bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2385: Targeting mannose receptor expression on macrophages for sentinel lymph node mapping in endometrial cancer: murine model
Authors: Cho Hyun-Woong , Jeon OK Hwa , Lee Sanghoon , Kim Hyun Koo , Lee Jae Kwan , Hong Jin Hwa 
Published: April 2023

Abstract
Background: Sentinel lymph node (SLN) mapping has been used in various cancer surgery including endometrial cancer as a targeted assessment tool for identifying lymph node metastases, an alternative for complete lymphadenectomy to minimize surgical morbidity. Neomannosyl human serum albumin (MSA) targets the macrophage mannose receptor CD206 which is highly expressed in metastatic lymph node. The aim of this study was to evaluate the effectiveness of indocyanine green-neomannosyl human serum albumin (MSA:ICG) which targets macrophage mannose receptor CD206 for SLN mapping.
Methods: LN targeting ability was examined on mouse footpad models of uterine cancer using MSA:ICG and ICG for comparison. Seven mice with uterine cancer and 2 mice without cancer as a control group were each assigned to MSA:ICG and ICG groups. After injection of tracers, fluorescence images were taken and SLN biopsy was done to confirm LN metastasis status. We compared the signal-to-background ratio (SBR) according to time.
Results: In both MSA:ICG and ICG group, 16 lymph nodes out of 18 were detected using fluorescence imaging (detection rate: 88.9%). Four lymph nodes in MSA:ICG group and 5 lymph nodes in ICG group were metastatic among 16 lymph node each group. Excluding lymph nodes that were not detected, the SBR after the injection of MSA:ICG group was significantly higher than ICG group in metastatic LN (MSA:ICG 4.36 vs ICG 3.07, p&lt;0.001), non-metastatic lymph nodes (MSA:ICG 3.11 vs ICG 1.93, p=0.001), and normal control lymph nodes (MSA:ICG 1.38 vs ICG 0.54, p&lt;0.001). Comparing signal intensity according to CD206 expression, there was no difference in SBR values between the two groups in patients without CD206 expression, but the MSA group had a statistically significantly higher SBR value than the ICG group (p&lt;0.001) in patients with CD206 moderate or high expression.
Conclusions: This study showed that MSA:ICG may be an effective tracer for sentinel lymph node mapping. In addition, the metastatic lymph nodes expressing CD206 showed higher signal than normal lymph nodes in MSA:ICG group, unlike in ICG group. Further studies using larger animal models and clinical trials are needed to confirm this result.
Citation Format: Hyun-Woong Cho, OK Hwa Jeon, Sanghoon Lee, Hyun Koo Kim, Jae Kwan Lee, Jin Hwa Hong. Targeting mannose receptor expression on macrophages for sentinel lymph node mapping in endometrial cancer: murine model [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 2385.
Abstract 2394: Activatable fluorogenic probe for two-photon imaging of heparanase in vivo
Authors: Rabinowitz Zachary , Wang Zhishen , Somers Johnathan , Liu Jun , Jiang Joyce , Zhang Nina , Cui Lina 
Published: April 2023

Abstract
Heparanase, an endo-β-glucuronidase, is the only known enzyme that is responsible for the cleavage of heparan sulfate chains of heparan sulfate proteoglycans. Its enzymatic activity plays a key role in remodeling and degradation of the extracellular matrix, generation of biologically active carbohydrate fragments, and liberation of effector molecules, such as growth factors and chemokines, that are bound to the heparan sulfate side chains. Overexpression of heparanase has been implicated in most types of cancers and various inflammatory diseases that usually involve extensive heparan sulfate degradation and extracellular matrix remodeling. In particular, the role of heparanase in cancer is highly significant as it regulates multiple biological activities that fosters tumor progression, angiogenesis, metastases. Consequently, heparanase has been considered a biological target for various therapeutic applications including anti-cancer drug development. However, one of the major challenges in this research area is the development of robust and feasible heparanase probes to study the enzymes’ fundamental biology in the extracellular matrix, to provide heparanase-targeted diagnostics, and to aid in drug discovery efforts. Our lab has been developing various small-molecule-based heparanase activatable probes, and we have successfully developed chemical strategies that allow sensitive detection of heparanase activity in various contexts. Two-photon microscopy allows for deeper tissue penetration, excellent spatial resolution, and efficient light detection with reduced photobleaching effects. Herein, we extend our chemical strategies to develop a heparanase-activatable two-photon fluorogenic probe for real-time detection of heparanase activity in animal models of highly-aggressive brain cancer using two-photon imaging.
Citation Format: Zachary Rabinowitz, Zhishen Wang, Johnathan Somers, Jun Liu, Joyce Jiang, Nina Zhang, Lina Cui. Activatable fluorogenic probe for two-photon imaging of heparanase in vivo [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 2394.
Abstract 2396: Longitudinal monitoring of stromal stiffness predicts immune escape in preclinical hepatocellular carcinoma
Authors: Minamiguchi Kiyoyuki , Cortes Andrea , Lopez Patricia Da Costa , Williams Malea , Anfossi Simone , Melancon Marites , Avritscher Rony 
Published: April 2023

Abstract
Background/Objectives: Increased tumor stiffness enhances disease progression and aggressiveness in several cancers. Stiffer extracellular tumor matrix hinders T cell trafficking and promotes immune escape. The interplay between liver tumor mechanical properties and hepatocellular immune cell landscape has not been fully investigated. The aim of our study is to correlate tumor stiffness quantified with shear wave elastography and tumor-infiltrating lymphocyte accumulation using a syngeneic orthotopic rat model of hepatocellular carcinoma (HCC).
Methods: Rat hepatoma cell line McA-RH7777 were implanted in the left liver lobe of Buffalo rats. Maximum tumor size and stiffness were evaluated 3 weeks after implantation (baseline) and weekly for 14 days using ultrasound. The maximum tumor size of each rat was evaluated on transverse view of B-mode ultrasound. The elasticity of each rat was evaluated by shear wave elastography (SWE), and SWE measurements were obtained at the maximum tumor size in m/s. A circular region of interest was put manually on the SWE images to calculate tumor stiffness. SWE was performed 3 times for each rat at each time point, and the mean value of tumor stiffness was used for analysis. After 14 days, tumors were harvested for histology and immune cell isolation. Isolated cells were stained with CD3, CD4, CD8, CD25, CD45, CD103, CD161, CD279 (PD-1), FOXP3, IL17A, and INF-g and submitted to spectral cytometry.
Results: Shear wave speed at baseline and at 14 days ranged from 1.95 to 3.07 m/s and from 2.25 to 3.26 m/s, respectively. The rate of longitudinal increase or decrease in tumor stiffness measured by SWE is inversely correlated with intratumoral infiltration of CD45+/CD3+, CD3+/CD8+ T cells and IFN-producing CD3+/CD8+ T cells (P=0.015, r=-0.62[-0.857, -0.15], P&lt;0.01, r=-0.74[-0.913, -0.346], P=0.02, r=-0.6[-0.859, -0.107]). Intratumoral CD3+/CD4+ T cells did not significantly correlate with the rate of change in stiffness but did correlate with the rate of change in tumor size measured by B-mode ultrasound (P=0.03, r=-0.58[-0.850, -0.0730]).
Conclusion: Our results confirm previous reports of immune escape in stiffer solid tumors in the context of HCC. Findings suggest that longitudinal monitoring of tumor stiffness can be useful for the assessment of immune cell infiltration.
Citation Format: Kiyoyuki Minamiguchi, Andrea Cortes, Patricia Da Costa Lopez, Malea Williams, Simone Anfossi, Marites Melancon, Rony Avritscher. Longitudinal monitoring of stromal stiffness predicts immune escape in preclinical 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 2396.
Abstract 2403: Divergent evolutionary response to multiple fractions of radiation (MF2) therapy in cervical cancer cell lines (CCCL)
Authors: Kelley Johanna , Durmaz Arda , Kuznicki Michelle , Petty Aaron , Scott Jacob , Vargas Roberto 
Published: April 2023

Abstract
Introduction: Treatment for locally-advanced cervical cancer is not currently tailored based on genomic markers of treatment response. We aim to explore the potential for differential evolutionary trajectories of radiation (RT) resistance throughout treatment using two in vitro models.
Methods: Sixteen cervical cancer cell lines ( CCCL) were exposed to 1.8 Gy fractions of RT radiation for five sequential days and the surviving fraction (MF2) calculated. Differential gene expression (DGE) was performed on pre and post - treatment samples. Partial least squares (PLS) regression was completed with MF2 as the endpoint . Protein-protein interaction (PPI) network and overrepresentation analysis of genes was also performed. Four CCCL (BOKU, SKG II SF, ME180, and HeLa) were serially exposed to 50 Gy of gamma radiation RT given in 2Gy fractions. Five evolutionary replicates and three passage-controls were maintained. The mean integral survival as a function of dose (AUC) was calculated and ANOVA analysis performed.
Results: MF2 as the phenotypic endpoint identified 19 DE genes. PLS identified histones (H4C8, H2BC18, H2BC4) as positively associated and transcriptional regulators (NR2F1, KALRN) as negatively associated with MF2 (Figure 1AB). PPI and Reactome Pathways also highlighted histone deacetylase pathways, nucleosome assembly and regulation of membrane potentials (Figure 1BC). Longitudinal treatment RT identified differential evolutionary trajectories between CCCL replicates. Two BOKU (p = 0.005 and 0.0090), one SKG II SF (p = 0.0146), and one ME180 (p = 0.0384) replicates became resistant. Four SKG II SF (p &lt; 0.0001), and two HeLa (p = 0.0005 and p = 0.0068) became more sensitive to radiationRT (1C).
Conclusion: Divergent evolutionary trajectories under therapeutic stress can be elicited using in vitro evolutionary experimentation with cervical cancer cell linesCCCL. Genomic correlation with divergent evolutionary trajectories may allow for the identification of real-time markers of resistance or sensitivity and allow for true RT radiotherapy personalization.
Citation Format: Johanna Kelley, Arda Durmaz, Michelle Kuznicki, Aaron Petty, Jacob Scott, Roberto Vargas. Divergent evolutionary response to multiple fractions of radiation (MF2) therapy in cervical cancer cell lines (CCCL) [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 2403.
Abstract 249: A novel suite of enzyme mixes enable robust hybrid capture sequencing from low quality FFPE DNA
Authors: Heider Margaret R. , Sun Jian , Sexton Brittany S. , Langhorst Bradley W. , Gray Andrew , Higgins Lauren , Chen Lixin , Apone Lynne , Evans Thomas C. , Nichols Nicole M. , Liu Pingfang 
Published: April 2023

Abstract
In cancer genomics, a common source of DNA is formalin-fixed, paraffin-embedded (FFPE) tissue from patient surgical samples, where in most cases high-quality fresh or frozen tissue samples are not available. FFPE DNA poses many notable challenges for preparing NGS libraries, including low input amounts and highly variable damage from fixation, storage, and extraction methods. Due to the high cost of sequencing and variability of coverage, regions of interest are often specifically enriched using hybrid capture-based approaches, but these methods require a high input of diverse, uniform DNA library to achieve the coverage required for somatic mutation identification in tumor samples. We developed a new DNA repair enzyme mix, enzymatic fragmentation mix, and library amplification PCR master mix, optimizing the activities of these mixes using FFPE samples ranging from DIN 1.8 to 6.8 to maximize yield, WGS library quality, and target enrichment library performance. Combining DNA damage repair and a novel enzymatic fragmentation mix upstream of library preparation reduced the false positive rate in somatic variant detection by repairing damage-derived mutations, and also improved the library yield, quality metrics (including mapping, chimeras, and properly-paired reads), complexity, coverage uniformity, and hybrid capture library quality metrics. The new PCR master mix boosts the library yield without compromising library quality in FFPE-derived samples, allowing flexibility in the PCR cycles used to accommodate high-throughput processing of FFPE samples of highly varied quality. This library prep workflow was evaluated with multiple sequencing platforms including Illumina, MGI, and Element Biosciences. This new suite of enzyme mixes allows even highly damaged FFPE samples to achieve high-quality libraries with sufficient input for hybrid capture. Increasing the useable reads and coverage enables robust detection of somatic variants as demonstrated using both reference standard DNA and patient-derived FFPE samples. Finally, the use of enzymatic fragmentation and a flexible PCR master mix make this FFPE library prep workflow compatible with high-throughput and automation-based workflows.
Citation Format: Margaret R. Heider, Jian Sun, Brittany S. Sexton, Bradley W. Langhorst, Andrew Gray, Lauren Higgins, Lixin Chen, Lynne Apone, Thomas C. Evans, Nicole M. Nichols, Pingfang Liu. A novel suite of enzyme mixes enable robust hybrid capture sequencing from low quality FFPE DNA [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 249.
Abstract 2494: Heterogeneous tumor-driven immune landscapes between lung adenocarcinomas in ever and never-smokers
Authors: Kang Xiaozheng , Wang Xin , Ji Liyan , Yan Bingfa , Gao Xuan , Xia Xuefeng , Hu Xingsheng 
Published: April 2023

Abstract
To depict the genomic and immune landscapes of lung adenocarcinomas (ADCs) in ever and never-smokers and guide the design of immunotherapy strategies, we applied multiple deconvolution methods that allow the identification of immune cell infiltration and immune pathway enrichment using a whole exome and transcriptome sequencing-based approach in 145 patient-matched lung ADC and non-malignant lung parenchymal tissue pairs from ever and never smokers in our in-house cohort. Results were subsequently validated by an external lung ADC cohort, including 108 never-smokers and 61 ever-smokers. Firstly, we showed that ever-smokers had an increased abundance of neutrophils and macrophage infiltration, an elevated antigen processing and presentation capacity, and activated T-cell-mediated immunity. Secondly, ever-smokers revealed elevated macrophages in acinar ADCs, decreased mast cells in lepidic ADCs, and increased neutrophils in papillary ADCs, suggesting the tumor-driven immune characteristic discrepancies among various pathologic subtypes of ADC. Thirdly, we identified mutational disparities in tumor mutation burdens, subclonal single nucleotide variants, and the predicted and expressed neoantigens between ever and never-smokers. The mutant gene KRAS preferably occurred in ever-smokers, further contributing to the infiltration of macrophages and expression of cytokines. The copy number variations of immune-related genes (NFIB, TNFAIP3) were identified as conferring to the dysregulated immune environment in ever-smokers. Moreover, a higher genomic instability index was observed in ever-smokers (p = 0.008). Fourthly, the neoantigen was significantly increased in ever-smoker lung ADCs without nodal disease. While DNA immunoediting preferably occurred in never-smokers. Notably, in lung ADC patients with nodal disease, ever-smokers exhibited slightly more homogenous mutations (p = 0.094), consistent with the evolutionary bottleneck during cancer progression. Finally, the lower immunoediting and higher microenvironment scores significantly determined the more prolonged progression-free survival in never-smokers (p &lt; 0.050). Our multiscale genomic and immune profiling analyses thus offer valuable knowledge of tumor-driven immune disparity arising from smoking and provide a robust solution to the rational design of immune therapies.
Citation Format: Xiaozheng Kang, Xin Wang, Liyan Ji, Bingfa Yan, Xuan Gao, Xuefeng Xia, Xingsheng Hu. Heterogeneous tumor-driven immune landscapes between lung adenocarcinomas in ever and never-smokers [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 2494.
Abstract 2508: Clinical significance of PARP7 (TIPARP) gene copy number alterations in human non-small cell and head & neck carcinomas
Authors: Ahumada Viviana A. , McEachern Kristen , Kuplast-Barr Kristy , Schalper Kurt Alex 
Published: April 2023

Abstract
Introduction: PARP7, encoded by the TIPARP gene, is a monoART involved in cellular stress responses and with immunomodulatory functions in cancer. The PARP7 gene is amplified in a subset of squamous cell carcinomas and ongoing clinical studies are assessing its role as anti-cancer therapeutic target (NCT04053673, NCT05127590) Here, we analyzed the frequency of PARP7 copy number alterations and its association with tumor immune microenvironment (TIME) features and outcomes in non-small cell lung cancer (NSCLC) and head & neck squamous-cell carcinoma (HNSCC) cohorts.
Methods: The PARP7 gene copy number and amplification was analyzed using a dual probe fluorescence in situ hybridization (FISH) assay in two retrospective cohorts of NSCLC (Cohort #1, n=124) and HNSCC (Cohort #2, n=83) represented in tissue microarray format. In a subset of cases, the PARP7 copy number was also studied using whole exome DNA sequencing. The TIME was assessed on consecutive tumor sections using a multiplexed quantitative immunofluorescence panel including the markers DAPI, cytokeratin, CD4, CD8 and PD-L1 coupled to computational pathology analysis. The association between the markers, with clinicopathologic variables and survival was studied.
Results: Increased PARP7 copy number (&gt;2 copies/cell) was identified in 55% of NSCLCs (85% of them of squamous-cell histology) and 76% of HNSCCs. A high copy number (&gt;3 copies/cell) was identified in 22% cases from both tumor type cohorts. After adjustment of the PARP7 gene copy number by the chromosome 3 centromeric probe (CEN3) signal, PARP7 amplification (&gt;1.5 PARP7/CEN3 signal) was detected in 22% of NSCLC cases and 34% of HNSCC. A higher number of cases with PARP7 copy number gains were identified using FISH than with whole exome DNA sequencing. No significant associations between the PARP7 gains/losses and major clinicopathologic variables were found. However, higher PARP7 copy number was associated with reduced CD8+ or CD4+ tumor infiltrating lymphocytes (TILs) and a numerically lower tumor PD-L1 protein levels in HNSCC. Elevated PARP7 copy number was associated with shorter overall survival in both studied tumor types.
Conclusion: Elevated PARP7 gene copy number identifies a subset of lung and head & neck squamous-cell carcinomas with unfavorable TIME features and adverse prognosis. Detection of PARP7 gene abnormalities using FISH in tumor biopsy samples is sensitive and has potential as a predictive biomarker.
Citation Format: Viviana A. Ahumada, Kristen McEachern, Kristy Kuplast-Barr, Kurt Alex Schalper. Clinical significance of PARP7 (TIPARP) gene copy number alterations in human non-small cell and head & neck carcinomas [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 2508.
Abstract 2516: Analysis of CLL Celllular Environment and Response (ACCER) is a novel method to understand the microenvironment in CLL
Authors: Gibson Spencer , Choquette Tricia , Henson Elizabeth S. , Yang Xioyan , Johnston James B. 
Published: April 2023

Abstract
Microenvironments such as lymph nodes and bone marrow allow chronic lymphocytic leukemia (CLL) cells to survive after drug treatments. There are limited methods to study the to study the contribution of the microenvironment. We have adapted a solid tumour microenvironment cell culture system that provides elements of the CLL microenvironment called Analysis of CLL Cellular Environment and Response (ACCER). We optimized the cell number for patient’s primary CLL cells and HS-5 human bone marrow stromal cell line that will give sufficient cell number and viability with the ACCER. We then determined the amount of collagen type 1 to give the best extracellular matrix to seed CLL cells to the membrane. Finally, we determined that ACCER provide CLL cell protection against cell death following treatment with fludarabine and ibrutinib compared to co-culture conditions. This describes novel microenvironment model to investigate factors that promote drug resistance and cell survival in CLL. In the future, this will further validate new treatment strategies to overcome microenvironmental CLL cell survival signals.
Citation Format: Spencer Gibson, Tricia Choquette, Elizabeth S. Henson, Xioyan Yang, James B. Johnston. Analysis of CLL Celllular Environment and Response (ACCER) is a novel method to understand the microenvironment in CLL [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 2516.