tbuckley/cabot-search huggingface dataset:
Abstract 3185: Complement C5 promotes male bias of pancreatic neuroendocrine tumor metastasis
Authors: Tanupriya Contractor, Chang Chan, Shinta Kobayashi, Richard Clausen, Yvonne Sun, Edaise da Silva, Evan Vosburgh, Arnold J. Levine, Laura Tang, Chris R. Harris
Journal: Cancer Research (2015)

Abstract Among patients with neuroendocrine tumors, males are more likely than females to develop liver metastatic disease. We show that this male bias toward liver metastasis is also observed in a mouse model for pancreatic neuroendocrine tumorigenesis (PanNETs). Interestingly, primary tumors from mice with metastatic disease display hepatomimicry, expressing genes normally expressed in liver. Both male and female primary tumors from mice with metastatic disease show hepatomimicry, although one of the liver genes, complement C5, is only induced in males. In mice knocked out for the complement C5 gene, the frequency of liver metastasis dropped significantly; moreover, males and females lacking a gene for complement C5 developed liver metastasis at the same frequency. Liver metastasis was also prevented by PMX53, a small molecule antagonist of C5aR1/CD88, which is the receptor for complement C5a. Thus complement C5 is epistatic to metastasis and promotes gender bias of liver metastatic disease. Citation Format: Tanupriya Contractor, Chang Chan, Shinta Kobayashi, Richard Clausen, Yvonne Sun, Edaise da Silva, Evan Vosburgh, Arnold J. Levine, Laura Tang, Chris R. Harris. Complement C5 promotes male bias of pancreatic neuroendocrine tumor metastasis. [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 3185. doi:10.1158/1538-7445.AM2015-3185
Phase I Trial of the 131I-Labelled Anti-CD25 Antibody Basiliximab in the Treatment of Patients with Relapsed or Refractory Lymphoma.
Authors: Gairin Dancey, John Violet, Shokri Othman, Sweta Parker, Alan Green, Surinder Sharma, Ros Francis, Natalie Griffin, Pei-San Chan, Peter Amlot, Anmol Malhotra, Nicholas Woodward, Peter Isaacson, Thomas A. Lister, John Buscombe, Richard Begent, Christopher McNamara
Journal: Blood (2007)
GSK3β Signaling Regulates the Motility of Hematopoietic Progenitors Via Prune.
Authors: Kfir Lapid, Gabriele D‘Uva, Alexander Kalinkovich, Aya Ludin, Karin Golan, Tomer Itkin, Massimo Zollo, Tsvee Lapidot
Journal: Blood (2010)
STEM-02TRANSCRIPTIONAL NETWORKS OF Sox2 IN GLIOBLASTOMA
Authors: Arlet Maria Acanda de la Rocha, Naiara Martínez Velez, Enric Xipell, Marisol González-Huarriz, Marta M Alonso Roldán
Journal: Neuro-Oncology (2015)

Glioblastoma multiforme (GBM), the most aggressive primary brain tumor, shows enrichment in gene expression related to a stem cell signature. Sox2 has been described as frequently overexpressed in poorly differentiated gliomas, and has emerged as a lineage-survival oncogene amplified in several tumors. Even though Sox2 is a critical transcription regulator of embryonic and neural normal stem cell function, the description of Sox2-regulated molecular circuitries remains poorly understood. Here we used array based approaches in a brain tumor stem cell line (BTSCs) where Sox2 was inhibited using siRNA to characterize the transcriptional networks regulated at the mRNA, microRNAs (miRNAs) and long non coding RNAs (lncRNAs) level. Among the most significant pathways down-regulated by Sox2 inhibition were cell cycle cascade, spliceosome genes and p53 signaling. On the other hand lysosome genes, endocytosis, insulin pathway and amino acids degradation are among the most upregulated. We also analyzed differentially expressed (p < 0.05) lncRNAs regulated by Sox2, including antisense, intergenic, processed transcripts, pseudogenes and other types. We choose the top 5 scoring lncRNAs to validate the array, using RT-PCR in several BTSCs, confirming the expression of two of them. We use the UCSC tool to examine expression levels in various human tissues and chromatin signatures. We also obtained a list of miRNAs significantly overexpressed (35 candidates) and down-regulated (22 candidates) by Sox2 (p < 0.01). We validate these results using different BTSCs lines. We analyzed the function of the 2 miRNAs; miR-301 and miR-182. The downregulation of both of them promoted the inhibition of migration/invasion and a change in the expression profile of angiogenic proteins. These data suggested the implication of Sox2 in the proangiogenic phenotype of GBM. Moreover, this analysis reveals an ample repertoire of functions that Sox2 regulates in GBM, providing insights into disease development.
Differential protein stability and clinical responses ofEML4-ALK fusion variants to various ALK inhibitors in advancedALK-rearranged non-small cell lung cancer
Authors: C.G. Woo, S. Seo, S.W. Kim, S.J. Jang, K.S. Park, J.Y. Song, B. Lee, M.W. Richards, R. Bayliss, D.H. Lee, J. Choi
Journal: Annals of Oncology (2016)
678. Increasing AAV Vector Yield By Riboswitch-Mediated Attenuation of Toxic Transgene Effects in HEK-293 Producer Cells
Authors: Benjamin Strobel, Benedikt Klauser, Thorsten Lamla, Florian Gantner, Sebastian Kreuz
Journal: Molecular Therapy (2015)

Adeno-associated virus (AAV) vectors are among the most promising viral vector systems for human gene therapy and have also been used extensively to investigate gene function in preclinical research. Achievement of high-titer vector yields regardless of the packaged transgene hence is a key goal of process optimization. However, transgenes expressed by constitutive, ubiquitously active promoters (such as the CMV promoter) often impair producer cell performance due to cytotoxic, anti-proliferative or other unknown effects, resulting in low vector yield. In our study, we explored artificial aptazyme riboswitches as novel RNA-intrinsic tools to regulate vector transgene activity during AAV production in HEK-293 cells. To this end, we integrated the guanine-responsive GuaM8HDV aptazyme in the UTR of a standard AAV transgene cassette and explored switching behavior under AAV production conditions. Our results demonstrate that transgene expression can be efficiently attenuated by a single addition of guanine in a routine medium exchange step during AAV production, thereby decreasing producer cell performance-impairing transgene effects such as cytotoxicity. In a proof-of-concept study using transgenes with both known (e.g. pro-apoptotic) as well as unknown modes of producer cell impairment, AAV vector yields could be boosted up to 23-fold with the riboswitch approach as compared to conventional vectors. As expected, this effect worked independently of the AAV serotype/capsid variant used. Importantly, GuaM8HDV-harboring AAV vectors preserved functionality (i.e. the ability to express the transgene) in vivo, as demonstrated in a mouse model of AAV-TGFb1-induced pulmonary fibrosis. Contrary to other inducible systems for gene expression control, the riboswitch system presented here does not require expression of additional transcription factors, but works in a small-molecule regulatable, RNA-intrinsic manner. Moreover, the riboswitch sequence only occupies ≈100 base pairs of plasmid space – a particular advantage for AAV vectors. Finally, this approach should in principle be expandable to other viral vector systems produced in mammalian cell culture such as Adenoviral vectors. Thus, we propose riboswitches as novel tools to foster transgeneindependent, high-titer production of viral vectors in mammalian cell culture systems. Moreover, our study further supports exploration of this technology for other purposes such as studying transgene dynamics and controlling transgene expression as a safety module in next-generation gene therapy vectors.
Treosulfan-Based Conditioning in Pediatric Hematopoietic Stem Cell Transplantation: A Prospective Study on Pharmacokinetics and Early Clinical Outcomes
Authors: Marloes H ten Brink, Robbert G.M. Bredius, Juliëtte Zwaveling, Oliver Ackaert, Jan den Hartigh, Frans J. Smiers, Henk-Jan Guchelaar, Arjan Lankester
Journal: Blood (2014)
Abstract 410: SPARC expression enhances cellular aggregation and resistance to gemcitabine in pancreatic cancer cells
Authors: Edgardo Salvatierra, Elvia Rivas, Leandro Guttlein, Emily Robitschek, Andrea Llera, Osvaldo Podhajcer
Journal: Cancer Research (2015)

Abstract Pancreatic cancer (PaCa) is a very aggressive disease with a high mortality rate, characterized by a survival time of only few months after diagnosis. Pancreatic cancers also demonstrate great resistance to chemotherapeutic regimes, associated with an extensive desmoplastic reaction. The matricelular protein SPARC is involved in the interaction between the cell and the extracellular matrix, and its expression has been associated with worse prognosis in general, and in patients treated with gemcitabine. To evaluate its role in pancreatic cancer and chemotherapeutic resistance, we overexpressed SPARC in the SPARC-negative pancreatic cancer cells lines Miapaca2, Sw1990, and Panc1. The in vitro growth of two stable clones obtained from the different cell lines was compared with eGFP-transduced controls. No significant differences were observed in the 2D in vitro growth or the clonogenic capacity between pancreatic cancer cells expressing or not expressing SPARC. However, cell growth in 3D spheroid culture was markedly different. Indeed, SPARC-expressing cells exhibited more compact structures, with 45% reduction in spheroid size compared to control eGFP-expressing cells. This could partially be explained by the fact that the SPARC-expressing cells themselves exhibited more than 50% reduction in their size compared to the eGFP cells. While SPARC expression in pancreatic cancer cells did not affect Gemcitabine EC50 in 2D culture, SPARC-positive Panc1 and SW1990 cells exhibited six to ten times increased EC50 in 3D spheroids. Because the cell-cell interactions could potentially affect drug efficacy, and because increased resistance to gemcitabine has been associated with epithelial-mesenchymal transition (EMT), we analyzed the expression of EMT-associated genes (SNAI1 and OCLN), and genes also involved in cellular junctions (CDH1 and OCLN). SPARC-positive pancreatic cancer cells down regulated the expression of SNAI1 and CDH2, while CDH1 and OCLN were up-regulated Taken together, these data indicate that SPARC expression in PaCa cell lines diminishes cells size and modulates gemcitabine resistance in 3D models of cell culture, possibly through the modulation of epithelial genes related to cell-cell connections and EMT. Citation Format: Edgardo Salvatierra, Elvia Rivas, Leandro Guttlein, Emily Robitschek, Andrea Llera, Osvaldo Podhajcer. SPARC expression enhances cellular aggregation and resistance to gemcitabine in pancreatic cancer cells. [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 410. doi:10.1158/1538-7445.AM2015-410
Resected pancreatic neuroendocrine tumors: Patterns of failure and disease-related outcomes with or without radiotherapy.
Authors: T. M. Zagar, R. R. White, C. G. Willett, P. Papavassiliou, D. S. Tyler, K. Papalezova, C. Guy, R. Clough, B. G. Czito
Journal: Journal of Clinical Oncology (2011)

325 Background: Pancreatic neuroendocrine tumors (NET) are rare with improved prognosis compared to adenocarcinomas. Surgical resection remains the standard of care although many patients present with unresectable/metastatic disease. While many resected patients will fail distantly, little is known regarding the use of adjuvant radiotherapy. To define this and establish specific patterns of failure, an analysis of resected patients from a single institution was performed. Methods: From 1994 to 2009, 33 patients with NET of the pancreatic head underwent resection with curative intent at Duke University. Sixteen patients were treated with surgical resection alone, and an additional 17 underwent resection with adjuvant (n=10) or neoadjuvant (n=7) radiation therapy, usually with concurrent fluoropyrimidine-based chemotherapy (CMT). Median radiation dose was 50.4 Gy and median follow-up 28 months. Results: Patients receiving radiation therapy were more likely to have involved nodes (47% vs 19%, p=0.09), more mitoses per high power field (p=0.10) and involved margins (47% vs 31%, p=0.20) compared to surgery alone patients. Median survival for the whole cohort was 52 months. Two-year survival was 68% for the CMT group and 93% for the surgery alone group (p=0.03). Two-year local control was 85% for the CMT and 90% for the surgery group (p=0.49). Two-year metastasis-free survival was 45% and 69% for the CMT and surgery patients, respectively (p=0.02). Conclusions: Patients receiving CMT were more likely to have adverse pathologic features compared to surgery-alone patients. Survival outcomes were high in both groups, although less so in the CMT group. Distant metastasis development dominated patterns of failure. Local failure following resection of NETs is uncommon, and the role of adjuvant radiotherapy in this setting remains unclear. No significant financial relationships to disclose.
82. Scalable, Animal-Free, Suspension-Based Production of Siv Lentiviral Vectors
Authors: Stephen C. Hyde, Lee A. Davies, Ian A. Pringle, Makoto Inoue, Mamoru Hasegawa, A. Christopher Boyd, Uta Griesenbach, Eric W.F.W. Alton, Deborah R. Gill
Journal: Molecular Therapy (2015)

We are developing lung gene transfer vectors to direct abundant, sustained transgene expression in three therapeutic compartments: (i) within lung cells to treat lung disorders such as cystic fibrosis (CF), (ii) secreted from lung cells into the lung lumen to treat viral infections and airway diseases such as alpha1 anti-trypsin deficiency, (iii) secreted from nasal and lung cells into the circulatory system to treat hematologic and a range of other disorders. Such diseases are associated with a high burden of care often involving frequent antibiotic treatments, physiotherapy and supportive systemic infusions; and considerable patient morbidity and mortality. We have developed an efficient lung gene transfer platform based on a European and US Pharmacopoeial compliant, minimal recombinant SIV lentiviral vector which is specifically pseudotyped with the Sendai virus envelope proteins F and HN (rSIV.F/HN). Initially, production of rSIV.F/HN vectors was established in a serum-dependent, calcium phosphate-mediated, transient transfection process. Here we report the development of a scalable, animal-free, cGMP-compliant suspension cell culture based upstream production (USP) method. Serum-free media screening identified a suspension cell growth conditions that support efficient (>70%) multiple plasmid transient transfection of HEK293T cells with a range of cGMP-compliant liposomal and polymeric gene transfer agents. Small volume (40–400mL) studies in Erlenmeyer shake flasks and Design Of Experiments statistical approaches identified robust growth and transfection conditions that yield ≥5e6 TU/mL of unpurified rSIV. F/HN vectors. These parameters supported transition to 1L and 5L scale WAVE bioreactor cultures, where virus yield is maintained and plasmid DNA usage (a high proportion of the cGMP cost of goods) has been reduced to 0.33mg/L. F/HN pseudotype specific DNA removal and virus activation steps are incorporated into the downstream purification (DSP) method which relies on anion-exchange membrane virus capture and hollow-fibre UF/DF for vector purification and final formulation. In 56 independent, pH-controlled WAVE bioreactor cultures, purified yield exceeds 2.0e9 TU/L for a range of reporter gene constructs with a variety of promoters and 1.2e9 TU/L for a range of CFTR constructs (p>0.05; n=42/14 respectively). The final product directs abundant in vivo airway gene transfer, transducing 14.1% epithelial cells in the murine lung (p<0.001; 8e8 TU rSIV.F/HN hCEF EGFP), and directing CFTR transgene expression at ~30% of endogenous CFTR mRNA levels in the ovine lung (p<0.001; 8e8 TU rSIV.F/HN hCEF soCFTR2), exceeding presumed therapeutic levels. While these regulator friendly USP/DSP approaches have been tuned to yield highly purified and potent rSIV.F/HN vectors, the methodology is readily transferrable to VSV-G pseudotype production.
Association Between Hospitalization for Infection and Suicide—Reply
Authors: Helene Lund-Sørensen, Michael Eriksen Benros, Annette Erlangsen
Journal: JAMA Psychiatry (2016)

In Reply We appreciate the observations and comments raised in the letters from Regenold as well as from Silverman and Bondy regarding our study on the association between hospitalizations with infection and risk of death by suicide.1
Aggressive NK Cell Leukemia (ANKL): Experience with 34 Patients and Therapeutic Potentials of L-Asparaginase and Allogeneic Hematopoietic Cell Transplantation - A Japan-Korea Multicenter Study for ANKL (ANKL07) -
Authors: Fumihiro Ishida, Won Seog Kim, Young Hyeh Ko, Junji Suzumiya, Yasushi Isobe, Kazuo Oshimi, Shigeo Nakamura, Ritsuro Suzuki
Journal: Blood (2010)
PEMETREXED-RELATED RENAL TOXICITY IN PATIENTS (PTS) WITH THORACIC MALIGNANCIES
Authors: Trenta Patrizia, Iacovelli Roberto, Palazzo Antonella, D. Conte, F. Morano, G. Campenni, E. Risi, K. Truscelli, Mezi Silvia, Cortesi Enrico
Journal: Journal of Thoracic Oncology (2010)
Treatment Patterns and Outcomes of DLBCL after Failure of Front-Line Immunochemotherapy
Authors: Umar Farooq, Matthew J Maurer, Stephen M Ansell, Tasha Lin, Grzegorz S. Nowakowski, Luis Porrata, David J. Inwards, William Macon, Syrbu Sergei, James Cerhan, Thomas E. Witzig, Brian K Link, Thomas M. Habermann, Carrie A. Thompson
Journal: Blood (2015)
Treadmill stress test using body surface mapping in coronary artery disease. The clinical significance of ST depression.
Authors: Isao Kubota, Yoshihiko Watanabe, Masao Harada, Tetsuji Kaminishi, Kai Tsuiki, Shoji Yasui
Journal: Circulation (1982)

In this study we assessed in 27 patients with coronary artery disease whether the size of the ST-depression area, which was measured by body surface maps recorded before and after treadmill exercise, could be a useful indicator for evaluating coronary artery disease (CAD) quantitatively. The patients were divided into 3 groups on the basis of the findings of the left ventriculograms: patients with anterior asynergy (n = 6), those with inferior asynergy (n = 6) and those with no asynergy (n = 15). Coronary arteriograms were evaluated according to Pujadas, and ΣGrade, as an index of the severity of CAD, was developed by adding the grade numbers of the 4 main coronary stems (right coronary artery, main trunk of the left coronary artery, left anterior descending artery and left circumflex artery). Patients with inferior asynergy and with no asynergy have ST-depression areas in proportion to their ΣGrade (r = 0.845, p < 0.001), whereas none of the patients with anterior asynergy showed ST-depression areas regardless of their Grade. Of 6 patients who had anterior asynergy, 5 (83%) had pathologic Q waves in the left anterior chest leads. These findings emphasize the clinical value of the ST-depression area for the quantitative and non-invasive diagnosis of CAD, especially in patients without pathologic Q waves in the left anterior chest leads.
TREATMENT Toxicity in Adolescents and Young ADULT (AYA) PATIENTS COMPARED with Younger PATIENTS TREATED for HIGH RISK B-Precursor ACUTE LYMPHOBLASTIC LEUKEMIA (HR-ALL): A REPORT From the CHILDREN'S Oncology GROUP STUDY AALL0232
Authors: Eric C. Larsen, Wanda Salzer, James Nachman, Meenakshi Devidas, David R. Freyer, Elizabeth A. Raetz, Naomi Winick, Stephen P. Hunger, William L. Carroll
Journal: Blood (2011)
Abstract 1988: Role of N- ZEB1 in epithelial-mesenchymal transition (EMT)
Authors: M Candelaria Llorens, Ana M. Cabanillas
Journal: Cancer Research (2015)

Abstract Background: ZEB1 (Zn Finger E-box Binding Homeobox) transcription factor is important in both development and disease, including the TGFβ-induced epithelial-mesenchymal transition (EMT) by which many tumors undergo metastasis. ZEB1 contains 2 Zn finger domains (ZD1-ZD2) which bind DNA independently. ZEB1 expresses as two phosphorylated forms important for its biological role. We had characterized the role of phosphorylated C-term ZEB1. Aim: Our goal is to uncover the role of signaling pathway/s in the phosphorylation on N-term ZD1 (N-ZEB1) and characterize the functional role of N-ZEB1 in the process of EMT in mammary epithelial cells NMuMG. Results: A 728 aa fragment of N-ZEB1 was overexpressed in HEK293T cells and Immunoprecipitation with N-ZEB1 antibodies followed by western blot analysis with anti phospho kinases (AKT, MEK/ERK, PKC or PKA) substrate Antibodies. The results revealed that N-ZEB1 is solely phosphorylated by PI3K (AKT), MAPK and PKC pathways. IGF1-mediated phosphorylation can regulate nuclear localization of C-term ZEB1. Two N-ZEB1-GFP clones harboring first 490aa (eGFPZ1) and a 2nd clone of 130 aa, eGFPZ2 (included in the former) were transfected to CHO-K1 cells and treated with inhibitors and activators of kinase pathways for 15-60 minutes in serum free medium. Fluorescence microscopy techniques showed that IGF-1 induced relocation of a nuclear eGFPZ1 into the cytosol of CHO-K1 cells; on the contrary, eGFPZ2 was unresponsive to IGF-1. PMA/IONO (activator of PKC) treatment relocated both clones in the cytosol. Later on, NMuMG cells were used to investigate the role of N-ZEB1 in EMT. These epithelial cells, that can turn into mesenchymal type under TGFβ treatment, were stably transfected with eGFPZ2 or empty vector (control). The epithelial markers E-cadherin and actin assessed by Western blot and confocal microscopy were diminished or absent in eGFPZ2 cells. The activity of Matrix Metallo Proteases 2 was also increased in NMuMG-GFPZ2 cells. Also, proliferation, migration and invasion were significantly increased (P&amp;lt;0.001, P&amp;lt;0.001 and P&amp;lt;0.05, respectively) in NMuMG-GFPZ2 cells vs. controls. Taking together, these results show that the cells were induced to EMT by N-ZEB1. Conclusions: We have identified a small fragment in N-ZEB1 that is able to elicit the EMT program in a TGFβ independent manner. In addition, changes in ZEB1 cellular localization induced by either PKC or IGF-1 could regulate this transcription factor biological activity. Citation Format: M Candelaria Llorens, Ana M. Cabanillas. Role of N- ZEB1 in epithelial-mesenchymal transition (EMT). [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 1988. doi:10.1158/1538-7445.AM2015-1988