bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A16: The potential of circulating cell-free tumor DNA as a diagnostic marker of ovarian cancer
Authors: Yamamoto Misa , Sawada Kenjiro , Shimizu Aasa , Matsumoto Yuri , Kodama Michiko , Hashimoto Kae , Kimura Tadashi 
Published: June 2020

Abstract
Objective: Circulating cell-free tumor DNA (ctDNA) is fragmented DNA released from cancer cells into the circulation. Technological development of digital PCR allows us to detect a small quantity of ctDNA in the circulation, suggesting its possibility for a future noninvasive biomarker. The aim of this study is to pursue its potential as a diagnostic biomarker to detect ovarian cancer using patients’ plasma.
Methods: Twenty-five plasma samples from patients were collected before treatment. The corresponding tumors were also collected, and DNA was extracted. As nonmalignant controls, 10 samples were collected from patients with benign endometrial cysts. Three primers to detect PIK3CA mutations for endometriosis-related carcinoma and three primers to detect TP53 mutations for serous carcinoma were prepared. The presence of these mutations in ctDNA existing in patients’ plasma was confirmed with digital PCR method. PCR data were validated with tumor DNAs.
Results: There were 7 cases of clear cell carcinoma,1 endometrioid carcinoma, and 7 serous carcinoma. Among 8 patients with endometriosis-related cancers (clear cell and endometrioid), PIK3CA mutations in plasma were detected in 6 cases, while mutations were not detected in benign endometrial cysts. Among 7 patients with high-grade serous carcinoma, TP53 mutations in patients’ plasma were detected in all cases. The presence of these mutations was confirmed by tumor DNAs.
Conclusion: PIK3CA mutation in endometriosis-related cancer and p53 mutation in serous carcinoma were successfully detected in patients’ plasma, suggesting the potential of ctDNAs as a future noninvasive biomarker for ovarian cancer.
Citation Format: Misa Yamamoto, Kenjiro Sawada, Aasa Shimizu, Yuri Matsumoto, Michiko Kodama, Kae Hashimoto, Tadashi Kimura. The potential of circulating cell-free tumor DNA as a diagnostic marker of ovarian 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 A16.
Abstract A32: Clinical significance of liquid biopsy in glioblastoma patients through tissue analysis
Authors: Rana Rashmi , Acharya Rajesh , Chhabra Satnam Singh , Jain Sunila 
Published: June 2020

Abstract
Glioblastoma multiforme is the most fatal form of brain tumor, distinguished as an aggressive growth and assists annexing by cell relocation and mortification of extracellular matrix with average survival rate of approximately 6-14 months. The majority of patients suffer recurrence due to molecular heterogeneity of glioblastoma and deregulation of many signaling pathways involved in proliferation, survival, and apoptosis. However, genetic profiling of the tumor is shown to classify disease and therapy response. Although brain surgery is involved for tissue collection, repeated tumor biopsies may be necessary for accurate genotyping over the course of the disease. While the detection of circulating tumor DNA (ctDNA) in the blood of patients with primary brain tumors remains challenging, sequencing of ctDNA from the tissue may provide an alternative way to glioblastoma genotype with morbidity and lower cost. We therefore evaluated the depiction of the glioblastoma genome in tissue from 40 patients with glioblastoma. Here we demonstrated that tumor-derived DNA was detected in tissue from 40 patients and was associated with disease load and adverse effect. The genomic landscape of glioblastoma in the tissue included a broad spectrum of genetic alterations and directly resembled the genomes of tumor biopsies. Alterations that were found during tumorigenesis and mutations in the metabolic pathway gene isocitrate dehydrogenase (IDH1, IDH2) were shared in all matched ctDNA-positive tissue-tumor pairs, whereas growth factor receptor signaling pathways showed significant progress. The ability to monitor the evolution of the glioblastoma genome through an invasive technique could advance the clinical application and use of genotype-directed therapies for glioblastoma, one of the most aggressive human cancers.
Citation Format: Rashmi Rana, Rajesh Acharya, Satnam Singh Chhabra, Sunila Jain. Clinical significance of liquid biopsy in glioblastoma patients through tissue analysis [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 A32.
Abstract B04: Using PSA dynamics to forecast individual responses to intermittent androgen deprivation
Authors: Brady Renee , Enderling Heiko 
Published: June 2020

Abstract
Intermittent androgen-deprivation therapy (IADT) is an attractive treatment approach for biochemically recurrent prostate cancer (PCa), whereby cycling treatment on and off has been shown to limit toxicities and reduce cumulative dose. While IADT has been shown to delay the development of treatment resistance, underlying mechanisms and actionable biomarkers are required to accurately predict when resistance will emerge and how to maximally delay time to progression. We developed a quantitative framework to simulate the enrichment of prostate cancer stem cell dynamics during treatment as a plausible mechanism of resistance evolution. Using simulated dynamics of cancer stem cells and nonstem cancer cells, we derive longitudinal blood serum prostate-specific antigen (PSA) concentrations that were calibrated to and validated with data of 70 patients undergoing multiple cycles of IADT. Model analysis suggests that cancer stem cell proliferation patterns correlate with PSA dynamics and patient outcomes. Learning these dynamics adaptively from the earlier treatment cycles in individual patients can predict the evolution of resistance in subsequent IADT cycles with a predictive power of 90%, which warrants prospective evaluation in a clinical setting. The model is used to simulate and predict alternative treatment options. In particular, simulations show that response dynamics from the first IADT cycle can be used to identify patients who would benefit from concurrent docetaxel.
Citation Format: Renee Brady, Heiko Enderling. Using PSA dynamics to forecast individual responses to intermittent androgen deprivation [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 B04.
Abstract B06: Proteomic biomarker for detection of ovarian cancer using gynecologic liquid biopsy
Authors: Barnabas Georgina D. , Bahar-Shany Keren , Sapoznik Stav , Korach Jacob , Perri Tamar , Friedman Eitan , Stockheim David , Jakobson-Setton Ariella , Eitan Ram , Helpman Limor , Kadan Yfat , Aviel-Ronen Sarit , Harel Michal , Geiger Tamar , Levanon Keren 
Published: June 2020

Abstract
The vast majority of high-grade ovarian cancer (HGOC) patients are diagnosed at a metastatic stage, resulting in exceptionally low cure rates. Current screening options fail to improve mortality due to the absence of early-stage-specific biomarkers and the poor systemic representation of early-stage tumors. We postulated that a gynecologic liquid biopsy, such as utero-tubal lavage (UtL), may identify localized lesions better than systemic approaches of serum/plasma analysis. Furthermore, while mutation-based assays are challenged by the rarity of tumor DNA within nonmutated DNA, analyzing the proteomic profile may potentially enable earlier detection, as it reveals perturbations in both the tumor compartment as well as in its microenvironment. To attain deep proteomic coverage and overcome the high dynamic range of this body fluid, we isolated microvesicles and performed mass spectrometric proteomic analysis of the UtL samples. Liquid biopsies from HGOC patients (n=85), controls (n=183), and healthy BRCA mutation carriers (n=37), were divided into discovery and validation sets. Data-dependent analysis of the samples on the Q-Exactive mass spectrometer provided depth of 8,578 UtL proteins in total, and on average ~3,000 proteins per sample. We used support vector machine algorithms for sample classification, and crossed three feature-selection algorithms, to construct and validate a 9-protein classifier with 63% sensitivity and 73% specificity. The signature correctly identified all Stage I lesions and highlighted increased risk in healthy BRCA carriers. These results demonstrate the potential power of microvesicle-based proteomic biomarkers for early cancer diagnosis but require integration with other biomarker types for improved prediction.
Citation Format: Georgina D. Barnabas, Keren Bahar-Shany, Stav Sapoznik, Jacob Korach, Tamar Perri, Eitan Friedman, David Stockheim, Ariella Jakobson-Setton, Ram Eitan, Limor Helpman, Yfat Kadan, Sarit Aviel-Ronen, Michal Harel, Tamar Geiger, Keren Levanon. Proteomic biomarker for detection of ovarian cancer using gynecologic liquid biopsy [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 B06.
Abstract B08: Tumor-educated platelets for early prostate cancer diagnosis, and therapy stratification in patients with metastasized castration resistant prostate cancer
Authors: Tjon-Kon-Fat Lee-Ann , Köhn Linda , Best Myron , Lundholm Marie , Wurdinger Thomas , Widmark Anders , Thellenberg-Karlsson Camilla , Wikström Pernilla , Nilsson Jonas 
Published: June 2020

Abstract
One in every ten men diagnosed with prostate cancer will have metastases at some point, causing the high mortality of prostate cancer. Only earlier diagnosis has the chance to save those lives. However, correct therapy stratification may prolong the life of the patients without severely reducing the quality of life, thereby possibly turning a deadly disease into a chronic disease. For this to happen, we need predictive biomarkers that can be employed to longitudinally follow the disease in order to identify vulnerabilities and to monitor acquired resistance for personalized medicine. Using the platelet-enriched fraction of a blood sample, we here show that we can use the ability of platelets to sequester material during circulation to provide information derived from the tumor. This information could be used for early detection of prostate cancer. By using the platelet test in combination with PSA measurements, we may be able to rule out a majority of the false negatives associated with the PSA test. Furthermore, the platelet platform can be used in synergy with other biomarker sources such as circulating tumor DNA or protein biomarkers, providing the possibility to predict and monitor outcome of abiraterone therapy, and providing alternatives to the nonfunctional therapy by guiding therapy switching, in metastatic castration-resistant patients.
Citation Format: Lee-Ann Tjon-Kon-Fat, Linda Köhn, Myron Best, Marie Lundholm, Thomas Wurdinger, Anders Widmark, Camilla Thellenberg-Karlsson, Pernilla Wikström, Jonas Nilsson. Tumor-educated platelets for early prostate cancer diagnosis, and therapy stratification in patients with metastasized castration resistant 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 B08.
Abstract B11: Whole-exome sequencing analysis of urine transrenal tumor DNA in metastatic colorectal cancer patients
Authors: Crisafulli Giovanni , Mussolin Benedetta , Cassingena Andrea , Montone Monica , Bartolini Alice , Barault Ludovic , Martinetti Antonio , Morano Federica , Pietrantonio Filippo , Sartore-Bianchi Andrea , Siena Salvatore , Di Nicolatonio Federica , Marsoni Silvia , Bardelli Alberto , Siravegna Giulia 
Published: June 2020

Abstract
Background: The analysis of circulating free tumor DNA (ctDNA) in blood, commonly referred to as liquid biopsy, is being used to characterize patients with solid cancers. Tumor-specific genetic variants can also be present in DNA isolated from other body fluids such as urine. Unlike blood, urine sampling is noninvasive, can be self-performed, and allows recurrent longitudinal monitoring. The features of tumor DNA that clears from the glomerular filtration barrier (transrenal tumor DNA, hereafter trtDNA) are largely unexplored.
Patients and Methods: Specimens were collected from 24 patients with KRAS or BRAF mutant metastatic colorectal cancer (mCRC). Driver mutations were assessed by droplet digital PCR (ddPCR) in ctDNA from plasma and trtDNA from urine. Whole-exome sequencing (WES) was performed in DNA isolated from tissue, plasma, and urine.
Results: Out of the 24 CRC cases, only four had sufficient DNA to allow WES analyses in urine and plasma. We found that tumor alterations reside primarily in low-molecular-weight fragments. In patients where trtDNA was more than 2.69% of the urine-derived DNA, cancer-specific molecular alterations, mutational signatures, and copy number profiles identified in urine DNA are comparable with those detected in plasma ctDNA.
Conclusions: With current technologies, WES analysis of trtDNA is feasible in a small fraction of mCRC patients. Tumor-related genetic information is mainly present in shorter DNA fragments. Although the limited amounts of trtDNA pose analytical challenges, enrichment of low-molecular-weight DNA and optimized computational tools improve detection of tumor-specific genetic information in urine.
Citation Format: Giovanni Crisafulli, Benedetta Mussolin, Andrea Cassingena, Monica Montone, Alice Bartolini, Ludovic Barault, Antonio Martinetti, Federica Morano, Filippo Pietrantonio, Andrea Sartore-Bianchi, Salvatore Siena, Federica Di Nicolatonio, Silvia Marsoni, Alberto Bardelli, Giulia Siravegna. Whole-exome sequencing analysis of urine transrenal tumor DNA in metastatic colorectal 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 B11.
Abstract B16: Noninvasive liquid biopsies for guideline-compliant diagnostic assessment in ovarian cancers
Authors: Akolkar Dadasaheb B. , Patil Darshana , Patil Revati , Devhare Pradip , Fulmali Pradip , Fulmali Pooja , Patel Shoeb , Srivastava Navin , Datta Vineet , Sime Cynthe , Srinivasan Ajay , Datar Rajan 
Published: June 2020

Abstract
Diagnosis of ovarian adenocarcinomas is based on histopathologic analysis of tumor tissue obtained by invasive biopsies. However, invasive biopsies are associated with procedural expenses, sequelae, and risk of complications. Though immunocytochemistry (ICC) profiling of circulating tumor cells (CTCs, defined as EpCAM+, panCK+, CD45-) has been previously considered for diagnosis in some cancers, the attempts have been unsuccessful. We used a novel approach for enrichment of sufficient viable CTCs that permit meaningful ICC profiling for diagnosis of ovarian cancers in suspected cases. We obtained 15 mL of venous blood draw from 248 patients with confirmed diagnosis of ovarian cancer. PMBCs were isolated by centrifugation. CTCs were enriched from PBMC 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. Deep ICC profiling of these CTCs was performed with organ-specific markers CA125 and WT1 as well as P63 as a nonspecific marker. Viable CTCs could be obtained from 225 samples (90.7%) out of 248. Among the 100 samples characterized by deep ICC profiling, 70 samples (70%) were positive for CA125 and WT1. None of the samples was positive for P63. Our results show that ICC-based characterization of CTCs can provide necessary diagnostic information noninvasively to substitute conventional procedures dependent on tissue extraction.
Citation Format: Dadasaheb B. Akolkar, Darshana Patil, Revati Patil, Pradip Devhare, Pradip Fulmali, Pooja Fulmali, Shoeb Patel, Navin Srivastava, Vineet Datta, Cynthe Sime, Ajay Srinivasan, Rajan Datar. Noninvasive liquid biopsies for guideline-compliant diagnostic assessment in ovarian cancers [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 B16.
Abstract B17: An mRNA signature that accurately discerns gliomas from healthy individuals
Authors: Apurwa Sachin , Fulmali Pooja , Akolkar Dadasaheb , Patil Darshana , Pawar Sushant , Puranik Sneha , Todarwal Vipul , Ainwale Akshay , Devhare Pradip , Datta Vineet , Sims Cynthe , Srinivasan Ajay , Datar Rajan 
Published: June 2020

Abstract
Diagnosis of suspected cases of gliomas such as intracranial space-occupying lesions (ICSOLs) is based on histopathologic analysis of tumor tissue obtained by invasive biopsies, which are, however, associated with risk of serious complication, high rates of mortality, procedural expenses, sequelae, and other risks. Liquid biopsy (LB)-based noninvasive approaches for diagnosis of gliomas based on circulating tumor biomarkers in peripheral blood have hence gained considerable interest. We describe the discovery of a unique 20 exosomal mRNA signature that can discern gliomas from healthy individuals. We obtained 15 mL of peripheral blood by venous draw from 222 individuals, among whom 47 had confirmed diagnosis of gliomas and 175 were asymptomatic. Exosomes were enriched from peripheral blood and were used for isolation of mRNAs. Exosomal mRNAs were used for expression analysis of 20,802 gene transcripts, including 18,574 coding genes and 2,228 noncoding genes based on University of California Santa Cruz (UCSC) hg19 annotation. Differentially expressed mRNAs were analyzed using a machine learning algorithm to identify transcripts that were unique to or uniquely absent in known cases of gliomas and in healthy individuals. The machine learning algorithm identified a 20-mRNA signature that discerned gliomas from healthy individuals with high sensitivity (87%) and specificity (95%) with an overall accuracy of 94%. The differentially expressed transcripts included MST4, RARRES3, TARP, IL32, PPP3CC, RSL1D1, RSL24D1, EIF4B, ARHGEF3, DENND2D, EVL, SEC11A, RPL22L1, HIST1H1C, IRF8, SOS2, GLTSCR2, GIMAP7, HIST1H4D, and CDK11. These differentially expressed transcripts are potentially involved in various functions such as tumor suppression, protein phosphorylation-dephosphorylation, signal transduction (ligand binding), and cell cycle regulation. Our data indicate that exosomal mRNA profiling is a viable approach for discerning suspected cases of gliomas from healthy individuals. The noninvasive nature of this approach coupled with high sensitivity and specificity favor potential clinical application.
Citation Format: Sachin Apurwa, Pooja Fulmali, Dadasaheb Akolkar, Darshana Patil, Sushant Pawar, Sneha Puranik, Vipul Todarwal, Akshay Ainwale, Pradip Devhare, Vineet Datta, Cynthe Sims, Ajay Srinivasan, Rajan Datar. An mRNA signature that accurately discerns gliomas from healthy individuals [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 B17.
Abstract B23: PMN-MDSCs enhance CTC metastatic properties through reciprocal interactions via ROS/Notch/Nodal Nodal signaling
Authors: Sprouse Marc , Welte Thomas , Boral Debasish , Vishnoi Monika , Liu Haowen , Glitza-Oliva Isabella , Marchetti Dario 
Published: June 2020

Abstract
Intratumoral infiltration of myeloid-derived suppressor cells (MDSCs) is known to promote neoplastic growth by inhibiting the tumoricidal activity of T cells. However, direct interactions between patient-derived MDSCs and circulating tumors cells (CTCs) within the microenvironment of blood remain unexplored. Dissecting interplays between CTCs and circulatory MDSCs by heterotypic CTC/MDSC clustering is critical as a key mechanism to promote CTC survival and sustain the metastatic process. We characterized CTCs and polymorphonuclear-MDSCs (PMN-MDSCs) isolated in parallel from peripheral blood of metastatic melanoma and breast cancer patients by multiparametric flow cytometry. Transplantation of both cell populations in the systemic circulation of mice revealed significantly enhanced dissemination and metastasis in mice coinjected with CTCs and PMN-MDSCs compared to mice injected with CTCs or MDSCs alone. Notably, CTC/PMN-MDSC clusters were detected in vitro and in vivo either in patients’ blood or by longitudinal monitoring of blood from animals. This was coupled with in vitro coculturing of cell populations, demonstrating that CTCs formed physical clusters with PMN-MDSCs, and induced their protumorigenic differentiation through paracrine Nodal signaling, augmenting the production of reactive oxygen species (ROS) by PMN-MDSCs. These findings were validated by detecting significantly higher Nodal and ROS levels in blood of cancer patients in the presence of naïve, heterotypic CTC/PMN-MDSC clusters. Augmented PMN-MDSC ROS upregulated Notch1 receptor expression in CTCs through the ROS-NRF2-ARE axis, thus priming CTCs to respond to ligand-mediated (Jagged1) Notch activation. Jagged1-expressing PMN-MDSCs contributed to enhanced Notch activation in CTCs by engagement of Notch1 receptor. The reciprocity of CTC/PMN-MDSC bidirectional paracrine interactions and signaling was functionally validated in inhibitor-based analyses, demonstrating that combined Nodal and ROS inhibition abrogated CTC/PMN-MDSC interactions and led to a reduction of CTC survival and proliferation. This study provides seminal evidence showing that PMN-MDSCs, additive to their immunosuppressive roles, directly interact with CTCs and promote their dissemination and metastatic potency. Targeting CTC/PMN-MDSC heterotypic clusters and associated crosstalks can therefore represent a novel therapeutic avenue for limiting hematogenous spread of metastatic disease.
Citation Format: Marc Sprouse, Thomas Welte, Debasish Boral, Monika Vishnoi, Haowen Liu, Isabella Glitza-Oliva, Dario Marchetti. PMN-MDSCs enhance CTC metastatic properties through reciprocal interactions via ROS/Notch/Nodal Nodal signaling [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 B23.