bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A56: Identification of circulating miRNA signatures in rectal cancer
Authors: Cervena Klara , Opattova Alena , Pardini Barbara , Naccarati Alessio , Vodicka Pavel , Vymetalkova Veronika 
Published: June 2020

Abstract
Colorectal cancer is the third most common cancer and the second leading cause of cancer death in Europe. Therefore, the search for new biomarkers to enable facilitate early diagnosis, prognosis, and individualized treatment is particularly warranted. From a clinical point of view, malignancies in the colon and the rectum (RC) present two distinct entities that require different treatment strategies, so CRC might not be considered as a single enteropathogenic entity. MicroRNA (miRNAs) are small noncoding RNA molecules involved in the post-transcriptional and translational regulation of gene expression. The discovery that miRNAs may act either as oncogenes or tumor suppressors has initiated extensive research. It was recently discovered that extracellular miRNAs circulate in the bloodstream and that such circulating miRNAs are remarkably stable. This has raised the possibility that miRNAs might serve as novel markers for disease diagnosis and prognosis. In the present study, we aimed to identify circulating miRNAs enabling early diagnosis and prognosis of RC. MiRNA expression levels (from plasma and plasma exosomes) were characterized by next-generation sequencing (NGS) in 24 patients with RC collected at 2-time intervals. The first sampling was collected at the time of diagnosis and the second sampling was conducted around 1 year after the diagnosis. The expression levels of miR-122 and miR-142 were identified to be associated with overall survival in RC patients. Their functional characteristics were tested in vitro on rectal cancer cell lines HRA16 and SW1463. Increased levels of miRNAs were associated with decreased long-term survival of cells. Identified miRNAs are currently being verified on a larger population of RC patients. This has raised the question whether miRNA can serve as biomarkers for rectal cancer, but prior to its clinical applications, clinical trials are warranted. Acknowledgments: This work was supported by AZV 17-30920A, GA17-16857S, and GA UK 302119.
Citation Format: Klara Cervena, Alena Opattova, Barbara Pardini, Alessio Naccarati, Pavel Vodicka, Veronika Vymetalkova. Identification of circulating miRNA signatures in rectal cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr A56.
Abstract B28: Large and polymorphonuclear circulating cancer-associated cell with dual epithelial and macrophage/myeloid phenotype as a liquid biomarker in non-small cell lung cancer patients
Authors: Manjunath Yariswamy , Avella Diego M. , Kimchi Eric T. , Staveley-O'Carroll Kevin F. , Deroche Chelsea B. , Li Gunagfu , Kaifi Jussuf T. 
Published: June 2020

Abstract
Purpose: In addition to the FDA-approved definition of a circulating tumor cell (CTC), various phenotypes of circulating cancer-associated cells in the blood have been described. A distinct large (&gt;30μm), polymorphonuclear, circulating, cancer-associated cell (CCAC) with a dual epithelial and macrophage/myeloid phenotype has been identified in solid cancer patients. The goal of the study was to identify and further characterize these hybrid CCACs in non-small cell lung cancer (NSCLC) patients.
Experimental Design: In a prospective trial, 7.5 mL of peripheral blood was collected from 167 subjects. CTCs and CCACs were isolated by size-based exclusion with a microfilter and immunofluorescence staining was performed (cytokeratin (CK) 8/18/19, EpCAM, CD14/45, DAPI).
Results: 78 NSCLC patients and 89 control subjects (69 chronic smokers with and without lung nodules on screening LDCT, 20 healthy never-smokers) were enrolled. Distinct, large, polymorphonuclear CKpos/EpCAMpos/CD14/45pos CCACs were detected at lower rates than traditional CKpos/EpCAMpos/CD45negCTCs, but significantly higher in subjects with NSCLC in comparison to controls (p&lt;0.05). These cells and traditional CTCs were absent in 20 healthy controls. In contrast to CTCs, counts of large and polymorphonuclear CCACs were not associated with tumor stages. However, ≥2 CCACs correlated with significantly poorer survival and higher recurrence rates by uni- and multivariate analysis (p&lt;0.05).
Conclusions and Future Perspectives: This study shows that in addition to CTCs, a distinct, large, polymorphonuclear CCAC with a dual epithelial and macrophage/myeloid phenotype is associated with an aggressive clinical behavior in NSCLC patients. The biologic role of these unique cells will need to be further investigated, as these may have a potential impact on the immune response towards the cancer.
Citation Format: Yariswamy Manjunath, Diego M. Avella, Eric T. Kimchi, Kevin F. Staveley-O'Carroll, Chelsea B. Deroche, Gunagfu Li, Jussuf T. Kaifi. Large and polymorphonuclear circulating cancer-associated cell with dual epithelial and macrophage/myeloid phenotype as a liquid biomarker in non-small cell lung cancer patients [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr B28.
Abstract B34: The number of tumorspheres cultured from peripheral blood is directly related to presence of metastasis in breast cancer patients
Authors: Pizon Monika , Schott Dorothea , Pachmann Ulrich , Pachmann Katharina 
Published: June 2020

Abstract
Background: Cancer stem cells (CSCs) are the critical subpopulation of cancer cells involved in tumor formation, progression, metastasis, and drug resistance. CSCs also have been considered the main cause of cancer recurrence, and the identification of targets and biomarkers is still under development. In this study, primary cultures from peripheral blood were established, using sphere-forming assays for CSC enrichment, and correlated with clinicopathologic features.
Methods: Circulating cancer stem cells were cultured under conditions favoring growth of tumorspheres from 72 patients with breast cancer, including a subpopulation of 23 patients with metastatic disease. Cell viability, stem cell marker expression, and ALDH 1 activity were evaluated by fluorescence scanning microscope (Olympus Scan®R).
Results: Sphere formation was observed in 79% of patients with breast cancer. In the current study we found that the number of tumorspheres depended on stage of disease. Patients with metastatic disease had statistically significantly more tumorspheres compared to patients without metastasis (median 30 vs. 10; p=0.002). Furthermore, patients with multiple metastases had more tumorspheres as compared to patients with single metastasis (median 30 vs. 60; p&lt;0.05). Analysis of surface marker expression profile of tumorspheres cultured from peripheral blood showed that spheres had typical phenotype of cancer stem cells with a high enzymatic activity for ALDH 1. There was no sphere formation in a control group with 20 healthy donors.
Conclusion: Identifying the circulating cancer stem cell may provide more clinically useful prognostic information and can be the basis for developing novel therapies.
Citation Format: Monika Pizon, Dorothea Schott, Ulrich Pachmann, Katharina Pachmann. The number of tumorspheres cultured from peripheral blood is directly related to presence of metastasis in breast cancer patients [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr B34.
Abstract B39: Changes in the number of residual circulating epithelial tumor cells (CETCs) and their programmed cell death ligand 1 (PD-L1) status during radiotherapy in breast cancer patients
Authors: Schott Dorothea , Pizon Monika , Pachmann Katharina , Pachmann Ulrich , Maeurer Matthias 
Published: June 2020

Abstract
Background: Preclinical studies have suggested that radiotherapy (RT) followed by immunotherapy could be a promising strategy for synergistic enhancement of treatment efficacy. RT induces immunogenic changes in cancer cells that can lead to adaptive upregulation of PD-L1 expression. Moreover, RT not only reduces local recurrence but also improves overall survival by preventing distant metastases, which indicates its influence on the remaining occult tumor, such as circulating tumor cells. For this reason, the aim of this study was to determine the PD-L1 status on CETCs before and during RT.
Methods: CETCs were determined in 54 primary breast cancer patients in early and locally advanced stages. The number of CETCs and their expression of PDL-L1 were investigated using the maintrac method. The fraction of PD-L1 positive CETCs was assessed prior to (baseline), 3 and 6 weeks after the start of RT.
Results: We found a correlation between the PD-L1 status of CETCs and aggressiveness of cancer disease prior to radiotherapy. Patients with positive lymph node status presented more PD-L1 positive CETCs compared to patients with negative lymph nodes (mean 73% vs. 50%, p&lt;0.01). Moreover, the HER2 expression of the primary tumor was also positively correlated with PD-L1 expression. Lower numbers of CETCs were detected in patients who had not received chemotherapy or adjuvant chemotherapy before RT than in those who received neoadjuvant chemotherapy (median 20 vs. 25 vs. 120 CETC/100μL blood, p&lt;0.001). Surprisingly, the fraction of PD-L1 positive CETCs decreased during radiotherapy only in patients who had received neoadjuvant chemotherapy.
Conclusion: Although the number of CETCs and the fraction of PD-L1 positive CETCs were higher in patients who had received neoadjuvant chemotherapy, radiotherapy reduced both measured biomarkers. In the future PD-1/PD-L1 checkpoint inhibitors after radiotherapy might have additional benefit in breast cancer patients.
Citation Format: Dorothea Schott, Monika Pizon, Katharina Pachmann, Ulrich Pachmann, Matthias Maeurer. Changes in the number of residual circulating epithelial tumor cells (CETCs) and their programmed cell death ligand 1 (PD-L1) status during radiotherapy in breast cancer patients [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr B39.
Abstract B53: Extracellular vesicle-based liquid biopsy via lipid-based nanoprobes
Authors: Zheng Siyang , He Hongzhang , Wang Faming , Wan Yuan 
Published: June 2020

Abstract
Extracellular vesicles (EVs) can mediate intercellular communication by transferring cargo proteins and nucleic acids between cells. The pathophysiologic roles and clinical value of EVs are under intense investigation, yet most studies are limited by technical challenges in the isolation of nanoscale EVs (nEVs). Here, we report a lipid-nanoprobe system that enables spontaneous labeling of nEVs for subsequent magnetic enrichment in 15 minutes, with isolation efficiency and cargo composition similar to what can be achieved by the much slower and bulkier method of ultracentrifugation. We also show that this approach allows for downstream analyses of nucleic acids and proteins, enabling the identification of EGFR and KRAS mutations following nEV isolation from the blood plasma of non-small cell lung cancer patients. The efficiency and versatility of the lipid-nanoprobe approach open up opportunities in point-of-care cancer diagnostics.
Citation Format: Siyang Zheng, Hongzhang He, Faming Wang, Yuan Wan. Extracellular vesicle-based liquid biopsy via lipid-based nanoprobes [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr B53.
Abstract B61: Encyclopedic noninvasive liquid biopsies for differential diagnosis in prostate cancer
Authors: Patil Darshana A. , Akolkar Dadasaheb , Patil Revati , Fulmali Pooja , Fulmali Pradip , Ainwale Akshay , Srivastava Navin , Datta Vineet , Sims Cynthe , Srinivasan Ajay , Datar Rajan 
Published: June 2020

Abstract
Differential diagnosis of prostatic adenocarcinomas is based on histopathologic analysis of tumor tissue obtained by transrectal ultrasound (TRUS)-guided biopsies. However, such invasive biopsies are associated with pain, procedural expenses, sequelae, and risk of complications. Though immunocytochemistry (ICC) profiling of circulating tumor cells (CTCs, defined as EpCAM+, panCK+, CD45-) has been previously attempted for diagnosis in some cancers, it has been unviable due to limited yields of CTCs. For the first time we used enrichment of CTCs that permit meaningful ICC profiling for diagnosis of prostate cancers in suspected cases as contradistinguished from cases of benign enlargement of prostate (BEP). We obtained 15 mL of venous blood draw from 650 individuals, of whom 65 had a confirmed diagnosis of either prostate adenocarcinoma and 585 were diagnosed with benign prostate hyperplasia. CTCs were enriched from PBMCs fraction using an epigenetically acting enrichment process that is lethal towards normal (nonmalignant) cells but confers survival privilege on apoptosis-resistant CTCs. Harvested CTCs were confirmed by immunostaining for EpCAM and pan-CK. ICC profiling of these CTCs was also performed with organ-specific markers PSMA and AMACR. Viable CTCs could be obtained from 58 samples (89.2%) out of 65 confirmed prostate cancer cases. Among the 40 samples that were characterized by deep ICC profiling, all samples (100%) were positive for PSMA and AMACR. Among the benign cases, CTCs were observed in 10 samples (1.7%), of which all 10 were positive for PSMA but negative for AMACR. These patients are being followed up. Possibility of other cancers is not ruled out in these patients. Our results show that ICC-based characterization of CTCs can provide necessary diagnostic information noninvasively to substitute for conventional procedures dependent on tissue extraction.
Citation Format: Darshana A. Patil, Dadasaheb Akolkar, Revati Patil, Pooja Fulmali, Pradip Fulmali, Akshay Ainwale, Navin Srivastava, Vineet Datta, Cynthe Sims, Ajay Srinivasan, Rajan Datar. Encyclopedic noninvasive liquid biopsies for differential diagnosis in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr B61.
Abstract IA11: Clinical applications of liquid biopsy in multiple myeloma
Authors: Trudel Suzanne , Pugh Trevor 
Published: June 2020

Abstract
Multiple myeloma (MM) is characterized by recurrent cytogenetic and molecular abnormalities that have the potential to profoundly impact therapeutic decisions. Conventional karyotyping and/or FISH cytogenetics studies have identified translocations and copy number abnormalities (CNAs) that predict clinical outcomes. More recently, MM whole-exome sequencing studies have uncovered recurrent mutations in genes associated with prognosis and others that are potentially actionable and/or implicated in drug resistance. These observations highlight the need for advanced genomic platforms to inform prognosis and therapeutic decisions.
Currently, molecular profiling of MM is performed on bone marrow (BM) aspirates; however, the genetic information obtained from aspirates is confounded by spatial and temporal intratumor genetic heterogeneity. Genomic studies of MM have confirmed the bias introduced by single-site biopsies, demonstrating that not all mutations are shared between targeted biopsies of extramedullary sites and BM. Further, longitudinal whole-genome sequencing studies have not only uncovered tumor heterogeneity at diagnosis but also subclonal competition with a shifting dominance of tumor clones and accumulation of genetic events during progression that are particularly affected by therapeutic pressures. Thus, information acquired from a single biopsy provides a spatially and temporally limited snapshot of a tumor that likely underestimates the complexity of the tumor genomic landscape.
Analysis of circulating tumor DNA (ctDNA) and in blood plasma has the potential to overcome these barriers, providing access to the genetic landscape of all cancerous lesions and allowing for noninvasive tracking of genomic evolution over time. Circulating biomarkers can provide a “liquid biopsy” alternative to tissue biopsy, providing new opportunities for treatment tailoring based on real-time monitoring from a simple blood test. Here I will discuss the current liquid biopsy technologies under evaluation for genomic characterization of multiple myeloma. I will also describe the potential clinical applications for liquid biopsies to identify patients for targeted therapies, to track genomic changes, and to follow disease burden in patients with multiple myeloma.
Citation Format: Suzanne Trudel, Trevor Pugh. Clinical applications of liquid biopsy in multiple myeloma [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr IA11.
Abstract IA12: Response in plasma cfDNA as an early marker of treatment effect in advanced cancer
Authors: Oxnard Geoffrey R. 
Published: June 2020

Abstract
Plasma cfDNA genotyping has been adopted widely as a tool for genotyping of advanced cancer at diagnosis and after treatment resistance. In addition, cfDNA genomics is a highly quantitative biomarker that could be used dynamically to evaluate the effective of a therapy. Our data point to the potential clinical meaning of changes in plasma mutation levels and support specific best practices regarding the clinical integration of this approach. In addition, these data allow us to envision a number of creative clinical applications for cfDNA-based response assessment. Finally, we must evaluate whether existing cfDNA genotyping technologies are well suited to this application, and whether new techniques must be considered in order to meet the practical requirements of a real-time clinical monitoring test.
Citation Format: Geoffrey R. Oxnard. Response in plasma cfDNA as an early marker of treatment effect in advanced cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr IA12.
Abstract IA14: Liquid biopsies for tracking molecular resistance in cancer
Authors: Dawson Sarah-Jane 
Published: June 2020

Abstract
Cell-free circulating tumor DNA (ctDNA) can be found in the bloodstream of cancer patients and is increasingly being explored as an important biomarker to monitor adaptive changes to cancer therapies. Cell-free DNA fragments from multiple lesions mix together in the peripheral blood; hence, ctDNA contains a wide representation of the genomes from multiple metastatic sites. For this reason, genome-wide analysis of ctDNA has the potential to provide an unprecedented insight into changes in the genomic landscape that occur during the development of disease and in response to cancer therapies. To date, the use of ctDNA to monitor the tumor landscape has been limited to tracking genomic evolution. However, it is now clear that cancers can also adapt to therapeutic pressure by significantly altering their transcriptome. Currently we have a limited understanding of how “nongenomic” transcriptional adaptation leads to clonal dominance or the evasion of cancer therapies. Here I will provide an overview of the use of ctDNA-based approaches to track both genomic evolution and transcriptional changes in real time to improve our understanding of the mechanisms leading to molecular resistance in cancer.
Citation Format: Sarah-Jane Dawson. Liquid biopsies for tracking molecular resistance in cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr IA14.
Abstract IA25: Detection of somatic mutations and HPV in saliva of patients with head and neck squamous cell carcinoma
Authors: Agrawal Nishant 
Published: June 2020

Abstract
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy in the world and is associated with significant morbidity and mortality. HNSCC develops in the oral cavity, pharynx, and larynx and is associated with tobacco exposure, alcohol abuse, and infection with oncogenic viruses. Despite numerous diagnostic and therapeutic advances, HNSCC often presents with advanced disease and the long-term survival for patients with HPV-negative SCC has remained ~55%. Conventional analysis of tissue through cytopathology or histopathology is the mainstay of diagnosis. There are no useful biomarkers for disease diagnosis or surveillance. The genetic landscape of HNSCC has demonstrated that these tumors are largely driven by tumor-suppressor mutations. The broad mutation spectrum detected in HNSCC by these sequencing studies not only sheds light on its molecular pathogenesis, but also serves as a molecular signature that is exquisitely specific to the individual tumor. Therefore, methods that use these molecular signatures and biomarkers and aid in improved screening/early detection, prognostication, monitoring, and surveillance are paramount for improving outcomes. We will explore tumor DNA (somatic mutations and HPV DNA) in saliva and plasma for screening, monitoring, and surveillance and outline resulting implications for personalized medicine. In HNSCC, analysis of tumor DNA has the potential to enhance tumor profiling, aid in determining patient prognosis, and guide treatment decisions.
Citation Format: Nishant Agrawal. Detection of somatic mutations and HPV in saliva of patients with head and neck squamous cell carcinoma [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr IA25.