tbuckley/cabot-search huggingface dataset:
Abstract 2320: Prox1 marks a stem cell population that promotes tumor progression in intestinal adenomas
Authors: Zoltan Wiener, Jenny Högström, Ville Hyvönen, Pauliina Kallio, Sarika Heino, Kari Alitalo
Journal: Cancer Research (2015)

Abstract Colorectal cancer (CRC) initiation and growth is often attributed to stem cells, yet little is known about the regulation of this cell population. We have shown that a subpopulation of cells expressing the Prox1 transcription factor have stem cell activity in intestinal adenomas, but not in the normal intestine. Using in vivo models and 3D ex vivo organoid cultures of mouse adenomas and human CRC, we found that Prox1 deletion reduced the number of stem cells and cell proliferation and decreased intestinal tumor growth in multiple CRC model systems. Loss of Prox1 also decreased autophagy and the survival of hypoxic tumor cells in tumor transplants. Thus, Prox1 is essential for the expansion of the stem cell pool in intestinal adenomas and CRC without being critical for the normal functions of the gut. To further study the adenoma stem cells in relation to the Prox1-positive cell population, we analyzed Apc-mutant intestinal organoids derived from Prox1-CreER; tdTomatoflox/Stop/flox; Apcmin/+ mice. In this lineage tracing model, the induction of Cre activity results in the expression of the red fluorescent protein tdTomato only in the Prox1-positive adenoma cells. FACS sorted tdTomato-positive cell population displayed a highly elevated capability to form new organoids compared to the tdTomato-negative cells, consistent with stem cells enrichment in the Prox1-positive cell population. Gene expression analysis provided new clues about the identity of the Prox1 positive cells. Citation Format: Zoltan Wiener, Jenny Högström, Ville Hyvönen, Pauliina Kallio, Sarika Heino, Kari Alitalo. Prox1 marks a stem cell population that promotes tumor progression in intestinal adenomas. [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 2320. doi:10.1158/1538-7445.AM2015-2320
Mantle Cell Lymphoma Genotypes Identified with CGH to BAC Microarrays Define Clinical Subgroups of Disease and Strongly Predict Patient Outcome.
Authors: Jose A. Martinez-Climent, Fanny Rubio-Moscardo, Joan Climent, Maria J. Terol, Elena T. Sarsotti, Isabel Benet, Reiner Siebert, Miguel A. Piris, Inaki Martin-Subero, Martin J.S. Dyer, Daniel Pinkel, Javier Garcia-Conde
Journal: Blood (2004)
CSF3R Mutations Represent a Novel Therapeutic Target in Pediatric AML with a High Degree of Overlap with CEBPA Mutations: a Report from COG AAML0531 and COG/NCI Target AML Initiative
Authors: Julia Elizabeth Maxson, Rhonda Ries, Yi-Cheng Wang, Robert B. Gerbing, E. Anders Kolb, Sarah L Thompson, Jaime M. Guidry Auvil, Marco A Marra, Yussanne Ma, Stuart Zong, Andrew J. Mungall, Richard Moore, William Long, Patee Gesuwan, Tanja M. Davidsen, Leandro C. Hermida, Jason E. Farrar, Jerald P. Radich, Malcolm A. Smith, Daniela S. Gerhard, Alan S. Gamis, Todd A. Alonzo, Soheil Meshinchi
Journal: Blood (2015)
A prospective study of S-1 + Irinotecan plus bevacizumab as second-line therapy in metastatic colorectal cancer (KSCC1102)
Authors: Hiroaki Tanioka, Akihito Tsuji, Yasunori Emi, Shimokawa Mototsugu, Yuji Miyamoto, Eiji Oki, Yoshito Akagi, Hideo Baba, Yutaka Ogata, Yoshihiko Maehara
Journal: Annals of Oncology (2015)
Abstract B28: Dynamic interplay between type I collagen signaling and invasion in pancreatic cancer
Authors: Mario A. Shields, Pascal Maguin, Sarah L. Dallas, Mikala Egeblad
Journal: Cancer Research (2016)

Abstract The stroma of pancreatic cancer can restrict as well as promote tumor progression. Why the stroma exhibits these paradoxical functions remains unclear. One of the major components of the pancreatic cancer stroma is fibrillar type I collagen. High levels of collagen in primary tumor specimens have been associated with poor survival and resistance to therapy in pancreatic cancer patients. To determine the effects of type I collagen on cancer cell behavior, we performed intravital confocal microscopic imaging in mice. We used mice that expressed GFPtopaz fused to the α2 chain of type I collagen under control of a 3.6kb fragment of the COL1A1 promoter [α2(I)-col-GFP mice]. Live imaging of pancreatic tumors, formed after orthotopic injection of cells derived from the classical KPC mouse models, showed that type I collagen architecture in the tumors was heterogeneous. Strikingly, we observed that invasive cancer cells migrated out of the tumors on linear type I collagen. Linearization of collagen fibers through cross-linking, catalyzed by lysyl oxidases (LOXs), is inversely correlated with metastasis-free survival in breast cancer. However, in our pancreatic cancer model, inhibiting LOX promoted collagen linearization, tumor growth and metastatic spread. Elevated collagen-mediated signaling, through activation of focal adhesion kinase (FAK) and discoidin domain receptor (DDR1), was also observed in the tumors treated with lysyl oxidase inhibitor. Lysyl oxidase inhibition also promoted cell contractility as shown by elevated phosphorylated mysosin light chain 2 (p-MLC2) in vivo and by in collagen contractility assays in vitro. TGF-β signaling is a potent stimulator of collagen secretion and of invasive behavior, and it is aberrantly regulated in pancreatic cancer. We observed that lysyl oxidase inhibitor increased phosphorylated Smad3, a downstream effector of TGF-β signaling. Together, our data suggest that the influence of collagen on tumor behavior depends on its architecture. In areas of linear collagen, we find high cancer cell motility out of the tumors and this correlates with increased FAK and TGF-β signaling activity. The architecture-specific function of collagen could potentially explain the paradoxical role for the stroma in pancreatic cancer progression. Citation Format: Mario A. Shields, Pascal Maguin, Sarah L. Dallas, Mikala Egeblad.{Authors}. Dynamic interplay between type I collagen signaling and invasion in pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr B28.
Abstract 5079: Parasympathetic signaling suppresses pancreatic cancer development
Authors: Bernhard W. Renz, Marina Macchini, Yoku Hayakawa, C. Benedikt Westphalen, Michael Churchill, Suchetak Kar, Xiaowei Chen, Karan Nagar, Yagnesh Tailor, Daniel L. Worthley, Alina C. Iuga, Ken P. Olive, Timothy C. Wang
Journal: Cancer Research (2015)

Abstract Background/Aims: The parasympathetic nervous system plays an important role in the regulation of epithelial homeostasis and has also been postulated to play a role in tumorigenesis. However, the exact role of the vagus nerve in pancreatic carcinogenesis is not well understood. Here we study the effects of muscarinic signaling on pancreatic tumorigenesis in a genetically engineered mouse model of pancreatic cancer (PDx1-Cre/KRasG12D (KC). Methods: Mice were either vagotomized at 8 weeks or treated with a cholinergic agonist. Pancreatic tissue was collected and analyzed by immunohistochemistry and RT-PCR at 20 weeks of age; cells were isolated and assayed for colony and sphere forming assays. Different human (AsPC-1, BxPC-3, Mia PaCa-2, Panc-1) and murine (K-2548 and K-8282) pancreatic cancer cell lines were subjected to cholinergic and anti-cholinergic drugs and assayed by RT-PCR, Western blot and flow cytometry. Results: In pancreatic organoid cultures derived from pancreata harboring an oncogenic KRas mutation, cholinergic agonists suppressed sphere formation significantly. Furthermore, pharmacological inhibition or genetic knockout of the muscarinic M3 receptor abolished this effect in vitro. In human and murine pancreatic cancer cells, anchorage independent growth and tumor sphere forming capacity were reduced by pretreatment with cholinergic agonists. Further evaluation revealed that parasympathetic agonists decrease the CD44+CD24+EpCAM+ proved CSC's population. Vagotomy, when performed in KC mice at 8 weeks resulted in pancreatic cancer development in 20% of the animals at 20 week of age. Treatment with the direct muscarinic agonist bethanechol caused a significant delay of PanIN progression in KC mice. Conclusions: Taken together, our findings suggest that vagal innervation has a regulatory role in pancreatic tumorigenesis via M3 receptor-mediated suppression of CSCs. Since current surgical approaches to resection of PDAC from the head of the pancreas are necessarily associated with a parasympathetic denervation of the pancreas, and thereby a loss of its suppressive effect, this fact may might partly explain the high local recurrence rate of this dismal disease. Additional treatment with cholinergic agonists should be considered in future regimen. Citation Format: Bernhard W. Renz, Marina Macchini, Yoku Hayakawa, C. Benedikt Westphalen, Michael Churchill, Suchetak Kar, Xiaowei Chen, Karan Nagar, Yagnesh Tailor, Daniel L. Worthley, Alina C. Iuga, Ken P. Olive, Timothy C. Wang. Parasympathetic signaling suppresses pancreatic cancer development. [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 5079. doi:10.1158/1538-7445.AM2015-5079
Post-Transplant Cyclophosphamide (PTCY) Vs Anti-Thymoglobulin (ATG) As Part of the Gvhd Prophylaxis for Fludarabine/Clofarabine/Busulfan Reduced Intensity Conditioning (RIC) in Allogeneic Stem Cell Transplantation (allo-SCT): Influence on Early Immune Reconstitution
Authors: Christelle Retiere, Catherine Willem, Thierry Guillaume, Henri Vié, Laetitia Gautrot-Rolland, Emmanuel Scotet, Xavier Saulquin, Katia Gagne, Beatrice Clemenceau, Pierre Peterlin, Alice Garnier, Marie-Christine Bene, Patrice Chevallier
Journal: Blood (2015)
Relationship between CCR5(WT/Δ32) heterozygosity and HIV-1 reservoir size in adolescents and young adults with perinatally acquired HIV-1 infection
Authors: M. Martínez-Bonet, A. González-Serna, M.I. Clemente, S. Morón-López, L. Díaz, M. Navarro, M.C. Puertas, M. Leal, E. Ruiz-Mateos, J. Martinez-Picado, M.A. Muñoz-Fernández
Journal: Clinical Microbiology and Infection (2016)

Several host factors contribute to human immunodeficiency virus (HIV) disease progression in the absence of combination antiretroviral therapy (cART). Among them, the CC-chemokine receptor 5 (CCR5) is known to be the main co-receptor used by HIV-1 to enter target cells during the early stages of an HIV-1 infection.We evaluated the association of CCR5(WT/Δ32) heterozygosity with HIV-1 reservoir size, lymphocyte differentiation, activation and immunosenescence in adolescents and young adults with perinatally acquired HIV infection receiving cART.CCR5 genotype was analysed in 242 patients with vertically transmitted HIV-1 infection from Paediatric Spanish AIDS Research Network Cohort (coRISpe). Proviral HIV-1 DNA was quantified by digital-droplet PCR, and T-cell phenotype was evaluated by flow cytometry in a subset of 24 patients (ten with CCR5(Δ32/WT) genotype and 14 with CCR5(WT/WT) genotype).Twenty-three patients were heterozygous for the Δ32 genotype but none was homozygous for the mutated CCR5 allele. We observed no difference in the HIV-1 reservoir size (455 and 578 copies of HIV-1 DNA per million CD4+ T cells in individuals with CCR5(WT/WT) and CCR5(Δ32/WT) genotypes, respectively; p 0.75) or in the immune activation markers between both genotype groups. However, we found that total HIV-1 DNA in CD4+ T cells correlated with the percentage of memory CD4+ T cells: a direct correlation in CCR5(WT/Δ32) patients but an inverse correlation in those with the CCR5(WT/WT) genotype.This finding suggests a differential distribution of the viral reservoir compartment in CCR5(WT/Δ32) patients with perinatal HIV infection, which is a characteristic that may affect the design of strategies for reservoir elimination.
675. High Quality Plasmid DNA Manufacturing for Ex-Vivo Protein Synthesis and Viral Vector Production for Gene Therapy
Authors: Neha Tiwari, Jill Beilowitz, Carlos Sampson, Dorothy Peterson
Journal: Molecular Therapy (2015)

High quality plasmid DNA is required for a variety of therapeutic purposes. Although use as a DNA vaccine is the most popular, a high quality plasmid DNA product is also required as the raw material for processes like viral vector production for gene therapy, ex-vivo protein synthesis, etc. Contrary to a DNA vaccine, plasmid products used as raw materials have varied requirements in terms of purity and presence of contaminant levels in the final product. It is essential to have a large scale plasmid production method which can be tailored for the specific plasmid product based on its potential use.
A Novel Denaturing-High Performance Liquid Chromatography (D-HPLC)-Based Method for Kit Mutation Screening of Patients (pts) with Systemic Mastocytosis (SM) Allows the Identification of Unreported Kit Variants.
Authors: Sabrina Colarossi, Simona Soverini, Alessandra Gnani, Michela Rondoni, Simona Gatto, Serena Merante, Enrico Gottardi, Daniela Cilloni, Pellegrino Musto, Mario Tiribelli, Roberta Zanotti, Giovanni Martinelli, Michele Baccarani
Journal: Blood (2006)
Doxycycline Regulatable Expression of Cytidine Deaminase Mediates Myeloprotection and Avoids Lymphotoxicity in a Murine Transplant Model
Authors: Nico Lachmann, Sebastian Brennig, Nils Pfaff, Heiko Schermeier, Axel Schambach, Christopher Baum, Thomas Moritz
Journal: Blood (2011)
Abstract 3373: Identification of inflammation-related genes that regulate tumor-associated stemness using high-throughput siRNA screening
Authors: Junling Xie, Huiwen He, Chong Chen, Lipeng Bai, Wei Wang, Yan Liu, Jian Guo, Peng Wu, Rong Xiang, Yunping Luo
Journal: Cancer Research (2015)

Abstract Cancer associated stem cells (CSCs) are considered to be responsible for tumor recurrence, metastasis as well as chemoresistance. These properties of tumor associated stemness are maintained by specialized microenvironment, including inflammation which is a key component of the tumor microenvironment. To study the relationship between inflammation and stemness of CSCs, here, we established a robust high-throughput RNAi screen platform for a global survey of inflammation-related genes affecting CSCs identity via alteration of Oct4 expression. Consequently, we found 72 novel genes from 1027 inflammation-related genes which could significantly affect OCT4 expression. These genes are functionally distinct including cytokines, adhesion molecules, apoptotic molecules, kinase, metabolism-related enzymes and transcriptional factors. Further, we carry out a functional validation of the 72 hits by mean of ALDEFLUORTM assay and we demonstrate that silence genes expression of IL-1A, IL-1B, ICAM3, CCL16, TRAF6, PRTN3, PDE3A, BCAR1, NFKB1 and IKK-β by siRNA would dramatically downregulate of the ALDH+ subpopulation cells. Moreover, we studied the functional roles of these factors on different kinds of tumor cell lines and mult-organ tumor tissue microarray. We observed that knockdown TRAF6 (TNF-α receptor associated factor 6) would reduce the expression of stemness associated genes SOX2, OCT4, NANOG, LIN28b, IKK-β β-catenin, and abate sphere-forming ability of breast cancer MDA-MB-231 cells, lung cancer A549 cells, liver cancer HepG2 cells and colon cancer SW-480 cells. It was also found that the expression of TRAF6 has a conspicuous relationship with multiple tumor occurrence and malignancy on tissue microarray. Most importantly, we found that knockdown the expression of TRAF6 could markedly suppressed tumor growth and metastasis of MDA-MB-231 in NOD/SCID mice model. Together, we uncovers a wealth of novel inflammatory regulators of CSCs by a high-throughput siRNA screen and validated the cytokine TRAF6 could govern tumor associated stemness in different tumors in vitro and in vivo, which would be a potential therapeutical target. Citation Format: Junling Xie, Huiwen He, Chong Chen, Lipeng Bai, Wei Wang, Yan Liu, Jian Guo, Peng Wu, Rong Xiang, Yunping Luo. Identification of inflammation-related genes that regulate tumor-associated stemness using high-throughput siRNA screening. [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 3373. doi:10.1158/1538-7445.AM2015-3373
Abstract 2: Metabolomics analysis reveals distinct profiles of non-muscle invasive and muscle-invasive bladder cancer
Authors: Divya Sahu, Yair Lotan, Bryan Wittmann, Bruce Neri, Donna Hansel
Journal: Cancer Research (2016)

Abstract Background: Bladder cancer affects &amp;gt;70,000 patients annually in the United States. Despite its high incidence, therapeutic options are limited in early or late stage. We wanted to identify key metabolic pathways that were altered in bladder cancer development and progression. Experimental Design: We performed global metabolomics profiling of benign urothelium, high-grade non-muscle invasive bladder cancer and advanced, muscle-invasive bladder cancer using GC-MS and LC-MS platforms. This analysis was coupled with publicly available data on transcriptomics of key enzymes, to determine pathways that may be suitable for future therapeutics development. Results: Categorical pathways globally dysregulated in cancer relative to benign urothelium included glucose, TCA cycle, lipid, amino acid and nucleotide pathways. Bladder cancers demonstrated Warburg metabolism, with elevated glucose utilization to drive glycolysis and sorbitol pathway intermediates. Elevated late TCA cycle intermediates, coupled with higher levels of amino acids and dipeptides, suggest the possibility of anaplerotic activity in bladder cancer as a mechanism to sustain energy production. Medium and long chain fatty acids were produced at the expense of dicarboxylic fatty acids. Muscle-invasive bladder cancers showed enhanced use of COX and LOX metabolomics pathways and a possible role for inflammation in regulating NAD+ synthesis in muscle-invasive bladder cancer. Transcriptomic profiling validated that the majority of metabolomics pathway alterations corresponded to gene expression changes of enzymes responsible for metabolite production. Conclusions: This study identifies multiple parallel metabolomics changes unique to non-muscle invasive and muscle-invasive bladder cancer that can be used to justify testing novel therapeutics targeting metabolic pathways in bladder cancer. Citation Format: Divya Sahu, Yair Lotan, Bryan Wittmann, Bruce Neri, Donna Hansel. Metabolomics analysis reveals distinct profiles of non-muscle invasive and muscle-invasive bladder cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2.
PET -CT Adapted Therapy After 3 Cycles of ABVD for All Stages of Hodgkin Lymphoma. Preliminary Results in 193 Patients
Authors: Astrid Pavlovsky, Isolda Fernandez, Virginia Prates, Miguel A Pavlovsky, Lucia Zoppegno, Ana Lisa Basquiera, Federico Sackmann, Francisco Lastiri, Gustavo Milone, Santiago Pavlovsky
Journal: Blood (2011)
Allogeneic Hematopoietic Stem Cell Transplantation Could Improve Survival of Cytogenetically Normal Adult Acute Myeloid Leukemia Patients with DNMT3A Mutations
Authors: Yang Xu, Yanjun Sun, Hongjie Shen, Zhen Yang, Huiying Qiu, Aining Sun, Suning Chen, Wu Depei
Journal: Blood (2015)
Vascular Endothelial Growth Factor (VEGF) promoter gene polymorphism in mastocytosis. A study of the European Competence Network on Mastocytosis (ECNM)
Authors: M. Niedoszytko, B. Nedoszytko, M. Lange, J. van Doormaal, J. Glen, Otna M. Zab, J. Renke, J. Varkonyi, E. Jassem, J. Roszkiewicz, P. Valent
Journal: Allergy (2008)
Levels of Phosphorylated P70 S6 Kinase and Phosphorylated ERK1&amp;2 Predict Overall Survival and Time to First Treatment In Chronic Lymphocytic Leukaemia
Authors: James R Bailey, Gina L Eagle, Pointon Jo, Ria Brathwaite, Abbott Jody, Russell Patmore, Paul Evans, John Greenman, Lynn Cawkwell, David J Allsup
Journal: Blood (2010)
Themis2 lowers the threshold for B cell activation during positive selection
Authors: Daian Cheng, Mukta Deobagkar-Lele, Ekaterina Zvezdova, Seeyoung Choi, Shoji Uehara, Delphine Baup, Sophia C Bennett, Katherine R Bull, Tanya L Crockford, Helen Ferry, Claude Warzecha, Marlène Marcellin, Anne Gonzalez de Peredo, Renaud Lesourne, Consuelo Anzilotti, Paul E Love, Richard J Cornall
Journal: Nature Immunology (2016)
Abstract 4071: Cancer stem cell-induced vascularization of skin cancer tumors
Authors: Dan Grun, Gautam Adhikary, Richard Eckert
Journal: Cancer Research (2015)

Abstract Our previous studies identify a subpopulation of epidermal cancer stem (ECS) cells in human squamous cell carcinoma that are efficient tumor formers. These cells display enhanced invasion and migration, and form large, invasive and highly aggressive tumors. We now show that ECS cells produce highly vascularized tumors. This is confirmed visually and by detection of increased expression of the CD31 endothelial cell marker. To understand the molecular basis for increased vascularization, we assayed for ECS cell and non-stem cancer cell production of angiogenic factors. Pro-angiogenic factors, including VEGF-A, HIF-1α and MMP9, are produced at high level in ECS cell-derived tumors, as compared to non-stem cancer cell tumors. In addition, anti-angiogenic factor production (thrombospondin-1, endothelin-1, serpin B5) is reduced. This is consistent with the finding that ECS cell tumor extracts more efficiently stimulate HUVEC cell tube formation. Moreover, these ECS tumor-derived cells display enhanced spheroid formation, and cell migration and invasion. Knockdown of VEGF-A or VEGFR2, or treatment with anti-VEGF-A attenuates these events. In addition, treatment with bevacizumab (anti-VEGF-A) suppresses tumor formation in vivo. These studies suggest that the VEGF-A signaling pathway is enhanced in ECS cells and is in part responsible the ability of these cells to form aggressive and highly vascularized tumors. Citation Format: Dan Grun, Gautam Adhikary, Richard Eckert. Cancer stem cell-induced vascularization of skin cancer tumors. [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 4071. doi:10.1158/1538-7445.AM2015-4071
Direct Effect on the Stroma by the Conventional Anti-Multiple Myeloma Drug Dexamethasone Results In Resistance of Multiple Myeloma Plasma Cells Against Therapy. Sensitisation to Dexamethasone by the Kinase Inhibitor Dasatinib
Authors: Karthik Ramasamy, Hazera Khatun, Lee Macpherson, Ghulam J. Mufti, Stephen Schey, Yolanda Calle
Journal: Blood (2010)
Increased Immune Suppressive CD14+ hla-DRneg Circulating Monocytes Are Found in Aggressive Non-Hodgkin's Lymphoma and Correlated with Increased Arginase I Level.
Authors: Yi Lin, Michael P. Gustafson, Peggy A Bulur, Mary Maas, Amy Mohr, Thomas E Witzig, Allan Dietz
Journal: Blood (2009)