tbuckley/cabot-search huggingface dataset:
NIMG-08. EVALUATING THE APPLICABILITY OF TUMOR PROBABILITY MAPS AS A RESOURCE FOR IMPROVED BRAIN TUMOR SEGMENTATION
Authors: Edgar Rios Piedra, Benjamin Ellingson, Suzie El-Saden, Timothy Cloughesy, Ricky Taira, Alex Bui, William Hsu
Journal: Neuro-Oncology (2017)

Quantitative measurement and assessment of magnetic resonance images (MRI) has an important role in the diagnosis, evaluation, and follow-up of brain tumors. Unfortunately, defining tumor boundaries on such images is a difficult task for automated methods – and even trained radiologists – as tumors tend to have irregular shapes, ill-defined margins, and various degrees of heterogeneity. In this work, we demonstrate that binary pixel classification of tumor regions is sub-optimal in reflecting the underlying biology of different tumor compartments and propose that pixel-wise probability maps are a more appropriate representation of tumor extent, providing volumetric approximations with error estimates. We present a framework that performs multimodal analysis of a tumor boundary using different perspectives to identify regions of high heterogeneity and that, together with error analysis, can be used as reference to identify instances on which the tumor segmentation is unclear and can be employed to improve performance of the segmentation algorithm on future cases. This approach was evaluated on a set of 110 cases of high grade gliomas obtained from The Cancer Genome Atlas (TCGA) for which a manual tumor region of interest (ROI) was available. From these cases, our algorithm automatically generated binary and probability masks for the dataset; comparison with the manual ROI resulted in a Dice coefficient of 0.8. It was qualitatively observed that the derived probability maps (overlaid as color maps on an MRI volume) provide a better visualization of tumor burden and its heterogeneous characteristics, which can be valuable during treatment planning (e.g., radiotherapy) and evaluation of disease progression over time.
Les SARM produisant la leucocidine de Panton-Valentine : la situation aux Pays-Bas en 2003
Authors: W J B Wannet, M E Heck, G N Pluister, E Spalburg, M G Van Santen, X W Huijsdans, E Tiemersma, A J de Neeling
Journal: Eurosurveillance (2004)

Aux Pays-Bas en 2003, l'analyse des isolats de Staphylococcus aureus resistants a la methicilline (SARM) a revele que 8% des isolats provenant d'hopitaux etaient porteurs de genes pour la leucocidine de Panton-Valentine (LPV). Le sous-typage moleculaire a montre qu'aux Pays-Bas la plupart des genotypes de LPV-SARM correspondaient a des types epidemiques globaux bien connus. Les plus frequentes etaient les sequences de types ST8, ST22, ST30, ST59 et ST80. Aux Pays-Bas, les SARM ST8 ont augmente de 1% en 2002 a 17% en 2003. Il est important de noter que l'emergence des LPV-SARM concerne non seulement la communaute, mais aussi les hopitaux.
P1.16-012 Application of Fluorescent and Iodized Dual Marker for Pre-Operative Localization and Image-Guided Surgery of Pulmonary Nodule
Authors: J. Rho, J.W. Lee, Y.H. Quan, B.H. Choi, R. Xu, K.N. Han, Y.H. Choi, H.S. Yong, H.K. Kim
Journal: Journal of Thoracic Oncology (2017)
Stromal peritumoral and intratumoral infiltrating lymphocytes: how immunity influences prognosis in triple negative breast cancer
Authors: A. Della Mora, L. Bastianelli, M. Pistelli, A. Santinelli, L. Cantini, A. Doria, F. Merloni, A. Lucarelli, A. Savini, E. Maccaroni, Z. Ballatore, A. Pagliacci, R. Berardi
Journal: Annals of Oncology (2017)
EXTH-61. TARGETED NANOPARTICLE DELIVERY OF THERAPEUTIC ANTIMIR-21 AND ANTIMIR-10B PRESENSITIZES GLIOBLASTOMA TO LOWER EFFECTIVE DOSES OF TEMOZOLOMIDE IN CELLS AND XENOGRAFTS
Authors: Meenakshi Malhotra, Thillai Sekar, Rammohan Devulapally, Rayhaneh Afjei, Ramasamy Paulmurugan, Tarik Massoud
Journal: Neuro-Oncology (2017)

MiR-21 and miR-10b are oncomiRs overexpressed in glioblastoma (GBM). Therapeutic antisense microRNAs (antimiRs) can effectively initiate cellular apoptosis. We hypothesized that encapsulating antimiR-21 and antimiR-10b into c-RGD peptide surface tagged PLGA nanoparticles (NPs) would lead to enhanced GBM cell uptake of NPs, efficient in vivo antimiR delivery, and greater chemosensitization to concurrent temozolomide (TMZ). We developed and characterized c-RGD-targeted and non-targeted NPs. We first treated U-87MG and Ln229 cells with NPs, with and without different doses of TMZ to determine cellular uptake, toxicity, anti-proliferation, and apoptosis by qRT-PCR and an immunoassay for key target genes of miR-21 and miR-10b. We then treated mouse U-87MG xenografts to measure changes in tumor volumes. In culture, we found higher (p<0.001) cellular uptake of targeted versus non-targeted NPs, and increased chemosensitivity (p<0.01) towards TMZ at lower concentrations (62.75 µM). There was increased cell cycle arrest at G2/M phase, especially for targeted NPs plus TMZ. We observed an increase in U-87MG cell expression of miR-21 key target genes: PTEN, PDCD4, Caspase 3, and p53, when treated with NPs. In mice there was significant (p<0.01) reduction in tumor volumes after Day 6 of TMZ treatment (25 mg/kg) for NPs irrespective of surface modifications. However, in a dose escalation study of TMZ following delivery of targeted NPs, we found a reduction (p<0.01) in tumor volumes starting at 6.25 mg/kg TMZ. Tagging NPs with c-RGD enhances their targeting to GBM cells in culture. Although passive tumor targeting of NPs in vivo may be a key mechanism for NP tumor localization, chemosensitization of cancer cells with antimiRs leads to a reduction in tumor volumes at lower TMZ dosages. Thus, NP-assisted silencing of miR-21 and miR-10b prior to TMZ treatment is an effective molecular theranostic strategy that may lead to improved treatment options for GBM.
Potential contribution of the study nurse to colorectal cancer (CRC) translational research
Authors: I. Rigotto, M. Schirripa, D. Costardi, F. Loupakis, C. Magro, O. Diamanti, C. Lando, G. Pauletti, E. Zemella, C. Fano, F. Bonadies, G. Gottardo, F. Bergamo, I. Beriotto, F. Buggin, S. Lonardi, V. Zagonel, D. Grosso
Journal: Annals of Oncology (2017)
Gestione Enter-net delle indagini sui focolai internazionali alimentari provocati da patogeni gastrointestinali
Authors: J C Desenclos, I. S.T. Fisher, O N Gill
Journal: Eurosurveillance (1999)

La libera circolazione di persone, beni e alimenti all'interno dell'Unione Europea (UE) ha aumentato l'opportunita del verificarsi di focolai internazionali di infezioni alimentari, malgrado gli sforzi per ridurre la contaminazione microbiologica degli alimenti. Il potenziamento della rete di sorveglianza internazionale Enter-net (precedentemente chiamata Salm-net) dovrebbe permettere un riconoscimento e un'indagine precoci di questi focolai internazionali (1).
TMIC-47. IMMUNOBIOLOGICAL CHARACTERIZATION OF CNS GERMINOMAS – EVIDENCE FOR INFLAMMATORY AND SUPPRESSIVE IMMUNOLOGICAL MECHANISMS
Authors: Pia Zapka, Evelyn Doerner, Verena Dreschmann, Noriaki Sakamoto, Glen Kristiansen, Gabriele Calaminus, Christian Vokuhl, Ivo Leuschner, Torsten Pietsch
Journal: Neuro-Oncology (2017)

Germinomas of the CNS are characterized by a massive immune cell infiltrate. Aim of our study was to systematically characterize and quantify these immune cells. Immunohistochemistry was performed on FFPE sections of 28 germinomas using antibodies specific for different immune cell populations. Cells were quantified using an image analysis work station (Definiens Tissue Studio). Tumor infiltrating lymphocytes (TILs) were composed of 61.8 ± 3.1% (mean ± SE) CD3+ T cells, including 45.2 ± 3.5% of CD4+ T helper cells, 23.4 ± 1.5% of CD8+ cytotoxic T cells, 5.5 ± 0.9% of FoxP3+ regulatory T cells and 11.9 ± 1.3 % PD-1+ TILs. B cells accounted for 35.8 ± 2.9% of TILs and plasma cells for 9.3 ± 1.6%. Tumor-associated macrophages were characterized by clusters of activated macrophages positive for PD-L1 and interspersed anti-inflammatory macrophages expressing CD163. Germinoma cells did not express PD-L1. mRNA expression was quantified by Nanostring technology using barcoded probes specific for individual gene transcripts. We detected high expression of primordial germ cell markers. The expression of genes encoding immune cell markers and cytokines was high and comparable to mRNA levels in lymph node tissue. In situ RNA hybridization (RNAscope, Advanced Cell Diagnostics) was performed targeting mRNA of PD-L1 and its modulating cytokines IL-10 and IFNG and combined with immunohistochemistry for PD-L1 and CD163. IFNG mRNA was highly expressed in interspersed TILs and at lower level in PD-L1+ macrophages. IL-10 mRNA was detected in a subfraction of TILs and in PD-L1+ and CD163+ macrophages. Taken together, the strong immune reaction observed in germinomas involves inflammatory (e.g. IFNG expression) as well as various suppressive mechanisms, with the latter probably representing an adaptive response. Expression of PD-1 and PD-L1 and infiltration of cytotoxic T cells are biomarkers predictive of response to anti-PD-1/PD-L1 therapies, constituting a rationale for possible novel treatment approaches.
IMMU-07. DIRECT CANCER CELL TO DENDRITIC CELL CONVERSION: A NOVEL IMMUNOTHERAPY FOR GLIOBLASTOMA
Authors: Mathew Sebastian, Changwang Deng, Son Le, Nagheme Thomas, David Tran
Journal: Neuro-Oncology (2017)

Cell-based immunotherapy has shown encouraging results in solid cancers including glioblastoma (GBM). However, major limitations of cell-based immunotherapy in GBM include difficulty with isolation and generation of effective antigen-presenting or immune effector cells, inadequate migration of immune cells across the blood brain barrier, and the high cost of cell-based vaccines. One approach to overcome these barriers is to convert GBM cells directly into immune cells of interest. Transdifferentiation, the transformation of one differentiated cell type directly into another without an intermediate pluripotent stage, has shown early promise in regenerative medicine, but has had a limited role in cancer therapy, especially for solid tumors. This is in large part due to the laborious and time-consuming process of identifying experimentally master fate determinants of various cell types. To enable this novel application, we have developed and experimentally validated two tandem computational platforms, GeneRep and nSCORE. Applying this novel tool to large quantities of published datasets, we successfully predicted cell fate determinants of tens of different cell types with several having been validated in transdifferentiation experiments by others and us, such as the conversions of astrocytes to neuronal stem cells and of fibroblasts to macrophages, etc. Here, we describe the process of combining a core set of hematopoietic stem cell, myeloid, and macrophage or dendritic cell (DC) fate determinants as predicted by GeneRep-nSCORE to efficiently transdifferentiate GBM cells into functional macrophages or dendritic cells, respectively, while neutralizing their malignant phenotype. This novel transdifferentiation has the potential for transformative impacts in many areas including DC vaccine immunotherapy and cancer therapy in general, and pioneers the concept that solid tumor cells can be converted into another cell type, and not just any cell type, but one that potentially can elicit a therapeutic response against itself.
Adaphostin induced toxicity in lung tumor cell lines implicates oxidative stress that is mediated through the Nrf-2/heme oxygenase pathway
Authors: Nicole D. Reifsnider, Curtis D. Hose, Anne Monks
Journal: Cancer Research (2006)

4648  We evaluated 2 agents that contain an active lactone moiety, curcumin (a plant derivative) and simvastatin (a statin), as cytostatic agents for the treatment of breast cancer. The anti-tumor activity of these 2 agents is currently speculative. Evidence points to curcumin as a potent antioxidant and anti-inflammatory agent, both desirable properties that have been reported to play key roles in inhibiting carcinogenesis. Simvastatin, sold under the brand name Zocor for the treatment of high blood cholesterol, is being intensely investigated for the treatment of Alzheimer’s and other neurodegenerative disorders. In this report, we describe a plausible mechanism of the potential cytostatic action of both curcumin and simvastatin through the proteasome proteolytic pathway. Using cell culture models and a variety of biochemical in vitro assays, we found that curcumin and simvastatin function, albeit weakly, like classic proteasome inhibitors such as MG-132 and PS-341. Using a panel of 3 breast tumor cell culture models (MDA-MB-231, MDA-MB-436, and Hs578T), we showed that these 2 agents mediate their cell cycle inhibitory activities by blocking the chymotrypsin-like activity of the proteasome in vitro. Using a vector that expresses a fusion protein of green fluorescent protein (gfp) and Mouse Ornithine Decarboxylase (MODC) in our model cell lines, we also showed qualitatively (microscopically) and quantitatively (flow cytometrically) that these 2 agents inhibit proteasomal degradation of MODC ex vivo. These results were indicative of increased MODC accumulation (as measured by increased gfp). Similarly, because the cyclin-dependent kinase inhibitors p21 and p27 are normally degraded by the proteasome, treatment of our model cell lines with curcumin and simvastatin prevented the degradation of p21 and p27. This failure to degrade resulted in the accumulation of p21 and p27 and their ubiquitinated forms and thus led to G1 arrest in the MDA-MB-231 and Hs578T models. However, the MDA-MB-436 model, which lacks p21, failed to arrest after treatment with either agent, although the proteasome activity in the cell extract was inhibited. Furthermore, in preliminary clonogenic assays, we found that both curcumin and simvastatin affected synergistic cell killing in combination with ionizing radiation. Collectively, our data suggest that both curcumin and simvastatin mediate G1 arrest and possibly cytostasis and apoptosis by blocking the proteasome activity and upregulating the p21 protein in breast cancer cells.
P1.02-014 TGFalpha Promotes Growth of Lung Tumors Carrying EGFR Mutation but not KRAS Mutation in Transgenic Mouse Models in Vivo
Authors: K. Tomoshige, G. Minzhe, T. Tsuchiya, T. Fukazawa, Y. Naomoto, T. Nagayasu, Y. Maeda
Journal: Journal of Thoracic Oncology (2017)
La robustesse de l’immunité contre la rougeole chez les parturientes de Guipúzcoa (Pays basque, Espagne) : bilan post-vaccination
Authors: G Cilla, E Serrano-Bengoechea, D Vicente, M Montes, E Pérez-Trallero
Journal: Eurosurveillance (2007)

Les nourrissons nes de meres presentant une immunite induite par le vaccin perdent les anticorps anti-rougeole acquis passivement plus tot que les nourrissons des meres infectees naturellement.
CSIG-09. REPROGRAMMING OF SCHWANN CELLS BY LATS1/2-TAZ/YAP SIGNALING DRIVES MALIGNANT PERIPHERAL NERVE SHEATH TUMORIGENESIS
Authors: Lai Man (Natalie) Wu, Richard Lu
Journal: Neuro-Oncology (2017)

Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive Schwann cell (SC)-lineage derived sarcomas with poor prognosis. The molecular events underlying SC lineage cells-to-MPNST transformation remain elusive. Here, we show that human MPNSTs exhibit elevated HIPPO-TAZ/YAP expression, and that TAZ/YAP hyperactivity in SCs caused by Lats1/2 loss potently induces high-grade nerve-associated tumors with full penetrance. Lats1/2 deficiency reprograms SCs to a cancerous, progenitor-like phenotype and promotes hyper-proliferation. Conversely, disruption of TAZ/YAP activity alleviates tumor burden in Lats1/2-deficient mice and inhibits human MPNST cell proliferation. Moreover, genome-wide target profiling reveals that TAZ/YAP-TEAD1 directly activates a set of oncogenic programs in SCs including PDGFR/RAF signaling. Co-targeting TAZ/YAP and PDGFR/RAF signaling efficaciously reduces tumorigenicity in Lats1/2-deficient tumors. Thus, our findings establish a previously unrecognized convergence between LATS1/2-TAZ/YAP pathway and MPNST pathogenesis, suggesting that combined inhibition of TAZ/YAP-PDGFR/RAF signaling may be beneficial in MPNSTs.
P2.03-006 How Many Years of Life Have We Lost in Brazil Due to the Lack of Access to Anti-EGFR TKIs in the National Public Health System?
Authors: P. Aguiar, F. Roitberg, H. Tadokoro, R.A. De Mello, A. Del Giglio, G. Lopes
Journal: Journal of Thoracic Oncology (2017)
TMIC-42. TOCA 511 AND 5-FC INDUCES T CELL-MEDIATED ANTITUMOR IMMUNITY IN A MOUSE GLIOMA MODEL WHICH IS ENHANCED BY THE ADDITION OF A THERAPEUTIC ANTIBODY AGAINST CTLA-4 AND CORRELATIVE WITH A REDUCTION IN MEMORY T REGULATORY CELLS.
Authors: Douglas Jolly, Leah Mitchell, Kader Yagiz, Fernando Lopez Espinoza, Daniel Mendoza, Anthony Munday, Harry Gruber
Journal: Neuro-Oncology (2017)

Toca 511 (vocimagene amiretrorepvec) is a gamma retroviral replicating vector that selectively infects cancer cells in vivo and encodes cytosine deaminase. In combination with the prodrug, 5-fluorocytosine (5-FC), Toca 511 produces 5-fluorouracil (5-FU) locally in the tumor microenvironment. This work aimed to determine if the addition of a checkpoint inhibitor, αCTLA-4 would provide therapeutic benefit to Toca 511 and 5-FC in a mouse model of glioma. Initially, we noted that Toca 511 and 5-FC was highly efficacious and that it provided little room for improvement and therefore combination with αCTLA-4 was not able to show additive benefit against the primary cancer. Further examination revealed that tumor associated Regulatory T cells were significantly reduced with αCTLA-4 treatment and long term memory was shown to be significantly improved with the combination. Adoptive transfer of immune cells from animals that cleared their primary tumor through Toca 511, 5-FC, and αCTLA-4 showed 100% survival benefit to animals bearing orthotopic gliomas; significantly greater than the ~50% survival seen with transfer from animals that cleared primary tumor through Toca 511 and 5-FC alone. Further, αCTLA-4 treatment during clearance of primary tumors resulted in a marked reduction of memory T regulatory cells in secondary tumors. Finally, we wanted to determine if αCTLA-4 in combination with Toca 511 and 5-FC significantly reduced tumor burden in a model using a submaximal infection level of Toca 511. Specifically, restricting Toca 511 infection to only 2% of tumor cells limited the activity of 5-FC in a subcutaneous setting and the loss of efficacy with 2% infection was rescued when 5-FC treatment was combined with αCTLA-4. These data suggest that αCTLA-4, and other compounds that target T regulatory cells, should be evaluated in patients receiving Toca 511 and Toca FC to determine if the combination confers additional clinical benefits.
David Ian Hamilton
Authors: James L Wilkinson
Journal: BMJ (2017)

David Ian Hamilton was born in Stockton on Tees. His father was a civil engineer whose area of expertise was bridge building. The family moved to London when David was 6, and where the building of the stone Wandsworth Bridge, over the Thames, was his father’s responsibility. David was a keen rugby player at school—being selected for the English Schools’ XV to play against a French schools’ team in April 1949. He decided that he wanted to become a surgeon because it would allow him to use the manual skills, learned from his father, who was an expert handyman.

After national service, he studied medicine …
Preventing Obstructions of Nanosized Drug Delivery Systems by the Extracellular Matrix
Authors: Luise Tomasetti, Miriam Breunig
Journal: Advanced Healthcare Materials (2017)

Although nanosized drug delivery systems are promising tools for the treatment of severe diseases, the extracellular matrix (ECM) constitutes a major obstacle that endangers therapeutic success. Mobility of diffusing species is restricted not only by small pore size (down to as low as 3 nm) but also by electrostatic interactions with the network. This article evaluates commonly used in vitro models of ECM, analytical methods, and particle types with respect to their similarity to native conditions in the target tissue. In this cross-study evaluation, results from a wide variety of mobility studies are analyzed to discern general principles of particle-ECM interactions. For instance, cross-linked networks and a negative network charge are essential to reliably recapitulate key features of the native ECM. Commonly used ECM mimics comprised of one or two components can lead to mobility calculations which have low fidelity to in vivo results. In addition, analytical methods must be tailored to the properties of both the matrix and the diffusing species to deliver accurate results. Finally, nanoparticles must be sufficiently small to penetrate the matrix pores (ideally Rd/p < 0.5; d = particle diameter, p = pore size) and carry a neutral surface charge to avoid obstructions. Larger (Rd/p >> 1) or positively charged particles are trapped.
QLIF-16. CLINICAL AND SOCIAL CHALLENGES &amp; OPPORTUNITIES IN TREATING GLIOBLASTOMA WITH TUMOR TREATMENT FIELDS, A CASE SERIES
Authors: Minhdan Nguyen, Judy Truong, Marlon Saria, Santosh Kesari
Journal: Neuro-Oncology (2017)

Tumor Treatment Fields (TTFields) is the most recent FDA-approved intervention for glioblastoma (GBM). Although TTFields has now been FDA approved for recurrent disease for the past 6 years, it was more recently approved for newly diagnosed GBMs (in 2015). We report clinical and social observations of treating three specific patients and their unique approaches to this intervention. Patient 1, a 52-year-old single female living independently, diagnosed with GBM in 5/2016, underwent a gross total resection (GTR) followed by Temozolomide (TMZ) 75mg/m2 daily plus radiation therapy (RT). She began monthly TMZ (200mg/m2 days 1-5) and was offered TTFields as well. Due to independent living and neurological symptomology, she would be agreeable to TTFields in clinic, but would decline treatment at home. Patient 2, a 77-year-old male, diagnosed with GBM in 5/2016, underwent GTR followed by TMZ 75 mg/m2 with RT for six weeks complicated with thrombocytopenia. TTFields device and 7 cycles of dose reduced 5-day TMZ 100mg/m2 followed. Patient was highly compliant with TTFields and TMZ and had little to no obstructions in his active lifestyle. Patient 3, a 72-year-old male diagnosed with GBM in 4/2016, who received GTR followed by RT and TMZ 75 mg/m2 without complications. He initiated TTFields with 5-day TMZ at 150mg/m2 but began having symptoms of hydrocephalus after cycle 1. Post ventriculoperitoneal (VP) shunt placement, patient restarted TTFields treatment without any complications to TTFields device or VP shunt settings. Each patient faced different medical and social barriers that may contribute to level of compliance for TTFields intervention. TTFields therapy can significantly improve survival outcomes and therefore both medical and social challenges should be addressed to optimize patient treatment.
P3.02a-010 Evaluation of Aberrant ALK Expression in Lung Cancer by RT-PCR and Comparison with FISH and Immunohistochemistry
Authors: Mirella Giordano, Rossella Bruno, Greta Alì, Agnese Proietti, Antonio Chella, Alfredo Mussi, Gabriella Fontanini
Journal: Journal of Thoracic Oncology (2017)
Cas de chikungunya importés des îles du Sud-Ouest de l’Océan Indien à Paris, France
Authors: P Hochedez, P Hausfater, S Jaureguiberry, A Datry, M Danis, F Bricaire, P Bossi
Journal: Eurosurveillance (2007)

Une epidemie de chikungunya sevit dans les iles du Sud-Ouest de l’Ocean Indien depuis le debut de 2005. Nous decrivons ici les manifestations cliniques et biologiques observees chez 80 patients ayant consulte pour un chikungunya confirme dans notre departement de Maladies Infectieuses entre mars 2005 et aout 2006. Quarante-huit patients etaient des femmes (60 %) et l'âge median etait de 50 ans (min 15- max 75). Le delai median entre le debut des symptomes et la consultation etait de 35 jours (2 jours-9 mois). Tous les patients ont presente de la fievre et des douleurs articulaires. La duree mediane de la fievre etait trois jours (1-7).