tbuckley/cabot-search huggingface dataset:
Molecular Subgroups of Hyperdiploidy and Their Prognostic Relevance - an Analysis of 1,036 Myeloma Trial Patients
Authors: Martin F Kaiser, Eileen Mary Boyle, Brian A Walker, Dil B Begum, Paula Proszek, David C Johnson, Charlotte Pawlyn, John R Jones, Suvi Savola, Roger G Owen, Mark T Drayson, David A Cairns, Gordon Cook, Walter M Gregory, Richard S Houlston, Faith E Davies, Graham H Jackson, Gareth J Morgan
Journal: Blood (2015)
Abstract 3364: Epithelial-mesenchymal transition is associated with a profound inflammatory tumor microenvironment in lung adenocarcinoma
Authors: Yanyan Lou, Lixia Diao, Parra Cuentas Edwin Roger, Warren L. Denning, Limo Chen, Youhong Fan, Jaime Rodriguez, Lauren Byers, Jing Wang, Vassiliki Papadimitrakopoulou, Behrens Carmen, Ignacio I. Wistuba, Patrick Hwu, John V. Heymach, Don L. Gibbons
Journal: Cancer Research (2015)

Abstract Promising results in the treatment of non-small cell lung cancer (NSCLC) have been seen with immunomodulatory agents targeting immune checkpoints, such as programmed cell death 1 (PD-1) or programmed cell death 1 ligand (PD-L1). However, only a select group of patients respond to these interventions. The identification of biomarkers that predict clinical benefit to immune-based approaches, such as immune checkpoint blockade, is critical to successful translation of these agents. By using integrated gene array analysis in three large independent NSCLC patient datasets along with immunohistochemistry study (IHC), reverse phase protein array (RPPA) and in vivo animal study, we demonstrated that epithelial-mesenchymal transition (EMT) is highly associated with a profound inflammatory tumor microenvironment in lung adenocarcinoma. Our data revealed immune activation and simultaneous development of multiple immune suppressive mechanisms, including elevation of immune checkpoints such as PD-L1, PD-L2, PD-1, TIM-3, BTLA and CTLA-4, as well as an increase in tumor infiltrating CD4+Foxp3+ regulatory T cells, IL-6 and indoleamine 2,3-dioxygenase (IDO) in lung adenocarcinomas with a mesenchymal phenotype. Our data suggested that EMT might represent a potential biomarker to select the patients who will benefit from immune checkpoint blockade agents and other immunotherapies in NSCLC and possibly other cancers. Note: This abstract was not presented at the meeting. Citation Format: Yanyan Lou, Lixia Diao, Parra Cuentas Edwin Roger, Warren L. Denning, Limo Chen, Youhong Fan, Jaime Rodriguez, Lauren Byers, Jing Wang, Vassiliki Papadimitrakopoulou, Behrens Carmen, Ignacio I. Wistuba, Patrick Hwu, John V. Heymach, Don L. Gibbons. Epithelial-mesenchymal transition is associated with a profound inflammatory tumor microenvironment in lung adenocarcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3364. doi:10.1158/1538-7445.AM2015-3364
QOL-01THE ADULT EPENDYMOMA OUTCOMES PROJECT (AEO)
Authors: Alvina Acquaye, Elizabeth Vera-Bolanos, Terri Armstrong, Mark Gilbert
Journal: Neuro-Oncology (2015)

INTRODUCTION: Understanding the disease presentation and experience of patients remains an uncharted domain for patients with rare tumors. The Adult Ependymoma Outcomes (AEO) Project is an on-line questionnaire established in 2009 that has been investing the data gleaned from this self-reported information to allow physicians to better understand this uncommon tumor. METHODS: This report includes data from M.D. Anderson Symptom Inventory (MDASI) for Brain or Spine and the Ependymoma Outcomes Questionnaire (EOQ), a disease specific instrument that explores disease presentation and clinical course. Descriptive statistics were used to describe patient and clinical characteristics. RESULTS: The AEO was completed by 264 ependymoma patients; the majority were female (56%) with a median age of 47 (range 18-77). Participants were diagnosed with either ependymoma in the brain (43%) or spine (59%). Approximately 50% of patients with brain tumors were symptomatic for less than 3-4 months before diagnosis. Conversely, over 70% of spine patients were symptomatic for a year or more before surgery. The majority of patients had a grade II ependymoma, although 50% of spine patients were uncertain about their tumor grade. Over half (54% brain, 60% spine) of the patients had some form of treatment after surgery. There were a high number of participants reporting no tumor recurrence (brain 68%, spine 73%). However, despite prolonged tumor control, a high symptom burden was reported. Most patients had follow-up care provided by a neurosurgeon (approximately 50%) or by a family care provider (20%). CONCLUSTION: In conclusion, vital information can be collected from online questionnaires about the experience of patients with rare tumors. Although results are limited to patients with access and interest, these results can provide guidance to develop education and interventions for specific symptoms, and generate research questions. Furthermore, these results underscore the importance of early detection to improve quality of life.
Abstract 750: Overcoming resistance to anti-EGFR therapy in non-small cell lung cancer with a T-type Ca2+ channels inhibitor
Authors: Barbara Dziegielewska, Lloyd S. Gray, Jaroslaw Dziegielewski
Journal: Cancer Research (2015)

Abstract This study's aim was to define a novel molecular target and to develop an effective agent capable of overcoming intrinsic and acquired resistance to anti-EGFR therapy. Despite introduction of new therapies, lung cancer is a major cause of cancer death. One of its characteristics is the expression and activation of epidermal growth factor receptor (EGFR). Activating mutations in EGFR are present in approximately 20% of patients with non-small cell lung cancer (NSCLC), mostly in never-smokers. While most patients initially respond to treatment with anti-EGFR therapy, essentially all patients develop acquired drug resistance. T-type calcium channels, are present in lung cancer and support cell proliferation. Importantly, their expression often coincides with abnormal expression or mutations in EGFR. In this study, we investigated the effects of T-type channel inhibition on NSCLC survival and resistance to targeted therapy in vitro. We used a panel of cell lines differing in EGFR mutation status and sensitivity to EGFR tyrosine kinase inhibitors (TKIs). Our results show that T-type channel inhibitors alone arrest cells in the G1/G0 phase of the cell cycle and induce cell death. The treatment reduces activity of both PI3K/AKT/mTOR and JAK2/STAT5 pathways, often upregulated as a mechanism of acquired resistance to TKIs. Importantly, combined treatment with TKI, gefitinib, and T-type channels inhibitor, mibefradil, resulted in synergistic growth inhibition. Our results demonstrate a connection between T-type Ca2+ channels and aberrant EGFR activity in NSCLC, and provide the rationale for future use of two targeted therapies together. Since T-type calcium channel inhibitors are already undergoing clinical trials, our discoveries could be quickly translated into clinical practice. Citation Format: Barbara Dziegielewska, Lloyd S. Gray, Jaroslaw Dziegielewski. Overcoming resistance to anti-EGFR therapy in non-small cell lung cancer with a T-type Ca2+ channels inhibitor. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 750. doi:10.1158/1538-7445.AM2015-750
Sequential Phase II Studies of Flavopiridol by 72-Hour Continuous Infusion and 1-Hour Intravenous Bolus for the Treatment of Relapsed B-Cell Chronic Lymphocytic Leukemia: Results from CALGB Study 19805.
Authors: John C. Byrd, Bercedis L. Peterson, Janice L. Gabrilove, Olatoyosi M. Odenike, Michael R. Grever, Kanti R. Rai, James W. Vardiman, Richard A. Larson
Journal: Blood (2004)
Spleen Status and Engraftment After Allogeneic Hematopoietic Stem Cell Transplantation (HCT).
Authors: Gorgun Akpek, Marcelo C Pasquini, Manza-A Agovi, Brent Logan, Kenneth R. Cooke, Richard T Maziarz, Vikas Gupta, Hillard M. Lazarus, Gregory A. Hale, David I. Marks, Dipnarine Maharaj, Uday Popat, Matthew Carabasi, Martin Bornhaeuser, Brian J. Bolwell, Olle Ringden, Karen K Ballen, J. Douglas Rizzo, Philip L. McCarthy, Vincent T Ho
Journal: Blood (2010)
Abstract A1-36: The genomics of young lung cancer
Authors: Barbara J. Gitlitz, Deborah Morosini, Alicia Sable-Hunt, Bonnie J. Addario, Geoffrey R. Oxnard
Journal: Cancer Research (2015)

Abstract Primary lung cancer is increasingly understood as a heterogeneous disease made up of genomically defined subtypes requiring distinct treatment strategies. We hypothesize young age at diagnosis (&amp;lt;40 years) is a clinical characteristic associated with an increased chance for a targetable mutation. Our study will prospectively characterize the somatic and germline genomics of young lung cancer (GYLC). Our goals are to identify a genomically enriched subtype of lung cancer, facilitate delivery of targeted therapy and lay the groundwork for further studies of heritable and environmental lung cancer risk factors. A website allows for virtual consenting so patients can participate remotely and use social media to share our trial. We have defined 7 genomic alterations of interest, based on the lung cancer mutational consortium (LCMC) (EGFR, KRAS, HER2, BRAF, ALK, ROS1, RET). Subjects will undergo CLIA genomics to ensure that all of these genes have been tested. Those who are wild type will receive additional CLIA genomics using the FoundationOne® Heme panel, with the goal of identifying novel oncogenic drivers. Additional investigational genomics will include blood for germline testing. We believe the prevalence of targetable mutations will be greater in our population as compared to the LCMC and have powered our study to show an increase from 35% to 50%; and an improvement in the use of targeted therapy from 22% to 40%. The trial is currently accruing (NCT02273336). Preliminary results at 20% accrual show over 60% of pts with ALK, ROS1 or EGFR mutations. Further results to be presented at the meeting. (This trial is facilitated by the Addario Lung Cancer Medical Institute) Citation Format: Barbara J. Gitlitz, Deborah Morosini, Alicia Sable-Hunt, Bonnie J. Addario, Geoffrey R. Oxnard. The genomics of young lung cancer. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A1-36.
Renin-Angiotensin System Fingerprints of Heart Failure With Reduced Ejection Fraction
Authors: Noemi Pavo, Raphael Wurm, Georg Goliasch, Johannes Franz Novak, Guido Strunk, Mariann Gyöngyösi, Marko Poglitsch, Marcus D. Säemann, Martin Hülsmann
Journal: Journal of the American College of Cardiology (2016)
A Non-Internalizing Anti-CD40 Antibody, CHIR-12.12, Blocks CD40L-Induced Cytokine Production and Mediates Greater ADCC Than Rituximab in Primary CLL Cells.
Authors: Xia Tong, Sharon Lea Aukerman, Karen Lin, Natasha Aziz, Cheryl Goldbeck, Georgios V. Georgakis, Anas Younes, Wen-Kai Weng, Susan O’Brien, William Wierda, Bahija Jallal, Mohammad Luqman
Journal: Blood (2005)
Genome-Wide ChIP-Seq Reveals a Dramatic Shift in the EKLF Binding Profile Between Erythroid Progenitors and Erythroblasts.
Authors: Andre M. Pilon, Subramanian S. Ajay, Hatice Ozel Abaan, Elliott H. Margulies, Patrick G. Gallagher, David M. Bodine
Journal: Blood (2009)
Abstract 570: PD-L1 expression in paired non-small cell lung cancer tumor samples
Authors: Jhingook Kim, Steffen Filskov Sorensen, Yoon-La Choi, Zhen (Adelle) Wang, Jong-Mu Sun, Hyejoo Choi, Jeanette Baehr Georgsen, Marisa Dolled-Filhart, Kenneth Emancipator, Dianna Y. Wu, Peter Meldgaard, Wei Zhou, Henrik Hager
Journal: Cancer Research (2015)

Abstract Background There is limited information on changes over time in programmed death ligand 1 (PD-L1) expression in non-small cell lung cancer (NSCLC). Methods PD-L1 expression was assessed in paired tumor samples collected at different time points from the same patient using a prototype immunohistochemistry (IHC) assay with the 22C3 antibody. PD-L1 strong and weak positivity were defined to be traceable to the 1% and 50% cutoffs used in the clinical trial version of the assay. Concordance of PD-L1 expression between samples was analyzed by treating the IHC proportional score as a continuous and categorical variable. Results 90 patients were included (73 from Korea, 17 from Denmark). 75% were male, 37% had squamous cell carcinoma, and 83% had stage I-IIIA disease. 97% of first samples and 53% of second samples were from lung. 89% and 63%, respectively, were surgical samples, with a median interval of 20.9 months (range, 0.1-94.0) between collection dates; 91% of paired samples were collected &amp;gt;3 months apart. A significant correlation of the PD-L1 IHC proportional score was observed for the paired samples (Pearson correlation coefficient, 0.62; P &amp;lt; 0.001). At the second time point, scores were identical in 39% of paired samples, higher in 32%, and lower in 29%. Of note, 12% of PD-L1-negative cases became positive and 20% of PD-L1-positive cases become negative at the second time point. The concordance rate was 56% (95% CI, 46%-67%) when PD-L1 expression was categorized as strong or weak positive or negative (Table). Conclusion Although a significant correlation of the PD-L1 IHC proportional score was observed, this preliminary analysis suggested a discordance rate of 44% between initial and subsequent NSCLC tumor samples when patients were categorized by PD-L1 expression level. Similar results were observed when analyzing paired melanoma samples. This discordance should be considered if PD-L1 expression is used for selection of enrollment in clinical trials. Table. Concordance of PD-L1 Expression in Paired NSCLC Samples (N = 90) Later Time PointPD-L1 ExpressionStrong positive, n (%)Weak positive, n (%)Negative, n (%)Earlier Time PointStrong positive3 (3)3 (3)1 (1)Weak positive7 (8)20 (22)17 (19)Negative011 (12)28 (31) Citation Format: Jhingook Kim, Steffen Filskov Sorensen, Yoon-La Choi, Zhen (Adelle) Wang, Jong-Mu Sun, Hyejoo Choi, Jeanette Baehr Georgsen, Marisa Dolled-Filhart, Kenneth Emancipator, Dianna Y. Wu, Peter Meldgaard, Wei Zhou, Henrik Hager. PD-L1 expression in paired non-small cell lung cancer tumor samples. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 570. doi:10.1158/1538-7445.AM2015-570
Niche WNT5A regulates the actin cytoskeleton during regeneration of hematopoietic stem cells
Authors: Christina Schreck, Rouzanna Istvánffy, Christoph Ziegenhain, Theresa Sippenauer, Franziska Ruf, Lynette Henkel, Florian Gärtner, Beate Vieth, M. Carolina Florian, Nicole Mende, Anna Taubenberger, Áine Prendergast, Alina Wagner, Charlotta Pagel, Sandra Grziwok, Katharina S. Götze, Jochen Guck, Douglas C. Dean, Steffen Massberg, Marieke Essers, Claudia Waskow, Hartmut Geiger, Mathias Schiemann, Christian Peschel, Wolfgang Enard, Robert A.J. Oostendorp
Journal: The Journal of Experimental Medicine (2016)

Here, we show that the Wnt5a-haploinsufficient niche regenerates dysfunctional HSCs, which do not successfully engraft in secondary recipients. RNA sequencing of the regenerated donor Lin− SCA-1+ KIT+ (LSK) cells shows dysregulated expression of ZEB1-associated genes involved in the small GTPase-dependent actin polymerization pathway. Misexpression of DOCK2, WAVE2, and activation of CDC42 results in apolar F-actin localization, leading to defects in adhesion, migration and homing of HSCs regenerated in a Wnt5a-haploinsufficient microenvironment. Moreover, these cells show increased differentiation in vitro, with rapid loss of HSC-enriched LSK cells. Our study further shows that the Wnt5a-haploinsufficient environment similarly affects BCR-ABLp185 leukemia-initiating cells, which fail to generate leukemia in 42% of the studied recipients, or to transfer leukemia to secondary hosts. Thus, we show that WNT5A in the bone marrow niche is required to regenerate HSCs and leukemic cells with functional ability to rearrange the actin cytoskeleton and engraft successfully.
Abstract 2649: Inhibition of mTOR, but not PI3K, is required for the anti-tumor efficacy in breast cancer of dual PI3K/mTOR inhibitors given in combination with MEK inhibitors
Authors: Aleisha M. Smith, Jessie Xiong, Lucas Hunter, Jamie Jordan, Kelly Clark, David B. Darr, Sharpless Norman, Charles M. Perou, William Y. Kim
Journal: Cancer Research (2015)

Abstract Background: The mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathways are deregulated in many cancers including breast cancer. Additionally, studies have shown that significant crosstalk exists between these pathways; often making single pathway inhibition ineffective. While, combined PI3K/mTOR and MEK inhibition appears highly active in pre-clinical models, the combination has been reported to be toxic in human use. In an effort to produce a more targeted regimen, we examined whether both PI3K and mTOR inhibition are required for pre-clinical anti-tumor efficacy in combination with a MEK inhibitor. Methods: In vivo studies assessed overall survival and best tumor response upon administration of dual PI3K/mTOR (BEZ235 and GSK806) versus allosteric mTOR inhibition (Everolimus) in combination with MEK inhibition (AZD244 and GSK212) in genetically engineered murine models (GEMM) of breast cancer [T11 and C(3)Tag]. Activation and response of the PI3K/mTOR and MEK/ERK pathways to dual PI3K/mTOR, allosteric mTOR inhibition, and MEK inhibition were assessed in vitro in murine cell lines derived from the above GEM models. Results: Single agent regimens of MEK, allosteric mTOR, or dual PI3K/mTOR inhibition were minimally effective in C(3)Tag or T11 tumors in vivo. As previously reported, combined PI3K/mTOR and MEK inhibition showed potent pre-clinical activity in both the T11 and C3Tag models, prolonging overall survival relative to both vehicle or single-agent treated mice. Surprisingly, combinations of MEK inhibitors with allosteric mTOR inhibitors were as active as the MEK/PI3K/mTOR combination. In vitro studies in cell lines derived from these tumor models showed that mTORC1 inhibition, but not PI3K inhibition, resulted in compensatory activation of MEK. Conclusions: Combined targeting of the mTOR and MEK pathways results in improved response and survival in faithful GEM models of breast cancer. The combination of dual PI3K/mTOR catalytic inhibitors with MEK inhibition does not afford benefit over combined allosteric mTOR and MEK inhibition Citation Format: Aleisha M. Smith, Jessie Xiong, Lucas Hunter, Jamie Jordan, Kelly Clark, David B. Darr, Sharpless Norman, Charles M. Perou, William Y. Kim. Inhibition of mTOR, but not PI3K, is required for the anti-tumor efficacy in breast cancer of dual PI3K/mTOR inhibitors given in combination with MEK inhibitors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2649. doi:10.1158/1538-7445.AM2015-2649
Dysregulation of IL12 Signaling As a Novel Cause of an Autoimmune Lymphoproliferative like Syndrome
Authors: Schafiq Nabhani, Sebastian Ginzel, Hagit Miskin, Shoshana Revel-Vilk, Dan Harlev, Bernhard Fleckenstein, Andrea Höhnscheid, Prasad T. Oommen, Michaela Kuhlen, Ralf Thiele, Hans-Jürgen Laws, Arndt Borkhardt, Polina Stepensky, Ute Fischer
Journal: Blood (2014)
Abstract 5571: Technologies for molecular epidemiology in cancer
Authors: Rao L. Divi, Mukesh Verma, Anthony Dickherber
Journal: Cancer Research (2015)

Abstract Future success in molecular epidemiology depends on how quickly epidemiology adopts, optimizes and validates emerging technologies for molecular-scale analysis. In order to advance molecular epidemiology in cancer, the National Cancer Institute (NCI) supports the development of novel, next-generation, and cutting-edge molecular and cellular analysis technologies. Here we present past and present technology development efforts and their impact on cancer epidemiology. Some of the technologies, whose early-stage development was supported by the NCI, such as resequencing arrays, gene expression assay system, technologies which enable next generation sequencing, RNA preservative, rolling circle amplification of DNA, digital PCR system, functionalization of quantum dots, chromatin immunoprecipitation with next gen Sequencing, and multidimensional protein identification technology are now mainstay in basic and clinical research laboratories for genomic, epigenomic, transcriptomic and proteomic analysis. Additionally, these technologies have significantly contributed in identifying molecular determinants of cancer, and in assessing risk, disease progression and prognosis in large scale cancer epidemiology. Current awards support developing technologies for single cell analysis which can capture heterogeneity, simultaneous detection of multiple oncogenes, sensitive sequencing of geneomic/somatic mutations, targeted sequencing, rare variant detection, sequencing of ultralow-frequency mutations, epigenetic changes, kinome, multiplexed detection of microRNA, proteins, cytokines and metabolites, circulating tumor cells, and highthroughput protein-DNA interactions assessment. In addition, several novel biospecimen collection, preservation and processing technologies are also being supported with the potential to define the future of molecular epidemiology. Collectively, these technology development efforts supported by NCI provide a tremendous opportunity for molecular epidemiologists wishing to study archived samples collected in large-scale epidemiology efforts, and optimize and validate them for new molecular analyses. Citation Format: Rao L. Divi, Mukesh Verma, Anthony Dickherber. Technologies for molecular epidemiology in cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5571. doi:10.1158/1538-7445.AM2015-5571
Diagnostic Efficacy of Whole-Exome Sequencing in 250 Patients with Congenital Bone Marrow Failure
Authors: Hideki Muramatsu, Yusuke Okuno, Kenichi Yoshida, Sayoko Doisaki, Asahito Hama, Xinan Wang, Atsushi Narita, Nozomu Kawashima, Yinyan Xu, Hirotoshi Sakaguchi, Yoshiyuki Takahashi, Masashi Sanada, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Seishi Ogawa, Seiji Kojima
Journal: Blood (2014)