bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 7412: METI: Deep profiling of tumor ecosystems by integrating cell morphology and spatial transcriptomics
Authors: Jiang Jiahui , Liu Yunhe , Qin Jiangjiang , Wu Jingjing , Chen Jianfeng , Pizzi Melissa , Segura Rossana , Yamashita Kohei , Xu Zhiyuan , Pei Guangsheng , Cho Kyung Serk , Chu Yanshuo , Sinjab Ansam , Peng Fuduan , Han Guangchun , Wang Ruiping , Yan Xinmiao , Dai Enyu , Li Mingyao , Futreal Andrew , Maitra Anirban , Lazar Alexander , Cheng Xiangdong , Kadara Humam , Ajani Jaffer , Jazaeri Amir , Hu Jian , Wang Linghua , Gao Jianjun
Published: March 2024

The recent progression in spatial transcriptomics (ST) offers invaluable perspectives on the structure and dynamics of cells within the tumor microenvironment (TME). Though several analytical tools exist for tasks like spatial clustering and spatially variable gene identification, most of them are general methods lacking consideration of histological features in spatial data analysis. This oversight compromises their performance and interpretability when studying the TME. Here, we introduce a computational framework, the Morphology-Enhanced Spatial Transcriptome Analysis Integrator (METI). METI provides a comprehensive framework for spatially mapping both cancer cells and various TME cells, robust stratification of cell type and transcriptional states, and cell co-localization analysis. By integrating spatial transcriptomics with cell morphology and curated gene signatures, METI deepens our insight into the molecular landscape and cellular interactions within tissues, paving the way for intricate studies of the TME and its consequential impacts. The performance of METI has been assessed using ST data derived from a range of tumor tissues, encompassing gastric, lung, and bladder cancers, and premalignant tissues. Throughout these varied tissues and conditions, METI consistently exhibited robust performance.

Citation Format: Jiahui Jiang, Yunhe Liu, Jiangjiang Qin, Jingjing Wu, Jianfeng Chen, Melissa Pizzi, Rossana Segura, Kohei Yamashita, Zhiyuan Xu, Guangsheng Pei, Kyung Serk Cho, Yanshuo Chu, Ansam Sinjab, Fuduan Peng, Guangchun Han, Ruiping Wang, Xinmiao Yan, Enyu Dai, Mingyao Li, Andrew Futreal, Anirban Maitra, Alexander Lazar, Xiangdong Cheng, Humam Kadara, Jaffer Ajani, Amir Jazaeri, Jian Hu, Linghua Wang, Jianjun Gao. METI: Deep profiling of tumor ecosystems by integrating cell morphology and spatial transcriptomics [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 7412.
Abstract 7422: Enabling biomarkers of chromosomal instability for tumor only targeted gene panel sequencing
Authors: Gómez-Sánchez David , Thompson Joe Sneath , Hernando Barbara , García-López Diego , de Galard Hector , Roy Abhipsa , Cullen Amy , Madrid Laura , Teles José , Piskorz Ania , Yip Jason , Cádiz Alice , Escobar-Rey Maria , Moreno-Vellisca Roberto , Carrizo Nuria , Álvarez Eva , Quintela-Fandino Miguel , Barbacid Mariano , Ramos-Paradas Javier , Coya Juan Manuel , Ferrer Irene , Zugazagoitia Jon , Paz-Ares Luis , Macintyre Geoff
Published: March 2024

Capture-based targeted sequencing is routinely used for small variant detection in cancer clinical care. Alongside targeted DNA, off-target DNA is also sequenced. These off-target reads are distributed across the genome, allowing for a whole genome copy number profile to be derived without the need for a SNP backbone. Here we present CopyRight, a method that generates robust genome-wide copy number profiles, which can be used for downstream chromosomal instability (CIN) quantification, overcoming various sources of technical noise with a novel approach that only requires a single tumor sample.

We analyzed a variety of capture-based NGS protocols using our novel computational method, including the TruSight Oncology 500 (TSO500) panel, and compared them to the current gold standard for genome-wide copy number profiling from FFPE tissues: shallow whole genome sequencing (sWGS). Comparable results were obtained from targeted sequencing depending on sample purity, preservation method, and read depth. Additionally, benchmarks of CopyRight against other computational algorithms show an improvement in performance without the need for a matched normal tissue, the usual drawback for other methods in the cancer field.

CIN signatures are a new set of emerging biomarkers that reflect the diversity of defective pathways that have operated in a tumor, which require robust genome-wide copy number profiles. These CIN signatures can be used to predict response to cytotoxic agents and targeted therapies and could ultimately help guide therapy selection in patients. As most clinical sequencing workflows rely on targeted sequencing, CopyRight can be included in current clinical assays, enabling CIN biomarker quantification with no extra technical or experimental requirements.

Citation Format: David Gómez-Sánchez, Joe Sneath Thompson, Barbara Hernando, Diego García-López, Hector de Galard, Abhipsa Roy, Amy Cullen, Laura Madrid, José Teles, Ania Piskorz, Jason Yip, Alice Cádiz, Maria Escobar-Rey, Roberto Moreno-Vellisca, Nuria Carrizo, Eva Álvarez, Miguel Quintela-Fandino, Mariano Barbacid, Javier Ramos-Paradas, Juan Manuel Coya, Irene Ferrer, Jon Zugazagoitia, Luis Paz-Ares, Geoff Macintyre. Enabling biomarkers of chromosomal instability for tumor only targeted gene panel sequencing [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 7422.
Abstract 7487: Construction of a reliable CTC detection method and validity evaluation of CTC markers in colorectal cancer
Authors: Takahashi Yusuke , Ijiri Yuichi , Fujino Shiki , Elnaz Nakhaei , Kishimoto Ayuko , Shirai Kentaro , Iwanaga Shigeki , Yanagida Masatoshi , Bhagat Ali Asgar , Miyoshi Norikatsu
Published: March 2024

Even in modern times when medical technology has advanced, cancer remains a life-threatening disease, and recurrence and metastasis are major issues in cancer treatment. The characteristics of cancer cells change with progression and treatment. Therefore, timely evaluation on their characteristics and decision on the treatment strategy are required. Circulating tumor cells (CTCs) are released into blood vessels in solid tumors and promote metastasis by circulating in the blood. CTCs are thus attractive targets for liquid biopsy and can provide useful information for selection of appropriate treatment. To obtain reliable results from CTC testing, it is important to prove that the detected cells are derived from cancerous tissue. In molecular tests targeting CTCs, it is still unclear whether the detected cells are derived from cancer tissue displaying genetic mutations. Aiming to establish reliable CTC testing, we have developed a simple method using molecular imaging flow cytometry to detect APC gene mutation together with Cytokeratin and Vimentin, which are epithelial-mesenchymal transition markers. Since, abnormalities in the APC gene are detected in 60-70% of colorectal cancer patients, detecting such mutations provides strong evidence that the detected cells are derived from cancerous tissue. Here, we show that upon evaluation of analytical performance of our method using cells isolated from cancerous tissue, our method showed high concordance rate against APC gene mutation. A clinical proof-of-concept using 5 mL of whole blood from colorectal cancer patients revealed that counts of cells with APC mutation in blood and cells with Cytokeratin and/or Vimentin expression in blood are highly correlated. Our results demonstrated a pathological stage-dependent increase in the count and frequency of Cytokeratin and/or Vimentin positive CTCs. We believe that our study not only establishes a practical approach for identifying CTCs in cancer patients but also provides potential implications in clinical practice, prognostic evaluation, and selection of treatment strategies.

Citation Format: Yusuke Takahashi, Yuichi Ijiri, Shiki Fujino, Nakhaei Elnaz, Ayuko Kishimoto, Kentaro Shirai, Shigeki Iwanaga, Masatoshi Yanagida, Ali Asgar Bhagat, Norikatsu Miyoshi. Construction of a reliable CTC detection method and validity evaluation of CTC markers in 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 7487.
Abstract 7489: Peripheral blood liquid biopsy for the screening of lung cancer
Authors: Seo Jiyoun , Shishido Stephanie N. , Mason Jeremy , Velasco Carmen Ruiz , Chen Andrew , Rothwell Dominic , Crosbie Phil , Hicks James , Dive Caroline , Kuhn Peter
Published: March 2024

Lung cancer is the second most common type of cancer in both men and women and the leading cause of cancer-related mortality. Unfortunately, most patients have advanced stages (stage III or IV) at the time of diagnosis and the only U.S. Preventive Services Task Force-recommended screening test, Low Dose CT scan (LDCT), has a high false-positive rate. Therefore, there is an urgent need for the early detection of lung cancer with better discrimination between individuals with lung cancer and those without. In this study, we demonstrate the capability of a non-enrichment-based liquid biopsy workflow, the High Definition Single Cell Assay (HDSCA) to be used as a complementary tool to the current screening methodology. The HDSCA workflow can detect circulating cells of epithelial, mesenchymal, endothelial, and hematological origin, as well as acellular events such as oncosomes. This allows the investigation of the broad spectrum of circulating rare events for the potential identification of biomarkers associated with lung cancer. We investigated 52 peripheral blood samples collected from the second annual screening round of Manchester’s 'Lung Health Check' pilot of a community-based lung cancer screening cohort. Of these, 7 were subsequently diagnosed with non-small cell lung cancer, 2 with small cell lung cancer, and 43 were deemed at high risk of developing lung cancer. We additionally investigated 60 peripheral blood samples from individuals with no known pathology to use as controls. Within the screening cohort, a number of single rare analytes were found to have statistically significant differences between the lung cancer, high-risk cohort, and normal blood donor samples, which can potentially be biomarkers used to differentiate the cohorts. We also built a multi-analyte patient-level classification model utilizing the rare cellular and acellular events that stratified lung cancer patients from the normal donor individuals and high-risk cohort with high accuracy. Our results demonstrate the potential of liquid biopsy as a complementary screening approach for lung cancer.

Citation Format: Jiyoun Seo, Stephanie N. Shishido, Jeremy Mason, Carmen Ruiz Velasco, Andrew Chen, Dominic Rothwell, Phil Crosbie, James Hicks, Caroline Dive, Peter Kuhn. Peripheral blood liquid biopsy for the screening of 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 7489.
Abstract 7545: Epigenetic plasticity in rewiring DNMT1/UHRF1-RB1- NFkB signaling circuit regulates asbestos-induced mesothelial malignant transformation
Authors: Xi Sichuan , Wu Xinwei , Straughan David M , Payabyab Eden C , Wang Haitao , Wang Ruihong , Zhang Mary , Carr Shamus R. , Hoang Chuong D. , Schrump David S.
Published: March 2024

The exact mechanisms underlying the causal relationship between asbestos exposure and malignant mesothelioma (MM) have yet to be elucidated. Widespread genomic and epigenomic alterations are being implicated in rewiring of oncogenic signaling networks which may contribute to initiation and progression of MM. In the present study, we examined the molecular profiles of mesothelial cells exposed to asbestos in-vitro and found that asbestos-induced activation of DNMT1/UHRF1 mediated epigenetic repression of RB1 in normal mesothelial cells as well as mesothelioma cells via promoter-specific methylation mechanisms. RB1, as a noncanonical transcription factor, was capable of also negatively modulating the transcriptional activities of DNMT1/UHRF1 mesothelium and mesothelioma. Functioning as one of the downstream effectors of RB1, NFkB was also involved in the transcriptional regulation of DNMT1/UHRF1 directly in a promoter-selective manner and played a pivotal role in the acute as well as chronic functional and phenotypic changes of mesothelial cells following asbestos exposure. Pharmacological interference of the dysregulated RB1-DNMT1/UHRF1- RB1-NFkB signaling circuit constitutively arrested the invasive growth of MPM cells. In-vivo studies using FVB genetic background wild-type and Bap1+/- mice further revealed involvement of epigenetically dysregulation of the RB1-DNMT1/UHRF1- RB1-NFkB signaling circuit during asbestos-induced malignant transformation of mesothelial cells. Taken together, our data are the first to describe that asbestos epigenetically rewires the RB1-DNMT1/UHRF1- RB1-NFkB signaling circuit during mesothelioma development and suggest potential novel strategies to reverse these epigenetic perturbations for MPM treatment in the clinic.

Citation Format: Sichuan Xi, Xinwei Wu, David M Straughan, Eden C Payabyab, Haitao Wang, Ruihong Wang, Mary Zhang, Shamus R. Carr, Chuong D. Hoang, David S. Schrump. Epigenetic plasticity in rewiring DNMT1/UHRF1-RB1- NFkB signaling circuit regulates asbestos-induced mesothelial malignant transformation [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 7545.
Abstract 7559: Multi-state gene cluster switches determining the adaptive mitochondrial and metabolic landscape of breast cancer
Authors: Menegollo Michela , Bentham Robert , Patani Neill , Stein Robert C. , Yuneva Mariia , Szabadkai Gyorgy
Published: March 2024

Adaptive metabolic switches are proposed to underlie conversions between cellular states during normal development as well as in cancer evolution, where they represent important therapeutic targets. However, the full spectrum, characteristics and regulation of existing metabolic switches are unknown. We propose that metabolic switches can be recognised by locating large alternating gene expression patterns and associate them with specific metabolic states. We developed a method to identify interspersed genesets by massive correlated biclustering (MCbiclust) and to predict their metabolic wiring. Testing the method on major breast cancer transcriptome datasets we discovered a series of gene sets with switch-like behaviour, predicting mitochondrial content, activity and central carbon fluxes in tumours associated with different switch positions. The predictions were experimentally validated by bioenergetic profiling and metabolic flux analysis of 13C-labelled substrates and were ultimately extended by geneset analysis to link metabolic alterations to cellular states, thus predicting tumour pathology, prognosis and chemosensitivity. The method is applicable to any large and heterogeneous transcriptome dataset to discover metabolic and associated pathophysiological states.

Citation Format: Michela Menegollo, Robert Bentham, Neill Patani, Robert C. Stein, Mariia Yuneva, Gyorgy Szabadkai. Multi-state gene cluster switches determining the adaptive mitochondrial and metabolic landscape of breast 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 7559.
Abstract 7583: Discovery of a potent small molecule MALT1 protease inhibitor for the treatment of cancer
Authors: Zhou Yuzhen , Fu Bang , Chen Jie , Cai Weidong , Sun Xiao , Li Yinlong , Ren Wei , Shen Qichao , Du Guolong , Zhou Xiaojun , Zou Zhengyao , Chen Haibo , Liu Xiaoyun , Yang Cheng , Liu Xiangyong , Guo Jing , Wu Hao , Ding Lieming , Wang Jiabing , Lan Hong
Published: March 2024

The paracaspase mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1), as the core component of CBM complex (CARD9/10/11/14-BCL10-MALT1), plays an essential role in activating the NF-κB pathway and regulating the cell proliferation, differentiation and immunity. Inhibiting of MALT1 is considered a promising therapeutic approach for the treatment of several non-Hodgkin B-cell lymphomas, chronic lymphocytic leukemia (CLL), solid tumors and autoimmune diseases. Herein, we report the discovery of a novel potent MALT1 allosteric inhibitor, BPI-530616, which strongly inhibited MALT1 protease activity with subnanomolar IC50, and low off-target activity on other proteases. BPI-530616 can inhibit the proliferation of B-cell diffuse large B-cell lymphoma (ABC-DLBCL) cell line, OCI-ly3, bearing CD79b and CARD11 mutations. The cell line is intrinsically resistant to covalent and non-covalent Bruton's Tyrosine Kinase (BTK) inhibitors. Meanwhile, BPI-530616 suppressed the cellular cytokine secretion (e.g.IL-10, IL-2) or MALT1 direct substrate cleavage (e.g. CYLD). In vivo, BPI-530616 dose-dependently suppressed tumor growth and inhibited the cleavage of CYLD in OCI-ly3 xenograft mouse model. To address the role of MALT1 inhibitor in the contest of immune-oncology, a CT26 syngeneic mouse model was set up. Oral administration of BPI-530616 exhibited a good antitumor effect comparable to that of the anti-PD1 antibody, with no observable adverse effects. Additionally, BPI-530616 displayed desirable drug-like properties, including low clearance and good oral bioavailability across multiple pre-clinical species. Taken together, our research has led to the discovery of a novel, potent, selective, and orally bioavailable small molecule MALT1 inhibitor, BPI-530616. It demonstrated anti-tumor efficacy in the DLBCL animal model and showed promising effects in an immune-oncology animal model.

Citation Format: Yuzhen Zhou, Bang Fu, Jie Chen, Weidong Cai, Xiao Sun, Yinlong Li, Wei Ren, Qichao Shen, Guolong Du, Xiaojun Zhou, Zhengyao Zou, Haibo Chen, Xiaoyun Liu, Cheng Yang, Xiangyong Liu, Jing Guo, Hao Wu, Lieming Ding, Jiabing Wang, Hong Lan. Discovery of a potent small molecule MALT1 protease inhibitor for the treatment of 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 7583.
Abstract 759: Soy protein diet changes metabolic profile in liver of 7,12-dimethylbenz(α)anthracene (DMBA)-induced mammary tumors in obese zucker rats
Authors: Hakkak Reza , Melnyk Stepan
Published: March 2024

Obesity is associated with the risk of certain types of cancers development including breast cancer. Previously, we reported that obesity increased mammary tumor development using obese Zucker rat model. Several studies have shown the health benefit of soy protein consumption. However, the effects of soy protein diet on liver of mammary tumor for oxidative stress and DNA reaction is less known. We used DMBA induced-mammary tumor model to investigate the effects of soy protein diet on pro-oxidative environment and oxidative DNA modification in liver of obese DMBA mammary tumors rats. Female obese zucker rats (n=45) were either fed casein as control (OC; n=20) or soy protein isolate (OS; n=25), received DMBA (65mg/kg BW) at the age 50 days and sacrificed 20 weeks later. We used HPLC-ECD, HPLC-UV and LC-MS techniques for liver metabolic analysis. Comparing liver of OS vs. OC, soy protein 1) decreased the level of Methionine (P<0.02), increased 2) free reduced Homocysteine (P<0.02), 3) S-Adenosylmethionine (SAM, P<0.03), 4) S-Adenosyhomocysteine (SAH, P<0.001) and 5) 5methyl-Cytosine (5mC, P<0.03). Also, soy protein decreased (P<0.003) level of free oxidized Glutathione (GSSG), increased (P<0.02) GSH/GSSG oxidative stress ratio, without any changes a level of free reduced Glutathione (GSH), followed decrease (P<0.04) in liver DNA level of 8-OH-Guanosine (8-OH-G) and level (P<0.02) of 5hmethyl-Cytosine (5hmC). Our results shows soy protein diet capable change liver metabolism: a. Modify a methylation status by increasing levels of SAM (universal methyl group donor) following global liver DNA hypermethylation (5mC), and SAH (methylases inhibitor); b. Alleviate level of oxidative stress in liver by decreasing level of GSSG (not active glutathione), increasing GSH/GSSG ratio (antioxidative capacities), following lower ROS liver DNA damages by decrease levels of 8-OH-G and 5hmC. In conclusion, using obese DMBA-induced mammary tumor Zucker rat model, soy diet making a complex and significantly modification of metabolic conditions in liver affecting both methionine cycle and transsulfuration metabolic pathways.

Citation Format: Reza Hakkak, Stepan Melnyk. Soy protein diet changes metabolic profile in liver of 7,12-dimethylbenz(α)anthracene (DMBA)-induced mammary tumors in obese zucker rats [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 759.
Abstract 7593: Photodynamic therapy improves therapeutic management of glioblastoma
Authors: Vasyliv Nazar , Williams Karin
Published: March 2024

Glioblastoma (GBM) remains a formidable challenge in the realm of oncology, primarily due to the limitations of the standard of care therapies. Photodynamic therapy (PDT), which exploits the light-activated potential of 5-aminolevulinic acid (5-ALA), emerges as a promising avenue to combat GBM. In this study, primary patient-derived cell lines, Ox5 core, and G7, served as critical subjects, exposed to light excitation at wavelengths of 410 nm, 528 nm, and 810 nm, both with and without 5-ALA (protoporphyrin IX). The central objective was to rigorously assess the efficacy of PDT, either with or without 5-ALA, in reducing cell viability and curtailing clonogenic expansion. This evaluation was performed within the context of the existing standard of care for GBM, encompassing Temozolomide (TMZ) and Radiotherapy. Our results unveiled striking insights into the potential of PDT as an innovative therapeutic strategy. Notably, Ox5 cells exhibited a remarkable reduction in viability, exceeding 70%, following exposure to PDT with 410 nm light and 5-ALA at a concentration of 50μM. A similar, albeit slightly less profound, effect was observed in G7 cells, with a viability decrease of more than 53%. These outcomes, meticulously quantified through the MTT viability assay (n=4), were reinforced by statistical significance, as indicated by p-values falling below 0.05 and, lower 0.001. Furthermore, clonogenic assays employing G7 cells provided an additional layer of evidence, demonstrating a substantial inhibition of clonogenic potential following PDT treatment with 410 nm light and 5-ALA. Immunohistochemistry techniques, particularly focusing on the cleaved caspase-3 marker, in both Ox5 core and G7 cells, underscoring the mechanistic basis of the observed cell death. In stark contrast, the conventional standard of care, involving TMZ monotherapy, was tested, and the results across four biological replicates were less significant. The relative viability of Ox5 and G7 cells exhibited no statistical significance, with p-values exceeding 0.05, implying a limited impact of this regimen on cell viability. Moreover, clonogenic assays conducted under the standard of care protocol (TMZ+/-Radiotherapy) unveiled the persistence of colonies, even at higher radiation doses of 4 and 6 Gy.In summary, PDT, specifically when implemented with 410 nm light and 5-ALA, represents a breakthrough strategy that leads to substantial cell death in both Ox5 and G7 cells. This compelling alternative therapy shines a hopeful light on the horizon of GBM treatment, providing a potentially transformative approach that can augment the current standard of care.

Citation Format: Nazar Vasyliv, Karin Williams. Photodynamic therapy improves therapeutic management of glioblastoma [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 7593.
Abstract 7620: Immuno-transcriptomic profiling of blood and tumor tissue identifies gene signatures associated with immunotherapy response in metastatic bladder cancer
Authors: Romero Pedro J. , Desponds Emma , Croci Davide , Wosika Victoria , Hadadi Noushin , Cost Sara Fonseca , Ciarloni Laura , Ongaro Marco , Zdimerova Hana , Leblond Marine M. , Hosseinian-Ehrensberger Sahar , Verdeil Grégory
Published: March 2024

Muscle-invasive bladder cancer (MIBC) accounts for 25% of bladder cancer cases. Despite the broader usage of immune checkpoint blockade targeting the PD-1/PD-L1 axis, the response rate and survival of patients remain low for this disease. Redirecting swiftly these patients toward alternative therapeutic strategies upon immunotherapy failure should be a priority. So far, no marker allows to precisely determine early outcome to the treatment.Blood-based biomarkers represent ideal candidates for the development of non-invasive immuno-oncology-based assays. However, to date, no blood biomarker has been validated to predict clinical response to immunotherapy. In this study, we used next generation sequencing (RNAseq) on bulk RNA extracted from whole blood and tumor samples in a pre-clinical MIBC mouse model. We aimed at identifying biomarkers associated with immunotherapy response and to assess the potential application of simple non-invasive blood biomarkers as therapeutic decision-making assay compared to tissue-based biomarkers. We established that circulating immune cells and the tumor microenvironment (TME) display highly organ-specific transcriptional responses to ICI. Interestingly, a common lymphocytic activation signature can be identified in both compartments associated with the efficient response to immunotherapy, including a blood specific CD8+ T cell activation/proliferation signature which predicts immunotherapy response.

Citation Format: Pedro J. Romero, Emma Desponds, Davide Croci, Victoria Wosika, Noushin Hadadi, Sara Fonseca Cost, Laura Ciarloni, Marco Ongaro, Hana Zdimerova, Marine M. Leblond, Sahar Hosseinian-Ehrensberger, Grégory Verdeil. Immuno-transcriptomic profiling of blood and tumor tissue identifies gene signatures associated with immunotherapy response in metastatic bladder 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 7620.
Abstract 789: GrafGen: Distance-Based Inference of Population Ancestry for Helicobacter pylori Genomes
Authors: Wheeler William , Wang Difei , Zhao Isaac , Jin Yumi , Rabkin Charles S.
Published: March 2024

BACKGROUND: The 1.67 megabase H. pylori genome contains ~143,000 biallelic single-nucleotide polymorphisms (SNP) with minor allele frequency > 1%. Confounding by population stratification is a major source of bias requiring adjustment in genome-wide association studies (GWAS). Previous model- and distance-based methods for bacterial genomes yield varying results depending upon which strains are included for comparison in analyses. We therefore developed a robust classification of H. pylori ancestry to facilitate generalizable inferences about disease associations. METHODS: GrafGen is an R software package adapted from the GrafPop tool for human ancestry (Jin et al., 2017; Jin et al., 2019). The underlying classification algorithm compares SNPs of an individual genome with frequencies in reference populations to estimate subject ancestry and ancestral proportions based on calculated genetic distances. Outputs incorporate visualization tools that provide natural geometric interpretation of population structure. RESULTS: Training data were obtained from the H. pylori Genome Project (HpGP), a global survey of 1011 H. pylori genomes collected across 51 countries (Thorell et al., 2023). Based on genetic distances, HpGP sequences clustered into nine mutually exclusive populations designated by their predominant geographic source. Previously published population assignments for a test set of 255 sequences obtained from GenBank mapped to specific GrafGen classifications (Table). GrafGen assignments based on randomly selected sets of 14,300 and 1430 SNPs were >97% and >90% identical, respectively, to those based on all 143,000 SNPs. CONCLUSIONS: GrafGen's universal categorization of H. pylori ancestry has utility for bacterial GWAS. The software code is publicly available for research on this important pathogen. Theoretically, the same algorithm can be implemented to infer ancestry of any single chromosome haploid species that has sufficient sequence data for references.

Citation Format: William Wheeler, Difei Wang, Isaac Zhao, Yumi Jin, Charles S. Rabkin. GrafGen: Distance-Based Inference of Population Ancestry for Helicobacter pylori Genomes [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 789.
Abstract 802: Molecular profile of gastric cancer in Hispanics living in Puerto Rico
Authors: Montes-Rodriguez Ingrid , Centeno-Girona Hilmaris , Rivera Noridza , Cruz-Correa Marcia
Published: March 2024

Gastric cancer (GC) is the 4th leading cause of cancer death globally. The incidence and mortality rates of GC differ dramatically between racial/ethnic groupings. In the United States (U.S.), Hispanics, non-Hispanic Blacks, and Asian or Pacific Islanders are more likely to be diagnosed with GC and have a higher mortality rate than non-Hispanic Whites. Among the Hispanic population living in Puerto Rico (PRH), GC ranks among the top ten leading causes of cancer death, whereas this malignancy is not a major cause of cancer mortality in the mainland U.S. Tumor profiling approaches have resulted in the discovery of actionable gene alterations, which serve as a guide for treatment strategies and ultimately enhance the overall survival rates of individuals diagnosed with cancer. However, descriptive information regarding the genetic mutational landscape of GC tumors from PRH is limited. This study aims to describe the genomic profile of GC tumors in PRH and to identify the most prevalent genetic mutations. We retrospectively examined GC tumor mutational profiles from 106 PRH that underwent NGS testing from 2015 to 2022 (provided by CARIS Life Sciences and the Precision Oncology Alliance). We compared PRH GC tumor somatic mutation prevalence to TCGA and the AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE), both available through the cBioPortal for Cancer Genomics. Descriptive statistics were performed to characterize the database. Among the top mutated genes for GC tumors in PRH were TP53 (54.1%, n=85), ARID1A (34.2%, n=73), KMT2D (30.5%, n=82), CDH1 (29.4%, n=85) and ZFHX3 (27.3%, n=55). The most frequent gene amplifications were ERBB2 (7.1%, n=84), KRAS (6.0%, n=84), and CCNE1 (4.9%, n=81). Compared to other datasets, PRH had significantly different mutational frequencies of GC driver genes like TP53, ARID1A, CDH1, and KMT2D. This study is the first to report PRH GC tumor mutational profiles and compare the mutational frequencies to other non-Hispanic and U.S. mainland Hispanic populations using TCGA and GENIE data sets. Furthermore, our study provides data on the specific mutational landscape for Hispanics with GC and the implications on therapeutic options and clinical outcomes. Developing new treatments for genomically diverse populations requires understanding the most common carcinogenic molecular pathways that affect Hispanics with GC.

Citation Format: Ingrid Montes-Rodriguez, Hilmaris Centeno-Girona, Noridza Rivera, Marcia Cruz-Correa. Molecular profile of gastric cancer in Hispanics living in Puerto Rico [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 802.
Abstract 84: StarBright Dyes: Fluorophores with superior performance for multiplexing in flow cytometry and Western blotting
Authors: Sanderson Sharon , Rosenwasser Oliver , Blundell Michael
Published: March 2024

New StarBrightTM Dyes from Bio-Rad are bright fluorescent fluorophores ideal for many antibody-based applications, for example, western blotting and flow cytometry. Traditional fluorophores can be dim, have high cross laser excitation, or don’t work with all protocols, leading to poor data. StarBright Dyes have been designed to address these pain points.

Western blotting secondary antibodies are available conjugated to StarBright Blue 700 and StarBright Blue 520 Dyes. Their brightness, the short exposure time required, and low background make them ideal for detection of a single target, or as shown here for multiplex detection of several proteins in combination with other common fluorophores.

For flow cytometry, we have a full range of 32 StarBright Dyes excited by the most common laser lines: 355 nm, 405 nm, 488 nm, 561 nm, or 640 nm. They are available conjugated to highly cited clones against common immunophenotyping targets. Data shown here on the ZE5 Cell Analyser demonstrates how the features of StarBright Dyes can improve multiplexing immunophenotyping data. They have narrow excitation and emission spectral profiles, which reduce compensation and spread. This, combined with their exceptional brightness, enables high resolution of cell populations. They work in all buffers and fixatives, so including them in existing panels does not require a change in protocol. They can also be premixed in a master mix for over six months with no loss in performance. Premixes are ideal when using the same panel over an extended period, such as in clinical and longitudinal studies, to ensure reproducible results, also saving time and money.

StarBright Dyes are ideal for multiplexing assays in both western blotting and flow cytometry.

BIO-RAD and STARBRIGHT are trademarks of Bio-Rad Laboratories, Inc. in certain jurisdictions. All trademarks used herein are the property of their respective owner.

Citation Format: Sharon Sanderson, Oliver Rosenwasser, Michael Blundell. StarBright Dyes: Fluorophores with superior performance for multiplexing in flow cytometry and Western blotting [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 84.
Immunoglobulin E-Mediated Food Sensitization in a Moroccan Pediatric Population with Celiac Disease
Authors: Ait Said Hasna , Elmoumou Lahcen , Guennouni Morad , Rherissi Bouchra , Oujamaa Ider , Eddehbi Fatima-ezzahra , Lamjadli Saad , Hazime Raja , Bourrahouat Aïcha , Ait Sab Imane , Admou Brahim , El Kadmiri Nadia
Published: March 2024

Introduction: Celiac disease is a chronic autoimmune disorder that occurs following the ingestion of gluten, in genetically predisposed individuals. Patients with celiac disease, especially children, are likely prone to develop allergic reactions to different food allergens. However, the relationship between food allergy and celiac disease remains not elucidated. The aim of this pioneering study was to evaluate the prevalence of allergic food sensitization in children with celiac disease in Morocco. Methods: A total of 57 children with confirmed celiac disease, including 25 males and 32 females with a mean age of 8.6 ± 4.4 years, underwent a food allergen-specific immunoglobulin E (IgE) screening. This screening was conducted using a multiparametric immunodot assay (Euroline Food “Maghreb,” Euroimmun). Statistical analysis was performed using R software. Results: Among the 57 cases tested, the overall rate of IgE-mediated sensitization to food allergens was found to be 48% (27/57), dominated by chicken, with 51.9% (14/27), followed by almond, 40.7% (11/27), sesame, 40.7% (11/27), potato 33.3% (9/27), and apple 18.5% (5/27). Of the s-IgE positive cases, 74% were sensitized at least to one allergen, 37% (10/27) were sensitized to both chicken and almond allergens. A significant correlation was observed between almond, sesame, chicken, and potato. Conclusion: The current study highlighted a high prevalence of food allergen sensitization in children with celiac disease. This underlines the potential benefit in screening for food allergy in celiac patients.
Found Footage: Some Thoughts
Authors: Le Grice Malcolm
Published: March 2024

Então, novamente em retrospecto, o que eu (intuitivamente) queria ou exigia do material de found footage? Primeiramente busquei uma qualidade de mistério sobre uma imagem - o que agora chamo de “latência” - encontrando algum aspecto da sequência que não foi visto ou intencionalmente colocado ali pelo diretor de fotografia original e que, quando em contexto, abriu significados novos e surpreendentes.
Found Footage / Objetos perdidos
Authors: Beauvais Yann
Published: March 2024

Historicamente, o recurso ao found footage remete em primeiro lugar ao cinema; no entanto, foi com o surgimento do vídeo e dos videocassetes domésticos que ele se expandiu a ponto de ser banalizado, uma vez que ficou mais fácil se apropriar de trechos de filmes e criar compilações pessoais, assim como já se fazia em áudio com as fitas cassete. Subitamente, estava ao alcance do espectador criar suas próprias montagens de filmes.
Muros brutalmente modernos: a supremacia do edifício híbrido na arquitetura paulista dos anos 1960
Authors: Bahima Carlos Fernando
Published: March 2024

La visión de una arquitectura con soportes específicos a imagen del Partenón capta los deseos de los arquitectos en relación a la construcción amurallada. En el Renacimiento, además de las columnas destacadas, la representación del esqueleto aparece entre las superficies: Brunelleschi en la Capilla Pazzi; Alberti en el Palacio Rucellai. A fines del siglo XIX, la armazón estructural finalmente se materializó: la estructura independiente con puntos de soportes hizo muros obsoletos. Durante su asimilación, Le Corbusier promovió una estructura independiente específica, del tipo propuesto en las casas Domino, sin vigas aparentes que comprometieran la libre disposición de los muros. En Brasil, la estructura tipo Dom-ino es entendida por Lucio Costa como preferida. Sin embargo, la preferencia no excluye arreglos híbridos con otras estructuras. En São Paulo, ejemplos híbridos del Brutalismo Paulista muestran la coexistencia de apoyos puntuales y continuos. Este artículo discute las transformaciones radicales de esta arquitectura no por su materialidad, caracterizada por la fascinación del hormigón aparente, sino por la ruptura de este sistema jerárquico. El muro es agente de mutación sistémica, con percepción híbrida - formal y constructiva. La investigación relaciona la importancia de las soluciones híbridas bajo tensiones entre el comportamiento estructural y las exigencias formales.
Fostering Reasoning in the Politically Disengaged: The Role of Deliberative Minipublics
Authors: Veri Francesco
Published: March 2024

Political engagement is vital to the functioning of democratic systems, yet a significant portion of the population remains disengaged from conventional political activities as voting. These individuals often lack the opportunities and motivation to cultivate their reasoning abilities for understanding politics. This study explores the potential of deliberative minipublics to foster the development of reasoning skills among those excluded from the political discourse. By focusing on individuals with low levels of political engagement, the study investigates three minipublics on the topic of climate change in Switzerland. Utilizing the Deliberative Reason Index, the analysis uncovers how dialogue-driven engagement can enhance political understanding and involvement. The results demonstrate the potential of deliberative practices to bridge the gap between the politically disengaged and the complex world of political participation, offering fresh insights into citizens’ capabilities to deliberate on intricate issues.
Omentin-1 inhibits the development of benign prostatic hyperplasia by attenuating local inflammation
Authors: Wang Yi-Yi , Zhu Guo-Qiang , Xia Kun , Zeng Hong-Bo , He Yun-Hui , Xie Hui , Wang Zhen-Xing , Xu Ran
Published: March 2024

Background

Benign prostatic hyperplasia (BPH) is a prevalent disease affecting elderly men, with chronic inflammation being a critical factor in its development. Omentin-1, also known as intelectin-1 (ITLN-1), is an anti-inflammatory protein primarily found in the epithelial cells of the small intestine. This study aimed to investigate the potential of ITLN-1 in mitigating BPH by modulating local inflammation in the prostate gland.

Methods

Our investigation involved two in vivo experimental models. Firstly, ITLN-1 knockout mice (Itln-1−/−) were used to study the absence of ITLN-1 in BPH development. Secondly, a testosterone propionate (TP)-induced BPH mouse model was treated with an ITLN-1 overexpressing adenovirus. We assessed BPH severity using prostate weight index and histological analysis, including H&E staining, immunohistochemistry, and enzyme-linked immunosorbent assay. In vitro, the impact of ITLN-1 on BPH-1 cell proliferation and inflammatory response was evaluated using cell proliferation assays and enzyme-linked immunosorbent assay.

Results

In vivo, Itln-1−/− mice exhibited elevated prostate weight index, enlarged lumen area, and higher TNF-α levels compared to wild-type littermates. In contrast, ITLN-1 overexpression in TP-induced BPH mice resulted in reduced prostate weight index, lumen area, and TNF-α levels. In vitro studies indicated that ITLN-1 suppressed the proliferation of prostate epithelial cells and reduced TNF-α production in macrophages, suggesting a mechanism involving the inhibition of macrophage-mediated inflammation.

Conclusion

The study demonstrates that ITLN-1 plays a significant role in inhibiting the development of BPH by reducing local inflammation in the prostate gland. These findings highlight the potential of ITLN-1 as a therapeutic target in the management of BPH.
HIHISIV: a database of gene expression in HIV and SIV host immune response
Authors: Costa Raquel L. , Gadelha Luiz , D’arc Mirela , Ribeiro-Alves Marcelo , Robertson David L. , Schwartz Jean-Marc , Soares Marcelo A. , Porto Fábio
Published: March 2024

In the battle of the host against lentiviral pathogenesis, the immune response is crucial. However, several questions remain unanswered about the interaction with different viruses and their influence on disease progression. The simian immunodeficiency virus (SIV) infecting nonhuman primates (NHP) is widely used as a model for the study of the human immunodeficiency virus (HIV) both because they are evolutionarily linked and because they share physiological and anatomical similarities that are largely explored to understand the disease progression. The HIHISIV database was developed to support researchers to integrate and evaluate the large number of transcriptional data associated with the presence/absence of the pathogen (SIV or HIV) and the host response (NHP and human). The datasets are composed of microarray and RNA-Seq gene expression data that were selected, curated, analyzed, enriched, and stored in a relational database. Six query templates comprise the main data analysis functions and the resulting information can be downloaded. The HIHISIV database, available at https://hihisiv.github.io, provides accurate resources for browsing and visualizing results and for more robust analyses of pre-existing data in transcriptome repositories.
Integrative proteomics and metabolomics data analysis exploring the mechanism of brain injury after cardiac surgery in chronic stress rats
Authors: Yan Haoqi , Wang Hongbai , Chen Wenlin , Jia Yuan , Yan Fuxia , Yuan Su
Published: March 2024

Objective

Preoperative chronic stress (CS) is associated with postoperative brain injury in patients undergoing open heart cardiac surgery. This research is to explore the potential molecular biological mechanisms of brain damage following cardiac surgery in preoperative CS rats by the analyses combining proteomics and metabolomics.

Methods

We constructed the chronic unpredictable stress (CUS) and cardiac surgery models in adult rats. We proved the brain injury in CUS cardiac surgery rats by Hematoxylin–Eosin (H&E) staining, followed by separating the hippocampal tissue and investigating the potential mechanisms of brain injury by the methods of data-independent acquisition proteomics and untargeted metabolomics.

Results

The signaling pathways of glycoproteins and metabolism of amino acids were the main possible mechanisms of brain injury in CUS rats following cardiac surgery according to the proteomics and metabolomics. In addition, the pathways of animo acids metabolism such as the pathways of lysine degradation and β-alanine metabolism may be the main mechanism of cardiac surgery related brain injury in preoperative CUS rats.

Conclusions

The pathways of animo acids metabolism such as lysine degradation and β-alanine metabolism may be the potential mechanisms of brain injury in CUS rats following cardiac surgery. We should focus on the varieties of bioproteins and metabolites in these pathways, and related changes in other signaling pathways induced by the two pathways.