tbuckley/cabot-search huggingface dataset:
Abstract 204:In vitrometabolomics of mesothelioma: Challenges and outcomes
Authors: Sabrina Lagniau, Kevin Lamote, Lore Vandermeersch, Herman Van Langenhove, Jan P. van Meerbeeck, Karim Y. Vermaelen
Journal: Cancer Research (2017)

Abstract Introduction Early detection of malignant pleural mesothelioma (MPM) is likely to improve outcome in affected patients. From our previous studies (MesoBreath 1 &amp; 2) we developed a screening tool in which volatile organic compounds (VOCs) in breath allowed discrimination of MPM patients from at risk controls. However it is not yet clear which VOCs arise from the neoplastic cells themselves or from the host response. Identifying the cancer cell-specific compounds should increase the specificity of our breathomic signature model. Therefore, we set up an in vitro experimental setup model for VOC analysis from the headspace of mesothelioma cell lines. Methods Standard polystyrene culture flasks (NunclonTM Delta Surface, Thermo Scientific) were mounted with an adapted cap accommodating teflon inlet and outlet tubes. The inlet tube provides environmental air while an external pump (Gilian GilAir Plus, Sensidyne) draws headspace air from the outlet tube over an adsorption column (Tenax GR, Markes International, UK). The adsorption columns were further processed on a GC-MS platform (GC: Focus GC, Thermo Finnigan, Milan, Italy; DSQII Single Quadrupole MS, Thermo Finnigan, Austin, TX, USA). VOC profiles were processed using supervised clustering algorithms and principal component analysis. Results Using this setup, we have investigated the impact of flow and total sampled volume on the concentration and range of VOCs detected. For a constant flow, VOCs were detected in higher concentrations with increasing sample volume. For a constant volume, a lower sampling flow yielded a higher concentration of detected VOCs. Most of the VOCs obtained were alkanes and ketones. We will show data illustrating the differential VOC profiles of container plastic, cell culture medium and growing mesothelioma cancer cells, as well as the differential VOC output of epithelioid vs sarcomatoid mesothelioma cell lines. Conclusions We have succesfully developed an in vitro experimental setup allowing collection and analysis of VOCs emanating from mesothelioma cancer cell line cultures. This platform will allow us to investigate how VOC profiles are impacted in different experimental conditions (e.g. hypoxia, nutrient deprivation, cytostatics, co-culture with leukocytes). The data collected will help us to pinpoint the cancer cell-derived VOCs from patient exhaled breath, and increase the robustness of our mesothelioma breathomic signature. Note: This abstract was not presented at the meeting. Citation Format: Sabrina Lagniau, Kevin Lamote, Lore Vandermeersch, Herman Van Langenhove, Jan P. van Meerbeeck, Karim Y. Vermaelen. In vitro metabolomics of mesothelioma: Challenges and outcomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 204. doi:10.1158/1538-7445.AM2017-204
Abstract 926: Generation of a potential breast cancer stem cell model from induced pluripotent stem cells
Authors: Neha Nair, Anna Sanchez Calle, Maram Hussein Zahra, Aung Ko Ko Oo, Arun Vaidyanath, Shinobu Masuda, Tomonari Kasai, Masaharu Seno
Journal: Cancer Research (2017)

Abstract The role of cancer stem cells (CSC) in the present scenario of breast cancer research is perceived as indispensable in the development and progression of the disease. The CSC niche maintains a heirarchy of heterogeneous cells, which facilitates the inception of the tumor until its invasion. Therefore, our study focuses on the development of an effective breast cancer stem cell model from mouse induced pluripotent stem cells (miPSCs). Taking into consideration the intertumor heterogeneity of breast cancer, three human breast cancer cell lines, namely BT549, SKBR3 and T47D representing three major hormone subtypes were used to derive respective conditioned medium. The miPSCs were treated with these conditioned media separately for a period of one month following the protocol previously established by our laboratory. The resulting survived cells were subcutaneously and orthotopically transplanted into Balb/c nude mice. Within a short span of 15-20 days, both subcutaneous and orthotopic tumors were developed. Serial transplantations in to nude mice also generated malignant tumors with same vigor. Histopathological studies of these tumors confirmed a malignant infiltrating ductal carcinoma with apparent desmoplasia in orthotopic tumor and Her2 expression in comparison with subcutaneous ones, all of which confirmed us the conversion of miPSCs to CSCs. Presence of lung metastatic nodes further ascertained the invasiveness of this in vitro generated CSCs. Marked expression of prominent CSC markers namely CD44, Nanog, Sox2 and CD49f were observed in primary cells generated from these tumors. Tumor sphere formation assay further confirmed the presence of a good population of self renewing CSC population in the tumor tissues. This study attempts to recapitulate human breast cancer disease in mice without any genetic manipulation, but by exploiting the tumor microenvironment in the form of conditioned medium. This should pave the way for the establishment of personalized therapy and a model to assess effective therapeutic interventions. Citation Format: Neha Nair, Anna Sanchez Calle, Maram Hussein Zahra, Aung Ko Ko Oo, Arun Vaidyanath, Shinobu Masuda, Tomonari Kasai, Masaharu Seno. Generation of a potential breast cancer stem cell model from induced pluripotent stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 926. doi:10.1158/1538-7445.AM2017-926
Abstract LB-079: Expression of evolutionarily novel genes in tumors
Authors: Andrei Kozlov, Larisa Krukovskaya, Nikolai Samusik, Andrei Makashov, Ekaterina Matyunina, Julia Karnaukhova, Tamara Kurbatova, Alexander Emelyanov
Journal: Cancer Research (2017)

Abstract Several genes with dual specificity - evolutionarily novel and expressed specifically or predominantly in tumors (OTP, ESRG, PVT1, ELFN1-AS1, HHLA1, DCD, SPRR1A, PBOV1 and others), have been described in our lab. We suggested to call such genes Tumor Specifically Expressed, Evolutionarily Novel (TSEEN) genes. We also described the evolutionary novelty of the whole classes of genes expressed predominantly in tumors, e.g. CT-X genes and genes of noncoding tumor specifically expressed RNAs. We studied the phylogenetic distribution of the orthologs of genes expressed in tumors and found that different functional gene classes have different evolutionary novelty. Some of them are enriched with evolutionarily novel genes. We showed that phylogenetic distribution curves of oncogenes, tumor suppressor genes and differentiation genes almost coincide, i.e. their evolution proceeds in a parallel manner. Using zebrafish transgenic inducible tumor model we discovered that some human genes which determine progressive traits originated in fishes and were first expressed in fish tumors. Our data and the data published by other authors suggest that genes originated by gene duplication; from endogenous retroviruses; by exon shuffling; and de novo are expressed in tumors, sometimes with high tumor specificity. The expression of evolutionarily novel genes in tumors may be a novel biological phenomenon with important evolutionary role. Citation Format: Andrei Kozlov, Larisa Krukovskaya, Nikolai Samusik, Andrei Makashov, Ekaterina Matyunina, Julia Karnaukhova, Tamara Kurbatova, Alexander Emelyanov. Expression of evolutionarily novel genes in tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-079. doi:10.1158/1538-7445.AM2017-LB-079
Abstract 2639: Development of small molecule selective inhibitors of GCN2 as an immunotherapy aimed at preventing immune escape of tumor cells
Authors: Michał Gałęzowski, Kamil Sitarz, Eliza Majewska, Stefan Chmielewski, Kinga Michalik, Magdalena Masiejczyk, Agnieszka Adamus, Arkadiusz Białas, Joanna Fogt, Marcin Bień, Mateusz Świrski, Maciej Mikulski, Julian Zachmann, Krzysztof Brzózka
Journal: Cancer Research (2017)

Abstract GCN2 is a protein kinase capable of sensing amino acid (AA) shortage. It gets activated by binding of unloaded tRNAs and subsequently phosphorylates translation initiation factor 2 alpha (eIF2α) eventually leading to induction of ATF4-mediated integrated stress response (ISR). Elevated catabolism of one of the essential amino acids - tryptophan (Trp), driven by overexpression of critical enzymes in Trp metabolism - IDO and TDO, leads to immunosuppressive microenvironment in many types of cancer. GCN2 is a key effector signaling component for IDO/TDO and is considered as a metabolic checkpoint of highly Trp-dependent T-cells. GCN2 activation through accumulation of unloaded tRNAs leads to inhibition of CD8+ effector T-cells and increase in generation and activation of regulatory T-cells. According to these findings, selective inhibition of GCN2 may be an effective strategy for targeting Trp-dependent immunosurveillance of tumor cells. In this study, we report the results for a series of novel small molecule GCN2 kinase inhibitors that have been developed at Selvita and, to our best knowledge, are the most potent GCN2 inhibitors reported so far. Newly synthesized compounds exert low nanomolar potency for GCN2, good selectivity as well as ADME profiles. Profound assessment of the compounds potency and efficacy using a selection of in vitro activity/binding assays will be presented. Citation Format: Michał Gałęzowski, Kamil Sitarz, Eliza Majewska, Stefan Chmielewski, Kinga Michalik, Magdalena Masiejczyk, Agnieszka Adamus, Arkadiusz Białas, Joanna Fogt, Marcin Bień, Mateusz Świrski, Maciej Mikulski, Julian Zachmann, Krzysztof Brzózka. Development of small molecule selective inhibitors of GCN2 as an immunotherapy aimed at preventing immune escape of tumor cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2639. doi:10.1158/1538-7445.AM2017-2639
<scp>EAACI</scp> guidelines on allergen immunotherapy: Hymenoptera venom allergy
Authors: G. J. Sturm, E.‐M. Varga, G. Roberts, H. Mosbech, M. B. Bilò, C. A. Akdis, D. Antolín‐Amérigo, E. Cichocka‐Jarosz, R. Gawlik, T. Jakob, M. Kosnik, J. Lange, E. Mingomataj, D. I. Mitsias, M. Ollert, J. N. G. Oude Elberink, O. Pfaar, C. Pitsios, V. Pravettoni, F. Ruëff, B. A. Sin, I. Agache, E. Angier, S. Arasi, M. A. Calderón, M. Fernandez‐Rivas, S. Halken, M. Jutel, S. Lau, G. B. Pajno, R. van Ree, D. Ryan, O. Spranger, R. G. van Wijk, S. Dhami, H. Zaman, A. Sheikh, A. Muraro
Journal: Allergy (2017)

Hymenoptera venom allergy is a potentially life-threatening allergic reaction following a honeybee, vespid, or ant sting. Systemic-allergic sting reactions have been reported in up to 7.5% of adults and up to 3.4% of children. They can be mild and restricted to the skin or moderate to severe with a risk of life-threatening anaphylaxis. Patients should carry an emergency kit containing an adrenaline autoinjector, H1 -antihistamines, and corticosteroids depending on the severity of their previous sting reaction(s). The only treatment to prevent further systemic sting reactions is venom immunotherapy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on Venom Immunotherapy as part of the EAACI Guidelines on Allergen Immunotherapy initiative. The guideline aims to provide evidence-based recommendations for the use of venom immunotherapy, has been informed by a formal systematic review and meta-analysis and produced using the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included representation from a range of stakeholders. Venom immunotherapy is indicated in venom-allergic children and adults to prevent further moderate-to-severe systemic sting reactions. Venom immunotherapy is also recommended in adults with only generalized skin reactions as it results in significant improvements in quality of life compared to carrying an adrenaline autoinjector. This guideline aims to give practical advice on performing venom immunotherapy. Key sections cover general considerations before initiating venom immunotherapy, evidence-based clinical recommendations, risk factors for adverse events and for relapse of systemic sting reaction, and a summary of gaps in the evidence.
Abstract 2042: Nano-tetraiodothyroacetic acid (NDAT) potentiates gefitinib-induced antiproliferation in colorectal cancer cells by inhibiting EGFR sialylation and PI3K activation
Authors: Yu-Tang Chin, Chi-Yu Lin, Chun A. Changou, Jacqueline Whang-Peng, Paul J. Davis, Hung-Yun Lin
Journal: Cancer Research (2017)

Abstract The resistance of gefitinib has been revealed to complicate cancer therapy. Tetraiodothyroacetic acid (tetrac) and its nanoparticulate derivative (NDAT, nano-tetrac) have been proved in vitro and in vivo xenograft demonstrating anti-proliferative and anti-angiogenetic activities. It also indicates that they potentiate anti-cancer agent-induced anti-proliferation in cancer cells. In this study, we investigated the effects of NDAT on gefitinib-induced anti-cancer activities in human colorectal cancer cells. Gefitinib inhibited cell proliferation at concentration 1 μM in K-ras wild type HT29 cell and NDAT enhanced the anti-proliferation-induced gefitinib significantly. Meanwhile, both inhibited proliferative and metastatic genes expression in HT29 cells. On the other hand, 10 μM gefitinib inhibited cell proliferation in K-ras mutant HCT116 cell which was further enhanced by NDAT. Different from results in HT-29 cells, only NDAT inhibited proliferative and metastatic genes expression significantly and enhanced the effect of gefitinib in HCT116 cells. ST6Gal-1 catalyzes sialylation of EGFR and induces gefitinib-resistant in colorectal cancers. In addition, NDAT did reduced not only ST6Gal-1 gene expression, but also its protein production. However, the inhibition of ST6Gal-1 expression may not be sufficient to induced anti-proliferation in colorectal cancer cells. PI3K inhibitor, LY294002, was able to potentiate the gefitinib-induced anti-proliferation in HCT116 cells suggesting that constitutive activation of PI3K may play a key role on gefitinib-resistance in HCT116 cells. In summary, NDAT potentiated gefitinib-induced anti-proliferation via inhibiting the activity of ST6Gal-1 and PI3K activation in gefitinib-resistant colorectal cancer cells. Citation Format: Yu-Tang Chin, Chi-Yu Lin, Chun A. Changou, Jacqueline Whang-Peng, Paul J. Davis, Hung-Yun Lin. Nano-tetraiodothyroacetic acid (NDAT) potentiates gefitinib-induced antiproliferation in colorectal cancer cells by inhibiting EGFR sialylation and PI3K activation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2042. doi:10.1158/1538-7445.AM2017-2042
Morris Karlynn Barrett
Authors: Edward J. Breyere
Journal: JNCI Journal of the National Cancer Institute (1968)

Journal Article Morris Karlynn Barrett Get access Edward J. Breyere Edward J. Breyere Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 40, Issue 4, April 1968, Pages III–V, https://doi.org/10.1093/jnci/40.4.III Published: 01 April 1968
Abstract 5689: Identify tissue-of-origin in cancer cfDNA by whole genome sequencing
Authors: Yaping Liu, Sarah Reed, Atish D. Choudhury, Heather A. Parsons, Daniel G. Stover, Gavin Ha, Gregory Gydush, Justin Rhoades, Denisse Rotem, Samuel Freeman, Viktor Adalsteinsson, Manolis Kellis
Journal: Cancer Research (2017)

Abstract Cell free DNA (cfDNA) has been shown to be an emerging non-invasive biomarker to monitor tumor progression in cancer patients. Elevated cfDNA has been found not only from tumors, but also from normal tissues. Thus, the identification of cfDNA’s tissue-of-origin is critical to understand the mechanism of cfDNA release and tumor progression. Recent efforts to identify cfDNA’s tissue-of-origin begin to utilize cfDNA’s epigenomic status, such as DNA methylation and nucleosome spacing. However, both of these methods have limitations: (1) For nucleosome positioning, lack of reference nucleosome maps in different tumor and normal tissues has limited its application to tissue-of-origin deconvolution; (2) For DNA methylation, large DNA degradation during whole genome bisulfite sequencing (WGBS) library preparation, even with current low-input DNA technology, is still the major hurdle for its clinical application, although extensive DNA methylation studies by WGBS in tumor and normal tissues during the last decade have provided many reference maps. Very recently, a pioneer study showed significant differences between DNA fragment lengths of methylated and unmethylated cfDNA. Taking advantage of this experimental observation, we developed a machine learning approach to infer the base pair resolution DNA methylation level from fragment size information in whole genome sequencing (WGS). The predicted DNA methylation, from not only high coverage but also dozens of ultra-low-pass WGS (ULP-WGS), showed high concordance with the ground truth DNA methylation level from WGBS in the same cancer patients. Furthermore, by using hundreds of WGBS datasets from different tumor and normal tissues/cells as the reference map, we deconvoluted cfDNA’s tissue-of-origin status by inferred DNA methylation level at ULP-WGS from thousands of breast/prostate cancer samples and healthy individuals. The cfDNA’s tissue-of-origin status in cancer patients showed high concordance with confirmed metastasis tissues from physicians. Interestingly, some clinical information, such as cancer grades/stages, seemed to be correlated with cfDNA’s tissue-of-origin status. Overall, our methods here pave the road for cfDNA’s application in clinical diagnosis and monitoring. Citation Format: Yaping Liu, Sarah Reed, Atish D. Choudhury, Heather A. Parsons, Daniel G. Stover, Gavin Ha, Gregory Gydush, Justin Rhoades, Denisse Rotem, Samuel Freeman, Viktor Adalsteinsson, Manolis Kellis. Identify tissue-of-origin in cancer cfDNA by whole genome sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5689. doi:10.1158/1538-7445.AM2017-5689
Abstract 1164: A novel hypoxia-inducible factor-1 inhibitor IDF-11774 regulates cancer metabolism, thereby suppressing tumor growth
Authors: Misun Won, Hyun Seung Ban, Kyeong Lee, Hongsub Lee, Bo-Kyung Kim, Hwan Mook Kim, Ravi Naik, Song-Kyu Park, Joon-Tae Park, Inhyub Kim, Miso Nam, Geum-Sook Hwang
Journal: Cancer Research (2017)

Abstract HIF-1 is associated with poor patient prognosis and therapeutic resistance of cancer. We have developed a novel hypoxia-inducible factor (HIF)-1 inhibitor, IDF-11774, as a clinical candidate for cancer therapy. Under hypoxic condition, IDF-11774 inhibited the accumulation of HIF-1α in vitro and in vivo in colorectal carcinoma HCT116 cells. IDF-11774 suppressed the angiogenesis of cancer cells by reducing the expression of HIF-1 target genes. Moreover, IDF-11774 reduced glucose uptake, leading sensitizing cell growth on low glucose condition. IDF-11774 also decreased the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR). Metabolic profile of IDF-11774-treated cells revealed low levels of NAD+, lactate, and intermediates in glycolysis and tricarboxylic acid (TCA) cycle. More importantly, we observed elevated AMP and diminished ATP level, leading high AMP/ATP ratio. Apparently, phosphorylation of AMPK increased, leading inhibition of mTOR signaling in cells. In vivo xenograft assays demonstrated that IDF11774 has significant anti-cancer efficacy by targeting cancer metabolism in mouse models containing the KRAS, PTEN or VHL mutation, which often occurs in many malignant cancers. Collectively, IDF-11774 suppresses the hypoxia-induced HIF-1α accumulation, thereby repressing tumor growth by regulating cancer metabolism. Citation Format: Misun Won, Hyun Seung Ban, Kyeong Lee, Hongsub Lee, Bo-Kyung Kim, Hwan Mook Kim, Ravi Naik, Song-Kyu Park, Joon-Tae Park, Inhyub Kim, Miso Nam, Geum-Sook Hwang. A novel hypoxia-inducible factor-1 inhibitor IDF-11774 regulates cancer metabolism, thereby suppressing tumor growth [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1164. doi:10.1158/1538-7445.AM2017-1164
MicroRNA-21 regulates peroxisome proliferator–activated receptor alpha, a molecular mechanism of cardiac pathology in Cardiorenal Syndrome Type 4
Authors: Sandra Chuppa, Mingyu Liang, Pengyuan Liu, Yong Liu, Marc C. Casati, Allen W. Cowley, Leah Patullo, Alison J. Kriegel
Journal: Kidney International (2017)
Abstract 4004: Rapamycin selectively targets obesity-polarized macrophages in the prostate tumor microenvironment
Authors: Gloria C. Galván, Tommy Pham, Brittany Harlow, Christian Johnson, Riddhi Patodia, Duan Quach, Michael A. Liss, Linda A. deGraffenried
Journal: Cancer Research (2017)

Abstract Background: Obesity is associated with prostate cancer progression and mortality. Previous studies in our laboratory suggest that obesity drives prostate cancer progression in part by increasing macrophage recruitment and by polarizing macrophages in the tumor microenvironment into a tumor promoting M2/TAM phenotype. Rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, has been used for several decades in transplant patients, and in the last several years has been shown to be an effective disease suppressor in certain cancer types. Intriguingly, mTOR has been shown to be especially important for M2 polarization and stabilization. Hypothesis: Based upon published data and our preliminary studies, we hypothesize that rapamycin will selectively target obesity-polarized macrophages and will provide a survival benefit to the obese prostate cancer patient. Methods: To address this hypothesis, we used our in vitro model of obesity-induced macrophage polarization that includes two different prostate cancer cell lines, macrophages, and sera from obese and non-obese men. qPCR was used to measure expression levels of markers associated with an M2/TAM phenotype. MTT assays were conducted to measure cell viability, and flow cytometry and Western blot analyses were used to determine cell cycle status and apoptosis. Results: Obese conditions increased expression of M2/TAM markers in macrophages and rapamycin selectively decreased viability of obesity-activated M2/TAMs compared to M1 macrophages. Conclusions: Our in vitro study suggests that obesity promotes a tumor-associated phenotype in macrophages and that the mTOR pathway is involved in the survival of M2/TAM macrophages. This study offers a novel mechanistic approach to treat obese patients with prostate cancer. Citation Format: Gloria C. Galván, Tommy Pham, Brittany Harlow, Christian Johnson, Riddhi Patodia, Duan Quach, Michael A. Liss, Linda A. deGraffenried. Rapamycin selectively targets obesity-polarized macrophages in the prostate tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4004. doi:10.1158/1538-7445.AM2017-4004