tbuckley/cabot-search huggingface dataset:
Abstract 1112: miR-550a-x fuctions as a tumor suppressor by inhibiting the oncogenic YAP1 in human cancers
Authors: Min Ho Choe, Joon Kim, Young-Hoon Han, Jae-Sung Kim
Journal: Cancer Research (2016)

Abstract Although Yes-associated protein 1 (YAP1), an essential downstream effector of hippo pathway, is a potent oncogene and amplified in human cancers, the overexpression mechanism is unclear. Herein, this study shows that miR-550a-x directly inhibits the oncogenic YAP1 and functions as a tumor suppressor in various human cancer cells. Ectopic overexpression of miRNA-550a-x suppressed proliferation and survival of various cancer cells via inducing apoptosis. miR-550a-x also had a capacity to suppress cell migration, epithelial-mesenchymal transition and tumor sphere formation. Using bioinformatics and microarray analysis, we found YAP1 as a putative target gene. miR-550a-x decreased the mRNA and protein levels of YAP1 in various cancer cells and significantly repressed YAP1 activity with its downstream target genes including CTGF and CYR61. The expression level of miRNA-550a-x were inversely correlated with the YAP1 expression in normal and colorectal cancer samples. Therefore, our data suggest that miRNA-550X functions as a tumor suppressor by targeting YAP1, which may provide a novel therapeutic option for cancer treatment. Citation Format: Min Ho Choe, Joon Kim, Young-Hoon Han, Jae-Sung Kim. miR-550a-x fuctions as a tumor suppressor by inhibiting the oncogenic YAP1 in human cancers. [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 1112.
Preclinical evaluation of platelet derived growth factor receptor β (PDGFR-β) as a predictive marker of response in renal cell cancer (RCC).
Authors: Carmen Garrigós, Marta Espinosa Montano, Clara Beatriz García, Maria Angeles Castilla, Ignacio Duran
Journal: Journal of Clinical Oncology (2015)

e15625 Background: Angiogenesis plays an essential role in tumor growth and metastasis and is a major target in RCC therapeutics. VEGF, PDGF and their cognate receptors are key players involved in this process. Single nucleotide polymorphisms (SNPs) in PDGFRβ (such as c.2601A > G, rs246395) have already been associated with increased pathway activation and poorer survival in other tumor types treated with antiangiogenics (Estevez-Garcia P, BMC Cancer 2012). The current study aimed to analyze the expression of PDGFRβ and the incidence of the SNP PDGFRβ c.2601A > G, rs246395 in RCC cell lines and evaluate its potential predictive value of response to antiangiogenic agents. Methods: Four commercial cell lines of RCC (Caki-1, Caki-2, ACHN and A498) were cultured. DNA was extracted and sequencing was determined. PDGFRß and the phosphorylated PDGFR ß (Tyr751) (pPDGFR ß) expression were evaluated by RT-PCR and Western Blot. The IC50 of each cell line was determined with the following tyrosine kinase inhibitors targeting PDGFR: Sunitinib (SUN), Sorafenib (SOR), Pazopanib (PAZ) and Axitinib (AXI). Results: PDGFRß was expressed in all cell lines and Caki-2 presented the highest levels of the activated form (pPDGFRß). The SNP of interest (rs246395-PDGFRß) was only found in Caki-2 and did not determine a statistically significant difference in drug responses as measured by IC50. SUN and SOR were the most effective therapies to inhibit cell proliferation (IC50 µM SUN/SOR: 2.48/5.29 Caki1, 2.30/5.51 Caki2, 1.45/5.58 ACHN, 1.59/10.29 A498,) while PAZ and AXI reached IC50 values > 150 µM. Currently, we are overexpressing PDFGRß wild type and with the SNP of interest in all cell lines to further assess the predictive value of this genetic variant. Conclusions: PDGFRß is commonly expressed in commercially available RCC cell lines. The SNP rs246395-PDGFRß was observed in one of the four cell lines tested (Caki-2) and did not determine the response to treatment in our study. Nevertheless, Caki-2 cells showed higher protein levels of p-PDGFRβ suggesting increase pathway activation. Ongoing work will most likely define the true predictive role of the SNP rs246395-PDGFRß.
Early oral immunotherapy in peanut-allergic preschool children is safe and highly effective
Authors: Brian P. Vickery, Jelena P. Berglund, Caitlin M. Burk, Jason P. Fine, Edwin H. Kim, Jung In Kim, Corinne A. Keet, Michael Kulis, Kelly G. Orgel, Rishu Guo, Pamela H. Steele, Yamini V. Virkud, Ping Ye, Benjamin L. Wright, Robert A. Wood, A. Wesley Burks
Journal: Journal of Allergy and Clinical Immunology (2016)
Predominant expression of Alzheimer’s disease-associated BIN1 in mature oligodendrocytes and localization to white matter tracts
Authors: Pierre De Rossi, Virginie Buggia-Prévot, Benjamin L. L. Clayton, Jared B. Vasquez, Carson van Sanford, Robert J. Andrew, Ruben Lesnick, Alexandra Botté, Carole Deyts, Someya Salem, Eshaan Rao, Richard C. Rice, Angèle Parent, Satyabrata Kar, Brian Popko, Peter Pytel, Steven Estus, Gopal Thinakaran
Journal: Molecular Neurodegeneration (2016)

Abstract Background Genome-wide association studies have identified BIN1 within the second most significant susceptibility locus in late-onset Alzheimer’s disease (AD). BIN1 undergoes complex alternative splicing to generate multiple isoforms with diverse functions in multiple cellular processes including endocytosis and membrane remodeling. An increase in BIN1 expression in AD and an interaction between BIN1 and Tau have been reported. However, disparate descriptions of BIN1 expression and localization in the brain previously reported in the literature and the lack of clarity on brain BIN1 isoforms present formidable challenges to our understanding of how genetic variants in BIN1 increase the risk for AD. Methods In this study, we analyzed BIN1 mRNA and protein levels in human brain samples from individuals with or without AD. In addition, we characterized the BIN1 expression and isoform diversity in human and rodent tissue by immunohistochemistry and immunoblotting using a panel of BIN1 antibodies. Results Here, we report on BIN1 isoform diversity in the human brain and document alterations in the levels of select BIN1 isoforms in individuals with AD. In addition, we report striking BIN1 localization to white matter tracts in rodent and the human brain, and document that the large majority of BIN1 is expressed in mature oligodendrocytes whereas neuronal BIN1 represents a minor fraction. This predominant non-neuronal BIN1 localization contrasts with the strict neuronal expression and presynaptic localization of the BIN1 paralog, Amphiphysin 1. We also observe upregulation of BIN1 at the onset of postnatal myelination in the brain and during differentiation of cultured oligodendrocytes. Finally, we document that the loss of BIN1 significantly correlates with the extent of demyelination in multiple sclerosis lesions. Conclusion Our study provides new insights into the brain distribution and cellular expression of an important risk factor associated with late-onset AD. We propose that efforts to define how genetic variants in BIN1 elevate the risk for AD would behoove to consider BIN1 function in the context of its main expression in mature oligodendrocytes and the potential for a role of BIN1 in the membrane remodeling that accompanies the process of myelination.
P0373 : Twelve-year outcomes of radiofrequency ablation as first line treatment for hepatocellular carcinoma in milan criteria: Analysis of 804 patients in a single center
Authors: S.Y. Jang, S.Y. Park, W.Y. Tak, Y.O. Kweon, S. Lee, Y.R. Lee, M.H. Kim, S.J. Yeo
Journal: Journal of Hepatology (2015)
Abstract 549: Immune profiling uncovers neo-antigens and TCR repertoire responding to WX-mPD-1 and WX-mPD-L1 immune checkpoint inhibitors in syngeneic mouse xenograft models
Authors: Hua Dong, Yan Lu, Qiyao Zhang, Lingling Zhang, Xiaoyue Chen, Guizhu Yang, Shuqun Yang, Miao He, Xuzhen Tang, Yuxin Qin, Yong Zheng, Jiexing Cai, Yong Cang, Shaoyu Yan, Jing Li, Qunsheng Ji
Journal: Cancer Research (2016)

Abstract Introduction: PD-1 and PD-L1antibodies have shown impressive clinical benefits to cancer patients. However, still a significant number of patients fail to respond to those checkpoint inhibitors. To understand the underlying mechanism, we performed genomic and immune profiling of both tumor tissues and cytotoxic T cells isolated from syngeneic mouse xenograft models treated with in-house WuXi anti-mouse PD-1(WX-mPD-1) and anti-mouse PD-L1 (WX-mPD-L1) antibodies. Material and methods: Syngeneic mouse xenograft models from melanoma cell lines, CloudmanS91 and B16-F10, were used to evaluate the anticancer efficacy of WX-mPD-1 and WX-mPD-L1 antibodies. Cancer cells and xenograft tumors before and after treatment were collected for RNASeq profiling, from which mRNA expression and DNA mutations were called and neo-antigens were predicted. FACS analysis and TCR sequencing were also performed to examine the tumor infiltrating lymphocytes (TILs) population and TCR repertoire diversity, respectively. Results: Among forty-eight established syngeneic models, nine had been tested with WX-mPD-1 and WX-mPD-L1 antibodies as single agent or in combination. More importantly, we have investigated the expression, mutation loads, neo-antigens for responsive model from CloudmanS91 and partially responsive model from B16-F10. CloudmanS91 model had 8 fold increases in mutation loads compared with B16-F10 model. Neo-antigens identified in CloudmanS91 cells were further knocked out to dissect their roles in activating immune response to WX-mPD-1 and WX-mPD-L1 antibodies in vivo. Conclusions: WX-mPD-1 and WX-mPD-L1 antibodies as well as syngeneic tumor models are useful tools for pre-clinical combination and MoA studies for cancer immunotherapy. Analysis of Neo-antigen and TCR repertoire helps us better understand immune response to these antibodies in preclinical settings, and suggest novel approaches to enhance the current immunotherapeutic interventions. Citation Format: Hua Dong, Yan Lu, Qiyao Zhang, Lingling Zhang, Xiaoyue Chen, Guizhu Yang, Shuqun Yang, Miao He, Xuzhen Tang, Yuxin Qin, Yong Zheng, Jiexing Cai, Yong Cang, Shaoyu Yan, Jing Li, Qunsheng Ji. Immune profiling uncovers neo-antigens and TCR repertoire responding to WX-mPD-1 and WX-mPD-L1 immune checkpoint inhibitors in syngeneic mouse xenograft models. [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 549.
Low-Dose Mixture Hypothesis of Carcinogenesis Workshop: Scientific Underpinnings and Research Recommendations
Authors: Mark F. Miller, William H. Goodson, Masoud H. Manjili, Nicole Kleinstreuer, William H. Bisson, Leroy Lowe
Journal: Environmental Health Perspectives (2016)

The current single-chemical-as-carcinogen risk assessment paradigm might underestimate or miss the cumulative effects of exposure to chemical mixtures, as highlighted in recent work from the Halifax Project. This is particularly important for chemical exposures in the low-dose range that may be affecting crucial cancer hallmark mechanisms that serve to enable carcinogenesis.Could ongoing low-dose exposures to a mixture of commonly encountered environmental chemicals produce effects in concert that lead to carcinogenesis? A workshop held at the NIEHS in August 2015 evaluated the scientific support for the low-dose mixture hypothesis of carcinogenesis and developed a research agenda. Here we describe the science that supports this novel theory, identify knowledge gaps, recommend future methodologies, and explore preventative risk assessment and policy decision-making that incorporates cancer biology, environmental health science, translational toxicology, and clinical epidemiology.The theoretical merits of the low-dose carcinogenesis hypothesis are well founded with clear biological relevance, and therefore, the premise warrants further investigation. Expert recommendations include the need for better insights into the ways in which noncarcinogenic constituents might combine to uniquely affect the process of cellular transformation (in vitro) and environmental carcinogenesis (in vivo), including investigations of the role of key defense mechanisms in maintaining transformed cells in a dormant state. The scientific community will need to acknowledge limitations of animal-based models in predicting human responses; evaluate biological events leading to carcinogenesis both spatially and temporally; examine the overlap between measurable cancer hallmarks and characteristics of carcinogens; incorporate epigenetic biomarkers, in silico modelling, high-performance computing and high-resolution imaging, microbiome, metabolomics, and transcriptomics into future research efforts; and build molecular annotations of network perturbations. The restructuring of many existing regulatory frameworks will require adequate testing of relevant environmental mixtures to build a critical mass of evidence on which to base policy decisions. Citation: Miller MF, Goodson WH III, Manjili MH, Kleinstreuer N, Bisson WH, Lowe L. 2017. Low-Dose Mixture Hypothesis of Carcinogenesis Workshop: scientific underpinnings and research recommendations. Environ Health Perspect 125:163-169; http://dx.doi.org/10.1289/EHP411.
Detection of Zika virus in Brazilian patients during the first five days of infection – urine versus plasma
Authors: Rodrigo Pessôa, João Veras Patriota, Maria de Lourdes de Souza, Ahmed Abd El Wahed, Sabri Saeed Sanabani
Journal: Eurosurveillance (2016)

Advantages of testing for Zika virus (ZIKV) in urine have been reported, such as the persistence of ZIKV in this type of specimen for up to 20 days after ZIKV disease onset. We investigate 61 patients in the first 5 days post-symptom onset and find more patients testing positive for ZIKV in plasma samples (n=46), than in corresponding urine samples (n=37). For patients respectively testing positive in both plasma and urine (n=28), respective viral loads appeared similar.
MUNC13–4 Mutations in Patients with Hemophagocytic Lymphohistiocytosis Are Scattered over the Functional Domains of the Protein.
Authors: Alessandra Santoro, Sonia Cannella, Giovanna Bossi, Federico Gallo, Antonino Trizzino, Daniela Pende, Francesco Dieli, Giuseppa Bruno, Jane C. Stinchcombe, Caterina Putti, Carmela De Fusco, Cesare Danesino, Lorenzo Moretta, Luigi D. Notarangelo, Gillian Griffiths, Maurizio Aricò
Journal: Blood (2006)
Ikaros Inhibits Group 3 Innate Lymphoid Cell Development and Function by Suppressing the Aryl Hydrocarbon Receptor Pathway
Authors: Shiyang Li, Jennifer J. Heller, John W. Bostick, Aileen Lee, Hilde Schjerven, Philippe Kastner, Susan Chan, Zongming E. Chen, Liang Zhou
Journal: Immunity (2016)
The Efficacy of Tyrosine Kinase Inhibitors with Steroid As First Line Induction Therapy in Ph+ Acute Lymphoblastic Leukemia
Authors: Gunhan Gurman, Mustafa Merter, Pinar Ataca, Mehmet Ozen, Berna Atesagaoglu, Mehmet Gunduz, Gultekin Pekcan, Ugur Sahin, Selami Kocak Toprak, Pervin Topcuoglu, Muhit Ozcan, Osman Ilhan, Erden Atilla
Journal: Blood (2014)
New Cancer Drugs Fund is flawed without NICE reform, says Roche
Authors: Nigel Hawkes
Journal: BMJ (2016)

The drug company Roche has called for a review of how the National Institute for Health and Care Excellence (NICE) approves drugs for use on the NHS after the launch of the revamped Cancer Drugs Fund, which it says will deny patients access to new medicines.

The fund opened for business on 29 July under a new model, designed to give new drugs a chance to prove their clinical value without breaking the public purse.

Under its new guise the fund will pay for drugs for a limited period in the hope that real life experience will prove their worth and enable them to meet the cost effectiveness threshold for NHS use. Drugs that fail will be rejected from NHS reimbursement and will fall out of the fund. Those that succeed will be given NICE’s blessing and will become reimbursable.

Under its original format the fund would pay for any cancer drug that was not available to NHS patients, which many saw as a political …
Clinical Considerations for Use of Initial Combination Therapy in Type 2 Diabetes
Authors: Avivit Cahn, William T. Cefalu
Journal: Diabetes Care (2016)

Type 2 diabetes is a progressive disorder characterized by increasing hyperglycemia and the need to gradually intensify therapy in order to achieve and maintain glycemic control. Early initiation of combination therapy has been proposed as an approach to achieve glycemic goals earlier and delay the deterioration of glycemic control and with possible better preservation of β-cell function. We discuss in this article the pros and cons of this approach, focusing on individuals with HbA1c at diagnosis of 7.5-9.0%, where difference of opinion still exists on management. Initial combination therapy is proposed to lead to better and faster achievement of glycemic targets versus monotherapy and to impede clinical inertia and may possibly slow the deterioration of β-cell function. However, treating patients with sequential therapy is proposed to allow one to fully assess the efficacy and risk-to-benefit ratio of each drug as it is added. Furthermore, there is no evidence to support that rapid addition and titration of medications according to the glycemic profile achieved are inferior to initial combination therapy if glycemic targets are attained in a timely manner. Initial combination therapy is argued to postpone clinical inertia to the next decision point but does not eliminate it. Additionally, it may have been the agents chosen and not the timing of their initiation that led to improved β-cell function in the studies of initial combination therapy, and there are no data currently comparing use of the same drugs initiated simultaneously or sequentially. Heightened awareness of providers, individualization of therapy and setting, and reaching glycemic targets remain the mainstays of care.
Bone Marrow Failure with 13q Deletion: A Distinct Clinicopathological Entity with Immune Pathophysiology,
Authors: Kohei Hosokawa, Takamasa Katagiri, Naomi Sugimori, Ken Ishiyama, Yumi Sasaki, Yu Seiki, Aiko Sato-Otsubo, Masashi Sanada, Seishi Ogawa, Shinji Nakao
Journal: Blood (2011)
A Phase II Study of PF-03446962 in Patients with Advanced Malignant Pleural Mesothelioma. CCTG Trial IND.207
Authors: Paul Wheatley-Price, Quincy Chu, Maria Bonomi, Jean Seely, Ashish Gupta, Glenwood Goss, John Hilton, Ronald Feld, Christopher W. Lee, John R Goffin, Andrew Maksymiuk, Nevin Murray, Linda Hagerman, Penelope A. Bradbury
Journal: Journal of Thoracic Oncology (2016)
Histone deacetylase 3 associates with MeCP2 to regulate FOXO and social behavior
Authors: Alexi Nott, Jemmie Cheng, Fan Gao, Yuan-Ta Lin, Elizabeta Gjoneska, Tak Ko, Paras Minhas, Alicia Viridiana Zamudio, Jia Meng, Feiran Zhang, Peng Jin, Li-Huei Tsai
Journal: Nature Neuroscience (2016)
IMPACT OF IMMEDIATE INVASIVE STRATEGY IN PATIENTS WITH NON-ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION
Authors: Doo Sun Sim, Woo Jin Kim, Myung Ho Jeong, Youngkeun Ahn, Young Jo Kim, Shung Chull Chae, Taek Jong Hong, In Whan Seong, Jei Keon Chae, Chong Jin Kim, Myeong Chan Cho, Seung-Woon Rha, Jang Ho Bae, Ki Bae Seung, Seung Jung Park
Journal: Journal of the American College of Cardiology (2016)
Evidence for chemokine synergy during neutrophil migration in ARDS
Authors: Andrew E Williams, Ricardo J José, Paul F Mercer, David Brealey, Dhruv Parekh, David R Thickett, Cecelia O'Kane, Danny F McAuley, Rachel C Chambers
Journal: Thorax (2016)

Acute respiratory distress syndrome (ARDS) is a life-threatening condition characterised by pulmonary oedema, respiratory failure and severe inflammation. ARDS is further characterised by the recruitment of neutrophils into the lung interstitium and alveolar space.The factors that regulate neutrophil infiltration into the inflamed lung and our understanding of the pathomechanisms in ARDS remain incomplete. This study aimed at determining the role of the chemokine (C-C motif) ligand (CCL)2 and CCL7 in ARDS.CCL2 and CCL7 protein levels were measured in bronchoalveolar lavage (BAL) fluid obtained from lipopolysaccharide(LPS)-challenged human volunteers and two separate cohorts of patients with ARDS. Neutrophil chemotaxis to ARDS BAL fluid was evaluated and the contribution of each was assessed and compared with chemokine (C-X-C motif) ligand 8 (CXCL8). Chemokine receptor expression on neutrophils from blood or BAL fluid of patients with ARDS was analysed by flow cytometry.CCL2 and CCL7 were significantly elevated in BAL fluid recovered from LPS-challenged volunteers and patients with ARDS. BAL fluid from patients with ARDS was highly chemotactic for human neutrophils and neutralising either CCL2 or CCL7 attenuated the neutrophil chemotactic response. Moreover, CCL2 and CCL7 synergised with CXCL8 to promote neutrophil migration. Furthermore, neutrophils isolated from the blood or BAL fluid differentially regulated the cell surface expression of chemokine (C-X-C motif) receptor 1 and C-C chemokine receptor type 2 during ARDS.This study highlights important inflammatory chemokines involved in regulating neutrophil migration, which may have potential value as therapeutic targets for the treatment of ARDS.
Abstract 2485: Heterozygous deletion of RUNX3 promotes vasculogenesis by enhancing endothelial progenitor cells function
Authors: Su Young Oh, Se-Hyung Lee, Sun Hee Lee, You Mie Lee
Journal: Cancer Research (2016)

Abstract Endothelial progenitor cells (EPCs) are bone marrow (BM) -derived stem cells to be committed and differentiated into mature endothelial cells. Runt-related transcription factor 3 (RUNX3) is a tumor suppressor involved in TGF-β signaling pathway and participate in cell cycle arrest and anti-angiogenesis. RUNX3 is frequently deleted or transcriptionally silenced in a variety of cancers by epigenetic mechanisms. The aim of study was to determine the role of RUNX3 in EPC function and vasculogenesis. Here we found that RUNX3 homozygous knockout (Rx3-/-) embryos had vascular defects in embryonic day (ED) 10 and developmental abnormalities in ED 16.5 organs. The number of EPC colonies and circulating EPCs (CD34+/VEGFR2+ cells), migration and tube formation capacity of EPCs derived from RUNX3 heterozygous (Rx3+/-) mice were increased in compared to those wild type (WT) mice, suggesting that deletion of RUNX3 can enhance vasculogenesis. Expression level of VEGF, VEGFR2, SDF-1, CXCR4 and endothelial nitric oxide synthase (eNOS) mRNA was significantly up-regulated in Rx3+/- EPCs. Protein expression of VEGF, p-VEGFR2, p-Akt, p-ERK, p-SAPK/JNK and p-eNOS was also augmented in Rx3+/- EPCs. Finally, we found that recovery of blood flow was highly stimulated in Rx3+/- mice using hindlimb ischemia mouse models. Taken together, our study revealed that RUNX3 might inhibit vasculogenic processes in physiological ischemia by inhibition of EPC functions. Citation Format: Su Young Oh, Se-Hyung Lee, Sun Hee Lee, You Mie Lee. Heterozygous deletion of RUNX3 promotes vasculogenesis by enhancing endothelial progenitor cells function. [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 2485.
Stromal Incorporation of VEGFR-1+, CD68+ and α-SMA+ Hemangiogenic Cells Correlates with Histologic Subtype in Non-Hodgkin’s Lymphoma.
Authors: Jia Ruan, Elizabeth Hyjek, Andrea T. Hooper, Loic Vincent, Pouneh Kermani, Paul J. Christos, Sherry Ikalowych, Morton Coleman, Barbara Hempstead, John P. Leonard, Amy Chadburn, Shahin Rafii
Journal: Blood (2005)