bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5613: Tumor glucose metabolism profiles detected via [18F]-FDG PET/CT correlate with the immune landascape in soft-tissue sarcomas
Authors: Crombe Amandine , Bertolo Frédéric , Guegan Jean-Philippe , Bessede Alban , Perret Raul , Spalato-Ceruso Mariella , Toulmonde Maud , Laroche Audrey , Loarer Francois Le , Chaire Vanessa , Kind Michèle , Lucchesi Carlo , Italiano Antoine 
Published: April 2023

Abstract
Background: Improving the assessment of the immune landscape of soft-tissue sarcoma (STS) through imaging biomarkers could help better selecting and monitoring patients that could benefit from immunotherapy. Our aim was identify whether metabolic patterns of soft-tissue sarcoma (STS) on pre-treatment 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography (PET/CT) were associated with different immune profiles on molecular and cellular levels.
Methods: This single-center prospective study included consecutive adult patients with newly-diagnosed, non-metastatic, high-grade STS treated in a curative intent with available pre-treatement 18F-FDG-PET/CT. Maximal standardized uptake value (SUVmax), SUVpeak, SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were extracted. A cross-validated principal component analysis (PCA) was developed on the PET/CT metrics. The first two principal components (PC1 and PC2) and an unsupervised metabolic classifications were computed.
Differential gene expression (DGE), oncogenesis pathways analyses, complexity index in sarcoma (CINSARC) molecular signature and immunohistochemistry panels (CD8, CD14, CD20, CD45, CD68, c-MAF) were performed. Correlations between nuclear imaging, immunohistochemistry and transcriptomics data were achieved.
Results: 85 patients were included (median age: 62 years, 37 women) between 2016 and 2021. The robust PCA defined 3 metabolic groups (high [n=21], intermediate [n=15] and low [n=49]). PC1 reflected the tumor metabolism and PC2 the size and amount of necrosis. Transcriptomics and immunohistochemistry data were available in 32 and 31 patients, respectively. PC1 was significantly positively correlated with CINSARC (P=0.0029) and the cellular densities in CD8+, CD14+, CD45+, CD68+ and c-MAF (range of P-values: 0.0175-0.0499). The metabolic-high group was characterized by the upregulation of 13 immune pathways, including ICOS, CD27, IFNG, CXCL9-10/CXCL3 genes.
Conclusion: Metabolic profiles on 18F-FDG-PET/CT of high-grade STS highlights distinct immune profiles, which could pave the way for potential biomarkers of STS immunophenotyping.
Citation Format: Amandine Crombe, Frédéric Bertolo, Jean-Philippe Guegan, Alban Bessede, Raul Perret, Mariella Spalato-Ceruso, Maud Toulmonde, Audrey Laroche, Francois Le Loarer, Vanessa Chaire, Michèle Kind, Carlo Lucchesi, Antoine Italiano. Tumor glucose metabolism profiles detected via [18F]-FDG PET/CT correlate with the immune landascape in soft-tissue sarcomas. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5613.
Abstract 5631: Expanding tools for multiplex mRNA imaging in spatialomics through the ViewRNA tissue assay kits
Authors: Mooney Nancie 
Published: April 2023

Abstract
Spatialomics is a rapidly growing field as it allows researchers to gain a deeper understanding of transcriptomes and corresponding protein expression profiles in cells within complex tissue microenvironments. One critical technology for spatialomics is in-situ hybridization (ISH) technology, which enables direct visualization and quantitation of nucleic acid in cells with single molecule resolution. The Invitrogen ViewRNA ISH assays incorporate branched DNA (bDNA) technology provides tools for interrogating multiple RNA transcripts at the same time, paving the way for improved spatialomics research. This technology is a powerful tool for spatialomics, giving insight into important mechanisms within cells and tissue. With researchers increasingly using spatialomic data in fields like neuroscience, immuno-oncology & single-cell analysis, these scientists will need the rapid and efficient detection of mRNA co-expression profiles that ViewRNA portfolio provides. In our newest offering, ViewRNA fluorescence tissue kits we extended our branched DNA technology, proprietary probe set design and signal amplification technology with Alexa Fluor probes offering a unique, robust, and sensitive in situ hybridization assay for RNA localization in fixed tissues. With fluorescence detection using Alexa Fluor 488, Alexa Fluor 546, Alexa Fluor 594, Alexa Fluor 647, and Alexa Fluor 750, these kits allow multiplexed detection and imaging paving the way for improved spatialomics. This technology lays the foundation for expanded fluorescent profiles to provide scientists additional tools to probe multiple transcripts per sample, allow broader spatialomics research. For Research Use Only. Not for use in diagnostic procedures.
Citation Format: Nancie Mooney. Expanding tools for multiplex mRNA imaging in spatialomics through the ViewRNA tissue assay kits. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5631.
Abstract 5652: IL-19 blockade reprograms glioblastoma immunosuppressive microenvironment and overcomes chemo-resistance as revealed by single-cell transcriptome analyses
Authors: Lee Gilbert A. , Chen Cheng-Yu 
Published: April 2023

Abstract
Glioblastoma multiforme (GBM) is the most aggressive brain tumor with chemo-resistant, immunosuppressive, and invasive property. Despite the application of standard therapies which include a combination of surgery, radiotherapy, and temozolomide (TMZ) chemotherapy, tumor inevitably recurred (in patients) at peritumoral region. Targeting multiple arms of the GBM-mediated immunosuppressive ability and their invasiveness can improve therapeutic efficacy. Genomic screening identified that IL-19 is a predicted immune suppressive cytokine in peritumoral region and was associated with poor survival in patients with GBM. IL-19 blockade inhibited both TMZ-sensitive and resistant tumor progression. Molecular studies revealed that silencing IL-19 markedly abrogated IL-19-WISP1-AKT signaling to inhibit TMZ-resistant GBM cell invasion, as well as weaken its suppressive ability on CD8+T cell activation. Single cell transcriptome analysis revealed that IL-19 blockade promoted T cell activation, upregulated effector function of T cell subsets, and reprogrammed tumor-associated macrophage subsets toward a weakened pro-tumoral phenotypes. Thus, Targeting IL-19 can be a novel therapeutic strategy to reverse immunosuppressive microenvironment and restrict invasiveness of chemo-resistant GBM.
Citation Format: Gilbert A. Lee, Cheng-Yu Chen. IL-19 blockade reprograms glioblastoma immunosuppressive microenvironment and overcomes chemo-resistance as revealed by single-cell transcriptome analyses. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5652.
Abstract 570: Dual acting bone defender agents inhibit prostate cancer-mediated bone destruction
Authors: Qiao Fangfang , Gordon Ryan , Pattanayak Abhinandan , O’Neill Katelyn , Chaika Nina , Chen Weining , Rhatigan Rachel , Bergan Raymond 
Published: April 2023

Abstract
Introduction: Bone metastasis is clinically observed in approximately 90% of patients with advanced prostate cancer (PCa). Metastatic bone destruction is driven by a self-reinforcing process coupling osteoclast (OC)-mediated bone degradation to PCa growth, and where cell movement acts to keep these two cooperating cell types in close proximity and to move them across the bone surface. We sought to create a new class of therapeutics that would be highly effective at inhibiting PCa-mediated bone destruction by targeting both OC function and cell motility.
Methods: We synthesized new chemical entities, termed Dual Acting Bone Defender agents (DABDs), that couple the small molecule anti-motility agent, KBU2046, with bisphosphonate (bis), through a chemical linker. Assays for in vitro efficacy included: cell migration and invasion, binding to bone mineral, inhibiting osteoclast (OC)-mediated bone destruction, inhibition of Raf1 phosphorylation and inhibition of protein prenylation. In vivo assays included intra-cardiac (IC) injection of human PCa cells into mice, followed by real time monitoring of tumor growth and bone destruction by IVIS and CT imaging, respectively.
Findings: We successfully created a novel route of chemical synthesis allowing us to access and probe unique chemical space, providing for single small molecules with bis functional groups linked to a KBU2046 core through a linker moiety. DABDs retain the cellular and molecular characteristics of KBU2046 and bis. Like KBU2046, they inhibit PCa cell motility and phosphorylation of Raf1 on its activation motif. They also inhibit the motility of breast and lung cancer cells. Like bis, they inhibit OC-mediated bone mineral destruction, prenylation of Ras small GTPase proteins, and chemically bind hydroxyapatite. Administered prior to IC injection, DABDs are so effective that they prolong animal survival and inhibit bone destruction in a dose-dependent manner. In mice with established bone metastasis to the femur, after IC injection, DABDs inhibit the growth of tumors. Doses 3,000 fold higher than that required for efficacy had no clinical or critical organ toxicity.
Conclusions: DABDs represent a new multifunctional class of therapeutic agents that inhibit PCa-mediated bone destruction and have a high potential for advancing clinical efficacy in PCa patients with bone metastasis.
Citation Format: Fangfang Qiao, Ryan Gordon, Abhinandan Pattanayak, Katelyn O’Neill, Nina Chaika, Weining Chen, Rachel Rhatigan, Raymond Bergan. Dual acting bone defender agents inhibit prostate cancer-mediated bone destruction [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 570.
Abstract 5710: Detection and monitoring of t(11;14) in liquid biopsies from patients with relapsed/refractory multiple myeloma treated with venetoclax-based regimens
Authors: Li Xiaotong , Saal Lao H. , Brueffer Christian , Chen Yilun , Asklin Johanna , Alvi Saman , Venkatram Srinivas , Ross Jeremy A. 
Published: April 2023

Abstract
Venetoclax (Ven) is a selective B-cell lymphoma 2 inhibitor being studied in t(11;14)+ relapsed/refractory multiple myeloma (MM) Detection of t(11;14) in MM requires bone marrow (BM) aspiration and evaluation of CD138+ plasma cells by fluorescence in situ hybridization (FISH) Innovative techniques may provide less invasive detection of t(11;14) in liquid biopsies Here we present results of the SAGAsign® integrated approach combining low-coverage whole-genome sequencing (WGS) to characterize t(11;14) breakpoints together with personalized digital polymerase chain reaction (dPCR) assays to efficiently detect and monitor the genomic rearrangements in circulating tumor DNA (ctDNA) Baseline BM aspirates were collected from 270 patients (pts) from Ven clinical trials (NCT02755597, NCT01794520, NCT03314181, NCT02899052) Previously generated WGS to an average coverage ~22 × was used Paired samples of peripheral blood mononuclear cell (PBMC) DNA and plasma circulating cell-free DNA (cfDNA) were analyzed by dPCR at timepoints after Ven-based treatment Of the 90 t(11;14)+ pts by FISH, 160 t(11;14) breakpoints were identified by WGS in 74 pts (concordance in Table) At the time of data cutoff, dPCR assays were designed and evaluated in 8 t(11;14)+ pts; 7/8 (88%) and 6/8 (75%) pts had detectable t(11;14) in cfDNA or PBMCs, respectively Higher levels of t(11;14) mutant allele frequency (MAF) were observed in cfDNA compared with PBMCs After Ven-based treatment, t(11;14) MAF in cfDNA became undetectable in pts with a complete response In conclusion, this approach has the capability to reconstruct t(11;14) breakpoints from WGS data that is highly concordant with FISH; translocations appear more readily detectable in cfDNA than PBMC samples from pts with MM SAGAsign assays detected and monitored t(11;14) in liquid biopsies thus highlighting its potential utility for identifying pts with t(11;14) for targeted therapies
Concordance between WGS and FISH testing for t(11;14) Samples, n FISH+ FISH− Total WGS+ 74 11 83 WGS− 16 169 187 Total 90 180 270 Concordance, % n/N 95% CI t(11;14) positive 82.2 74/90 72.7-89.5 t(11;14) negative 93.9 169/180 89.3-96.9 Overall testing 90.0 243/270 85.8-93.3
Citation Format: Xiaotong Li, Lao H. Saal, Christian Brueffer, Yilun Chen, Johanna Asklin, Saman Alvi, Srinivas Venkatram, Jeremy A. Ross. Detection and monitoring of t(11;14) in liquid biopsies from patients with relapsed/refractory multiple myeloma treated with venetoclax-based regimens. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5710.
Abstract 5753: RUNX3 disrupts MYC/MAX complex and promotes MYC degradation
Authors: Ito Yoshiaki , Oei Vincent , Chuang Linda , Matsuo Junichi , Srivastava Supriya , Teh Ming 
Published: April 2023

Abstract
We reported earlier that heterozygous deletion of RUNX3 in the mouse induces adenoma in small intestine, mammary gland (1) and lung (2) and a precancerous stomach epithelium that is highly sensitive to a chemical carcinogen (3). We therefore propose that RUNX3 is a gatekeeper of cancer development (1).
In our recent study on how RUNX3 inhibits early-stage cancer development in multiple tissues, we uncovered a previously unknown mode of MYC destabilization by RUNX3. From RNA sequencing, knockdown experiments, tumorigenic assays, protein interaction and ubiquitination studies, we show that the strong inhibitory effects of RUNX3 on proliferation and tumor growth may, in part, be attributed to its ability to promote MYC degradation. The evolutionarily conserved Runt domain of RUNX3 interacts directly with the basic helix-loop-helix leucine zipper of MYC, resulting in the disruption of MYC/MAX interaction, enhanced GSK3β-mediated phosphorylation of MYC protein at threonine-58 and its subsequent degradation via the ubiquitin-proteasomal pathway (4). MYC inhibitor Omomyc, a short peptide comprising the b HLH LZ domain of MYC with 4 amino acid substitutions, is extremely effective in disrupting MYC/MAX interaction (5). RUNX3 appears to function similarly to Omomyc: is RUNX3 a Nature-designed Omomyc?
References:(1) Ito K et al, Cancer Cell 14;226-237, 2008; (2) Lee YS et al, Cancer Cell 24: 603-616, 2013; (3) Ito K et al, Gastroenterol 140:1536-1546, 2011; (4) Oei V, Chuang LSH, et al, Submitted; (5) Soucek et al, Nature 455:679-683, 2008
Citation Format: Yoshiaki Ito, Vincent Oei, Linda Chuang, Junichi Matsuo, Supriya Srivastava, Ming Teh. RUNX3 disrupts MYC/MAX complex and promotes MYC degradation. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5753.
Abstract 5767: Pan-viral response in African Americans and European Americans with hepatocellular carcinoma
Authors: Ewa Theressa , Do Whitney L. , Wang Limin , Forgues Marshonna , Wang Xin W. 
Published: April 2023

Abstract
Hepatocellular carcinoma (HCC) is often diagnosed at late-stages, with African Americans (AA) being diagnosed at a later stage with worse prognosis and high mortality rates. The poor screening and diagnosis of HCC and differences between racial/ethnic groups show a disproportion in mortality rates. Examining an individual’s viral exposure history might serve as a useful biomarker of early disease that could address and, potentially, alleviate this disparity. We aim to investigate whether viral features can be used to identify HCC and individuals at high risk (HR) of HCC. Additionally, we examine the racial/ethnic differences in viral exposures and whether viral exposure history accounts for epidemiological disparity described previously. Herein we use a technique called VirScan, which conjugates Phage Immunoprecipitation sequencing (PhIP-seq) and DNA sequencing, to profile an individual’s epitope antibody repertoire upon viral exposure. We performed VirScan on serum and plasma samples from 199 AA (130 HR and 79 HCC) and 260 European Americans (EA) (210 HR and 50 HCC) participants from the NCI-UMD cohort (NCT00913757; clinicaltrials.gov). We used a machine-learning XGBoost model to classify viral features that can discriminate HCC or HR. A composite viral score was generated using the SHAP value of the most significant viral features from the model with a higher score more predictive of HCC. Secondary analyses using Wilcoxon-Rank sums tests and Cox proportional hazard analysis revealed that while race/ethnicity did not differentially predict HCC in this cohort, the viral score was significantly higher in AA compared to EA in the HR group (p = 0.027). XGBoost search identified 235 important viral features which distinguish HCC from HR. Out of the 235 viral features, 20 viruses were different between AA and EA (FDR &lt; 0.05). We also found the viral score was positively associated with incident mortality in HCC group over the study period of 8 years (p=0.03). Thus, we demonstrate that the viral history of an individual might be useful in early detection of HCC. This approach could be used to account for the disparities we see in both incidence and mortality of HCC between AA and EA.
Citation Format: Theressa Ewa, Whitney L. Do, Limin Wang, Marshonna Forgues, Xin W. Wang. Pan-viral response in African Americans and European Americans with hepatocellular carcinoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5767.
Abstract 5841: Exploring the role of versican in immune exclusion within triple negative breast cancer
Authors: Hirani Priyanka , Alonge Kimberly M. , Pennington Daniel J. , Cutillas Pedro R. , Wight Thomas N. , Pearce Oliver M. 
Published: April 2023

Abstract
Immunotherapy has found limited success in solid tumors such as triple negative breast cancer (TNBC). The poor response can be attributed to the presence of the extracellular matrix (ECM) that can act biochemically or physically to interfere with cytotoxic T cell migration, leading to a limitation in tumor cell killing. Through previous work on deconstructing this matrix and outlining the spatial arrangement of proteins, we were able to identify versican as a key protein in T cell location. Versican is a chondroitin sulfate proteoglycan and has multiple functions in the ECM due to its ability to bind many ECM components. Using immunohistochemistry in this study, we analyzed the localization of CD8+ T cells within human TNBC tissues to classify them as inflamed (tumorhi, stromahi), desert (tumorlo, stromalo) or immune excluded (tumorlo, stromahi). From the analysis of 26 tissues, nearly half were classified as immune excluded with most of the CD8+ T cells restricted to the stroma, whilst only a quarter were inflamed. When comparing this to versican accumulation we noticed that immune excluded tissues have significantly higher levels of versican in the tumor epithelium compared to inflamed tissues where versican is mostly found within the stroma. To investigate the function of versican’s structure, we carried out transwell migration assays using versican enriched protein treated with or without chondroitinase ABC and showed that the chondroitin sulfates attached to versican’s peptide backbone are an important factor towards T cell trafficking with a reduction in migration following chondroitinase ABC treatment. Comparison of versican levels to chondroitin sulfate via immunohistochemistry showed a positive correlation within inflamed tissues, however no correlation was observed in immune excluded tissues. Versican isoforms expression in TNBC tissues and cell lines was examined with qRT-PCR which showed that within all tissues and cell lines the V0 and V1 isoform are the highest expressed out of the 5 isoforms. Overall, in this work, we have found that versican is differentially expressed in excluded tissues in comparison to inflamed tissues. With chondroitin sulfate shown to play a major role in immune cell trafficking, understanding how it differs between inflamed and excluded tumors can help identify potential targets to improve immunotherapy response.
Citation Format: Priyanka Hirani, Kimberly M. Alonge, Daniel J. Pennington, Pedro R. Cutillas, Thomas N. Wight, Oliver M. Pearce. Exploring the role of versican in immune exclusion within triple negative breast cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5841.