tbuckley/cabot-search huggingface dataset:
Abstract 663: Diagnostic screen for lung cancer using high throughput metabolomics screen
Authors: Robert S. Plumb, Lee Gethings, Andrew Peck
Journal: Cancer Research (2019)

Abstract Lung cancer is one of the most common cancers in the world. It is a leading cause of cancer death in men and women in the United States, cigarette smoking being leading cause of lung cancer. There are two main types of lung cancer small cell and non-small cell lung cancer (NSCLC). The most common type being NSCLC which accounts for 80-85% of all reported cases. The ability to rapidly detect / diagnose lung cancer at an early stage is critical to successful treatment selection and patient survival. The use of metabolic profiling in biomedical applications metabolic profiling is being deployed as a method for finding novel, mechanistic, biomarkers of disease with obvious potential for improving diagnosis, and patient stratification. Here we present a rapid, simple and reliable high throughput targeted LC/MS single platform, for the quantification/monitoring of small molecule metabolites, lipids and peptides. The methodology employs a single set of LC/MS conditions which facilitate TCA cycle, bile acids, biogenic amine, free fatty acids, acyl carnitines, lipids and 100 protein panel without need for user intervention. Plasma from pilot cohort of lung cancer a health control samples were evaluated using this new methodology. The methodology showed excellent reproducibility and accuracy. The peptide analysis showed that 10 peptides were shown to be markers of lung cancer, these are listed in Table 1. Acylcarnitines were quantified over a range of 5 - 625ng/mL data showed that the C14:2 tetradecadienoyl carnitine and C16:1 palmitoleoyl carnitine were elevated in lung cancer samples whereas the C8:1 octenoyl carnitine level was reduced in the lung cancer samples . Although deoxycholic acid and chendeoxycholic acid appeared to be reduced in the lung cancer samples this was determined to be not statistically relevant. A total of 29 amino acids were measured during the analysis. Using t-test with p-value FDR cutoff adjusted to 0.01 the data clearly showed that sarcosine was highly over-expressed in lung cancer samples. Table 1P02749Apolipoprotein HP19652Alpha-1-acid glycoprotein 2P68871Hemoglobin subunit betaP02671Fibrogen alpha chainP02656Apolipoprotein C-IIIP02750Leucine-rich alpha 2-glycoprotein (LRG)P00738HaptoglobinP02748Complement component C9P02763Alpha-1-acid glycoprotein 1P01011Alpha-1-antichymotrypsin Note: This abstract was not presented at the meeting. Citation Format: Robert S. Plumb, Lee Gethings, Andrew Peck. Diagnostic screen for lung cancer using high throughput metabolomics screen [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 663.
Impaired memory B‐cell development and antibody maturation with a skewing toward IgE in patients with STAT3 hyper‐IgE syndrome
Authors: Willem van de Veen, Carolin E. Krätz, Craig I. McKenzie, Pei M. Aui, Jens Neumann, Carel J. M. van Noesel, Oliver F. Wirz, Beate Hagl, Carolin Kröner, Benedikt D. Spielberger, Cezmi A. Akdis, Menno C. van Zelm, Mübeccel Akdis, Ellen D. Renner
Journal: Allergy (2019)

Abstract Background Signal transducer and activator of transcription 3 hyper‐IgE syndrome (STAT3‐HIES) is caused by heterozygous mutations in the STAT3 gene and is associated with eczema, elevated serum IgE, and recurrent infections resembling severe atopic dermatitis, while clinically relevant specific IgE is almost absent. Methods To investigate the impact of STAT3 signaling on B‐cell responses, we assessed lymph node and bone marrow, blood B and plasma cell subsets, somatic hypermutations in Ig genes, and in vitro proliferation and antibody production in STAT3‐HIES patients and healthy controls. Results Lymph nodes of STAT3‐HIES patients showed normal germinal center architecture and CD138 + plasma cells residing in the paracortex, which expressed IgE, IgG, and IgM but not IgA. IgE + plasma cells were abundantly present in STAT3‐HIES bone marrow. Proliferation of naive B cells upon stimulation with CD40L and IL‐4 was similar in patients and controls, while patient cells showed reduced responses to IL‐21. IgE, IgG1, IgG3 and IgA1 transcripts showed reduced somatic hypermutations. Peripheral blood IgE + memory B‐cell frequencies were increased in STAT3‐HIES, while other memory B‐cell frequencies except for IgG4 + cells were decreased. Conclusions Despite impaired STAT3 signaling, STAT3‐HIES patients can mount in vivo T‐cell–dependent B‐cell responses, while circulating memory B cells, except for those expressing IgG4 and IgE, were reduced. Reduced molecular maturation demonstrated the critical need of STAT3 signaling for optimal affinity maturation and B‐cell differentiation, supporting the need for immunoglobulin substitution therapy and explaining the high IgE serum level in the majority with absent allergic symptoms.
Role of chemoradiation (CRT) in the adjuvant treatment of radically resected pancreatic cancer (PC) patients (pts): a mono-institutional retrospective analysis
Authors: L. Salvatore, G. Mattiucci, M. Bensi, B. Di Stefano, F. Cellini, C. Bagalà, I. Zurlo, S. Reina, V. Masiello, P. De Franco, G. Quero, F. Giuliante, S. Alfieri, V. Valentini, G. Tortora
Journal: Annals of Oncology (2019)
Predictive Potential of Head and Neck Squamous Cell Carcinoma Organoids
Authors: Sarah J. Hill, Alan D. D'Andrea
Journal: Cancer Discovery (2019)

Abstract Summary: In this issue of Cancer Discovery, Driehuis and colleagues establish culture conditions for the rapid, efficient, and long-term expansion of healthy human oral mucosa and head and neck squamous cell carcinoma (HNSCC) tumor organoids. The HNSCC tumor organoids provide a functional platform for analyzing tumor cell phenotype, tumorigenic potential, and drug and radiotherapy response, and they have a potential role in clinical decision-making. See related article by Driehuis et al., p. 852.
Electroencephalography-Guided Anesthetic Administration and Postoperative Delirium
Authors: Finn M. Radtke, Martin Franck, Claudia D. Spies
Journal: JAMA (2019)

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Abstract 16981: Innate Immune Activation and Endothelial Cell Dysfunction in Acute Kawasaki Disease
Authors: Ming He, Marcy Martin, Wei-Ting Wang, Chisato Shimizu, Adriana H Tremoulet, Hal M Hoffman, Moshe Arditi, Jane C Burns, John Y Shyy
Journal: Circulation (2017)

Introduction: Kawasaki disease (KD), the most common cause of acquired heart disease in children, is a systemic vasculitis of unknown etiology. Recently, we demonstrated that acute KD not only impa...
Malala Yousafzai: lack of female representation in top positions is a global issue
Authors: Abi Rimmer
Journal: BMJ (2019)

The Nobel peace laureate Malala Yousafzai has said that women, including female doctors, need to break gender stereotypes and tackle their own insecurities to enter more senior positions.

Speaking at the annual scientific meeting of the British Association of Oral and Maxillofacial Surgeons held in Birmingham on 3 July, Yousafzai also spoke fondly of the time she had spent in hospital in the city.

She was asked by Sat Parmar, the association’s president, whether she had any messages for female doctors in the UK given that, despite the high proportion of women entering medical school, few continued to …
Outcomes of Chronic Phase Chronic Myeloid Leukemia (CP-CML) after Sequential Treatment with Tyrosine Kinase Inhibitors (TKI)
Authors: Jee Hyun Kong, Elliott F. Winton, Leonard Heffner, Manila Gaddh, Brittany Hill, Martha L. Arellano, Fuad El-Rassi, Audrey Kim, Vamsi Kota
Journal: Blood (2017)
Longitudinal evaluation of angiogenesis-related circulating biomarkers during second-line treatment with paclitaxel and ramucirumab in advanced gastroesophageal cancer
Authors: L. Fornaro, C. Vivaldi, P. Orlandi, G. Musettini, I. Pecora, D. Gentile, S. Catanese, M. Lencioni, F. Salani, G. Pasquini, V. Massa, T. Di Desidero, A. Falcone, E. Vasile, G. Bocci
Journal: Annals of Oncology (2019)
Immobilizing A Moving Target: CAR T Cells Hit CD22
Authors: Sonia Guedan, Julio Delgado
Journal: Clinical Cancer Research (2019)

A key mechanism of resistance to chimeric antigen receptor-modified T cells (CAR-T) is loss or downregulation of target antigens. Low antigen expression on cancer cells prevents full CAR-T-cell activation and persistence. Pharmacologic modulation of target antigen expression offers a novel therapeutic strategy to drive more potent and durable responses.See related article by Ramakrishna et al., p. 5329.
Abstract 2238: Characterization of T cell clonality and tumor mutation burden utilizing the TCRSeq NGS and the comprehensive NGS assays
Authors: Hua C. Gong, Hua Gong, Andreas Papoutsis, Wen Wu, Christian Laing
Journal: Cancer Research (2019)

Abstract Background: Somatic mutations are the basis for the generation of potential neoantigens recognized by antitumor T lymphocytes, which may contribute to increase T cell diversity [1]. Next-generation sequencing of expressed T cell receptor (TCR) transcripts allows for quantification and assessing clonality of T cell diversity [2]. Tumors that exhibit a low TCR diversity and potentially having a high clonality have been shown to be lower responders to immunotherapy treatments. Methods: Utilizing the Shannon entropy to arrive at a clonality readout, we sought to gain mechanistic insights and demonstrate a link between clonality and total mutation load. We conducted the analysis using a diverse set of solid tumors and hematological malignancies across three different specimen types (bone marrow (BM), peripheral blood (PB), formalin-fixed paraffin embedded (FFPE tissue)). Specifically, we used the beta TCRSeq NGS and the Comprehensive NGS assays (internally developed) to characterize sample clonality and mutation load respectively. Results: The TCRSeq NGS assay sequences the V(D)J domains of the variable region of the TCR heavy chain (involved in epitope recognition), while the hybrid capture Comprehensive NGS assay detects variants across a 236 gene panel optimized for SNV and INDEL detection. Initial analysis across the different specimen types resulted in average clonalities of BM = 0.255, PB = 0.149, FFPE = 0.092, with average tumor mutation loads of 7.6, 7.6, and 21 respectively. Categorization of all samples by increasing clonality, independent of specimen type, established a clear differentiator with samples harboring a clonality of less than 0.10 to exhibit an average mutation load of 26.33. This was statistically significant from samples harboring clonalities between 0.10 and 0.19, which had an average mutation load of 7.86, and samples with clonalities equal to or greater than 0.20, having an average mutation load of 7.67. Conclusions: Based on two different categorical analyses, lower T cell clonality readouts appear to be associated with solid tumors harboring greater genetic diversity/neoantigen burden than hematological malignancies with higher clonalities. As tumor mutation burden has been correlated with clinical outcomes of varying efficacy, this study provides further insight into the utility of T cell clonality as a “molecular tag” for immune response and resistance in oncological therapeutics. Citation Format: Hua C. Gong, Hua Gong, Andreas Papoutsis, Wen Wu, Christian Laing. Characterization of T cell clonality and tumor mutation burden utilizing the TCRSeq NGS and the comprehensive NGS assays [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 2238.
Abstract 1991: Exploring the potential of exosomes for cancer diagnosis and management: Comparative analysis of isolation methods for optimum yield purity and downstream applications
Authors: Girijesh K. Patel, Mohammad Aslam Khan, Haseeb Zubair, Sanjeev Kumar Srivastava, Moh’d Khushman, Seema Singh, Ajay Pratap Singh
Journal: Cancer Research (2019)

Abstract Exosomes have received significant attention due to their involvement in several diseases, including cancer, and are being explored as a tool for disease diagnosis and management. As a result, several kits based on different principles are now available in the market for exosome isolation. In this study, we have compared the relative efficacy of four commercial kits from Invitrogen, 101Bio, Wako and iZON along with conventional ultracentrifugation-based method for exosome yield, purity and quality for downstream applications. Cancer cell culture supernatant was used as an abundant and uniform source of exosomes for all methods and exosome quantity, size distribution, zeta potential, marker expression, RNA (qRT-PCR) and protein (mass spectrometry) quality was determined. The Invitrogen method showed the highest yield but the preparation showed broader size distribution likely due to co-precipitation of microvesicles and had the least magnitude of zeta potential (dispersion stability). Exosome preparations from other methods showed accepted size range (&amp;lt;150 nm) with a variable zeta potential (-12mV to -29mV) with good purity. The gel filtration method; however, showed a broader size distribution in the lower size range, which could be due contamination of aggregates of proteins and vitamins molecules. Quality of RNA isolated from all preparations was comparable; however, proteins isolated from Invitrogen method-based exosomal preparation showed contamination of polyethylene glycol (PEG) in mass spectrometry analyses. Similarly, other chemical impurities coming from the precipitant in Invitrogen kit could also be the reason for toxicity of resultant exosomal preparation in biological growth measurement assay. Together, these findings from comparative analyses should serve as a guide for choice and further optimization of exosome isolation methods for their desired downstream applications in cancer biology, therapy and/or biomarker discovery. Citation Format: Girijesh K. Patel, Mohammad Aslam Khan, Haseeb Zubair, Sanjeev Kumar Srivastava, Moh’d Khushman, Seema Singh, Ajay Pratap Singh. Exploring the potential of exosomes for cancer diagnosis and management: Comparative analysis of isolation methods for optimum yield purity and downstream applications [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 1991.
T follicular helper cells in human efferent lymph retain lymphoid characteristics
Authors: Laura A. Vella, Marcus Buggert, Sasikanth Manne, Ramin S. Herati, Ismail Sayin, Leticia Kuri-Cervantes, Irene Bukh Brody, Kaitlin C. O’Boyle, Hagop Kaprielian, Josephine R. Giles, Son Nguyen, Alexander Muselman, Jack P. Antel, Amit Bar-Or, Matthew E. Johnson, David H. Canaday, Ali Naji, Vitaly V. Ganusov, Terri M. Laufer, Andrew D. Wells, Yoav Dori, Maxim G. Itkin, Michael R. Betts, E. John Wherry
Journal: Journal of Clinical Investigation (2019)

T follicular helper cells (Tfh), a subset of CD4+ T cells, provide requisite help to B cells in the germinal centers (GC) of lymphoid tissue. GC Tfh are identified by high expression of the chemokine receptor CXCR5 and the inhibitory molecule PD-1. Although more accessible, blood contains lower frequencies of CXCR5+ and PD-1+ cells that have been termed circulating Tfh (cTfh). However, it remains unclear whether GC Tfh exit lymphoid tissues and populate this cTfh pool. To examine exiting cells, we assessed the phenotype of Tfh present within the major conduit of efferent lymph from lymphoid tissues into blood, the human thoracic duct. Unlike what was found in blood, we consistently identified a CXCR5-bright PD-1–bright (CXCR5BrPD-1Br) Tfh population in thoracic duct lymph (TDL). These CXCR5BrPD-1Br TDL Tfh shared phenotypic and transcriptional similarities with GC Tfh. Moreover, components of the epigenetic profile of GC Tfh could be detected in CXCR5BrPD-1Br TDL Tfh and the transcriptional imprint of this epigenetic signature was enriched in an activated cTfh subset known to contain vaccine-responding cells. Together with data showing shared TCR sequences between the CXCR5BrPD-1Br TDL Tfh and cTfh, these studies identify a population in TDL as a circulatory intermediate connecting the biology of Tfh in blood to Tfh in lymphoid tissue.
Abstract 2147: Galectin-1: A marker for claudin-low breast cancer
Authors: Kassondra Balestrieri, Moses McDaniel, Christiana Shoopman, Nasreen Vohra, Kathryn Verbanac
Journal: Cancer Research (2019)

Abstract Metastasis and mortality among patients with triple negative breast cancer (TNBC) of the claudin-low subtype remain high because these tumors are clinically aggressive, chemoresistant, and lack targeted therapies. We have previously used proteomic approaches to analyze orthotopic and metastatic tumors from the syngeneic murine T11 tumor model, which displays gene expression profiles that mirror human claudin-low TNBC. These studies identified Galectin-1 (Gal-1), an N-acetyllactosamine-binding protein, as an overexpressed protein in cultured T11 cells, primary tumors, and lung metastases compared to normal lung and mammary fat pad tissue from healthy control mice. These results were confirmed by Western immunoblot and immunohistochemistry and were further supported by analysis of murine tumor microarray data sets, which revealed Gal-1 overexpression in the claudin-low subtype compared to other breast cancer subtypes. Here we extend our murine studies to investigate Gal-1 expression in breast cancer patients, with specific inclusion of claudin-low tumors. To compare differential Gal-1 expression across breast cancer subtypes, we initially analyzed published human microarray data sets from normal breast and primary breast tumors (total n=423, of which 51 are the claudin-low subtype): the highest Gal-1 expression was observed in claudin-low breast cancer. In order to validate these findings, we are examining breast cancer specimens from a unique cohort of ethnically diverse patients from rural Eastern North Carolina with a median follow-up of over 8 years. RNASeq data from a subset of this cohort (n=121) was used to assign subtypes (using PAM50 and the claudin-low classifier). Further studies are in progress to compare Gal-1 expression between subtypes and correlate with clinicopathologic factors and outcome. Immunohistochemical Gal-1 staining of primary tumor tissue blocks is underway to confirm expression in each subtype at the protein level. Immunohistochemistry will also define Gal-1 expression in the cell types comprising the heterogeneous tumor microenvironment (tumor, stromal, immune cells) and its subcellular localization (nuclear, cytoplasmic, membrane-associated). Through this ongoing work evaluating Gal-1 across breast cancer subtypes, we will help corroborate initial findings from the T11 claudin-low mouse model and yield further insights into the role of Gal-1 in breast cancer progression. Citation Format: Kassondra Balestrieri, Moses McDaniel, Christiana Shoopman, Nasreen Vohra, Kathryn Verbanac. Galectin-1: A marker for claudin-low breast 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 2147.
Abstract 3414: Identifying dysregulated lncRNAs and miRNAs in low grade glioma: Uncovering signaling pathways and novel therapeutic targets
Authors: Stephen Carney, Felipe Nuñez, Pedro R. Lowenstein, Maria G. Castro
Journal: Cancer Research (2019)

Abstract A molecular subtype of low grade gliomas (LGG) is characterized by mutations in Alpha-Thalassemia Mental Retardation X-linked (ATRX), TP53 and isocitrate dehydrogenase 1 (IDH1R132H, mIDH1). Our lab has generated a genetically engineered mouse model that harbors the characteristic genetic lesions found in this molecular subtype of LGG. We determined that mouse neurospheres (NS) bearing these mutations showed downregulation of signaling pathways involved in oligodendrocyte differentiation. The production of 2-hydroxyglutarate (2HG) by mIDH1 induces histone and DNA hypermethylation, which has been shown to impair neural precursor cells’ differentiation. We aim to investigate how the presence of mIDH1 impacts the epigenetic regulation of long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and mRNAs in human mutant IDH1 glioma cell cultures obtained from patients at the time of surgery. We hypothesize that the dysregulation/remodeling of lncRNAs, miRNAs and mRNAs contributes to the invasiveness, differentiation status and stemness of glioma cells. Only a handful of lncRNAs have been studied in relation to their role in neural cells’ lineage commitment and glioma stem cells’ biology. We identified 127 differentially expressed (DE) lncRNA (FDR&amp;lt;0.01) in a human primary glioma cell culture SJGBM2, which has a ATRX mutation and was stably-transfected to express mIDH1. Of the 14 DE miRNAs identified, hsa-miR-210-3p and hsa-miR-4461, which have been linked to tumor invasiveness. The results from this work will reveal novel mechanistic pathways by which lncRNA/miRNAs and differentially expressed mRNAs impact downstream signaling pathways in LGG and uncover new therapeutic targets for this molecular glioma subtype. SC is supported by the T32 Cancer Biology Training Grant, the work is supported by grants from NIH/NINDS to MGC and PRL. Citation Format: Stephen Carney, Felipe Nuñez, Pedro R. Lowenstein, Maria G. Castro. Identifying dysregulated lncRNAs and miRNAs in low grade glioma: Uncovering signaling pathways and novel therapeutic targets [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 3414.