tbuckley/cabot-search huggingface dataset:
Effects of Niflumic Acid on Thrombocytic Cytoplasmic Free Calcium and Platelet Aggregation in Patients with Diabetes Mellitus.
Authors: Danian NIE, Songmei Yin, Shuangfeng Xie, Xiaogang Wang, Yiqing Li, Liping Ma, Xiuju Wang, Yudan Wu, Jianhong Feng
Journal: Blood (2006)
CD62L+ NKT cells have prolonged persistence and antitumor activity in vivo
Authors: Gengwen Tian, Amy N. Courtney, Bipulendu Jena, Andras Heczey, Daofeng Liu, Ekaterina Marinova, Linjie Guo, Xin Xu, Hiroki Torikai, Qianxing Mo, Gianpietro Dotti, Laurence J. Cooper, Leonid S. Metelitsa
Journal: Journal of Clinical Investigation (2016)

Vα24-invariant natural killer T cells (NKTs) localize to tumors and have inherent antitumor properties, making them attractive chimeric antigen receptor (CAR) carriers for redirected cancer immunotherapy. However, clinical application of CAR-NKTs has been impeded, as mechanisms responsible for NKT expansion and the in vivo persistence of these cells are unknown. Here, we demonstrated that antigen-induced expansion of primary NKTs in vitro associates with the accumulation of a CD62L+ subset and exhaustion of CD62L– cells. Only CD62L+ NKTs survived and proliferated in response to secondary stimulation. When transferred to immune-deficient NSG mice, CD62L+ NKTs persisted 5 times longer than CD62L– NKTs. Moreover, CD62L+ cells transduced with a CD19-specific CAR achieved sustained tumor regression in a B cell lymphoma model. Proliferating CD62L+ cells downregulated or maintained CD62L expression when activated via T cell receptor alone or in combination with costimulatory receptors. We generated HLAnull K562 cell clones that were engineered to express CD1d and costimulatory ligands. Clone B-8-2 (HLAnullCD1dmedCD86high4-1BBLmedOX40Lhigh) induced the highest rates of NKT expansion and CD62L expression. B-8-2–expanded CAR-NKTs exhibited prolonged in vivo persistence and superior therapeutic activities in models of lymphoma and neuroblastoma. Therefore, we have identified CD62L as a marker of a distinct NKT subset endowed with high proliferative potential and have developed artificial antigen-presenting cells that generate CD62L-enriched NKTs for effective cancer immunotherapy.
Retrospective study on complications of upper arm central venous access ports
Authors: Kei Onodera, Yuki Hayashi, Shinichi Kanno, Kentaro Kawakami, Toshiyuki Kubo, Eiichiro Yamamoto, Katsuhiko Nousho, Kentaro Yamashita, Yoshiaki Arimura, Yasuhisa Shinomura
Journal: Annals of Oncology (2015)
A Phase III Randomized, Double-Blind, Trial Comparing Sorafenib Plus Capecitabine Versus Placebo Plus Capecitabine in the Treatment of Locally Advanced or Metastatic Her2-Negative Breast Cancer (Resilience)
Authors: J. Baselga, C. Zamagni, P. Gomez, B. Bermejo, S. Nagai, B. Melichar, A. Chan, L. Mangel, J. Bergh, F.P. Costa, H.L. Gomez, W. Gradishar, C.A. Hudis, B. Rapoport, H. Roche, P. Maeda, L. Huang, J. Zhang, L. Schwartzberg
Journal: Annals of Oncology (2014)
Abstract 12128: Impact of Diabetes Mellitus on Vessel Response in the Drug-Eluting Stent Era: Pooled Volumetric Intravascular Ultrasound Analysis
Authors: Kenji Sakata, Katsuhisa Waseda, Hiromasa Otake, Daisaku Nakatani, Teruyoshi Kume, Paul G Yock, Peter J Fitzgerald, Yasuhiro Honda
Journal: Circulation (2010)

Background: The primary mechanism for increased restenosis in diabetes mellitus (DM) is considered exaggerated neointimal hyperplasia in bare-metal stent implantation. In contrast, the vessel respo...
Rectal Cancer: Assessment of Neoadjuvant Chemoradiation Outcome based on Radiomics of Multiparametric MRI
Authors: Ke Nie, Liming Shi, Qin Chen, Xi Hu, Salma K. Jabbour, Ning Yue, Tianye Niu, Xiaonan Sun
Journal: Clinical Cancer Research (2016)

Abstract Purpose: To evaluate multiparametric MRI features in predicting pathologic response after preoperative chemoradiation therapy (CRT) for locally advanced rectal cancer (LARC). Experimental Design: Forty-eight consecutive patients (January 2012–November 2014) receiving neoadjuvant CRT were enrolled. All underwent anatomical T1/T2, diffusion-weighted MRI (DWI) and dynamic contrast-enhanced (DCE) MRI before CRT. A total of 103 imaging features, analyzed using both volume-averaged and voxelized methods, were extracted for each patient. Univariate analyses were performed to evaluate the capability of each individual parameter in predicting pathologic complete response (pCR) or good response (GR) evaluated based on tumor regression grade. Artificial neural network with 4-fold validation technique was further utilized to select the best predictor sets to classify different response groups and the predictive performance was calculated using receiver operating characteristic (ROC) curves. Results: The conventional volume-averaged analysis could provide an area under ROC curve (AUC) ranging from 0.54 to 0.73 in predicting pCR. While if the models were replaced by voxelized heterogeneity analysis, the prediction accuracy measured by AUC could be improved to 0.71–0.79. Similar results were found for GR prediction. In addition, each subcategory images could generate moderate power in predicting the response, which if combining all information together, the AUC could be further improved to 0.84 for pCR and 0.89 for GR prediction, respectively. Conclusions: Through a systematic analysis of multiparametric MR imaging features, we are able to build models with improved predictive value over conventional imaging metrics. The results are encouraging, suggesting the wealth of imaging radiomics should be further explored to help tailoring the treatment into the era of personalized medicine. Clin Cancer Res; 22(21); 5256–64. ©2016 AACR.
Abstract 11788: Dyslipidemia Affects the Lipid Ratio in Culprit Lesions of Negative Remodeling Vessels in Patients with Acute Coronary Syndrome
Authors: Hirofumi Hioki, Kyuhachi Otagiri, Setsuo Kumazaki, Yusuke Miyashita, Shinichi Aso, Tatsuya Saigusa, Soichiro Ebisawa, Tomonori Yaguchi, Kazunori Aizawa, Megumi Koshikawa, Hiroki Kasai, Atsushi Izawa, Takeshi Tomita, Jun Koyama, Uichi Ikeda
Journal: Circulation (2011)

Introduction: Dyslipidemia is a major risk factor for ischemic heart disease. Positive remodeling occurs more commonly in acute coronary syndrome (ACS) than in stable angina pectoris (SAP). However...
Abstract 15686: PGD2 Protects Cardiomyocytes Against Ischemia Reperfusion Injury via the FP Receptor, but Not the Canonical PGD2 Receptor
Authors: Yoshinori Katsumata, Motoaki Sano, Hideaki Ito, Tomohiro Matsuhashi, Shintaro Morizane, Ken Shinmura, Keiichi Fukuda
Journal: Circulation (2010)
Abstract 15177: Uptitration of Neurohumoral Blockers in Hospitalized Heart Failure Patients With Reduced versus Preserved Ejection Fraction
Authors: Frederik H Verbrugge, Matthias Dupont, Philippe B Bertrand, Jurgen Duchenne, W.H. Wilson Tang, Wilfried Mullens
Journal: Circulation (2013)

Objective:  To assess the impact of renin angiotensin system (RAS) blocker and β-blocker uptitration in heart failure patients with reduced (HFrEF) versus preserved (HFpEF) ejection fraction after a hospital admission.   Background:  In ambulatory HFrEF patients, RAS and β-blockers at guideline-recommended target dose reduce all-cause mortality and readmissions. Benefits in HFpEF, as well as uptitration after a hospitalization, remain uncertain.   Methods:  In consecutive patients (209 HFrEF and 108 HFpEF with ejection fraction    Results:  Patients who received uptitration were significantly younger, with a higher heart rate and better renal function. Both RAS and β-blocker uptitration were associated with significant reductions in the composite end-point of all cause mortality or heart failure readmission in HFrEF [HR(95%CI)=0.36(0.22-0.60) and 0.51(0.32-0.81), respectively]. After correction for age, heart rate, blood pressure and renal function, this association remained significant for RAS blockers [HR(95%CI)=0.54(0.31-0.93); P-value=0.025], but not for β-blockers [HR(95%CI)=0.65(0.40-1.07); P-value=0.093]. No benefit of RAS or β-blocker uptitration was observed in HFpEF.   Conclusion:  Uptitration of neurohumoral blockers after a heart failure hospitalization is more feasible in younger patients with low co-morbidity burden. RAS blocker uptitration independently predicts clinical outcome in HFrEF but not HFpEF patients.
O<scp>pening the</scp> D<scp>ebate on the</scp> N<scp>ew</scp> S<scp>epsis</scp> D<scp>efinition</scp>. Precision Medicine: An Opportunity to Improve Outcomes of Patients with Sepsis
Authors: Carolyn S. Calfee
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

composition of the acellular BAL microbiome.The increase in Prevotella spp.and Veillonella spp.during HAART-induced immune reconstitution is provocative.When previously observed in the lung, these taxa (both common oral commensals) have had consistent associations with lung health (10, 13), and their relative abundance has been positively associated with enhanced alveolar inflammation (7, 8).Although it is tempting to speculate that the enrichment with these microorganisms observed during HAART-induced immune reconstitution may contribute to a pro-inflammatory state involved in chronic lung pathology, we do not yet know whether this change in immune tone is protective, pathogenic, or both.The next step in our understanding of the lung microbiome will be determining how it intersects with the host immune response and disease pathogenesis.The only way to accomplish this will be by summoning a variety of complementary approaches: metagenomics, transcriptomics, and metabolomics to determine function; animal models to identify mechanism; longitudinal human studies to understand stability and natural history; and clinical trials to identify therapeutic targets.The current study is an important step in this direction.
A Validation Study for the Use of ROS1 Immunohistochemical Staining in Screening for ROS1 Translocations in Lung Cancer
Authors: Patrizia Viola, Manisha Maurya, James Croud, Jana Gazdova, Nadia Suleman, Eric Lim, Tom Newsom-Davis, Nick Plowman, Alexandra Rice, M. Angeles Montero, David Gonzalez de Castro, Sanjay Popat, Andrew G. Nicholson
Journal: Journal of Thoracic Oncology (2016)
Urinary Concentrations of Bisphenol A and Phthalate Metabolites Measured during Pregnancy and Risk of Preeclampsia
Authors: David E. Cantonwine, John D. Meeker, Kelly K. Ferguson, Bhramar Mukherjee, Russ Hauser, Thomas F. McElrath
Journal: Environmental Health Perspectives (2016)

Preeclampsia represents a major cause of maternal mortality and morbidity worldwide. Although it is known that the placenta plays a central role in development of preeclampsia, investigation into the contribution of environmental toxicants to the risk of preeclampsia has been sparse.In the present study we examined the relationship between longitudinally measured urinary BPA and phthalate metabolite concentrations during gestation and preeclampsia.A nested case-control study of preterm birth was performed in 2011 from women enrolled in a prospective birth cohort study at Brigham and Women's Hospital in Boston. There were 50 cases of preeclampsia as part of this study. Urine samples were analyzed for concentrations of BPA and nine phthalate metabolites several times during pregnancy. Adjusted Cox proportional hazard models were used to calculate hazard ratios of preeclampsia in association with an interquartile range increase in BPA and phthalate concentrations and were weighted to reflect results generalizable to the base population.Adjusted hazard ratios indicated that an interquartile range increase of urinary concentrations of BPA (1.53; 95% CI: 1.04, 2.25) and MEP (monoethyl phthalate) (1.72; 95% CI: 1.28, 2.30) at 10 weeks gestation was associated with onset of preeclampsia, whereas significantly elevated hazard ratios were found across gestation for all DEHP [di(2-ethylhexyl) phthalate] metabolites. These relationships differed based on infant sex.Urinary concentrations of BPA and several phthalate metabolites were significantly associated with increased risk of preeclampsia. If validated, these results indicate an environmental contribution of endocrine-disrupting chemicals to preeclampsia and suggest a modifiable means to reduce the mortality and morbidity associated with this condition.Cantonwine DE, Meeker JD, Ferguson KK, Mukherjee B, Hauser R, McElrath TF. 2016. Urinary concentrations of bisphenol A and phthalate metabolites measured during pregnancy and risk of preeclampsia. Environ Health Perspect 124:1651-1655; http://dx.doi.org/10.1289/EHP188.
Calreticulin-mutant proteins induce megakaryocytic signaling to transform hematopoietic cells and undergo accelerated degradation and Golgi-mediated secretion
Authors: Lijuan Han, Claudia Schubert, Johanna Köhler, Mirle Schemionek, Susanne Isfort, Tim H. Brümmendorf, Steffen Koschmieder, Nicolas Chatain
Journal: Journal of Hematology & Oncology (2016)

Somatic calreticulin (CALR), Janus kinase 2 (JAK2), and thrombopoietin receptor (MPL) mutations essentially show mutual exclusion in myeloproliferative neoplasms (MPN), suggesting that they activate common oncogenic pathways. Recent data have shown that MPL function is essential for CALR mutant-driven MPN. However, the exact role and the mechanisms of action of CALR mutants have not been fully elucidated. The murine myeloid cell line 32D and human HL60 cells overexpressing the most frequent CALR type 1 and type 2 frameshift mutants were generated to analyze the first steps of cellular transformation, in the presence and absence of MPL expression. Furthermore, mutant CALR protein stability and secretion were examined using brefeldin A, MG132, spautin-1, and tunicamycin treatment. The present study demonstrates that the expression of endogenous Mpl, CD41, and the key megakaryocytic transcription factor NF-E2 is stimulated by type 1 and type 2 CALR mutants, even in the absence of exogenous MPL. Mutant CALR expressing 32D cells spontaneously acquired cytokine independence, and this was associated with increased Mpl mRNA expression, CD41, and NF-E2 protein as well as constitutive activation of downstream signaling and response to JAK inhibitor treatment. Exogenous expression of MPL led to constitutive activation of STAT3 and 5, ERK1/2, and AKT, cytokine-independent growth, and reduction of apoptosis similar to the effects seen in the spontaneously outgrown cells. We observed low CALR-mutant protein amounts in cellular lysates of stably transduced cells, and this was due to accelerated protein degradation that occurred independently from the ubiquitin-proteasome system as well as autophagy. CALR-mutant degradation was attenuated by MPL expression. Interestingly, we found high levels of mutated CALR and loss of downstream signaling after blockage of the secretory pathway and protein glycosylation. These findings demonstrate the potency of CALR mutants to drive expression of megakaryocytic differentiation markers such as NF-E2 and CD41 as well as Mpl. Furthermore, CALR mutants undergo accelerated protein degradation that involves the secretory pathway and/or protein glycosylation.
cRGD-functionalized reduction-sensitive shell-sheddable biodegradable micelles mediate enhanced doxorubicin delivery to human glioma xenografts in vivo
Authors: Yaqin Zhu, Jian Zhang, Fenghua Meng, Chao Deng, Ru Cheng, Jan Feijen, Zhiyuan Zhong
Journal: Journal of Controlled Release (2016)
Bone Marrow Angiogenesis: Angiogenesis in Liquid Tumors: An In Vitro Assay for Leukemic Cell Induced Bone Marrow Angiogenesis (Adv. Healthcare Mater. 9/2016)
Authors: Yi Zheng, Yubing Sun, Xinwei Yu, Yue Shao, Ping Zhang, Guohao Dai, Jianping Fu
Journal: Advanced Healthcare Materials (2016)

A microengineered 3D biomimetic culture system developed by J. Fu and colleagues enables to study leukemic-cell-induced bone marrow angiogenesis in vitro. Their approach that is presented on page 1014 could be applied to evaluate the effect of anti-angiogenic drug treatments on the disease progression of individual leukemia treatments.
Abstract 10716: Vitamin D Deficiency and Cardiovascular Disease Amongst Minority Ethnic Groups in the UK: A Cross Sectional Study
Authors: Paramjit Gill, Jeetesh Patel, Julia Chackathayi, Elizabeth A Hughes, Craig Webster, Gregory Lip
Journal: Circulation (2012)

Background Vitamin D deficiency is common amongst minority groups in Britain but its magnitude amongst South Asian and Black African-Caribbean groups is not well defined. The steroidal, endocrine n...
<i>In Vivo</i> Genetic Screens of Patient-Derived Tumors Revealed Unexpected Frailty of the Transformed Phenotype
Authors: Daniela Bossi, Angelo Cicalese, Gaetano I. Dellino, Lucilla Luzi, Laura Riva, Carolina D'Alesio, Giuseppe R. Diaferia, Alessandro Carugo, Elena Cavallaro, Rossana Piccioni, Massimo Barberis, Giovanni Mazzarol, Alessandro Testori, Simona Punzi, Isabella Pallavicini, Giulio Tosti, Luciano Giacó, Giorgio Melloni, Timothy P. Heffernan, Gioacchino Natoli, Giulio F. Draetta, Saverio Minucci, PierGiuseppe Pelicci, Luisa Lanfrancone
Journal: Cancer Discovery (2016)

The identification of genes maintaining cancer growth is critical to our understanding of tumorigenesis. We report the first in vivo genetic screen of patient-derived tumors, using metastatic melanomas and targeting 236 chromatin genes by expression of specific shRNA libraries. Our screens revealed unprecedented numerosity of genes indispensable for tumor growth (∼50% of tested genes) and unexpected functional heterogeneity among patients (<15% in common). Notably, these genes were not activated by somatic mutations in the same patients and are therefore distinguished from mutated cancer driver genes. We analyzed underlying molecular mechanisms of one of the identified genes, the Histone-lysine N-methyltransferase KMT2D, and showed that it promotes tumorigenesis by dysregulating a subset of transcriptional enhancers and target genes involved in cell migration. The assembly of enhancer genomic patterns by activated KMT2D was highly patient-specific, regardless of the identity of transcriptional targets, suggesting that KMT2D might be activated by distinct upstream signaling pathways. Drug targeting of biologically relevant cancer-associated mutations is considered a critical strategy to control cancer growth. Our functional in vivo genetic screens of patient-derived tumors showed unprecedented numerosity and interpatient heterogeneity of genes that are essential for tumor growth, but not mutated, suggesting that multiple, patient-specific signaling pathways are activated in tumors. Cancer Discov; 6(6); 650-63. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 561.
Primary Friedlander–Bacillus Peritonitis
Authors: Melvin P. Osborne
Journal: New England Journal of Medicine (1948)

PRIMARY unexplained infection of the peritoneum by the Friedländer bacillus (Klebsiella pneumoniae) is a condition of evident rarity. The case reported below (the second in the medical literature) describes a disease that is a distinct though little known clinical entity. Additional reports will aid in delineating possible similarity to the better known idiopathic pneumococcal and streptococcal peritonitides of infants and children.Case ReportE. I., an 8-year-old girl of Irish descent, was referred to the hospital in April, 1943, by her family physician with the diagnosis of appendicitis with perforation. The immediate history dated to 4 days before . . .
Palliative chemotherapy with vinorelbine or capecitabine in women with anthracycline and taxane refractory metastatic breast cancer
Authors: M. J. Clemons, S. Verma, V. Leung, G. Dranitsaris, I. Shalaby, S. Oldfield, F. Charbonneau, A. Giotis, T. Petrella, M. Trudeau
Journal: Journal of Clinical Oncology (2004)

773 Background: Clinicians are often faced with metastatic breast cancer refractory to anthracyclines and taxanes and must determine which subsequent type of chemotherapy produces the most benefit. Therapeutic alternatives commonly used in clinical practice include vinorelbine and capecitabine. The primary objective of this retrospective study was to compare overall survival following treatment with vinorelbine, capecitabine or both agents sequentially in women with metastatic breast cancer refractory to both anthracyclines and taxanes. Methods: Electronic patient records and charts of patients who previously received an anthracycline, taxane and vinorelbine and/or capecitabine at Toronto Sunnybrook Regional Cancer Center and Women's College Hospital, Toronto, Canada, between November 1st 1994 and June 1st, 2003 were retrospectively reviewed. 82 patients were entered into the study: 44 received vinorelbine as a single agent, 22 received capecitabine as a single agent and 16 patients received both agents sequentially. The primary endpoint for analysis was overall survival from the first day of therapy with either vinorelbine or capecitabine. Results: The mean duration of therapy was 63.5 days with vinorelbine and 138 days with capecitabine. Median overall survival time was 102 days for the vinorelbine group and 185 days for capecitabine (p=0.054). In the group of patients who received both agents sequentially, the mean duration of therapy was 104 days with vinorelbine and 91.5 days with capecitabine, the median overall survival was 309 days. Survival at 1 year was 15.9% for the vinorelbine group, 22.7% for the capecitabine group and 43.8% for the combined group (p=0.078). Conclusions: The findings of this exploratory analysis suggest that patients considered refractory to anthracyclines or taxanes can still obtain significant survival benefit from further chemotherapy. Capecitabine alone or sequentially with vinorelbine may offer additional survival benefits in these patients. The results of this analysis will be of value in the design of trials evaluating the benefits of chemotherapy in this setting. No significant financial relationships to disclose.
Identification of B Cell Receptor Antigens in the Chronic Lymphocytic Leukemia Microenvironment
Authors: Elisa ten Hacken, Thomas Oellerich, Maria Gounari, Julia Hoellenriegel, Kuan-Ting Pan, Susan O'Brien, William Wierda, Alessandra Ferrajoli, Zeev Estrov, Michael J. Keating, Henning Urlaub, Paolo Ghia, Jan A. Burger
Journal: Blood (2015)