tbuckley/cabot-search huggingface dataset:
TMIC-40. ASSESSMENT OF THE KYNURENINE PATHWAY OF TRYPTOPHAN METABOLISM IN PRIMARY BRAIN TUMORS
Authors: Anthony R Guastella, Sam Kiousis, Neil V Klinger, Hassan A Fadel, William Kupsky, Sharon K Michelhaugh, Sandeep Mittal
Journal: Neuro-Oncology (2017)

There is a mounting body of data supporting the role of tryptophan metabolism via the kynurenine pathway (KP) in the pathophysiology of primary brain tumors. In the current study, we examined the differences in KP protein expression, as well as pharmacological inhibition of the KP in WHO grade II-IV gliomas, as well as WHO grade I-III meningiomas. Active tumor tissue was acquired immediately following microsurgical resection, and the tumor was dissociated into a single-cell suspension for performance of in vitro experiments. Immunohistochemical and immunocytochemical staining was performed with antibodies specific for: human indoleamine 2,3-dioxygenase (IDO) 1; IDO2; tryptophan 2,3-dioxygenase (TDO2); and the aryl hydrocarbon receptor (AhR), formerly known as the dioxin receptor, a transcription factor associated with carcinogenesis that is activated by KP metabolites. Tissue sections were scored from 0-3 based on staining intensity. Primary patient-derived cell cultures were treated with commercially available small molecule inhibitors for IDO1 (epacadostat), IDO2 (tenatoprazole), TDO2 (680C91), and AhR (CH-223191). Cell viability was measured via MTT assay, while cell killing was measured via colony formation assay. For both primary brain tumor types, TDO2 and AhR had the highest intensity staining. Moreover, WHO grade IV gliomas showed significantly (p<0.001, ANOVA) higher levels of KP enzymes than any other primary brain tumor type. Nevertheless, MTT data showed markedly diminished cell viability in response to CH-223191 (AhR), regardless of tumor type or grade. Furthermore, colony formation assay revealed that inhibition of AhR lead to the greatest amount of cell death in both tumor types, again regardless of histopathologic grade. These results suggest that inhibition of AhR, and not the rate-limiting enzymes of the KP, may offer a novel therapeutic target for a patient population with highly limited treatment options.
Abstract 20942: Non-Invasive Isolation of the Pulmonary Veins in an Animal Model
Authors: Glenn Van Langenhove, Tim Boussy
Journal: Circulation (2017)

Introduction: Pulmonary vein isolation (PVI) is well established as the preferred treatment for symptomatic paroxsysmal atrial fibrillation (pAF). We introduce a novel technique in which PVI is aimed for in a pig model, by non invasive heating of the proximal ring of an implant inserted in the pulmonary veins. Hypothesis: Non-invasive heating of an implant in the PV is feasible and safe Methods: A self-expanding nitinol-based implant was positioned in the common inferior pulmonary vein of 11 pigs, using a fluoroscopy guided transatrial approach. In a second part of the experiment, implants were positioned in the superior caval vein through a transfemoral approach of another 6 animals. Ablation was performed through a contactless energytransfer from a primary extracorporal coil to a secondary heatring (HR) embedded in the proximal part of the implant. Electrophysiological properties were assessed prior to and post ablation. Histological samples were obtained after 3 months. Results: In total, eightteen PV-implants were succesfully positioned. Ablation was performed in a safe manner, without injury of adjacent structures. PVI and bidirectional block was confirmed in all PV cases, and bidirectional block in 5 of the 6 caval vein implants (entry block shown in the figure-the heatring is at the level of the white arrow). Only mild neointimal proliferation was observed 3 months post ablation. Conclusions: Non-invasive ablation using self-expanding stents in the PV is safe and feasible, bidirectional isolation can be demonstrated in almost all cases, whilst no significant neointimal formation is observed:
STEM-40. THE ROLE OF SYMMETRIC CELL DIVISION IN POST THERAPY GLIOMA STEM CELL EXPANSION
Authors: Shivani Baisiwala, Robert Hall, Cheol Park, Atique Ahmed
Journal: Neuro-Oncology (2017)

Glioblastoma is an aggressive primary malignancy of the brain with almost 100% recurrence rate. Our lab and others have shown that GBM contains a subpopulation of glioma stem cells (GSCs) that may drive the therapeutic resistance capabilities of recurrent GBM. We have shown that the GSC population expands following administration of temozolomide (TMZ). While it has been suggested that this expansion relies solely on Darwinian selection, we and others have demonstrated that cellular plasticity-driven expansion of therapy resistance GSCs post-therapy may play a role in disease recurrence. GSCs can divide in three ways: (1) asymmetric division, which produces one GSC and one differentiated cancer cell, (2) symmetric division that promotes self-renewal by forming two daughter GSCs or (3) symmetric division that supports differentiation by forming two mature cancer cells. Here, we show that symmetric self-renewing cell division—where one GSC gives rise to two daughter GSCs—occurs at a rate of 24% in GBM cells treated with control vehicle, yet at a rate of 54% following TMZ therapy (p<0.0001). Gene expression analysis during therapeutic stress revealed that the LNX1 pathway, a Notch co-regulator known to control symmetric divisions, increases 8.7-fold in patient-derived xenograft (PDX) cells (p<0.0001). Furthermore, a comparative examination of PDX cells under therapeutic stress showed that Notch antagonist Numb is significantly downregulated. Studies of protein expression in GBM cells treated with TMZ and vehicle show similar trends, with LNX1 expression increasing upon treatment and Numb expression decreasing. Based on these observations, we propose that therapeutic stress mediates alterations in the Notch pathway which subsequently allow symmetric self-renewal to predominate in GBM. Such shift from asymmetric to symmetric self-renewal of GSCs is a possible mechanism by which GSCs expand under therapeutic stress and potentially a valuable therapeutic target.
PUB001 Epid-Based in Vivo Dosimetry for Accurate Delivery of Lung Stereotactic Radiotherapy Using Breath-Hold Segmented VMAT
Authors: S. Cilla, A. Ianiro, M. Craus, P. Viola, F. Deodato, G. Macchia, L. Azario, A. Fidanzio, M. De Spirito, A. Morganti, V. Valentini, A. Piermattei
Journal: Journal of Thoracic Oncology (2017)
Diagnostics des infections sexuellement transmissibles non virales en Lituanie et recommandations internationales
Authors: A Vagoras, R Butylkina, V Juseviciute, A Hallén, M Unemo, M Domeika
Journal: Eurosurveillance (2006)

L’objectif de cette etude, menee en Lituanie de septembre 2002 a decembre 2003, est d’evaluer le choix, la qualite et la disponibilite des laboratoires de diagnostics des infections sexuellement transmissibles (IST) non virales , c.a.d. C. trachomatis, N. gonorrhoeae, T. vaginalis et T. pallidum. 
Les donnees de surveillance decrivant l’organisation et les caracteristiques des services de diagnostics des IST non virales en Lituanie ont ete recueillies au moyen d’un questionnaire, puis de visites sur site. Les recommandations internationales basees sur des evidences concernant le diagnostic d’IST non virales ont ete utilisees pour evaluer la qualite des diagnostics d’IST. 
Il existait 171 etablissements possedant des services de diagnostic des IST non virales pour les 3,5 millions d’habitants de la Lituanie. Cependant, seuls 6% (n=9) des repondants (n=153) ont pu fournir un diagnostic de confirmation, en accord avec les recommandations internationales, pour l’ensemble des IST non virales importantes en Lituanie, soit C. trachomatis, N. gonorrhoeae, T. pallidum, et T. vaginalis. De plus, l’acces a ces services etait tres variable d’une province a l’autre. Parmi les repondants, plusieurs avaient tres peu de prelevements a analyser chaque annee, et globalement, le nombre de prelevements etait tres faible, en particulier pour le diagnostic de C. trachomatis . 
En Lituanie, il est essentiel d’optimiser le diagnostic des IST non virales ainsi que la surveillance epidemiologique et la gestion de ces infections. Une solution pourrait etre de diminuer le nombre de laboratoires, permettant ainsi d’optimiser les diagnostics d’IST, selon les recommandations internationales dans les laboratoires restants, de les standardiser et d’en assurer la qualite grâce a des controles de qualite systematiques internes et externes. De plus, il est vivement recommande de mettre en place des reseaux nationaux de laboratoires et des centres nationaux de reference pour les IST non virales.
ATIM-23. PHASE I TRIAL OF ANTI-LAG-3 OR ANTI-CD137 ALONE AND IN COMBINATION WITH ANTI-PD-1 IN PATIENTS WITH RECURRENT GBM
Authors: Michael Lim, Xiaobu Ye, Burt Nabors, Anna F Piotrowski, Joy Fisher, Serena Desideri, Megan Sims, Patrick Wen, Stuart A Grossman
Journal: Neuro-Oncology (2017)

Given the success of immunotherapy in other solid tumors, immunotherapy is being actively investigated in GBM. Preclinical data with the checkpoint molecules anti-Lag-3 and anti-CD137 have effectively induced an anti-tumor immune response with resultant improved survival when combined with anti-PD-1. The Adult Brain Tumor Consortium (ABTC) 1501 trial is a phase I, open label, multicenter, multi-arm dose-finding/safety study of anti-LAG-3 (BMS-986016) or anti-CD137 (BMS-663513) alone and in combination with anti-PD-1 in patients at first recurrence of GBM. The primary objective is to define MTD for the mono and combinational treatment. The major secondary objective is to explore for a signal in efficacy. The key inclusion criteria are adults, first recurrence of GBM following RT+TMZ, TLC≥1000/ul, KPS≥ 60%, stable corticosteroid regimen, measurable disease, and written informed consent. Sequential allocation is used for the treatment assignment at starting dose of 80mg for anti-LAG-3 and 8mg for anti-CD137. Anti-PD-1will be given at a flat dose of 240 mg in the combination treatment arms. The 3 + 3 design is used for the dose finding with a target DLT rate ≤ 33%. 7 patients have been enrolled in the initial single dose arms with an average age at 60 and KPS at 80%. Three patients were treated with anti-LAG-3 at 80 mg and 4 patients were on 8mg anti-CD137. One patient had a grade 2 headache attributed to anti-CD137. There were a grade 2 fatigue and a grade 3 leukocytosis attributed to anti-LAG-3. No DLT was observed. The trial is ongoing. The first dose of both anti-LAG-3 and anti-CD137 were well tolerated. The single agent arms and a combination arm with anti-PD-1 are open for accrual.
OA 04.08 Is Lobe-Specific Lymph Node Dissection in Clinical N0-1 Non-Small Cell Lung Cancer Adequate for Pathological Nodal Staging
Authors: A. Tantraworasin, S. Siwachat, N. Lertprasertsuke, S. Kongkarnka, J. Euathrongchit, Y. Wannasopha, N. Tanatip, E. Taioli, S. Saeteng
Journal: Journal of Thoracic Oncology (2017)
Cardiac safety of adjuvant non-pegylated liposomal doxorubicin combined with cyclophosphamide and followed by paclitaxel in older breast cancer patients
Authors: L. Coltelli, S. Cappelli, A. Fontana, S. Lucchesi, G. Bocci, A. Farnesi, G. Arrighi, C. Finale, B. Salvadori, C. De Angelis, L. Ginocchi, A. Falcone, I. Fabiani, G. Allegrini
Journal: Annals of Oncology (2017)
Safety and Antitumor Activity of the Anti–Programmed Death-1 Antibody Pembrolizumab in Patients With Advanced Esophageal Carcinoma
Authors: Toshihiko Doi, Sarina A. Piha-Paul, Shadia I. Jalal, Sanatan Saraf, Jared Lunceford, Minori Koshiji, Jaafar Bennouna
Journal: Journal of Clinical Oncology (2017)

Purpose The anti-programmed death-1 antibody pembrolizumab was evaluated in KEYNOTE-028, a multicohort, phase IB study of patients with programmed death ligand-1 (PD-L1)-positive advanced solid tumors. Results from the esophageal carcinoma cohort are reported herein. Patients and Methods Eligible patients with squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction in whom standard therapy failed and who had PD-L1-positive tumors received pembrolizumab 10 mg/kg every 2 weeks for up to 2 years or until confirmed disease progression or intolerable toxicity. Response was assessed every 8 weeks up to 6 months and every 12 weeks thereafter. Primary end points were safety and overall response rate, determined by investigator review per Response Evaluation Criteria in Solid Tumors (version 1.1). Results Among 83 patients with esophageal carcinoma and samples evaluable for PD-L1 expression, 37 (45%) had PD-L1-positive tumors, and 23 were enrolled. Median age was 65 years; 78% had squamous histology; and 87% received ≥ two prior therapies for advanced/metastatic disease. As of the data cutoff (February 20, 2017), median follow-up was 7 months (range, 1 to 33 months). Nine patients (39%) experienced treatment-related adverse events, most commonly decreased appetite, decreased lymphocyte count, generalized rash, and rash (two patients [9%] each). No grade 4 adverse events or deaths were attributed to pembrolizumab. Overall response rate was 30% (95% CI, 13% to 53%); median duration of response was 15 months (range, 6 to 26 months). A six-gene interferon-γ gene expression signature analysis suggested that delayed progression and increased response occur among pembrolizumab-treated patients with higher interferon-γ composite scores. Conclusion Pembrolizumab demonstrated manageable toxicity and durable antitumor activity in patients with heavily pretreated, PD-L1-positive advanced esophageal carcinoma.
NIMG-32. DIFFERENTIATION OF PSEUDOPROGRESSION FROM TUMOR PROGRESSION IN GLIOBLASTOMA PATIENTS BASED ON FET PET RADIOMICS
Authors: Philipp Lohmann, Christoph Lerche, Elena Bauer, Jan Steger, Gabriele Stoffels, Tobias Blau, Veronika Dunkl, Christian P Filss, Carina Stegmayr, Bernd Neumaier, Nadim J Shah, Gereon Fink, Karl-Josef Langen, Norbert Galldiks
Journal: Neuro-Oncology (2017)

Differentiation of pseudoprogression (PsP) from tumor progression (TP) in glioblastoma patients can be difficult with standard MRI. Textural feature analysis as part of the concept of radiomics offers a quantitative method to describe tumor heterogeneity. We investigated the potential of textural features of O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET to discriminate between PsP and TP in glioblastoma patients. Twenty-six newly diagnosed glioblastoma patients with MRI findings suspicious for TP within 12 weeks after completion of chemoradiation with temozolomide underwent an additional dynamic FET PET scan. Volumes-of-interest were defined on summed images (20-40 min post-injection) by a 3-dimensional auto-contouring process using a tumor-to-brain ratio (TBR) of 1.6 or more. TBRs and time-activity curves (TACs) of FET uptake were determined. Dynamic FET PET parameters time-to-peak (TTP) and slope (slope of the linear regression line 20-50 min post-injection) were evaluated. Additionally, 39 textural parameters were calculated using the software LifeX. The diagnostic accuracy of TBRs, TTP, slope, and textural parameters to discriminate between PsP and TP was evaluated using ROC analyses using the results of histopathology or of the clinico-radiological course as reference. In order to further increase the diagnostic accuracy, parameters were combined using linear logistic regression for classification of PsP and TP. Fifteen patients had TP and 11 patients had PsP. The parameters TBRmean, TBRmax and TTP yielded a diagnostic accuracy to discriminate between PsP and TP of 70%, 74%, 59%, respectively. The dynamic FET PET parameter slope yielded the highest diagnostic accuracy of 81%. The two best textural features showed an accuracy of 74%. Combining TBR with textural features lead to an improved accuracy of 78%. Textural features might yield additional valuable information for this highly relevant clinical problem without the need for acquiring a more time-consuming dynamic PET acquisition and should be further evaluated prospectively in larger cohorts.
The Role of Lipoprotein(a) in Calcific Aortic Valve Disease
Authors: Vidu Garg
Journal: JAMA Cardiology (2017)

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Abstract 19570: Efficacy and Barriers to Evolocumab Therapy in Real-World, High Risk Secondary Prevention Patients Not at LDL Targets
Authors: Avinash K Pandey, Harpreet Bajaj, Vinay Garg, A. Shekhar Pandey, Subodh Verma
Journal: Circulation (2017)

Introduction: LDL cholesterol lowering, especially with statins, results in reduction of cardiovascular disease. A significant proportion of patients are unable to achieve target LDL levels on stat...
Abstract SY08-01: Cancer in immunosuppressed populations: Epidemiologic clues to causation
Authors: Eric A. Engels
Journal: Cancer Research (2010)

Abstract Epidemiologic studies of immunosuppressed populations (HIV-infected people and solid organ transplant recipients) can identify candidate malignancies where infection, immunity, and inflammation are likely to be etiologically important. Such studies have revealed markedly elevated risk for cancers linked to oncogenic viral infections, e.g., Kaposi sarcoma (caused by human herpesvirus 8), some non-Hodgkin lymphoma subtypes and Hodgkin lymphoma (Epstein Barr virus), anogenital cancers (human papillomavirus), and liver cancer (hepatitis B and C viruses). For these cancers, the heightened risk arises from a high prevalence of viral infection and/or loss of immune control of the infection. In contrast, risk is not elevated in immunosuppressed populations for common malignancies not strongly linked to infection (e.g., colon, prostate, and breast cancers), arguing against a more general role for immune surveillance in protecting healthy people from cancer. For a few remaining cancers, an elevated risk is observed among both HIV-infected people and transplant recipients, but the increase is not as great as for malignancies known to be caused by viruses, or data are less clearcut. Examples include various skin cancers, lung cancer, and multiple myeloma. These increased risks suggest that specific infections (with either a known or unknown agent) or altered immunity are relevant for development of these malignancies. Another possibility is that repeated or chronic infections with diverse microbes, or chronic inflammation, play a role. Citation Format: Eric A. Engels. Cancer in immunosuppressed populations: Epidemiologic clues to causation [abstract]. In: Proceedings of the AACR 101st Annual Meeting 2010; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr SY08-01
ANGI-15. NANOFORMULATION OF A VASCULAR DISRUPTING AGENT FOR THE TREATMENT OF GLIOMA WITH MRI MONITORING
Authors: Meser Ali, Sunalee Jayasundara, Ana deCarvalho, James Ewing
Journal: Neuro-Oncology (2017)

Anti-angiogenesis therapy VEGF-VEGF receptors axis alone or in combination with other therapeutic agents have demonstrated mixed results, with the majority of reports indicating that glioblastoma (GBM) developed resistance against anti-angiogenesis therapy as well as small molecular receptor tyrosine kinase inhibitors. This result is perhaps not unexpected, because angiogenesis is obviously complex, involving dozens of different growth factors that trigger a cascade of subsequent events. Even if a drug effectively blocks one angiogenic growth factor, such as VEGF, blood vessels may still develop via activating alternative pathways. Yet without a sufficient blood supply, cancerous tumors can’t grow larger than the head of a pin and are unlikely to become lethal. Therefore, tumor vascularization is a critical process that determines tumor growth, progression and metastasis. Thus, tumor vasculature has become an emerging target for new chemotherapeutic drugs. Vascular disrupting agents (VDAs) for example, combretastatin (CA4), represent a new class of chemotherapeutic agent that targets the newly formed vasculature in solid tumors. Preclinical and early phase trials have demonstrated the promising therapeutic benefits of CA4. Nevertheless, the clinical translation of CA4 has been significantly hampered due to its poor systemic bioavailability and the non-specific distribution of CA4 throughout the body when administered intravenously. Thus, it is reasonable to explore novel formulations of CA4 that overcome the limitations mentioned above. We have engineered dendrimer-based nano-sized CA4 conjugate which demonstrates high water solubility. Preliminary intravenous (i.v.) delivery of nano-combretastatin in an orthotropic glioma model demonstrated a necrosis at the core of the tumor leaving a rim of viable tissue. The MRI-determined tissue parameters Ktrans, blood flow (CBF), DWI, ADC map, distribution volume and tumor size indicated the effectiveness of nano-combretastatin treatment. The overall therapeutic effect from G3-CA4 alone or in combination with SRS/TMZ will be evaluated by image-guided MRI monitoring of long-term survival rats.