tbuckley/cabot-search huggingface dataset:
GW28-e1163 Safety and efficacy of transcatheter closure of ruptured sinus of Valsalva aneurysm using the occluder of patent ductus arteriosus and ventricular septal defect
Authors: Jiawang Xiao, Zhu Xianyang, Wang Qiguang, Zhang Duanzhen, Cui Chunsheng, Chen Huo Yuan, Meng Lili, Wang Shuang
Journal: Journal of the American College of Cardiology (2017)
Readthrough response of pathogenic premature termination codons at PTEN gene: implications in precision therapy for PHTS patients
Authors: S. Luna, J. Mingo, L. Amo, I. Rodríguez-Escudero, A. Erramuzpe, M. Molina, C. Nunes-Xavier, I. Tejada, J.I. López, J. Cortés, V.J. Cid, R. Pulido
Journal: Annals of Oncology (2017)
NF-κB and Prox1 directly regulate expression of vascular endothelial growth factor receptor (VEGFR)-3
Authors: Michael Flister, Kelly Hall, Lucio Miele, Sophia Ran
Journal: Cancer Research (2008)

5850  Introduction: New lymphatic vessel formation, i.e., lymphangiogenesis, is frequently induced by chronically inflamed malignancies and correlates with increased lymphatic metastasis. Lymphangiogenesis is mediated primarily by VEGFR-3 expressed in lymphatic endothelial cells (LECs). The mechanisms underlying VEGFR-3 expression and its regulation of lymphangiogenesis are currently poorly understood. In this study, we investigated regulation of VEGFR-3 expression in cultured LECs by two transcription factors, NF-κB and Prox1, which regulate inflammatory response and lymphangiogenesis, respectively.  Methods: The human VEGFR-3 promoter encompassing -849 to +55bp (VEGFR-3-849/+55) was subcloned into the pGL4 luciferase vector. The VEGFR-3-849/+55 promoter was co-transfected with Prox1, NF-κB proteins p50 or p65, or empty vector. Promoter activity was measured by a dual luciferase assay. VEGFR-3 ChIP analysis was performed using Prox1, p50 or p65 antibodies and primers flanking transcription factor binding sites. LECs were stained with anti-VEGFR-3, Prox1, p50 or p65 antibodies. In some experiments, prior to analysis of VEGFR-3 transcription or immunostaining, cells were treated with the NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC).  Results: Activation of VEGFR-3-849/+55 as well as VEGFR-3 mRNA and protein expression were highest in LECs and lowest in non-endothelial cells. Sequence analysis of the VEGFR-3 promoter identified multiple putative Prox1 and NF-κB binding sites. VEGFR-3-849/+55 was activated by co-transfection with Prox1 (3.4 fold), p50 (7.8 fold), p65 (2.8 fold) or p50 and p65 (7.3 fold) expression plasmids. PDTC blocked NF-κB activation and inhibited constitutive VEGFR-3 expression in unstimulated LECs. Additionally, PDTC inhibited VEGFR-3-849/+55 activation induced by ectopic expression of p50 and p65 by 38% and 22%, respectively. Immunostaining of LECs showed constitutive Prox1 signaling. PDTC treatment inhibited Prox1 mRNA and its nuclear localization, which preceded down-regulation of VEGFR-3. ChIP analysis showed direct binding of Prox1, p50 and p65 transcription factors to VEGFR-3 promoter.  Conclusions: We propose that VEGFR-3 is an NF-κB target gene because (1) VEGFR-3-849/+55 contains consensus NF-κB binding sites, (2) both p50 and p65 NF-κB proteins directly bind VEGFR-3 promoter as demonstrated by ChIP assay; (3) NF-κB expression plasmids activate VEGFR-3-849/+55; and (4) the NF-κB inhibitor, PDTC, blocks VEGFR-3expression. We also discovered that Prox1 directly activates VEGFR-3 promoter and is susceptible to PDTC inhibition. This suggests that Prox1 might mediate NF-κB dependent regulation of VEGFR-3 expression under inflamed conditions. Collectively, our data suggest a central mechanism underlying tumor-induced inflammation, lymphangiogenesis and metastasis, and present new targets for anti-metastatic therapy.
Infezioni da Escherichia coli O157 e latte non pastorizzato
Authors: F Allerberger, M Wagner, P Schweiger, H P. Rammer, A Resch, M P Dierich, A W Friedrich, H Karch
Journal: Eurosurveillance (2001)

Riportiamo il caso di due bambini con infezione da Escherichia coli O157, uno dei quali ha sviluppato la sindrome emolitico-uremica (SEU). Entrambi avevano ingerito latte di mucca o di capra non pastorizzato durante la settimana precedente l’insorgenza della malattia. Attraverso la tipizzazione molecolare e stato identificato un ceppo di Escherichia coli O157:H fermentante il sorbitolo da una mucca da latte. Questo ceppo differiva dai ceppi di Escherichia coli O157:H produttori di tossina Shiga isolati dal bambino di 6 anni con SEU. Questo risultato mette in evidenza la necessita di indagare su altre cause di infezione, nonostante sia stato documentato il consumo di latte non pastorizzato. Nel secondo paziente, il ceppo umano di Escherichia coli O157:H non fermentante il sorbitolo e i ceppi di origine animale isolati dalle capre erano identici. L’isolamento di ceppi identici di Escherichia coli O157:H non fermentanti il sorbitolo provenienti da contatto con animali supporta l’ipotesi dell’associazione tra SEU e consumo di latte di capra non pastorizzato ed enfatizza nuovamente l’importanza di sottoporre il latte al processo di pastorizzazione.
Improved overall and progression free survival after surgery in expert sites for sarcoma patients: A nationwide study of FSG-GETO/NETSARC
Authors: J.-Y. Blay, E. Stoeckle, A. Italiano, R.A. Rochwerger, F. Duffaud, S. Bonvalot, C. Honore, G. Decanter, C. Maynou, P. Anract, G. Ferron, F. Guillemin, F. Gouin, M. Rios, J.E. Kurtz, P. Meeus, J.M. Coindre, I. Ray-Coquard, N. Penel, A. Le Cesne
Journal: Annals of Oncology (2017)
Overexpression of NQO1 protects Jurkat leukemia cells from apoptosis
Authors: Chao Yan, Biehuoy Shieh, David Siegel, David Ross
Journal: Cancer Research (2007)

4862  NAD(P)H:quinone oxidoreductase (NQO1) is a flavoenzyme whose primary function is to catalyze the two-electron reduction of quinones to hydroquinones. NQO1 can bioactivate a wide range of anti-tumor quinones. In addition, NQO1 has been shown to be expressed at high levels in many solid tumors including lung, colon, pancreas and breast. Under normal conditions NQO1 is not expressed in human blood cells including leukemias. However, NQO1 can be induced in these cells by xenobiotic exposure and/or oxidative stress. To investigate the role of NQO1 as a drug target in leukemia cells we transfected the Jurket human T cell leukemia cell line with the pcDNA 3.0 mammalian expression vector containing the full length NQO1 coding region under control of the CMV promoter and generated stable clones using G418 selection. Clones were screened for NQO1 activity and confirmed by immnoblot analysis. The NQO1 activity in D15 and E17 clones was 340 and 380 nmole DCPIP/min/mg protein respectively. We then examined the NQO1-null parental Jurket cell line and the NQO1 overexpressing D15 and E17 clones for their ability to bioactivate antitumor quinones. Polarographic studies following treatment with the redox cycling quinone β-lapachone clearly demonstrated a significant increase in oxygen consumption in the D15 and E17 clones compared to parental cells confirming increased bioactivation in NQO1-transfected cells. Treatment with streptonigrin or RH-1, quinones efficiently bioactivated by NQO1, induced significantly higher levels of apoptosis in the transfected clones compared to the parental cells. These results are consistent with the role of NQO1 as a target for the bioactivation of antitumor quinones. However, when we treated parental and NQO1-transfected cells with general apoptosis inducers such as hydrogen peroxide, etoposide and staurosporine we observed a significantly lower level of apoptosis in the D15 and E17 cells comparing to parental Jurkat cells. Moreover, inhibition of NQO1 catalytic activity by pretreatment with ES936, a mechanism-based inhibitor of NQO1, did not restore the level of apoptosis in NQO1 transfectants, suggesting that the protection from apoptosis by NQO1 is independent of its catalytic activity. Our results clearly show that NQO1 can bioactivate antiumor quinones in NQO1-transfected human Jurkat leukemia cells but also suggests that NQO1 may have an anti-apoptotic role when transfected in Jurkat cells that is unrelated to the catalytic activity of the enzyme (supported by CA51210).
Glut3 addiction is a druggable vulnerability for a molecularly defined subpopulation of glioblastoma
Authors: É Cosset, S. Ilmjärv, V. Dutoit, K. Elliott, T. von Schalscha, A. Reiss, M.F. Camargo, T. Moroishi, L. Seguin, G. Gomez, J.S. Moo, O. Preynat-Seauve, K.H. Krause, H. Chneiweiss, K.L. Guan, P.Y. Dietrich, S.M. Weis, P.S. Mischel, D.A. Cheresh
Journal: Annals of Oncology (2017)
Safety of retreatment with immunotherapy after immune-related toxicity in patients with lung cancers treated with anti-PD(L)-1 therapy.
Authors: Fernando Costa Santini, Hira Rizvi, Olivia Wilkins, Martine van Voorthuysen, Elizabeth Panora, Darragh Halpenny, Mark G. Kris, Charles M. Rudin, Jamie E. Chaft, Matthew David Hellmann
Journal: Journal of Clinical Oncology (2017)

9012 Background: Anti-PD(L)-1 therapy is generally well tolerated, but immune-related adverse events (irAEs) can occur. No data currently exists to guide decisions related to considering re-treatment following an irAE. Methods: Patients (pts) with lung cancer treated with anti-PD(L)-1 (+/- anti-CTLA-4) between 4/2011 to 5/2016 who had a treatment delay of at least one week were identified. Those in whom delay was a result of a definite irAE were included, and subsequent treatment details and outcomes were captured. Pts with an irAE concurrent with disease progression were excluded. Results: Among 482 pts treated, 71 (14.7%) had treatment delay related to an irAE. Most events were Grade 2 (38/71, 54%) or Grade 3 (30/71, 42%), and predominantly included pneumonitis (21%), colitis (17%), rash (14%), or hepatitis (13%). 32 pts (45%) were permanently discontinued after the irAE and 39 (55%) were later retreated with anti-PD(L)-1 therapy. In retreated pts, the same irAE recurred in 10/39 (26%), a new irAE occurred in 9/39 (23%), and 20/39 (51%) had no subsequent irAE. The rate of recurrent/new irAEs was similar in those with Grade 3 compared to Grade 2 irAEs (p = 1.0), but were more common following initial irAE that occurred early ( &lt; 3 months) compared to later (≥3 months) in treatment course (16/24 [67%] vs 3/15 [20%], p = 0.0079). The rate of recurrent/new irAE was 33% (2/6) in those with pneumonitis, 40% (2/5) with rash, 57% (4/7) with colitis, and 80% (4/5) with arthralgia. Recurrent/new irAEs were successfully managed with immunosuppression in 17/19 (90%) pts. However, 2 pts died, both related to a new irAE different from the one initially experienced. Of the pts retreated, 3 (8%) had onset of objective response to anti-PD(L)-1 therapy following resumption of treatment. Conclusions: In pts who develop irAEs and improve, re-treatment with anti-PD(L)-1 therapy was associated with recurrent or new irAEs in half of pts, and was more common in early-onset irAEs. The majority of the pts with recurrent/new irAEs were managed successfully, but two deaths occured. Few objective responses occurred following retreatment.
Overall survival (OS) and forced vital capacity (FVC) results from the LUME-Meso study of nintedanib (N) + pemetrexed/cisplatin (PEM/CIS) vs placebo (P) + PEM/CIS in chemo-naïve patients (pts) with malignant pleural mesothelioma (MPM)
Authors: S. Novello, A.K. Nowak, F. Grosso, N. Steele, S. Popat, L. Greillier, T. John, N.B. Leighl, M. Reck, N. Pavlakis, J.B. Sorensen, D. Planchard, G.L. Ceresoli, B. Hughes, J. Mazieres, M.A. Socinski, U. von Wangenheim, J. Barrueco, N. Morsli, G. Scagliotti
Journal: Annals of Oncology (2017)
Prognostic impact of recurrence score (RS), grade/Ki67 central pathological review, and acycline (A)-free vs. A-containing chemotherapy (CT) on distant and locoregional disease-free survival (DDFS/LRFS) in high clinical risk HER2- early breast cancer (EBC): WSG PlanB trial results
Authors: O. Gluz, U. Nitz, M. Christgen, W. Malter, M. Clemens, T. Reimer, B. Nuding, B. Aktas, A. Stefek, A. Ppllmanns, F. Lorenz-Salehi, C. Uleer, P. Krabisch, S. Kümmel, C. Liedtke, S. Shak, R. Kates, R. Wurstlein, H.H. Kreipe, N. Harbeck
Journal: Annals of Oncology (2017)
Red blood cell storage and in-hospital mortality: a secondary analysis of the INFORM randomised controlled trial
Authors: Richard J Cook, Nancy M Heddle, Ker-Ai Lee, Donald M Arnold, Mark A Crowther, Philip J Devereaux, Martin Ellis, Priscilla Figueroa, Andrea Kurz, David Roxby, Daniel I Sessler, Yehudit Sharon, Magdalena Sobieraj-Teague, Theodore E Warkentin, Kathryn E Webert, Rebecca Barty, Yang Liu, John W Eikelboom
Journal: The Lancet Haematology (2017)
Genomic Heterogeneity as a Barrier to Precision Medicine in Gastroesophageal Adenocarcinoma
Authors: Eirini Pectasides, Matthew D. Stachler, Sarah Derks, Yang Liu, Steven Maron, Mirazul Islam, Lindsay Alpert, Heewon Kwak, Hedy Kindler, Blase Polite, Manish R. Sharma, Kenisha Allen, Emily O'Day, Samantha Lomnicki, Melissa Maranto, Rajani Kanteti, Carrie Fitzpatrick, Christopher Weber, Namrata Setia, Shu-Yuan Xiao, John Hart, Rebecca J. Nagy, Kyoung-Mee Kim, Min-Gew Choi, Byung-Hoon Min, Katie S. Nason, Lea O'Keefe, Masayuki Watanabe, Hideo Baba, Rick Lanman, Agoston T. Agoston, David J. Oh, Andrew Dunford, Aaron R. Thorner, Matthew D. Ducar, Bruce M. Wollison, Haley A. Coleman, Yuan Ji, Mitchell C. Posner, Kevin Roggin, Kiran Turaga, Paul Chang, Kyle Hogarth, Uzma Siddiqui, Andres Gelrud, Gavin Ha, Samuel S. Freeman, Justin Rhoades, Sarah Reed, Greg Gydush, Denisse Rotem, Jon Davison, Yu Imamura, Viktor Adalsteinsson, Jeeyun Lee, Adam J. Bass, Daniel V. Catenacci
Journal: Cancer Discovery (2017)

Abstract Gastroesophageal adenocarcinoma (GEA) is a lethal disease where targeted therapies, even when guided by genomic biomarkers, have had limited efficacy. A potential reason for the failure of such therapies is that genomic profiling results could commonly differ between the primary and metastatic tumors. To evaluate genomic heterogeneity, we sequenced paired primary GEA and synchronous metastatic lesions across multiple cohorts, finding extensive differences in genomic alterations, including discrepancies in potentially clinically relevant alterations. Multiregion sequencing showed significant discrepancy within the primary tumor (PT) and between the PT and disseminated disease, with oncogene amplification profiles commonly discordant. In addition, a pilot analysis of cell-free DNA (cfDNA) sequencing demonstrated the feasibility of detecting genomic amplifications not detected in PT sampling. Lastly, we profiled paired primary tumors, metastatic tumors, and cfDNA from patients enrolled in the personalized antibodies for GEA (PANGEA) trial of targeted therapies in GEA and found that genomic biomarkers were recurrently discrepant between the PT and untreated metastases. Divergent primary and metastatic tissue profiling led to treatment reassignment in 32% (9/28) of patients. In discordant primary and metastatic lesions, we found 87.5% concordance for targetable alterations in metastatic tissue and cfDNA, suggesting the potential for cfDNA profiling to enhance selection of therapy. Significance: We demonstrate frequent baseline heterogeneity in targetable genomic alterations in GEA, indicating that current tissue sampling practices for biomarker testing do not effectively guide precision medicine in this disease and that routine profiling of metastatic lesions and/or cfDNA should be systematically evaluated. Cancer Discov; 8(1); 37–48. ©2017 AACR. See related commentary by Sundar and Tan, p. 14. See related article by Janjigian et al., p. 49. This article is highlighted in the In This Issue feature, p. 1
Second or 3rd line nivolumab (Nivo) versus nivo plus ipilimumab (Ipi) in malignant pleural mesothelioma (MPM) patients: Updated results of the IFCT-1501 MAPS2 randomized phase 2 trial
Authors: G. Zalcman, J. Mazieres, L. Greillier, S. Lantuejoul, P. Dô, O. Bylicki, I. Monnet, R. Corre, C. Audigier-Valette, M. Locatelli-Sanchez, O. Molinier, L. Thiberville, T. Urban, D. Planchard, C. Ligeza-Poisson, E. Amour, F. Morin, D. Moro-Sibilot, A. Scherpereel
Journal: Annals of Oncology (2017)
Epidémiologie de la rubéole en Finlande
Authors: I Davidkin, H Peltola, P Leinikki
Journal: Eurosurveillance (2004)

Avant la mise en place de programmes de vaccination, la rubeole etait prevalente chez les enfants finlandais. Des foyers epidemiques apparaissaient de maniere recurrente a quelques annees d'intervalle. La rubeole etait contractee le plus souvent entre 2 et 12 ans. Les vaccinations visant specifiquement l'eradication de la rubeole ont ete mises en place au milieu des annees 1970 avec un vaccin monovalent. Quant au programme de vaccinations en deux injections contre la rougeole, les oreillons et la rubeole (ROR), il a debute en 1982. Une nette diminution des cas de rubeole est apparue quelques annees apres le lancement du programme de vaccination ROR. La circulation du virus autochtone de la rubeole dans la population finlandaise a ete stoppee a la fin des annees 1990, grâce a une couverture vaccinale suffisamment elevee (g95% depuis 1987). Apres l'eradication, quelques cas de rubeole ont ete importes en Finlande, sans entrainer de cas secondaires. Ceci prouve que la protection contre la rubeole reste efficace, en depit de la baisse des niveaux d'anticorps dus au vaccin mise en evidence lors de nos etudes de cohorte. Le programme de vaccination ROR a egalement permis d'eliminer le syndrome de rubeole congenitale (SRC) dans le pays. Le dernier cas de SRC declare remonte a 1986. Grâce a la forte couverture vaccinale du ROR en deux doses, la rubeole a ete endiguee en Finlande. Il reste dorenavant a voir combien de temps durera la protection acquise.
Viral infections in allergy and immunology: How allergic inflammation influences viral infections and illness
Authors: Michael R. Edwards, Katherine Strong, Aoife Cameron, Ross P. Walton, David J. Jackson, Sebastian L. Johnston
Journal: Journal of Allergy and Clinical Immunology (2017)

Viral respiratory tract infections are associated with asthma inception in early life and asthma exacerbations in older children and adults. Although how viruses influence asthma inception is poorly understood, much research has focused on the host response to respiratory viruses and how viruses can promote; or how the host response is affected by subsequent allergen sensitization and exposure. This review focuses on the innate interferon-mediated host response to respiratory viruses and discusses and summarizes the available evidence that this response is impaired or suboptimal. In addition, the ability of respiratory viruses to act in a synergistic or additive manner with T
The Histologic Analysis of Mammary Tumors of Mice. II. The Histology of Responsiveness and Progression. The Origins of Tumors&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: Foulds, L.
Journal: JNCI Journal of the National Cancer Institute (1956)

An earlier paper (1) described clinical observations on spontaneous mammary tumors that developed in certain hybrid mice and their inbred descendants.Many of the tumors were notably responsive to reproductive activity of their hosts; the tumors grew during pregnancy and regressed partially or completely after parturition.Other tumors were unresponsive and grew steadily from their first appearance, independently of reproductive activity.The responsive tumors often altered their behavior while under observation, losing their responsiveness unpredictably and usually abruptly as a result of an irreversible qualitative change or progression in the tumors.The altered tumors then grew like the primarily unresponsive tumors.The present paper deals with the histology of early stages of mammary neoplasia in these mice and with the histologic manifestations of responsiveness and progression.
Durvalumab and tremelimumab in metastatic breast cancer (MBC): Immunotherapy and immunopharmacogenomic dynamics.
Authors: Cesar Augusto Santa-Maria, Taigo Kato, Jae-Hyun Park, Lisa E. Flaum, Sarika Jain, Claudia Tellez, Regina Michelle Stein, Ami N. Shah, Leeaht Gross, Regina Uthe, William John Gradishar, Massimo Cristofanilli, Yusuke Nakamura, Francis J. Giles
Journal: Journal of Clinical Oncology (2017)

3052 Background: PD-1/PD-L1 inhibitors produce modest responses in MBC; adding CTLA-4 inhibitors can augment anti-tumor activity in other cancers. Immunopharmacogenomics characterize immune-cancer cell interactions and may predict response. Methods: A single arm study was designed to determine the efficacy of durvalumab (PD-L1 inhibitor) and tremelimumab (CTLA-4 inhibitor), and immunopharmacogenomics in pts with metastatic ER+ or TNBC. The primary clinical endpoint was to assess ORR using a Simon 2-stage design (28 pts needed for type 1 error rate of 4%, 80% power). 18 pts were enrolled in the first stage; ≥4 responses were needed to proceed with the second stage. Pts were treated with durvalumab 1500mg IV and tremelimumab 75mg IV monthly for 4 doses, then durvalumab 750mg every 2 weeks to complete 1 year of therapy (option to renew for an additional year); biopsies at baseline and 2 months were collected. T-cell receptor (TCR) sequencing using mRNA isolates was conducted at baseline and 2 months, whole exome sequencing and immune-gene expression profiling were conducted at baseline. Results: From 01-09/2016, 18 evaluable pts were accrued (11 ER+; 7 TNBC). Responses are shown in the table below; the ORR did not meet criteria to proceed to the second stage. Notably, one pt with TNBC with PD had pseudoprogression, thus 5/7 (71%) pts with TNBC had clinical benefit. Median PFS was 3.8 months (95%CI 2.2-11.2) for the entire cohort (TNBC not reached), and median OS has not been reached. No grade 4 AEs were observed; grade 3 immune-related AEs included hepatitis (n = 3), nephritis (n = 1), and myocarditis (n = 1). Proportions of abundant TCR-β clonotypes (≥ 0.5% frequency) were increased in 2-month samples compared to baseline in TNBC compared to ER+, p = 0.004, and associated with responses. Remaining correlative analysis is ongoing and will be presented at ASCO. Conclusions: Response rates to PDL-1 and CTLA-4 inhibition were low in unselected MBC, however, high rates of clinical benefit were observed in TNBC. Immunopharmacogenomic may help identify phenotypes most likely to respond. Future studies in TNBC are warranted to confirm findings. Clinical trial information: NCT02536794. [Table: see text]