tbuckley/cabot-search huggingface dataset:
Bridging Knowledge Gaps to Understand How Zika Virus Exposure and Infection Affect Child Development
Authors: Bill G. Kapogiannis, Nahida Chakhtoura, Rohan Hazra, Catherine Y. Spong
Journal: JAMA Pediatrics (2017)

<h3>Importance</h3> The Zika virus (ZIKV) epidemic has profoundly affected the lives of children and families across the Americas. As the number of children born with ZIKV-related complications continues to grow, the long-term developmental trajectory for these children and the effect on their families remains largely unknown. In September 2016, the Eunice Kennedy Shriver National Institute of Child Health and Human Development and partner National Institutes of Health institutes convened a workshop to develop a research agenda to improve the evaluation, monitoring, and management of neonates, infants, or children affected by ZIKV and its complications. The agenda also aims to optimally address the prospective effect of ZIKV exposure on the developing child. <h3>Observations</h3> The full clinical spectrum of congenital ZIKV syndrome has yet to be elucidated. In addition to the well-described anatomic and neurologic manifestations, clinicians are now describing infants with exaggerated primitive reflexes, epilepsy, acquired hydrocephalus and microcephaly, neurodevelopmental delay, gastrointestinal motility problems, and respiratory complications, such as pneumonia. While we are still learning more about the myriad clinical presentations in these severely affected children, it is also paramount to address the larger proportion of ZIKV-exposed infants who are asymptomatic at birth but, we assume, may develop problems later in life. The available evidence for neurologic, neurodevelopmental, neurobehavioral, auditory, and vision assessments and management for infants with congenital ZIKV syndrome was critically evaluated. Lessons from other congenital infections provide valuable clues about the complexities of management and the optimal approaches for evaluating, treating, and caring for the children, which include engaging and involving parents and caregivers in their treatment. <h3>Conclusions and Relevance</h3> Rigorous research is key to improving the identification of ZIKV-infected mothers and babies. Research also is critical to increasing basic understanding of the neuropathogenesis of congenital ZIKV disease and of the spectrum of clinical presentations of ZIKV infection so that agents to prevent and treat this devastating disease can be rapidly developed and studied.
Abstract P6-02-08: Modulation of indoleamine 2, 3-dioxygenase (IDO1) expression in breast cancer cells by activated CD8+ T cells is controlled by DNA promoter methylation
Authors: F Gu, SK Noonepalle, E-J Lee, J-H Choi, AY Shull, L Pei, A Sreekumar, S Ambs, H Shi
Journal: Cancer Research (2017)

Abstract Tumor infiltrating lymphocytes (TILs) play a critical role in regulating the immunomodulatory properties of triple negative breast cancer (TNBC). However, the specific adaptations that TNBC tumors undergo when challenged by lymphocyte infiltration remain unclear. In order to address this gap in knowledge, we conducted an immuno-phenotype comparison using mRNA sequencing between the TNBC cell line MDA-MB-231 and the luminal breast cancer cell line MCF7 after both were co-cultured with activated human T-cells. Although the cytokine-induced immune signature of the two cell lines were similar, MDA-MD-231 cells were able to transcribe the tryptophan catabolizing enzyme IDO1 at a significantly higher level than MCF7 cells. Stimulation with IFNg was able to differentially induce IDO protein expression and enzymatic activity in ER- cell lines compared to ER+ cell lines, though no differences were observed in upstream JAK/STAT1 signaling or IDO1 mRNA stability between the two cell lines. Further experiments showed that treatment with the demethylating agent 5-aza-deoxycytidine was able to reverse suppression of IDO1 expression in MCF7 cells, suggesting that DNA methylation serves as a potential determinant in IDO1 induction. Analysis of TCGA and other previously published breast cancer datasets revealed subtype-specific mRNA and promoter methylation differences in IDO1, with TNBC/basal-like subtypes exhibiting lower promoter methylation and higher mRNA expression than ER+/luminal subtypes. Bisulfite pyrosequencing validated the subtype-specific association of decreased promoter methylation with increased IDO1 expression in breast cancer cell lines and an independent cohort of primary breast tumors. In addition, decreased IDO1 promoter methylation and elevated IDO1 expression in basal-like breast tumors was found to be associated with increased levels of kynurenine, the metabolic product of IDO1, as well as higher numbers of CD8+ TILs. Furthermore, high kynurenine levels in breast tumors were associated with worse patient survival. Taken together, these findings suggest that subtype-specific IDO1 promoter methylation regulates the ability of breast tumors to escape from antitumor immune responses driven by CD8+ TILs and could be used as a predictive biomarker for IDO inhibitor-based immunotherapy. Citation Format: Gu F, Noonepalle SK, Lee E-J, Choi J-H, Shull AY, Pei L, Sreekumar A, Ambs S, Shi H. Modulation of indoleamine 2, 3-dioxygenase (IDO1) expression in breast cancer cells by activated CD8+ T cells is controlled by DNA promoter methylation [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-02-08.
Incidence and Risk-Factors of Secondary Myelodysplastic Syndrome/Acute Leukemia Following High-Dose Chemotherapy and Autograft: A Long-Term Analysis on 307 Lymphoma Patients.
Authors: Davide Bono, Manuela Zanni, Irene Ricca, Daniele Caracciolo, Elisa Dama, Corrado Magnani, Paolo Gavarotti, Luciana Bergui, Alessandra Cuttica, Marco Ladetto, Mario Boccadoro, Dario Ferrero, Corrado Tarella
Journal: Blood (2004)
Current vs past use of NSAIDs was linked to increased risk for first HF hospitalization; risk varied by drug
Authors: Steven M. Belknap
Journal: Annals of Internal Medicine (2017)

Source Citation Arfè A, Scotti L, Varas-Lorenzo C, et al; Safety of Non-steroidal Anti-inflammatory Drugs (SOS) Project Consortium. Non-steroidal anti-inflammatory drugs and risk of heart failure in four European countries: nested case-control study. BMJ. 2016;354:i4857. 27682515
Driver Mutation in Waldenstrom's Macroglobullinemia and Their Clonal Heterogeneity during Progression and Relapse
Authors: Jihye Park, Antonio Sacco, Salomon Manier, Karma Salem, Mira Mashood, Adriana Perilla-Glen, Yosra Aljawai, Jiantao Shi, Eliezer Van Allen, Marzia Capelletti, Irene M. Ghobrial, Aldo M. Roccaro
Journal: Blood (2016)
Over-Expression of the Local Bone Marrow Renin-Angiotensin System in Acute Myeloid Leukemia.
Authors: Yavuz Beyazit, Salih Aksu, Ibrahim Celalettin Haznedaroglu, Murat Kekilli, Muge Misirlioglu, Serdar Tuncer, Ebru Koca, Deniz Cetiner, Yahya Buyukasik, Nilgun Sayinalp, Hakan Goker, Osman Ilhami Ozcebe
Journal: Blood (2005)
Annals Story Slam - 30 Days: Dead or Cured
Authors: David Mayer Smith
Journal: Annals of Internal Medicine (2017)

Web Exclusives7 March 2017Annals On Being a Doctor Story Slam - 30 Days: Dead or CuredFREEDavid Mayer SmithDavid Mayer SmithSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W17-0024 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - 30 Days: Dead or Cured "30 Days: Dead or Cured," by David Mayer Smith (Duration 7:00)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Current Author Address: David Mayer Smith; e-mail, [email protected]com. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 7 March 2017Volume 166, Issue 5Page: SS1 ePublished: 7 March 2017 Issue Published: 7 March 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.Loading ...
RETRACTED ARTICLE: MicroRNA-30d promotes angiogenesis and tumor growth via MYPT1/c-JUN/VEGFA pathway and predicts aggressive outcome in prostate cancer
Authors: Zhuo-yuan Lin, Guo Chen, Yan-qiong Zhang, Hui-chan He, Yu-xiang Liang, Jian-heng Ye, Ying-ke Liang, Ru-jun Mo, Jian-ming Lu, Yang-jia Zhuo, Yu Zheng, Fu-neng Jiang, Zhao-dong Han, Shu-lin Wu, Wei-de Zhong, Chin-Lee Wu
Journal: Molecular Cancer (2017)

Abstract Background Even though aberrant expression of microRNA (miR)-30d has been reported in prostate cancer (PCa), its associations with cancer progression remain contradictory. The aim of this study was to investigate clinical significance, biological functions and underlying mechanisms of miR-30d deregulation in PCa. Methods Involvement of miR-30d deregulation in malignant phenotypes of PCa was demonstrated by clinical sample evaluation, and in vitro and in vivo experiments. The mechanisms underlying its regulatory effect on tumor angiogenesis were determined. Results miR-30d over-expression was observed in both PCa cells and clinical specimens. High-miR-30d was distinctly associated with high pre-operative PSA and Gleason score, advanced clinical and pathological stages, positive metastasis and biochemical recurrence (BCR), and reduced overall survival of PCa patients. Through gain- and loss-of-function experiments, we found that miR-30d promoted PCa cell proliferation, migration, invasion, and capillary tube formation of endothelial cells, as well as in vivo tumor growth and angiogenesis in a mouse model. Simulation of myosin phosphatase targeting subunit 1 (MYPT1), acting as a direct target of miR-30d, antagonized the effects induced by miR-30d up-regulation in PCa cells. Notably, miR-30d/MYPT1 combination was identified as an independent factor to predict BCR of PCa patients. Furthermore, miR-30d exerted its pro-angiogenesis function, at least in part, by inhibiting MYPT1, which in turn, increased phosphorylation levels of c-JUN and activated VEGFA-induced signaling cascade in endothelial cells. Conclusions miR-30d and/or its target gene MYPT1 may serve as novel prognostic markers of PCa. miR-30d promotes tumor angiogenesis of PCa through MYPT1/c-JUN/VEGFA pathway.
PP68. APTAMER TARGETING OF KU 70/80 IN GLIOMA
Authors: Dr Mohit Arora, Dr Jane Alder, Dr Clare Lawrence, Dr Lisa Shaw
Journal: Neuro-Oncology (2017)

INTRODUCTION: Aptamers are in vitro generated DNA and RNA sequences. Aptamer sequences have multiple permutations and combinations of nucleotides and are then ‘selected’, using Sequential Enumeration of Ligands by Exponential Enrichment (SELEX) towards the desired, known or unknown target. Modified aptamers based on published sequences against glioma cell lines and newly generated sequences were used in the project to identify and confirm the targets. METHODS: Commercially available glioma cell lines and short term cultures from anonymised patient tissue were used. Fluorescent and biotin conjugated aptamers were incubated with glioma cell cultures and imaged using confocal or light microscopy. Aptamers were then reacted with glial cell lysate and subjected to precipitation using streptavidin agarose beads and SDS polyacrylamide electrophoresis. Proteins were analysed by mass spectroscopy. Ku 70 (X-ray Repair Cross Complementing protein 6), and Ku80 (X-ray Repair Cross Complementing protein 5) were identified as the most abundant protein when compared to control aptamer precipitation. Western blot analysis and siRNA knockdown was used to further confirm the target. RESULTS: Ku70 and Ku80 were precipitated along with known proteins associated proteins such as nucleolin as well as a few unknown proteins. Western blot analysis confirmed abundant precipitation of Ku70 and Ku80 when compared to control aptamer. DAB staining of cell cultures revealed over-expression of Ku70 and Ku80 throughout the cell. Knock down with siRNA showed reduced binding of the aptamer to the nucleus when compared to untreated cell cultures. CONCLUSIONS: Certain aptamers appear to be targeting DNA repair proteins Ku70 and Ku80 and could be used for developing targeted therapy towards glioma. Western and knockdown analysis, confirm the specificity of binding and leads the way for in-vivo testing of aptamers.
CD147 Is a Novel Regulator of Progression and Proliferation of Multiple Myeloma Plasma Cells
Authors: Bonnie K. Arendt, Denise K. Walters, Xiaosheng Wu, Renee C. Tschumper, Paul M. Huddleston, Kimberly J. Henderson, Angela Dispenzieri, Diane F. Jelinek
Journal: Blood (2011)
microRNA (miRNA) expression profiling predicts clinical outcome of carboplatin/paclitaxel-based therapy (CP) in metastatic melanoma (MM) treated on the intergroup trial E2603.
Authors: Liza Cosca Villaruz, Grace Huang, Marjorie Romkes, John M. Kirkwood, Shama C. Buch, Tomoko Nukui, Keith Flaherty, Sandra J. Lee, Adrian Lee, Kusum Pandit, Irina Abecassis, Katherine L. Nathanson, Panayiotis V Benos, Hussein Abdul-Hassan Tawbi
Journal: Journal of Clinical Oncology (2014)

9048 Background: Chemotherapy continues to be a commonly used modality in MM despite the recent successes of immunotherapy and targeted therapy. CP with or without sorafenib (S) results in objective response rates of 16-18% in unselected chemotherapy-naïve patients (intergroup trial E2603). Our primary objective was to identify molecular predictors of survival and response to CP-based chemotherapy in MM. Methods: E2603 randomized 823 MM pts to CP+S vs CP alone. This analysis was performed on pre-treatment formalin fixed paraffin-embedded (FFPE) tumor tissues from 115 pts balanced across treatment arms, BRAF status, and clinical outcome. We used technology optimized for FFPE samples: Nanostring miRNA expression array and DASL/Illumina microarrays (HT12 v4) for mRNA expression. Integrative analysis was performed using a novel Tree-guided Recursive Cluster Selection (T-ReCS) algorithm to select the most informative features/genes; TargetScan Human v6.2 for miRNA target prediction and mirConnX for network inference. Results: High quality miRNA and mRNA expression data were generated from legacy samples from 115 MM pts treated in E2603 (median progression-free survival (PFS) 4.4 mos). T-ReCS identified miR-659-3p as the primary miRNA associated positively with PFS together with miR-219-1-3p, miR-516a-5p. miR-659-3p was differentially expressed based on PFS but not on treatment arm (CP+S vs CP; p=0.6), BRAF status (p=0.3), or NRAS status (p=0.6). Dichotomized by PFS < 4 mos vs > 4 mos, higher miR-659-3p expression remained prognostic of longer PFS (p=0.03). High miR-659-3p expression distinguished patients with responsive disease (complete or partial) from patients with stable disease (p=0.04.) Predicted gene targets using TargetScan and mirConnX included BRAF, PIK3C2A, FGF12, FGF18 and RAC1. Conclusions: Novel integrative analysis reveals miR-659-3p as a predictive biomarker in MM pts treated with platinum-based chemotherapy and may serve to improve patient selection. Validation in an independent population is ongoing and functional studies to elucidate the mechanisms underlying this observation are planned.
Coprogression of Cardiovascular Risk Factors in Type 1 Diabetes During 30 Years of Follow-up in the DCCT/EDIC Study
Journal: Diabetes Care (2016)

OBJECTIVE The Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study has demonstrated the beneficial effect of intensive therapy on atherosclerosis and clinical cardiovascular outcomes, while identifying hyperglycemia as a dominant risk factor for type 1 diabetes. The current analyses evaluate the extent to which glycemic exposure influences long-term changes in established risk factors for cardiovascular disease (CVD) among patients with type 1 diabetes. RESEARCH DESIGN AND METHODS The DCCT study randomized 1,441 participants to receive intensive or conventional diabetes therapy; and after an average of 6.5 years of follow-up, 96% of the surviving cohort enrolled in the EDIC observational study for an additional 20 years of follow-up. Annual visits included a detailed medical history and physical examination. Blood and urine samples were collected and assayed centrally. Longitudinal models for repeated measurements were used. RESULTS Higher HbA1c level was a significant correlate of the longitudinal changes in all of the traditional CVD risk factors over the 30-year follow-up. The strongest longitudinal associations were among the lipid measurements and concurrent glycemia. CONCLUSIONS A better understanding of the interrelationships between diabetes-related risk factors and traditional CVD risk factors may assist with the development of targeted treatment regimens for persons with type 1 diabetes who are at risk for CVD.
Phospho-Specific Flow Cytometry of Fixed Whole Blood Demonstrates In Vivo FLT3 Inhibition in Circulating Leukemic Blasts During AC220 Therapy and Accurately Detects the Development of Therapeutic Resistance,
Authors: Alexander E Perl, Grace R Jeschke, Catherine C. Smith, James K. Mangan, Selina M. Luger, Martin Carroll
Journal: Blood (2011)
Lymphoid Subpopulations and Safety Profile in Untreated-Follicular Lymphoma Receiving Rituximab Monotherapy as Induction and Maintenance Therapy.
Authors: S. Bassi, P. Mancuso, F. Gigli, P. Antoniotti, P. Bertazzoni, J. Quarna, D. Laszlo, G. Pruneri, L. Orlando, L. Calabrese, C. Cassatella, F. Bertolini, Giovanni Martinelli
Journal: Blood (2006)
Abstract P6-01-20: Effects of local and radiation enhanced TGFβ on the invasive nature of inflammatory breast cancer cells
Authors: S Barkataki, K van Golen
Journal: Cancer Research (2017)

Abstract Inflammatory Breast Cancer (IBC) is the deadliest form of epithelial breast cancer, accounting for ~10% of breast cancer deaths in the United States. A hallmark of IBC is the formation intralymphatic emboli that are known to be chemotherapy and radiation resistant and contribute to rapid metastasis. This form of breast cancer progresses very quickly, expressing aggressive behavior. IBC and melanoma share a number of similarities in disease presentation and progression. Both spread via dermal lymphatics, form intralymphatic emboli and have a propensity to form cutaneous metastases. Melanoma can also present as “inflammatory melanoma”, which resembles IBC phenotypically. Thus, new leads for studying cutaneous metastasis can be gathered from the melanoma literature. Studies demonstrate a role for transforming growth factor beta (TGFβ) in the etiology of melanoma cutaneous metastasis. TGFβ promotes tumor cell invasion and its expression can be induced in the stroma by radiation treatment. Recently, our lab has demonstrated low expression of TGFβ in IBC patients, which we believe promotes cohesive invasion of IBC cells. Stimulation of IBC cells with 2ng/ml of TGFβ causes altered tumor cell behavior such as stimulating single cell invasion. The invasion of KPL4, SUM149 and MDA-MB231 cell lines were significantly higher in TGFβ stimulated cells compared to non-stimulated cells. As in melanoma cells we hypothesize that radiation enhanced local TGFβ production in the stroma. We radiated normal human epidermal fibroblasts cells with 0gy, 0.5gy, 1.0gy, 2.5gy and 5.0gy intensity and observed that the invasion was significantly higher in 1.0gy, 2.5gy and 5.0gy. We have also looked at the levels of TGFβ-1 in different conditioned medium. ELISA results don't show significant level of increase in TGFβ-1. Since there are two more TGFβ receptors in the TGFβ pathway (TGFβ -2 TGFβ -3), next I will look at the level of TGFβ-2 and 3 on the different intensity of radiation-conditioned medium. Our prediction is that the increase in the invasion of IBC cells is because of TGFβ, which alters the cohesive nature of IBC cells, and enhance single cell invasion. Moreover, radiation increases TGFβ levels in the stroma, which is responsible for rapid metastasis of IBC cells to the skin. Citation Format: Barkataki S, van Golen K. Effects of local and radiation enhanced TGFβ on the invasive nature of inflammatory breast cancer cells [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-01-20.
Poor Graft Function in Recipients of T Cell Depleted (TCD) Allogeneic Hematopoietic Stem Cell Transplants (HSCT) Is Mostly Related to Viral Infections and Anti-Viral Therapy.
Authors: Roni Tamari, Sheetal Ramnath, Deborah Kuk, Craig S. Sauter, Doris M Ponce, Sean Devlin, James W. Young, Sergio Giralt, Hugo R Castro-Malaspina
Journal: Blood (2012)
Abstract P2-08-11: An orally bioavailable selective estrogen receptor downregulator
Authors: G Wang, J Liu, S Zheng, L Miele, T Wiese, Q Zhong, S Guo
Journal: Cancer Research (2017)

Abstract Orally bioavailable selective estrogen receptor downregulators (SERDs) may offer greater systemic drug exposure, improved clinical efficacy, and more durable treatment outcome for breast cancer patients with disease progression following antiestrogen or aromatase inhibitor therapy. We report the design and synthesis of ZB716, a C-3 position boronic acid modified fulvestrant, which behaves as a steroidal SERD suitable for oral administration. ZB716 binds to ERa competitively at an IC50 of 4.1 nM as compared to 3.9 nM for fulvestrant, and it effectively downregulates ERa (IC50=12.7 nM) in both tamoxifen-sensitive (T47D) and tamoxifen-resistant (T47D/PKCa) breast cancer cells. It acts as an antiestrogen that exerts potent antiproliferative effects on tamoxifen-resistant breast cancer cells (MCF-7/TamR, T47D/PKCa, and T47D/Y537S). When orally administered to mice, rats, and Beagle dogs, ZB716 demonstrates superior oral bioavailability in all animal-based pharmacokinetic studies when compared to fulvestrant administered by subcutaneous injection. More importantly, orally administered ZB716 was found to potently inhibit xenograft tumor growth in mice. These pre-clinical data strongly suggest that ZB716 is a promising SERD drug that could offer significant improvement over existing SERD regimen of Faslodex. ZB716 is being prepared in an IND application for phase 1 clinical trial in ER+, HER2- advanced breast cancer patients. Citation Format: Wang G, Liu J, Zheng S, Miele L, Wiese T, Zhong Q, Guo S. An orally bioavailable selective estrogen receptor downregulator [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-08-11.
In stable COPD with moderate desaturation, long-term supplemental oxygen did not reduce deaths or hospitalizations
Authors: Simon O'Connor
Journal: Annals of Internal Medicine (2017)

Source Citation Long-Term Oxygen Treatment Trial Research Group, Albert RK, Au DH, et al. A randomized trial of long-term oxygen for COPD with moderate desaturation. N Engl J Med. 2016;375:1617-27. 27783918
Lenalidomide (L) in Combination with Dexamethasone (D) Improves Survival and Time to Progression in Elderly Patients (pts) with Relapsed or Refractory (rel/ref) Multiple Myeloma (MM).
Authors: Asher Alban Chanan-Khan, Donna Weber, Meletius Dimopoulos, Christine Chen, Reuben Niesvizky, Michael Wang, Andrew Belch, Michel Attal, Andrew Spencer, Miles Prince, Marta Olesnyckyj, Jerome Zeldis, Zhinuan Yu, Robert Knight
Journal: Blood (2006)
Cytogenetic Diagnostics and Outcome in a Series of Thirty Three Greek Pediatric Acute Myeloid Leukemia Patients
Authors: Kalliopi N Manola, Agapi Parcharidou, Vassilios Papadakis, Maria Kalntremtziou, Chryssa Stavropoulou, Vasileios Georgakakos, Anna Paisiou, Ioulia Peristeri, Gabriel Pantelias, Constantina Sambani, Sophia Polychronopoulou
Journal: Blood (2008)