Marshall, Dan Need, Ryan Dittamore, Santosh Kesari, Ekokobe Fonkem. Non-intrusive, non-invasive and patient friendly focused ultrasound device as a delivery vehicle for CNS tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 386.
Abstract 3864: Cytometric analysis of immune cell populations in clinical tumor biopsy tissue microarrays for immuno-oncology
Authors: Villani Tom , Patel Jigar , Collins Kim , Tunstall Kate Lillard , Krisanits Bradley 
Published: June 2022

Abstract
Over the past decade, a new focus on the interactions between the immune system and the development and progression of cancer has led to a wide array of research into medical treatments which leverage activation or modulation of the immune system to aid in treatment. Research in the field of immuno-oncology and elucidation of the biological mechanisms by which cancer cells suppress immunological function has led to new biological treatments for cancer, such as pembrolizumab, which have shown great clinical success since their advent. Population-level analysis of immune cell populations is critical for understanding the immune-component of disease progression, and flow cytometry is a commonly utilized technique for this purpose. However, flow cytometry requires dissolution of tissue specimens, and is incompatible with formalin-fixed paraffin-embedded (FFPE) samples, the gold standard in tissue archives. In order to allow for cytometric analysis of FFPE tissues, we have developed a digital pathology technique for the quantitative assessment of immune-cell populations within tissue microarrays prepared from archived FFPE clinical tissue specimens from patient biopsies. The technique involves a combination of HALO® image analysis using the Highplex FL, Spatial Analysis, and TMA modules, and custom scripting to develop imaging cytometry scatterplots. Bioinformatics techniques were utilized to assess features correlated with tumor progression from the quantitative data extracted from the tissue microarrays.
Citation Format: Tom Villani, Jigar Patel, Kim Collins, Kate Lillard Tunstall, Bradley Krisanits. Cytometric analysis of immune cell populations in clinical tumor biopsy tissue microarrays for immuno-oncology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3864.
Abstract 3877: Deep ultrahigh-plex spatial phenotyping of human cancer tissues
Authors: Jhaveri Niyati , Nikulina Nadya , Zong Hailing , Ma Ning , Cheikh Bassem Ben , Pratapa Aditya , Kassim Yasmin , Anand Bhaskar , Prater Michael , Basu Subham , Braubach Oliver 
Published: June 2022

Abstract
Spatial phenotyping is poised to revolutionize cancer research and treatment. Technologies like CO-Detection by indEXing (CODEX), which enable the detection of dozens of protein biomarkers in situ, have already transformed immuno-oncology and are expected to play formative roles in future research. To further support the implementation of CODEX in cancer research, we present a comprehensive 100 antibody panel that is aimed at in-depth identification of immune cell lineages, activation states, immune checkpoints, tissue structure, cellular signaling, apoptosis, DNA damage and cellular metabolism. Deployment of this panel is possible at high-throughput on the CODEX platform, which is a fully-integrated spatial biology solution that provides cyclical multiplexed imaging at unprecedented resolution and rapid turn-around time. The key features of this novel spatial biology system include: 1) true single-cell and sub-cellular resolution, 2) unparalleled biomarker imaging depth on whole FFPE samples, 3) wide-ranging compatibility with whole slide FFPE tissues, 4) panel customization and flexibility via dedicated barcodes, 5) uncompromised access to whole tissues, and 6) sophisticated single-cell analytical metrics. In this study, we generate a comprehensive account of the spatial biology in different tumor tissues including lung cancer, colon cancer, and melanoma using the CODEX instrument. Single-cell spatial phenotyping coupled with deep bioinformatic analyses reveals new quantitative phenotypic and spatial information that will be essential to gain further insights into distinct cellular neighborhoods and their role in regulating immune and metabolic functions of certain cancers.
Citation Format: Niyati Jhaveri, Nadya Nikulina, Hailing Zong, Ning Ma, Bassem Ben Cheikh, Aditya Pratapa, Yasmin Kassim, Bhaskar Anand, Michael Prater, Subham Basu, Oliver Braubach. Deep ultrahigh-plex spatial phenotyping of human cancer tissues [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3877.
Abstract 3882: Translating genotype to immunophenotype in HRAS mutated head and neck squamous cell carcinoma (HNSCC) to identify effective Tipifarnib partners for optimal patient outcomes
Authors: Psyrri Amanda , Anastasiou Miriam , Spathis Aris , Doumas Stergios , Economopoulou Panagiota , Kotsantis Ioannis , Pantazopoulos Anastasios , Kyriazoglou Anastasios , Kavourakis George , Rampias Theodoros , Foukas Periklis 
Published: June 2022

Abstract
Background: Tipifarnib is a highly selective farnesyltransferase inhibitor that has shown promising activity in HRAS mutant recurrent/metastatic HNSCC. The incidence of HRAS mutations in HNSCC is 4-10%. Since HRAS mutated HNSCC can be successfully targeted with Tipifarnib, we sought to analyze the immune and genomic landscape of these tumors to guide combinatorial strategies.
Methods: We identified thirteen patients with HRAS mutant tumors. We included in the analysis 50 patients with HRAS wild-type tumors. Genomic DNA from baseline biopsies of tumors was purified and subjected to targeted sequencing (TruSightTM Oncology 500 panel). PD-L1 expression in formalin-fixed tumor samples was assessed using the PD-L1 IHC 22C3 pharmDx assay (Agilent Technologies, Carpinteria, CA, USA) and characterized by the combined positive score (CPS). Assessment of PD-L1+ cells inside and at the periphery of the tumor was performed. HRAS mutational status was correlated with PD-L1 status. The genomic data derived from the targeted gene panel of HRAS mutant tumors were compared to those with wild-type HRAS.
Results: Thirty-seven patients had both genomic and PD-L1 expression data available. The presence of HRAS mutations was associated with higher TPS PD-L1 scores (26% vs 40% vs 100% in TPS &lt;1%, 1-49% and &gt;50% respectively, p=0.043). Similar results were obtained for CPS (28% vs 80% in CPS &lt;10% and =&gt;10%, p=0.047). HRAS mutations were more commonly found with TP53 mutations (16% in WT TP53 and 55.6% in mutated TP53, p=0.073). Higher PD-L1 TPS showed increased survival without reaching significance when measuring either in the margins (64.1 vs 35.8, p=0.066) or the center of the tumor (p=0.097) due to the small sample size.
Conclusions: HRAS mutant HNSCC are associated with high PD-L1 expression and co-occurrence of p53 mutations. Combinations of tipifarnib with an anti-PD1 antibody, an anti-PDL1 antibody, or an anti-CTLA-4 antibody warrant clinical investigation in this rare subset of HNSCC.

Citation Format: Amanda Psyrri, Miriam Anastasiou, Aris Spathis, Stergios Doumas, Panagiota Economopoulou, Ioannis Kotsantis, Anastasios Pantazopoulos, Anastasios Kyriazoglou, George Kavourakis, Theodoros Rampias, Periklis Foukas. Translating genotype to immunophenotype in HRAS mutated head and neck squamous cell carcinoma (HNSCC) to identify effective Tipifarnib partners for optimal patient outcomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3882.
Abstract 3894: WNT5B in osteosarcoma stem cells
Authors: Perkins Rachel S. , Suthon Sarocha , Miranda-Carboni Gustavo A. , Krum Susan A. 
Published: June 2022

Abstract
Osteosarcoma is a rare but deadly pediatric bone cancer. As it stands, there is no targeted therapy available for osteosarcoma. Therefore, patients are left with chemotherapy and surgical resection as their only treatment options. Further, osteosarcoma frequently metastasizes to the lungs and patients with metastatic disease have a dismal overall survival rate of 20% due to the lack of targeted therapy. Therefore, the goal of this study is to understand the role of the WNT5B signaling pathway in osteosarcoma, as it could be a potential therapeutic target. Using RNA sequencing from publicly available data sets and immunohistochemistry on tumor microarrays, we show that WNT5B is overexpressed in a subset of osteosarcoma patients. In these high expressing patients, WNT5B’s overexpression correlates to metastasis and worse overall survival. Due to the significant increase in WNT5B expression between primary tumors and metastasis, we began looking at the stem cell population of osteosarcoma cells. By selecting for the osteosarcoma stem cells using spheroid assays, we show that both protein and mRNA levels of WNT5B are enhanced in the stem cell population compared to the standard adherent cell population. Then, we looked at stemness markers and we show that WNT5B regulates the stemness gene SOX2. We then performed limiting dilution sphere assays to assess the role of WNT5B in sphere forming. We reveal that WNT5B is directly responsible for the sphere forming efficiency, as evidenced by a 50% reduction in spheres formed between 143B control and 143B WNT5B knockdown cells. Additionally, WNT5B drives proliferation and migration of osteosarcoma cancer stem cells as there is significantly decreased sphere size and migratory distance in WNT5B knockdown cells compared to control cells, and there is significantly increased sphere size and migration with the addition of recombinant WNT5B. Through revealing a novel role for WNT5B in osteosarcoma cancer stem cells, we present the WNT5B pathway as a candidate for therapeutically targeting the clinical implications of cancer stem cells, that is, the development of chemoresistance, metastasis and relapse.
Citation Format: Rachel S. Perkins, Sarocha Suthon, Gustavo A. Miranda-Carboni, Susan A. Krum. WNT5B in osteosarcoma stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3894.
Abstract 3900: Β3 adrenergic receptor blockade impairs compensatory mechanism to overcome nutrient deprivation in malignant rhabdoid tumor of the kidney
Authors: Subbiani Angela , Boaretto Alessia , Buonvicino Daniela , Cecchi Cecilia , Favre Claudio , Calvani Maura 
Published: June 2022

Abstract
In this study, the effects of nutrient deprivation in regulating tumor growth and metabolism in Malignant Rhabdoid Tumor of the Kidney (MRTK) was investigated. MRTK is a rare and highly aggressive tumor occurring in infancy and early childhood. Unfortunately, there are not many studies to date that can help us better understand the involvement of metabolism in MRTK growth and progression. However, it is now well known that nutrient deprivation is an environmental stress factor that can influence the behavior of cancer cells leading to reprogramming in metabolism. Here, we first evaluated the effects on cell survival and metabolic adaptation of MRTK G-401 cells after glutamine or tyrosine/phenylalanine deprivation, or both. Then, the involvement of the β3-adrenergic receptor (β3-AR) in regulating the metabolic changes in G-401 cells exposed to limited conditions was investigated. We demonstrated that deprivation of glutamine alone or in combination with tyrosine/phenylalanine enhanced the expression of the glucose transporter GLUT1, associated with increased glucose uptake, ATP production, and oxidative stress, as a compensatory mechanism following amino acid deprivation partially regulated via β3-AR. Indeed, β3-AR antagonism was able to decrease the expression of GLUT1, glucose uptake and survival in G-401 cells. Furthermore, exposure of G-401 cells to limited conditions induced an improved activity of the TCA cycle enzymes leading to a different and enhanced fumarate production. Overall, our results indicate that tyrosine/phenylalanine and glutamine deprivation in MRTK is able to trigger a compensatory mechanism to sustain tumor growth and proliferation.
Citation Format: Angela Subbiani, Alessia Boaretto, Daniela Buonvicino, Cecilia Cecchi, Claudio Favre, Maura Calvani. Β3 adrenergic receptor blockade impairs compensatory mechanism to overcome nutrient deprivation in malignant rhabdoid tumor of the kidney [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3900.
Abstract 3902: TRIM33 interacts with HSF1 in osteosarcoma development
Authors: Lallier Morgane , Tefaye Robel , Moukengué Brice , Charrier Céline , Thepault Rose-Anne , Royer Benedicte Brounais-Le , Baud'huin Marc , Verrecchia Franck , Ory Benjamin , Lamoureux François 
Published: June 2022

Abstract
Osteosarcoma (OS) is the most common primary malignant bone tumor in oncopediatrics. Despite therapeutic advances, the 5-year survival rate is 30% in bad responders to treatment or when pulmonary metastases are present at diagnosis. It is therefore urgent to better understand the molecular mechanisms involved in the development of OS in order to identify new therapeutic targets. As a major player in the stress response, it has recently been shown that the transcription factor HSF1 coordonates a stress-independent transcriptional program involving it in many pro-tumor biological processes in different cancers. A better understanding of the mechanisms by which HSF1 activity participates in tumor development is therefore essential to consider its therapeutic targeting. The co-partners of HSF1 to DNA, by modulating its transcriptional activity, could explain its pleiotropic effects. Based on this hypothesis, TRIM33 was identified by RIME. TRIM33 is known as a transcriptional cofactor and its involvement in various cancers. In this context, our objective is to study the interaction between TRIM33 and HSF1, their common genomic localization and to investigate the involvement of TRIM33 in the development of OS. Our results show that TRIM33 and HSF1 co-localize in the nucleus in OS TMA and by immuno-fluorescence in tumor cells and preclinical models. Furthermore, we observed by chIP-seq that TRIM33 and HSF1 share common DNA binding sites. Finally, our preliminary results show that TRIM33 invalidation by RNA interference in OS cell lines decreases tumor cell proliferation. Thus, in view of its role as a DNA partner of HSF1, TRIM33 is an interesting therapeutic target in OS.
This work was supported by la Fédération Enfants et Santé, la SFCE et La ligue Contre le Cancer (comités 44, 49)
Citation Format: Morgane Lallier, Robel Tefaye, Brice Moukengué, Céline Charrier, Rose-Anne Thepault, Benedicte Brounais-Le Royer, Marc Baud'huin, Franck Verrecchia, Benjamin Ory, François Lamoureux. TRIM33 interacts with HSF1 in osteosarcoma development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3902.
Abstract 3939: Preclinical development of embryonic ectoderm development (EED) inhibitor APG-5918/EEDi-5273 for cancer therapy
Authors: Zhu Saijie , Fang Douglas D. , Li Qiang , Yang Dongmei , Gu Shoulai , Wang Shaomeng , Yang Dajun , Zhai Yifan 
Published: June 2022

Abstract
Three core components constitute the polycomb repressive complex 2 (PRC2), a multiprotein complex that catalyzes methylation of histone H3 at lysine 27 (H3K27): (1) enhancer of zeste homolog 2 (EZH2), (2) EED, and (3) suppressor of zeste 12 protein homolog (SUZ12). Dysregulated function of PRC2 is implicated in the development of various cancer types. With regulatory approval of EZH2 inhibitor tazemetostat, a potentially effective successful cancer therapeutic strategy is now available for patients with epitheloid sarcoma and relapsed or refractory follicular lymphoma. However, EZH2 inhibitor activity might be reduced because of acquired resistance through secondary mutations in EZH2 or its inability to inhibit paralogs of EZH2 (including EZH1). Because binding of EED with trimethylated H3K27 (H3K27me3) is required to activate methyltransferase activity of EZH2, allosterically targeting EED is emerging as a novel approach to inhibit PRC2 (Qi et al, Nat Chem Biol 2017). APG-5918/EEDi-5273 is a well-documented, investigational, novel, bioactive, and potent EED inhibitor (Rej et al, JMC 2021). The aim of this study was to further characterize the anticancer therapeutic activity of APG-5918 in the preclinical setting.
APG-5918/EEDi-5273 showed high-affinity binding to EED protein in a biochemical assay (IC50 = 1.2 nM). It also exerted potent antiproliferative activity in several EZH2 mutant (EZH2mut) diffuse large B-cell lymphoma (DLBCL) cell lines, with IC50 values in the nanomolar range and inhibitory effects that were approximately 5 times lower than those with tazemetostat. In a mouse xenograft model derived from EZH2mut KARPAS-422 DLBCL cells, single-agent APG-5918 conferred potent and dose-dependent antitumor activity, resulting in durable complete tumor regression that correlated with inhibition of H3K27me3, induction of PRC2 target genes, and drug exposure in tumors. In summary, our results provide scientific rationale for the clinical development of APG-5918/EEDi-5273 in EZH2mut lymphomas and, potentially, other hematologic malignancies and solid tumors.
Citation Format: Saijie Zhu, Douglas D. Fang, Qiang Li, Dongmei Yang, Shoulai Gu, Shaomeng Wang, Dajun Yang, Yifan Zhai. Preclinical development of embryonic ectoderm development (EED) inhibitor APG-5918/EEDi-5273 for cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3939.
Abstract 3952: A novel Mcl-1 inhibitor induces cells death in a caspase-dependent manner and increases the efficacies of Venetoclax and ABT-737 in multiple myeloma cells
Authors: Al-Odat Omar S. , Tripathi Rahul S. , Srivastava Sandeep K. , Gowda Krishne , Amin Shantu G. , Budak-Alpdogan Tulin , Jonnalagadda Subash C. , Pandey Manoj K. 
Published: June 2022

Abstract
Multiple myeloma (MM) is a deadly malignancy of the blood, characterized by the uncontrolled proliferation of plasma cells. MM is challenging to diagnose and treat, accounting for approximately 12% of hematologic malignancies. The overexpression of anti-apoptotic proteins, particularly Myeloid cell leukemia 1 (Mcl-1), play a significant role in the pathogenesis of MM. The overexpression of Mcl-1 is associated with acquired resistance and poor prognosis. Thus, inhibition of the Mcl-1 protein is an attractive therapeutic strategy against myeloma cells. We synthesized and developed a novel Mcl-1 inhibitor, KS18. The preclinical testing of this novel agent is investigated in MM cell lines. Through docking studies, we predicted that KS18 interacts with Mcl-1. KS18 down-regulates the expression of Mcl-1 in MM cells in a dose- and time-dependent manner. Suppression of Mcl-1 expression by KS18 correlated with activation of caspases, PARP- cleavage, and apoptosis. However, this molecule had no effect on the expression of Bcl-2 and Bcl-xL proteins. Importantly, KS18 markedly enhances the efficacies of Venetoclax and ABT-737 in MM cells. Our results propose that targeting Mcl-1 by KS18 may represent a new viable strategy for MM treatment.
Citation Format: Omar S. Al-Odat, Rahul S. Tripathi, Sandeep K. Srivastava, Krishne Gowda, Shantu G. Amin, Tulin Budak-Alpdogan, Subash C. Jonnalagadda, Manoj K. Pandey. A novel Mcl-1 inhibitor induces cells death in a caspase-dependent manner and increases the efficacies of Venetoclax and ABT-737 in multiple myeloma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3952.