bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1352: Serum neurofilament light (NfL), glial fibrillary acidic protein (GFAp) and tau protein are possible serum biomarkers for activity of brain metastases and gliomas
Authors: Porter Jason , Hepner Adriana , Pandey Manjari , Prouet Philippe , Hare Felicia , Nasir Syed S. , Boles Madison , Zetterberg Henrik , Blennow Kaj , Martin Michael 
Published: August 2019

Abstract
Introduction: While the morbidity and mortality attributable to gliomas and brain metastases is significant, there are currently no approved biomarkers for detecting and monitoring intracranial disease and imaging remains the primary modality. Blood levels of the neurofilament light (NfL) and tau, as well as glial fibrillary acidic protein (GFAp) show promise as biomarkers for brain injury. We therefore hypothesized that these biomarkers would correlate with CNS activity of gliomas and brain metastases.
Methods: Serum concentrtaions of NfL, tau and GFAp were measured using the ultrasensitive single molecule array (Simoa) technology (Quanterix, Lexington, MA). Levels of the three proteins were then correlated with status of gliomas and brain metastases in the patients. Statistical analysis was performed using GraphPad Prism7 and all p-values were 2-tailed with an accepted 2-sided alpha level of 0.05 as statistically significant.
Results: 36 patients were enrolled with varying malignancies. Both serum NfL and GFAp levels were significantly associated with the state of intracranial disease (ANOVA psNfL= 0.0307; ANOVA pGFAp=0.0348). In contrast, serum tau levels were discordant with brain involvement with cancer (ANOVA pTau= 0.1453).
Conclusion: Serum NfL and GFAp both apparently vary closely with presence and activity of gliomas and brain metastases. Our studies are among the first to identify possible candidate serum biomarkers for screening and monitoring cancer patients for CNS involvement with malignancy. Further studies in larger populations are needed to expand these findings.
Citation Format: Jason Porter, Adriana Hepner, Manjari Pandey, Philippe Prouet, Felicia Hare, Syed S. Nasir, Madison Boles, Henrik Zetterberg, Kaj Blennow, Michael Martin. Serum neurofilament light (NfL), glial fibrillary acidic protein (GFAp) and tau protein are possible serum biomarkers for activity of brain metastases and gliomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1352.
Abstract 1359: Detection of PD-L1 positive circulating tumor cells from patient with bladder cancer
Authors: Suh Yongjoon , Kim Seong-Kun , Lee Hye Seon , Jeong Yun-Gyu , Moon Jeong-Mi , Kim Myoung Shin , Jeon Byung Hee , Ha U-Syn 
Published: August 2019

Abstract
Immunotherapy with PD-L1 inhibitors greatly enhanced the clinical outcomes of patients with late stage metastatic bladder cancer. However, a concern has been raised in the front-line clinical use of PD-L1 inhibitors (permbrolizumab and atezolizumab) as a single treatment to PD-L1-low patients, due to a poorer overall survival compared with patients treated with plantinum-based chemotherapy. In accordance, reliable evaluation of PD-L1 expression is required for selecting patients relevant for treatment with PD-L1 inhibitors. However, due to the regional heterogeneity in primary tumor, evaluation of PD-L1 levels in tissue biopsy might be less reliable than the levels in circulating tumor cells (CTCs). Here, we developed the evaluating system of PD-L1 levels in CTCs isolated from the blood of patients with bladder cancer. Initially, CTCs were enriched by Smart Biopsy Cell Isolator (CytoGen), which utilizes the size-based gravity filtration for CTC isolation. The isolated CTCs were then validated with the expression of EpCAM, Vimentin and CK as well as a negative selection with CD45, and were analyzed for PD-L1 expression status by immunocytochemical staining. Using the evaluating system, we show that PD-L1 (+) cancer cell was efficiently recovered from the healthy human blood samples in a spike and recovery experiment. Furthermore, we evaluated PD-L1 expression status in CTCs isolated from ~25 patients with bladder cancer. Collectively, this study implicates the possibility that PD-L1 expression status could be analyzed at the levels of CTCs instead of the matching primary tumor tissue biopsy, probably with a better clinical diagnostic option.
Citation Format: Yongjoon Suh, Seong-Kun Kim, Hye Seon Lee, Yun-Gyu Jeong, Jeong-Mi Moon, Myoung Shin Kim, Byung Hee Jeon, U-Syn Ha. Detection of PD-L1 positive circulating tumor cells from patient with bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1359.
Abstract 1372: Detection of early stage pancreatic cancer using 5–hydroxymethylcytosine signatures in circulating cell free DNA
Authors: Collin Francois , Ning Yuhong , Guler Gulfem D. , Phillips Tierney , McCarthy Erin , Scott Aaron , Ellison Chris , Ku Chin-Jen , Chau Kim , Ashworth Alan , Quake Stephen R. , Levy Samuel 
Published: August 2019

Abstract
Pancreatic cancers are typically diagnosed at late stage where disease prognosis is poor as exemplified by a 5-year survival rate of 8.2%. Earlier diagnosis would be beneficial by enabling surgical resection or earlier application of therapeutic regimens. We investigated the detection of pancreatic ductal adenocarcinoma (PDAC) in a non-invasive manner by interrogating changes in 5-hydroxymethylated cytosines (5hmC) in circulating cell free DNA in the plasma of a PDAC cohort (n=51) in comparison with a non-cancer cohort (n=41). 5hmC profiles from PDAC and non-cancer samples were generated using a previously published modified hMe-Seal protocol that utilizes chemical labeling of 5hmC by β-glucosyltransferase and allows detection of cell free 5hmC from small amounts of cfDNA (1). We found that 5hmC sites are enriched in a disease and stage specific manner in exons, 3’UTRs and transcription termination sites. Our data show that 5hmC density is reduced in promoters and histone H3K4me3 associated sites with progressive disease suggesting increased transcriptional activity. 5hmC density is differentially represented in thousands of genes, and a stringently filtered set of the most significant genes points to biology related to pancreas (GATA4, GATA6, PROX1, ONECUT1) and/or cancer development (YAP1, TEAD1, PROX1, ONECUT1, ONECUT2, IGF1 and IGF2). Regularized regression models were built using 5hmC densities in a comprehensive set of genes with the most variable 5hmC counts and performed with an AUC = 0.94 - 0.96 on training data. We tested the ability to classify PDAC and non-cancer samples with the Elastic net and Lasso models on three independent pancreatic cancer 5hmC data sets (n = 26, 23 and 7) compared with corresponding independent non-cancer cohorts (n =103, 53 and 10), and found validation performance to be AUC = 0.74 - 0.97. The findings suggest that 5hmC changes enable classification of PDAC patients with high fidelity and are worthy of further investigation on larger cohorts of patient samples. Reference: 1. Song, C. - X. et al. 5 - Hydroxymethylcytosine signatures in cell-free DNA provide information about tumor types and stages. Cell Res 27, 1231 (2017).
Citation Format: Francois Collin, Yuhong Ning, Gulfem D. Guler, Tierney Phillips, Erin McCarthy, Aaron Scott, Chris Ellison, Chin-Jen Ku, Kim Chau, Alan Ashworth, Stephen R. Quake, Samuel Levy. Detection of early stage pancreatic cancer using 5–hydroxymethylcytosine signatures in circulating cell free DNA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1372.
Abstract 1382: Megakaryocyte potentiating factor as a predictive biomarker for therapies against malignant mesothelioma
Authors: Cao Liang , Yu Yunkai , Thomas Anish. , Zhang Jingli , Onda Masanori , Meltzer Paul , Hassan Raffit , Pastan Ira 
Published: August 2019

Abstract
Objectives: Effective biomarkers for malignant mesothelioma (MM) are needed for clinical management and the development of cell surface mesothelin-targeted therapies. We evaluated serum megakaryocyte potentiating factor (MPF) as a biomarker predictive of clinical outcome in MM patients, for patient monitoring, and for developing mesothelin-targeted therapies.
Patients and Methods: Serial serum samples from MM patients in two clinical trials of an anti-mesothelin immunotoxin were tested for serum MPF. For the purpose, we developed a new MPF assay and conducted both analytical and clinical validation. Correlative studies were performed to determine the test effectiveness in treatment monitoring and outcome prediction. MPF was further evaluated for an association with response to an anti-mesothelin therapy and for disease monitoring.
Results: Our data showed that in MM patients, elevated serum MPF is a predictor of poor survival with a hazard ratio (HR) = 2.46 (Log Rank P = 0.003; n = 95). In refractory MM patients, elevated MPF is a strong predictor of poor outcome with a HR = 6.12 (Log Rank P = 0.0007; n = 57). There was a significant reduction of serum MPF in patients with elevated baseline and radiological response, with an average change from -52% to -78% after 1 to 6 cycles. Using a -50% change as the cutoff, MM patients with a positive MPF-response had significantly improved progression-free survival (PFS) (P &lt; 0.0001), with median extended from 1.9 to 11.3 months. These MPF-response patients further exhibited improved overall survival (OS) (P = 0.004), with median extended from 8.8 to 22.3 months. In refractory MM patients, there was an association between elevated pre-treatment serum MPF and radiological response to an experimental anti-mesothelin therapy (P = 0.033). Furthermore, in these response patients, serum MPF was monitored between 32.2 and 63.8 months and found to reflect the response and disease progression.
Conclusion: In MM patients, elevated MPF was observed in 2/3rd of the patients and is a predictor for poor survival, throughout the course of the disease. Following systemic therapies, a &gt; -50% reduction in MPF was associated with improved clinical outcome, both PFS and OS. An elevated baseline serum MPF may be a predictor of response to an experimental anti-mesothelin therapy in refractory MM patients, however, the finding needs to be confirmed in a larger study.
Citation Format: Liang Cao, Yunkai Yu, Anish. Thomas, Jingli Zhang, Masanori Onda, Paul Meltzer, Raffit Hassan, Ira Pastan. Megakaryocyte potentiating factor as a predictive biomarker for therapies against malignant mesothelioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1382.
Abstract 1389: Single-cell sequencing to identify genetic variant accelerating shedding of CTCs into peripheral blood in gastric cancer patients
Authors: Li Yilin , Zhang Xiaotian , Gong Jifang , Wang Daisy Dandan , Qi Mingxia , Li Yanyan , Liu Dan , Wang Chunxiang , Lin Peter Ping , Shen Lin 
Published: August 2019

Abstract
Circulating tumor cells (CTCs) are shed from primary or metastatic tumors into blood circulation, which may carry specific genetic characteristics related to hematogenous metastasis. Drawbacks of conventional EpCAM or cell size-dependent CTC detection and relevant single-cell sequencing technologies have limited discovery of specific genetic variants in CTCs. In the current study, a novel integrated SE-iFISH strategy, despite cell size or epithelial marker status, was applied to detect CTCs in advanced gastric cancer (GC) patients. Obtained CTCs were classified into diverse subtypes upon different chromosome ploidy. Fifty-three aneuploid CTCs identified by iFISH in 6 of naïve GC patients were isolated by a novel non-laser microscopic single cell manipulator (NMSCM), and subjected to modified Multiple Displacement Amplification (MDA) and subsequent single-cell sequencing. Compared with the conventional PCR, MDA generates 2 to 100-kb products with a lower error rate and achieves high fidelity whole genome amplification. Sequencing targeting 50 tumor genes of single CTC as well as paired primary tumor specimens was performed. Moreover, leukocytes genomic DNA as germline controls were included. Obtained results showed that high frequent SNV in genes such as TP53 were detected in both CTCs and the paired primary tumor mass. Furthermore, CTCs had considerable
genetic heterogeneity compared to the paired primary tumor lesions. In particular, the CDKN2AA68V variant is frequently detected in CTCs but the paired primary GC tumor. We propose that the specific CDKN2AA68V variant carried by GC CTCs with high frequency, but low in the examined whole population of cancer cells in paired primary tumor lesions, may serve as the driver to promote CTCs shed into peripheral blood and to further facilitate hematogenous metastasis. Systematic in vitro and ex vivo studies are in progress to investigate roles of CDKN2A mutation in hematogenous dissemination in GC.
Citation Format: Yilin Li, Xiaotian Zhang, Jifang Gong, Daisy Dandan Wang, Mingxia Qi, Yanyan Li, Dan Liu, Chunxiang Wang, Peter Ping Lin, Lin Shen. Single-cell sequencing to identify genetic variant accelerating shedding of CTCs into peripheral blood in gastric cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1389.
Abstract 1391: Development of in vitro multiplex colorectal cancer associated mutation detection assay powered with xenonucleic acid
Authors: Sha Michael Y. , Lee Anna J. , Powell Michael J. , Zhang Aiguo 
Published: August 2019

Abstract
Precise detection of cancer associated mutations have many advantages including diagnosis and monitoring of the disease and monitoring development of drug resistance. However, unlike germline mutations, somatic mutations in cancer are found at a much lower frequency. For this reason it remains a challenge especially when trying to detect mutations from limited amount of patient tissue biopsy or liquid samples. Currently, detection and genotyping of these mutations is heavily dependent on deep NGS methods. These procedures, however, are costly and time consuming. Here, we developed an alternative high-throughput method that combines DiaCarta’s proprietary xenonucleic acid (XNA) technology that allows target enrichment, and Luminex MAGPIX platform technology that enables simultaneous detection of up to 50 mutation targets. Briefly, multiplex PCR amplification of cancer associated genes is conducted in the presence of XNA. In this reaction, XNA specifically suppresses the wild-type DNA from being amplified and thus, only generates amplicons from the genes that carry mutations. The amplicons are then hybridized in a single tube that contains a set of magnetic beads. Each bead is uniquely color-coded for identification, and each corresponds to a single mutation of interest. The beads are analyzed on Luminex platform for genotyping of the mutations. Using this method, we compared conditions with or without XNA for target amplification. Our preliminary data show that when we tested the cancer oncogene KRAS exon 2 mutation variations, we find that 100% correct allele call was made with XNA for all 7 reference mutations genes. However, in conditions without XNA, the PCR product was composed of mostly wild-type sequences, and thus, only two correct allele calls (28.6%) were made. Consequently we have showed a clear advantage of XNA technology for efficient mutant target enrichment, followed by Luminex MAGPIX platform technology for simultaneous detection of multiple genetic targets. Multiplex capacity of both PCR and Luminex MAGPIX platform allows a significant reduction in the total amount of patient samples needed for precise mutation detection from each assay, especially for the mutations with low allelic frequency. Further development on this assay will provide a more reliable, sensitive and quick method for simultaneously detecting mutations associated with cancer in a single reaction.
Citation Format: Michael Y. Sha, Anna J. Lee, Michael J. Powell, Aiguo Zhang. Development of in vitro multiplex colorectal cancer associated mutation detection assay powered with xenonucleic acid [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1391.
Abstract 1396: Detection and local histological staging of prostate cancer foci in H&E whole slide images using convolutional neural networks
Authors: Stürenberg Carolin , Khan Umair , Sandeman Kevin , Gencoglu Oguzhan , Malen Adrian , Erickson Andrew , Heikkinen Timo , Rannikko Antti , Mirtti Tuomas 
Published: August 2019

Abstract
A pathologist’s histological diagnosis is the gold standard of prostate cancer diagnostic measures. In addition to cancer grade, the stage of cancer determines the follow-up and possible adjuvant therapies after surgery. Not only glandular pattern recognition but also the assessment of three-dimensional extent and size of cancer, in relation to the whole organ, are parts of the subjective diagnosis, which may vary among pathologists. Furthermore, evaluation of lymph nodes for any possible metastases is time-consuming and missing cancer in lymph nodes can lead to undertreatment of the patient. For the abovementioned reasons, our team is developing an algorithm that calculates the amount of cancer tissue objectively, assisting the pathologist in the diagnostic procedure. In addition, we are creating an assistant for cancer detection in lymph nodes, which are removed for histological evaluation. All in all, we aim to create a tool that will help pathologists to a better, faster, more secure and more accurate diagnosis. Our material consists of full sets of scanned whole slide images from 302 prostates that were retrieved by radical prostatectomy. After supervised learning procedure, convolutional neural networks were employed for the classification of cancerous and non-cancerous regions in the images. A tiling based approach was used in which a slide was divided into square shaped small tiles. Millions of cancerous and non-cancerous tiles were sampled from the dataset for training and validation. During the convolutional neural network training, several different tile sizes were used, i.e., 256x256, 512x512, 1024x1024 pixels. Four different types of architectures were fine-tuned and trained for the task of tile-wise binary classification, namely InceptionV3, Xception, ResNet50 and a custom convolutional neural network architecture. In our preliminary assays for cancer detection, in both pixel-wise and tile-wise evaluation, InceptionV3 performed outstandingly well with an AUC score of 0.97 and 0.951, respectively. In conclusion, our algorithm has developed very well thus far with an accuracy in cancer detection of 97%. It is not only a versatile assisting tool, aiding pathologists to a more objective, standardized and accurate diagnosis, but also serves as a second opinion in difficult and challenging diagnostic cases.
Citation Format: Carolin Stürenberg, Umair Khan, Kevin Sandeman, Oguzhan Gencoglu, Adrian Malen, Andrew Erickson, Timo Heikkinen, Antti Rannikko, Tuomas Mirtti. Detection and local histological staging of prostate cancer foci in H&E whole slide images using convolutional neural networks [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1396.
Abstract 1400: C1GALT1 regulates malignant phenotypes of cholangiocarcinoma cells
Authors: Chen Po-Da , Chang Ai-An , Huang Min-Chuan , Wu Yao-Ming 
Published: August 2019

Abstract
Identifying molecular targets for cholangiocarcinoma is an urgent need to overcome the treatment failure and death from cancer cell invasion and metastasis. Core 1 β1,3-galactosyltransferase (C1GALT1) has been documented as the key enzyme in morphogenesis and cellular adhesion, for it adds galactose to form Gal-GalNAc-Ser/Thr structure (T antigen); whereas abnormal C1GALT1 expression and aberrant O-glycans are commonly associated with tumor progression. However, functional roles of C1GALT1 in cholangiocarcinoma remains unclear. With clinical correlation, the immunohistochemistry confirmed that higher expression of C1GALT1 in cancer tissue is associated with larger tumor size, advanced cell grade and overall staging. Consistently, stable knockdown of C1GALT1 regarding cholangiocarcinoma cell lines inhibits cell viability, migration, and invasion; whereas the overexpressed C1GALT1 promotes cell viability, migration, and invasion of cholangiocarcinoma cell lines. Additionally, control of C1GALT1 regulates the colony formation, as well as sphere formation of cholangiocarcinoma cells. Moreover, our data suggest that down-regulated C1GALT1 modifies AAL, VVA, PNA, LEL, and MALII lectin, in correlation with the cell malignant behaviors. Given that, C1GALT1 is sufficient to regulate malignant behaviors of cholangiocarcinoma cells with a significant correlation between gene expression and clinical prognosis, implying that C1GALT1 plays a crucial role in cancer progress of cholangiocarcinoma.
Citation Format: Po-Da Chen, Ai-An Chang, Min-Chuan Huang, Yao-Ming Wu. C1GALT1 regulates malignant phenotypes of cholangiocarcinoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1400.
Abstract 1403: Combining oligonucleotide library-based RNA fluorescence in situ hybridization and fluorescent immunohistochemistry on the same tissue section
Authors: Ach Robert A. , Tom-Moy May , Tsang Peter , Kroeger Kelly 
Published: August 2019

Abstract
The ability to visualize both RNA and protein expression in a single formalin-fixed paraffin-embedded (FFPE) tissue section is a powerful technique for studying biological problems such as the regulation of protein expression and RNA/protein interactions, as well as for antibody characterization and validation. We have leveraged our ability to chemically synthesize oligonucleotides in massively parallel reactions to produce DNA libraries that can be used to generate probes for the detection of DNA or RNA by Fluorescence in situ Hybridization (FISH). The sequences of the oligonucleotides in these libraries are selected in silico using empirically determined criteria so as to avoid repetitive elements or regions homologous to other non-targeted nucleic acids. We have used these oligonucleotide library-derived FISH probes in combination with a novel signal amplification technique to detect the localization of a variety of both coding and non-coding RNAs in fixed tissue culture cells and FFPE tissue sections, using both conventional fluorescence and structured illumination microscopy. We report here combining our RNA FISH methodology with antibody-based fluorescent immunohistochemistry (IHC) detection of proteins on the same FFPE slide. We show that our combined RNA FISH/IHC protocol works on a variety of RNA probe/antibody combinations for both nuclear and cytoplasmic proteins. We also show that our fluorescent assay can be converted to a colorimetric one for both the RNA and protein detection.
Citation Format: Robert A. Ach, May Tom-Moy, Peter Tsang, Kelly Kroeger. Combining oligonucleotide library-based RNA fluorescence in situ hybridization and fluorescent immunohistochemistry on the same tissue section [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1403.