tbuckley/cabot-search huggingface dataset:
Concordance Between Different Amyloid Immunoassays and Visual Amyloid Positron Emission Tomographic Assessment
Authors: Shorena Janelidze, Josef Pannee, Alvydas Mikulskis, Ping Chiao, Henrik Zetterberg, Kaj Blennow, Oskar Hansson
Journal: JAMA Neurology (2017)

Visual assessment of amyloid positron emission tomographic (PET) images has been approved by regulatory authorities for clinical use. Several immunoassays have been developed to measure β-amyloid (Aβ) 42 in cerebrospinal fluid (CSF). The agreement between CSF Aβ42 measures from different immunoassays and visual PET readings may influence the use of CSF biomarkers and/or amyloid PET assessment in clinical practice and trials.To determine the concordance between CSF Aβ42 levels measured using 5 different immunoassays and visual amyloid PET analysis.The study included 262 patients with mild cognitive impairment or subjective cognitive decline from the Swedish BioFINDER (Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably) cohort (recruited from September 1, 2010, through December 31, 2014) who had undergone flutemetamol F 18 ([18F]flutemetamol)-labeled PET. Levels of CSF Aβ42 were analyzed using the classic INNOTEST and the newer modified INNOTEST, fully automated Lumipulse (FL), EUROIMMUN (EI), and Meso Scale Discovery (MSD) assays. Concentrations of CSF Aβ were assessed using an antibody-independent mass spectrometry-based reference measurement procedure.The concordance of CSF Aβ42 levels and Aβ42:Aβ40 and Aβ42:tau ratios with visual [18F]flutemetamol PET status.Of 262 participants (mean [SD] age, 70.9 [5.5] years), 108 were women (41.2%) and 154 were men (58.8%). The mass spectrometry-derived Aβ42 values showed higher correlations with the modified Aβ42-INNOTEST (r = 0.97), Aβ42-FL (r = 0.93), Aβ42-EI (r = 0.93), and Aβ42-MSD (r = 0.95) assays compared with the classic Aβ42-INNOTEST assay (r = 0.88; P ≤ .01). The signal in the classic Aβ42-INNOTEST assay was partly quenched by recombinant Aβ1-40 peptide. However, the classic Aβ42-INNOTEST assay showed better concordance with visual [18F]flutemetamol PET status (area under the receiver operating characteristic curve [AUC], 0.92) compared with the newer assays (AUCs, 0.87-0.89; P ≤ .01). The accuracies of the newer assays improved significantly when Aβ42:Aβ40 (AUCs, 0.93-0.95; P ≤ .01), Aβ42 to total tau (T-tau) (AUCs, 0.94; P ≤ .05), or Aβ42 to phosphorylated tau (P-tau) (AUCs, 0.94-0.95; P ≤ .001) ratios were used. A combination of the Aβ42:Aβ40 ratio and T-tau or P-tau level did not improve the accuracy compared with the ratio alone.Concentrations of CSF Aβ42 derived from the new immunoassays (modified INNOTEST, FL, EI, and MSD) may correlate better with the antibody-independent mass spectrometry-based reference measurement procedure and may show improved agreement with visual [18F]flutemetamol PET assessment when using the Aβ42:Aβ40 or Aβ42:tau ratios. These findings suggest the benefit of implementing the CSF Aβ42:Aβ40 or Aβ42:tau ratios as a biomarker of amyloid deposition in clinical practice and trials.
Association of Warfarin Use With Lower Overall Cancer Incidence Among Patients Older Than 50 Years
Authors: Gry S. Haaland, Ragnhild S. Falk, Oddbjørn Straume, James B. Lorens
Journal: JAMA Internal Medicine (2017)

In cancer models, warfarin inhibits AXL receptor tyrosine kinase-dependent tumorigenesis and enhances antitumor immune responses at doses not reaching anticoagulation levels. This study investigates the association between warfarin use and cancer incidence in a large, unselected population-based cohort.To examine the association between warfarin use and cancer incidence.This population-based cohort study with subgroup analysis used the Norwegian National Registry coupled with the Norwegian Prescription Database and the Cancer Registry of Norway. The cohort comprised all persons (N = 1 256 725) born between January 1, 1924, and December 31, 1954, who were residing in Norway from January 1, 2006, through December 31, 2012. The cohort was divided into 2 groups-warfarin users and nonusers; persons taking warfarin for atrial fibrillation or atrial flutter were the subgroup. Data were collected from January 1, 2004, to December 31, 2012. Data analysis was conducted from October 15, 2016, to January 31, 2017.Warfarin use was defined as taking at least 6 months of a prescription and at least 2 years from first prescription to any cancer diagnosis. If warfarin treatment started after January 1, 2006, each person contributed person-time in the nonuser group until the warfarin user criteria were fulfilled.Cancer diagnosis of any type during the 7-year observation period (January 1, 2006, through December 31, 2012).Of the 1 256 725 persons in the cohort, 607 350 (48.3%) were male, 649 375 (51.7%) were female, 132 687 (10.6%) had cancer, 92 942 (7.4%) were classified as warfarin users, and 1 163 783 (92.6%) were classified as nonusers. Warfarin users were older, with a mean (SD) age of 70.2 (8.2) years, and were predominantly men (57 370 [61.7%]) as compared with nonusers, who had a mean (SD) age of 63.9 (8.6) years and were mostly women (613 803 [52.7%]). Among warfarin users and compared with nonusers, there was a significantly lower age- and sex-adjusted incidence rate ratio (IRR) in all cancer sites (IRR, 0.84; 95% CI, 0.82-0.86) and in prevalent organ-specific sites (lung, 0.80 [95% CI, 0.75-0.86]; prostate, 0.69 [95% CI, 0.65-0.72]; and breast, 0.90 [95% CI, 0.82-1.00]). There was no observed significant effect in colon cancer (IRR, 0.99; 95% CI, 0.93-1.06). In a subgroup analysis of patients with atrial fibrillation or atrial flutter, the IRR was lower in all cancer sites (IRR, 0.62; 95% CI, 0.59-0.65) and in prevalent sites (lung, 0.39 [95% CI, 0.33-0.46]; prostate, 0.60 [95% CI, 0.55-0.66]; breast, 0.72 [95% CI, 0.59-0.87]; and colon, 0.71 [95% CI, 0.63-0.81]).Warfarin use may have broad anticancer potential in a large, population-based cohort of persons older than 50 years. This finding could have important implications for the selection of medications for patients needing anticoagulation.
O Epidemic Intelligence Service (EIS) nos Estados Unidos
Authors: Stephen M. Ostroff
Journal: Eurosurveillance (2001)

O Epidemic Intelligence Service (Servico de Investigacao Epidemica) (EIS) – o programa de formacao em epidemiologia aplicada, com a duracao de dois anos, dos Centros para o Controlo e Prevencao de Doencas (Centers for Disease Control and Prevention (CDC)) nos Estados Unidos (EU) – celebra o 50o aniversario em 2001. Desenvolvido durante a guerra da Coreia, cinco anos apenas apos a criacao dos CDC, o estimulo subjacente ao desenvolvimento do EIS foi a falta de investigadores de campo especializados na eventualidade de serem utilizados agentes biologicos contra a populacao dos EU. Foi, no entanto, gracas a Alexander Langmuir, o principal responsavel pela epidemiologia no CDC e fundador do EIS, que os participantes foram envolvidos numa grande variedade de actividades e ajudaram a preencher as lacunas existentes nos EU relativamente a epidemiologistas com capacidades e experiencia de campo pratica para a investigacao e controlo dos surtos de doencas.
Abstract 16597: Economic Evaluations of PCSK9 Inhibitors in Reducing Cardiovascular Risk From Societal & United States Payer Perspective
Authors: Khurram Nasir, Alejandro Arrieta, Emir Veledar
Journal: Circulation (2015)

Introduction:  We aim to evaluate cost-effectiveness of recent FDA advisory committee recommended PCSK9 inhibitors for reducing cardiovascular disease (CVD) risk from societal & U.S. third-party payer perspective.   Methods:  A Markov model was used to evaluate costs and effects associated with addition of PCSK9 inhibitor to standard of care (SOC) based on a) estimated 53% 1-year relative risk reduction (SOC 1 year CVD event rate: 2.18%, PCSK9 inhibitor+SOC: 0.95%), b) indirect annual CVD reduction probability (using Framingham risk) via mean 61% LDL lowering among at CV risk patients. The model considers cycles of 1 year. Post CVD events last 5 years, after that time individuals go back to treatment state if no subsequent CVD observed. Health state costs were derived from published evidence. Survival probabilities >1 year were transformed to annual probabilities assumed on survival models. From societal perspective, cost per Quality-Adjusted Life Years (QALYs) gained are presented. We estimated payer’s perspective on net benefit balancing treatment vs. avoided cost and premium revenues over patient lifespan.   Results:  The table highlights societal gains and payer’s net benefit across range of estimated annual drug cost. At willingness-to-pay threshold of $100,000/QALY, PCSK9 inhibitors appear cost-effective if priced annually at $2500. At annual cost of $10,000, cost/QALY gained with PCSK9 inhibitor is nearly $400,000. From payer’s perspective, approximate net benefit was -$11,000 to -$51,000 per patient treated across annual drug cost range. Net benefits were only positive if treatment priced around $500/year.   Conclusion:  This study provides insights to facilitate discussion among healthcare stakeholders for considering future PCSK9 inhibitor’s utility balancing estimated benefits while accounting need for additional financial resources. Gaps between social & private benefits need to be aligned for appropriate PCSK9 inhibitors adoption in U.S.
Abstract 13229: Varying ABCG1 Expression is Associated With Macrophage Apoptosis&Phagocytosis
Authors: Si-Qi Shen, Fang Liu, Wei Wang, Lian-Feng Chen, Xiao-Wei Yan
Journal: Circulation (2016)

Introduction: ATP-binding cassette transporter G1(ABCG1)is a transmembrane protein mediated efflux of cellular cholesterol to HDL, which plays a vital part in macrophage lipid homeostasis, but the ...
A Phase II Study of Trastuzumab Emtansine in HER2-Positive Non–Small Cell Lung Cancer
Authors: Katsuyuki Hotta, Keisuke Aoe, Toshiyuki Kozuki, Kadoaki Ohashi, Kiichiro Ninomiya, Eiki Ichihara, Toshio Kubo, Takashi Ninomiya, Kenichi Chikamori, Daijiro Harada, Naoyuki Nogami, Taizo Hirata, Shiro Hinotsu, Shinichi Toyooka, Katsuyuki Kiura
Journal: Journal of Thoracic Oncology (2017)
Abstract 1583: Eicosapentaenoic Acid Up-Regulates Adiponectin Expression in Peri-adventitial Adipose Tissue and Suppresses Atherosclerotic Lesion Formation in ApoE-Deficient Mice
Authors: Miwa Matsumoto, Masataka Sata, Masaaki Soma, Ryozo Nagai
Journal: Circulation (2006)

Background:  Accumulating evidence demonstrates that dietary intake of n-3 polyunsaturated fatty acids (PUFA) has beneficial effects on cardiovascular events through various mechanisms. We examined the effect of eicosapentaenoic acid (EPA), a major component of n-3 PUFA, on adiponectin expression and atherosclerosis development in ApoE-deficient mice. Adiponectin is a circulating adipose-derived cytokine that has anti-atherogenic and anti-inflammatory properties.   Methods and Results:  Male five-week-old ApoE-deficient mice were orally fed a western-type diet including or not including 5% EPA (EPA group n=7, Control n=5) for 13 weeks. Fatty acid composition analysis of liver homogenates revealed that total tissue content of n-3 PUFA had markedly increased with oral administration of EPA.EPA increased triglyceride levels but had no significant effect on total or HDL cholesterol levels. Adiponectin mRNA expression was remarkably up-regulated by EPA in peri-adventitial and subcutaneous adipose tissues, but not in visceral tissue. Our in vitro mouse culture cell experiment confirmed that EPA significantly increased adiponectin secretion from differentiated 3T3L1 adipocytes (2.1 ± 0.34 vs. 1.4 ± 0.15 ng/ml,  p  p  p  p  p    Conclusions:  EPA enhances adiponectin expression in selected adipose tissue and reduces and stabilizes atherosclerotic lesions. Enhanced adiponectin expression in peri-adventitial tissue may thus partly contribute to EPA’s anti-atherosclerotic effects.
P1.02-018 Number of Cancer Cells in Lung Adenocarcinoma Specimen – Correlation with Noguchi's Classification, WHO Pathologic Type, and Prognosis
Authors: T. Inoue, Y. Nakazato, M. Nishihira, O. Araki, Y. Karube, S. Maeda, S. Kobayashi, M. Chida
Journal: Journal of Thoracic Oncology (2017)
PDTM-25. GENETIC SUSCEPTIBILITY AND EVOLUTION OF PEDIATRIC IDH-MUTANT INFILTRATING ASTROCYTOMAS
Authors: Miriam Bornhorst, Jeremy Goecks, Daniel R Boue, Alberto Broniscer, Eugene Hwang, Carl Koschmann, Asher Marks, Rajen Mody, Sabine Mueller, Brent Orr, Roger Packer, David A Solomon, Joyce Turner, Alexander Vortmeyer, Javad Nazarian, Cheng-Ying Ho
Journal: Neuro-Oncology (2017)

IDH mutations are considered rare in pediatric gliomas, especially in children under 14 years of age. Therefore, IDH-mutant pediatric gliomas have not been well characterized. Through this multi-institution study (5 institutions), we analyzed a total of 20 IDH1/2-mutant pediatric/AYA infiltrating astrocytoma specimens from 18 patients aged 4-26. The specimens include 15 low-grade (WHO grade II) and 5 high-grade (WHO grade III or IV) astrocytomas. A majority of the tumors appear to be early lesions based on the low cellularity, making them suitable for studying the order of driver mutations. Similar to their adult counterparts, nearly all pediatric IDH-mutant infiltrating astrocytomas (17 tumors, 85%) harbor TP53 mutation. In comparison, ATRX mutations are less frequent, detected in only 9 tumors (45%) including 4 low-grade (26% of all low-grade) and 5 high-grade tumors (100% of all high-grade). Six patients (30%) carry germline mutations in tumor suppressor or mismatch repair genes including TP53, MSH6, and RB1. All patients (N=3) with a germline mutation in MSH6 (a mismatch repair gene) had high-grade IDH-mutant astrocytomas with high genomic instability. In contrast, patients with germline TP53 mutation (Li-Fraumeni syndrome, LFS-N=2) had low-grade tumors with low mutation burden, morphologically and genetically similar to the sporadic cases. Notably, 7 out of 12 sporadic tumors harboring TP53 mutations had a TP53 mutant allele frequency that is greater than twice the IDH1/2 allelic frequency, after adjustment for TP53 loss of heterozygosity in 2 cases. This finding, together with the LFS-associated tumors, suggests that TP53 mutation may precede, or predispose to, IDH mutations in a significant fraction of astrocytomas in young patients. Our results not only define the molecular architecture of pediatric IDH-mutant infiltrating astrocytomas, but also provide insight into the genetic evolution of these tumors.
American Cancer Society (ACS) Nutrition and Physical Activity Guidelines after colon cancer diagnosis and disease-free (DFS), recurrence-free (RFS), and overall survival (OS) in CALGB 89803 (Alliance).
Authors: Erin Van Blarigan, Charles S. Fuchs, Donna Niedzwiecki, Xing Ye, Sui Zhang, Mingyang Song, Leonard Saltz, Robert J. Mayer, Rex B. Mowat, Renaud Whittom, Alexander Hantel, Al Bowen Benson, Daniel M. Atienza, Michael J. Messino, Hedy L. Kindler, Alan P. Venook, Shuji Ogino, Walter C. Willett, Edward L. Giovannucci, Jeffrey A. Meyerhardt
Journal: Journal of Clinical Oncology (2017)

10006 Background: The ACS Nutrition and Physical Activity Guidelines for Cancer Survivors include: 1) healthy body weight; 2) physical activity; and 3) a diet high in vegetables, fruits, and whole grains. It is not known whether colon cancer patients who follow these guidelines have improved DFS, RFS, or OS. Methods: We conducted a prospective study among 992 stage III colon cancer patients enrolled in an adjuvant chemotherapy trial in 1999-2001. Lifestyle was assessed twice. We applied a score developed by McCullough ML et al. to quantify adherence to the ACS guidelines based on BMI; physical activity; and intake of vegetables, fruits, whole grains, and red/processed meats (range: 0-6; higher = more healthy behaviors). Alcohol is included in the ACS guidelines for cancer prevention, but not cancer survivors; we tested the score without and with alcohol using McCullough et al.’s cut points: 0 pts = &gt;1/d for women, &gt;2/d for men; 1 pt = no alcohol; 2 pts = &gt;0-1/d for women, &gt;0-2/d for men. We estimated hazard ratios (HR) and 95% confidence intervals (CI) for DFS, RFS, and OS adjusting for clinical, demographic, and lifestyle factors. Results: Over 7 y median follow-up, we observed 335 recurrences and 299 deaths (43 without recurrence). Compared to patients with 0-1 pt (262, 26%), patients with 5-6 pts (91, 9%) had 42% lower risk of death (HR: 0.58; 95% CI: 0.34, 0.99; p-trend: 0.01) and a trend toward improved DFS (HR: 0.69; 95% CI: 0.45, 1.06; p-trend: 0.03). When including alcohol in the score, the adjusted HR’s comparing patients with 6-8 pts (162; 16%) to 0-2 pts (187; 91%) were: 0.49 for OS (95% CI: 0.32, 0.76; p-trend: 0.002), 0.58 for DFS (95% CI: 0.40, 0.84; p-trend: 0.01), and 0.64 for RFS (95% CI: 0.44, 0.94; p-trend: 0.05). Conclusions: Colon cancer patients with a healthy body weight who engaged in physical activity, ate a diet high in whole grains, vegetables, and fruits and low in red/processed meats, and drank moderate alcohol had longer DFS and OS than patients who did not engage in these behaviors. Support: U10CA180821, U10CA180882, U10CA180820, K07CA197077, R01CA118553, P50CA127003, R35CA197735. ClinicalTrials.gov:NCT00003835.
Simultaneous Care clinic: a three-year monoinstitutional experience
Authors: S. Stragliotto, E. Lamberti, I. Guglieri, S. Schiavon, M. Nardi, L. Procaccio, A. Brunello, V. Dadduzio, S. Galuppo, V. Zagonel, S. Murgioni
Journal: Annals of Oncology (2017)
SCDT-18. EXPRESSION OF ABC TRANSPORTERS AS PROGNOSTIC BIOMARKERS FOR GLIOBLASTOMA
Authors: Laurent-Olivier Roy, Myriam Lemelin, Marie-Belle Poirier, Marie Blanchette, David Fortin
Journal: Neuro-Oncology (2017)

Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumour in adults. Standard therapy, consisting in surgery followed by concomitant radio- and chemotherapy, only offers palliative benefits. Indeed, recurrence is inevitable and this disease remains incurable with an overall survival of 14.6 months. We believe that the chemoresistant phenotype of GBM is supported by their expression of several efflux pumps (ABC transporters). We thus hypothesized that gene expression of these transporters could correlate with patients clinical surrogates and be used as prognostic biomarkers. We investigated the expression of ABCB1, ABCC1, ABCC3 and ABCG2 by qPCR in 159 GBM specimens collected during surgery and 22 non-tumoral brain tissue. With the exception of ABCB1, all three efflux pumps were significantly overexpressed in GBM. While ABCB1 had no effect on clinical surrogates, ABCC1 and ABCC3 expression correlated with drastically shorter overall survival (OS) and progression-free survival (PFS) in newly diagnosed patients. Moreover, our multivariate analysis showed that patients with high and moderate levels of ABCC3 had a considerably poorer prognosis than patients with low expressing tumours (hazard ratio [95% CI] was 2.424 [1.340 - 4.531]; p<0.001). However, in recurrent tumours, these transporters showed no correlation with clinical outcome. Interestingly, high ABCG2 expression correlated with better prognosis in both newly diagnosed and recurrent tumours (hazard ratio [95% CI] was 0.564 [0.323 - 0.986]; p=0.044). This study shows that ABCC1, ABCC3 and ABCG2 transporters are upregulated in GBM tumours. Moreover, our data suggest that expression of these efflux pumps could be quantified upon diagnosis and serve as prognostic biomarkers for GBM patients. Therefore, we truly feel that ABCC1, ABCC3 and ABCG2 expression levels could be used to influence treatment and clinical management of patients.
EXTH-69. AN ENGINEERED microRNA CLUSTER FOR BROAD TARGETING OF EPIGENETIC COMPLEXES IN GBM
Authors: Vivek Bhaskaran, Mahmoud Idriss, Sean E Lawler, E Antonio Chiocca, Pier Paolo Peruzzi
Journal: Neuro-Oncology (2017)

Epigenetic deregulation is a hallmark of glioblastoma (GBM), causing tumor cells to be refractory to differentiation, hyperproliferative and resistant to multiple genotoxic insults, including radiation and TMZ-induced DNA damage. Analysis of TCGA data revealed a highly significant inverse correlation between the expression of a group of microRNAs belonging to the neural lineage, downregulated in GBM, and several target proteins with epigenetic functions, including EZH2, BMI1 and LSD1, known oncogenes upregulated in the tumor. Consequently, we engineered an artificial DNA sequence encoding 5 of the above microRNAs arranged as a genetic cluster, and delivered to human GBM stem cells by lentiviral infection. The artificial transgene correctly produced all 5 mature microRNAs, and resulted in profound downregulation not only of putative targets, but also of other non-target oncogenes with epigenetic functions like DNMT1 and MYC, suggesting a synergistic effect caused by the combination of microRNAs. This combination determined a much more marked phenotypic effect than each single microRNA, both in vitro, measured as cell proliferation, induction of differentiation and clonogenic capacity, and in vivo, resulting in more than double survival time in mice with intracranial GBM xenografts. After temozolomide treatment, 90% of GBM cells overexpressing the multi-microRNA cluster underwent apoptotic cell death, as compared to 10–15% observed with single microRNA upregulation. Importantly, this effect was independent of MGMT expression status. Finally, co-culture experiments showed that all 5 overexpressed microRNAs were actively transferred from transduced cells to non-transduced ones, retaining their biological function in the acceptor cells. This suggests the potential for a vector-mediated delivery of clustered microRNAs in the clinical setting. In conclusion, we show a new microRNA-based gene therapy approach for GBM, which takes advantage of small size, ease of genetic manipulation, broad molecular targeting and cell-to-cell diffusivity proper of microRNAs.
P1.07-040 Prognosis-Relevant Subgroups in NSCLC According to Granulocytic Myeloid-Derived Suppressor Cell Frequency and Cytokine Levels
Authors: L. Barrera, E. Montes-Servin, J. Hernandez Martinez, M. Orozco Morales, E. Montes Servin, O. Arrieta
Journal: Journal of Thoracic Oncology (2017)
P1.16-011 The Role of 3D-CT in Patients with Pulmonary Malignancies Undergoing Segmentectomy
Authors: A. Amiraliev, O. Pikin, A. Ryabov, N. Rubtsova, A. Khalimon, D. Vursol, V. Barmin, O. Alexandrov, N. Epifanov
Journal: Journal of Thoracic Oncology (2017)
Identification of ceruloplasmin as a biomarker of chronic kidney disease in urine of sickle cell disease patients by proteomic analysis
Authors: Marina Jerebtsova, Santosh L. Saraf, Xionghao Lin, Gillian Lee, Elena Afia Adjei, Namita Kumari, Nowah Afangbedji, Rasha Raslan, Charlee McLean, Victor R. Gordeuk, Sergei Nekhai
Journal: American Journal of Hematology (2017)
Impact of metabolic syndrome on clinical outcome of castration resistant prostate cancer (CRPC) patients treated with abiraterone and enzalutamide
Authors: V. Conteduca, O. Caffo, L. Galli, A. Maugeri, E. Scarpi, F. Maines, V.E. Chiuri, C. Lolli, S. Kinspergher, G. Schepisi, M. Santoni, D. Santini, L. Fratino, S.L. Burgio, S. Salvi, C. Menna, U. de Giorgi
Journal: Annals of Oncology (2017)