tbuckley/cabot-search huggingface dataset:
TMOD-25. PEPTIDES OF IMMUNE CHECKPOINT PROTEIN, CD200 (OX2), ENHANCES THE RESPONSE TO VACCINE-BASED IMMUNOTHERAPY IN DOGS WITH HIGH-GRADE GLIOMA
Authors: Elizabeth Pluhar, Michael Olin, Matthew Hunt
Journal: Neuro-Oncology (2017)

Glioma is the most common primary intra-axial brain tumor in dogs and people and carries a poor prognosis. We have been testing novel glioma therapies in pet dogs with glioma. The median survival of dogs treated with surgery and autologous tumor lysate vaccine immunotherapy in a clinical trial was 209 days. Immune checkpoint inhibitors have been shown to enhance anti-tumor immunity for many different tumor types. We developed canine-specific peptides that inhibit the immunosuppressive effects of a novel immune checkpoint protein, CD200 (OX2). We hypothesized that the addition of these peptides to our previously tested autologous tumor lysate vaccine therapy would significantly increase overall survival (OS). Dogs were treated by surgical resection and injections of autologous tumor lysate/imiquimod + anti-CD200 peptides. Vaccines were given once a week for 3 weeks, then once a month for 3 vaccines, then once every 6-8 weeks until tumor recurrence, starting 10 days after surgery. MRIs were obtained immediately after and 4, 8, and 12 months after surgery. The primary outcome measured was OS. 19 dogs were recruited, primarily brachycephalic breeds with mean age of 8.1 years. All tumors were high-grade (grade III or IV) gliomas. The primary adverse effect was a steroid-responsive leukoencephalopathy; but owners assessed their dogs’ quality of life as excellent. For the first time in an immunotherapy trial, we observed radiographic regression in dogs that had a large volume of residual tumor. Median OS for the peptide treated dogs was 386 days, which is significantly longer that with vaccines alone from previous studies (209 days) (P=0.037). CD200 inhibitory peptides added to vaccine-based immunotherapy after tumor resection delayed tumor recurrence and significantly extended OS in dogs with spontaneous high-grade glioma, which may be translatable to human glioma patients.
Retracted: Worldwide burden of cancer attributable to diabetes and high body-mass index: a comparative risk assessment
Authors: Jonathan Pearson-Stuttard, Bin Zhou, Vasilis Kontis, James Bentham, Marc J Gunter, Majid Ezzati
Journal: The Lancet Diabetes & Endocrinology (2017)

Diabetes and high body-mass index (BMI) are associated with increased risk of several cancers, and are increasing in prevalence in most countries. We estimated the cancer incidence attributable to diabetes and high BMI as individual risk factors and in combination, by country and sex.
NIMG-20. ANALYSIS OF PERFUSION CT PARAMETERS FOR DIFFERENTIATING AMONG GLIOBLASTOMA, PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA AND BRAIN METASTASIS
Authors: Shumpei Onishi, Yoshinori Kajiwara, Takeshi Takayasu, Manish Kolakshyapati, Minoru Ishifuro, Vishwa Jeet Amatya, Yukio Takeshima, Kazuhiko Sugiyama, Kaoru Kurisu, Fumiyuki Yamasaki
Journal: Neuro-Oncology (2017)

Perfusion computed tomography (PCT) can reflect the blood flow and the capillary condition, which is valuable for the preoperative differentiation of brain tumors. We investigated PCT parameters at tumor and peritumoral lesions, and assessed the efficacy of the parameters for differentiating glioblastoma (GBM), primary central nervous system lymphoma (PCNSL), and brain metastasis (METs). We performed PCT in patients with 39 supratentorial malignant brain tumors (22 GBM, 6 PCNSL, 11 METs). Regions of interests were placed manually at the enhanced tumor area confirmed on contrast-enhanced CT image, peritumoral lesion and contralateral white matter. CBV (cerebral blood volume), CBF (cerebral blood flow), MTT (mean transit time) and PS (permeability surface) were measured. Normalized ratio of the PCT parameters obtained by using normal-appearing white matter as the denominator were used for analyses in all cases, respectively. Mann-Whitney U Test was used to compare all of the parameters. Logistic regression and receiver operating characteristic analyses were constructed to evaluate the preoperative diagnostic performance. nCBV and nCBF of GBM were statistically higher than those of PCNSL (p= 0.0002, 0.0005) and METs (p= 0.0028, 0.0044) at tumor area. At peritumoral lesion, nCBV and nCBF of GBM were statistically higher than those of PCNSL (p= 0.0002, 0.0005) and MET (p= 0.0028, 0.0044). nMTT of METs was statistically higher than that of GBM and PCNSL at peritumoral lesion (p= 0.0001, p= 0.0007). The logistic regression and receiver operating characteristic analyses indicated that GBM could differentiate from PCNSL and METs with sensitivity and specificity with 86.3% and 94.1%. METs could differentiate from PCNSL and MET with sensitivity and specificity with 90.9% and 96.4%. PCT parameters of GBM, PCNSL, METs and their peritumoral lesion provide the valuable information for the preoperative differentiation among these three types of tumors.
NCOG-18. PHASE I TRIAL OF DIMETHYL FUMARATE, TEMOZOLOMIDE AND RADIATION THERAPY IN NEWLY DIAGNOSED GLIOBLASTOMA MULTIFORME: A PRELIMINARY NEUROCOGNITIVE PERSPECTIVE
Authors: Ashlee Loughan, Danielle Shafer, Autumn Lanoye, Sarah Braun, Paul Dent, Mark Malkin
Journal: Neuro-Oncology (2017)

Cognitive deficits both prior to therapy and during treatment have been documented within the glioblastoma (GBM) population. As more effective therapies arise, the options to explore lasting cognitive effects broaden. Based on pre-clinical data demonstrating synergism with radiation (RT) and temozolomide (TMZ), a phase I study was conducted of dimethyl fumarate (DMF; provided by Biogen) in patients with newly diagnosed GBM in combination with standard therapy. To date, there is no documentation of neuropsychological correlates in the treatment of cancer patients undergoing this combination of therapy. At the highest dose level, six newly diagnosed GBM patients received DMF 240 mg tid with RT (60Gy) and concurrent TMZ 75mg/m2, followed by adjuvant DMF and TMZ (150-200mg/m2 on days 1-5 of each 28 day cycle) for up to 6 maintenance cycles. Neuropsychological evaluations were performed across three time points (0, 3, 6 months). Repeated measure ANOVAs and paired samples t-tests were conducted to compare neurocognitive functioning. There was a significant effect on language functioning across time, Wilks’ Lambda = .112, F (2,3) = 11.919, p = .037. A paired samples t-test indicated a significant difference in the scores between 3 (M=97.8, SD=8.47) and 6 (M=89.60, SD=7.60) months; t(4)=4.954, p=.008. All neurocognitive scores will be presented. Other cognitive domains and all emotional ratings were nonsignificant for effects across time. Although still within the average range, there was a negative trend in language functioning between 3 and 6 months. It will be important to further compare these results to individuals undergoing standard therapy alone. This study was supported by an Investigator-Initiated Trial grant from Biogen, and by the Massey Cancer Center.
A vigilância e a epidemiologia da sífilis no Reino Unido
Authors: A A Righarts, I Simms, L Wallace, M Solomou, K. A. Fenton
Journal: Eurosurveillance (2004)

O objectivo deste artigo e de descrever a evolucao da sifilis infecciosa no Reino Unido (RU) e particularmente o estudo da epidemia de sifilis de Londres, a mais importante do RU ate hoje. Analizou-se a vigilância de rotina dos dados provindo das clinicas de medicina genito-urinaria (genitourinary medicine, GUM), assim como os dados colhidos pelos sistemas reforcados de vigilância. Os diagnosticos de sifilis infecciosa aumentaram notavelmente entre 1998 e 2003, multiplicando-se por 25 (de 43 diagnosticos a 1 028) em homens que tem relacoes sexuais com outros homens (HRSH), por 6 (de 138 a 860) em homens heterosexuais e triplicado para mulheres (de 112 a 338). Essa tendencia nacional ao aumento foi iniciada por uma serie de surtos locais, o primeiro ocorrido em 1997. Depois da identificacao dos primeiros casos em 2001, 1 910 casos tem sido declarados em Londres. Numerosas coinfeccoes pelo VIH foram identificadas nos HRSH, sendo a maioria dos casos de etnia branca e nascidos no RU. Ao contrario, os pacientes heterosexuais eram mais frequentemente de etnia negra e nascidos fora do RU. A maior parte dos pacientes com sifilis foram infectados en Londres.
Situação actual da poliomielite face ao objectivo da sua erradicação, na Europa
Authors: S Wassilak, G Oblapenko, S Dittmann
Journal: Eurosurveillance (1997)

Em 1988, a Assembleia Mundial da Saude fixou como objectivo, para o ano 2000, a erradicacao mundial da poliomielite devida ao virus selvagem da polio. As estrategias da campanha sao: atingir e manter um nivel elevado de cobertura vacinal, por rotina, de toda a populacao; permitir uma vacinacao suplementar atraves de campanhas massivas, designadas por Dias Nacionais de Vacinacao (DNVs), as criancas sem ter em conta o seu estado vacinal anterior; realizar operacoes de vacinacao euxastivas (mopping up) por contacto porta-a-porta aos grupos de alto risco; e empreender uma vigilância activa da paralisia flacida aguda, para detectar rapidamente todos os possiveis casos de poliomielite e fornecer dados virulogicos que confirmem a ausencia de virus selvagem da polio, em circulacao. A erradicacao da poliomielite foi certificada, na Regiao das Americas da OMS, em 1994. Este relatorio apresenta os progressos actuais para atingir aquele objectivo nos 51 paises da Regiao Europeia da OMS, a qual inclui todos os paises dos Novos Estados Independentes (NEI) da antiga Uniao Sovietica, Turquia e Israel.
PATH-49. LIMITS OF IMMUNOHISTOCHEMISTRY IN DETECTION OF IDH1 MUTATIONS IN LOW GRADE GLIOMAS
Authors: Radim Jancalek, Marketa Hermanova, Ondrej Slaby
Journal: Neuro-Oncology (2017)

Mutations in the isocitrate dehydrogenase 1 (IDH1) gene are the most common mutations in low-grade gliomas (LGGs) with significant prognostic value and impact on the incidence of tumor associated epilepsy. The somatic mutations in IDH1 gene have approximately 55% to 80% of LGGs. Over 90% of them affect functionally important Arg at position 132 leading to Arg132 by His substitution (R132H) that can be detected by a routine immunohistochemical staining method. However, there are another at least five types of the IDH1 codon 132 mutations that cannot be revealed by the immunohistochemistry. Objective. The aim of our study was to assess the rate of R132H positivity by IDH1 sequencing in our set of LGGs and verify the rate of false negative results of the immunohistochemical method. Our pilot cohort of 26 patients suffering from the glioma of WHO grade 2 were tested for IDH1R132H positivity by the routine immunohistochemical staining method and direct IDH1R132 sequencing. We found the IDH1R132H immunohistochemical positivity in 13 of 26 LGGs (50,0%). The IDHR132 mutations were detected by direct DNA sequencing in 15 LGGs (57,7%) of which 2 tumors had IDH1R132C mutation that represents the false negative rate of immunohistochemistry. IDH1 wild type LGGs were found in 11 cases (42,3%). The rate of the IDH1R132H mutation in our set of LGGs corresponds with results of other studies. Our findings support the need for the direct DNA sequencing in LGGs with IDH1R132H immunohistochemical negative staining because of the risk of false negative results in gliomas with non-R132H IDH1 mutations.
MA 10.02 Nab-Paclitaxel + Durvalumab as Second- or Third-Line Treatment of Advanced NSCLC: Results from ABOUND.2L+
Authors: R. Govindan, M. Cobo Dols, S. Aix, P.E. Postmus, C. Lewanski, J. Bennouna, J. Fischer, O. Vidal, D. Stewart, A. Ardizoni, J. Weaver, M. Wolfsteiner, M. Reck, D. Talbot, D. Morgensztern, T.J. Ong
Journal: Journal of Thoracic Oncology (2017)
S-1, an oral fluoropyrimidine anticancer agent, enhances radiosensitivity of human oral squamous cell carcinoma xenografts resistant to 5-FU
Authors: Koji Harada, Yuichiro Kawashima, Hideo Yoshida, Mitsunobu Sato
Journal: Cancer Research (2006)

574   Purpose: S-1 is a new oral antineoplastic agent which can inhibit cell growth and induces apoptosis in certain types of cancer cells including gastric carcinomas, colorectal cancers, and head and neck cancers. Also, we have continued to investigate the combined effects of S-1 and radiation on human oral cancer cells (Oral Oncol 40, 2004, Int J Oncol 25, 905, 2004, Cancer Lett 226, 161, 2005). In the present study, we investigated whether S-1 enhances the therapeutic efficacy of radiation and if so what are the underlying mechanisms with the 5-FU resistant HSC2/FU and B88/FU human oral squamous cell carcinoma cell lines. Methods and materials: Nude mice bearing HSC2/FU or B88/FU tumor xenografts were treated with S-1 (10 mg/kg/day, 5 days/week, 3 weeks), radiation (1.5 Gy/day, 5 days/week, 3 weeks), or both. Tumor growth delay was the treatments9 endpoint. To determine whether S-1 enhances intrinsic cell radiosensitivity, we performed clonogenic cell survival assay. Also, we assessed the protein expression of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), and orotate phosphoribosyl transferase (OPRT) using immunohistochemistory, and the gene expression of them using microdissection and RT-PCR. Result: While S-1 or radiation were only slightly effective as single agents in delaying tumor growth, the combined treatment was highly effective. Clonogenic cell survival showed that S-1 strongly enhanced cell radiosensitivity. Immunohistochemistry showed that the expression of TS, DPD and TP was down-regulated, and that OPRT was up-regulated in tumors treated by S-1 and radiation. In the same way, microdissection and RT-PCR revealed that the expression of TS, DPD and TP mRNA was down-regulated, and that OPRT mRNA was up-regulated in tumors treated by combined treatment. Conclusions: Combined S-1 and radiation treatment resulted in a synergistic in therapy of 5-FU resistant human oral squamous cell carcinoma xenografts. The effect could be attributed to the ability of S-1 to increase cell radiosensitivity and to the down-regulation of TS, DPD and TP, or the up-regulation of OPRT involved in cellular processes leading to chemosensitivity with 5-FU.
CMET-18. EARLY POSTOPERATIVE MRI DETECTS UNEXPECTED RESIDUAL BRAIN METASTASES AFTER RESECTION IN A HIGH FREQUENCY OF CASES: A RETROSPECTIVE ANALYSIS IN THREE SPECIALIZED CENTERS
Authors: Barbara Kiesel, Johannes Kerschbaumer, Julia Furtner, Romana Prihoda, Franz Marhold, Mario Mischkulnig, Anna Sophie Berghoff, Matthias Preusser, Georg Widhalm, Christian Freyschlag
Journal: Neuro-Oncology (2017)

Surgical resection represents an important treatment option in brain metastases. In the last years, the extent of resection was identified as key factor in the postoperative patient prognosis in brain metastases. Although such tumors are the most common intracranial lesions, no postoperative imaging standards have been established so far. Recently, a single center study observed a relatively high portion of residual brain metastases after surgery. The aim of our study is thus to analyze the extent of resection in brain metastasis after surgery in a large patient cohort in multiple specialized centers. In this study, we retrospectively analyzed patients that underwent resection of brain metastases at three neurosurgical departments in Austria with available early postoperative MRI performed before discharge. The extent of resection was investigated using T1-weighted images with/without contrast medium (complete vs incomplete resection). Additionally, we compared the intraoperative impression of the neurosurgeon with regard to the extent of resection to the postoperative MRI data. Altogether 237 patients with surgically treated brain metastases were included. Lung cancer (46%) was the most common primary tumor followed by melanoma (15%). Postoperative MRI found a complete resection in 74% (n=175) of cases, whereas in 20% (n=48) an incomplete resection was detected. In the remaining 6% (n=14) of cases, no definite statement was possible regarding the extent of resection. The residual tumor was expected by the neurosurgeon in only 17% (n=8) of 48 cases. Thus, postoperative MRI detected an unexpected residual tumor in 17% (n=40) of all 237 cases. Our data of this large, multicenter center analysis indicate a high frequency of unexpected residual brain metastases after resection. Since an incomplete resection is an adverse prognostic factor, we recommend establishing a standardized postoperative imaging protocol to routinely assess the extent of resection in brain metastases.
OA 14.05 Phase 2 Basket Trial of Ado-Trastuzumab Emtansine in Patients with HER2 Mutant or Amplified Lung Cancers
Authors: B. Li, R. Shen, D. Buonocore, Z. Olah, A. Ni, M. Ginsberg, G. Ulaner, W. Weber, D. Tsui, M. Offin, H. Won, M. Ladanyi, G. Riely, D. Solit, D. Hyman, C. Rudin, M. Berger, J. Baselga, M. Scaltriti, M. Arcila, M. Kris
Journal: Journal of Thoracic Oncology (2017)
The raf kinase inhibitor sorafenib inhibits Jak-STAT signal transduction in human immune cells
Authors: Ene Raig, Sri Vidya Kondadasula, Thomas Olencki, J Monk, Gregory Lesinski, William Carson
Journal: Cancer Research (2008)

1434   Sorafenib is a novel anti-cancer agent that functions through its direct effects on tumor cells, namely via its ability to inhibit Raf kinase activity. This drug has shown efficacy in patients with metastatic renal cell carcinoma. Recent efforts have focused on its administration in combination with immunomodulatory cytokines such as IL- 2 and interferon-alpha (IFN-a), which also have efficacy in this disease. We hypothesized that sorafenib may have inhibitory effects upon immune effector cells, thereby impacting their responsiveness to endogenous and exogenous cytokines. Phosphorylation of signal transducer and activator of transcription 1 (STAT1) and STAT5 in response to IFN-a and IL-2 was evaluated by intracellular flow cytometry and validated via immunoblot analysis. Pre-treatment of peripheral blood mononuclear cells (PBMC) with sorafenib (10 uM) resulted in decreased phosphorylation of STAT1 (pSTAT1) following treatment with 10 5  U/mL IFN-a (Mean % pSTAT1 positive cells = 9.9 ± 7.1% for sorafenib pre-treatment vs. 89 ± 0.64% for vehicle pre-treatment). Pre-treatment of PBMC with sorafenib (10 uM) resulted in reduced phosphorylation of STAT5 (pSTAT5) following treatment with 8 nM IL-2 (Mean % pSTAT5 positive cells = 3.8 ± 2.9% for sorafenib pre-treatment vs. 78 ± 6.3% for vehicle pre-treatment, p 6  U/mL could not overcome the inhibitory effects of sorafenib pre-treatment of PBMC. Pre-treatment of PBMC with sorafenib also inhibited the expression of OAS1 and IFIT2, which are IFN-a regulated genes (mean fold induction = 24 ±5.2 and 3421 ±829 respectively in sorafenib pre-treated vs. 54 ±10 and 8454 ±1253 respectively in vehicle pre-treated cells). Similar reductions in IL-2 responsive genes (IFN-gamma, CIS, PIM-1) were also observed following sorafenib pre-treatment of PBMC. PBMC obtained from patients receiving 400 mg of sorafenib twice daily also show decreased responsiveness to IL-2 and IFN-a treatment  in vitro  as evidenced by decreased phosphorylation of STAT1 and STAT2 compared to pretreatment levels.  We conclude that sorafenib can act as a potent inhibitor of cytokine-induced signal transduction in off-target cells, such as immune effector cells. These data suggest that the order in which the combinations of sorafenib and immunomodulatory cytokines are administered will be critical to obtaining the maximum clinical benefit.
Une épidémie d'intoxications alimentaires à Salmonella enteritidis dans un hôpital psychiatrique à Dublin, Irlande
Authors: T Grein, D O’Flanagan, T McCarthy, T Prendergast
Journal: Eurosurveillance (1997)

Le 29 aout 1996, le Eastern Health Board (EHB) d'Irlande etait informe d'une epidemie de gastro-enterites dans un hopital psychiatrique a Dublin. Parmi les 240 membres du personnel et les 183 patients, 50 cas avaient ete identifies depuis le 27 aout 1996 et de nouveaux cas continuaient d'apparaitre. Le EHB a immediatement lance une enquete pour evaluer l'etendue de l'epidemie, identifier le mode et le vehicule de transmission et mettre en place des mesures de controle appropriees.
P2.03-039 Compassionate Use of Osimertinib: Argentine Experience
Authors: J. Minatta, L. Lupinacci, G. Recondo, S. Sena, G. Boggio, A. Muggeri, C. Rosenbrock, F. Cayol, M. Angel, M. Muñoz, S. Berutti, N. Castagneris, D. Gomez Bradley, J. Lastiri
Journal: Journal of Thoracic Oncology (2017)
P3.02-027 Lung Adenocarcinoma Patient with EGFR 19 Exon Insert Mutation: I740_K745insIPVAIK and Its Response to Icotinib: A Case Report
Authors: C. Xu, W. Wang, W. Zhuang, Y. Chen, G. Chen, M. Fang, R. Chen, Y. Guan, X. Yi, T. Lv, Y. Song
Journal: Journal of Thoracic Oncology (2017)
Should cost effectiveness analyses for NICE always consider future unrelated medical costs?
Authors: Pieter van Baal, Alec Morton, Werner Brouwer, David Meltzer, Sarah Davis
Journal: BMJ (2017)

More health would result from including all future care costs in decisions to approve interventions, write <b>Pieter van Baal and colleagues</b>. <b>Sarah Davis</b> worries that always including unrelated costs might lead to unfair distribution of care, including among people with incurable illness
OA 09.05 Identification of Novel Potentially Targetable Genomic Alterations in Paired Tumors with Acquired EGFR TKI Resistance by NGS
Authors: J. Robichaux, Y. Elamin, J. Zhang, A. Futreal, E. Roarty, W. Rinsurongkawong, J. Lewis, H. Tran, S. Swisher, J. Heymach
Journal: Journal of Thoracic Oncology (2017)
Preparazione e risposta delle istituzioni di sanità pubblica europee al bioterrorismo
Authors: B Coignard
Journal: Eurosurveillance (2001)

Gli attacchi terroristici dell'11 settembre 2001 e la deliberata diffusione di spore di antrace hanno avuto conseguenze sulla sanita pubblica non soltanto negli Stati Uniti ma anche in Europa. I servizi sanitari dei paesi europei hanno dovuto gestire una grande quantita di materiale postale potenzialmente contaminato da spore di antrace. La nostra inchiesta ha avuto lo scopo di documentare la risposta delle istituzioni europee di sanita pubblica ai recenti eventi bioterroristici per identificare le lacune che ancora devono essere colmate; hanno partecipato a questo Euroroundup 18 istituzioni di 16 paesi. Le minacce bioterroristiche in Europa si sono rivelate solo degli scherzi di cattivo gusto, da considerare come un'esercitazione di preparazione, dalla quale si possono trarre tre lezioni. Primo, lo scorso ottobre l'Europa non era affatto pronta a rispondere al bioterrorismo. Secondo, anche se le istituzioni europee hanno reagito prontamente, adattando le loro priorita a questo nuovo tipo di minaccia, avranno bisogno di un supporto adeguato e duraturo da parte dei loro rispettivi governi per mantenere la loro capacita globale. Terzo, la recente crisi ha dimostrato la necessita di maggiori investimenti nei programmi di formazione epidemiologica e di una unita di coordinamento tecnico per la sorveglianza e la risposta internazionale alle epidemie nell'Unione Europea.
P1.05-018 Prognostic Impact of Tumor Shadow Disappearance Rate in Patients with Clinical IA Lung Adenocarcinoma
Authors: J. Samejima, H. Ito, H. Nakayama, T. Nagashima, J. Osawa, K. Inafuku, M. Nito, T. Yokose, K. Yamada, M. Masuda
Journal: Journal of Thoracic Oncology (2017)