tbuckley/cabot-search huggingface dataset:
Potential molecular mechanisms of insulin like growth factor-1 (IGF-1)/insulin like growth factor-1 receptor (IGF-1R) interaction in prostate cancer invasion
Authors: Hemani C. Setya, Aline Fiebig, Gurmit Singh, Sujata Persad
Journal: Cancer Research (2004)

5030  Epidemiological studies suggest that elevated serum levels of the peptide growth factor, IGF-1 is linked to an increased risk of developing prostate cancer. However, little is known about a direct role of IGF-1/IGF-1R axis in prostate cancer progression to an invasive phenotype. The objective of this study is to investigate the role of IGF-1/IGF-1R in regulating the invasive phenotype of prostate cancer and evaluate the molecular mechanism/s involved in promoting this invasive potential. Binding of IGF-1 to its receptor IGF-1R is known to signal intracellularly via the phosphatidylinositol 3-kinase (PI3-K) pathway and the p42/44 mitogen activated protein kinase (MAPK) pathway. Invasion assays using Matrigel invasion chambers indicate that treatment of DU145 human prostate carcinoma cells with IGF-1 results in an increase in invasive potential of these cells and this stimulation is attenuated in the presence of the PI3-K inhibitor Wortmannin (W) and with the MAPK inhibitor PD98059 (PD). IGF-1 stimulation is also inhibited in the presence of an IGF-1R neutralizing antibody indicating the invasive phenotype of DU145 cells is due specifically to IGF-1 stimulation. The activities of the PI3-K and MAPK pathways, as determined by phosphorylation of protein kinase B and p42/44 MAP kinase respectively, indicated that both pathways are activated in the presence of IGF-1 and this stimulatory effect is inhibited in the presence of their inhibitors W and PD respectively. IGF-1/IGF-1R mediated regulation of the expression of matrix metalloproteinases (MMPs) was evaluated as a mechanism involved in promoting the invasive phenotype. Gelatin zymography identified that the activities of MMP-2 and –9 (two gelatinases highly associated with prostate cancer invasion) were stimulated by IGF-1 while MMP-1 activity remained unaltered. IGF-1 activation of MMP-2 and –9 was inhibited in the presence of W and PD. Western blot analysis of MMP-2 and MMP-9 protein expression showed that while MMP-9 expression paralleled the zymogram results, there was no change in MMP-2 expression. This indicates that while IGF-1 regulation of MMP-9 activity may be at the transcriptional level, MMP-2 is likely regulated by other mechanism/s. These results suggest that IGF-1 is involved in promoting prostate cancer invasion by regulating MMP-2 and 9 expression and activities through the PI3-K and MAPK pathways. (This research was supported by funds from the Hamilton Health Science research foundation).
Early participant-reported symptoms as predictors of adherence to anastrozole in the International Breast Cancer Intervention Studies II
Authors: I. Sestak, S.G. Smith, A. Howell, J.F. Forbes, J. Cuzick
Journal: Annals of Oncology (2017)

Anastrozole reduces breast cancer risk in women at high risk, but implementing preventive therapy in clinical practice is difficult. Here, we evaluate adherence to anastrozole in the International Breast Cancer Intervention Study (IBIS)-II prevention and ductal carcinoma in situ (DCIS) trials, and its association with early symptoms.
Brotes de origen alimentario en el norte de Portugal, 2002
Authors: A M Correia, G Gonçalves, Margarida Saraiva
Journal: Eurosurveillance (2004)

En octubre del 2001, los brotes de origen alimentario fueron incluidos en el sistema portugues de vigilancia de alertas y respuesta.
Las autoridades sanitarias de la region norte (Delegado Regional de Saude do Norte - DRSN) emprendieron entonces un programa de vigilancia de brotes de origen alimentario. Este articulo describe en breve los datos del ano 2002 obtenidos por este sistema.
Cada brote fue objeto de un informe por parte de las autoridades sanitarias locales (Delegado de Saude Concelhio - DSC).
El cincuenta y nueve por ciento de los 27 brotes estudiados por la DSC en 2002 fueron notificados dentro de las 72 horas siguientes a la fecha del inicio de los sintomas. 
De los 577 pacientes identificados, un 9,6 % fueron hospitalizados y no se declaro ninguna defuncion. 
El agente etiologico fue identificado en los pacientes en el 63% de los brotes, y en los alimentos en un 18,5 % de las situaciones.
Salmonella enterica fue la responsable del 73 % de los brotes en los que la presencia del agente habia sido confirmada en el laboratorio.
Los alimentos implicados en los brotes fueron preparados fundamentalmente en restaurantes o en el hogar (75% de las epidemias). Los principales factores contribuyentes notificados por las DSC, fueron la conservacion, preparacion o manipulacion de alimentos incorrectas.
La vigilancia y el control epidemiologico de los brotes de origen alimentario deben ser reforzados en Portugal en el marco de una estrategia mas amplia para promover la seguridad alimentaria.
Consumo de mariscos y conocimiento del riesgo de contraer hepatitis A en familias napolitanas - Italia, 1997
Authors: G Salamina, P D'Argenio
Journal: Eurosurveillance (1998)

En 1996, alrededor del 15% de todos los casos declarados de hepatitis A (n=8651) en Italia procedia de la region de Campania, siendo Napoles la ciudad que declaro la mayor incidencia de la region (34,9/100.000). Casi la mitad de los casos tenia entre 15 y 24 anos de edad. En los ultimos anos, el consumo de marisco, especialmente cuando se consume crudo o su coccion no es adecuada, ha sido responsable del 70% de los casos declarados de hepatitis A en Italia (1,2) y se le ha relacionado con varios brotes recientes de esta enfermedad (3-5).
SURG-18. RAMAN LASER DAMAGE THRESHOLD OF RAT PIAL CORTEX
Authors: Thomas Noh, Michelle Felicella, Laila Poisson, Hesham Mostafa Zakaria, Ana deCarvalho, Brandy Broadbent, Greg Auner, Steven Kalkanis
Journal: Neuro-Oncology (2017)

Raman spectroscopy utilizes a label-free modality of optical imaging that measures scattered photon shifts to give a unique biochemical signature. Its diagnostic capabilities are currently being explored including its applications to intraoperatively identify tissue and oncologic surgical margins. The goal of the present safety study was to assess the threshold at which a 785nM raman laser damages rat pial cortex. Sprague Dawley Rats underwent a craniotomy/durotomy and were randomly assigned to either a sham surgery or exposed to a 785nM raman laser. Initial experiments at 100mW failed to show any damage, and the laser was maximally increased to 180mW and exposure time increased to 10 minutes. Animals were then sacrificed immediately, 3 days and 7 days post-operatively and brains processed for pathologic analysis by 2 neuropathologists using H&E, NFAP, GFAP and Luxol fast blue staining. Two neuropathologists examined all slides and did not detect any changes on sham or exposed brains, thus the laser power was increased to 180mW and exposure time to 10 minutes. Even at the increased power and exposure time, there were no observed differences. A 785nM 180mW raman laser does not cause thermal damage to the rat pial cortical surface even with 10 minutes of exposure time. Current diagnostic lasers utilize much lower powers and exposure times. Since the absorption of cerebral components is similar in rat and human tissue, these diagnostic tools are likely safe to use intraoperatively. Further studies are needed at higher laser powers, increasing survival times and human tissue to observe delayed changes that may be detected by stains such as NFAP, GFAP and luxol blue.
P2.01-029 Real World Report of Clinical Outcomes of Bevacizumab in First-Line or Later-Line Treatment for Patients with Advanced NSCLC
Authors: Y. Wang, X. Hao, Y. Zhu, X. Hu, H. Wang, Y. Liu, Y. Mu, J. Li, Y. Wen, Y. Wang
Journal: Journal of Thoracic Oncology (2017)
P1.01-033 Thrombogenic Biomarkers in Patients with NSCLC – Associations with Thrombosis, Progression, and Survival
Authors: M. Alexander, D. Ball, B. Solomon, M. Macmanus, R. Manser, B. Riedel, D. Westerman, S. Evans, R. Wolfe, K. Burbury
Journal: Journal of Thoracic Oncology (2017)
CMET-43. COMPARISON OF LOCAL CONTROL OF BRAIN METASTASES WITH STEREOTACTIC RADIOSURGERY VERSUS SURGICAL RESECTION: A SECONDARY ANALYSIS OF EORTC 22952–26001
Authors: Thomas Churilla, Imran Chowdhury, Elizabeth Handorf, Laurence Collette, Sandra Collette, Yanqun Dong, Brian Alexander, Martin Kocher, Riccardo Soffietti, Elizabeth Claus, Stephanie Weiss
Journal: Neuro-Oncology (2017)

We sought to evaluate local control of brain metastases among patients treated with stereotactic radiosurgery (SRS) versus neurosurgical resection within EORTC 22952. We performed a post-hoc analysis of EORTC 22952 and included patients treated per-protocol who had 1–2 brain metastases <4 cm. The primary endpoint was local recurrence (previously treated site) defined from time of randomization. We compared modality-specific local control by calculating cumulative incidence of local recurrence and used competing risk regression to adjust for prognostic factors/competing mortality. Of 268 patients analyzed, 57.5% underwent SRS and 42.5% underwent surgical resection. Median follow-up was 13.5months. Compared to SRS, patients undergoing surgery had larger tumors (median 20mm vs. 28mm,p<0.001), more single brain metastases (74% vs. 98%,p<0.001), and different locations (p<0.001). Overall, SRS was associated with improved local control (p=0.015) in unadjusted analyses, but absolute differences in local control decreased with time (p<0.001 (interaction)). Unadjusted cumulative incidence of local recurrence by modality (SRS vs. surgery, respectively) are listed: 3months (2.0% vs. 15.8%), 6months (9.8% vs. 29.1%), 9months (17.0% vs. 35.4%), 12months (22.9% vs. 37.2%), and 24months (28.5% vs. 40.2%). Local control was similar by modality in the WBRT group (p=0.398) while SRS exhibited improved local control than surgery in the non-WBRT group (p=0.012). In adjusted models, surgical patients had a much higher early (0-3months) risk of local recurrence compared to SRS patients HR[95%CI]=5.94[1.72–20.45], but their risk decreased with time: 3-6months=1.37[0.64–2.90], 6-9months=0.75[0.28–2.00]. At >= 9months, local control appeared superior for surgery: 0.36[0.14–0.93]. Increased risk of local recurrence was also associated with increasing tumor size (p=0.031) and absence of extracranial disease (p=0.044). In this exploratory analysis, SRS appeared associated with improved early local control of treated lesions compared to patients treated surgically, although the relative benefit decreased with time. Variation in baseline patient characteristics limit this analysis warranting further study.
De la surveillance épidémiologique à l’intégration européenne
Authors: F Tissot
Journal: Eurosurveillance (1999)

Entre mars et juin 1999, 442 000 refugies kosovars sont arrives en Albanie. Le systeme de surveillance nationale n'etait pas pret a faire face a cette situation et un systeme de surveillance d'urgence des maladies transmissibles a ete mis en place pour detecter et controler les epidemies potentielles chez les refugies. Dans ce numero, Eurosurveillance publie un article presentant les resultats des neufs semaines de surveillance des maladies infectieuses chez les refugies kosovars en Albanie, cinq mois apres le debut du conflit dans l'ex-Yougoslavie. Des l’arrivee en Albanie des refugies kosovars, des epidemiologistes de l’Institut de Veille Sanitaire (InVS), a la demande du gouvernement francais, ont rejoint les equipes humanitaires. L’experience nous a en effet appris l'importance d'une intervention rapide, que ce soit pour evaluer l’etat de sante des refugies, creer des liens avec le reseau local de surveillance, ou definir et mettre en place des strategies et des outils de surveillance et d’intervention adaptes.
P3.13-026 Non-Small Cell Lung Cancer: Imaging of Recurrences After Surgery
Authors: H. Neji, M. Affes, O. Ghdes, M. Attia, H. Elbanna, I. Baccouche, A. Merghli, S. Hantous-Zannad, K. Ben Miled-M'Rad
Journal: Journal of Thoracic Oncology (2017)
Prevenção da infecção congénita por rubéola: um desafio para todos os países da Europa
Authors: N Crowcroft, R G Pebody
Journal: Eurosurveillance (2004)

O numero actual da Eurosurveillance introduz o tema comum da epidemiologia e controlo da infeccao congenita por rubeola (CRI) na Europa. Recorda que apesar da disponibilidade de uma vacina segura e eficaz ha muitos anos, CRI - a consequencia da infeccao da rubeola durante gravidez continua a representar um importante problema de saude publica, tanto na Uniao Europeia como a Regiao Europeia da OMS, mais abrangente. Os artigos que seguem descrevem os varios desafios operacionais enfrentados pelos programas nacionais de vacinacao na Europa. Ilustram as grandes diferencas do fardo da doenca e as desigualdades do acesso a servicos de saude preventivos tanto dentro como entre os paises.
Brote de Eschericha coli O157 en Suecia
Authors: T Ziese, Y Anderson, B de Jong, S Löfdahl, M Ramberg
Journal: Eurosurveillance (1996)

Las infecciones por Escherichia coli cursan con cuadros desde leves a severas colitis hemorragica y sindrome hemolitico uremico (SHU). Entre un 2% y un 21% de los casos pueden desarrollar SHU cuya tasa de letalidad es de un 3% a un 7% (1). E. coli se aisla de heces. El diagnostico del SHU es clinico y se confirma por el aislamiento del organismo o por la identificacion de anticuerpos frente a los lipopolisacaridos de E. coli O157 en sangre. Se han detectado varios brotes en Reino Unido, Canada, y Estados Unidos en los ultimos anos.
CBIO-23. CHARACTERIZATION OF BMP SYSTEM MUTATIONS IN RECURRENT PRIMARY GLIOBLASTOMA PRIMARY CELL CULTURES IN RELATION TO GLIOBLASTOMA INITIATING STEM-LIKE CELLS AND TEMOZOLOMIDE RESISTANCE
Authors: Iris Verploegh, Mani Venkatesan, Tessa Pierson, Andrea Conidi, Eskeww Mulugeta, Martine Lamfers, Jeroen de Vrij, Danny Huylebroeck, Sieger Leenstra
Journal: Neuro-Oncology (2017)

Glioblastoma multiforme (GBM) is the most prevalent and aggressive primary brain tumor. Its recurrence and rapidly acquired resistance to current therapies, including treatment with temozolomide (TMZ), results from the rapid expansion of re-emerging Glioblastoma Tumor Initiating stem cell-like Cells (GTICs). Targeted Exome Sequencing (TES) revealed that in such recurrent human GBM missense mutations arise in genes of the Bone Morphogenetic Protein (BMP) system in addition to those of other molecular systems found in primary GBM. To determine in which subpopulation BMP system mutations accumulate, we subjected two GBM primary cultures with a known mutations in ZFYVE16 (A290S) or BMPR1B (K222E) to targeted sequencing after FAC-sorting these cells based on the acknowledged stem cell markers CD44 and CD133. We found that ZFYVE16 (A290S) and BMPR1B (K222E) mutations accumulate within the CD133+/CD44- GTICs. Treatment of the primary culture with the latter mutation, with BMP4 suggests that the response to BMP signals is markedly reduced. Cells from these cultured were also cultured again after FAC-sorting for CD133 and CD44. Surprisingly, after three passages all subpopulations acquired a variation in expression of these markers specific for each patient. This shows that a 2D culture is able to loose and acquire stem cell markers and might resemble the original heterogeneity of the parental tumor more closely than we originally expected. In a separate set of experiments, RNA-sequencing of a TMZ-resistant primary GBM culture (GS295), created during the course of this work, compared to the TMZ-sensitive GS295, shows that several genes of the BMP system (NOGGIN, BMP7, ID1 and GATA3) are differentially expressed. Our results suggest that BMP system mutations tend to accumulate in CD133+ GTICs, that BMP signaling is altered within GBM primary cultures and that several mutated genes of the BMP system may correlate with acquisition of TMZ resistance.
P1.03-050 Clinical Consequences, Quality of Life, and Management of Neutropenic NSCLC Patients in the REVEL Trial
Authors: D. Ettinger, O. Arrieta, N. Karaseva, G. Chang, A. Rittmeyer, Y. Huang, R. Cheng, R. Varea, H. Ostojic, G. Mi, K. Winfree, E. Alexandris, F. Chan-Diehl, F. Cappuzzo
Journal: Journal of Thoracic Oncology (2017)
TMOD-20. EARLY DETECTION OF HDAC INHIBITION IN GLIOBLASTOMA USING ADVANCED HYPERPOLARIZED 13C MRSI
Authors: Marina Radoul, Myriam M Chaumeil, Pia Eriksson, Chloe Najac, Pavithra Viswanath, Anne Marie Gillespie, Joydeep Mukherjee, Russell Pieper, Sabrina Ronen
Journal: Neuro-Oncology (2017)

Today, there is no reliable noninvasive imaging method available to monitor glioblastoma (GBM) response to therapy and predict survival prior to tumor shrinkage. Dissolution Dynamic Nuclear Polarization (DNP) combined with hyperpolarized 13C Magnetic Resonance Spectroscopic Imaging (MRSI) is a novel imaging method that allows probing real-time tumor metabolism. Recent studies using 13C MRSI have shown decreased lactate production from pyruvate in GBM responsive to a dual PI3K/mTOR inhibitor and/or Temozolomide, mediated by lower expression of LDHA or PKM2 enzymes, respectively. SAHA, the histone deacetylase (HDAC) inhibitor, is a novel drug that inhibits cell proliferation by inducing cell cycle arrest followed by apoptosis. The goal of this study was to detect early HDAC inhibition using advanced 13C MRSI. Analysis of dynamic real-time cellular metabolic changes in SAHA-treated U87 live cells in bioreactors demonstrated a significant 37.7% decrease in hyperpolarized [1-13C]-lactate production. SAHA-treated cells also showed a 29.6% decrease of steady-state lactate level in cell extracts. Furthermore, we demonstrated a significant 30.3% decrease in hyperpolarized lactate-to-pyruvate ratio in SAHA-treated U87-bearing mice, which occurred prior to MRI-detectable changes in tumor size that was associated with enhanced animal survival. In order to mechanistically validate our findings, we tested the levels of expression of LDHA, MCT1 and MCT4, the main players in pyruvate-to-lactate interconversion. While expression of LDHA, the enzyme that catalyzes pyruvate-to-lactate conversion was independent of SAHA treatment, expression of both MCT1 and MCT4 transporters, that shuttle pyruvate and lactate in and out of the cell, are increased. We thus propose that increased MCT1/4 led to a decrease in lactate in response to HDAC inhibition and resulted in a reduced pyruvate-to-lactate conversion. Our findings confirm the potential translational value of the hyperpolarized lactate-to-pyruvate ratio as a biomarker for noninvasively assessing the early effects of emerging therapies for patients with GBM.
MA 05.09 Pre-Existing Immunity Measured by Teff Gene Expression in Tumor Tissue is Associated with Atezolizumad Efficacy in NSCLC
Authors: M. Kowanetz, W. Zou, M. Mccleland, D.R. Gandara, S. Gadgeel, A. Rittmeyer, F. Barlesi, K. Park, D. Shames, H. Koeppen, M. Ballinger, A. Sandler, P. Hegde
Journal: Journal of Thoracic Oncology (2017)
NTOX-10. POSTOPERATIVE DELIRIUM IN GLIOBLASTOMA PATIENTS: RISK FACTORS AND PROGNOSTIC IMPLICATIONS
Authors: Patrick M Flanigan, Arman Jahangiri, Drew Weinstein, Ishan Kanungo, Sarah Choi, Fara Dayani, Annette Molinaro, Michael McDermott, Mitchel S Berger, Manish Aghi
Journal: Neuro-Oncology (2017)

Delirium is a postoperative neurologic morbidity in glioblastoma whose risk factors, incidence, and prognostic implications remain undefined. We developed an algorithm using preoperative factors to predict postoperative delirium. Retrospective analysis of 554 consecutive patients (mean age=61.5 years; 42% female) undergoing first glioblastoma procedure at our institution 2005-2011. Postoperative delirium occurred in 7% of patients (n=37). Patients undergoing biopsy (10%;n=54) did not experience delirium. In patients undergoing resection (n=500), multivariate logistic regression identified four factors independently predicting postoperative delirium: age (>70 vs. 50-70 vs. <50 years) (13% vs. 7% vs. 3%;OR=2.2 [1.2-4.1]), bihemispheric tumors (13% vs. 6%;OR=2.4 [1.4-5.0]), tumor size (>4.5cm vs. 3-4.5cm vs. <3cm) (12% vs. 7% vs. 0%;OR=2.6 [0.8-5.0]), and chronic pulmonary disease (26% vs. 7%;OR=3.5 [1.3-9.8]). We developed a score function entitled “GRAD” (Glioblastoma-Risk-Assesment-for-Delirium) to stratify patients into risk categories using the relative magnitudes of regression coefficients of preoperative factors, assigning 1 point for “bihemispheric tumor”, age 50-70y, or tumor size=3-4.5cm and two points for chronic pulmonary disease, age >75y, or tumor size >4.5cm. Point totals were summed: patients with 0-1 (n=63), 2-3 (n=275), and 4-7 (n=91) points were designated as low-, intermediate-, and high-risk with post-operative delirium rates of 0% vs. 7% vs. 21%, respectively (chi-square;p<0.001), with the model validated using Brier scores. Patients with postoperative delirium had longer hospital stays (p<0.001) and decreased likelihood of discharge home (p<0.001). Postoperative delirium was independently associated with decreased survival (5.5 vs. 12.0 months, HR=1.8 [1.1-2.7]) in multivariate analysis. We developed a model to predict development of postoperative delirium using two tumor-specific (bihemispheric tumors and tumor size) and two patient-specific (age and chronic pulmonary disease) factors. High-risk patients and their families should be counseled preoperatively and this risk could be considered in the choice of biopsy versus resection, and resection patients should be monitored closely postoperatively.
QLIF-42. INCIDENCE AND CHARACTERIZATION OF DERMATOLOGIC ADVERSE EVENTS IN PATIENTS TREATED WITH TUMOR TREATING FIELDS AND IMPACT ON OVERALL SURVIVAL
Authors: Ashley Sumrall, Serena Perera, Daniel Haggstrom, David Jennings, James Symanowski, Myra Robinson
Journal: Neuro-Oncology (2017)

TTFields interfere with glioma cell division and are delivered via arrays applied to the scalp. Recommended treatment for glioblastoma involves administration of TTFields at a daily compliance rate of 75% (18 of 24 hours) to prolong OS. Given that the primary adverse effect of TTFields involves skin changes, disruptions in treatment may result from dermatologic adverse effects (dAE). Prior studies reveal an incidence of dAE between 16-43%, but they are poorly categorized. Little is known about time to onset or duration of dAE. We reviewed a cohort of patients (n=33) treated with TTFields between 2014-2017. Median duration of treatment with TTFields was 5.3 months (1.1-19.4). We identified 10 episodes of contact dermatitis, 8 erosions, 4 cases of folliculitis, and 2 ulcerations. Median time to onset of dAE was 69 days (13-123). Duration of dAE varied depending on subtype, but median duration was 64 days (13-397). Of 13 patients who developed dAE, 4 (30.8%) had a delay. Median treatment time with TTFields was 1815 hours (86 – 9446) with median daily compliance of 11.3 hours per day (0.5-22.1). Median OS of entire cohort was 8.7 months (95% CL: 7.0 – 12.1 months). Threshold analyses using Cox proportional hazards regression identified the best cutpoint for cumulative hours of treatment associated with OS. This value was used to evaluate association with incidence of dAE. Per 1000 hour increase in hours worn, HR = 0.812. The optimal cumulative hours worn identified for OS benefit is 2987 hours. The risk of death in those with at least 2987 cumulative hours worn is 0.208 times the risk of death in those with fewer hours worn. Of 13 patients with dAE, 4 (66.7%) received greater than 2987 total hrs. Comparatively, of 20 patients without dAE, only 2 (10.0%) received greater than 2987 hrs (p = 0.1824).
ASTRIS, a real world treatment study of osimertinib in patients (pts) with EGFR T790M positive non-small cell lung cancer (NSCLC): preliminary analysis of the Italian cohort
Authors: A. Passaro, G. Metro, M. Tiseo, M.R. Migliorino, A. Santo, F. Sperandi, P. Maione, G. Puppo, F. Grossi, H.J. Soto Parra, G. Borra, E. Roca, D. Rocco, I. Stasi, D. Galetta, A.M. Carta, M. Milella, G. Fasola, V. Gebbia, S. Ferrari, F. De Marinis
Journal: Annals of Oncology (2017)